David Rosenthal

All Publications

• ACTION-ARC Pediatric and Adult Congenital Heart Disease Ventricular Assist Device Adverse Event Definitions-2023. ASAIO journal (American Society for Artificial Internal Organs : 1992) Lorts, A., VanderPluym, C., Adachi, I., Perry, T., Alexander, P. M., Almond, C. S., Auerbach, S. R., Barbaro, R. P., Bhavsar, S., Bourque, K., Conway, J., Danziger-Isakov, L. A., Davies, R. R., Eghtesady, P., Hirata, Y., Ichord, R. N., Kormos, R. L., Kroslowitz, R., Krucoff, M., Lantz, J., Mehegan, M., Mehran, R., Morales, D. L., Murray, J., Niebler, R. A., O'Connor, M. J., Pagani, F. D., Peng, D. M., Rossano, J. W., Spitzer, E., Steiner, M. E., Sutcliffe, D. L., Taylor, J. M., Villa, C. R., Wearden, P. D., Rosenthal, D. 2024

  Abstract

  Adverse events (AEs) experienced by children and adults with congenital heart disease (CHD) on ventricular assist devices (VADs) are sometimes unique to these populations. The Advanced Cardiac Therapies Improving Outcomes Network (ACTION) and the Academic Research Consortium (ARC) aimed to harmonize definitions of pediatric and CHD AEs for use in clinical trials, registries, and regulatory evaluation. Data from the ACTION registry and adjudication committee were used to adapt general mechanical circulatory support ARC definitions. This ACTION-ARC international expert panel of trialists, clinicians, patients, families, statisticians, biomedical engineers, device developers, and regulatory agencies drafted and iterated definitions harmonized to ACTION data and existing literature during sessions conducted between December 2022 and May 2023, followed by dissemination across clinical/research audiences and professional organizations and further revision. Both email-linked, internet-based surveys and in-person discussions were used as a modified Delphi process. Nineteen AE types were identified and defined, including seven new event types and six event types that were deleted and will no longer be collected, achieving consensus. ACTION-ARC paired rigorous development with methodical stakeholder involvement and dissemination to define pediatric VAD AEs to facilitate assimilation of data across future clinical trials and evaluation of devices for VAD-supported children and adults with CHD.

  View details for DOI 10.1097/MAT.0000000000002288

  View details for PubMedID 39330959

• Pediatric Combined Heart-liver Transplantation: A Single-center Long-term Experience. Transplantation direct Levitte, S., Nilkant, R., Chen, S., Beadles, A., Lee, J., Bonham, C. A., Rosenthal, D., Gallo, A., Hollander, S., Esquivel, C., Ma, M., Zhang, K. Y. 2024; 10 (9): e1696

  Abstract

  Combined heart liver transplant (CHLT) continues to gain attention as a surgical treatment for patients with end-stage heart and liver disease but remains rare. We present our institutional longitudinal experience with up to 14 y of follow-up, focused on long-term outcomes in CHLT recipients.We conducted a single-institutional, retrospective review from January 1, 2010, to December 31, 2023, including 7 patients ages 7-17 y who underwent CHLT.Most patients were surgically palliated via Fontan procedure pretransplant (n = 6), and all had evidence of advanced fibrosis or cirrhosis before transplant. The 30-d mortality was 14.3% (n = 1, multiorgan failure). During the follow-up period, 1 patient developed acute heart rejection which required treatment and 2 developed acute liver rejection. In all cases, rejection was successfully treated. Two patients developed acute heart rejection which did not require treatment (grade 1R). No patients developed chronic or refractory rejection. No patients developed allograft coronary artery vasculopathy.CHLT remains a rarely performed treatment for pediatric patients with end-stage heart and liver disease, but our long-term data suggest that this treatment strategy should be considered more frequently.

  View details for DOI 10.1097/TXD.0000000000001696

  View details for PubMedID 39165490

  View details for PubMedCentralID PMC11335332

• Development and Validation of a Novel Pediatric Mechanical Circulatory Support Risk Stratification Tool: The Advanced Cardiac Therapies Improving Outcomes Network (ACTION) Ventricular Assist Device Score. ASAIO journal (American Society for Artificial Internal Organs : 1992) Bonilla-Ramirez, C., Lorts, A., Spinner, J. A., Wright, L., Niebler, R. A., Peng, D. M., Davies, R. R., Rosenthal, D. N., O'Connor, M. J. 2024

  Abstract

  We sought to develop and validate a new risk stratification score for mortality for children supported with a ventricular assist device (VAD). This retrospective, multicenter study used data from patients undergoing VAD implantation between April 2018 and February 2023 at 44 participating institutions in the Advanced Cardiac Therapies Improving Outcomes (ACTION) network. Multivariable Cox proportional-hazards modeled mortality after VAD implantation. A total of 1,022 patients were enrolled. The 1 year mortality was 19% (95% confidence interval [CI]: 16-23). The multivariable model was used to build the ACTION VADs risk stratification score with four components: ventilation, advanced organ support (dialysis or ECMO), diagnosis, and size (weight ≤5 kg). One point is added for each risk factor. Based on the sum of the risk factors, patients were classified into four classes: class 0-green (4% mortality at 1 year), class 1-yellow (16% mortality at 1 year), class 2-orange (21% mortality at 1 year), and class 3 or higher-red (42% mortality at 1 year). The score performed well, with area under the curve (AUC) of 0.72 and excellent calibration. The ACTION VADs score for mortality can be calculated easily and offers risk stratification and prognostic information for pediatric VAD candidates. This is the first validated risk assessment tool for pediatric mechanical circulatory support.

  View details for DOI 10.1097/MAT.0000000000002297

  View details for PubMedID 39150771

• Contemporary Pediatric Heart Transplant Waitlist Mortality. Journal of the American College of Cardiology Power, A., Sweat, K. R., Roth, A., Dykes, J. C., Kaufman, B., Ma, M., Chen, S., Hollander, S. A., Profita, E., Rosenthal, D. N., Barkoff, L., Chen, C. Y., Davies, R. R., Almond, C. S. 2024; 84 (7): 620-632

  Abstract

  In 2016, the United Network for Organ Sharing revised its pediatric heart transplant (HT) allocation policy.This study sought to determine whether the 2016 revisions are associated with reduced waitlist mortality and capture patient-specific risks.Children listed for HT from 1999 to 2023 were identified using Organ Procurement and Transplantation Network data and grouped into 3 eras (era 1: 1999-2006; era 2: 2006-2016; era 3: 2016-2023) based on when the United Network for Organ Sharing implemented allocation changes. Fine-Gray competing risks modeling was used to identify factors associated with death or delisting for deterioration. Fixed-effects analysis was used to determine whether allocation changes were associated with mortality.Waitlist mortality declined 8 percentage points (PP) across eras (21%, 17%, and 13%, respectively; P < 0.01). At listing, era 3 children were less sick than era 1 children, with 6 PP less ECMO use (P < 0.01), 11 PP less ventilator use (P < 0.01), and 1 PP less dialysis use (P < 0.01). Ventricular assist device (VAD) use was 13 PP higher, and VAD mortality decreased 9 PP (P < 0.01). Non-White mortality declined 10 PP (P < 0.01). ABO-incompatible listings increased 27 PP, and blood group O infant mortality decreased 13 PP (P < 0.01). In multivariable analyses, the 2016 revisions were not associated with lower waitlist mortality, whereas VAD use (in era 3), ABO-incompatible transplant, improved patient selection, and narrowing racial disparities were. Match-run analyses demonstrated poor correlation between individual waitlist mortality risk and the match-run order.The 2016 allocation revisions were not independently associated with the decline in pediatric HT waitlist mortality. The 3-tier classification system fails to adequately capture patient-specific risks. A more flexible allocation system that accurately reflects patient-specific risks and considers transplant benefit is urgently needed.

  View details for DOI 10.1016/j.jacc.2024.05.049

  View details for PubMedID 39111968

• A Comprehensive, Multi-Faceted Strategy to Increase Pediatric Donor Heart Utilization. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Hollander, S. A., Chen, S., Dykes, J., Kaufman, B. D., Lee, E., Wujcik, K., Profita, E., Schmidt, J., Rosenthal, D. N. 2024

  Abstract

  Many hearts offered for pediatric heart transplantation (HT) are not placed. In 2016, we initiated a quality improvement endeavor to increase heart offer acceptance. This study assessed the effect of these interventions at our center.Evaluation of pre-/post-implementation cohorts (1/1/2008-12/31/2016 vs. 1/1/2017- 7/1/2023) comparing donor heart utilization. Six interventions were iterated over time to increase offer acceptance ("extended criteria"): ABO-incompatible transplant, ex vivo perfusion for distanced donors, 3-dimensional total cardiac volume (TCV) assessment, acceptance of Hepatitis-C or SARS-COV-2 infected donors, and institutional culture change favoring consideration of donors previously considered unacceptable (Public Health Service Risk, long CPR duration, etc.). Outcomes studied included annual HT volume, median waitlist duration, sequence number at acceptance, and post-transplant clinical outcomes.From 1/2008-7/2023 annual transplant volume increased from 16/year to 25/year pre-/post-implementation. Three hundred-thirteen/389 (80%) listed patients were transplanted. Waitlist duration shortened post-implementation (P=0.01), as did the percentage of accepted heart offers utilizing at least one extended criterion (P<0.001). Institutional culture change and TCV assessment had the largest impact on donor heart utilization (P=0.04 &P<0.001). There was no difference in post-HT intubation or cardiovascular intensive care unit (CVICU) days (P= 0.05-0.9), though post-transplant hospitalization duration (P<0.001) increased. Post-transplant survival was unaffected by use of extended criteria hearts (P=0.3).We report increased donor heart offer acceptance resulting from a longitudinal, multi-faceted effort to increase organ offer utilization, with institutional culture change and TCV assessments having the greatest impact. Use of extended criteria hearts was not associated with inferior survival.

  View details for DOI 10.1016/j.healun.2024.06.015

  View details for PubMedID 38945282

• Mechanical Ventilation and Outcomes of Children Who Undergo Ventricular Assist Device Placement: 2014-2020 Linked Analysis From the Advanced Cardiac Therapies Improving Outcomes Network and Pediatric Cardiac Critical Care Consortium Registries. Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies Perry, T., Rosenthal, D. N., Lorts, A., Zafar, F., Zhang, W., VanderPluym, C., Dewitt, A. G., Reichle, G., Banerjee, M., Schumacher, K. R. 2024

  Abstract

  Placement of a ventricular assist device (VAD) improves outcomes in children with advanced heart failure, but adverse events remain important consequences. Preoperative mechanical ventilation (MV) increases mortality, but it is unknown what impact prolonged postoperative MV has.Advanced Cardiac Therapies Improving Outcomes Network (ACTION) and Pediatric Cardiac Critical Care Consortium (PC4) registries were used to identify and link children with initial VAD placement admitted to the cardiac ICU (CICU) from August 2014 to July 2020. Demographics, cardiac diagnosis, preoperative and postoperative CICU courses, and outcomes were compiled. Univariable and multivariable statistics assessed association of patient factors with prolonged postoperative MV. Multivariable logistic regression sought independent associations with outcomes.Thirty-five pediatric CICUs across the United States and Canada.Children on VADs included in both registries.None.Two hundred forty-eight ACTION subjects were linked to a matching patient in PC4. Median (interquartile) age 7.7 years (1.5-15.5 yr), weight 21.3 kg (9.1-58 kg), and 56% male. Primary diagnosis was congenital heart disease (CHD) in 35%. Pre-VAD explanatory variables independently associated with prolonged postoperative MV included: age (incidence rate ratio [IRR], 0.95; 95% CI, 0.93-0.96; p < 0.01); preoperative MV within 48 hours (IRR, 2.76; 95% CI, 1.59-4.79; p < 0.01), 2-7 days (IRR, 1.82; 95% CI, 1.15-2.89; p = 0.011), and greater than 7 days before VAD implant (IRR, 2.35; 95% CI, 1.62-3.4; p < 0.01); and CHD (IRR, 1.96; 95% CI, 1.48-2.59; p < 0.01). Each additional day of postoperative MV was associated with greater odds of mortality (odds ratio [OR], 1.09 per day; p < 0.01) in the full cohort. We identified an associated greater odds of mortality in the 102 patients with intracorporeal devices (OR, 1.24; 95% CI, 1.04-1.48; p = 0.014), but not paracorporeal devices (77 patients; OR, 1.04; 95% CI, 0.99-1.09; p = 0.115).Prolonged MV after VAD placement is associated with greater odds of mortality in intracorporeal devices, which may indicate inadequacy of cardiopulmonary support in this group. This linkage provides a platform for future analyses in this population.

  View details for DOI 10.1097/PCC.0000000000003520

  View details for PubMedID 38619330

• Cardiac transplantation in pediatric patients with inborn errors of metabolism: Outcomes from a single center Null, E., Tolani, D., Rosenthal, D. N., Enns, G. M. ACADEMIC PRESS INC ELSEVIER SCIENCE. 2024

  View details for DOI 10.1016/j.ymgme.2024.108237

  View details for Web of Science ID 001300271800084

• Achieving consensus, severity-graded definitions of Fontan-associated complications to characterize Fontan circulatory failure. Journal of cardiac failure Schumacher, K. R., Cedars, A., Allen, K., Goldberg, D., Batazzi, A., Reichle, G., DiPaola, F., Selewski, D., Cousino, M., Rosenthal, D. N. 2024

  Abstract

  Fontan physiology leads to chronic changes in other organ systems that may affect long-term survival and the success of heart transplantation. Inadequate assessment and treatment of the extra-cardiac effects of Fontan may contribute to poor outcomes. Severity graded/ordinal consensus definitions of Fontan complications are lacking which limits understanding of how Fontan-specific morbidity affects patient outcomes.A panel of Fontan patient and physiology experts, including pediatric, adult congenital, heart failure, and critical care cardiology, and pediatric nephrology, hepatology and psychology, convened to develop definitions of Fontan complications. Definitions were created using a severity-graded, ordinal scale: grade 1 - mild; grade 2 moderate; grade 3 - severe; grade 4 - disabling or life-threatening. Following definition creation, a second panel of 21 experts in Fontan circulatory failure used a modified Delphi methodology to modify and vote on definitions until consensus (>90% agreement without recommended further modification) was reached on final definitions. After three rounds of modification and voting, consensus agreement was achieved on all Fontan-specific definitions. The defined complications and morbidities of Fontan include: anatomic Fontan pathway obstruction, cyanosis, systemic venous abnormalities resulting from venous insufficiency, atrial arrhythmia, ventricular arrhythmia, bradycardia, chronic pleural effusions, chronic ascites, protein-losing enteropathy, plastic bronchitis, hemoptysis and pulmonary hemorrhage, sleep apnea, Fontan-associated liver disease, portal and hepatic variceal disease, acute kidney injury affecting clinical treatment, polycythemia, thrombotic disease, recurrent or severe bacterial infection, skin atrophy, adrenal insufficiency, physical impact of previous stroke, mood/behavior disorder and neurodevelopmental disorder.Consensus, severity-graded definitions of Fontan-specific cardiac and extra-cardiac complications were achieved and are available for use in research. They will allow future robust analyses of Fontan patient outcomes.

  View details for DOI 10.1016/j.cardfail.2024.02.015

  View details for PubMedID 38452996

• Multicenter Study of Survival Benefit of Cardiac Resynchronization Therapy in Pediatric and Congenital Heart Disease. JACC. Clinical electrophysiology Chubb, H., Mah, D. Y., Shah, M., Lin, K. Y., Peng, D. M., Hale, B. W., May, L., Etheridge, S., Goodyer, W., Ceresnak, S. R., Motonaga, K. S., Rosenthal, D. N., Almond, C. S., McElhinney, D. B., Dubin, A. M. 2023

  Abstract

  BACKGROUND: Evidence for the efficacy of cardiac resynchronization therapy (CRT) in pediatric and congenital heart disease (CHD) has been limited to surrogate outcomes.OBJECTIVES: This study aimed to assess the impact of CRT upon the risk of transplantation or death in a retrospective, high-risk, controlled cohort at 5 quaternary referral centers.METHODS: Both CRT patients and control patients were<21 years of age or had CHD; had systemic ventricular ejection fraction<45%; symptomatic heart failure; and significant electrical dyssynchrony (QRS duration z score >3 or single-site ventricular pacing >40%) at enrollment. Patients with CRT were matched with control patients via 1:1 propensity score matching. CRT patients were enrolled at CRT implantation; control patients were enrolled at the outpatient clinical encounter where inclusion criteria were first met. The primary endpoint was transplantation or death.RESULTS: In total, 324 control patients and 167 CRT recipients were identified. Mean follow-up was 4.2 ± 3.7 years. Upon propensity score matching, 139 closely matched pairs were identified (20 baseline indices). Of the 139 matched pairs, 52 (37.0%) control patients and 31 (22.0%) CRT recipients reached the primary endpoint. On both unadjusted and multivariable Cox regression analysis, the risk reduction associated with CRT for the primary endpoint was significant (HR: 0.40; 95%CI: 0.25-0.64; P< 0.001; and HR: 0.44; 95%CI: 0.28-0.71; P=0.001, respectively). On longitudinal assessment, the CRT group had significantly improved systemic ventricular ejection fraction (P< 0.001) and shorter QRS duration (P=0.015), sustained to 5 years.CONCLUSIONS: In pediatric and CHD patients with symptomatic systolic heart failure and electrical dyssynchrony, CRT was associated with improved heart transplantation-free survival.

  View details for DOI 10.1016/j.jacep.2023.11.008

  View details for PubMedID 38206260

• Reducing donor acceptance practice variation - Learnings from a discussion forum. Pediatric transplantation Bansal, N., Jeewa, A., Watanabe, K., Richmond, M. E., Alzubi, A., D'Souza, N., Bano, M., Lorts, A., Rosenthal, D. N., Taylor, K., O'Shea, C., Smyth, L., Koehl, D., Zhao, H., Hollander, S. A. 2023: e14635

  Abstract

  Although waitlist mortality is unacceptably high, nearly half of donor heart offers are rejected by pediatric heart transplant centers. The Advanced Cardiac Therapy Improving Outcome Network (ACTION) and Pediatric Heart Transplant Society (PHTS) convened a multi-institutional donor decision discussion forum (DDDF) aimed at assessing donor acceptance practices and reducing practice variation.A 1-h-long virtual DDDF for providers across North America, the United Kingdom, and Brazil was held monthly. Each session typically included two case presentations posing a real-world donor decision challenge. Attendees were polled before the presenting center's decision was revealed. Group discussion followed, including a review of relevant literature and PHTS data. Metrics of participation, participant agreement with presenting center decisions, and impact on future decision-making were collected and analyzed.Over 2 years, 41 cases were discussed. Approximately 50 clinicians attended each call. Risk factors influencing decision-making included donor quality (10), size discrepancy (8), and COVID-19 (8). Donor characteristics influenced 63% of decisions, recipient factors 35%. Participants agreed with the decision made by the presenting center only 49% of the time. Post-presentation discussion resulted in 25% of participants changing their original decision. Survey conducted reported that 50% respondents changed their donor acceptance practices.DDDF identified significant variation in pediatric donor decision-making among centers. DDDF may be an effective format to reduce practice variation, provide education to decision-makers, and ultimately increase donor utilization.

  View details for DOI 10.1111/petr.14635

  View details for PubMedID 37957127

• Differences in Quality of Life in Children Across the Spectrum of Congenital Heart Disease. The Journal of pediatrics O'Connor, A. M., Cassedy, A., Wray, J., Brown, K. L., Cohen, M., Franklin, R. C., Gaynor, J. W., MacGloin, H., Mahony, L., Mussatto, K., Newburger, J. W., Rosenthal, D. N., Teitel, D., Ernst, M. M., Wernovsky, G., Marino, B. S. 2023: 113701

  Abstract

  OBJECTIVE: To create complexity groups based upon a patient's cardiac medical history and to test for group differences in health-related quality of life (HRQOL).METHODS: Patients 8-18 years with congenital heart disease (CHD) and parent-proxies from the Pediatric Cardiac Quality of Life Inventory (PCQLI) Testing Study were included. Outcome variables included PCQLI Total, Disease Impact, and Psychosocial Impact scores. Using a patient's medical history (cardiac, neurologic, psychological, cognitive diagnosis), latent class analysis (LCA) was used to create CHD complexity groups. Covariates included demographics and burden of illness (number of: school weeks missed, physician visits in the past year, daily medications). Generalized estimation equations tested for differences in burden of illness and patient and parent-proxy PCQLI scores.RESULTS: Using 1,482 CHD patients (60% male; 84% white; age 12.3±3.0 years), LCA estimates showed four distinct CHD complexity groups (Mild, Moderate 1, Moderate 2, and Severe). Increasing CHD complexity was associated with increased risk of learning disorders, seizures, mental health problems, and history of stroke. Greater CHD complexity was associated with greater burden of illness (p<0.01) and lower patient- and parent-reported PCQLI scores (p<0.001).CONCLUSION: LCA identified four CHD complexity groupings. Increasing CHD complexity was associated with higher burden of illness and worse patient- and parent-reported HRQOL.

  View details for DOI 10.1016/j.jpeds.2023.113701

  View details for PubMedID 37640230

• The Widening Care Gap in VAD Therapy. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Conway, J., Amdani, S., Morales, D., Lorts, A., Rosenthal, D. N., Jacobs, J., Rossano, J., Koehl, D., Kirklin, J. K., Auerbach, S. R. 2023

  Abstract

  INTRODUCTION: The removal of the HeartWare Ventricular Assist Device (HVAD) due to pump malfunctions and inferior outcomes compared to HeartMate 3 (HM3) in adults has created a care gap for younger patients. It is unclear if the reported HVAD survival differs by age and if the initial experience with HM3 can bridge the gap.METHODS: Using the STS Intermacs and Pedimacs registries, durable VAD implants between 09/12-12/21 where identified. Young adults (YA) were defined as <40yrs old in Intermacs. Pts were excluded if they had an isolated right VAD (RVAD) or were implanted as destination therapy (DT). Survival analysis by Kaplan Meier (KM) and Competing Outcomes Curves (COC) was performed, and 1-year survival is reported.RESULTS: The Intermacs cohort consisted of YA (n=1226; HVAD 818; HM3 408) with a median age of YA was 32.07 (26.66-36.27) (yrs) and weight (wt) 83.2 (68-104.2) Kg. Most had cardiomyopathy (CM) (92.2%). The Pedimacs cohort was 668 pt [median age 9.47 (1.82-14.23) yrs, wt 27.2 (10-57.05) Kg, and most also had CM (70.5%). Device breakdown included: HVAD (n=326), Berlin EXCOR (n=277) and HM3 (n=65). HVAD survival differed by age in adults, with YA fairing better than adults >40 yrs old (88.8% vs. 79.4% at 1 yr, p<0.0001). YA survival was also better compared to Pedimacs pt (88.9% vs. 83.7%, p=0.0002) but when competing events were analyzed, mortality was similar to YA (9.2% vs. 9.6%, p=0.1) with a higher proportion of pt undergoing transplant at 1 year in Pedimacs (74% vs. 31.3 %, p<0.0001). Survival by device differed between HVAD and HM3 in YA (88.8% vs. 94.4%, p=0.0025). This difference in device survival was not seen in all children (83.7% vs. 87.3%, p=0.21), including those ≥25Kg. Adverse event profiles also differed across the groups with adults seeing less adverse events with the HM3 but the same was not found (including stroke) in the pediatric cohort. Survival outcomes for patients between 10-25Kg were similar with the HVAD compared to the Berlin Heart EXCOR (p=0.4290), with similarities in stroke risk.CONCLUSION: The removal of the HVAD device may result in a care gap in younger pt whose survival outcomes do not mirror that of older adults. The HM3 can fill a portion of this gap with good survival but there remains a subset of pediatric pt that based on initial HM3 use will no longer have access to intracorporeal support and therefore, despite reasonable outcomes with the Berlin Heart EXCOR will not be able to be discharged home. Lastly, it is essential that future changes to the availability of devices take into account the various patient populations that utilize the device to avoid unintended consequences of access inequality.

  View details for DOI 10.1016/j.healun.2023.08.009

  View details for PubMedID 37591455

• Pulmonary Vasodilator Therapy in Pediatric Patients on Ventricular Assist Device Support: A Single-Center Experience and Proposal for Use. ASAIO journal (American Society for Artificial Internal Organs : 1992) Schramm, J. E., Dykes, J. C., Hopper, R. K., Feinstein, J. A., Rosenthal, D. N., Kameny, R. J. 2023

  Abstract

  Pediatric precapillary pulmonary hypertension can develop in response to systemic atrial hypertension. Systemic atrial decompression following ventricular assist device (VAD) implantation may not sufficiently lower pulmonary vascular resistance (PVR) to consider heart transplant candidacy. Prostacyclins have been used in adult VAD patients with success, but pediatric data on safety and efficacy in this population are limited. We sought to describe our center's experience to show its safety and to present our current protocol for perioperative use. We reviewed our use of prostacyclin therapy in pediatric patients on VAD support with high PVR from 2016 to 2021. Of the 17 patients who met inclusion, 12 survived to transplant and 1 is alive with VAD in situ. All patients survived posttransplant. With continuous intravenous (IV) epoprostenol or treprostinil therapy, there were no bleeding complications or worsening of end-organ function. A significant reduction was observed in vasoactive inotropic scores by 49% in the first 24 hours post-prostacyclin initiation. The proportion of patients surviving to transplant in this high-risk cohort is favorable. In conclusion, prostacyclins may be safe to use in patients with elevated PVR as part of their VAD and transplant course and may provide a transplant option in those otherwise not candidates.

  View details for DOI 10.1097/MAT.0000000000002023

  View details for PubMedID 37556563

• Successful implementation of telehealth visits in the paediatric heart failure and heart transplant population. Cardiology in the young Bansal, N., D'Souza, N., Wisotzkey, B. L., Albers, E., Shih, R., Exil, V., McQueen, M., Hillenburg, J. P., Azeka, E., Law, S., Peng, D. M., O'Connor, M., Gajarski, R., Vanderpluym, C., Lorts, A., Barnes, A., Sojka, M., Bano, M., Keating, M., Rosenthal, D. N., Conway, J., Schroeder, K., Nandi, D. 2023: 1-4

  Abstract

  The Advanced Cardiac Therapies Improving Outcomes Network (ACTION) and Pediatric Heart Transplant Society (PHTS) convened a working group at the beginning of 2020 during the COVID-19 pandemic, with the aim of using telehealth as an alternative medium to provide quality care to a high-acuity paediatric population receiving advanced cardiac therapies. An algorithm was developed to determine appropriateness, educational handouts were developed for both patients and providers, and post-visit surveys were collected. Telehealth was found to be a viable modality for health care delivery in the paediatric heart failure and transplant population and has promising application in the continuity of follow-up, medication titration, and patient education/counselling domains.

  View details for DOI 10.1017/S1047951123001312

  View details for PubMedID 37518866

• An integrated program to expand donor utilization in pediatric heart transplantation: Case report of successful transplant with multiple donor risk factors. Pediatric transplantation Torpoco Rivera, D. M., Hollander, S. A., Almond, C., Profita, E., Dykes, J. C., Raissadati, A., Lee, J., Sacks, L. D., Kleiman, Z. I., Lee, E., Rosenthal, A., Rosenthal, D. N., Nasirov, T., Ma, M., Martin, E., Chen, S. 2023: e14584

  Abstract

  Pediatric heart transplantation (HT) continues to be limited by the shortage of donor organs, distance constraints, and the number of potential donor offers that are declined due to the presence of multiple risk factors.We report a case of successful pediatric HT in which multiple risk factors were mitigated through a combination of innovative donor utilization improvement strategies.An 11-year-old, 25-kilogram child with cardiomyopathy and pulmonary hypertension, on chronic milrinone therapy and anticoagulated with apixaban, was transplanted with a heart from a Hepatitis C virus positive donor and an increased donor-to-recipient weight ratio. Due to extended geographic distance, an extracorporeal heart preservation system (TransMedics™ OCS Heart) was used for procurement. No significant bleeding was observed post-operatively, and she was discharged by post-operative day 15 with normal biventricular systolic function. Post-transplant Hepatitis C virus seroconversion was successfully treated.Heart transplantation in donors with multiple risk factor can be achieved with an integrative team approach and should be taken into consideration when evaluating marginal donors in order to expand the current limited donor pool in pediatric patients.

  View details for DOI 10.1111/petr.14584

  View details for PubMedID 37470130

• Major Adverse Dystrophinopathy Events (MADE) Score as Marker of Cumulative Morbidity and Risk for Mortality in Boys with Duchenne Muscular Dystrophy. Progress in pediatric cardiology Kaufman, B. D., Garcia, A., He, Z., Tesi-Rocha, C., Buu, M., Rosenthal, D., Gordish-Dressman, H., Almond, C. S., Duong, T. 2023; 69

  Abstract

  Overlapping symptoms from cardiomyopathy, respiratory insufficiency, and skeletal myopathy confound assessment of heart failure in Duchenne Muscular Dystrophy. We developed an ordinal scale of multiorgan clinical variables that reflect cumulative disease burden-the Major Adverse Dystrophinopathy Event (MADE) Score. We hypothesized that a higher MADE score would be associated with increased mortality in boys with Duchenne Muscular Dystrophy. The Cooperative International Neuromuscular Research Group Duchenne Natural History Study dataset was utilized for validation.Duchenne Natural History Study variables were selected based on clinical relevance to prespecified domains: Cardiac, Pulmonary, Myopathy, Nutrition. Severity points (0-4) were assigned and summed for study visits. MADE score for cohorts defined by age, ambulatory status, and survival were compared at enrollment and longitudinally.Associations between MADE score and mortality were examined.Duchenne Natural History Study enrolled 440 males, 12.6 ±6.1 years old, with 3,559 visits over 4.6 ±2.8 years, 45 deaths. MADE score increased with age and nonambulatory status. Mean MADE score per visit was 19 ±10 for those who died vs. 9.8 ±9.3 in survivors p=0.03. Baseline MADE score >12 predicted mortality independent of age (78% sensitivity, CPE.70). Rising MADE score trajectory was associated with mortality in models adjusted for enrollment age, follow-up time, and ambulatory status, all p<.001.A multiorgan severity score, MADE, was developed to track cumulative morbidities that impact heart failure in Duchenne muscular dystrophy. MADE score predicted Duchenne Natural History Study mortality. MADE score can be used for serial heart failure assessment in males and may serve as an endpoint for Duchenne muscular dystrophy clinical research.

  View details for DOI 10.1016/j.ppedcard.2023.101639

  View details for PubMedID 37990740

  View details for PubMedCentralID PMC10659574

• Taking ACTION: A Prognostic Tool for Pediatric Ventricular Assist Device Mortality. ASAIO journal (American Society for Artificial Internal Organs : 1992) Boucek, K., Alzubi, A., Zafar, F., O'Connor, M. J., Mehegan, M., Mokshagundam, D., Davies, R. R., Adachi, I., Lorts, A., Rosenthal, D. N. 2023; 69 (6): 602-609

  Abstract

  We sought to develop a contemporary risk assessment tool for use in pediatric ventricular assist device (VAD) candidates to estimate risk for mortality on the device using readily available preimplantation clinical data. Training and testing datasets were created from Advanced Cardiac Therapies Improving Outcomes Network (ACTION) registry data on patients supported with a VAD from 2012 to 2021. Potential risk factors for mortality were assessed and incorporated into a simplified risk prediction model utilizing an open-source, gradient-boosted decision tree machine learning library, known as random forest. Predictive performance was assessed by the area under the receiver operating characteristic curve in the testing dataset. Nine significant risk factors were included in the final predictive model which demonstrated excellent discrimination with an area under the curve of 0.95. In addition to providing a framework for establishing pediatric-specific risk profiles, our model can help inform team expectations, guide optimal patient selection, and ultimately improve patient outcomes.

  View details for DOI 10.1097/MAT.0000000000001899

  View details for PubMedID 37261722

• Major Adverse Dystrophinopathy Events (MADE) score as marker of cumulative morbidity and risk for mortality in boys with Duchenne muscular dystrophy PROGRESS IN PEDIATRIC CARDIOLOGY Kaufman, B. D., Garcia, A., He, Z., Tesi-Rocha, C., Buu, M., Rosenthal, D., Gordish-Dressman, H., Almond, C. S., Duong, T., CINRG DUCHENNE NAT HIST STUDY 2023; 69

  View details for DOI 10.1016/j.ppedcard.2023.101639

  View details for Web of Science ID 000984595500001

• Vigorous Exercise in Patients With Hypertrophic Cardiomyopathy. JAMA cardiology Lampert, R., Ackerman, M. J., Marino, B. S., Burg, M., Ainsworth, B., Salberg, L., Tome Esteban, M. T., Ho, C. Y., Abraham, R., Balaji, S., Barth, C., Berul, C. I., Bos, M., Cannom, D., Choudhury, L., Concannon, M., Cooper, R., Czosek, R. J., Dubin, A. M., Dziura, J., Eidem, B., Emery, M. S., Estes, N. A., Etheridge, S. P., Geske, J. B., Gray, B., Hall, K., Harmon, K. G., James, C. A., Lal, A. K., Law, I. H., Li, F., Link, M. S., McKenna, W. J., Molossi, S., Olshansky, B., Ommen, S. R., Saarel, E. V., Saberi, S., Simone, L., Tomaselli, G., Ware, J. S., Zipes, D. P., Day, S. M., LIVE Consortium, Abrahms, D., Ashley, E., Aziz, P., Batra, A., Cerrone, M., Colan, S., Erickson, C., Ferhaan, A., Gollob, M. J., Johnsrude, C., Kannankeril, P., Kanter, R., Li, W., Masri, A., Murphy, A., Nandi, D., Perez, M., Perry, J., Popjes, E., Rao, R., Rosenthal, D., Sanatani, S., Semsarian, C., Shah, M., Skinner, J., Tardif, J., Towbin, J., Turer, A., Webster, G., Wever-Pinzon, O., Wong, T. 2023

  Abstract

  Importance: Whether vigorous intensity exercise is associated with an increase in risk of ventricular arrhythmias in individuals with hypertrophic cardiomyopathy (HCM) is unknown.Objective: To determine whether engagement in vigorous exercise is associated with increased risk for ventricular arrhythmias and/or mortality in individuals with HCM. The a priori hypothesis was that participants engaging in vigorous activity were not more likely to have an arrhythmic event or die than those who reported nonvigorous activity.Design, Setting, and Participants: This was an investigator-initiated, prospective cohort study. Participants were enrolled from May 18, 2015, to April 25, 2019, with completion in February 28, 2022. Participants were categorized according to self-reported levels of physical activity: sedentary, moderate, or vigorous-intensity exercise. This was a multicenter, observational registry with recruitment at 42 high-volume HCM centers in the US and internationally; patients could also self-enroll through the central site. Individuals aged 8 to 60 years diagnosed with HCM or genotype positive without left ventricular hypertrophy (phenotype negative) without conditions precluding exercise were enrolled.Exposures: Amount and intensity of physical activity.Main Outcomes and Measures: The primary prespecified composite end point included death, resuscitated sudden cardiac arrest, arrhythmic syncope, and appropriate shock from an implantable cardioverter defibrillator. All outcome events were adjudicated by an events committee blinded to the patient's exercise category.Results: Among the 1660 total participants (mean [SD] age, 39 [15] years; 996 male [60%]), 252 (15%) were classified as sedentary, and 709 (43%) participated in moderate exercise. Among the 699 individuals (42%) who participated in vigorous-intensity exercise, 259 (37%) participated competitively. A total of 77 individuals (4.6%) reached the composite end point. These individuals included 44 (4.6%) of those classified as nonvigorous and 33 (4.7%) of those classified as vigorous, with corresponding rates of 15.3 and 15.9 per 1000 person-years, respectively. In multivariate Cox regression analysis of the primary composite end point, individuals engaging in vigorous exercise did not experience a higher rate of events compared with the nonvigorous group with an adjusted hazard ratio of 1.01. The upper 95% 1-sided confidence level was 1.48, which was below the prespecified boundary of 1.5 for noninferiority.Conclusions and Relevance: Results of this cohort study suggest that among individuals with HCM or those who are genotype positive/phenotype negative and are treated in experienced centers, those exercising vigorously did not experience a higher rate of death or life-threatening arrhythmias than those exercising moderately or those who were sedentary. These data may inform discussion between the patient and their expert clinician around exercise participation.

  View details for DOI 10.1001/jamacardio.2023.1042

  View details for PubMedID 37195701

• Impact of Weight on Ventricular Assist Device Outcomes in Dilated Cardiomyopathy Patients in Pediatric Centers: An ACTION Registry Study. ASAIO journal (American Society for Artificial Internal Organs : 1992) Kwiatkowski, D. M., Shezad, M., Barnes, A. P., Ploutz, M. S., Law, S. P., Zafar, F., Morales, D. L., O'Connor, M. J. 2023

  Abstract

  Ventricular assist device (VAD) options vary for children in different weight groups. This study evaluates contemporary device usage and outcomes for children based on weight. Data from the Advanced Cardiac Therapies Improving Outcomes Network (ACTION) registry were examined for patients with dilated cardiomyopathy (DCM) in 4 weight cohorts: <8 kg, 8-20 kg, 21-40 kg, and >40 kg, for devices implanted 3/2013-10/2020. Adverse event rates and ultimate outcome (deceased, alive on device, transplanted, or ventricular recovery) were analyzed. 222 DCM patients were identified with 24% in cohort 1, 23% in cohort 2, 15% in cohort 3, and 38% in cohort 4. Of 272 total implants, paracorporeal pulsatile devices were most common (95%) in cohorts 1 and 2 and intracorporeal continuous devices (81%) in cohorts 3 and 4. Stroke was noted in 17%, 12%, 6%, and 4% of cohorts, respectively (Cohort 1 vs. 4 and 2 vs. 4 - p = 0.01; other comparisons - not significant). Incidences of major bleeding, device malfunction, and infection was not different. All cohorts had >90% positive outcomes. Stroke incidence was higher in smaller cohorts, but other outcomes were similar. Positive outcomes were attained in over 90% across all weight groups, demonstrating excellent outcomes using current VADs in this DCM population.

  View details for DOI 10.1097/MAT.0000000000001861

  View details for PubMedID 37071761

• Multidisciplinary Stroke Pathway for Children Supported with Ventricular Assist Devices. ASAIO journal (American Society for Artificial Internal Organs : 1992) Lee, S., Ryan, K. R., Murray, J., Chen, S., Grant, G. A., Wilkins, S., Yarlagadda, V. V., Wintermark, M., Dodd, R., Rosenthal, D., Teuteburg, J., Navaratnam, M., Lee, J., Jordan, L. C., Almond, C. S. 2023

  Abstract

  Mechanical circulatory support (MCS), including ventricular assist device (VAD) support, is a leading cause of stroke in children; however, existing pediatric stroke recommendations do not apply to many pediatric VAD patients. We sought to develop a multidisciplinary pathway to improve timely and effective acute stroke care and examine the early performance of the pathway in expediting stroke care. Stakeholders from pediatric heart failure, cardiac intensive care, neurology, interventional radiology, neuroradiology, neurosurgery, pharmacy, and adult VAD care convened at Stanford University in August 2017 to discuss the challenges of providing high-quality acute stroke care to children on VAD support, and to develop multidisciplinary acute stroke pathways. Stakeholders identified multiple barriers to providing timely acute stroke care to pediatric VAD patients. These include delayed recognition of stroke, and lack of clarity related to the optimal imaging technique, when to emergently reverse antithrombotic therapy (AT), pediatric indications for thrombectomy and cranial decompression, and strategies to avoid unnecessary serial CTS. Four stroke pathways were created including evaluation and management of the pediatric patient with (1) an acute neurologic change before an imaging diagnosis; (2) an arterial ischemic stroke (AIS); (3) an intracerebral hemorrhage (ICH); and (4) a subdural hematoma (SDH). With the implementation of the stroke pathway, the median time-to-first-CT image decreased by 43 minutes from 66 to 23 minutes (P < 0.001) while the proportion with a CT within 30 minutes increased from 0% to 67% (P < 0.001). Despite a variety of challenges, multidisciplinary consensus can be achieved on a rapid stroke management pathway for children on VAD support that addresses important barriers to timely stroke care. Although too few stoke events occurred to differentiate clinical outcomes, the time-to-first-CT image was significantly shorter after pathway implementation.

  View details for DOI 10.1097/MAT.0000000000001822

  View details for PubMedID 36917842

• Considerations for Advanced Heart Failure Consultation in Individuals With Fontan Circulation: Recommendations From ACTION. Circulation. Heart failure Lubert, A. M., Cedars, A., Almond, C. S., Amdani, S., Conway, J., Friedland-Little, J. M., Gajarski, R. J., Kindel, S. J., Lorts, A., Morales, D. L., O'Connor, M. J., Peng, D. M., Rosenthal, D. N., Smyth, L., Sutcliffe, D. L., Schumacher, K. R. 2023: e010123

  Abstract

  Individuals with Fontan circulation are at risk of late mortality from both cardiac and noncardiac causes. Despite the known risk of mortality, referral indications for advanced heart failure care vary between centers, and many individuals die from Fontan circulation-related complications either after late consideration for advanced heart failure therapies or having never seen a heart failure specialist. There is a critical need for guidelines to direct appropriately timed referral for advanced heart failure consultation. The Advanced Cardiac Therapies Improving Outcomes Network (ACTION) Fontan Committee has developed recommended thresholds for advanced heart failure referral to guide primary cardiologists. These recommendations are divided into 4 categories of clinical Fontan circulatory dysfunction including (1) cardiac/systemic ventricular dysfunction, (2) Fontan pathway dysfunction, (3) lymphatic dysfunction, and (4) extracardiac dysfunction.

  View details for DOI 10.1161/CIRCHEARTFAILURE.122.010123

  View details for PubMedID 36786204

• Patient and parent-reported outcomes in paediatric ventricular assist device support: a multi-center ACTION learning network feasibility and pilot experience. Cardiology in the young Cousino, M. K., May, L. J., Smyth, L., McQueen, M., Thompson, K., Hunter, T., Ventresco, C., Fields, K., Murray, J., Machado, D. S., Shezad, M., Zafar, F., Rosenthal, D. N., Lorts, A., Blume, E. D. 2023: 1-9

  Abstract

  BACKGROUND: Patient- and proxy-reported outcomes (PROs) are an important indicator of healthcare quality and can be used to inform treatment. Despite the widescale use of PROs in adult cardiology, they are underutilised in paediatric cardiac care. This study describes a six-center feasibility and pilot experience implementing PROs in the paediatric and young adult ventricular assist device population.METHODS: The Advanced Cardiac Therapies Improving Outcomes Network (ACTION) is a collaborative learning network comprised of 55 centres focused on improving clinical outcomes and the patient/family experience for children with heart failure and those supported by ventricular assist devices. The development of ACTION's PRO programme via engagement with patient and parent stakeholders is described. Pilot feasibility, patient/parent and clinician feedback, and initial PRO findings of patients and families receiving paediatric ventricular assist support across six centres are detailed.RESULTS: Thirty of the thirty-five eligible patients (85.7%) were enrolled in the PRO programme during the pilot study period. Clinicians and participating patients/parents reported positive experiences with the PRO pilot programme. The most common symptoms reported by patients/parents in the first month post-implant period included limitations in activities, dressing change distress, and post-operative pain. Poor sleep, dressing change distress, sadness, and fatigue were the most common symptoms endorsed >30 days post-implant. Parental sadness and worry were notable throughout the entirety of the post-implant experience.CONCLUSIONS: This multi-center ACTION learning network-based PRO programme demonstrated initial success in this six-center pilot study experience and yields important next steps for larger-scale PRO collection, research, and clinical intervention.

  View details for DOI 10.1017/S1047951122004048

  View details for PubMedID 36655506

• Clinical approach to mechanical circulatory support in the transplant patient from the Pediatric Heart Transplant Society. Pediatric transplantation Bearl, D. W., Jeewa, A., Auerbach, S. R., Azeka, E., Phelps, C., Sacks, L. D., Rosenthal, D., Conway, J. 2022; 26 (8): e14391

  Abstract

  The use of mechanical circulatory support (MCS) for pediatric patients who have undergone heart transplant has grown rapidly in the past decade. This includes support in the immediate post-transplant period and "rescue" therapy for patient later in their transplant course. Extracorporeal membrane oxygenation (ECMO) remains a standard modality of support for intraoperative concerns and for acute decompensation in the immediate post-transplant period. However, both pulsatile and continuous flow ventricular assist devices (VADs) have been used with increasing success in transplant patients for longer durations of support. Centers participating in the Pediatric Heart Transplant Society (PHTS) were queried to provide their internal protocols and rationale for mechanical circulatory support following heart transplant. These protocols coupled with evidence-based literature were used to provide the following description of clinical approaches to MCS in the transplant patient highlighting areas of both broad consensus and significant practice variation.

  View details for DOI 10.1111/petr.14391

  View details for PubMedID 36377328

• Home Milrinone in Pediatric Hospice Care of Children with Heart Failure. Journal of pain and symptom management Hollander, S. A., Wujcik, K., Schmidt, J., Liu, E., Lin, A., Dykes, J., Good, J., Brown, M., Rosenthal, D. 2022

  Abstract

  CONTEXT: The symptom profile of children dying from cardiac disease, especially heart failure, differs from those with cancer and other non-cardiac conditions. Treatment with vasoactive infusions at home may be a superior therapy for symptom control for these patients, rather than traditional pain and anxiety management with morphine and benzodiazepines.OBJECTIVES: We report our experience using outpatient milrinone in children receiving hospice care for end-stage heart failure.METHODS: Retrospective review of a contemporary cohort of all patients at Lucile Packard Children's Hospital, Stanford who were discharged on intravenous milrinone and hospice care between 2008-2021. Clinical data, including cardiac diagnosis, milrinone dose and route of administration, total milrinone days, symptoms reported, rehospitalization rates, concurrent therapies and complications were analyzed.RESULTS: Among 8 patients, median duration of home milrinone infusion was 191 (33, 572) days with the longest support duration 1054 days. All (100%) patients were also receiving diuretics at the time of death. Five (63%) were receiving no other pain control medications until the active phase of dying. From milrinone initiation to last outpatient assessment, a reduction in the number of patients reporting respiratory discomfort, abdominal pain, weight loss/lack of appetite, and fatigue was observed. Six (75%) died at home.CONCLUSION: We used milrinone with oral diuretics effectively for symptom control in children with heart failure on palliative care. Our experience was that this combination can be used safely in the outpatient setting for long-term use without the addition of opiates, benzodiazepines, or supplemental oxygen in most cases.

  View details for DOI 10.1016/j.jpainsymman.2022.11.014

  View details for PubMedID 36417945

• Increased risk of infections in pediatric Fontan patients after heart transplantation. Pediatric transplantation Ahmed, H., Lee, J., Bernstein, D., Rosenthal, D., Dykes, J., Lee, D., Barkoff, L., Weinberg, K., Hollander, S. A., Chen, S. 2022: e14421

  Abstract

  BACKGROUND: Infectious complications are a major cause of morbidity and mortality after HT. Fontan patients may be more susceptible to post-HT infections.METHODS: This was a single-center, retrospective cohort analysis of pediatric patients undergoing HT for FF physiology or DCM, who underwent induction with ATG. The primary endpoint was an infection in the first 180days post-HT, defined as positive (1) blood/urine/respiratory culture; (2) viral PCR; (3) skin or wound infection; and/or (4) culture-negative infection if ≥5days of antibiotics were completed. Secondary endpoints included (1) cell counts after ATG; (2) PTLD; and (3) rejection (≥Grade 2R ACR or pAMR2) in the first 180days post-HT.RESULTS: A total of 59 patients (26 FF, 33 DCM) underwent HT at 14.7 (IQR 10.6, 19.5) and 11.7 (IQR 1.4, 13.6) years of age, respectively. The median total ATG received was 7.4 (IQR 4.9, 7.7) vs 7.5 (IQR 7.3, 7.6) mg/kg (p=NS) for FF and DCM patients, respectively. Twenty-three patients (39%) developed an infection 180days post-HT, with a higher rate of infection in FF patients (54% vs 27%, p=.03). Adjusted for pre-transplant absolute lymphocyte count, FF patients had a higher risk of infection at 30days post-HT (OR 7.62, 95% CI 1.13-51.48, p=.04). There was no difference in the incidence of PTLD (12% vs 0%; p=.08) or rejection (12% vs 21%; p=.49).CONCLUSION: Compared to DCM patients, FF patients have a higher risk of infection. Modifications to induction therapy for FF patients should be considered.

  View details for DOI 10.1111/petr.14421

  View details for PubMedID 36303275

• Evaluating predicted heart mass in adolescent heart transplantation. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Lee, J. Y., Zawadzki, R. S., Kidambi, S., Rosenthal, D. N., Dykes, J. C., Nasirov, T., Ma, M. 2022

  Abstract

  BACKGROUND: Predicted Heart Mass (PHM) has emerged as an attractive size matching metric in adult cardiac transplantation. However, since PHM was derived from a healthy adult cohort, its generalizability to the pediatric population is unclear. We hypothesize that PHM can be extended to older adolescents, and potentially broaden the donor pool available to this group.METHODS: The United Network for Organ Sharing database was retrospectively analyzed for patients aged 13 to 18 undergoing heart transplantation. Recipients were divided into quintiles (Q1-Q5) based on donor-to-recipient predicted heart mass ratios (PHMR). Primary end-point was graft survival at 5 years.RESULTS: Two thousand sixty-one adolescent heart transplant recipients between January 1994 and September 2019 were retrospectively analyzed. The median PHMR's for each quintile was 0.84 (0.59-0.92), 0.97 (0.92-1.02), 1.08 (1.02-1.14), 1.21 (1.14-1.30), and 1.44 (1.30-2.31). Kaplan-Meier survival curves demonstrated comparable survival across all quintiles of PHMR (p=0.9). Multivariate Cox regression showed no significant difference in graft failure of the outer quintiles when compared to the middle quintile (Q1: 1.04 HR, p=0.80; Q2: 1.02 HR, p=0.89; Q4: 1.19 HR, p=0.28; Q5: 1.02 HR, p=0.89). Significant covariates included transplant year (HR: 0.95, p < 0.0001), serum bilirubin (HR: 1.04, p=0.0004), ECMO at transplantation (HR: 2.85, p < 0.0001), and underlying diagnosis of dilated cardiomyopathy (vs congenital heart disease, HR: 0.66, p=0.0004).CONCLUSIONS: Matching by PHM is not associated with survival or risk in adolescent heart transplant recipients. Our results underscore the ongoing need to develop an improved size-matching method in pediatric heart transplantation.

  View details for DOI 10.1016/j.healun.2022.08.027

  View details for PubMedID 36210265

• Weight Matching in Infant Heart Transplantation: A National Registry Analysis. The Annals of thoracic surgery Lee, J. Y., Kidambi, S., Zawadzki, R. S., Rosenthal, D. N., Dykes, J. C., Nasirov, T., Ma, M. 2022

  Abstract

  BACKGROUND: Infants account for a significant proportion of pediatric heart transplants, but also suffer from a high waitlist mortality. Donor oversizing by weight-based criteria is common practice in transplantation and is prevalent in this group. We sought to analyze the impact of oversizing on outcomes in infants.METHODS: Infant heart transplantations reported to the United Network for Organ Sharing from 01/1994 to 09/2019 were retrospectively analyzed. 2384 heart transplantation recipients were divided into quintiles (Q1-Q5) based on donor-to-recipient weight ratios (DRWR). Multivariate Cox regression was used to estimate the effect of DRWR. The primary endpoint of graft survival at one year.RESULTS: The median DRWR for each quintile was 0.90 (0.37 to 1.04), 1.17 (1.04 to 1.29), 1.43 (1.29 to 1.57), 1.74 (1.58 to 1.97), and 2.28 (1.97 to 5.00). Pairwise comparisons showed improved survival for Q3 and Q4 over each of the bottom two quintiles and the top quintile, respectively. Regression analyses found that Q3 and Q4 were protective against graft failure when compared to the bottom two quintiles, respectively. There was no difference in hazard amongst the top three quintiles. Significant covariates included primary diagnosis, ischemic time, serum bilirubin, transplant year, mechanical ventilation at transplantation, extracorporeal membrane oxygenation at transplantation. Gender, female-to-male transplantation, and mechanical circulatory support at transplantation were not significant in univariate analyses.CONCLUSIONS: Modest oversizing by DRWR (1.29 to 1.97) is associated with increased survival and lower risk in infant heart transplantation. Additional investigation is needed to establish best practices for size-matching in this population.

  View details for DOI 10.1016/j.athoracsur.2022.05.067

  View details for PubMedID 35835207

• Global best practices consensus: Long-term management ofpatients with hybrid centrifugal flow left ventricular assist device support. The Journal of thoracic and cardiovascular surgery Hayward, C., Adachi, I., Baudart, S., Davis, E., Feller, E. D., Kinugawa, K., Klein, L., Li, S., Lorts, A., Mahr, C., Mathew, J., Morshuis, M., Muller, M., Ono, M., Pagani, F. D., Pappalardo, F., Rich, J., Robson, D., Rosenthal, D. N., Saeed, D., Salerno, C., Sauer, A. J., Schloglhofer, T., Tops, L., VanderPluym, C. 2022

  Abstract

  OBJECTIVES: Six months after withdrawal of the HeartWare HVAD System (HVAD; Medtronic) from sale, approximately 4000 patients continue ongoing support with this device. In light of the diminishing experience, this global consensus document summarizes key management recommendations.METHODS: International experts with experience in the management of patients with ongoing HVAD support were invited to summarize key aspects of patient and pump management and highlight differences in the current HeartMate 3 (Abbott Laboratories) ventricular assist device. Clinicians from high-implanting HVAD sites reviewed current literature and reported experience to generate a consensus statement.RESULTS: Specific guidelines to assist in the management of ongoing HVAD patients are developed. Key management protocols and helpful techniques developed from experienced clinicians are combined into a short guideline document. As experience with HeartMate 3 increases, key differences in approach to management are highlighted, where appropriate.CONCLUSIONS: With decreasing worldwide experience in the ongoing management of HVAD-supported patients, this consensus guideline provides a summary of best practice techniques from international centers. Differences in HeartMate 3 management are highlighted.

  View details for DOI 10.1016/j.jtcvs.2022.03.035

  View details for PubMedID 35624053

• MILESTONE: More Than 1,200 Children Bridged to Heart Transplantation with Mechanical Circulatory Support. ASAIO journal (American Society for Artificial Internal Organs : 1992) Thangappan, K., Zafar, F., Lorts, A., Adachi, I., Rosenthal, D., Rossano, J., Maeda, K., Morales, D. L. 2022; 68 (4): 577-583

  Abstract

  Pediatric mechanical circulatory support (MCS) has been successfully used to bridge numerous children to transplantation who otherwise would have been unlikely to survive on the waitlist and, in many cases, make them better transplant candidates. The purpose of this study was to analyze what the pediatric heart failure community has achieved over the last 15 years in reaching 1,200 cases of bridging children to heart transplantation. The United Network for Organ Sharing database was used to identify MCS patients ages 0-18 at the time of listing for heart transplantation between 2005 and 2019, divided into three eras: first (2005-2009), second (2010-2014), and third (2015-2019). From 2005 to 2019, 1,289 pediatric cases were identified. More patients were successfully bridged to transplantation with MCS in the third-era (28%) [vs. first-era (16%), second-era (24%), p ≤ 0.004]. The proportion of discharges on ventricular assist device has increased as well from 3% to 22% (p < 0.001). Post-transplant survival was significantly better in the third era (1-year survival: 96%; 3-year survival: 89%) compared to the two previous eras (p = 0.006). On MCS, renal dysfunction, ventilator dependence, inotrope use, and functional status improved from the time of listing to transplantation (p < 0.01). Hepatic dysfunction (p < 0.001), renal dysfunction (p = 0.004), congenital heart disease (p = 0.023), and infant age (p = 0.002) were risk factors for post-transplant mortality. Over the last 15 years, pediatric MCS has become an accepted and increasingly used strategy for bridging children to transplantation. MCS therapy is associated with improved end-organ function at the time of transplantation, perhaps contributing to the increasing post-transplantation survival of patients bridged with MCS.

  View details for DOI 10.1097/MAT.0000000000001635

  View details for PubMedID 35349524

• Decreased Risk of Strokes in Children with Ventricular Assist Devices Within ACTION. Pediatric cardiology Peng, D. M., Shezad, M. F., Lorts, A., Gajarski, R. J., VanderPluym, C., Murray, J. M., Hawkins, B., Villa, C. R., Zafar, F., Rosenthal, D. N., ACTION 2022

  Abstract

  We sought to characterize strokes in children with ventricular assist devices. Of 407 patients in the ACTION registry (4/1/18-5/3/2021), 45 (11%) experienced 52 strokes (45 ischemic and 7 hemorrhagic). Median time to stroke was 23.5days and 19/52 (37%) occurred≤10days. Stroke rate was 0.09 and 0.63 strokes per patient-year for implantable continuous and paracorporeal devices, respectively. Patients with stroke were younger, more likely to have congenital heart disease and have been on extracorporeal membrane oxygenation at time of VAD. Based on these data, ACTION is now focused on decreasing strokes in these higher-risk patients with particular attention to the peri-implant period.

  View details for DOI 10.1007/s00246-022-02863-7

  View details for PubMedID 35247057

• A Mechanistic Lumped Parameter Model of the Berlin Heart EXCOR to Analyze Device Performance and Physiologic Interactions. Cardiovascular engineering and technology Yuan, V., Verma, A., Schiavone, N. K., Rosenthal, D. N., Marsden, A. L. 2022

  Abstract

  The Berlin Heart EXCOR (BH) is the only FDA-approved, extracorporeal pulsatile ventricular assist device (VAD) for infants and children with heart failure. Clinicians control four settings on the device-systolic and diastolic drive pressures, device pump rate, and systolic time as a percentage of the pump cycle. However, interactions between BH pneumatics and the native circulation remain poorly understood. Thus, establishing appropriate device size and settings can be challenging on a patient-to-patient basis.In this study we develop a novel lumped parameter network based on simplified device mechanics. We perform parametric studies to characterize device behavior, study interactions between the left ventricle (LV) and BH across different device settings, and develop patient-specific simulations. We then simulate the impact of changing device parameters for each of three patients.Increasing systolic pressure and systolic time increased device output. We identified previously unobserved cycle-to-cycle variations in LV-BH interactions that may impact patient health. Patient-specific simulations demonstrated the model's ability to replicate BH performance, captured trends in LV behavior after device implantation, and emphasized the importance of device rate and volume in optimizing BH efficiency.We present a novel, mechanistic model that can be readily adjusted to study a wide range of device settings and clinical scenarios. Physiologic interactions between the BH and the native LV produced large variability in cardiac loading. Our findings showed that operating the BH at a device rate greater than the patient's native heart decreases variability in physiological interactions between the BH and LV, increasing cardiac offloading while maintaining cardiac output. Device rates that are close to the resting heart rate may result in unfavorable cardiac loading conditions. Our work demonstrates the utility of our model to investigate BH performance for patient-specific physiologies.

  View details for DOI 10.1007/s13239-021-00603-1

  View details for PubMedID 34997556

• Significant Variation in Exercise Recommendations for Youth With Cardiomyopathies or Fontan Circulation: An Advanced Cardiac Therapies Improving Outcomes Network Learning Survey. Circulation. Heart failure Khoury, M., Wittekind, S., Lal, A. K., Conway, J., Bansal, N., Lorts, A., Rosenthal, D., Burstein, D. 2021: CIRCHEARTFAILURE121008738

  View details for DOI 10.1161/CIRCHEARTFAILURE.121.008738

  View details for PubMedID 34517722

• Variation in Cardiac Rehabilitation for Pediatric Ventricular Assist Device Recipients Across North America ASAIO JOURNAL Burstein, D. S., McBride, M., Lorts, A., Rosenthal, D., Peng, D. M., Lantz, J., Tunuguntla, H., Zinn, M., Curran, T., Wittekind, S. 2021; 67 (9): 1045-1050

  Abstract

  Despite increasing utilization of continuous-flow pediatric ventricular assist devices (VAD) in children, data on exercise testing and cardiac rehabilitation (CR) are unknown. We described variation in CR practices and identified barriers to exercise testing and CR. A survey was performed through the Advanced Cardiac Therapies Improving Outcomes Network (ACTION) representing pediatric VAD centers across North America. Descriptive statistics were performed. A multidisciplinary cohort of 52 respondents from 28 pediatric VAD centers responded. Although 38% reported performing exercise testing, most (65%) used 6 minute walk tests rather than formal cycle or treadmill exercise testing. While all respondents refer to physical therapy during the initial inpatient stay for VAD placement, only 52% refer to a CR program. When performed, CR was performed at an ACTION center (84%), a local specialized center (21%), or a home-based CR program (26%). Commonly cited barriers to either CR or exercise testing were inadequate resources, inadequate implementation logistics knowledge, concerns about safety, inability of patients to travel to a CR facility, and concern about utility of exercise testing or CR. Over 90% of centers were interested in implementing a standardized pediatric VAD CR program. Utilization of exercise testing and CR after VAD placement is variable. Despite perceived barriers, most pediatric VAD centers are interested in implementing a standardized CR program for recipients. In response to this interest, we plan to implement a standardized CR protocol to all ACTION pediatric VAD centers in an effort to improve pretransplant waitlist rehabilitation and post-transplant outcomes.

  View details for DOI 10.1097/MAT.0000000000001335

  View details for Web of Science ID 000692194400019

  View details for PubMedID 33590993

• Significance of pre and post-implant MELD-XI score on survival in children undergoing VAD implantation. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Amdani, S., Boyle, G. J., Cantor, R. S., Conway, J., Godown, J., Kirklin, J. K., Koehl, D., Lal, A. K., Law, Y., Lorts, A., Rosenthal, D. N. 2021

  Abstract

  BACKGROUND: Derangements in liver and renal function often accompany end-stage heart failure. We sought to assess the utility of an objective risk assessment tool, the Model for End-stage Liver Disease eXcluding INR (MELD-XI), to identify pediatric patients at increased risk for adverse outcomes post-ventricular assist device (VAD) implantation.METHODS: The Pedimacs database was queried for all pediatric patients who underwent VAD implantation from September 19, 2012 to December 31, 2019. Pre-implant and early (1-week) post-implant MELD-XI scores were used to stratify patients into low, intermediate and high score cohorts. Comparison of pre-implant characteristics and post-implant outcomes were conducted across groups. Multiphase parametric hazard modeling was utilized to identify independent predictors of post-implant mortality.RESULTS: A total of 742 patients had a calculable MELD-XI score pre-implant. When stratified by MELD-XI scores pre-implant, patients in the high MELD-XI score cohort (score >13.6) had inferior survival and increased bleeding, renal dysfunction and respiratory failure post-implant compared to intermediate and low score cohorts. Risk factors for mortality post-VAD implantation were: increasing MELD-XI scores (HR 1.1 per 1 unit rise), Pedimacs profile 1 (HR 1.6), congenital heart disease (HR 2.3) and being on a percutaneous VAD (HR 2.7). Importantly, MELD-XI score was a better predictor of post-VAD implant mortality than bilirubin or creatinine alone, neither of which were significant in the final model. Patients with increasing or continued high MELD-XI scores early post-implant had the worst survival.CONCLUSION: The MELD-XI is an easily calculated score that serves as a promising risk assessment tool in identifying children at risk for poor outcomes post VAD implantation.

  View details for DOI 10.1016/j.healun.2021.08.013

  View details for PubMedID 34598872

• The darker side of device evolution: Children get left behind. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Hollander, S. A., Rosenthal, D. N., Lorts, A., ACTION Network 2021

  View details for DOI 10.1016/j.healun.2021.07.019

  View details for PubMedID 34417109

• Clinical and hemodynamic characteristics of the pediatric failing Fontan. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Dykes, J. C., Rosenthal, D. N., Bernstein, D., McElhinney, D. B., Chrisant, M. R., Daly, K. P., Ameduri, R. K., Knecht, K., Richmond, M. E., Lin, K. Y., Urschel, S., Simmonds, J., Simpson, K. E., Albers, E. L., Khan, A., Schumacher, K., Almond, C. S., Chen, S., Pediatric Heart Transplant Society 2021

  Abstract

  AIM: To describe the clinical and hemodynamic characteristics of Fontan failure in children listed for heart transplant.METHODS: In a nested study of the Pediatric Heart Transplant Society, 16 centers contributed information on Fontan patients listed for heart transplant between 2005and 2013.Patients were classified into four mutually exclusive phenotypes: Fontan with abnormal lymphatics (FAL), Fontan with reduced systolic function (FRF), Fontan with preserved systolic function (FPF), and Fontan with "normal" hearts (FNH). Primary outcome was waitlist and post-transplant mortality.RESULTS: 177 children listed for transplant were followed over a median 13 (IQR 4-31) months, 84 (47%) were FAL, 57 (32%) FRF, 22 (12%) FNH, and 14 (8%) FPF. Hemodynamic characteristics differed between the 4 groups: Fontan pressure (FP) was most elevated with FPF (median 22, IQR 18-23, mmHg) and lowest with FAL (16, 14-20, mmHg); cardiac index (CI) was lowest with FRF (2.8, 2.3-3.4, L/min/m2). In the entire cohort, 66% had FP >15 mmHg, 21% had FP >20 mmHg, and 10% had CI <2.2 L/min/m2. FRF had the highest risk of waitlist mortality (21%) and FNH had the highest risk of post-transplant mortality (36%).CONCLUSIONS: Elevated Fontan pressure is more common than low cardiac output in pediatric failing Fontan patients listed for transplant. Subtle hemodynamic differences exist between the various phenotypes of pediatric Fontan failure. Waitlist and post-transplant mortality risks differ by phenotype.

  View details for DOI 10.1016/j.healun.2021.07.017

  View details for PubMedID 34412962

• Learning networks in pediatric heart failure and transplantation. Pediatric transplantation O'Connor, M. J., Lorts, A., Kwiatkowski, D., Butts, R., Barnes, A., Jeewa, A., Knoll, C., Fenton, M., McQueen, M., Cousino, M. K., Shugh, S., Rosenthal, D. N. 2021: e14073

  Abstract

  BACKGROUND: Learning networks have emerged in medicine as a novel organizational structure that contains elements of quality improvement, education, and research with the goal of effecting rapid improvements in clinical care. In this article, the concept of a learning network is defined and highlighted in the field of pediatric heart failure and transplantation.METHODS: Learning networks are defined, with particular attention paid to the recent creation of the Advanced Cardiac Therapies Improving Outcomes Network (ACTION) for children with heart failure and those being supported with ventricular assist devices (VAD).RESULTS: The mission, goals, and organizational structure of ACTION are described, and recent initiatives promoted by ACTION are highlighted, such as stroke reduction initiatives, practice harmonization protocols, and use of ACTION data to support the recent US Food and Drug Administration approval of newer VAD for pediatric patients.CONCLUSIONS: The learning network, exemplified by ACTION, is distinguished from traditional clinical research collaboratives by contributions in research, quality improvement, patient-reported outcomes, and education, and serves as an effective vehicle to drive clinical improvement in the care of children with advanced heart failure.

  View details for DOI 10.1111/petr.14073

  View details for PubMedID 34138489

• ISHLT consensus statement for the selection and management of pediatric and congenital heart disease patients on ventricular assist devices Endorsed by the American Heart Association. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Lorts, A., Conway, J., Schweiger, M., Adachi, I., Amdani, S., Auerbach, S. R., Barr, C., Bleiweis, M. S., Blume, E. D., Burstein, D. S., Cedars, A., Chen, S., Cousino-Hood, M. K., Daly, K. P., Danziger-Isakov, L. A., Dubyk, N., Eastaugh, L., Friedland-Little, J., Gajarski, R., Hasan, A., Hawkins, B., Jeewa, A., Kindel, S. J., Kogaki, S., Lantz, J., Law, S. P., Maeda, K., Mathew, J., May, L. J., Miera, O., Murray, J., Niebler, R. A., O'Connor, M. J., Ozbaran, M., Peng, D. M., Philip, J., Reardon, L. C., Rosenthal, D. N., Rossano, J., Salazar, L., Schumacher, K. R., Simpson, K. E., Stiller, B., Sutcliffe, D. L., Tunuguntla, H., VanderPluym, C., Villa, C., Wearden, P. D., Zafar, F., Zimpfer, D., Zinn, M. D., Morales, I. R., Cowger, J., Buchholz, H., Amodeo, A. 2021

  View details for DOI 10.1016/j.healun.2021.04.015

  View details for PubMedID 34193359

• Stroke in pediatric ventricular assist device patients-a pedimacs registry analysis. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Niebler, R. A., Amdani, S., Blume, B., Cantor, R. S., Deng, L., Kirklin, J. K., Lorts, A., Morales, D. L., Rosenthal, D. N., Ghanayem, N. S. 2021

  Abstract

  BACKGROUND: Cerebralvascular accidents (CVA) are common complications of pediatric ventricular assist devices (VADs). We employed the Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs) to investigate rates, risk factors, and outcomes of CVA in pediatric patients supported on VAD.METHODS: Analysis of Pedimacs (September 2012-June 2019) data to determine rates of all neurologic events and specifically CVA. Risk factors were determined by a multiphase parametric hazard model. Outcomes of patients with CVA were compared with patients without CVA.RESULTS: We included 662 patients in our analysis. In total, 87 CVA events occurred in 71 patients (10.7%). The proportion of patients with CVA was highest in the paracorporeal pulsatile group (16.9%) followed by the paracorporeal continuous group (10.4%). However, the rate of CVA was lower in the paracorporeal pulsatile group compared to the paracorporeal continuous group (6.4 vs 11.1 events/100 patient months), which reflects differences in support duration. Ascites, higher patient profile groups, and implants within small volume centers were associated with the occurrence of CVA. Our analysis found that the recent era (i.e., June 2017), and intracorporeal continuous implants were protective. Mortality was higher in patients following a CVA diagnosis compared to those without a CVA diagnosis.CONCLUSIONS: CVA continues to be a problem in pediatric VAD support, though the overall percent is now <11%. Data from the most recent era are encouraging, but CVA is still significantly associated with mortality. Future efforts should focus on pre-implant and early support periods.

  View details for DOI 10.1016/j.healun.2021.03.008

  View details for PubMedID 33824064

• Berlin Heart EXCOR and ACTION post-approval surveillance study report. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Zafar, F., Conway, J., Bleiweis, M. S., Al-Aklabi, M., Ameduri, R., Barnes, A., Bearl, D. W., Buchholz, H., Church, S., Do, N. L., Duffy, V., Dykes, J. C., Eghtesady, P., Fisher, L., Friedland-Little, J., Fuller, S., Fynn-Thompson, F., George, K., Gossett, J. G., Griffiths, E. R., Griselli, M., Hawkins, B., Honjo, O., Jeewa, A., Joong, A., Kindel, S., Kouretas, P., Lorts, A., Machado, D., Maeda, K., Maurich, A., May, L. J., McConnell, P., Mehegan, M., Monge, M., Morales, D. L., Murray, J., Niebler, R. A., O'Connor, M., Peng, D. M., Phelps, C., Philip, J., Ploutz, M., Profsky, M., Reichhold, A., Rosenthal, D. N., Said, A. S., Schumacher, K. R., Si, M., Simpson, K. E., Sparks, J., Louis, J. S., Steiner, M. E., VanderPluym, C., Villa, C., ACTION Learning Network Investigators 2021

  Abstract

  BACKGROUND: The Berlin Heart EXCOR Pediatric (EXCOR) ventricular assist device (VAD) was introduced in North America nearly 2 decades ago. The EXCOR was approved under Humanitarian Device Exemption status in 2011 and received post-market approval (PMA) in 2017 from Food and Drug Administration. Since the initial approval, the field of pediatric mechanical circulatory support has changed, specifically with regard to available devices, anticoagulation strategies, and the types of patients supported. This report summarizes the outcomes of patients supported with EXCOR from the Advanced Cardiac Therapies Improving Outcomes Network (ACTION) registry. These data were part of the PMA surveillance study (PSS) required by the Food and Drug Administration.METHODS: ACTION is a learning collaborative of over 40 pediatric heart failure programs worldwide, which collects data for all VAD implantations as one of its initiatives. All patients in North America with EXCOR implants reported to ACTION from 2018 to 2020 (n = 72) who had met an outcome were included in the EXCOR PSS group. This was compared with a historical, previously reported Berlin Heart EXCOR study group (Berlin Heart study [BHS] group, n = 320, 2007‒2014).RESULTS: Patients in the PSS group were younger, were smaller in weight/body surface area, were more likely to have congenital heart disease, and were less likely to receive a bi-VAD than those in the BHS group. Patients in the PSS group were less likely to be in Interagency Registry for Mechanically Assisted Circulatory Support Profile 1 and were supported for a longer duration. The primary anticoagulation therapy for 92% of patients in the PSS group was bivalirudin. Success, defined as being transplanted, being weaned for recovery, or being alive on a device at 180 days after implantation, was 86% in the PSS group compared with 76% in the BHS group. Incidence of stroke was reduced by 44% and the frequency of pump exchange by 40% in the PSS group compared with those in the BHS group. Similarly, all other adverse events, including major bleeding, were reduced in the PSS group.CONCLUSIONS: The PSS data, collected through ACTION, highlight the improvement in outcomes for patients supported with EXCOR compared with the outcomes in a historical cohort. These findings may be the result of changes in patient care practices over time and collaborative learning.

  View details for DOI 10.1016/j.healun.2021.01.010

  View details for PubMedID 33579597

• Alternative to heart-lung transplantation for end-stage tetralogy of Fallot with major aortopulmonary collaterals: Simultaneous heart transplantation and pulmonary artery reconstruction. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Adamson, G. T., Profita, E. L., Quinonez, Z. A., McElhinney, D. B., Rosenthal, D. N., Ma, M. n. 2021

  View details for DOI 10.1016/j.healun.2021.02.003

  View details for PubMedID 33674153

• Adverse Events Associated with Cardiac Catheterization in Children Supported with Ventricular Assist Devices. ASAIO journal (American Society for Artificial Internal Organs : 1992) Power, A., Navaratnam, M., Murray, J. M., Peng, L. F., Rosenthal, D. N., Dykes, J. C., Yarlagadda, V. V., Maeda, K., Almond, C. S., Chen, S. 2021

  Abstract

  Children on ventricular assist device (VAD) support can present several unique challenges, including small patient size, univentricular or biventricular congenital heart disease (1V- or 2V-CHD) and need for biventricular VAD (BiVAD) support. While cardiac catheterization can provide valuable information, it is an invasive procedure with inherent risks. We sought to evaluate the safety of catheterization in pediatric patients on VAD support. We performed a retrospective review of patients on VAD support who underwent catheterization at Lucile Packard Children's Hospital between January 1, 2014 and September 1, 2019. Using definitions adapted from Pedimacs, adverse events (AEs) after catheterization were identified, including arrhythmia; major bleeding or acute kidney injury within 24 hours; respiratory failure persisting at 24 hours; and stroke, pericardial effusion, device malfunction, bacteremia or death within 7 days. AEs were categorized as related or unrelated to catheterization. Sixty procedures were performed on 39 patients. Underlying diagnoses were dilated cardiomyopathy (48%), 1V-CHD (35%), 2V-CHD (8%), and other (8%). Devices were implantable continuous flow (72%), paracorporeal pulsatile (18%) and paracorporeal continuous flow (10%). Catheterizations were performed on patients in the ICU (60%), on inotropic support (42%), with deteriorating clinical status (37%) and on BiVAD support (12%). There were 9 AEs possibly related to catheterization including 6 episodes of respiratory failure, 2 major bleeding events, and 1 procedural arrhythmia. AE occurrence was associated with ICU status (P = 0.01), BiVAD support (P = 0.04) and procedural indication to evaluate worsening clinical status (P = 0.04). Despite high medical acuity, catheterization can be performed with an acceptable AE profile in children on VAD support.

  View details for DOI 10.1097/MAT.0000000000001627

  View details for PubMedID 34967779

• Compassionate Deactivation of Pediatric Ventricular Assist Devices: A Review of 14 Cases. Journal of pain and symptom management Hollander, S. A., Kaufman, B. D., Bui, C. n., Gregori, B. n., Murray, J. M., Sacks, L. n., Ryan, K. R., Ma, M. n., Rosenthal, D. N., Char, D. n. 2021

  Abstract

  Compassionate deactivation (CD) of ventricular assist device (VAD) support is a recognized option for children when the burden of therapy outweighs the benefits.To describe the prevalence, indications, and outcomes of CD of children supported by VADs at the end of life.Review of cases of CD at our institution between 2011-2020. To distinguish CD from other situations where VAD support is discontinued, patients were excluded from the study if they died during resuscitation (including ECMO), experienced brain or circulatory death prior to deactivation, or experienced a non-survivable brain injury likely to result in imminent death regardless of VAD status.Of 24 deaths on VAD, 14 (58%) were CD. Median age was 5.7 (IQR 0.6, 11.6) years; 6 (43%) had congenital heart disease; 4 (29%) were on a device that can be used outside of the hospital. CD occurred after 40 (IQR: 26, 75) days of support; none while active transplant candidates. CD discussions were initiated by the caregiver in 6 (43%) cases, with the remainder initiated by a medical provider. Reasons for CD were multifactorial, including end-organ injury, infection, and stroke. CD occurred with endotracheal extubation and/or discontinuation of inotropes in 12 (86%) cases, and death occurred within 10 (IQR: 4, 23) minutes of CD.CD is the mode of death in more than half of our VAD non-survivors and is pursued for reasons primarily related to noncardiac events. Caregivers and providers both initiate CD discussions. Ventilatory and inotropic support is often withdrawn at time of CD with ensuing death.

  View details for DOI 10.1016/j.jpainsymman.2021.01.125

  View details for PubMedID 33910026

• Hemodynamic Predictors of Renal Function After Pediatric Left Ventricular Assist Device Implantation. ASAIO journal (American Society for Artificial Internal Organs : 1992) Chen, C. Y., Montez-Rath, M. E., May, L. J., Maeda, K., Hollander, S. A., Rosenthal, D. N., Krawczeski, C. D., Sutherland, S. M. 2021; 67 (12): 1335-1341

  Abstract

  Although renal function often improves after pediatric left ventricular assist device (LVAD) implantation, recovery is inconsistent. We aimed to identify hemodynamic parameters associated with improved renal function after pediatric LVAD placement. A single-center retrospective cohort study was conducted in patients less than 21 years who underwent LVAD placement between June 2004 and December 2015. The relationship between hemodynamic parameters and estimated glomerular filtration rate (eGFR) was assessed using univariate and multivariate modeling. Among 54 patients, higher preoperative central venous pressure (CVP) was associated with eGFR improvement after implantation (p = 0.012). However, 48 hours postimplantation, an increase in CVP from baseline was associated with eGFR decline over time (p = 0.01). In subgroup analysis, these associations were significant only for those with normal pre-ventricular assist device renal function (p = 0.026). In patients with preexisting renal dysfunction, higher absolute CVP values 48 and 72 hours after implantation predicted better renal outcome (p = 0.005). Our results illustrate a complex relationship between ventricular function, volume status, and renal function. Additionally, they highlight the challenge of using CVP to guide management of renal dysfunction in pediatric heart failure. Better methods for evaluating right heart function and volume status are needed to improve our understanding of how hemodynamics impact renal function in this population.

  View details for DOI 10.1097/MAT.0000000000001460

  View details for PubMedID 34860188

• Heart failure in children: Priorities and approach of the ACTION collaborative PROGRESS IN PEDIATRIC CARDIOLOGY Bansal, N., Burstein, D. S., Lorts, A., Smyth, L., Rosenthal, D. N., Peng, D. M. 2020; 59

  View details for DOI 10.1016/j.ppedcard.2020.101313

  View details for Web of Science ID 000600976600016

• Discharge and Readmissions After Ventricular Assist Device Placement in the US Pediatric Hospitals: A Collaboration in ACTION. ASAIO journal (American Society for Artificial Internal Organs : 1992) Bearl, D. W., Feingold, B., Lorts, A., Rosenthal, D., Zafar, F., Conway, J., Elias, B., Tunuguntla, H., Thurm, C., Amdani, S., Jaworski, N., Godown, J. 2020

  Abstract

  Discharging children on ventricular assist device (VAD) support offers advantages for quality of life. We sought to describe discharge and readmission frequency in children on VAD support. All VAD-implanted patients aged 10-21 years at Advanced Cardiac Therapies Improving Outcomes Network (ACTION) centers were identified from the Pediatric Health Information System database (2009-2018). Discharge frequency on VAD was calculated. Patients discharged on VAD were compared with those not discharged. Freedom from readmission was assessed using the Kaplan-Meier method. A total of 298 VAD-implanted patients from 25 centers were identified, of which 163 (54.7%) were discharged. Discharges increased over time (36.9% [2009-2012] vs. 59.7% [2013-2018], p = 0.001). Of 144 discharged patients with follow-up, 96 (66.7%) were readmitted for reasons other than transplantation. Heart failure was the most common reason for readmission (27.7%), followed by infection (25.8%) and hematologic concerns (16.8%). In-hospital mortality on readmission was uncommon (1.8%) and the median length of stay was 6 days (interquartile range 2-19 days). Discharge of children on VAD support has increased over time, although variability exists across centers. Readmissions are common with diverse indications; however, the risk of mortality is low. Further interventions, including collaboration in ACTION, are critical to increasing discharges and optimizing outpatient management.

  View details for DOI 10.1097/MAT.0000000000001307

  View details for PubMedID 33196481

• The Stanford acute heart failure symptom score for patients hospitalized with heart failure. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Almond, C. S., Chen, S., Dykes, J. C., Kwong, J., Burstein, D. S., Rosenthal, D. N., Kipps, A. K., Teuteberg, J., Murray, J. M., Kaufman, B. D., Hollander, S. A., Profita, E., Yarlagadda, V. Y., Sacks, L. D., Chen, C. 2020

  Abstract

  BACKGROUND: Currently, there are no simple tools to evaluate the acute heart failure (HF) symptom severity in children hospitalized with acute decompensated HF (ADHF). We sought to develop an inpatient HF score (HFS) that could be used as a clinical tool and for clinical trials.METHODS: Pediatric HF clinicians at Stanford reviewed the limitations of existing HFSs, which include lack of calibration to the inpatient setting, omission of gastrointestinal symptoms, need for multiple age-based tools, and scores that prioritize treatment intensity over patient symptoms. To address these, we developed an acute HFS corresponding to the 3 cardinal symptoms of HF: difficulty with breathing, feeding, and activity. The score was iteratively improved over a 3-year pilot phase until no further changes were made. The inter-rater reliability (IRR) across a range of providers was assessed using the final version. Peak HFSs were analyzed against mortality and length of stay (LOS) for all pediatric HF discharges between July and October 2019.RESULTS: The final HFS was a 4-point ordinal severity score for each of the 3 symptom domains (total score 0-12). Among clinicians who scored 12 inpatients with ADHF simultaneously, the intraclass correlation (ICC) was 0.94 (respiratory ICC = 0.89, feeding ICC = 0.85, and activity ICC = 0.80). Score trajectory reflected our clinical impression of patient response to HF therapies across a range of HF syndromes including 1- and 2-ventricle heart disease and reduced or preserved ejection fraction. Among the 28 patients hospitalized during a 3-months period (N = 28), quartiles of peak score were associated with LOS (p < 0.01) and in-hospital mortality (p < 0.01): HFS 0 to 3 (median LOS of 5 days and mortality of 0%), HFS 4 to 6 (median LOS of 18 days and mortality of 0%), HFS 5 to 9 (median LOS of 29 days and mortality of 23%), and HFS 10 to 12 (median LOS of 121 days and mortality of 50%).CONCLUSION: This simple acute HFS may be a useful tool to quantify and monitor day-to-day HF symptoms in children hospitalized with ADHF regardless of etiology or age group. The score has excellent IRR across provider levels and is associated with major hospital outcomes supporting its clinical validity. Validation in a multicenter cohort is warranted.

  View details for DOI 10.1016/j.healun.2020.08.002

  View details for PubMedID 33032871

• Donor heart selection during the COVID-19 pandemic: A case study JOURNAL OF HEART AND LUNG TRANSPLANTATION Chen, C., Chen, S. F., Hollander, S. A., Rosenthal, D., Maeda, K., Burgart, A., Almond, C. S., Chen, S. 2020; 39 (5): 497–98

  View details for Web of Science ID 000535430200015

• Updated definitions of adverse events for trials and registries of mechanical circulatory support: A consensus statement of the mechanical circulatory support academic research consortium. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Kormos, R. L., Antonides, C. F., Goldstein, D. J., Cowger, J. A., Starling, R. C., Kirklin, J. K., Rame, J. E., Rosenthal, D., Mooney, M. L., Caliskan, K., Messe, S. R., Teuteberg, J. J., Mohacsi, P., Slaughter, M. S., Potapov, E. V., Rao, V., Schima, H., Stehlik, J., Joseph, S., Koenig, S. C., Pagani, F. D. 2020

  View details for DOI 10.1016/j.healun.2020.03.010

  View details for PubMedID 32386998

• RAPID AORTIC HOMOGRAFT DEGENERATION AND VAD SUPPORT IN A NEONATE WITH SINGLE VENTRICLE HEART DISEASE Ahmed, H., Chen, S., Yarlagadda, V., Almond, C., Murray, J., Rosenthal, D. N., Ma, M., Dykes, J., Maeda, K. ELSEVIER SCIENCE INC. 2020: 2865

  View details for Web of Science ID 000522979102649

• RECENT TRENDS IN RIGHT HEART MECHANICAL SUPPORT STRATEGIES IN CHILDREN REQUIRING LVAD SUPPORT Dykes, J., Ahmed, H., Power, A., Murray, J., Chen, C., Chen, S., Rosenthal, D. N., Maeda, K., Almond, C. ELSEVIER SCIENCE INC. 2020: 1052

  View details for Web of Science ID 000522979101040

• Impact of Cardiac Resynchronization Therapy on Heart Transplant-Free Survival in Pediatric and Congenital Heart Disease Patients. Circulation. Arrhythmia and electrophysiology Chubb, H., Rosenthal, D. N., Almond, C. S., Ceresnak, S. R., Motonaga, K. S., Arunamata, A. A., Long, J., Trela, A. V., Hanisch, D., McElhinney, D. B., Dubin, A. M. 2020

  Abstract

  Background - Cardiac resynchronization therapy (CRT) studies in pediatric and/or congenital heart disease (CHD) patients have shown an improvement in ejection fraction and heart failure symptoms. However, a survival benefit of CRT in this population has not been established. This study aimed to evaluate the impact of CRT upon heart transplant-free survival in pediatric and CHD patients, using a propensity score-matched analysis. Methods - This single-center study compared CRT patients (implant date 2004-2017) and controls, matched by 1:1 propensity-score matching (PSM) using 21 comprehensive baseline indices for risk stratification. CRT patients were <21 years or had CHD; had systemic ventricular ejection fraction <;45%; symptomatic heart failure; and had significant electrical dyssynchrony, all prior to CRT implant. Controls were screened from non-selective imaging and ECG databases. Controls were retrospectively enrolled when they achieved the same inclusion criteria at an outpatient clinical encounter, within the same time period. Results - Of 133 patients who received CRT during the study period, 84 met all study inclusion criteria. 133 controls met all criteria at an outpatient encounter. Following PSM, 63 matched CRT-control pairs were identified with no significant difference between groups across all baseline indices. Heart transplant or death occurred in 12 (19%) PSM-CRT subjects and 37 (59%) PSM-controls with a median follow-up of 2.7 years (quartiles 0.8-6.1 years). CRT was associated with markedly reduced risk of heart transplant or death (hazard ratio 0.24 [95% CI 0.12-0.46], p<0.001). There was no CRT procedural mortality and one system infection at 54 months post-implant. Conclusions - In pediatric and CHD patients with symptomatic systolic heart failure and electrical dyssynchrony, CRT was associated with improved heart transplant-free survival.

  View details for DOI 10.1161/CIRCEP.119.007925

  View details for PubMedID 32202126

• Review of interactions between high-risk pediatric heart transplant recipients and marginal donors including utilization of risk score models. Pediatric transplantation Gossett, J. G., Amdani, S., Khulbey, S., Punnoose, A. R., Rosenthal, D. N., Smith, J., Smits, J., Dipchand, A. I., Kirk, R., Miera, O., Davies, R. R. 2020: e13665

  Abstract

  BACKGROUND: Donor organ acceptance practices vary among pediatric heart transplant professionals. We sought to understand what is known about the interactions between the "high-risk" recipient and the "marginal donor," and how donor risk scores can impact this discussion.METHODS: A systematic review of published literature on pediatric HTx was undertaken with the assistance of a medical librarian. Two authors independently assessed search results, and papers were reviewed for inclusion.RESULTS: We found that there are a large number of individual factors, and clusters of factors, that have been used to label individual recipients "high-risk" and individual donors "marginal." The terms "high-risk recipient" and "marginal donor" have been used broadly in the literature making it virtually impossible to make comparisons between publications. In general, the data support that patients who could be easily agreed to be "sicker recipients" are at more risk compared to those who are clearly "healthier," albeit still "sick enough" to need transplantation. Given this variability in the literature, we were unable to define how being a "high-risk" recipient interplays with accepting a "marginal donor." Existing risk scores are described, but none were felt to adequately predict outcomes from factors available at the time of offer acceptance.CONCLUSIONS: We could not determine what makes a donor "marginal," a recipient "high-risk," or how these factors interplay within the specific recipient-donor pair to determine outcomes. Until there are better risk scores predicting outcomes at the time of organ acceptance, programs should continue to evaluate each organ and recipient individually.

  View details for DOI 10.1111/petr.13665

  View details for PubMedID 32198806

• Evolution of Single Ventricular Assist Device Support for the Failing Bi-directional Glenn Patient. The Annals of thoracic surgery Maeda, K., Nasirov, T., Yarlagadda, V., Hollander, S. A., Navaratnam, M., Rosenthal, D. N., Dykes, J. C., Kaufman, B. D., Almond, C. S., Reinhartz, O., Murray, J., Chen, S. 2020

  Abstract

  BACKGROUND: Given poor outcomes, strategies to improve ventricular assist device (VAD) for single ventricle (SV) patients with bi-directional Glenn (BDG) palliation is needed.METHODS: Retrospective review of our institutional experience with VAD support for BDG patients from April 2011 to January 2019. Surgical strategies, complications and causes of death are described. Survival to transplant for various strategies are compared.RESULTS: Seven patients with BDG (weights 5.6-28.8 kg, ages 7 months - 11 years) underwent VAD implantation. Three patients received Berlin Heart EXCOR, 2 received Heartware HVADs and 2 patients received paracorporeal continuous flow devices. Four patients underwent ventricular inflow cannulation, and 3 underwent atrial inflow cannulation. At the time of VAD implant, the BDG was left intact in 3 patients, taken down in 3 patients, and created de novo in 1 patient. Over a total of 420 VAD support days, 2 patients survived to heart transplant; one with Heartware ventricular cannulation and intact BDG (after 174 days), and another with Berlin Heart atrial cannulation and BDG take-down (after 72 days). There were 3 deaths within 2 weeks of VAD implant (2 due to respiratory failure, 1 due to infection) and 2 deaths after 30 days due to strokes.CONCLUSIONS: The surgical strategy and postoperative management of VAD with BDG are still evolving. Successful support can be achieved with 1) both pulsatile and continuous flow pumps, 2) atrial or ventricular cannulation, and 3) with or without BDG take-down. Surgical strategy should be determined by individual patient anatomy, physiology and condition.

  View details for DOI 10.1016/j.athoracsur.2019.12.088

  View details for PubMedID 32151575

• Early experience with the HeartMate 3 continuous-flow ventricular assist device in pediatric patients and patients with congenital heart disease: A multicenter registry analysis. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation O'Connor, M. J., Lorts, A., Davies, R. R., Fynn-Thompson, F., Joong, A., Maeda, K., Mascio, C. E., McConnell, P. I., Monge, M. C., Nandi, D., Peng, D. M., Rosenthal, D. N., Si, M., Sutcliffe, D. L., VanderPluym, C. J., Viegas, M., Zafar, F., Zinn, M., Morales, D. L. 2020

  Abstract

  BACKGROUND: The HeartMate 3 ventricular assist device (VAD) is a newer centrifugal continuous-flow VAD used for bridge-to-transplant and destination therapy in adults. However, there is limited experience regarding its use in children and adults with complex congenital heart disease (CHD).METHODS: The Advanced Cardiac Therapies Improving Outcomes Network (ACTION) is a multicenter learning network comprised of pediatric hospitals implanting VADs in children and adults with complex CHD. We examined the outcomes of patients undergoing HeartMate 3 implantation at an ACTION center between December 2017 and September 2019.RESULTS: The HeartMate 3 was implanted in 35 patients at 9 ACTION centers, with a median age of 15.7 (8.8-47.3) years, median weight of 65.7 (19.1-114.1) kg, and median body surface area (BSA) of 1.74 (0.78-2.36) m2. Of the cohort, 14 patients (40%) weighed <60 kg. Diagnoses included dilated cardiomyopathy (63%), dilated cardiomyopathy in neuromuscular disease (20%), and CHD (17%). Of those with CHD, most had a Fontan circulation. With a median 78 days of follow-up, there was 1 death on device (97% survival); 20 out of 35 (57%) underwent transplantation with no post-transplantation mortality. There were no episodes of stroke or pump thrombosis.CONCLUSIONS: Use of the HeartMate 3 in ACTION centers was associated with a low incidence of mortality and adverse events. Patients as small as 19 kg (BSA 0.78 m2) were successfully implanted and supported, indicating that this device may be appropriate for older children and small adults.

  View details for DOI 10.1016/j.healun.2020.02.007

  View details for PubMedID 32111350

• A Predictive Model for Intracardiac Pressures in Patients Free from Rejection or Allograft Vasculopathy After Pediatric Heart Transplantation. Transplantation Mills, M. F., Long, J., Qin, F., Collins, R. T., Rosenthal, D. N., Almond, C. S., Hollander, S. A. 2020

  Abstract

  BACKGROUND: Despite the routine use of hemodynamic assessment in pediatric heart transplant (HT) patients, expected intracardiac pressure measurements in patients free of significant complications are incompletely described. A better understanding of the range of intracardiac pressures in these HT patients is important for the clinical interpretation of these indices and consequent management of patients.METHODS: We conducted a retrospective chart review of pediatric HT recipients who had undergone HT between January 2010 and December 2015 at Lucile Packard Children's Hospital. We analyzed intracardiac pressures measured in the first 12 months after HT. We excluded those with rejection, graft coronary artery disease, mechanical support, or hemodialysis. We used a longitudinal General Additive Model (GAM) with bootstrapping technique to generate age and donor-recipient size specific curves to characterize filling pressures through 1-year post-HT.RESULTS: Pressure measurements from the right atrium (RA), pulmonary artery (PA), and pulmonary capillary wedge (PCWP) were obtained in 85 patients during a total of 829 catheterizations. All pressure measurements were elevated in the immediate post-HT period and decreased to a stable level by post-HT day 90. Pressure measurements were not affected by age group, donor-recipient size differences, or ischemic time.CONCLUSION: Intracardiac pressures are elevated in the early post-HT period and decrease to levels typical of the native heart by 90 days. Age, donor-to-recipient size differences, and ischemic time do not contribute to differences in expected intracardiac pressures in the first year post-HT.

  View details for DOI 10.1097/TP.0000000000003166

  View details for PubMedID 32044891

• Bridge to Transplant with Ventricular Assist Device Support in Pediatric Patients with Single Ventricle Heart Disease ASAIO JOURNAL Chen, S., Rosenthal, D. N., Murray, J., Dykes, J. C., Almond, C. S., Yarlagadda, V. V., Wright, G., Navaratnam, M., Reinhartz, O., Maeda, K. 2020; 66 (2): 205–11

  View details for DOI 10.1097/MAT.0000000000000983

  View details for Web of Science ID 000530106400023

• A coordinated approach to improving pediatric heart transplant waitlist outcomes: A summary of the ACTION November 2019 waitlist outcomes committee meeting. Pediatric transplantation Hollander, S. A., Nandi, D. n., Bansal, N. n., Godown, J. n., Zafar, F. n., Rosenthal, D. N., Lorts, A. n., Jeewa, A. n. 2020: e13862

  Abstract

  The number of children needing heart transplantation continues to rise. Although improvements in heart failure therapy, particularly durable mechanical support, have reduced waitlist mortality, the number of children who die while waiting for a suitable donor organ remains unacceptably high. Roughly, 13% of children and 25% of infants on the heart transplant waitlist will not survive to transplantation. With this in mind, the Advanced Cardiac Therapies Improving Outcomes Collaborative Learning Network (ACTION), through its Waitlist Outcomes Committee, convened a 2-day symposium in Ann Arbor, Michigan, from 2-3 November 2019, to better understand the factors that contribute to pediatric heart transplant waitlist mortality and to focus future efforts on improving the organ allocation rates for children needing heart transplantation. Using improvement science methodology, the heart failure-transplant trajectory was broken down into six key steps, after which modes of failure and opportunities for improvement at each step were discussed. As a result, several projects aimed at reducing waitlist mortality were initiated.

  View details for DOI 10.1111/petr.13862

  View details for PubMedID 32985785

• ISHLT consensus statement on donor organ acceptability and management in pediatric heart transplantation. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Kirk, R. n., Dipchand, A. I., Davies, R. R., Miera, O. n., Chapman, G. n., Conway, J. n., Denfield, S. n., Gossett, J. G., Johnson, J. n., McCulloch, M. n., Schweiger, M. n., Zimpfer, D. n., Ablonczy, L. n., Adachi, I. n., Albert, D. n., Alexander, P. n., Amdani, S. n., Amodeo, A. n., Azeka, E. n., Ballweg, J. n., Beasley, G. n., Böhmer, J. n., Butler, A. n., Camino, M. n., Castro, J. n., Chen, S. n., Chrisant, M. n., Christen, U. n., Danziger-Isakov, L. n., Das, B. n., Everitt, M. n., Feingold, B. n., Fenton, M. n., Garcia-Guereta, L. n., Godown, J. n., Gupta, D. n., Irving, C. n., Joong, A. n., Kemna, M. n., Khulbey, S. K., Kindel, S. n., Knecht, K. n., Lal, A. K., Lin, K. n., Lord, K. n., Möller, T. n., Nandi, D. n., Niesse, O. n., Peng, D. M., Pérez-Blanco, A. n., Punnoose, A. n., Reinhardt, Z. n., Rosenthal, D. n., Scales, A. n., Scheel, J. n., Shih, R. n., Smith, J. n., Smits, J. n., Thul, J. n., Weintraub, R. n., Zangwill, S. n., Zuckerman, W. A. 2020

  Abstract

  The number of potential pediatric heart transplant recipients continues to exceed the number of donors, and consequently the waitlist mortality remains significant. Despite this, around 40% of all donated organs are not used and are discarded. This document (62 authors from 53 institutions in 17 countries) evaluates factors responsible for discarding donor hearts and makes recommendations regarding donor heart acceptance. The aim of this statement is to ensure that no usable donor heart is discarded, waitlist mortality is reduced, and post-transplant survival is not adversely impacted.

  View details for DOI 10.1016/j.healun.2020.01.1345

  View details for PubMedID 32088108

• Treprostinil improves hemodynamics and symptoms in children with mild pulmonary hypertension awaiting heart transplantation. Pediatric transplantation Hollander, S. A., Ogawa, M. T., Hopper, R. K., Liu, E. n., Chen, S. n., Rosenthal, D. N., Feinstein, J. A. 2020: e13742

  Abstract

  Treprostinil, a prostacyclin analog, is a safe and effective therapy for children with PAH; however, the use of this agent in children with mild PVR elevations related to HF, including those with SV congenital heart disease awaiting HT, is understudied. We describe the hemodynamic and symptomatic changes in pediatric patients awaiting HT treated with treprostinil.Single-center retrospective review of all patients was listed for HT who received treprostinil during the listing period. Changes in hemodynamic and functional indices between the baseline catheterization (prior to drug initiation), and prior to HT, and patient outcomes were analyzed.Among 16/17 (94%) who survived to HT, 8 (50%) were female, and 10 (63%) had SV physiology. The median age at drug initiation was 9 (IQR: 1, 14) years. The median duration of therapy prior to HT was 253 (IQR: 148, 504) days. Treprostinil significantly decreased PVR (3.8 vs 3.1 WU, P = .03), while mLA or mPCW pressure did not change (11 vs 13 mm Hg, P = .9). HF symptoms improved in 9/15 (60%) patients without VAD support prior to drug initiation, including 4/10 (40%) who did not receive a VAD any point while awaiting HT.Treprostinil may be used safely in patients with mild PAH awaiting HT, including those with SV disease. PVR falls without substantial increases in mLA/mPCW pressure. HF symptoms improve in some patients.

  View details for DOI 10.1111/petr.13742

  View details for PubMedID 32428328

• The Creation of a Pediatric Health Care Learning Network: The ACTION Quality Improvement Collaborative. ASAIO journal (American Society for Artificial Internal Organs : 1992) Lorts, A. n., Smyth, L. n., Gajarski, R. J., VanderPluym, C. J., Mehegan, M. n., Villa, C. R., Murray, J. M., Niebler, R. A., Almond, C. S., Thrush, P. n., O'Connor, M. J., Conway, J. n., Sutcliffe, D. L., Lantz, J. E., Zafar, F. n., Morales, D. L., Peng, D. M., Rosenthal, D. N. 2020; 66 (4): 441–46

  Abstract

  Improving the outcomes of pediatric patients with congenital heart disease with end-stage heart failure depends on the collaboration of all stakeholders; this includes providers, patients and families, and industry representatives. Because of the rarity of this condition and the heterogeneity of heart failure etiologies that occur at pediatric centers, learnings must be shared between institutions and all disciplines to move the field forward. To foster collaboration, excel discovery, and bring data to the bedside, a new, collaborative quality improvement science network-ACTION (Advanced Cardiac Therapies Improving Outcomes Network)-was developed to meet the needs of the field. Existing gaps in care and the methods of improvement that will be used are described, along with the mission and vision, utility of real-world data for regulatory purposes, and the organizational structure of ACTION is described.

  View details for DOI 10.1097/MAT.0000000000001133

  View details for PubMedID 32224822

• Establishing Baseline Metrics of Heart Failure Medication Use in Children: A Collaborative Effort from the ACTION Network. Pediatric cardiology Stidham, J. n., Feingold, B. n., Almond, C. S., Burstein, D. S., Krack, P. n., Price, J. F., Schumacher, K. R., Spinner, J. A., Rosenthal, D. N., Lorts, A. n., Godown, J. n. 2020

  Abstract

  Heart failure metrics specific to the pediatric population are required to successfully implement quality improvement initiatives in children with heart failure. Medication use at the time of discharge following admission for decompensated heart failure has been identified as a potential quality metric in this population. This study aimed to report medication use at discharge in the current era for children admitted with acute decompensated heart failure. All patients < 21 years of age with an index admission (1/1/2011-12/31/2019) for acute heart failure and a coexisting diagnosis of cardiomyopathy were identified from the Pediatric Health Information System. Medication use patterns were described and compared across age groups and centers. A total of 2288 patients were identified for inclusion. An angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker (ACEi/ARB) was prescribed in 1479 (64.6%), beta blocker in 1132 (49.5%), and mineralocorticoid receptor antagonist (MRA) in 864 (37.8%) patients at discharge. The use of ACEi/ARB at discharge has decreased over time (64.6% vs. 69.6%, p = 0.001) and the use of beta blockers has increased (49.5% vs. 36.8%, p < 0.001) compared to a historical cohort (2001-2010). There is considerable variability in medication use across centers with an overall increase in beta blocker and decrease in ACEi/ARB use over time. Collaborative efforts are needed to standardize care and define quality metrics to identify best practices in the management of pediatric heart failure.

  View details for DOI 10.1007/s00246-020-02485-x

  View details for PubMedID 33044586

• Healthy Hearts via Live Video Conferencing: An Exercise and Diet Intervention in Pediatric Heart Transplant Patients JAHA Chen, A. C., Ramirez, F., Rosenthal, D. N., Couch, S. C., Berry, S., Stauffer, K. J., Brabender, J., McDonald, N., Lee, D., Barkoff, L., Nourse, S. E., Kazmucha, J., Wang, C. J., Olson, I., Tierney, E. S. 2020

  View details for DOI 10.1161/JAHA.119.013816

• Healthy Hearts via Live Videoconferencing: An Exercise and Diet Intervention in Pediatric Heart Transplant Recipients. Journal of the American Heart Association Chen, A. C., Ramirez, F. D., Rosenthal, D. N., Couch, S. C., Berry, S. n., Stauffer, K. J., Brabender, J. n., McDonald, N. n., Lee, D. n., Barkoff, L. n., Nourse, S. E., Kazmucha, J. n., Wang, C. J., Olson, I. n., Selamet Tierney, E. S. 2020; 9 (3): e013816

  Abstract

  Background Pediatric heart transplant recipients have high-risk cardiovascular profiles that can affect their long-term outcomes; however, promoting exercise and healthy diet has not been a major focus in the field. The objective of this study was to test the feasibility and impact of a supervised exercise and diet intervention delivered via live videoconferencing in this population. Methods and Results Patients 8 to 19 years of age at least 1 year post heart transplantation were enrolled. The 12- to 16-week intervention phase included live video-supervised exercise (×3/week) and nutrition (×1/week) sessions. The 12- to 16-week maintenance phase included ×1/week live video-supervised exercise and nutrition sessions and ×2/week self-directed exercise sessions. Cardiac, vascular, nutritional, and functional health indices were obtained at baseline, after intervention, and after maintenance. Fourteen patients (median age, 15.2; interquartile range, 14.3-16.7 years) at a median of 3.3 (interquartile range, 1.5-9.7) years after heart transplant completed the intervention. Patients attended 89.6±11% of exercise and 88.4±10% of nutrition sessions during the intervention and 93.4±11% of exercise and 92.3±11% of nutrition sessions during maintenance. After intervention, body mass index percentile (median, -27%; P=0.02), endothelial function (median, +0.29; P=0.04), maximum oxygen consumption (median, +2 mL/kg per minute; P=0.002). Functional Movement Screening total score (median, +2.5; P=0.002) and daily consumption of saturated fat (median, -6 g; P=0.02) improved significantly. After maintenance, improvements in maximum oxygen consumption (median, +3.2 mL/kg per minute; P=0.02) and Functional Movement Screening total score (median, +5; P=0.002) were sustained. Conclusions In pediatric heart transplant recipients, a live video-supervised exercise and diet intervention is feasible. Our results demonstrate excellent adherence with significant improvements in cardiovascular and functional health. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02519946.

  View details for DOI 10.1161/JAHA.119.013816

  View details for PubMedID 31973598

• Part VII: Behavioral economics-A framework for donor organ decision-making in pediatric heart transplantation. Pediatric transplantation Butler, A. n., Chapman, G. n., Johnson, J. N., Amodeo, A. n., Böhmer, J. n., Camino, M. n., Davies, R. R., Dipchand, A. I., Godown, J. n., Miera, O. n., Pérez-Blanco, A. n., Rosenthal, D. N., Zangwill, S. n., Kirk, R. n. 2020: e13655

  Abstract

  The high discard rate of pediatric donor hearts presents a major challenge for children awaiting heart transplantation. Recent literature identifies several factors that contribute to the disparities in pediatric donor heart usage, including regulatory oversight, the absence of guidelines on pediatric donor heart acceptance, and variation among transplant programs. However, a likely additional contributor to this issue are the behavioral factors influencing transplant team decisions in donor offer scenarios, a topic that has not yet been studied in detail. Behavioral economics and decision psychology provide an excellent foundation for investigating decision-making in the pediatric transplant setting, offering key insights into the behavior of transplant professionals. We conducted a systematic review of published literature in pediatric heart transplant related to behavioral economics and the psychology of decision-making. In this review, we draw on paradigms from these two domains in order to examine how existing aspects of the transplant environment, including regulatory oversight, programmatic variation, and allocation systems, may precipitate potential biases surrounding donor offer decisions. Recognizing how human decision behavior influences donor acceptance is a first step toward improving utilization of potentially viable pediatric donor hearts.

  View details for DOI 10.1111/petr.13655

  View details for PubMedID 31985140

• Donor heart selection during the COVID-19 pandemic: A case study. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Chen, C. Y., Chen, S. F., Hollander, S. A., Rosenthal, D. n., Maeda, K. n., Burgart, A. n., Almond, C. S., Chen, S. n. 2020; 39 (5): 497–98

  View details for DOI 10.1016/j.healun.2020.03.018

  View details for PubMedID 32362395

• The Use of Clevidipine for Hypertension in Pediatric Patients Receiving Mechanical Circulatory Support. Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies Wu, M. n., Ryan, K. R., Rosenthal, D. N., Jahadi, O. n., Moss, J. n., Kwiatkowski, D. M. 2020

  Abstract

  Limited data exist regarding the management of hypertension in pediatric patients on mechanical circulatory support. Hypertension is a known risk factor for stroke and low cardiac output in patients requiring mechanical circulatory support and a narrow therapeutic window of blood pressure is often targeted. Traditional short-acting infusions to treat hypertension, such as sodium nitroprusside, may lead to accumulation of toxic metabolites in patients with renal dysfunction. Our primary objective was to describe use of clevidipine, a continuous short-acting calcium channel blocking medication, for blood pressure control in pediatric patients on mechanical circulatory support.Single-center retrospective cohort study.A 26-bed quaternary cardiovascular ICU in a university-based pediatric hospital in California.Mechanical circulatory support patients admitted to cardiovascular ICU who received clevidipine infusions between October 1, 2016, and March 31, 2019.Clevidipine infusion.Data from a cohort of 38 patients who received a total of 45 clevidipine infusions were reviewed. The cohort had a median age of 2.7 years and included neonates. No patient had record of hypotensive events, code events, or received low-dose epinephrine or code-dosed epinephrine related to a clevidipine infusion. Median duration of clevidipine infusion was 4.1 days (1.5-9.2 d). Eleven patients transitioned from clevidipine to enteral antihypertensive agents, and 26 clevidipine infusions were administered as a single agent without sodium nitroprusside. Seven patients were switched from sodium nitroprusside to clevidipine to avoid cyanide toxicity, a majority of whom had elevated serum creatinine.In this pediatric cardiac cohort, clevidipine infusions were effective at hypertension management and were not associated with hypotensive or code events. This report details the largest cohort and longest duration of clevidipine administration within a pediatric population and did not demonstrate hypotensive events, even among neonatal populations. Clevidipine may be a reasonable cost-effective alternative antihypertensive medication compared to traditional short-acting agents.

  View details for DOI 10.1097/PCC.0000000000002562

  View details for PubMedID 32796396

• Growth stunting in single ventricle patients after heart transplantation. Pediatric transplantation Power, A., Schultz, L., Dennis, K., Rizzuto, S., Hollander, A. M., Rosenthal, D. N., Almond, C. S., Hollander, S. A. 2019: e13634

  Abstract

  BACKGROUND: Malnutrition is common among children with single ventricle (SV) congenital heart disease (CHD). The impact of heart transplantation (HT) on nutritional status in SV patients is understudied. Our aim was to evaluate anthropometric changes in SV patients after HT, compared with those transplanted for cardiomyopathy (CM).METHODS: We performed a single-center retrospective chart review of SV and CM patients<18years who underwent HT from January 01, 2010 to December 05, 2017. Wasting and stunting were defined as z-scores for weight-for-age or height-for-age ≤-2, respectively. Changes in these indices between HT and 3years post-HT were analyzed.RESULTS: Of 86 eligible patients, 28 (33%) had SV CHD and 58 (67%) had CM. Data were available at 3years post-HT for 57 patients. At transplant, wasting was equally present in SV versus CM patients (7/28, 25% vs. 9/58, 16%, P=.22), which remained true at 3years post-HT (2/16, 13% vs. 3/41, 7%, P=.61). At transplant, stunting was more common in SV than CM patients (17/28, 61% vs. 8/58, 14%, P<.001). At 3years post-HT, 6 of 16 (38%) SV patients and 3 of 41 (7%) CM patients remained stunted (P=.01). Among all patients, wasting decreased from transplant to end-point (19% vs. 9%, P=.05), but stunting did not (29% vs. 16%, P=.2), such that wasting and stunting were associated at transplant (P<.001) but not at end-point (P=.17).CONCLUSIONS: Longitudinal growth remains impaired for several years after HT in SV patients, even when weight gain is achieved, suggesting that some factors contributing to growth impairment persist despite resolution of SV physiology.

  View details for DOI 10.1111/petr.13634

  View details for PubMedID 31845499

• Palliative Care Engagement for Pediatric Ventricular Assist Device Patients: A Single-Center Experience. ASAIO journal (American Society for Artificial Internal Organs : 1992) Knoll, C., Kaufman, B., Chen, S., Murray, J., Cohen, H., Sourkes, B. M., Rosenthal, D. N., Hollander, S. A. 2019

  Abstract

  Outcomes in pediatric patients with ventricular assist devices (VADs) for advanced heart failure (HF) are improving, but the risk of associated morbidity and mortality remains substantial. Few data exist on the involvement of pediatric palliative care (PPC) in this high-risk patient population. We aimed to characterize the extent of palliative care involvement in the care of patients requiring VAD placement at our institution. Single-center retrospective chart review analyzing all VAD patients at a large pediatric center over a 4 year period. Timing and extent of palliative care subspecialty involvement were analyzed. Between January 2014 and December 2017, 55 HF patients underwent VAD implantation at our institution. Pediatric palliative care utilization steadily increased over consecutive years (2014: <10% of patients, 2015: 20% of patients, 2016: 50% of patients, and 2017: 65% of patients) and occurred in 42% (n = 23) of all patients. Of these, 57% (n = 13) occurred before VAD placement while 43% (n = 10) occurred after implantation. Patients who died during their VAD implant hospitalization (24%, n = 13) were nearly twice as likely to have PPC involvement (62%) as those who reached transplant (38%). Of those who died, patients who had PPC involved in their care were more likely to limit resuscitation efforts before their death. Four patients had advanced directives in place before VAD implant, of which three had PPC consultation before device placement. Three families (5%) refused PPC involvement when offered. Pediatric palliative care utilization is increasing in VAD patients at our institution. Early PPC involvement occurred in the majority of patients and appears to lead to more frequent discussion of goals-of-care and advanced directives.

  View details for DOI 10.1097/MAT.0000000000001092

  View details for PubMedID 31789655

• Collaboration and new data in ACTION: a learning health care system to improve pediatric heart failure and ventricular assist device outcomes TRANSLATIONAL PEDIATRICS Peng, D. M., Rosenthal, D. N., Zafar, F., Smyth, L., VanderPluym, C. J., Lorts, A. 2019; 8 (4): 349–55

  View details for DOI 10.21037/tp.2019.07.12

  View details for Web of Science ID 000493139000012

• Marked Practice Variation in Antithrombotic Care with the Berlin Heart EXCOR Pediatric Ventricular Assist Device ASAIO JOURNAL May, L. J., Lorts, A., VanderPluym, C., Conway, J., Massicotte, M., Millar, M. M., Steiner, M. E., Rosenthal, D. N. 2019; 65 (7): 731–37

  View details for DOI 10.1097/MAT.0000000000000878

  View details for Web of Science ID 000483807100025

• Evaluation and Management of the Child and Adult With Fontan Circulation: A Scientific Statement From the American Heart Association CIRCULATION Rychik, J., Atz, A. M., Celermajer, D. S., Deal, B. J., Gatzoulis, M. A., Gewillig, M. H., Hsia, T., Hsu, D. T., Kovacs, A. H., McCrindle, B. W., Newburger, J. W., Pike, N. A., Rodefeld, M., Rosenthal, D. N., Schumacher, K. R., Marino, B. S., Stout, K., Veldtman, G., Younoszai, A. K., d'Udekem, Y., Amer Heart Assoc Council Cardiovas, Council Cardiovasc Stroke Nursing 2019; 140 (6): E234–E284

  Abstract

  It has been 50 years since Francis Fontan pioneered the operation that today bears his name. Initially designed for patients with tricuspid atresia, this procedure is now offered for a vast array of congenital cardiac lesions when a circulation with 2 ventricles cannot be achieved. As a result of technical advances and improvements in patient selection and perioperative management, survival has steadily increased, and it is estimated that patients operated on today may hope for a 30-year survival of >80%. Up to 70 000 patients may be alive worldwide today with Fontan circulation, and this population is expected to double in the next 20 years. In the absence of a subpulmonary ventricle, Fontan circulation is characterized by chronically elevated systemic venous pressures and decreased cardiac output. The addition of this acquired abnormal circulation to innate abnormalities associated with single-ventricle congenital heart disease exposes these patients to a variety of complications. Circulatory failure, ventricular dysfunction, atrioventricular valve regurgitation, arrhythmia, protein-losing enteropathy, and plastic bronchitis are potential complications of the Fontan circulation. Abnormalities in body composition, bone structure, and growth have been detected. Liver fibrosis and renal dysfunction are common and may progress over time. Cognitive, neuropsychological, and behavioral deficits are highly prevalent. As a testimony to the success of the current strategy of care, the proportion of adults with Fontan circulation is increasing. Healthcare providers are ill-prepared to tackle these challenges, as well as specific needs such as contraception and pregnancy in female patients. The role of therapies such as cardiovascular drugs to prevent and treat complications, heart transplantation, and mechanical circulatory support remains undetermined. There is a clear need for consensus on how best to follow up patients with Fontan circulation and to treat their complications. This American Heart Association statement summarizes the current state of knowledge on the Fontan circulation and its consequences. A proposed surveillance testing toolkit provides recommendations for a range of acceptable approaches to follow-up care for the patient with Fontan circulation. Gaps in knowledge and areas for future focus of investigation are highlighted, with the objective of laying the groundwork for creating a normal quality and duration of life for these unique individuals.

  View details for DOI 10.1161/CIR.0000000000000696

  View details for Web of Science ID 000478747900006

  View details for PubMedID 31256636

• Usefulness of anti-platelet therapy testing in children supported with a ventricular assist device JOURNAL OF HEART AND LUNG TRANSPLANTATION May, L. J., Liu, X., Tesoro, T., Yang, J., Lo, C., Chen, S., Murray, J., Rosenthal, D. N., Massicotte, P., Michelson, A. D., Almond, C. S. 2019; 38 (7): 781–83

  View details for DOI 10.1016/j.healun.2019.03.012

  View details for Web of Science ID 000473321800013

• Short-term outcomes of en bloc combined heart and liver transplantation in the failing Fontan CLINICAL TRANSPLANTATION Vaikunth, S. S., Concepcion, W., Daugherty, T., Fowler, M., Lutchman, G., Maeda, K., Rosenthal, D. N., Teuteberg, J., Woo, Y., Lui, G. K. 2019; 33 (6)

  View details for DOI 10.1111/ctr.13540

  View details for Web of Science ID 000473087200014

• A Quality Bundle to Support High-Risk Pediatric Ventricular Assist Device Implantation. Pediatric cardiology Knoll, C., Chen, S., Murray, J. M., Dykes, J. C., Yarlagadda, V. V., Rosenthal, D. N., Almond, C. S., Maeda, K., Shin, A. Y. 2019

  Abstract

  Pediatric ventricular assist device (VAD) implantation outcomes are increasingly promising for children with dilated cardiomyopathy and advanced decompensated heart failure (ADHF). VAD placement in patients with clinical features such as complex congenital cardiac anatomy, small body size, or major comorbidities remains problematic. These comorbidities have been traditionally prohibitive for VAD consideration leaving these children as a treatment-orphaned population. Here we describe the quality bundle surrounding these patients with ADHF considered high risk for VAD implantation at our institution. Over a 7-year period, a quality bundle aimed at the peri-operative care for children with high-risk features undergoing VAD implantation was incrementally implemented at a tertiary children's hospital. Patients were considered high risk if they were neonates (<30days), had single-ventricle physiology, non-dilated cardiomyopathy, biventricular dysfunction, or significant comorbidities. The quality improvement bundle evolved to include (1) structured team-based peri-operative evaluation, (2) weekly VAD rounds addressing post-operative device performance, (3) standardized anticoagulation strategies, and (4) a multidisciplinary system for management challenges. These measures aimed to improve communication, standardize management, allow for ongoing process improvement, and incorporate principles of a high-reliability organization. Between January 2010 and December 2017, 98 patients underwent VAD implantation, 48 (49%) of which had high-risk comorbidities and a resultant cohort survival-to-transplant rate of 65%. We report on the evolution of a quality improvement program to expand the scope of VAD implantation to patients with high-risk clinical profiles. This quality bundle can serve as a template for future large-scale collaborations to improve outcomes in these treatment-orphaned subgroups.

  View details for DOI 10.1007/s00246-019-02123-1

  View details for PubMedID 31087144

• Compassionate deactivation of ventricular assist devices in children: A survey of pediatric ventricular assist device clinicians' perspectives and practices PEDIATRIC TRANSPLANTATION Kaufman, B. D., Hollander, S. A., Zhang, Y., Chen, S., Bernstein, D., Rosenthal, D. N., Almond, C. S., Murray, J. M., Burgart, A. M., Cohen, H. J., Kirkpatrick, J. N., Blume, E. D. 2019; 23 (3)

  View details for DOI 10.1111/petr.13359

  View details for Web of Science ID 000476931300005

• Growth stunting persists in single ventricle patients after heart transplantation even when nutritional weight gain is achieved Power, A., Schultz, L., Dennis, K., Rizzuto, S., Hollander, A. M., Rosenthal, D. N., Almond, C. S., Hollander, S. A. WILEY. 2019

  View details for Web of Science ID 000485482200098

• Usefulness of anti-platelet therapy testing in children supported with a ventricular assist device. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation May, L. J., Liu, X., Tesoro, T., Yang, J., Lo, C., Chen, S., Murray, J., Rosenthal, D. N., Michelson, A. D., Almond, C. S. 2019

  View details for PubMedID 31006520

• Third Annual Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs) Report: Preimplant Characteristics and Outcomes ANNALS OF THORACIC SURGERY Morales, D. S., Rossano, J. W., VanderPluym, C., Lorts, A., Cantor, R., St Louis, J. D., Koeh, D., Sutcliffe, D. L., Adachi, I., Kirklin, J. K., Rosenthal, D. N., Blume, E. D., Pedimacs Investigators 2019; 107 (4): 993–1004

  View details for DOI 10.1016/j.athoracsur.2019.01.038

  View details for Web of Science ID 000462308000024

• Long-term outcomes after transplantation after support with a pulsatile pediatric ventricular assist device JOURNAL OF HEART AND LUNG TRANSPLANTATION Jeewa, A., Imamura, M., Canter, C., Niebler, R. A., VanderPluym, C., Rosenthal, D. N., Kirklin, J. K., Cantor, R. S., Tresler, M., McMullan, D., Morell, V. O., Turrentine, M., Ameduri, R., Nguyen, K., Kanter, K., Conway, J., Gajarski, R., Fraser, C. D. 2019; 38 (4): 449-455

  Abstract

  There has been increasing use of durable ventricular assist devices (VAD) in children as a bridge to transplantation (BTT). The Berlin Heart investigational device exemption (IDE) trial was the first pediatric VAD trial to demonstrate excellent survival outcomes as a BTT.Our aim was to compare the expanded post-transplant outcomes for children enrolled in the Berlin Heart IDE trial to a matched Pediatric Heart Transplant Study (PHTS) cohort not requiring mechanical circulatory support (MCS).University Hospitals.This was a retrospective review of linked PHTS and Berlin Heart IDE databases for pediatric (≤18 years) recipients transplanted from 2007-2011. Subjects with <5 years of follow up were excluded. VAD supported patients were matched 1:2 to non-VAD supported controls from the PHTS database.Among 109 Berlin Heart IDE study enrollees, 83 were merged with the PHTS database and matched to 166 non-MCS supported patients. There was no difference in diagnosis, status at listing, and age between groups with the expected difference in inotrope use in the non-MCS supported patients. Compared to their matched cohort, there was no statistical difference in 5-year patient survival between VAD and non-VAD patients (81% vs 88%; p = 0.09) nor was there a difference in freedom from rejection or infection.This data suggests that children supported with a Berlin Heart VAD had similar survival, infection and rejection rates compared to those not requiring MCS support. Continued surveillance of the Berlin Heart IDE trial population post heart transplantation is warranted.

  View details for DOI 10.1016/j.healun.2018.10.005

  View details for Web of Science ID 000465437900017

  View details for PubMedID 30466802

• Short-Term Outcomes of en bloc Combined Heart and Liver Transplantation in the Failing Fontan. Clinical transplantation Vaikunth, S. S., Concepcion, W., Daugherty, T., Fowler, M., Lutchman, G., Maeda, K., Rosenthal, D. N., Teuteberg, J., Joseph Woo, Y., Lui, G. K. 2019: e13540

  Abstract

  Patients with failing Fontan physiology and liver cirrhosis are being considered for combined heart and liver transplantation. We performed a retrospective review of our experience with en bloc combined heart and liver transplantation in Fontan patients > 10 years old from 2006-18 per Institutional Review Board approval. Six females and 3 males (median age 20.7, range 14.2-41.3 years) underwent en bloc combined heart and liver transplantation. Indications for heart transplant included ventricular dysfunction, atrioventricular valve regurgitation, arrhythmia and/or lymphatic abnormalities. Indication for liver transplant included portal hypertension and cirrhosis. Median Fontan/single ventricular end diastolic pressure was 18/12 mm Hg, respectively. Median Model for End-Stage Liver Disease excluding International Normalized Ratio score was 10 (7-26), eight patients had a Varices, Ascites, Splenomegaly, Thrombocytopenia score of>2, and all patients had cirrhosis. Median cardiopulmonary bypass and donor ischemic times were 262 (178-307) and 287 (227-396) minutes, respectively. Median intensive care and hospital stay were 19 (5-96) and 29 (13-197) days, respectively. Survival was 100% and rejection was 0% at 30 days and 1 year post-transplant. En bloc combined heart and liver transplantation is an acceptable treatment in the failing Fontan patient with liver cirrhosis. This article is protected by copyright. All rights reserved.

  View details for PubMedID 30891780

• Bridge to Transplant with Ventricular Assist Device Support in Pediatric Patients with Single Ventricle Heart Disease. ASAIO journal (American Society for Artificial Internal Organs : 1992) Chen, S., Rosenthal, D. N., Murray, J., Dykes, J. C., Almond, C. S., Yarlagadda, V. V., Wright, G., Navaratnam, M., Reinhartz, O., Maeda, K. 2019

  Abstract

  Ventricular assist device (VAD) support for children with single ventricle (SV) heart disease remains challenging. We performed a single-center retrospective review of SV patients on VAD support and examined survival to transplant using the Kaplan-Meier method. Patients transplanted were compared with those who died on support. Between 2009 and 2017, there were 14 SV patients with 1,112 patient-days of VAD support. Stages of palliation included pre-Glenn (n = 5), Glenn (n = 5), and Fontan (n = 4). Eight patients (57%) were successfully bridged to transplant at a median 107 days. Deaths occurred early (n = 6, median 16 days) and in smaller patients (10.1 vs. 28.3 kg, P = 0.04). All Fontan patients survived to transplant, whereas only 20% of Glenn patients survived to transplant. Adverse events occurred in 79% (n = 11). Five patients met hospital discharge criteria, with two patients (one pre-Glenn, one Glenn) discharged and transplanted after 219 and 174 days of VAD support. All transplanted patients were discharged at a median 21 days posttransplant. SV patients in various stages of palliation can be successfully bridged to transplant with VAD support. With use of intracorporeal continuous-flow devices, longer-term support and hospital discharge are possible.

  View details for PubMedID 30864969

• Parental Acquisition of Echocardiographic Images in Pediatric Heart Transplant Patients Using a Handheld Device: A Pilot Telehealth Study JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY Dykes, J. C., Kipps, A. K., Chen, A., Nourse, S., Rosenthal, D. N., Tierney, E. 2019; 32 (3): 404–11

  View details for DOI 10.1016/j.echo.2018.10.007

  View details for Web of Science ID 000459902800012

• Impact of ventricular assist device implantation on the nutritional status of children awaiting heart transplantation PEDIATRIC TRANSPLANTATION Hollander, S. A., Schultz, L. M., Dennis, K., Hollander, A. M., Rizzuto, S., Murray, J. M., Rosenthal, D. N., Almond, C. S. 2019; 23 (2)

  View details for DOI 10.1111/petr.13351

  View details for Web of Science ID 000459211900015

• Heart transplantation in two adolescents with Danon disease PEDIATRIC TRANSPLANTATION Oren, D., Chau, P., Manning, M., Kwong, J., Kaufman, B. D., Maeda, K., Rosenthal, D. N., Hollander, S. A. 2019; 23 (2)

  View details for DOI 10.1111/petr.13335

  View details for Web of Science ID 000459211900020

• Third Annual Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs) Report: Pre-Implant Characteristics and Outcomes. The Annals of thoracic surgery Morales, D. L., Rossano, J. W., VanderPluym, C., Lorts, A., Cantor, R., St Louis, J., Koeh, D., Sutcliffe, D. L., Adachi, I., Kirklin, J. K., Rosenthal, D. N., Blume, E. D., Pedimacs investigators 2019

  Abstract

  BACKGROUND: The influence of ventricular assist device (VAD) use in the care of children with end-stage heart failure is growing rapidly through increasing numbers, new devices, expanding indications, and improving outcomes. Pedimacs, a NIH-sponsored U.S. database, provides a platform to understand this emerging population.METHODS: Between 9/19/12-12/31/17, 30 hospitals implanted 508 devices in 423 patients under 19 years-of-age. This past year was one of evolution for the Database as its management was transitioned to the Society of Thoracic Surgery, therefore data from institutions not under contract by August 1st 2018 was not included in this report.RESULTS: Of the 423 patients, the diagnosis was cardiomyopathy in 261 (62%), myocarditis in 48 (11%), other in 28 (7%) and congenital heart disease in 86 (20%) with 52 of these patients having single ventricle physiology. The two most common support strategies included LVAD-342 (81%) and BiVAD-64 (15%). Positive Outcome (alive on device or bridge to transplantation/recovery) was 80% at 6-months (overall mortality of 20%). The patient cohort for implantable continuous flow (IC) pumps (n=197) [age at implant 13.4+/-3.8yrs., 19% INTERMACS profile-1, 21% intubated at implant and 12% with CHD] was significantly different from the paracorporeal continuous flow (PC) pump cohort (n=79) [age 3.9+/-5.2yrs, 49% INTERMACS profile-1, 86% intubated at implant, and 38% with CHD] and the paracorporeal pulsatile (PP) pump cohort (n=121) [age 3.3+/-3.9yrs, 41% INTERMACS profile-1, 77 % intubated at implant, and 21% with CHD]. Consistent with their cohort composition, device type positive outcomes at 6 months were PC-63%, PP-77% and IC-92%. Using Parametric Hazard Modeling, an early hazard for death was associated with INTERMACS profile-1, BiVAD, percutaneous devices, PC devices, small volume institutions, low age and low weight, while a constant hazard was associated with intubation and liver dysfunction at time of implant.CONCLUSIONS: IC VADs are the most common VAD type placed in children. The positive outcomes for the IC VADs are >90% at 6 months, which may represent our field's maturation in both patient selection and timing of implantation. Currently the PP/PC devices are limited to supporting our most challenging patients, those less than 20kg, and those with CHD. The introduction of new devices and our communities' commitment to shared learning and improvement will lead to more pediatric lives saved by VAD support, and will also focus on improving the quality of life of children supported with VADs.

  View details for PubMedID 30817920

• Compassionate deactivation of ventricular assist devices in children: A survey of pediatric ventricular assist device clinicians' perspectives and practices. Pediatric transplantation Kaufman, B. D., Hollander, S. A., Zhang, Y., Chen, S., Bernstein, D., Rosenthal, D. N., Almond, C. S., Murray, J. M., Burgart, A. M., Cohen, H. J., Kirkpatrick, J. N., Blume, E. D. 2019: e13359

  Abstract

  OBJECTIVES: This study's objective was to investigate compassionate ventricular assist device deactivation (VADdeact) in children from the perspective of the pediatric heart failure provider.BACKGROUND: Pediatric VAD use is a standard therapy for advanced heart failure. Serious adverse events may affect relative benefit of continued support, leading to consideration of VADdeact. Perspectives and practices regarding VADdeact have been studied in adults but not in children.METHODS: A web-based anonymous survey of clinicians for pediatric VAD patients (<18years) was sent to list-serves for the ISHLT Pediatric Council, the International Consortium of Circulatory Assist Clinicians Pediatric Taskforce, and the Pediatric Cardiac Intensivist Society.RESULTS: A total of 106 respondents met inclusion criteria of caring for pediatric VAD patients. Annual VAD volume per clinician ranged from <4 (33%) to >9 (20%). Seventy percent of respondents had performed VADdeact of a child. Response varied to VADdeact requests by parent or patient and was influenced by professional degree and region of practice. Except for the scenario of intractable suffering, no consensus on VADdeact appropriateness was reported. Age of child thought capable of making informed requests for VADdeact varied by subspecialty. The majority of respondents (62%) do not feel fully informed of relevant legal issues; 84% reported that professional society supported guidelines for VADdeact in children had utility.CONCLUSION: There is limited consensus regarding indications for VADdeact in children reported by pediatric VAD provider survey respondents. Knowledge gaps related to legal issues are evident; therefore, professional guidelines and educational resources related to pediatric VADdeact are needed.

  View details for PubMedID 30734422

• Healthy hearts in pediatric heart transplant patients with an exercise and diet intervention via live video conferencing-Design and rationale PEDIATRIC TRANSPLANTATION Chen, A. C., Rosenthal, D. N., Couch, S. C., Berry, S., Stauffer, K. J., Brabender, J., McDonald, N., Lee, D., Barkoff, L., Nourse, S. E., Kazmucha, J., Wang, C., Olson, I., Tierney, E. 2019; 23 (1)

  View details for DOI 10.1111/petr.13316

  View details for Web of Science ID 000457579500010

• Long-term surveillance biopsy: Is it necessary after pediatric heart transplant? PEDIATRIC TRANSPLANTATION Peng, D. M., Ding, V. Y., Hollander, S. A., Khalapyan, T., Dykes, J. C., Rosenthal, D. N., Almond, C. S., Sakarovitch, C., Desai, M., McElhinney, D. B. 2019; 23 (1)

  View details for DOI 10.1111/petr.13330

  View details for Web of Science ID 000457579500023

• Impact of ventricular assist device implantation on the nutritional status of children awaiting heart transplantation. Pediatric transplantation Hollander, S. A., Schultz, L. M., Dennis, K., Hollander, A. M., Rizzuto, S., Murray, J. M., Rosenthal, D. N., Almond, C. S. 2019: e13351

  Abstract

  BACKGROUND: Malnutrition is common in pediatric heart failure and is associated with mortality. The effect of VAD support on malnutrition in children is unknown. We sought to compare the prevalence and severity of malnutrition at HT in children on VAD support vs OMT to inform decisions regarding support strategies.METHODS: Retrospective chart review involving all patients <18years who underwent HT at Stanford between 1/1/2011 and 3/1/2018. Malnutrition diagnosis and severity were defined by ASPEN guidelines using the lowest age-adjusted z-score for weight (WAZ), height (HAZ), and BMI (BMIZ) when the patient was euvolemic. Changes in z-scores from baseline to HT and across groups were analyzed.RESULTS: A total of 104 patients (52 in each group) were included. Among all patients, WAZ (-0.9 vs 0.3, P<0.001) and BMIZ (0 vs 0.6, P<0.001) improved while HAZ (-0.9 vs -0.9, P=0.4) did not. Compared to children on OMT, children on VAD experienced greater increases in WAZ (0.8 vs 0.3, P<0.001) and BMIZ (0.7 vs 0.2, P<0.003) at HT. The prevalence of moderate-to-severe malnutrition decreased in VAD patients (40% to 19%, P<0.001) and increased in OMT patients (37% to 46%, P<0.001), leading to a lower prevalence of moderate-to-severe malnutrition at HT (19% vs 46%, P=0.003).CONCLUSIONS: Malnutrition is common in pediatric HT candidates. Compared to children on OMT, children on VAD support had greater improvement in nutritional status while awaiting HT, and a lower prevalence of malnutrition at HT.

  View details for PubMedID 30628144

• Pediatric waitlist and heart transplant outcomes in patients with syndromic anomalies. Pediatric transplantation Wilkens, S. J., Priest, J. n., Kaufman, B. D., Barkoff, L. n., Rosenthal, D. N., Hollander, S. A. 2019: e13643

  Abstract

  We sought to determine whether the presence of a systemic SA with potential complicating factors affects waitlist and post-HT outcomes in pediatric patients.This is a single-center retrospective review of pediatric patients listed for HT between January 1, 2009, and July 1, 2018. Patients were selected based on the presence of any underlying syndromes, which included chromosomal anomalies, skeletal myopathies, connective tissue disorders, mitochondrial disease,and other systemic disorders. Waitlist and post-HT outcomes were compared to those without SA.A total of 243 patients were listed for HT, of which 21 (9%) patients had associated SA. Of those, 16 (76%) survived to transplant, 3 (14%) died while on the waitlist, 1 (5%) improved and was removed from the waitlist, and 1 (5%) patient is currently listed. Waitlist survival was not different between those with/without an associated syndrome (P = 1.0). Among those who survived to HT, there was no difference in listing days (70 vs 90, P = .8), survival to hospital discharge [14 (93%) vs 150 (95%), P = .6], post-HT intubation days (2 vs 2 days, P = .6), or post-HT hospital length of stay (18 vs 18 days, P = .8). Overall survival during the study period post-HT was not different between groups (P = .8).A SA was present in 9% of pediatric patients wait-listed for HT, but was not associated with an increased waitlist mortality or post-HT hospital morbidity or long-term survival. For several anomalies, HT is safe and feasible.

  View details for DOI 10.1111/petr.13643

  View details for PubMedID 31891211

• Parental Acquisition of Echocardiographic Images in Pediatric Heart Transplant Patients Using a Handheld Device: A Pilot Telehealth Study. Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography Dykes, J. C., Kipps, A. K., Chen, A., Nourse, S., Rosenthal, D. N., Selamet Tierney, E. S. 2018

  Abstract

  BACKGROUND: Pediatric heart transplant patients (PedHtx) require frequent monitoring by echocardiography (echo); however, they often live far from hospitals with pediatric echo services, resulting in urgent/emergent transfers to specialized institutions. Our primary objective was to evaluate the feasibility of parental acquisition of echo images to assess left ventricular (LV) systolic function in PedHtx using a handheld echo device. Secondary objectives included retesting for skill maintenance and in patients with decreased LV systolic function.METHODS: During a routine clinic visit, parents received 1-hour training with a handheld echo device to acquire images in parasternal short-axis and apical views. Parents recorded images on their children at training completion and 24hours later at home. An independent echocardiographer assessed clinic, training, and home echos for LV systolic function.RESULTS: Fifteen PedHtx (mean age of 12.6years of age; range, 4.1-16.7) were enrolled. All parents could acquire home images adequate for qualitative assessment of LV systolic function with no discrepancy compared with clinical echos. LV ejection fraction (LVEF) could be calculated (5/6 area-length method) in 86% of training and 43% of home echos with <10% difference in LVEF measurements between home and clinic echos. Five parents repeated home echos >12months later. All home echos were adequate for qualitative assessment of LV systolic function (LVEF measurable in two). Additionally, five heart failure patients with decreased LV systolic function (mean age of 8.6years; range 1.9-15.1) were enrolled. All home echos were adequate for qualitative assessment of LV systolic function (LVEF measurable in one).CONCLUSIONS: Our results suggest that parental home echo acquisition using a handheld echo device is feasible and adequate for qualitative assessment of LV systolic function in PedHtx. However, quantitative assessment of LV systolic function, especially in patients with dysfunction, and retention of the skill set without additional training are suboptimal.

  View details for PubMedID 30598367

• Heart transplantation in two adolescents with Danon disease. Pediatric transplantation Oren, D., Chau, P., Manning, M., Kwong, J., Kaufman, B. D., Maeda, K., Rosenthal, D. N., Hollander, S. A. 2018: e13335

  Abstract

  Danon disease (DD) is an X-linked dominant disorder caused by a mutation in the lysosomal-associated membrane protein-2 (LAMP-2) gene coding for the LAMP-2 protein. We report two cases of successful heart transplantation (HT) in adolescent brothers with DD, including one who was bridged to HT for 34days with a HeartWare left ventricular assist device. In both patients, the post-transplant course was complicated by profound skeletal muscle weakness that resolved with corticosteroid withdrawal. These cases highlight that both HT and ventricular assist device support are feasible in patients with DD. Corticosteroid use may exacerbate skeletal myopathy, and therefore, steroid minimization may be warranted whenever possible.

  View details for PubMedID 30536852

• Long-term surveillance biopsy: Is it necessary after pediatric heart transplant? Pediatric transplantation Peng, D. M., Ding, V. Y., Hollander, S. A., Khalapyan, T., Dykes, J. C., Rosenthal, D. N., Almond, C. S., Sakarovitch, C., Desai, M., McElhinney, D. B. 2018: e13330

  Abstract

  Due to limited and conflicting data in pediatric patients, long-term routine surveillance endomyocardial biopsy (RSB) in pediatric heart transplant (HT) remains controversial. We sought to characterize the rate of positive RSB and determine factors associated with RSB-detected rejection. Records of patients transplanted at a single institution from 1995 to 2015 with >2year of post-HT biopsy data were reviewed for RSB-detected rejections occurring >2year post-HT. We illustrated the trajectory of significant rejections (ISHLT Grade ≥3A/2R) among total RSB performed over time and used multivariable logistic regression to model the association between time and risk of rejection. We estimated Kaplan-Meier freedom from rejection rates by patient characteristics and used the log-rank test to assess differences in rejection probabilities. We identified the best-fitting Cox proportional hazards regression model. In 140 patients, 86% did not have any episodes of significant RSB-detected rejection >2year post-HT. The overall empirical rate of RSB-detected rejection >2year post-HT was 2.9/100 patient-years. The percentage of rejection among 815 RSB was 2.6% and remained stable over time. Years since transplant remained unassociated with rejection risk after adjusting for patient characteristics (OR=0.98; 95% CI 0.78-1.23; P=0.86). Older age at HT was the only factor that remained significantly associated with risk of RSB-detected rejection under multivariable Cox analysis (P=0.008). Most pediatric patients did not have RSB-detected rejection beyond 2years post-HT, and the majority of those who did were older at time of HT. Indiscriminate long-term RSB in pediatric heart transplant should be reconsidered given the low rate of detected rejection.

  View details for PubMedID 30506612

• Characterization of Pediatric Patients With Syndromic Anomalies Listed for Heart Transplant: Waitlist and Post-Heart Transplant Outcomes Wilkens, S. J., Priest, J. R., Kaufman, B., Barkoff, L. M., Rosenthal, D. N., Hollander, S. A. LIPPINCOTT WILLIAMS & WILKINS. 2018

  View details for Web of Science ID 000528619407085

• Growth Stunting Persists in Single Ventricle Patients After Heart Transplantation Even When Nutritional Weight Gain is Achieved Power, A., Schultz, L., Dennis, K., Rizzuto, S., Hollander, A. M., Rosenthal, D. N., Almond, C. S., Hollander, S. D. LIPPINCOTT WILLIAMS & WILKINS. 2018

  View details for Web of Science ID 000528619402199

• Live-Video-Supervised Exercise and Diet Intervention in Pediatric Heart Transplant Patients Chen, A., Rosenthal, D., Ramirez, F., Stauffer, K., Berry, S., Brabender, J., McDonald, N., Lee, D., Barkoff, L., Nourse, S., Kazmucha, J., Wang, C., Olson, I., Couch, S., Tierney, S. LIPPINCOTT WILLIAMS & WILKINS. 2018

  View details for Web of Science ID 000528619406319

• Healthy hearts in pediatric heart transplant patients with an exercise and diet intervention via live video conferencing-Design and rationale. Pediatric transplantation Chen, A. C., Rosenthal, D. N., Couch, S. C., Berry, S., Stauffer, K. J., Brabender, J., McDonald, N., Lee, D., Barkoff, L., Nourse, S. E., Kazmucha, J., Wang, C. J., Olson, I., Selamet Tierney, E. S. 2018: e13316

  Abstract

  BACKGROUND: Pediatric heart transplant (PedHtx) patients have increased cardiovascular risk profiles that affect their long-term outcomes and quality of life. We designed a 12- to 16-week diet and exercise intervention delivered via live video conferencing to improve cardiovascular health. Our methodology and baseline assessment of the first 13 enrolled patients are reported.METHODS: Inclusion criteria are as follows: (a) 8-19years old; (b) heart transplant >12months; (c) ability to fast overnight; (d) cardiac clearance by cardiologist; and (e) presence of an adult at home during exercise sessions for patients <14years old. Exclusion criteria are as follows: (a) acute illness; (b) latex allergy; (c) transplant rejection <3months ago; and (d) multi-organ transplantation. The intervention consists of one diet and three exercise sessions weekly via live video conferencing. Study visits are conducted at baseline, intervention completion, and end of maintenance period.RESULTS: A total of 13 participants (15.2 [2.3]years) have been enrolled. Median percent-predicted VO2 max was 56.8 [20.7]% (10 patients <70%). Ten patients had abnormal endothelial function (reactive hyperemia index <1.9; 1.4 [0.325]) and 11 patients had stiff arteries (pulse wave velocity ≧5.5m/s for 15-19years, ≧4.5m/s for 8-14years; 5.6 [0.7]m/s). Patients had suboptimal diets (saturated fat: 22.7 [23.8]g/d, sodium: 2771 [1557]mg/d) and were sedentary at a median of 67.5 [13.8]% of their time.CONCLUSIONS: Baseline assessment confirms that PedHtx patients have abnormal cardiac, vascular, and functional health indices, poor dietary habits, and are sedentary. These results support the rationale to test the feasibility and impact of a non-pharmacologic lifestyle intervention in this patient population.

  View details for PubMedID 30393915

• An Alternative Approach by HeartWare Ventricular Assist Device in Hypertrophic Cardiomyopathy ANNALS OF THORACIC SURGERY Maeda, K., Nasirov, T., Rosenthal, D. N., Dykes, J. C. 2018; 106 (5): E231–E232

  View details for DOI 10.1016/j.athoracsur.2018.04.065

  View details for Web of Science ID 000448027400003

• Successful use of a ventricular assist device in a neonate with hypoplastic left heart syndrome with right ventricular dysfunction JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Maeda, K., Yarlagadda, V. V., Rosenthal, D. N., Almond, C. S. 2018; 156 (4): E171–E173

  View details for DOI 10.1016/j.jtcvs.2018.05.043

  View details for Web of Science ID 000445221200009

• Marked Practice Variation in Antithrombotic Care with the Berlin Heart EXCOR Pediatric Ventricular Assist Device. ASAIO journal (American Society for Artificial Internal Organs : 1992) May, L. J., Lorts, A., VanderPluym, C., Conway, J., Massicotte, M. P., Millar, M. M., Steiner, M. E., Rosenthal, D. N. 2018

  Abstract

  Management of antithrombotic therapy (ATT) for pediatric ventricular assist devices is challenging, and the Berlin EXCOR remains the only FDA-approved option. Among those on the EXCOR, 28% have neurologic complications and major bleeding occurs in 50%. The Edmonton Protocol was developed to guide ATT, but the adverse event rate remains high, leading most centers to make modifications. The objective of this study is to characterize antithrombotic practice variation among North American pediatric ventricular assist device programs, in order to guide future research. In this descriptive cross-sectional study, a survey assessing antithrombotic (AT) practices was distributed by Berlin Heart Inc. to centers that implanted ≥1 EXCOR between January 2012 and January 2016. Practices were compared at high- versus low-volume centers. High volume was defined as ≥14 implants in this period. Seventeen of 38 centers (44.7%) participated; 4 were high volume. At half of all centers (9/17), ≤2 clinicians managed all AT decisions. Although 47.1% (8/17) followed the protocol "extremely/very closely," only 5.9% (1/17) felt it to be "very effective." Most centers (10/15; 66.7%) deviated in ≥2 protocol aspects. Over half modified either recommended antiplatelet agents (5/15) or anticoagulants (4/15). Adjunct medication use was highly variable. Most (11/17; 64.7%) deviated from protocol in either timing or type of AT lab monitoring. Despite widespread use of Thromboelastography (TEG)/Platelet Mapping (PM), concerns of inaccuracy were common. Most high-volume centers (3/4; 75%) abandoned TEG/PM as a primary tool. These practice variation analyses have identified areas in ATT that are amenable to care standardization and further research. Systematic study of optimal AT medication dosing and monitoring is needed.

  View details for PubMedID 30234505

• Pathological antibody-mediated rejection in pediatric heart transplant recipients: Immunologic risk factors, hemodynamic significance, and outcomes PEDIATRIC TRANSPLANTATION Hollander, S. A., Peng, D. M., Mills, M., Berry, G. J., Fedrigo, M., McElhinney, D. B., Almond, C. S., Rosenthal, D. N. 2018; 22 (5)

  View details for DOI 10.1111/petr.13197

  View details for Web of Science ID 000438730000006

• Ventricular Assist Device Support as a Bridge to Transplantation in Pediatric Patients JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Dipchand, A. I., Kirk, R., Naftel, D. C., Pruitt, E., Blume, E. D., Morrow, R., Rosenthal, D., Auerbach, S., Richmond, M. E., Kirklin, J. K., Pediat Heart Transplant Study Inve 2018; 72 (4): 402–15

  Abstract

  Pediatric ventricular assist device (VAD) use has evolved dramatically over the last 2 decades.This study sought to describe the evolution of VAD support to heart transplantation (HTx) in children in a large international multicenter cohort.Using data from the Pediatric Heart Transplant Study, comparisons were made between children (<18 years) supported to HTx (January 1, 1993 to December 31, 2015) with VAD or extracorporeal membrane oxygenation (ECMO) to VAD support.Of 7,135 listed patients, 5,145 underwent HTx; 995 (19.3%) were supported by a VAD (113 with congenital heart disease [CHD]). Patients with a VAD as their first device (n = 821) were older, larger, and more likely to have cardiomyopathy (80%) than patients transitioned from ECMO to VAD (n = 164). In the VAD-only cohort, 79% underwent HTx and 14% died, compared with 69% and 24% in the ECMO-to-VAD cohort, respectively. Patients with cardiomyopathy achieved HTx 84% of the time, with a 9% waitlist mortality rate compared with 55% and 36%, respectively, for CHD. Among VAD-treated patients, 79% were age >10 years in the earliest era, a percentage decreasing to 34% more recently, though neonates still represent <1%. Overall, survival at 2 and 20 years showed no difference between VAD and no support (2 years: 75% vs. 80%; 20 years: 55% vs. 54%). Post-HTx outcomes were better for durable versus temporary VADs (p < 0.01) and for continuous versus pulsatile VADs (p < 0.01) from 2005 onward; timing of VAD had no impact on post-HTx survival (p = 0.65).For one-quarter of a century, major advances have occurred in mechanical support technology for children, thereby expanding the capability to bridge to HTx without compromising post-HTx outcomes. Significant challenges remain, especially for neonates and patients with CHD, but ongoing innovation portends improved methods of support during the next decade.

  View details for PubMedID 30025576

• Combined En-Bloc Heart Liver Transplantation in Children with Congenital Heart Disease Complicated by Cardiac Cirrhosis Conlon, S., Maeda, K., Reinhartz, O., Hollander, S., Rosenthal, D., Gallo, A., Concepcion, W., Esquivel, C., Bonham, A. LIPPINCOTT WILLIAMS & WILKINS. 2018: S295

  View details for Web of Science ID 000444541200473

• Successful use of a ventricular assist device in a neonate with hypoplastic left heart syndrome with right ventricular dysfunction. The Journal of thoracic and cardiovascular surgery Maeda, K., Yarlagadda, V. V., Rosenthal, D. N., Almond, C. S. 2018

  View details for PubMedID 29970231

• Characteristics of deposits and pump exchange in the Berlin Heart EXCOR ventricular assist device: Experience with 67 cases PEDIATRIC TRANSPLANTATION Maeda, K., Almond, C., Hollander, S. A., Rosenthal, D. N., Kaufman, B., Gowen, M. M., Murray, J., Shuttleworth, P., Reinhartz, O. 2018; 22 (4)

  View details for DOI 10.1111/petr.13181

  View details for Web of Science ID 000433590800012

• An Alternative Approach by HVAD Ventricular Assist Device in Hypertrophic Cardiomyopathy. The Annals of thoracic surgery Maeda, K., Nasirov, T., Rosenthal, D. N., Dykes, J. C. 2018

  Abstract

  Hypertrophic cardiomyopathy is known to be difficult to support by left ventricular assist device due to the small ventricular cavity and inadequate drainage. Therefore, instead of cannulating on the left ventricular apex, Heartware HVAD ventricular device was connected to the left atrium through right atrium onto atrial septum using ringed Goretex interposition graft. The patient has been discharged home after VAD implant and underwent successful heart transplant after 111 days of support without any complications including any thromboembolic events. This new trans-atrial left atrial cannulation technique can be an alternative approach for VAD cannulation in hypertrophic cardiomyopathy. It can be safely performed with the Heartware HVAD.

  View details for PubMedID 29807009

• Pathological antibody-mediated rejection in pediatric heart transplant recipients: Immunologic risk factors, hemodynamic significance, and outcomes. Pediatric transplantation Hollander, S. A., Peng, D. M., Mills, M., Berry, G. J., Fedrigo, M., McElhinney, D. B., Almond, C. S., Rosenthal, D. N. 2018: e13197

  Abstract

  Biopsy-diagnosed pAMR has been observed in over half of pediatric HT recipients within 6years of transplantation. We report the incidence and outcomes of pAMR at our center. All endomyocardial biopsies for all HT recipients transplanted between 2010 and 2015 were reviewed and classified using contemporary ISHLT guidelines. Graft dysfunction was defined as a qualitative decrement in systolic function by echocardiogram or an increase of ≥3mmHg in atrial filling pressure by direct measurement. Among 96 patients, pAMR2 occurred in 7 (7%) over a median follow-up period of 3.1years, while no cases of pAMR3 occurred. A history of CHD, DSA at transplant, and elevated filling pressures were associated with pAMR2. Five-sixths (83%) of patients developed new C1q+ DSA at the time of pAMR diagnosis. There was a trend toward reduced survival, with 43% of patients dying within 2.3years of pAMR diagnosis.

  View details for PubMedID 29729067

• Characteristics of deposits and pump exchange in the Berlin Heart EXCOR ventricular assist device: Experience with 67 cases. Pediatric transplantation Maeda, K., Almond, C., Hollander, S. A., Rosenthal, D. N., Kaufman, B., Gowen, M. M., Murray, J., Shuttleworth, P., Reinhartz, O. 2018: e13181

  Abstract

  Pump exchanges are frequently required in the Berlin Heart EXCOR VAD. We intended to describe the characteristics of pump deposits in a larger patient series and evaluate if changes in our exchange procedure over time have led to increased complications. We reviewed all EXCOR pump exchanges in our institution from July 2004 to October 2014. We gathered data on size and location of pump deposits and exchange procedures. EXCOR devices were implanted in 38 children. Support was LVAD only in 22, BiVAD in 13, and SVAD in 3 cases. Sixty-seven pumps were exchanged. The incidence of pump exchanges per month was higher for smaller pumps and for RVADs vs LVADs. Indications were visible pump deposit in 55, stroke without visible deposit in 5, incorporation of membrane oxygenator in 3, pump size change in 2, and sepsis in 1 case, respectively. Deposits were located in the outflow valve in 73%, inflow valve in 22%, pump body in 3%, and outflow cannula in 3%. EXCOR pumps are predominantly exchanged for deposits, which are most frequently located in the outflow valves. The procedure is now carried out without sedation at the bedside. No major complications were observed during exchanges.

  View details for PubMedID 29635728

• OUTCOME OF EN-BLOC COMBINED HEART AND LIVER TRANSPLANTATION IN THE ADULT FAILING FONTAN Vaikunth, S., Concepcion, W., Daugherty, T., Fowler, M., Lutchman, G., Maeda, K., Rosenthal, D., Teuteberg, J., Woo, Y., Lui, G. K. ELSEVIER SCIENCE INC. 2018: 539

  View details for DOI 10.1016/S0735-1097(18)31080-5

  View details for Web of Science ID 000429659701389

• QUALITY OF INR CONTROL IN A CENTRALIZED PHARMACIST-LED PEDIATRIC CARDIOLOGY WARFARIN MANAGEMENT PROGRAM Lee, J., Murray, J., Wilkens, S., Zhang, Y., Nishioka, F., Rosenthal, D., Roth, S., Murphy, D., McElhinney, D., Almond, C. ELSEVIER SCIENCE INC. 2018: 609

  View details for DOI 10.1016/S0735-1097(18)31150-1

  View details for Web of Science ID 000429659701459

• Ventricular Assist Devices for Neonates and Infants. Seminars in thoracic and cardiovascular surgery. Pediatric cardiac surgery annual Maeda, K., Rosenthal, D. N., Reinhartz, O. 2018; 21: 9–14

  Abstract

  Heart transplant waitlist survival in pediatric patients has been substantially improved since the introduction of pediatric-specific ventricular assist device. In neonates and infants, however, the waitlist mortality remains very high. The only long-term device currently approved for use in the United States is the Berlin Heart EXCOR, but this device has several important limitations because of the paracorporeal, pulsatile nature of the underlying technology. We reviewed Stanford ventricular assist experience on patients less than 1 year old since 2004. It shows overall 1-, 3-, and 5-year survival were 68%, 62%, and 49%, respectively. There are statistically significant differences in survival among cardiomyopathy group, end-stage congenital heart disease group and single ventricle group. In order to improve outcomes in this extremely high risk group, modifications were made to anticoagulation protocols, cannulation strategy in hypertrophic cardiomyopathy patients, and preferential use of continuous flow pumps in a single ventricle patients. The long-waited PumpKIN trial testing the Jarvik 2015 is about to start with the first human implant.

  View details for PubMedID 29425530

• The Pediatric Heart Failure Workforce: An International, Multicenter Survey PEDIATRIC CARDIOLOGY Auerbach, S. R., Everitt, M. D., Butts, R. J., Rosenthal, D. N., Law, Y. M. 2018; 39 (2): 307–14

  Abstract

  Our objective was to understand the scope of pediatric heart failure (HF) and the current staffing environment of HF programs. An online survey was distributed to members of the Pediatric Heart Transplant Study and the Pediatric Council of the International Society for Heart and Lung Transplantation. All participants received the primary 23-question survey. Additionally, HF program directors received a 32-question supplemental survey. Of 235 invitations sent, there were 69 (29%) primary surveys and 34 program director surveys completed (24 U.S. programs, 9 outside non-U.S., and one non-specified location). A formal HF program was reported by 88% of directors. There were 150 [IQR 50-200] outpatients/institution and 40% [25-50] of patients had congenital heart disease. Inpatient HF census was 3 [2-4] patients. Most programs (70%) used a consulting service model to provide HF specialty care, while only 10 (30%) utilized an inpatient HF service. Inpatient HF service programs had a higher daily inpatient census versus consult service model programs (4 [3-7] vs. 2 [1-4], respectively; p = 0.022) and had a higher number of full-time equivalents dedicated to HF (5.5 [2-7] vs. 2.5 [1-4], respectively; p = 0.024). Only 47% of programs report a general fellowship rotation devoted to HF. Advanced practice providers (APP) were utilized in 15 programs, nurse coordinators in 2, and both in 3. Most HF programs are formalized, utilize APP, and have inadequate HF staffing to utilize a separate inpatient HF service. Exposure of general pediatric cardiology fellows to HF care is variable between institutions.

  View details for PubMedID 29147800

• Second annual Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs) report: Pre-implant characteristics and outcomes JOURNAL OF HEART AND LUNG TRANSPLANTATION Blume, E. D., VanderPluym, C., Lorts, A., TimothyBaldwin, J., Rossano, J. W., Morales, D. S., Cantor, R. S., Miller, M. A., Louis, J., Koehl, D., Sutcliffe, D. L., Eghtesady, P., Kirklin, J. K., Rosenthal, D., Pedimacs Investigators 2018; 37 (1): 38-45

  Abstract

  Expanded use of pediatric ventricular assist devices (VADs) has decreased mortality in children awaiting heart transplantation. Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs), a National Heart, Lung, and Blood Institute-sponsored North American database, provides a platform to understand this emerging population.Between September 2012 and September 2016, patients aged younger than 19 years who underwent VAD implantation were enrolled in Pedimacs. FDA approved durable devices as well as temporary support devices were included. The second annual report updates the current Pedimacs data. Patients implanted with temporary devices are included in Pedimacs and this analysis includes this group of paracorporeal continuous flow VADs.Over the 4 years, 42 hospitals implanted 432 devices in 364 patients less than 19 yrs of age. Diagnoses included cardiomyopathy in 223 (61%), myocarditis in 41 (11%), and congenital heart disease in 77 (21%), of which 48 had single-ventricle physiology. At implant, 87% were at Intermacs patient profile 1 or 2. The age distribution of children (59% male) supported on VAD included 69 (19%) aged younger than 1 year, 66 (18%) aged 1 to 6 years, 56 (15%) aged 6 to 10 years, and 173 (48%) aged 11 to 19 years. Median follow-up was 2.2 months (range, 1 day to 41.5 months). Median (interquartile) age at implant was 1.7 (0.3-10.0) years for paracorporeal continuous-flow pumps (n = 60), 1.7 (0.4-5.3) years for paracorporeal pulsatile pumps (n = 105), and 15.0 (11.3-16.9) years for implantable continuous-flow pumps (n = 174). Support strategies included LVAD in 293 (80%), biventricular device in 55 (15%), and total artificial heart in 8 (2%). Nearly 50% of patients underwent transplantation within 6 months, with overall mortality of 19%. Adverse event burden continues to be high.Pedimacs constitutes the largest longitudinal pediatric VAD registry. Preimplant data across centers will be helpful at creating shared protocols with which to improve outcomes. Adverse events continue to be the major challenge, especially among the young critically ill children with complex congenital disease.

  View details for DOI 10.1016/j.healun.2017.06.017

  View details for Web of Science ID 000422767700006

  View details for PubMedID 28965736

• Variable clinical course of identical twin neonates with Alström syndrome presenting coincidentally with dilated cardiomyopathy. American journal of medical genetics. Part A Hollander, S. A., Alsaleh, N., Ruzhnikov, M., Jensen, K., Rosenthal, D. N., Stevenson, D. A., Manning, M. 2017; 173 (6): 1687-1689

  Abstract

  Alström Syndrome (AS) is a rare autosomal recessive disorder caused by mutations in the ALMS1 gene. We report monozygotic twin infants who presented concurrently with symptoms of congestive heart failure (CHF) due to dilated cardiomyopathy (DCM). Following their initial presentation, one twin improved both echocardiographically and functionally while the other twin showed a progressive decline in ventricular function and worsening CHF symptoms requiring multiple hospitalizations and augmentation of heart failure therapy. Concordant findings of nystagmus, vision loss, and developmental delay were noted in both twins. Additional discordant findings included obesity and signs of insulin resistance in one twin. Genetic testing on one sibling confirmed AS. These twins underscore the importance of considering AS in any child presenting with DCM, particularly in infancy, and highlights that, even in monozygotic twins, the clinical course of AS is variable with regard to both the cardiac and non-cardiac manifestations of the disease.

  View details for DOI 10.1002/ajmg.a.38200

  View details for PubMedID 28407410

• Development and validation of a major adverse transplant event (MATE) score to predict late graft loss in pediatric heart transplantation. journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Almond, C. S., Hoen, H., Rossano, J. W., Castleberry, C., Auerbach, S. R., Yang, L., Lal, A. K., Everitt, M. D., Fenton, M., Hollander, S. A., Pahl, E., Pruitt, E., Rosenthal, D. N., McElhinney, D. B., Daly, K. P., Desai, M. 2017

  Abstract

  There is inadequate power to perform a valid clinical trial in pediatric heart transplantation (HT) using a conventional end-point, because the disease is rare and hard end-points, such as death or graft loss, are infrequent. We sought to develop and validate a surrogate end-point involving the cumulative burden of post-transplant complications to predict death/graft loss to power a randomized clinical trial of maintenance immunosuppression in pediatric HT.Pediatric Heart Transplant Study (PHTS) data were used to identify all children who underwent an isolated orthotopic HT between 2005 and 2014 who survived to 6 months post-HT. A time-varying Cox model was used to develop and evaluate a surrogate end-point comprised of 6 major adverse transplant events (MATEs) (acute cellular rejection [ACR], antibody-mediated rejection [AMR], infection, cardiac allograft vasculopathy [CAV], post-transplant lymphoproliferative disease [PTLD] and chronic kidney disease [CKD]) occurring between 6 and 36 months, where individual events were defined according to international guidelines. Two thirds of the study cohort was used for score development, and one third of the cohort was used to test the score.Among 2,118 children, 6.4% underwent graft loss between 6 and 36 months post-HT, whereas 39% developed CKD, 34% ACR, 34% infection, 9% AMR, 4% CAV and 2% PTLD. The best predictive score involved a simple MATE score sum, yielding a concordance probability estimate (CPE) statistic of 0.74. Whereas the power to detect non-inferiority (NI), assuming the NI hazard ratio of 1.45 in graft survival was 10% (assuming 200 subjects and 6% graft loss rate), the power to detect NI assuming a 2-point non-inferiority margin was >85% using the MATE score.The MATE score reflects the cumulative burden of MATEs and has acceptable prediction characteristics for death/graft loss post-HT. The MATE score may be useful as a surrogate end-point to power a clinical trial in pediatric HT.

  View details for DOI 10.1016/j.healun.2017.03.013

  View details for PubMedID 28465118

• A novel inflow cannulation strategy for pediatric mechanical circulatory support in small left ventricles. journal of thoracic and cardiovascular surgery Ma, M., Yarlagadda, V. V., Rosenthal, D. N., Maeda, K. 2017

  View details for DOI 10.1016/j.jtcvs.2017.03.034

  View details for PubMedID 28416331

• Impact of Heart Transplantation on the Functional Status of US Children With End-Stage Heart Failure. Circulation Peng, D. M., Zhang, Y., Rosenthal, D. N., Palmon, M., Chen, S., Kaufman, B. D., Maeda, K., Hollander, S. A., McDonald, N., Smoot, L. B., Bernstein, D., Almond, C. S. 2017; 135 (10): 939-950

  Abstract

  There are limited data describing the functional status (FS) of children after heart transplant (HT). We sought to describe the FS of children surviving at least 1 year after HT, to evaluate the impact of HT on FS, and to identify factors associated with abnormal FS post-HT.Organ Procurement and Transplantation Network data were used to identify all US children <21 years of age surviving ≥1 year post-HT from 2005 to 2014 with a functional status score (FSS) available at 3 time points (listing, transplant, ≥1 year post-HT). Logistic regression and generalized estimating equations were used to identify factors associated with abnormal FS (FSS≤8) post-HT.A total of 1633 children met study criteria. At the 1-year assessment, 64% were "fully active/no limitations" (FSS=10), 21% had "minor limitations with strenuous activity" (FSS=9); and 15% scored ≤8. In comparison with listing FS, FS at 1 year post-HT increased in 91% and declined/remained unchanged in 9%. A stepwise regression procedure selected the following variables for association with abnormal FS at 1 year post-HT: ≥18 years of age (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.2-2.7), black race (OR, 1.5; 95% CI, 1.1-2.0), support with ≥inotropes at HT (OR, 1.7; 95% CI, 1.2-2.5), hospitalization status at HT (OR, 1.5; 95% CI, 1.0-2.19), chronic steroid use at HT (OR, 1.5; 95% CI, 1.0-2.2), and treatment for early rejection (OR, 2.0; 95% CI, 1.5-2.7).Among US children who survive at least 1 year after HT, FS is excellent for the majority of patients. HT is associated with substantial improvement in FS for most children. Early rejection, older age, black race, chronic steroid use, hemodynamic support at HT, and being hospitalized at HT are associated with abnormal FS post-HT.

  View details for DOI 10.1161/CIRCULATIONAHA.115.016520

  View details for PubMedID 28119383

• Functional status of United States children supported with a left ventricular assist device at heart transplantation. journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Bulic, A., Maeda, K., Zhang, Y., Chen, S., McElhinney, D. B., Dykes, J. C., Hollander, A. M., Hollander, S. A., Murray, J., Reinhartz, O., Gowan, M. A., Rosenthal, D. N., Almond, C. S. 2017

  Abstract

  As survival with pediatric left ventricular assist devices (LVADs) has improved, decisions regarding the optimal support strategy may depend more on quality of life and functional status (FS) rather than mortality alone. Limited data are available regarding the FS of children supported with LVADs. We sought to compare the FS of children supported with LVADs vs vasoactive infusions to inform decision making around support strategies.Organ Procurement and Transplant Network data were used to identify all United States children aged between 1 and 21 years at heart transplant (HT) between 2006 and 2015 for dilated cardiomyopathy and supported with an LVAD or vasoactive infusions alone at HT. FS was measured using the 10-point Karnofsky and Lansky scale.Of 701 children who met the inclusion criteria, 430 (61%) were supported with vasoactive infusions, and 271 (39%) were supported with an LVAD at HT. Children in the LVAD group had higher median FS scores at HT than children in the vasoactive infusion group (6 vs 5, p < 0.001) but lower FS scores at listing (4 vs 6, p < 0.001). The effect persisted regardless of patient location at HT (home, hospital, intensive care) or device type. Discharge by HT occurred in 46% of children in the LVAD group compared with 26% of children in the vasoactive infusion cohort (p = 0.001). Stroke was reported at HT in 3% of children in the LVAD cohort and in 1% in the vasoactive infusion cohort (p = 0.04).Among children with dilated cardiomyopathy undergoing HT, children supported with LVADs at HT have higher FS than children supported with vasoactive infusions at HT, regardless of device type or hospitalization status. Children supported with LVADs at HT were more likely to be discharged from the hospital but had a higher prevalence of stroke at HT.

  View details for DOI 10.1016/j.healun.2017.02.024

  View details for PubMedID 28363739

• Postapproval Outcomes: The Berlin Heart EXCOR Pediatric in North America. ASAIO journal Jaquiss, R. D., Humpl, T., Canter, C. E., Morales, D. L., Rosenthal, D. N., Fraser, C. D. 2017; 63 (2): 193-197

  Abstract

  The Berlin Heart EXCOR Pediatric Ventricular Assist Device (BH) was approved for use in the United States in December 2011, based on a prospective investigational device exemption (IDE) trial. Strict exclusion criteria for the trial selected a low-risk "ideal" cohort. We sought to determine whether postapproval usage of the BH in a "real world" cohort of recipients would result in similar outcomes. Preimplant diagnostic information was collected for all patients. Efficacy was evaluated by comparison of all children (efficacy group, n = 247) implanted between FDA approval and April 2015 to those in the IDE trial (IDE, n = 48), with regard to achievement of one of four end-states: transplanted, successful weaning, death/unsuccessful weaning, or still-on-device. Safety outcomes were compared between IDE patients and a subset of postapproval patients (safety group, n = 39) for whom adjudicated adverse events were tracked in a regulator-mandated dataset. Diagnostic categories were similar between groups: IDE (congenital 19%, dilated cardiomyopathy/myocarditis/other 81%) versus Efficacy Group (congenital 24%, dilated cardiomyopathy/myocarditis/other 75%). Patients in the IDE cohort were larger (median 14.8 kg, range 3.6-58.1 kg vs. 10.7 kg, 2.9-112.0 kg, p = 0.02). More IDE patients were successfully supported than in the efficacy group cohort (90% vs. 77%, p = 0.05). Proportions with bleeding and stroke were similar between the IDE and safety group cohorts (46% vs. 41%, p = 0.65; 29% vs. 33%, p = 0.68, respectively). With usage of the BH in a less-ideal population, rates of bridge to transplant and weaning have declined slightly, but remain encouragingly high. Bleeding and neurologic event rates have not increased.

  View details for DOI 10.1097/MAT.0000000000000454

  View details for PubMedID 28234657

• Long-term pediatric ventricular assist device therapy: a case report of 2100+ days of support. ASAIO journal Purkey, N. J., Lin, A., Murray, J. M., Gowen, M., Shuttleworth, P., Maeda, K., Almond, C. S., Rosenthal, D. N., Chen, S. 2017

  Abstract

  Ventricular assist devices (VADs) have been placed as destination therapy in adults for over twenty years but have only recently been considered an option in a subset of pediatric patients. A 2016 report from the Pediatric Interagency Registry for Mechanical Circulatory Support (PediMACS) revealed only eight pediatric patients implanted as destination therapy. We report the case of an adolescent male with Becker Muscular Dystrophy (BMD) who underwent VAD placement in 2011 as bridge to candidacy. He subsequently decided to remain as destination therapy and so far has accrued over 2100 days on VAD support, the longest duration of pediatric VAD support reported in the literature to date.

  View details for DOI 10.1097/MAT.0000000000000546

  View details for PubMedID 28195883

• Superior performance of continuous over pulsatile flow ventricular assist devices in the single ventricle circulation: A computational study. Journal of biomechanics Schmidt, T., Rosenthal, D., Reinhartz, O., Riemer, K., He, F., Hsia, T., Marsden, A., Kung, E. 2017; 52: 48-54

  Abstract

  This study compares the physiological responses of systemic-to-pulmonary shunted single ventricle patients to pulsatile and continuous flow ventricular assist devices (VADs). Performance differences between pulsatile and continuous flow VADs have been clinically observed, but the underlying mechanism remains poorly understood. Six systemic-to-pulmonary shunted single ventricle patients (mean BSA=0.30m(2)) were computationally simulated using a lumped-parameter network tuned to match patient specific clinical data. A first set of simulations compared current clinical implementation of VADs in single ventricle patients. A second set modified pulsatile flow VAD settings with the goal to optimize cardiac output (CO). For all patients, the best-case continuous flow VAD CO was at least 0.99L/min greater than the optimized pulsatile flow VAD CO (p=0.001). The 25 and 50mL pulsatile flow VADs exhibited incomplete filling at higher heart rates that reduced CO as much as 9.7% and 37.3% below expectations respectively. Optimization of pulsatile flow VAD settings did not achieve statistically significant (p<0.05) improvement to CO. Results corroborate clinical experience that continuous flow VADs produce higher CO and superior ventricular unloading in single ventricle patients. Impaired filling leads to performance degradation of pulsatile flow VADs in the single ventricle circulation.

  View details for DOI 10.1016/j.jbiomech.2016.12.003

  View details for PubMedID 28038771

• Rehospitalization after pediatric heart transplantation: Incidence, indications, and outcomes. Pediatric transplantation Hollander, S. A., McElhinney, D. B., Almond, C. S., McDonald, N., Chen, S., Kaufman, B. D., Bernstein, D., Rosenthal, D. N. 2017; 21 (1)

  Abstract

  We report the patterns of rehospitalization after pediatric heart transplant (Htx) at a single center. Retrospective review of 107 consecutive pediatric Htx recipients between January 22, 2007, and August 28, 2014, who survived their initial transplant hospitalization. The frequency, duration, and indications for all hospitalizations between transplant hospitalization discharge and September 30, 2015, were analyzed. A total of 444 hospitalization episodes occurred in 90 of 107 (84%) patients. The median time to first rehospitalization was 59.5 (range 1-1526) days, and the median length of stay was 2.5 (range 0-81) days. There were an average of two hospitalizations per patient in the first year following transplant hospitalization, declining to about 0.8 per patient per year starting at 3 years post-transplant. Admissions for viral infections were most common, occurring in 93 of 386 (24%), followed by rule out sepsis in 61 of 386 (16%). Admissions for suspected or confirmed rejection were less frequent, accounting for 41 of 386 (11%) and 31 of 386 (8%) of all admissions, respectively. Survival to discharge after rehospitalization was 97%. Hospitalization is common after pediatric Htx, particularly in the first post-transplant year, with the most frequent indications for hospitalization being viral illness and rule out sepsis. After the first post-transplant year, the risk for readmission falls significantly but remains constant for several years.

  View details for DOI 10.1111/petr.12857

  View details for PubMedID 27891727

• Does Small Size Matter With Continuous Flow Devices? Analysis of the INTERMACS Database of Adults With BSA <= 1.5 m(2) JACC-HEART FAILURE Zafar, F., Villa, C. R., Morales, D. L., Blume, E. D., Rosenthal, D. N., Kirklin, J. K., Lorts, A. 2017; 5 (2): 123-131

  Abstract

  This study investigated how small patient size affects clinical outcomes in patients implanted with a continuous flow left ventricular assist device (CFLVAD).The development of smaller CFLVADs has allowed ventricular assist device (VAD) use in anatomically smaller patients; however, limited outcome data exist regarding CFLVAD use in patients with a body surface area (BSA) ≤1.5 m(2).All CFLVAD patients entered in the Interagency Registry for Mechanically Assisted Circulatory Support registry April 2008 to September 2013 and with BSA data were included. Biventricular VAD patients were excluded. Patient characteristics and clinical outcomes were compared between patients with BSA ≤1.5 m(2) (small patients) and those >1.5 m(2).Of 10,813 CFLVAD recipients, 231 had a BSA ≤1.5 m(2). Small patients were more commonly female patients (68% vs. 20%; p < 0.01), Hispanic (10% vs. 6%; p < 0.03), and on intravenous inotropes (88% vs. 80%; p < 0.01). Small patients had higher bleeding (p < 0.01) and driveline infection (p < 0.01) rates, while exhibiting lower rates of right heart failure (p < 0.01) and renal dysfunction (p < 0.01). Device malfunction rate (p > 0.05), overall survival (p > 0.05), and 1-year competing outcomes (p > 0.05) were similar between BSA groups.Patients with a BSA ≤1.5 m(2) supported with a CFLVAD have similar survival to larger patients. These data support the use of CFLVAD in anatomically small patients.

  View details for DOI 10.1016/j.jchf.2016.09.009

  View details for Web of Science ID 000393635000008

• The End of Life Experience of Pediatric Heart Transplant Recipients. Journal of pain and symptom management Hollander, S. A., Dykes, J., Chen, S., Barkoff, L., Sourkes, B., Cohen, H., Rosenthal, D. N., Bernstein, D., Kaufman, B. D. 2017

  Abstract

  Despite advances in therapies, many pediatric heart transplant (Htx) recipients will die prematurely. We characterized the circumstances surrounding death in this cohort, including location of death and interventions performed in the final 24 hours.We reviewed all patients who underwent Htx at Lucile Packard Children's Hospital, Stanford, survived hospital discharge, and subsequently died between July 19, 2007 and September 13, 2015. The primary outcome studied was location of death, characterized as inpatient, outpatient, or emergency department. Circumstances of death (withdrawal of life-sustaining treatment, death during resuscitation, or death without resuscitation with/without do not resuscitate) and interventions performed in the last 24 hours of life were also analyzed.Twenty-three patients met the entry criteria. The median age at death was 12 (range 2-20) years, and the median time between transplant and death was 2.8 (range 0.8-11) years. Four (17%) died at home, and three (13%) died in the emergency department. Sixteen (70%) patients died in the hospital, 14 of 16 (88%) of whom died in an intensive care unit. Five of 23 (22%) patients experienced attempted resuscitation. Interventions performed in the last 24 hours of life included intubation (74%), mechanical support (30%), and dialysis (22%). Most patients had a recent outpatient clinical encounter with normal graft function within 60 days of dying.Death in children after Htx often occurs in the inpatient setting, particularly the intensive care unit. Medical interventions, including attempted resuscitation, are common at the end of life. Given the difficulty in anticipating life-threatening events, earlier discussions with patients regarding end-of-life wishes are appropriate, even in those with normal graft function.

  View details for DOI 10.1016/j.jpainsymman.2016.12.334

  View details for PubMedID 28063864

• Impact of the 18th birthday on waitlist outcomes among young adults listed for heart transplant: A regression discontinuity analysis. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Peng, D. M., Qu, Q. n., McDonald, N. n., Hollander, S. A., Bernstein, D. n., Maeda, K. n., Kaufman, B. D., Rosenthal, D. N., McElhinney, D. B., Almond, C. S. 2017; 36 (11): 1185–91

  Abstract

  Patients listed for heart transplant after their 18th birthday purportedly wait longer to receive a donor heart compared with patients listed before their 18th birthday. It is unclear whether there is an actual difference in wait times and whether any difference in wait time is associated with lower likelihood of transplant and/or higher risk of mortality.Organ procurement and transplant network data were used to identify all patients listed for heart transplant between 2006 and 2014 within a 1-year period before and after their 18th birthday. The primary study end-point was the waiting time to receive a donor heart. Secondary end-points included the probability of transplant and waitlist mortality. Regression discontinuity analysis was used to analyze the effect of age on either side of the sharp cut-off value of age 18 years (6,574 days of life), when allocation of donor hearts transitions from the pediatric to adult allocation system.A total of 360 patients met the study inclusion criteria, including 207 (57.5%) listed during the 12-month period before their 18th birthday under the pediatric allocation system, and 153 (42.5%) listed during the 12 months after their 18th birthday under the adult allocation system. The pediatric cohort was more likely to be listed Status 1A. Otherwise, the 2 groups shared similar baseline characteristics. Overall, patients listed after their 18th birthday waited 8.5 months longer to receive a transplant than adolescents listed before their 18th birthday (p = 0.01) and had a 47% lower probability of receiving a transplant (p = 0.001), but there was no difference in waitlist mortality (p = 0.37).Patients listed for heart transplant shortly after their 18th birthday have significantly longer wait-times compared with patients listed shortly before their 18th birthday and a lower probability of transplant, but no significant difference in waitlist mortality. For medically fragile adolescents at high risk of death, birth date may be a relevant factor in the timing of heart transplant listing.

  View details for PubMedID 28712678

• Adverse Events in Children Implanted with Ventricular Assist Devices in the US: Data from the Pediatric Interagency Registry for Mechanical Circulatory Support (PEDIMACS) (vol 35, pg 569, 2016) JOURNAL OF HEART AND LUNG TRANSPLANTATION Rosenthal, D. N. 2017; 36 (1): 116

  View details for DOI 10.1016/j.healun.2016.11.003

  View details for Web of Science ID 000392572600020

  View details for PubMedID 28109452

• Alternative Strategy for Biventricular Assist Device in an Infant With Hypertrophic Cardiomyopathy. The Annals of thoracic surgery Dykes, J. C., Reinhartz, O. n., Almond, C. S., Yarlagadda, V. n., Murray, J. n., Rosenthal, D. N., Maeda, K. n. 2017; 104 (2): e185–e186

  Abstract

  We report an infant with hypertrophic cardiomyopathy who underwent biventricular assist device placement with two 15-mL Berlin Heart EXCOR pediatric ventricular assist devices using an alternative atrial cannulation strategy. The systemic circulation was supported by left atrium (LA) to aorta cannulation. The LA was accessed through the right atrium by extending a 6-mm EXCOR cannula with a Gore-Tex graft connected to an atrial septal defect. The pulmonary circulation was supported with cannulation of the right atrium to pulmonary artery. This alternative cannulation strategy facilitated effective biventricular support and may be applicable to other patients with hypertrophic or restrictive physiology.

  View details for PubMedID 28734448

• Haemodynamic profiles of children with end-stage heart failure. European heart journal Chen, S. n., Dykes, J. C., McElhinney, D. B., Gajarski, R. J., Shin, A. Y., Hollander, S. A., Everitt, M. E., Price, J. F., Thiagarajan, R. R., Kindel, S. J., Rossano, J. W., Kaufman, B. D., May, L. J., Pruitt, E. n., Rosenthal, D. N., Almond, C. S. 2017; 38 (38): 2900–2909

  Abstract

  To evaluate associations between haemodynamic profiles and symptoms, end-organ function and outcome in children listed for heart transplantation.Children <18 years listed for heart transplant between 1993 and 2013 with cardiac catheterization data [pulmonary capillary wedge pressure (PCWP), right atrial pressure (RAP), and cardiac index (CI)] in the Pediatric Heart Transplant Study database were included. Outcomes were New York Heart Association (NYHA)/Ross classification, renal and hepatic dysfunction, and death or clinical deterioration while on waitlist. Among 1059 children analysed, median age was 6.9 years and 46% had dilated cardiomyopathy. Overall, 58% had congestion (PCWP >15 mmHg), 28% had severe congestion (PCWP >22 mmHg), and 22% low cardiac output (CI < 2.2 L/min/m2). Twenty-one per cent met the primary outcome of death (9%) or clinical deterioration (12%). In multivariable analysis, worse NYHA/Ross classification was associated with increased PCWP [odds ratio (OR) 1.03, 95% confidence interval (95% CI) 1.01-1.07, P = 0.01], renal dysfunction with increased RAP (OR 1.04, 95% CI 1.01-1.08, P = 0.007), and hepatic dysfunction with both increased PCWP (OR 1.03, 95% CI 1.01-1.06, P < 0.001) and increased RAP (OR 1.09, 95% CI 1.06-1.12, P < 0.001). There were no associations with low output. Death or clinical deterioration was associated with severe congestion (OR 1.6, 95% CI 1.2-2.2, P = 0.002), but not with CI alone. However, children with both low output and severe congestion were at highest risk (OR 1.9, 95% CI 1.1-3.5, P = 0.03).Congestion is more common than low cardiac output in children with end-stage heart failure and correlates with NYHA/Ross classification and end-organ dysfunction. Children with both congestion and low output have the highest risk of death or clinical deterioration.

  View details for PubMedID 29019615

• Temporary Circulatory Support in U.S. Children Awaiting Heart Transplantation. Journal of the American College of Cardiology Yarlagadda, V. V., Maeda, K. n., Zhang, Y. n., Chen, S. n., Dykes, J. C., Gowen, M. A., Shuttleworth, P. n., Murray, J. M., Shin, A. Y., Reinhartz, O. n., Rosenthal, D. N., McElhinney, D. B., Almond, C. S. 2017; 70 (18): 2250–60

  Abstract

  Extracorporeal membrane oxygenation (ECMO) has long served as the standard of care for short-term mechanical circulatory support in pediatrics. It is unknown whether newer-generation temporary circulatory support (TCS) devices afford children a meaningful survival advantage over ECMO.This study sought to determine whether bridge-to-heart transplant survival with a TCS device is superior to ECMO after adjusting for patient differences.All children ≤21 years of age listed for heart transplant from 2011 to 2015 who received a TCS device or ECMO as a bridge to transplant were identified using Organ Procurement and Transplantation Network data. Children supported with a TCS device were compared with a propensity score (PS)-matched cohort of children supported with ECMO as a bridge to transplant. The primary endpoint was Kaplan-Meier survival to transplant.The number of TCS devices implanted in children increased from ≤3 per year before 2011 to 50 in 2015. Overall, 93 patients implanted with TCS devices were included for analysis (59% left ventricular assist devices, 23% right ventricular assist devices, 18% biventricular assist devices). The most commonly used device was the CentriMag-PediMag system (65%), followed by TandemHeart (18%), Rotaflow (6%), and Impella (5%). Among 164 PS-matched patients, support duration was longer for the TCS cohort (median 19 days vs. 6 days; p < 0.001), and was longest for the CentriMag-PediMag (24 days vs. 6 days; p < 0.001) with 27% supported for >60 days. Compared with the ECMO cohort, the PS-matched TCS cohort had longer survival to transplant (hazard ratio: 0.49; 95% confidence interval: 0.30 to 0.79) and longer overall survival (hazard ratio: 0.61; 95% confidence interval: 0.39 to 0.96), with 90-day mortality before transplant that was modestly reduced (from 45% with ECMO to 39% with TCS).The use of TCS devices in children as a bridge to transplant has risen rapidly in recent years, led by the growth of magnetically levitated centrifugal flow pumps. Compared with conventional ECMO, TCS durations are longer, and more importantly, patient survival is superior.

  View details for PubMedID 29073953

• Impact of a modified anti-thrombotic guideline on stroke in children supported with a pediatric ventricular assist device. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Rosenthal, D. N., Lancaster, C. A., McElhinney, D. B., Chen, S. n., Stein, M. n., Lin, A. n., Doan, L. n., Murray, J. M., Gowan, M. A., Maeda, K. n., Reinhartz, O. n., Almond, C. S. 2017

  Abstract

  Stroke is the most feared complication associated with the Berlin Heart EXCOR pediatric ventricular assist device (VAD), the most commonly used VAD in children, and affects 1 in 3 children. We sought to determine whether a modified anti-thrombotic guideline, involving more intense platelet inhibition and less reliance on platelet function testing, is associated with a lower incidence of stroke.All children supported with the EXCOR at Stanford from 2009 to 2014 were divided into 2 cohorts based on the primary anti-thrombotic guideline used to prevent pump thrombosis: (1) the Edmonton Anti-thrombotic Guideline (EG) cohort, which included children implanted before September 2012 when dual anti-platelet therapy was used with doses titrated to Thromboelastrography/PlateletMapping (TEG/PM); and (2) the Stanford Modified Anti-thrombotic Guideline (SG) cohort, which included children implanted on or after September 2012 when triple anti-platelet therapy was used routinely and where doses were uptitrated to high, weight-based dosing targets, with low-dose steroids administered as needed for inflammation.At baseline, the EG (N = 16) and SG (N = 11) cohorts were similar. The incidence rate of stroke in the SG cohort was 84% lower than in the EG cohort (0.8 vs 4.9 events per 1,000 days of support, p = 0.031), and 86% lower than in the previous Investigational Device Exemption trial (p = 0.006). The bleeding rate was also lower in the SG cohort (p = 0.015). Target doses of aspirin, clopidogrel and dipyridamole were higher (all p < 0.003), with less dosing variability in the SG cohort than in the EG cohort. There was no difference in adenosine diphosphate inhibition by TEG/PM, but arachidonic acid inhibition was higher in the SG cohort (median 75% vs 39%, p = 0.008).Stroke was significantly less common in pediatric patients supported with the Berlin Heart EXCOR VAD using a triple anti-platelet regimen uptitrated to high, weight-based dosing targets as compared with the dual anti-platelet regimen titrated to PM, and without a higher risk of bleeding. Larger studies are needed to confirm these findings.

  View details for PubMedID 28606584

• Rehospitalization Patterns in Pediatric Outpatients with Continuous Flow VADs. ASAIO journal Hollander, S. A., Chen, S., Murray, J. M., Lin, A., McBrearty, E., Almond, C. S., Rosenthal, D. N. 2016

  Abstract

  As continuous flow ventricular assist devices (CF-VADs) are used increasingly in children and adolescents, more pediatric patients will be supported as outpatients. Herein we report the patterns of rehospitalization after CF-VAD implantation at a single center. We retrospectively reviewed the medical records of 19 consecutive patients who received CF-VADS between 6/12/2010 and 5/11/2016 and were discharged on device therapy. The frequency, duration, and indications for all hospitalizations between the time of implant hospitalization discharge and 8/01/2016 were analyzed. There were a total of 52 rehospitalization episodes in 16 (84%) patients over 5101 (median 93, IQR 38, 226) follow-up days. There were a median of 2 (IQR 1, 3) hospitalizations per patient. The median time to first hospitalization was 14 (IQR 7, 62) days. The most common admitting diagnoses were suspected infection 13 (28%) and suspected pump thrombosis in 8 (17%). 31 (60%) hospitalizations included procedures, including 7 (13%) requiring device-related surgery. Overall, 89% of post-implant discharge days were spent outside of the hospital. Children with CF-VADs can be discharged with acceptable readmission rates and significant time spent out of hospital. Most patients will be rehospitalized at least once between implant hospitalization and transplantation, often within 2 weeks of hospital discharge, with the most common indications for admission being suspected infection and suspected pump thrombosis. Device-related complications necessitating surgical intervention most frequently occur in destination therapy patients who are supported for longer periods of time.

  View details for DOI 10.1097/MAT.0000000000000505

  View details for PubMedID 28009712

• The evolution of medical therapy for children with heart failure PROGRESS IN PEDIATRIC CARDIOLOGY Law, Y., Rosenthal, D., Kantor, P. 2016; 43: 3–6

  View details for DOI 10.1016/j.ppedcard.2016.08.019

  View details for Web of Science ID 000394676700002

• Does Small Size Matter With Continuous Flow Devices?: Analysis of the INTERMACS Database of Adults With BSA =1.5 m(2). JACC. Heart failure Zafar, F., Villa, C. R., Morales, D. L., Blume, E. D., Rosenthal, D. N., Kirklin, J. K., Lorts, A. 2016

  Abstract

  This study investigated how small patient size affects clinical outcomes in patients implanted with a continuous flow left ventricular assist device (CFLVAD).The development of smaller CFLVADs has allowed ventricular assist device (VAD) use in anatomically smaller patients; however, limited outcome data exist regarding CFLVAD use in patients with a body surface area (BSA) ≤1.5 m(2).All CFLVAD patients entered in the Interagency Registry for Mechanically Assisted Circulatory Support registry April 2008 to September 2013 and with BSA data were included. Biventricular VAD patients were excluded. Patient characteristics and clinical outcomes were compared between patients with BSA ≤1.5 m(2) (small patients) and those >1.5 m(2).Of 10,813 CFLVAD recipients, 231 had a BSA ≤1.5 m(2). Small patients were more commonly female patients (68% vs. 20%; p < 0.01), Hispanic (10% vs. 6%; p < 0.03), and on intravenous inotropes (88% vs. 80%; p < 0.01). Small patients had higher bleeding (p < 0.01) and driveline infection (p < 0.01) rates, while exhibiting lower rates of right heart failure (p < 0.01) and renal dysfunction (p < 0.01). Device malfunction rate (p > 0.05), overall survival (p > 0.05), and 1-year competing outcomes (p > 0.05) were similar between BSA groups.Patients with a BSA ≤1.5 m(2) supported with a CFLVAD have similar survival to larger patients. These data support the use of CFLVAD in anatomically small patients.

  View details for DOI 10.1016/j.jchf.2016.09.009

  View details for PubMedID 27816511

• Can Destination Therapy be implemented in children with heart failure? A study of provider perceptions. Pediatric transplantation Char, D. S., Lee, S. S., Ikoku, A. A., Rosenthal, D., Magnus, D. 2016; 20 (6): 819-824

  Abstract

  DT is an established final therapeutic choice in adult patients with severe heart failure who do not meet criteria for cardiac transplantation. Patients are given VADs, without the prospect of care escalation to transplantation. VADs are now established therapy for children and are currently used as a bridge until transplantation can be performed or heart failure improves. For children who present in severe heart failure but do not meet transplantation criteria, the question has emerged whether DT can be offered. This qualitative study aimed to elicit the perspectives of early adopters of DT at one of the few institutions where DT has been provided for children. Responses were recorded and coded and themes extracted using grounded theory. Interviewees discussed: envisioning of the DT candidate; approach to evaluation for DT; contraindications to choosing DT; and concerns about choosing DT. Providers articulated two frameworks for conceptualizing DT: as a long bridge through resolution of problems that would initially contraindicate transplantation or, alternatively, as a true destination instead of transplantation. True destination, however, may not be the lasting concept for long-term VAD use in children given improvement in prognosis for current medical contraindications and improving VAD technology.

  View details for DOI 10.1111/petr.12747

  View details for PubMedID 27357389

• HeartWare HVAD for Biventricular Support in Children and Adolescents: The Stanford Experience. ASAIO journal Stein, M. L., Yeh, J., Reinhartz, O., Rosenthal, D. N., Kaufman, B. D., Almond, C. S., Hollander, S. A., Maeda, K. 2016; 62 (5): e46-51

  Abstract

  Despite increasing use of mechanical circulatory support in children, experience with biventricular device implantation remains limited. We describe our experience using the HeartWare HVAD to provide biventricular support to 3 patients and compare these patients with 5 patients supported with HeartWare LVAD. At the end of the study period, all three BiVAD patients had been transplanted and were alive. LVAD patients were out of bed and ambulating a median of 10.5 days post implantation. The BiVAD patients were out of bed a median of 31 days post implantation. Pediatric patients with both left ventricular and biventricular heart failure can be successfully bridged to transplantation with the HeartWare HVAD. Rapid improvement in functional status following HVAD implantation for isolated left ventricular support is seen. Patients supported with BiVAD also demonstrate functional recovery, albeit more modestly. In the absence of infection, systemic inflammatory response raises concern for inadequate support.

  View details for DOI 10.1097/MAT.0000000000000356

  View details for PubMedID 26919182

• Recovery From Acute Kidney Injury and CKD Following Heart Transplantation in Children, Adolescents, and Young Adults: A Retrospective Cohort Study. American journal of kidney diseases Hollander, S. A., Montez-Rath, M. E., Axelrod, D. M., Krawczeski, C. D., May, L. J., Maeda, K., Rosenthal, D. N., Sutherland, S. M. 2016; 68 (2): 212-218

  Abstract

  Acute kidney injury (AKI) is common in children following surgery for congenital heart disease and has been associated with poor long-term kidney outcomes. Children undergoing heart transplantation may be at increased risk for the development of both AKI and chronic kidney disease (CKD). This study examines AKI rates in children, adolescents, and young adults after heart transplantation and analyzes the relationship between AKI and CKD in this population.Retrospective cohort study.88 young patients who underwent heart transplantation at Lucile Packard Children's Hospital, Stanford, CA, September 1, 2007, to November 30, 2013.The primary independent variable was AKI within the first 7 postoperative days, ascertained according to the KDIGO (Kidney Disease: Improving Global Outcomes) creatinine criteria (increase in serum creatinine ≥ 1.5 times baseline within 7 days).Recovery from AKI at 3 months, ascertained as serum creatinine level < 1.5 times baseline; and development of CKD at 6 and 12 months, ascertained as estimated glomerular filtration rate < 60mL/min/1.73m(2) for more than 3 months.63 (72%) patients developed AKI; 57% had moderate (stage 2 or severe stage 3) disease. Recovery occurred in 39 of 63 (62%), 50% for stage 2 or 3 versus 78% for stage 1 (P=0.04). At 6 and 12 months, 3 of 82 (4%) and 4 of 76 (5%) developed CKD, respectively. At both time points, CKD was more common in those without recovery (3/22 [14%] vs 0/38 (0%); P=0.04, and 3/17 (18%) vs (0/34) 0%; P=0.03, respectively).Retrospective design, small sample size, and single-center nature of the study.AKI is common after heart transplantation in children, adolescents, and young adults. Nonrecovery from AKI is more common in patients with more severe AKI and is associated with the development of CKD during the first year.

  View details for DOI 10.1053/j.ajkd.2016.01.024

  View details for PubMedID 26970941

• Electrocardiographic repolarization abnormalities and increased risk of life-threatening arrhythmias in children with dilated cardiomyopathy HEART RHYTHM Chen, S., Motonaga, K. S., Hollander, S. A., Almond, C. S., Rosenthal, D. N., Kaufman, B. D., May, L. J., Avasarala, K., Dao, D. T., Dubin, A. M., Ceresnak, S. R. 2016; 13 (6): 1289-1296

  Abstract

  Life-threatening arrhythmia events (LTEs) occur in ~5% of children with dilated cardiomyopathy (DCM). While prolonged QRS duration has been shown to be associated with LTEs, electrocardiographic (ECG) repolarization findings have not been examined.We sought to determine the associations between ECG repolarization abnormalities and LTEs in children with DCM.A single-center retrospective review of children with DCM was performed. LTEs were defined as documented ventricular tachycardia or fibrillation requiring medical intervention. Three pediatric cardiologists, blinded to clinical events, evaluated ECGs obtained at the time of initial referral. Kaplan-Meier survival and Cox proportional hazards analyses were used to evaluate time to LTEs.A total of 137 patients (mean age 7.8 ± 6.7 years; 75(55%) male patients) with DCM (mean ejection fraction 35% ± 16%) were included; 67 patients (49%) had a corrected JT (JTc) interval of ≥340 ms, 72 (53%) had a corrected QT (QTc) interval of ≥450 ms, and 41 (30%) had abnormal T waves. LTEs occurred in 15 patients at a median of 12 months (interquartile range 3-36 months) after the initial ECG. Patients with LTEs had a longer JTc interval (371 ± 77 ms vs 342 ± 41 ms; P = .02) and a longer QTc interval (488 ± 96 ms vs 453 ± 44 ms; P = .01). In survival analysis, a JTc interval of ≥390 ms (hazard ratio [HR] 4.07; 95% confidence interval [CI] 1.12-14.83; P = .03), a QTc interval of ≥510 ms (HR 6.95; 95% CI 1.53-31.49; P = .01), abnormal T-wave inversion (HR 11.62; 95% CI 2.75-49.00; P = .001), and ST-segment depression (HR 6.91; 95% CI 1.25-38.27; P = .03) were associated with an increased risk of LTEs, even after adjusting for QRS duration and amiodarone use.Repolarization abnormalities are common in children with DCM. Certain ECG repolarization abnormalities, such as significantly prolonged JTc and QTc intervals, may be useful in identifying patients at risk of LTEs.

  View details for DOI 10.1016/j.hrthm.2016.02.014

  View details for Web of Science ID 000376334800016

  View details for PubMedID 26945851

• Compassionate deactivation of ventricular assist devices in pediatric patients JOURNAL OF HEART AND LUNG TRANSPLANTATION Hollander, S. A., Axelrod, D. M., Bernstein, D., Cohen, H. J., Sourkes, B., Reddy, S., Magnus, D., Rosenthal, D. N., Kaufman, B. D. 2016; 35 (5): 564-567

  Abstract

  Despite greatly improved survival in pediatric patients with end-stage heart failure through the use of ventricular assist devices (VADs), heart failure ultimately remains a life-threatening disease with a significant symptom burden. With increased demand for donor organs, liberalizing the boundaries of case complexity, and the introduction of destination therapy in children, more children can be expected to die while on mechanical support. Despite this trend, guidelines on the ethical and pragmatic issues of compassionate deactivation of VAD support in children are strikingly absent. As VAD support for pediatric patients increases in frequency, the pediatric heart failure and palliative care communities must work toward establishing guidelines to clarify the complex issues surrounding compassionate deactivation. Patient, family and clinician attitudes must be ascertained and education regarding the psychological, legal and ethical issues should be provided. Furthermore, pediatric-specific planning documents for use before VAD implantation as well as deactivation checklists should be developed to assist with decision-making at critical points during the illness trajectory. Herein we review the relevant literature regarding compassionate deactivation with a specific focus on issues related to children.

  View details for DOI 10.1016/j.healun.2016.03.020

  View details for Web of Science ID 000376951900004

  View details for PubMedID 27197773

• Outcomes of children implanted with ventricular assist devices in the United States: First analysis of the Pediatric Interagency Registry for Mechanical Circulatory Support (PediMACS) JOURNAL OF HEART AND LUNG TRANSPLANTATION Blume, E. D., Rosenthal, D. N., Rossano, J. W., Baldwin, J. T., Eghtesady, P., Morales, D. L., Cantor, R. S., Conway, J., Lorts, A., Almond, C. S., Naftel, D. C., Kirklin, J. K. 2016; 35 (5): 578-584

  Abstract

  Use of mechanical circulatory support in children has increased as more options have become available. A national account of the use of mechanical support in children and adolescents is essential to understanding outcomes, refining patient selection and improving quality of care.The Pediatric Interagency Registry for Mechanical Circulatory Support (PediMACS) is a National Heart, Lung, and Blood Institute-supported nationwide registry for temporary and durable ventricular assist device (VAD) use in patients <19 years of age. Between the launch in September 2012 and June 2015, 37 hospitals in the USA have enrolled patients. This first report of data from PediMACS analyzed pre-implant patient characteristics, survival using competing outcomes, and adverse events.Two hundred pediatric patients underwent 222 durable VAD implants. Patients' characteristics and outcomes of children supported with a temporary device (n = 41) were not analyzed in this report. The etiology of heart disease included 146 (73%) patients with cardiomyopathy and 35 (18%) with congenital heart disease. Thirty patients (15%) transitioned from extracorporeal membrane oxygenation (ECMO) and 76 (38%) had previous cardiac surgery. Most patients were Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) Level 1 (27%) or Level 2 (56%) at implant, with 13% at Level 3. Of the 200 patients supported with a durable device, 91 (46%) were supported with a pulsatile-flow device and 109 (55%) with a continuous-flow (CF) device. Patient age at first implant included 30 patients (15%) <1 year of age, 37 (19%) 1 to 5 years, 32 (16%) 6 to 10 years and 101 (51%) 10 to 18 years. Patients were supported with left ventricular assist device alone in 161 (81%), biventricular ventricular assist device in 29 (15%), right ventricular assist device in 4 (2.0%) and total artificial heart in 6 (3%), together comprising 783 months of follow-up. The 200 patients receiving primary durable devices had an actuarial survival of 81% at 6 months. Competing risk analysis at 6 months revealed that 58% of patients had been transplanted, 28% were alive on support, 14% had died and 0.6% recovered. In the overall cohort, there were 28 deaths. Reported serious adverse events included infection (n = 78), bleeding (n = 68), device malfunction (n = 79) and neurologic dysfunction (n = 52).PediMACS constitutes the largest single data repository with detailed information of pediatric patients implanted with VADs. The first PediMACS report reveals favorable outcomes despite the varying patient characteristics and pump types. However, the rate of adverse events remains high. With further data collection, analysis of patient risk factors critical to improving outcomes will be possible.

  View details for DOI 10.1016/j.healun.2016.01.1227

  View details for Web of Science ID 000376951900007

  View details for PubMedID 27009673

• Outcomes of pediatric patients supported with continuous-flow ventricular assist devices: A report from the Pediatric Interagency Registry for Mechanical Circulatory Support (PediMACS) JOURNAL OF HEART AND LUNG TRANSPLANTATION Rossano, J. W., Lorts, A., Vanderpluym, C. J., Jeewa, A., Guleserian, K. J., Bleiweis, M. S., Reinhartz, O., Blume, E. D., Rosenthal, D. N., Naftel, D. C., Cantor, R. S., Kirklin, J. K. 2016; 35 (5): 585-590

  Abstract

  Continuous-flow (CF) ventricular assist devices (VADs) have largely replaced pulsatile-flow VADs in adult patients. However, there are few data on CF VADs among pediatric patients. In this study we aimed to describe the overall use, patients' characteristics and outcomes of CF VADs in this population.The Pediatric Interagency Registry for Mechanical Circulatory Support (PediMACS) is a national registry for U.S. Food and Drug Adminstration (FDA)-approved VADs in patients <19 years of age. Patients undergoing placement of durable CF VADs between September 2012 and June 2015 were included and outcomes were compared with those of adults from the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS).CF VADs were implanted in 109 patients at 35 hospitals. The median age at implantation was 15 years (2.8 to 18.9 years) and median weight was 62 kg (range 16 to 141 kg). The underlying disease was cardiomyopathy in 89 (82%) patients. The INTERMACS level at time of implant was Level 1 in 20 (19%), Level 2 in 64 (61%) and Levels 3 to 7 in 21 (20%) patients. Most were implanted as LVADs (n = 102, 94%). Median duration of support was 2.3 months (range <1 day to 28 months). Serious adverse event rates were low, including neurologic dysfunction (early event rate 4.1 per 100 patient-months with 2 late events). Competing outcomes analysis at 6 months post-implant indicated 61% transplanted, 31% alive with device in place and 8% death before transplant. These outcomes compared favorably with the 3,894 adults supported with CF VADs as a bridge to transplant.CF VADs are commonly utilized in older children and adolescents, with excellent survival rates. Further study is needed to understand impact of patient and device characteristics on outcomes in pediatric patients.

  View details for DOI 10.1016/j.healun.2016.01.1228

  View details for Web of Science ID 000376951900008

  View details for PubMedID 27056612

• Adverse events in children implanted with ventricular assist devices in the United States: Data from the Pediatric Interagency Registry for Mechanical Circulatory Support (PediMACS) JOURNAL OF HEART AND LUNG TRANSPLANTATION Rosenthal, D. N., Almond, C. S., Jaquiss, R. D., Peyton, C. E., Auerbach, S. R., Morales, D. R., Epstein, D. J., Cantor, R. S., Kormos, R. L., Naftel, D. C., Butts, R. J., Ghanayem, N. S., Kirklin, J. K., Blume, E. D. 2016; 35 (5): 569-577

  Abstract

  Ventricular assist devices (VADs) have been used in children on an increasing basis in recent years. One-year survival rates are now >80% in multiple reports. In this report we describe adverse events experienced by children with durable ventricular assist devices, using a national-level registry (PediMACS, a component of INTERMACS) METHODS: PediMACS is a national registry that contains clinical data on patients who are <19 years of age at the time of VAD implantation. Data collection concludes at the time of VAD explantation. All FDA-approved devices are included. PediMACS was launched on September 1, 2012, and this report includes all data from launch until August 2014. Adverse events were coded with a uniform, pre-specified set of definitions.This report comprises data from 200 patients with a median age of 11 years (range 11 days to 18 years), and total follow-up of 783 patient-months. The diagnoses were cardiomyopathy (n = 146, 73%), myocarditis (n = 17, 9%), congenital heart disease (n = 35, 18%) and other (n = 2, 1%). Pulsatile-flow devices were used in 91 patients (45%) and continuous-flow devices in 109 patients (55%). Actuarial survival was 86% at 6 months. There were 418 adverse events reported. The most frequent events were device malfunction (n = 79), infection (n = 78), neurologic dysfunction (n = 52) and bleeding (n = 68). Together, these accounted for 277 events, 66% of the total. Although 38% of patients had no reported adverse event and 16% of patients had ≥5 adverse events. Adverse events occurred at all time-points after implantation, but were most likely to occur in the first 30 days. For continuous-flow devices, there were broad similarities in adverse event rates between this cohort and historic rates from the INTERMACS population.In this study cohort, the overall rate of early adverse events (within 90 days of implantation) was 86.3 events per 100 patient-months, and of late adverse events it was 20.4 events per 100 patient-months. The most common adverse events in recipients of pulsatile VADs were device malfunction, neurologic dysfunction, bleeding and infection. For continuous-flow VADs, the most common adverse events were infection, bleeding, cardiac arrhythmia, neurologic dysfunction and respiratory failure. Compared with an adult INTERMACS cohort, the overall rate and distribution of adverse events appears similar.

  View details for DOI 10.1016/j.healun.2016.03.005

  View details for Web of Science ID 000376951900006

  View details for PubMedID 27197775

• MOVING TOWARD A NATIONAL CONSENSUS ON PEDIATRIC HEART FAILURE QUALITY MEASURES: THE ACC QUALITY METRICS WORKING GROUP INITIATIVE Almond, C. D., Lorts, A., Daly, K., Liu, E., Rosenthal, D., Bulic, A., Gurvitz, M., Shin, A., Rossano, J., Price, J. ELSEVIER SCIENCE INC. 2016: 1002

  View details for DOI 10.1016/S0735-1097(16)31003-8

  View details for Web of Science ID 000375188701846

• Impact of ventricular assist device placement on longitudinal renal function in children with end-stage heart failure. journal of heart and lung transplantation May, L. J., Montez-Rath, M. E., Yeh, J., Axelrod, D. M., Chen, S., Maeda, K., Almond, C. S., Rosenthal, D. N., Hollander, S. A., Sutherland, S. M. 2016; 35 (4): 449-456

  Abstract

  Although ventricular assist devices (VADs) restore hemodynamics in those with heart failure, reversibility of end-organ dysfunction with VAD support is not well characterized. Renal function often improves in adults after VAD placement, but this has not been comprehensively explored in children.Sixty-three children on VAD support were studied. Acute kidney injury (AKI) was defined by Kidney Disease: Improving Global Outcomes criteria. Estimated glomerular filtration rate (eGFR) was determined by the Schwartz method. Generalized linear mixed-effects models compared the pre-VAD and post-VAD eGFR for the cohort and sub-groups with and without pre-VAD renal dysfunction (pre-VAD eGFR < 90 ml/min/1.73 m(2)).The pre-VAD eGFR across the cohort was 84.0 ml/min/1.73 m(2) (interquartile range [IQR] 62.3-122.7), and 55.6% (34 of 63) had pre-VAD renal dysfunction. AKI affected 60.3% (38 of 63), with similar rates in those with and without pre-existing renal dysfunction. Within the cohort, the nadir eGFR occurred 1 day post-operatively (62.9 ml/min/1.73 m(2); IQR, 51.2-88.9 ml/min/1.73 m(2); p < 0.001). By Day 5, however, the eGFR exceeded the baseline (99.0 ml/min/1.73 m(2); IQR, 59.3-146.7 ml/min/1.73 m(2); p = 0.03) and remained significantly higher through the first post-operative week. After adjusting for age, gender, and AKI, the eGFR continued to increase throughout the entire 180-day study period (β = 0.0025; 95% confidence interval, 0.0015-0.0036; p < 0.001). Patients with pre-VAD renal dysfunction experienced the greatest improvement in the eGFR (β = 0.0051 vs β = 0.0013, p < 0.001).Renal dysfunction is prevalent in children with heart failure undergoing VAD placement. Although peri-operative AKI is common, renal function improves substantially in the first post-operative week and for months thereafter. This is particularly pronounced in those with pre-VAD renal impairment, suggesting that VADs may facilitate recovery and maintenance of kidney function in children with advanced heart failure.

  View details for DOI 10.1016/j.healun.2015.10.039

  View details for PubMedID 26653933

• Outpatient Outcomes of Pediatric Patients with Left Ventricular Assist Devices. ASAIO journal Chen, S., Lin, A., Liu, E., Gowan, M., May, L. J., Doan, L. N., Almond, C. S., Maeda, K., Reinhartz, O., Hollander, S. A., Rosenthal, D. N. 2016; 62 (2): 163-168

  Abstract

  Outpatient experience of children supported with continuous flow ventricular assist devices (CFVAD) is limited. We reviewed our experience with children discharged with CF-VAD support.All pediatric patients <18 years old with CF-VADs implanted at our institution were included. Discharge criteria included a stable medication regimen, completion of a VAD education program and standardized rehabilitation plan, and presence of a caregiver. Hospital re-admissions (excluding scheduled admissions) were reviewed. Adverse events were defined by INTERMACS criteria.Of 17 patients with CF-VADs, 8(47%) were discharged from the hospital (1 Heartware HVAD, 7 Heartmate II). Median age was 15.3(range 9.6-17.1) years and weight was 50.6(33.6-141) kg. Device strategies were destination therapy (n=4) and bridge to transplant (n=4). Patients spent a median 49(26-107) days hospitalized post-implant and had 2(1-5) hospital re-admissions. Total support duration was 3154 patient-days, with 2413 as outpatient. Most frequent adverse events were device malfunction and arrhythmias. There was one death due to pump thrombosis, and no bleeding or stroke events. Overall adverse event rate was 15.22 per 100-patient-months.Early experience suggests that children with CF-VADs can be safely discharged. Device malfunction and arrhythmia were the most common adverse events but were recognized quickly with structured outpatient surveillance.

  View details for DOI 10.1097/MAT.0000000000000324

  View details for PubMedID 26720740

• A Pilot Study Assessing ECG versus ECHO Ventriculoventricular Optimization in Pediatric Resynchronization Patients. Journal of cardiovascular electrophysiology Punn, R., Hanisch, D., Motonaga, K. S., Rosenthal, D. N., Ceresnak, S. R., Dubin, A. M. 2016; 27 (2): 210-216

  Abstract

  Cardiac resynchronization therapy indications and management are well described in adults. Echocardiography (ECHO) has been used to optimize mechanical synchrony in these patients; however, there are issues with reproducibility and time intensity. Pediatric patients add challenges, with diverse substrates and limited capacity for cooperation. Electrocardiographic (ECG) methods to assess electrical synchrony are expeditious but have not been extensively studied in children. We sought to compare ECHO and ECG CRT optimization in children.Prospective, pediatric, single-center cross-over trial comparing ECHO and ECG optimization with CRT. Patients were assigned to undergo either ECHO or ECG optimization, followed for 6 months, and crossed-over to the other assignment for another 6 months. ECHO pulsed-wave tissue Doppler and 12-lead ECG were obtained for 5 VV delays. ECG optimization was defined as the shortest QRSD and ECHO optimization as the lowest dyssynchrony index. ECHOs/ECGs were interpreted by readers blinded to optimization technique. After each 6 month period, these data were collected: ejection fraction, velocimetry-derived cardiac index, quality of life, ECHO-derived stroke distance, M-mode dyssynchrony, study cost, and time. Outcomes for each optimization method were compared.From June 2012 to December 2013, 19 patients enrolled. Mean age was 9.1 ± 4.3 years; 14 (74%) had structural heart disease. The mean time for optimization was shorter using ECG than ECHO (9 ± 1 min vs. 68 ± 13 min, P < 0.01). Mean cost for charges was $4,400 ± 700 less for ECG. No other outcome differed between groups.ECHO optimization of synchrony was not superior to ECG optimization in this pilot study. ECG optimization required less time and cost than ECHO optimization.

  View details for DOI 10.1111/jce.12863

  View details for PubMedID 26515428

• Obesity and Premature Loss of Mobility in Two Adolescents with Becker Muscular Dystrophy After HeartMate II Implantation. ASAIO journal Hollander, S. A., Rizzuto, S., Hollander, A. M., Lin, A., Liu, E., Murray, J. M., Almond, C. S., Rosenthal, D. N. 2016; 62 (1): e5-7

  Abstract

  Weight gain is common following implantation of continuous flow ventricular assist devices (VADS). Obesity can have a significant negative impact on mobility. For adolescents with Becker Muscular Dystrophy (BMD) for whom the ability to ambulate often persists into the mid-third decade, preservation of functional ability is critical. We report two cases of Thoratec HeartMate II left ventricular assist device (LVAD) implantation in adolescents with Becker Muscular Dystrophy for whom post-operative weight gain contributed significantly to accelerated loss of ambulation and, in one case, drive line fracture in the context of repeated falls. As LVADS become an increasingly common therapy for end-stage heart failure in adolescents with BMD, care must focus not only on maintaining device functionality, but aggressive weight management and preservation of ambulation and skeletal muscle strength.

  View details for DOI 10.1097/MAT.0000000000000292

  View details for PubMedID 26461240

• Ventricular assist devices in a contemporary pediatric cohort: Morbidity, functional recovery, and survival. journal of heart and lung transplantation Stein, M. L., Dao, D. T., Doan, L. N., Reinhartz, O., Maeda, K., Hollander, S. A., Yeh, J., Kaufman, B. D., Almond, C. S., Rosenthal, D. N. 2016; 35 (1): 92-98

  Abstract

  Limited availability of donor organs has led to the use of ventricular assist devices (VADs) to treat heart failure in pediatric patients, primarily as bridge to transplantation. How effective VAD therapy is in promoting functional recovery in children is currently not known.We report morbidity and mortality as defined by the Interagency Registry for Mechanically Assisted Circulatory Support Modified for Pediatrics (PediMACS) and the use of the Treatment Intensity Score to assess functional status for 50 VAD patients supported at a single pediatric program from 2004 to 2013.In this cohort, 30-day survival on VAD was 98%, and 180-day survival was 83%. Stroke occurred in 11 patients (22%), with 8 (16%) resulting in persistent neurologic deficit or death. The adverse event rate was 2-fold to 3-fold higher in the first 7 days of support compared with the subsequent support period. Functional status, as measured by the Treatment Intensity Score, improved with duration of support. Successful bridge to transplantation was associated with fewer adverse events during support and greater improvement in the Treatment Intensity Score during the period of support.Overall survival in this cohort is excellent. The risk of serious adverse events decreases over the first month of support. However, a clinically significant risk of morbidity and mortality persists for the duration of pediatric VAD support. Measures of functional status improve with duration of support and are associated with survival to transplantation.

  View details for DOI 10.1016/j.healun.2015.06.006

  View details for PubMedID 26210751

• Obesity and Premature Loss of Mobility in Two Adolescents with Becker Muscular Dystrophy After HeartMate II Implantation ASAIO JOURNAL Holander, S. A., Rizzuto, S., Holander, A. M., Lin, A., Liu, E., Murray, J. M., Almond, C. S., Rosenthal, D. N. 2016; 62 (1): E5-E7

  View details for DOI 10.1097/MAT.0000000000000292

  View details for Web of Science ID 000367342800002

• Exploring Value in Congenital Heart Disease: An Evaluation of Inpatient Admissions. Congenital heart disease Shin, A. Y., Hu, Z., Jin, B., Lal, S., Rosenthal, D. N., Efron, B., Sharek, P. J., Sutherland, S. M., Cohen, H. J., McElhinney, D. B., Roth, S. J., Ling, X. B. 2015; 10 (6): E278-87

  Abstract

  Understanding value provides an important context for improvement. However, most health care models fail to measure value. Our objective was to categorize inpatient encounters within an academic congenital heart program based on clinical outcome and the cost to achieve the outcome (value). We aimed to describe clinical and nonclinical features associated with value.We defined hospital encounters based on outcome per resource utilized. We performed principal component and cluster analysis to classify encounters based on mortality, length of stay, hospital cost and revenue into six classes. We used nearest shrunken centroid to identify discriminant features associated with the cluster-derived classes. These features underwent hierarchical clustering and multivariate analysis to identify features associated with each class.We analyzed all patients admitted to an academic congenital heart program between September 1, 2009, and December 31, 2012.A total of 2658 encounters occurred during the study period. Six classes were categorized by value. Low-performing value classes were associated with greater institutional reward; however, encounters with higher-performing value were associated with a loss in profitability. Encounters that included insertion of a pediatric ventricular assist device (log OR 2.5 [95% CI, 1.78 to 3.43]) and acquisition of a hospital-acquired infection (log OR 1.42 [95% CI, 0.99 to 1.87]) were risk factors for inferior health care value.Among the patients in our study, institutional reward was not associated with value. We describe a framework to target quality improvement and resource management efforts that can benefit patients, institutions, and payers alike.

  View details for DOI 10.1111/chd.12290

  View details for PubMedID 26219731

• Group visits in the pediatric heart transplant outpatient clinic PEDIATRIC TRANSPLANTATION Hollander, S. A., McDonald, N., Lee, D., May, L. J., Doan, L. N., Kaufman, B. D., Rosenthal, D. N. 2015; 19 (7): 730-736

  Abstract

  The "GVM" has emerged as an alternative to traditional individualized appointments in the ambulatory care setting. We hypothesized that group visits could successfully be utilized in a PHtx clinic. Seven patients, ages 1-18 yr old, and their families participated in a total of 11 group visits in lieu of individualized appointments. Patients were divided into two groups based on whether they were greater or less than one yr post-transplant. Patient/provider satisfaction, medication adherence, and content retention were ascertained via questionnaires and free-response tests. Total clinic throughput time, including per-patient clinic utilization time, was compared to historical data. Six of seven patients completed the study with one dropout. Overall satisfaction ratings were 3.98 of 4 with all patients reporting that they would "strongly recommend" group visits to others. Health information retention tests demonstrated improvement between pre- and post-tests in eight of nine (89%) of the group visits. Overall clinic utilization decreased by nearly 50% while providing 70 min of face-to-face time with the provider. Medication adherence neared 100% for all patients. The GVM can be successfully applied to the PHtx population with high patient and provider satisfaction, more face-to-face time, excellent content retention, and greatly improved clinic efficiency.

  View details for DOI 10.1111/petr.12574

  View details for Web of Science ID 000362580100018

  View details for PubMedID 26250489

• Exploring Value in Congenital Heart Disease: An Evaluation of Inpatient Admissions CONGENITAL HEART DISEASE Shin, A. Y., Hu, Z., Jin, B., Lal, S., Rosenthal, D. N., Efron, B., Sharek, P. J., Sutherland, S. M., Cohen, H. J., McElhinney, D. B., Roth, S. J., Ling, X. B. 2015; 10 (6): E278-E287

  Abstract

  Understanding value provides an important context for improvement. However, most health care models fail to measure value. Our objective was to categorize inpatient encounters within an academic congenital heart program based on clinical outcome and the cost to achieve the outcome (value). We aimed to describe clinical and nonclinical features associated with value.We defined hospital encounters based on outcome per resource utilized. We performed principal component and cluster analysis to classify encounters based on mortality, length of stay, hospital cost and revenue into six classes. We used nearest shrunken centroid to identify discriminant features associated with the cluster-derived classes. These features underwent hierarchical clustering and multivariate analysis to identify features associated with each class.We analyzed all patients admitted to an academic congenital heart program between September 1, 2009, and December 31, 2012.A total of 2658 encounters occurred during the study period. Six classes were categorized by value. Low-performing value classes were associated with greater institutional reward; however, encounters with higher-performing value were associated with a loss in profitability. Encounters that included insertion of a pediatric ventricular assist device (log OR 2.5 [95% CI, 1.78 to 3.43]) and acquisition of a hospital-acquired infection (log OR 1.42 [95% CI, 0.99 to 1.87]) were risk factors for inferior health care value.Among the patients in our study, institutional reward was not associated with value. We describe a framework to target quality improvement and resource management efforts that can benefit patients, institutions, and payers alike.

  View details for DOI 10.1111/chd.12290

  View details for Web of Science ID 000367379300004

• Changes in Risk Profile Over Time in the Population of a Pediatric Heart Transplant Program. Annals of thoracic surgery Reinhartz, O., Maeda, K., Reitz, B. A., Bernstein, D., Luikart, H., Rosenthal, D. N., Hollander, S. A. 2015; 100 (3): 989-994

  Abstract

  Single-center data on pediatric heart transplantation spanning long time frames is sparse. We attempted to analyze how risk profile and pediatric heart transplant survival outcomes at a large center changed over time.We divided 320 pediatric heart transplants done at Stanford University between 1974 and 2014 into three groups by era: the first 20 years (95 transplants), the subsequent 10 years (87 transplants), and the most recent 10 years (138 transplants). Differences in age at transplant, indication, mechanical support, and survival were analyzed.Follow-up was 100% complete. Average age at time of transplantation was 10.4 years, 11.9 years, and 5.6 years in eras 1, 2, and 3, respectively. The percentage of infants who received transplants by era was 21%, 7%, and 18%, respectively. The indication of end-stage congenital heart disease vs cardiomyopathy was 24%, 22%, and 49%, respectively. Only 1 patient (1%) was on mechanical support at transplant in era 1 compared with 15% in era 2 and 30% in era 3. Overall survival was 72% at 5 years and 57% at 10 years. Long-term survival increased significantly with each subsequent era. Patients with cardiomyopathy generally had a survival advantage over those with congenital heart disease.The risk profile of pediatric transplant patients in our institution has increased over time. In the last 10 years, median age has decreased and ventricular assist device support has increased dramatically. Transplantation for end-stage congenital heart disease is increasingly common. Despite this, long-term survival has significantly and consistently improved.

  View details for DOI 10.1016/j.athoracsur.2015.05.111

  View details for PubMedID 26228604

• Changes in Risk Profile Over Time in the Population of a Pediatric Heart Transplant Program. Annals of thoracic surgery Reinhartz, O., Maeda, K., Reitz, B. A., Bernstein, D., Luikart, H., Rosenthal, D. N., Hollander, S. A. 2015; 100 (3): 989-995

  Abstract

  Single-center data on pediatric heart transplantation spanning long time frames is sparse. We attempted to analyze how risk profile and pediatric heart transplant survival outcomes at a large center changed over time.We divided 320 pediatric heart transplants done at Stanford University between 1974 and 2014 into three groups by era: the first 20 years (95 transplants), the subsequent 10 years (87 transplants), and the most recent 10 years (138 transplants). Differences in age at transplant, indication, mechanical support, and survival were analyzed.Follow-up was 100% complete. Average age at time of transplantation was 10.4 years, 11.9 years, and 5.6 years in eras 1, 2, and 3, respectively. The percentage of infants who received transplants by era was 21%, 7%, and 18%, respectively. The indication of end-stage congenital heart disease vs cardiomyopathy was 24%, 22%, and 49%, respectively. Only 1 patient (1%) was on mechanical support at transplant in era 1 compared with 15% in era 2 and 30% in era 3. Overall survival was 72% at 5 years and 57% at 10 years. Long-term survival increased significantly with each subsequent era. Patients with cardiomyopathy generally had a survival advantage over those with congenital heart disease.The risk profile of pediatric transplant patients in our institution has increased over time. In the last 10 years, median age has decreased and ventricular assist device support has increased dramatically. Transplantation for end-stage congenital heart disease is increasingly common. Despite this, long-term survival has significantly and consistently improved.

  View details for DOI 10.1016/j.athoracsur.2015.05.111

  View details for PubMedID 26228604

• Task Force 7: Pediatric Cardiology Fellowship Training in Pulmonary Hypertension, Advanced Heart Failure, and Transplantation JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Webber, S. A., Hsu, D. T., Ivy, D. D., Kulik, T. J., Pahl, E., Rosenthal, D. N., Morrow, W. R., Feinstein, J. A. 2015; 66 (6): 732-739

  View details for DOI 10.1016/j.jacc.2015.03.013

  View details for Web of Science ID 000359139600018

  View details for PubMedID 25777654

• Task Force 7: Pediatric Cardiology Fellowship Training in Pulmonary Hypertension, Advanced Heart Failure, and Transplantation (vol 66, pg 732, 2015) JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Webber, S. A., Hsu, D. T., Ivy, D. D., Kulik, T. J., Pahl, E., Rosenthal, D. N., Morrow, R., Feinstein, J. A. 2015; 66 (6): 763

  View details for DOI 10.1016/j.jacc.2015.06.1307

  View details for Web of Science ID 000359139600033

• Task Force 7: Pediatric Cardiology Fellowship Training in Pulmonary Hypertension, Advanced Heart Failure, and Transplantation CIRCULATION Webber, S. A., Hsu, D. T., Ivy, D. D., Kulik, T. J., Pahl, E., Rosenthal, D. N., Morrow, W. R., Feinstein, J. A. 2015; 132 (6): E99-E106

  View details for DOI 10.1161/CIR.0000000000000198

  View details for Web of Science ID 000359666700010

  View details for PubMedID 25769631

• Task Force 7: Pediatric Cardiology Fellowship Training in Pulmonary Hypertension, Advanced Heart Failure, and Transplantation. SPCTPD/ACC/AAP/AHA. Circulation Webber, S. A., Hsu, D. T., Ivy, D. D., Kulik, T. J., Pahl, E., Rosenthal, D. N., Morrow, W. R., Feinstein, J. A. 2015; 132 (6): e99-e106

  View details for DOI 10.1161/CIR.0000000000000198

  View details for PubMedID 25769631

• Quality of life in pediatric patients affected by electrophysiologic disease HEART RHYTHM Czosek, R. J., Cassedy, A. E., Wray, J., Wernovsky, G., Newburger, J. W., Mussatto, K. A., Mahony, L., Tanel, R. E., Cohen, M. I., Franklin, R. C., Brown, K. L., Rosenthal, D., Drotar, D., Marino, B. S. 2015; 12 (5): 899-908

  Abstract

  Treatment of electrophysiologic (EP) disease in pediatric patients has improved; however, the effects on quality of life (QOL) are unknown.The purpose of this study was to compare QOL within EP disease groups and to other congenital heart diseases, to evaluate the effects of cardiac rhythm devices on QOL, and to identify drivers of QOL in EP disease.Cross-sectional study of patient/parent proxy-reported Pediatric Cardiac Quality of Life Inventory scores (Total, Disease Impact, Psychosocial Impact) in subjects aged 8 to 18 years from 11 centers with congenital complete heart block (CCHB), ventricular tachycardia (VT), supraventricular tachycardia (SVT), and long QT syndrome (LQTS). QOL was compared between EP disease groups and congenital heart disease groups [bicuspid aortic valve (BAV), tetralogy of Fallot (TOF), and Fontan]. General linear modeling was used to perform group comparisons and to identify predictors of QOL variation.Among 288 patient-parent pairs, mean age was 12.8 ± 3.0 years. CCHB (μ = 83) showed higher patient Total QOL than other EP disease cohorts (P ≤ .02; LQTS μ = 73; SVT μ = 74). SVT (μ = 75) and LQTS (μ = 75) had lower patient Total scores than BAV (μ = 81; P ≤ .008). Patient/parent-proxy QOL scores for all EP disease groups were not different than TOF and higher than Fontan. The presence of a cardiac rhythm device was associated with lower QOL scores in LQTS (μ = 66 vs μ = 76; P < .01). Predictors of lower patient/parent-proxy QOL included EP disease type (P ≤ .03), increased medical care utilization (P ≤ .04), and no parental college degree (P ≤ .001).Given the significant variation in QOL in EP disease type, stratification by EP disease type and increased medical care utilization may allow for targeted interventions to improve QOL.

  View details for DOI 10.1016/j.hrthm.2015.01.022

  View details for Web of Science ID 000353333100011

  View details for PubMedID 25602174

• A novel pediatric treatment intensity score: development and feasibility in heart failure patients with ventricular assist devices. journal of heart and lung transplantation May, L. J., Ploutz, M., Hollander, S. A., Reinhartz, O., Almond, C. S., Chen, S., Maeda, K., Kaufman, B. D., Yeh, J., Rosenthal, D. N. 2015; 34 (4): 509-515

  Abstract

  The evolution of pharmacologic therapies and mechanical support including ventricular assist devices (VADs) has broadened the scope of care available to children with advanced heart failure. At the present time, there are only limited means of quantifying disease severity or the concomitant morbidity for this population. This study describes the development of a novel pediatric treatment intensity score (TIS), designed to quantify the burden of illness and clinical trajectory in children on VAD support.There were 5 clinical domains assessed: nutrition, respiratory support, activity level, cardiovascular medications, and care environment. A scale was developed through expert consensus. Higher scores indicate greater morbidity as reflected by intensity of medical management. To evaluate feasibility and face validity, the TIS was applied retrospectively to a subset of pediatric inpatients with VADs. The Bland-Altman method was used to assess limits of agreement.The study comprised 39 patients with 42 implantations. Bland-Altman interobserver and intraobserver comparisons showed good agreement (mean differences in scores of 0.02, limits of agreement ±0.12). Trends in TIS were concordant with the overall clinical impression of improvement. Scores remained ≥0.6 preceding VAD implantation and peaked at 0.71 3 days after VAD implantation.We describe a pediatric VAD scoring tool, to assess global patient morbidity and clinical recovery. We demonstrate feasibility of using this TIS in a test population of inpatients on VAD support.

  View details for DOI 10.1016/j.healun.2014.10.007

  View details for PubMedID 25538014

• Biventricular Berlin Heart EXCOR Pediatric Use Across the United States. The Annals of thoracic surgery Zafar, F., Jefferies, J. L., Tjossem, C. J., Bryant, R., Jaquiss, R. D., Wearden, P. D., Rosenthal, D. N., Cabrera, A. G., Rossano, J. W., Humpl, T., Morales, D. L. 2015; 99 (4): 1328-34

  Abstract

  Biventricular assist device (BiVAD) support was a strong predictor of early mortality in the Berlin Heart EXCOR Pediatric investigational device exemption (IDE) study (Assess Safety and Probable Benefit of the EXCOR Pediatric Ventricular Assist Device [VAD]). In adults, it has been identified that 5% to 10% of the VAD population is benefited by BiVAD support over left ventricular assist device (LVAD) support. An analysis of the Berlin Heart study cohort was performed to characterize patients supported with BiVAD, examine risk factors of mortality in this group, and identify subsets of patients in whom BiVAD is associated with survival.All EXCOR Pediatric devices (Berlin Heart, Inc, The Woodlands, TX) placed in North America between May 2007 and December 2010 comprised the study cohort of 204 patients (128 [63%] LVADs and 76 [37%] BiVADs). The following patient cohorts were analyzed to determine the effect of BiVAD use on survival: Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile 1 patients, patients with abnormal bilirubin levels, patients who received previous extracorporeal membrane oxygenation (ECMO), and patients with a 10-mL pump size.There were more patients with BiVADs in INTERMACS profile 1 (63% compared with 46%; p = 0.018). The incidence of major bleeding, neurologic and renal dysfunction, and infection was similar between BiVAD and LVAD groups. White race, abnormal glomerular filtration rate (GFR), sites with experience of less than 5 implantations, and use of 10-mL pumps were predictors of mortality in patients who received BiVADs. BiVADs were not associated with improved survival in any patient cohort; however, they were associated with increased mortality in patients who had undergone ECMO before receiving a VAD.BiVAD support was not associated with improved survival in any identified subset of patients. Although not randomized, these results (which were corrected for multiple possible risk factors) suggest that some children supported with BiVADs might have done better with LVADs alone. Further prospective studies will be needed to identify patient cohorts that will be better served with BIVAD support.

  View details for DOI 10.1016/j.athoracsur.2014.09.078

  View details for PubMedID 25704863

• Biventricular Berlin Heart EXCOR Pediatric Use Across the United States ANNALS OF THORACIC SURGERY Zafar, F., Jefferies, J. L., Tjossem, C. J., Bryant, R., Jaquiss, R. D., Wearden, P. D., Rosenthal, D. N., Cabrera, A. G., Rossano, J. W., Humpl, T., Morales, D. L. 2015; 99 (4): 1328-1334

  Abstract

  Biventricular assist device (BiVAD) support was a strong predictor of early mortality in the Berlin Heart EXCOR Pediatric investigational device exemption (IDE) study (Assess Safety and Probable Benefit of the EXCOR Pediatric Ventricular Assist Device [VAD]). In adults, it has been identified that 5% to 10% of the VAD population is benefited by BiVAD support over left ventricular assist device (LVAD) support. An analysis of the Berlin Heart study cohort was performed to characterize patients supported with BiVAD, examine risk factors of mortality in this group, and identify subsets of patients in whom BiVAD is associated with survival.All EXCOR Pediatric devices (Berlin Heart, Inc, The Woodlands, TX) placed in North America between May 2007 and December 2010 comprised the study cohort of 204 patients (128 [63%] LVADs and 76 [37%] BiVADs). The following patient cohorts were analyzed to determine the effect of BiVAD use on survival: Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile 1 patients, patients with abnormal bilirubin levels, patients who received previous extracorporeal membrane oxygenation (ECMO), and patients with a 10-mL pump size.There were more patients with BiVADs in INTERMACS profile 1 (63% compared with 46%; p = 0.018). The incidence of major bleeding, neurologic and renal dysfunction, and infection was similar between BiVAD and LVAD groups. White race, abnormal glomerular filtration rate (GFR), sites with experience of less than 5 implantations, and use of 10-mL pumps were predictors of mortality in patients who received BiVADs. BiVADs were not associated with improved survival in any patient cohort; however, they were associated with increased mortality in patients who had undergone ECMO before receiving a VAD.BiVAD support was not associated with improved survival in any identified subset of patients. Although not randomized, these results (which were corrected for multiple possible risk factors) suggest that some children supported with BiVADs might have done better with LVADs alone. Further prospective studies will be needed to identify patient cohorts that will be better served with BIVAD support.

  View details for DOI 10.1016/j.athoracsur.2014.09.078

  View details for Web of Science ID 000352162100042

• Quality of life and metrics of achievement in long-term adult survivors of pediatric heart transplant. Pediatric transplantation Hollander, S. A., Chen, S., Luikart, H., Burge, M., Hollander, A. M., Rosenthal, D. N., Maeda, K., Hunt, S. A., Bernstein, D. 2015; 19 (1): 76-81

  Abstract

  Many children who undergo heart transplantation will survive into adulthood. We sought to examine the QOL and capacity for achievement in long-term adult survivors of pediatric heart transplantation. Adults >18 yr of age who received transplants as children (≤18 yr old) and had survived for at least 10 yr post-transplant completed two self-report questionnaires: (i) Ferrans & Powers QLI, in which life satisfaction is reported as an overall score and in four subscale domains and is then indexed from 0 (very dissatisfied) to 1 (very satisfied); and (ii) a "Metrics of Life Achievement" questionnaire regarding income, education, relationships, housing status, and access to health care. A total of 20 subjects completed the survey. The overall mean QLI score was 0.77 ± 0.16. Subjects were most satisfied in the family domain (0.84 ± 0.21) and least satisfied in the psychological/spiritual domain (0.7 ± 0.28). Satisfaction in the domains of health/functioning and socioeconomic were intermediate at 0.78 and 0.76, respectively. Most respondents had graduated from high school, reported a median annual income >$50 000/yr, and lived independently. Adult survivors of pediatric heart transplant report a good QOL and demonstrate the ability to obtain an education, work, and live independently.

  View details for DOI 10.1111/petr.12384

  View details for PubMedID 25388808

• IVIG and graft coronary artery disease: A potentially deadly combination in pediatric heart transplant recipients PEDIATRIC TRANSPLANTATION Dorwart, E., McDonald, N., Maeda, K., Rosenthal, D. N., Hollander, S. A. 2015; 19 (1): 130-131

  View details for DOI 10.1111/petr.12377

  View details for PubMedID 25332012

• Neurological complications and outcomes in the Berlin Heart EXCOR® pediatric investigational device exemption trial. Journal of the American Heart Association Jordan, L. C., Ichord, R. N., Reinhartz, O., Humpl, T., Pruthi, S., Tjossem, C., Rosenthal, D. N. 2015; 4 (1)

  Abstract

  The Berlin Heart EXCOR(®) ventricular assist device has been approved for use in the United States as a bridge to heart transplantation in children. We sought to characterize neurological events in children supported with the Berlin Heart EXCOR(®) device.The multicenter prospective cohort consisted of all 204 children implanted with the Berlin Heart EXCOR(®) device at 47 centers in North America between May 2007 and December 2010. There were 73 neurological events in 59 patients, with 29% of the cohort experiencing ≥1 neurological event. Events included 52 strokes in 43 patients (21% of the cohort). The neurological event rate was 0.51 events per 100 patient-days. Many of the neurological events occurred early in the course of support, with 30 events recorded during the first 14 days of support. The mortality rate in participants with at least 1 neurological event was 42% (25 of 59), significantly higher than the 18% mortality rate (26 of 145) for those who did not have a neurological event (P=0.0006). Risk-factor analysis did not identify significant preimplantation predictors of neurological injury.Of children treated with the Berlin Heart EXCOR(®) device as a bridge to transplant, 29% experienced at least 1 neurological event. The majority of neurological events were ischemic strokes, and many of those occurred early in the course of support. Neurological injury was the leading cause of death after implantation of the Berlin Heart EXCOR(®) device. Risk stratification for stroke or neurological injury is not possible based on baseline preimplantation characteristics.www.clinicaltrials.gov. Unique Identifier: NCT00583661.

  View details for DOI 10.1161/JAHA.114.001429

  View details for PubMedID 25613996

• Neurological Complications and Outcomes in the Berlin Heart EXCOR® Pediatric Investigational Device Exemption Trial. Journal of the American Heart Association Jordan, L. C., Ichord, R. N., Reinhartz, O., Humpl, T., Pruthi, S., Tjossem, C., Rosenthal, D. N. 2015; 4 (1)

  Abstract

  The Berlin Heart EXCOR(®) ventricular assist device has been approved for use in the United States as a bridge to heart transplantation in children. We sought to characterize neurological events in children supported with the Berlin Heart EXCOR(®) device.The multicenter prospective cohort consisted of all 204 children implanted with the Berlin Heart EXCOR(®) device at 47 centers in North America between May 2007 and December 2010. There were 73 neurological events in 59 patients, with 29% of the cohort experiencing ≥1 neurological event. Events included 52 strokes in 43 patients (21% of the cohort). The neurological event rate was 0.51 events per 100 patient-days. Many of the neurological events occurred early in the course of support, with 30 events recorded during the first 14 days of support. The mortality rate in participants with at least 1 neurological event was 42% (25 of 59), significantly higher than the 18% mortality rate (26 of 145) for those who did not have a neurological event (P=0.0006). Risk-factor analysis did not identify significant preimplantation predictors of neurological injury.Of children treated with the Berlin Heart EXCOR(®) device as a bridge to transplant, 29% experienced at least 1 neurological event. The majority of neurological events were ischemic strokes, and many of those occurred early in the course of support. Neurological injury was the leading cause of death after implantation of the Berlin Heart EXCOR(®) device. Risk stratification for stroke or neurological injury is not possible based on baseline preimplantation characteristics.www.clinicaltrials.gov. Unique Identifier: NCT00583661.

  View details for DOI 10.1161/JAHA.114.001429

  View details for PubMedID 25613996

• Reliability of echocardiographic measurements of left ventricular systolic function in potential pediatric heart transplant donors. journal of heart and lung transplantation Chen, S., Selamet Tierney, E. S., Khush, K. K., Nguyen, J., Goldstein, B. A., May, L. J., Hollander, S. A., Kaufman, B. D., Rosenthal, D. N. 2015; 34 (1): 100-106

  Abstract

  Echocardiogram reports, but not images, are usually available for the evaluation of potential donor hearts. To assess the reliability of local reports of potential pediatric heart donors, we compared echocardiographic measurements of left ventricular (LV) systolic function between local hospitals and a central echocardiography laboratory.We identified all potential donors aged <18 years managed by the California Transplant Donor Network from 2009 to 2013. Echocardiograms and reports were obtained from local hospitals. All studies were reviewed in a central laboratory by an experienced pediatric cardiologist blinded to local reports. Local and central measurements of fractional shortening (FS) were compared using the Bland-Altman method (mean difference ± 2 standard deviations). LV function was categorized based on FS as normal or mild, moderately, or severely depressed.There were 70 studies from 59 donors with local and central measurements of FS. The mean difference between local and central FS was 3.9 ± 9.0. The limits of agreement ranged from -14.2 to 22. Twenty-five studies had discordant measurements of LV function, with 17 discordant by 1 category and 8 by 2 or more categories. Of 55 studies categorized as normal by local measurement, 6 were moderately to severely depressed by central review. Of 15 studies categorized as depressed by local measurement, 3 were normal by central review.Local and central measurements of LV systolic function were discordant in 36% of studies. Given such discordance, efforts to obtain and view actual echocardiographic images should be part of the standard evaluation of potential pediatric heart donors.

  View details for DOI 10.1016/j.healun.2014.08.019

  View details for PubMedID 25307622

  View details for PubMedCentralID PMC4278954

• HLA desensitization with bortezomib in a highly sensitized pediatric patient PEDIATRIC TRANSPLANTATION May, L. J., Yeh, J., Maeda, K., Tyan, D. B., Chen, S., Kaufman, B. D., Bernstein, D., Rosenthal, D. N., Hollander, S. A. 2014; 18 (8): E280-E282

  Abstract

  The proteasome inhibitor bortezomib has been used with variable success in the treatment of AMR following heart transplant. There is limited experience with this agent as a pretransplant desensitizing therapy. We report a case of successful HLA desensitization with a bortezomib-based protocol prior to successful heart transplantation. A nine-yr-old boy with dilated cardiomyopathy, not initially sensitized to HLA (cPRA of zero), required three days of ECMO, followed by implantation of a Heartmate II LVAD. Within six wk, the patient developed de novo class I IgG and C1q complement-fixing HLA antibodies with a cPRA of 100%. Two doses of IVIG (2 g/kg) failed to reduce antibody levels, although two courses of a novel desensitization protocol consisting of rituximab (375 mg/m(2) ), bortezomib (1.3 mg/m(2)  × 5 doses), and plasmapheresis reduced his cPRA to 0% and 87% by the C1q and IgG assays, respectively. He underwent heart transplantation nearly two months later. The patient is now >one yr post-transplant, is free of both AMR and ACR, and has no detectable donor-specific antibodies by IgG or C1q. Proteasome inhibition with bortezomib and plasmapheresis may be an effective therapy for HLA desensitization pretransplant.

  View details for DOI 10.1111/petr.12347

  View details for Web of Science ID 000344360500006

• HLA desensitization with bortezomib in a highly sensitized pediatric patient. Pediatric transplantation May, L. J., Yeh, J., Maeda, K., Tyan, D. B., Chen, S., Kaufman, B. D., Bernstein, D., Rosenthal, D. N., Hollander, S. A. 2014; 18 (8): E280-2

  Abstract

  The proteasome inhibitor bortezomib has been used with variable success in the treatment of AMR following heart transplant. There is limited experience with this agent as a pretransplant desensitizing therapy. We report a case of successful HLA desensitization with a bortezomib-based protocol prior to successful heart transplantation. A nine-yr-old boy with dilated cardiomyopathy, not initially sensitized to HLA (cPRA of zero), required three days of ECMO, followed by implantation of a Heartmate II LVAD. Within six wk, the patient developed de novo class I IgG and C1q complement-fixing HLA antibodies with a cPRA of 100%. Two doses of IVIG (2 g/kg) failed to reduce antibody levels, although two courses of a novel desensitization protocol consisting of rituximab (375 mg/m(2) ), bortezomib (1.3 mg/m(2)  × 5 doses), and plasmapheresis reduced his cPRA to 0% and 87% by the C1q and IgG assays, respectively. He underwent heart transplantation nearly two months later. The patient is now >one yr post-transplant, is free of both AMR and ACR, and has no detectable donor-specific antibodies by IgG or C1q. Proteasome inhibition with bortezomib and plasmapheresis may be an effective therapy for HLA desensitization pretransplant.

  View details for DOI 10.1111/petr.12347

  View details for PubMedID 25174602

• The International Society of Heart and Lung Transplantation Guidelines for the management of pediatric heart failure: Executive summary (vol 33, pg 888, 2014) JOURNAL OF HEART AND LUNG TRANSPLANTATION Kirk, R., Dipchand, A., Rosenthal, D. N., Addonizio, L., Burch, M., Chrisant, M., Dubin, A., Everitt, M., Gajarski, R., Mertens, L., Miyamoto, S., Morales, D., Pahl, E., Shaddy, R., Towbin, J. 2014; 33 (10)

  View details for DOI 10.1016/j.healun.2014.08.006

  View details for Web of Science ID 000342536200017

• The International Society for Heart and Lung Transplantation Guidelines for the management of pediatric heart failure: Executive summary. [Corrected]. journal of heart and lung transplantation Kirk, R., Dipchand, A. I., Rosenthal, D. N., Addonizio, L., Burch, M., Chrisant, M., Dubin, A., Everitt, M., Gajarski, R., Mertens, L., Miyamoto, S., Morales, D., Pahl, E., Shaddy, R., Towbin, J., Weintraub, R. 2014; 33 (9): 888-909

  View details for DOI 10.1016/j.healun.2014.06.002

  View details for PubMedID 25110323

• An inpatient rehabilitation program utilizing standardized care pathways after paracorporeal ventricular assist device placement in children. journal of heart and lung transplantation Hollander, S. A., Hollander, A. J., Rizzuto, S., Reinhartz, O., Maeda, K., Rosenthal, D. N. 2014; 33 (6): 587-592

  Abstract

  Structured rehabilitation programs in adults after ventricular assist device (VAD) placement result in improvements in physical function and exercise capacity, and have been shown to improve survival and accelerate post-transplant recovery. The objective of this study was to determine the safety and feasibility of an acute inpatient rehabilitation program for children utilizing standardized, age-appropriate, family-centered care pathways after paracorporeal VAD placement in both the ICU and acute-care inpatient settings.Between November 12, 2010 and March 15, 2013, 17 patients were referred to therapy after VAD implantation, 14 of whom were medically stable enough to participate. Beginning in the ICU, a structured physical and occupational therapy program was implemented utilizing novel age-appropriate, standardized care pathways for infants (age <1 year) and children (age 1 to 12 years). The infant and child pathways consisted of 8 and 10 goals, respectively. Retrospective review was conducted to ascertain the number of phases achieved per patient. Adverse events, defined as bleeding, physiologic instability, stroke, or device disruption during therapy, were also analyzed.The median age was 1.1 (range 0.5 to 14.4) years in the 14 patients considered medically stable enough to participate in rehabilitation. Nine of them were female. Eight patients participated in the infant standardized care pathway (SCP) and 6 participated in the child SCP. Seven patients were on biventricular support. Twelve patients were transplanted and survived. Two patients died while awaiting transplantation. There were 1,473 total days on the VAD (range 40 to 229 days). The median time to extubation was 2 days (range 1 to 8) and the median ICU stay was 6.5 days (range 3 to 152). Eleven patients achieved all goals of the SCP, including all of the patients in the child group. For the infant group, 5 patients achieved all goals of the SCP (range 5 to 8), and all but 1 patient achieved at least 7 goals of the SCP. There were no adverse events related to therapy.Standardized, family-centered inpatient rehabilitation care paths are safe for infants and children after paracorporeal device placement. Structured rehabilitation goals can be achieved by the majority of pediatric patients during VAD support. Early mobilization and inpatient rehabilitation in this cohort promotes normalization of function while awaiting cardiac transplantation.

  View details for DOI 10.1016/j.healun.2013.12.009

  View details for PubMedID 24468119

• Single Ventricle Reconstruction Trial A Work in Progress CIRCULATION Rosenthal, D. N. 2014; 129 (20): 2000–2001

  View details for PubMedID 24705120

  View details for PubMedCentralID PMC4084729

• In-hospital arrhythmia development and outcomes in pediatric patients with acute myocarditis. American journal of cardiology Miyake, C. Y., Teele, S. A., Chen, L., Motonaga, K. S., Dubin, A. M., Balasubramanian, S., Balise, R. R., Rosenthal, D. N., Alexander, M. E., Walsh, E. P., Mah, D. Y. 2014; 113 (3): 535-540

  Abstract

  Cardiac arrhythmias are a complication of myocarditis. There are no large studies of in-hospital arrhythmia development and outcomes in pediatric patients with acute myocarditis. This was a retrospective 2-center review of patients ≤21 years hospitalized with acute myocarditis from 1996 to 2012. Fulminant myocarditis was defined as the need for inotropic support within 24 hours of presentation. Acute arrhythmias occurred at presentation and subacute after admission. Eighty-five patients (59% men) presented at a median age of 10 years (1 day to 18 years). Arrhythmias occurred in 38 patients (45%): 16 acute, 12 subacute, and 9 acute and subacute (1 onset unknown). Arrhythmias were associated with low voltages on the electrocardiogram (14 of 34, 41% vs 6 of 47, 13%; odds ratio [OR] 4.78, 95% confidence interval [CI] 1.60 to 14.31) and worse outcome (mechanical support, orthotopic heart transplant, or death; OR 7.59, 95% CI 2.61 to 22.07) but were not statistically significantly associated with a fulminant course, ST changes, initial myocardial function, lactate, creatinine level, C-reactive protein and/or erythrocyte sedimentation rate, or troponin I level, after adjusting for multiple comparisons. Subacute arrhythmias were associated with preceding ST changes (10 of 15, 67% vs 15 of 59, 25%, OR 5.87, 95% CI 1.73 to 19.93). All patients surviving to discharge had arrhythmia resolution or control before discharge (10 on antiarrhythmic), with 1 exception (patient with complete heart block requiring a pacemaker). At 1-year follow-up, there were 3 recurrences of ventricular arrhythmias, but no arrhythmia-related mortality. In conclusion, arrhythmias are common in pediatric patients with myocarditis, occurring in nearly 1/2 of all hospitalized children and are associated with a worse outcome. Early identification of subacute arrhythmias using electrocardiographic changes may help management. A majority of patients do not require continued postdischarge arrhythmia treatment.

  View details for DOI 10.1016/j.amjcard.2013.10.021

  View details for PubMedID 24332245

• Successful bridge to transplant with a continuous flow ventricular assist device in a single ventricle patient with an aortopulmonary shunt. ASAIO journal Lal, A. K., Chen, S., Maeda, K., McCammond, A., Rosenthal, D. N., Reinhartz, O., Yeh, J. 2014; 60 (1): 119-121

  Abstract

  Ventricular assist devices are frequently used to bridge pediatric patients to cardiac transplantation; however, experience in single ventricle patients with aortopulmonary shunts remains limited. This case report addresses the challenge of balancing pulmonary and systemic circulation with a focus on the role of continuous versus pulsatile ventricular assist device support.

  View details for DOI 10.1097/MAT.0000000000000007

  View details for PubMedID 24270233

• Hot Topics in Tetralogy of Fallot JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Villafane, J., Feinstein, J. A., Jenkins, K. J., Vincent, R. N., Walsh, E. P., Dubin, A. M., Geva, T., Towbin, J. A., Cohen, M. S., Fraser, C., Dearani, J., Rosenthal, D., Kaufman, B., Graham, T. P. 2013; 62 (23): 2155-2166

  Abstract

  Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart defect. We explore "hot topics" to highlight areas of emerging science for clinicians and scientists in moving toward a better understanding of the long-term management of patients with repaired TOF. From a genetic perspective, the etiology of TOF is multifactorial, with a familial recurrence risk of 3%. Cardiac magnetic resonance is the gold standard assessment tool based on its superior imaging of the right ventricular (RV) outflow tract, pulmonary arteries, aorta, and aortopulmonary collaterals, and on its ability to quantify biventricular size and function, pulmonary regurgitation (PR), and myocardial viability. Atrial re-entrant tachycardia will develop in more than 30% of patients, and high-grade ventricular arrhythmias will be seen in about 10% of patients. The overall incidence of sudden cardiac death is estimated at 0.2%/yr. Risk stratification, even with electrophysiologic testing and cardiac magnetic resonance, remains imperfect. Drug therapy has largely been abandoned, and defibrillator placement, despite its high risks for complications and inappropriate discharges, is often recommended for patients at higher risk. Definitive information about optimal surgical strategies for primary repair to preserve RV function, reduce arrhythmia, and optimize functional status is lacking. Post-operative lesions are often amenable to transcatheter intervention. In selected cases, PR may be treated with transcatheter valve insertion. Ongoing surveillance of RV function is a crucial component of clinical assessment. Except for resynchronization with biventricular pacing, no medical therapies have been shown to be effective after RV dysfunction occurs. In patients with significant PR with RV dilation, optimal timing of pulmonary valve replacement remains uncertain, although accepted criteria are emerging.

  View details for DOI 10.1016/j.jacc.2013.07.100

  View details for Web of Science ID 000328073000002

  View details for PubMedID 24076489

• Genetic Variation Near HCRTR2 Associates With Dramatic Improvement of Heart Function in Patients With Heart Failure Perez, M. V., Pavlovic, A., Wheeler, M. T., Miller, C. L., Thanaporn, P., Dewey, F. E., Pan, S., Absher, D., Cretti, E., Southwick, A., Heidenreich, P., Sedehi, D., Brandimarto, J., Kao, D., Salisbury, H., Chan, K., Rosenthal, D., Bernstein, D., Fowler, M. B., Robbins, R. C., Meyers, R., Meyers, R., Quertermous, T., Cappola, T., Ashley, E. LIPPINCOTT WILLIAMS & WILKINS. 2013

  View details for Web of Science ID 000332162905323

• Orthotopic heart transplantation in two infants with histiocytoid cardiomyopathy and left ventricular non-compaction PEDIATRIC TRANSPLANTATION Siehr, S. L., Bernstein, D., Yeh, J., Berry, G. J., Rosenthal, D. N., Hollander, S. A. 2013; 17 (7): E165-E167

  Abstract

  HC is a rare cause of congestive heart failure that typically presents with malignant ventricular arrhythmias in infants, often requiring urgent intervention. Successful heart transplantation in a patient with HC has only been reported once (J Heart Lung Transplant 2004: 23: 902). The combination of HC with concurrent LVNC has only been described three times (Int J Legal Med 2009: 123: 47; Hum Pathol 2005: 36: 403; Pediatr Dev Pathol 2012: 15: 397). We report two rare cases of HC with LVNC in two infants presenting with cardiogenic shock, one requiring ECMO support who was successfully bridged to orthotopic heart transplantation with a Berlin Heart LVAD.

  View details for DOI 10.1111/petr.12141

  View details for Web of Science ID 000325369400004

  View details for PubMedID 24099092

• Long-term Cardiovascular Toxicity in Children, Adolescents, and Young Adults Who Receive Cancer Therapy: Pathophysiology, Course, Monitoring, Management, Prevention, and Research Directions A Scientific Statement From the American Heart Association CIRCULATION Lipshultz, S. E., Adams, J., Colan, S. D., Constine, L. S., Herman, E. H., Hsu, D. T., Hudson, M. M., Kremer, L. C., Landy, D. C., Miller, T. L., Oeffinger, K. C., Rosenthal, D. N., Sable, C. A., Sallan, S. E., Singh, G. K., Steinberger, J., Cochran, T. R., Wilkinson, J. D. 2013; 128 (17): 1927-1995

  View details for DOI 10.1161/CIR.0b013e3182a88099

  View details for Web of Science ID 000326026200019

  View details for PubMedID 24081971

• QRS prolongation is strongly associated with life-threatening ventricular arrhythmias in children with dilated cardiomyopathy. journal of heart and lung transplantation Dao, D. T., Hollander, S. A., Rosenthal, D. N., Dubin, A. M. 2013; 32 (10): 1013-1019

  Abstract

  The incidence of sudden death in children with dilated cardiomyopathy has been estimated at < 1% annually. This number, however, may underestimate the incidence of life-threatening arrhythmias. The objective of this study was to assess the incidence of and identify risk factors for life-threatening arrhythmias in children with dilated cardiomyopathy.We conducted a retrospective record review of 183 children with dilated cardiomyopathy treated at a single center between 2000 and 2011. Life-threatening arrhythmia was defined as any ventricular arrhythmia that resulted in syncope or hypotension and required medical intervention. Risk factors for life-threatening arrhythmias were identified with univariate analyses. A prediction model was constructed with multivariate logistic regression and receiver operating characteristic curves.Nineteen patients experienced life-threatening arrhythmias, representing an annualized rate of 4.9%. Outpatient life-threatening arrhythmias occurred at a rate of 2.2% per year. Predictors of outpatient life-threatening arrhythmias were longer QRS duration (p = 0.003) and increased left ventricular posterior wall (LVPWd) thickness (p = 0.03). Only QRS duration remained significant in multivariate logistic regression (odds ratio, 1.8 for every unit increase in z-score; 95% CI, 1.01-1.9; p = 0.04). For all life-threatening arrhythmias, prolonged QRS duration was the only significant risk factor in multivariate logistic regression (odds ratio, 1.5; 95% CI, 1.1-2.2; p = 0.02).In children with dilated cardiomyopathy, as QRS duration increases, so too does the risk of life-threatening arrhythmias. Life-threatening arrhythmias occurred at an annual rate of 5%, which was much higher than the previously reported rate of sudden cardiac death in this population.

  View details for DOI 10.1016/j.healun.2013.06.007

  View details for PubMedID 23932443

• Lower socioeconomic status is associated with worse outcomes after both listing and transplanting children with heart failure PEDIATRIC TRANSPLANTATION Davies, R. R., Russo, M. J., Reinhartz, O., Maeda, K., Rosenthal, D. N., Chin, C., Bernstein, D., Mallidi, H. R. 2013; 17 (6): 573-581

  Abstract

  The relationship between SES and outcomes surrounding pediatric cardiac transplantation is complex and influenced by recipient race. Broad-based studies of SES have not been performed. A retrospective review of all 5125 primary pediatric heart transplants performed in the United States between 2000 and 2011. Patients were stratified by SES based on zip code of residence and U.S. census data (low SES: 1637; mid-SES: 2253; high SES: 1235). Survival following listing and transplantation was compared across strata. Risk-adjusted long-term mortality on the waitlist was higher among low SES patients (hazard 1.32, CI 1.07-1.63). The relationship between SES and outcomes varied by race. Early risk-adjusted post-transplant outcomes were worst among high SES patients (10.8% vs. low SES: 8.9%, p < 0.05). The incidence of non-compliance was higher among low SES patients (p < 0.0001). Long-term risk-adjusted patient survival was poorer among low (hazard 1.41, CI 1.10-1.80) and mid-SES (1.29, 1.04-1.59) groups. Low SES is associated with worse outcomes on both the waitlist and late following transplantation. Higher SES patients had more complex transplants with higher early mortality. Further research should be directed at identifying and addressing underlying causal factors for these disparities.

  View details for DOI 10.1111/petr.12117

  View details for Web of Science ID 000322317700015

  View details for PubMedID 23834560

• Children with pulmonary arterial hypertension and prostanoid therapy: Long-term hemodynamics JOURNAL OF HEART AND LUNG TRANSPLANTATION Siehr, S. L., Ivy, D. D., Miller-Reed, K., Ogawa, M., Rosenthal, D. N., Feinstein, J. A. 2013; 32 (5): 546-552

  Abstract

  Pediatric patients with severe pulmonary arterial hypertension (PAH) are treated with intravenous epoprostenol or intravenous or subcutaneous treprostinil. Little is known about longitudinal hemodynamics and outcomes of epoprostenol, treprostinil, and transitions from epoprostenol to treprostinil.This was retrospective study of 77 pediatric patients (47 idiopathic PAH, 24 congenital heart disease-PAH) receiving epoprostenol or treprostinil from 1992 to 2010 at 2 centers. Outcomes were defined as living vs dead/transplant.Mean age at baseline was 7.7 ± 5.2 years, with follow-up of 4.3 ± 3.4 years. Thirty-seven patients were treated with epoprostenol, 20 with treprostinil, and 20 were transitioned from epoprostenol to treprostinil. Mean pulmonary-to-systemic vascular resistance ratio (Rp/Rs) for epoprostenol was 1.0 ± 0.4, 0.8 ± 0.4, 0.8 ± 0.4, 1.0 ± 0.4, and 1.2 ± 0.4, respectively, at baseline, 1, 2, 3, and 4 years. For treprostinil, Rp/Rs was 0.9 ± 0.3, 0.7 ± 0.3, 0.5 ± 0.2, (p < 0.01 vs baseline), and 1.1 ± 0.2, respectively, at baseline, 1, 2, and 3 to 4 years, respectively. There were similar changes in mean pulmonary artery pressure and pulmonary vascular resistance index. The Rp/Rs 1 year after epoprostenol to treprostinil transition increased from 0.6 to 0.8 (n = 7). Changes not statistically significant unless noted. Eight patients died or received a transplant within 2 years of baseline; compared with the rest of the cohort, mean baseline Rp/Rs, right atrial pressure, and pulmonary vascular resistance index were significantly worse in this group. Thirty-nine patients remain on prostanoids, 17 are off, 16 died, and 5 received heart-lung transplant. Kaplan-Meier 5-year transplant-free survival was 70% (95% confidence interval, 56%-80%).There was improvement in Rp/Rs on both therapies at 1 to 2 years that was not sustained. The 5-year transplant-free survival was better than in similar adult studies.

  View details for DOI 10.1016/j.healun.2013.01.1055

  View details for PubMedID 23453572

• Abdominal complaints as a common first presentation of heart failure in adolescents with dilated cardiomyopathy AMERICAN JOURNAL OF EMERGENCY MEDICINE Hollander, S. A., Addonizio, L. J., Chin, C., Lamour, J. M., Hsu, D. T., Bernstein, D., Rosenthal, D. N. 2013; 31 (4): 684-686

  Abstract

  We hypothesized that isolated gastrointestinal complaints (abdominal pain, nausea, anorexia, weight loss), in the absence of other symptoms, were a common mode of initial presentation in children with congestive heart failure (CHF).Ninety-eight patients younger than 18 years hospitalized with dilated cardiomyopathy at a single institution between January 1, 2000, and December 31, 2009, were included. Retrospective review of their presenting complaints was recorded and analyzed according to 3 age groups: 0 to 1 year (infants), 1 to 10 years (children), and 11 to 18 years (adolescents) of age.Respiratory symptoms were common in all age groups (range, 56%-63%). Gastrointestinal complaints were also common in all age groups (42%, 28%, and 65%, respectively) and were more frequent than respiratory complaints in adolescents. Adolescents were likely to present with abdominal pain as their only complaint (10/43, 23%). Chest pain, syncope, or cardiac arrest occurred rarely.Abdominal complaints are a common component of the presenting symptom complex of CHF in pediatric dilated cardiomyopathy in all age groups. In adolescents, abdominal complaints occur more frequently than respiratory complaints and often in the absence of any other symptoms. Unlike CHF in adults, chest pain, arrhythmia, or cardiac arrest occurs rarely at presentation in pediatric patients. Recognition of the different presenting symptoms of heart failure in children by primary providers is crucial to ensuring prompt diagnosis and timely initiation of therapy.

  View details for DOI 10.1016/j.ajem.2012.12.009

  View details for Web of Science ID 000316723400010

  View details for PubMedID 23380118

• Magnetic resonance imaging of the right ventricle in pediatric pulmonary arterial hypertension PULMONARY CIRCULATION Blalock, S., Chan, F., Rosenthal, D., Ogawa, M., Maxey, D., Feinstein, J. 2013; 3 (2): 350-355

  Abstract

  Pulmonary arterial hypertension (PAH) causes changes in the right ventricle (RV), affecting RV size and function, ultimately leading to death. These changes have been evaluated by cardiac MRI (CMR) in adults with PAH, but not in children. Using CMR in pediatric patients with PAH, we examined how RV size and function (1) compare to normal data, (2) change over time, and (3) compare to similar studies in the adult population. Data from two institutions were retrospectively reviewed. Subjects with PAH and a CMR were included. Baseline CMR variables (right and left ventricular end-diastolic and end-systolic volumes indexed for body surface area, and calculated stroke volume and ejection fraction) were compared to normative data and follow-up CMR data. Twenty-six subjects (15 female), age 2-16 (mean 11) years, with idiopathic PAH were included. All patients were on PAH medication, and 65% on prostacyclin therapy. The baseline 6-Minute Walk Distance (6MWD; 481 ± 137) was normal. RV volumes and ejection fraction were markedly abnormal compared to normal data (P < 0.001). Follow-up CMRs were analyzed in 15 patients. RV volumes and function and LV stroke volume showed no significant change over one year. Our pediatric patients with PAH have markedly abnormal right ventricles by CMR but have normal walk distances. The lack of change in CMR parameters over one year may represent a stable cohort and is different than similar studies in adults.

  View details for DOI 10.4103/2045-8932.114763

  View details for Web of Science ID 000209981500008

  View details for PubMedCentralID PMC3757829

• Pediatric Outpatient VAD Experience at Stanford 33rd Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation Lin, A., Liu, E., Keating, M., Maeda, K., Hollander, S., Rosenthal, D. ELSEVIER SCIENCE INC. 2013: S288–S288

  View details for Web of Science ID 000316712100799

• Magnetic resonance imaging of the right ventricle in pediatric pulmonary arterial hypertension. Pulmonary circulation Blalock, S., Chan, F., Rosenthal, D., Ogawa, M., Maxey, D., Feinstein, J. 2013; 3 (2): 350-355

  Abstract

  Pulmonary arterial hypertension (PAH) causes changes in the right ventricle (RV), affecting RV size and function, ultimately leading to death. These changes have been evaluated by cardiac MRI (CMR) in adults with PAH, but not in children. Using CMR in pediatric patients with PAH, we examined how RV size and function (1) compare to normal data, (2) change over time, and (3) compare to similar studies in the adult population. Data from two institutions were retrospectively reviewed. Subjects with PAH and a CMR were included. Baseline CMR variables (right and left ventricular end-diastolic and end-systolic volumes indexed for body surface area, and calculated stroke volume and ejection fraction) were compared to normative data and follow-up CMR data. Twenty-six subjects (15 female), age 2-16 (mean 11) years, with idiopathic PAH were included. All patients were on PAH medication, and 65% on prostacyclin therapy. The baseline 6-Minute Walk Distance (6MWD; 481 ± 137) was normal. RV volumes and ejection fraction were markedly abnormal compared to normal data (P < 0.001). Follow-up CMRs were analyzed in 15 patients. RV volumes and function and LV stroke volume showed no significant change over one year. Our pediatric patients with PAH have markedly abnormal right ventricles by CMR but have normal walk distances. The lack of change in CMR parameters over one year may represent a stable cohort and is different than similar studies in adults.

  View details for DOI 10.4103/2045-8932.114763

  View details for PubMedID 24015335

  View details for PubMedCentralID PMC3757829

• Low Dose Factor Eight Inhibitor Bypassing Activity (FEIBA) for Incessant Bleeding in Pediatric Patients on Mechanical Circulatory Support (MCS) 33rd Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation Maeda, K., Asija, R., Hollander, S., Williams, G., Yeh, J., Rosenthal, D., Reinhartz, O. ELSEVIER SCIENCE INC. 2013: S290–S290

  View details for Web of Science ID 000316712100803

• A Novel Scoring System for Recovery after VAD Implantation in Children: Initial Feasibility 33rd Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation Ploutz, M., Hollander, S., Reinhartz, O., Maeda, K., Yeh, J., Rosenthal, D. ELSEVIER SCIENCE INC. 2013: S289–S289

  View details for Web of Science ID 000316712100800

• Intermediate-term outcomes after combined heart-liver transplantation in children with a univentricular heart JOURNAL OF HEART AND LUNG TRANSPLANTATION Hollander, S. A., Reinhartz, O., Maeda, K., Hurwitz, M., Rosenthal, D. N., Bernstein, D. 2013; 32 (3): 368-370

  Abstract

  For patients with end-stage hepatic failure secondary to failing hemodynamics, combined heart-liver transplant (H-LT) remains the only option for long-term survival. We report a series of three pediatric patients who successfully underwent orthotopic H-LT for failed single-ventricle palliation. All three patients are currently living, now two, three, and five years post-transplant, and remain completely free of cardiac cellular allograft rejection despite reduced immunosuppression protocols. One patient, however, did develop acute antibody-mediated rejection in the immediate post-transplant period, suggesting that this protective effect may be less effective in attenuating humoral mechanisms of rejection.

  View details for DOI 10.1016/j.healun.2012.11.023

  View details for Web of Science ID 000315664600014

  View details for PubMedID 23415318

• Cognitive outcomes in pediatric heart transplant recipients bridged to transplantation with ventricular assist devices JOURNAL OF HEART AND LUNG TRANSPLANTATION Stein, M. L., Bruno, J. L., Konopacki, K. L., Kesler, S., Reinhartz, O., Rosenthal, D. 2013; 32 (2): 212-220

  Abstract

  Ventricular assist devices (VADs) have been associated with high rates of neurologic injury in pediatric patients during the period of support, but the delayed consequences of this type of injury have not been described in the literature.In this study we assess cognitive outcomes with indices of general intellectual functioning, including working memory, processing speed, perceptual reasoning and verbal comprehension, for pediatric heart transplant recipients who required VAD support as a bridge to transplant (n = 9). We present an aggregate of these VAD patients combined with heart transplant recipients who did not require mechanical circulatory support (n = 11), and compare the performance of all transplant patients (n = 20) to typically developing, healthy comparators (n = 12). We also present a post hoc analysis of those transplant recipients with significant medical morbidity in the first year of life, referred to as the "high-risk" transplant group (n = 5), and compare them with the "low-risk" transplant group (n = 15) and the typically developing comparators (n = 12).The mean performance of the VAD patients was in the average range for each of the examined indices of cognitive functioning. A total of 11% of the VAD patients performed in the impaired range and 78% performed in the average range, with 11% in the superior range on measures of general intellectual functioning. The typically developing participants performed significantly better than the aggregated transplant recipients on all indices except verbal comprehension. Lower cognitive performance in the combined transplant group appears to be associated with medical morbidity in the first year of life.Despite significant neurologic risk factors, this cohort of pediatric patients who were bridged to transplant with VAD demonstrated resiliency in terms of cognitive outcomes. In this heterogeneous population, it is likely that multiple factors contributed to the cognitive outcomes. As VAD use becomes more common in pediatric patients, a prospective evaluation of cognitive outcomes is warranted.

  View details for DOI 10.1016/j.healun.2012.11.006

  View details for Web of Science ID 000314445800006

  View details for PubMedID 23352393

• Adaptive radiotherapy for head and neck cancer-Dosimetric results from a prospective clinical trial RADIOTHERAPY AND ONCOLOGY Schwartz, D. L., Garden, A. S., Shah, S. J., Chronowski, G., Sejpal, S., Rosenthal, D. I., Chen, Y., Zhang, Y., Zhang, L., Wong, P., Garcia, J. A., Ang, K. K., Dong, L. 2013; 106 (1): 80-84

  Abstract

  To conduct a clinical trial evaluating adaptive head and neck radiotherapy (ART).Patients with locally advanced oropharyngeal cancer were prospectively enrolled. Daily CT-guided setup and deformable image registration permitted mapping of dose to avoidance structures and CTVs. We compared four planning scenarios: (1) original IMRT plan aligned daily to marked isocenter (BB); (2) original plan aligned daily to bone (IGRT); (3) IGRT with one adaptive replan (ART1); and (4) actual treatment received by each study patient (IGRT with one or two adaptive replans, ART2).All 22 study patients underwent one replan (ART1); eight patients had two replans (ART2). ART1 reduced mean dose to contralateral parotid by 0.6 Gy or 2.8% (paired t-test; p=0.003) and ipsilateral parotid by 1.3 Gy (3.9%) (p=0.002) over the IGRT alone. ART2 further reduced the mean contralateral parotid dose by 0.8 Gy or 3.8% (p=0.026) and ipsilateral parotid by 4.1 Gy or 9% (p=0.001). ART significantly reduced integral body dose.This pilot trial suggests that head and neck ART dosimetrically outperforms IMRT. IGRT that leverages conventional PTV margins does not improve dosimetry. One properly timed replan delivers the majority of achievable dosimetric improvement. The clinical impact of ART must be confirmed by future trials.

  View details for DOI 10.1016/j.radonc.2012.10.010

  View details for Web of Science ID 000316303800013

• Insights into dyssynchrony in Hypoplastic Left Heart Syndrome HEART RHYTHM Motonaga, K. S., Miyake, C. Y., Punn, R., Rosenthal, D. N., Dubin, A. M. 2012; 9 (12): 2010-2015

  Abstract

  Cardiac resynchronization therapy has been proposed for treatment of hypoplastic left heart syndrome (HLHS) patients with right ventricular (RV) failure. The role of dyssynchrony, however, is poorly understood in this population.The purpose of this study was to better understand the relationship between electrical and mechanical dyssynchrony in HLHS using 3-dimensional electrical mapping, tissue Doppler indices of wall motion, and vector velocity imaging.Eleven HLHS subjects with normal RV function and ten normal subjects (age 3-18 years) were studied. Electrical and mechanical activation times and dyssynchrony indices (electrical dyssynchrony index, mechanical dyssynchrony index) were calculated using 3-dimensional electrical mapping, tissue Doppler indices, and vector velocity imaging.No differences in measures of electrical dyssynchrony were seen when comparing HLHS patients and normal patients (electrical activation time 63.3 ± 22.8 ms vs 56.2 ± 11.2 ms, P = .38; electrical dyssynchrony index 13.7 ± 6.3 ms vs 11.6 ± 3.0 ms, P = .34). However, measures of mechanical dyssynchrony were markedly abnormal in HLHS patients despite normal RV function (mechanical activation time 16 ± 11.3 ms vs 0.9±1.9 ms, P = .01; mechanical dyssynchrony index 7.5 ± 5.5 vs 0.4 ± 0.8, P<.01).Patients with HLHS and preserved RV systolic function have normal electrical activation when compared to patients with normal right and left ventricles. In contrast, these patients demonstrate mechanical dyssynchrony compared to patients with normal right and left ventricles. This finding raises important questions about the indications for cardiac resynchronization therapy in this patient population.

  View details for DOI 10.1016/j.hrthm.2012.08.031

  View details for Web of Science ID 000311791900029

  View details for PubMedID 23085485

• QRS Duration is a Risk Factor for Life Threatening Ventricular Arrhythmias in Children with Dilated Cardiomyopathy Dao, D. T., Hollander, S. A., Rosenthal, D. N., Dubin, A. M. LIPPINCOTT WILLIAMS & WILKINS. 2012

  View details for Web of Science ID 000208885001061

• Ventricular Assist Device (VAD) Support as a Bridge To Pediatric Heart Transplantation: A Practice In Rapid Evolution Dipchand, A. I., Naftel, D. C., Tresler, M., Blume, E. D., Kirk, R., Morrows, W. R., Auerbach, S. R., Richmond, M. E., Rosenthal, D. N., Kirklin, J. K. LIPPINCOTT WILLIAMS & WILKINS. 2012

  View details for Web of Science ID 000208885002175

• Prospective Trial of a Pediatric Ventricular Assist Device NEW ENGLAND JOURNAL OF MEDICINE Fraser, C. D., Jaquiss, R. D., Rosenthal, D. N., Humpl, T., Canter, C. E., Blackstone, E. H., Naftel, D. C., Ichord, R. N., Bomgaars, L., Tweddell, J. S., Massicotte, M. P., Turrentine, M. W., Cohen, G. A., Devaney, E. J., Pearce, F. B., Carberry, K. E., Kroslowitz, R., Almond, C. S. 2012; 367 (6): 532-541

  Abstract

  Options for mechanical circulatory support as a bridge to heart transplantation in children with severe heart failure are limited.We conducted a prospective, single-group trial of a ventricular assist device designed specifically for children as a bridge to heart transplantation. Patients 16 years of age or younger were divided into two cohorts according to body-surface area (cohort 1, <0.7 m(2); cohort 2, 0.7 to <1.5 m(2)), with 24 patients in each group. Survival in the two cohorts receiving mechanical support (with data censored at the time of transplantation or weaning from the device owing to recovery) was compared with survival in two propensity-score-matched historical control groups (one for each cohort) undergoing extracorporeal membrane oxygenation (ECMO).For participants in cohort 1, the median survival time had not been reached at 174 days, whereas in the matched ECMO group, the median survival was 13 days (P<0.001 by the log-rank test). For participants in cohort 2 and the matched ECMO group, the median survival was 144 days and 10 days, respectively (P<0.001 by the log-rank test). Serious adverse events in cohort 1 and cohort 2 included major bleeding (in 42% and 50% of patients, respectively), infection (in 63% and 50%), and stroke (in 29% and 29%).Our trial showed that survival rates were significantly higher with the ventricular assist device than with ECMO. Serious adverse events, including infection, stroke, and bleeding, occurred in a majority of study participants. (Funded by Berlin Heart and the Food and Drug Administration Office of Orphan Product Development; ClinicalTrials.gov number, NCT00583661.).

  View details for DOI 10.1056/NEJMoa1014164

  View details for Web of Science ID 000307310800007

  View details for PubMedID 22873533

• Electrical and mechanical dyssynchrony in pediatric pulmonary hypertension JOURNAL OF HEART AND LUNG TRANSPLANTATION Hill, A. C., Maxey, D. M., Rosenthal, D. N., Siehr, S. L., Hollander, S. A., Feinstein, J. A., Dubin, A. M. 2012; 31 (8): 825-830

  Abstract

  Electrical and mechanical dyssynchrony are often seen in patients with left ventricular failure. In pediatric pulmonary hypertension (PH), right ventricular failure predominates; however, the prevalence of electrical and/or mechanical dyssynchrony in these patients is unknown. We examined the prevalence of electrical and mechanical dyssynchrony in pediatric PH patients.Medical records (including, functional status, electrocardiograms and echocardiograms) of pediatric PH patients were reviewed. QRS duration z-scores were calculated to determine electrical dyssynchrony. Echo vector velocity imaging was used to calculate the mechanical dyssynchrony index (DI).Seventy-seven PH patients (idiopathic pulmonary arterial hypertension [IPAH]: n = 26; congenital heart disease: n = 41; other: n = 10) were studied. Electrical dyssynchrony was seen in 84% (p < 0.01 vs historic controls), with a mean z-score of 4.3 (95% CI 3.5 to 5.1). There was no difference between those with IPAH, z = 3.6 (95% CI 2.5 to 4.6), and those without, z = 4.7 (95% CI 3.6 to 5.8). Mechanical dyssynchrony was seen in 76% of patients (mean DI = 66 ± 47 vs 18 ± 8 milliseconds in historic controls, p < 0.01) in both IPAH and non-IPAH patients. Post-operative congenital heart disease patients had the largest dyssynchrony index. No correlation was found among electrical or mechanical dyssynchrony, hemodynamics or disease severity.Significant electrical and mechanical dyssynchrony is present in pediatric PH patients, regardless of etiology. The overall effect of electrical and mechanical dyssynchrony on outcomes in this patient population is still unknown. Select patients may benefit from resynchronization therapy.

  View details for DOI 10.1016/j.healun.2012.04.004

  View details for PubMedID 22682994

• Risk Factors for Cognitive Impairment in Children Undergoing Pediatric Heart Transplant Smoot, L. B., VanderPluym, C., Oliva, M., Rosenthal, D. N., Bastardi, H., Singh, T. P., Gauvreau, K., Almond, C. S. CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS. 2012: S39–S40

  View details for DOI 10.1016/j.cardfail.2012.06.135

  View details for Web of Science ID 000307679700126

• Outcomes of Children Following a First Hospitalization for Dilated Cardiomyopathy CIRCULATION-HEART FAILURE Hollander, S. A., Bernstein, D., Yeh, J., Dao, D., Sun, H. Y., Rosenthal, D. 2012; 5 (4): 437-443

  Abstract

  We hypothesized that children with dilated cardiomyopathy who require hospital admission are at increased risk for death or transplantation during their first hospitalization and in the first year that follows. We also assessed the value of routine data collected during that time to predict death or the need for transplantation prior to discharge and within 1 year of admission.We conducted a retrospective review of 83 pediatric patients with dilated cardiomyopathy whose initial hospitalization fell between 2004 and 2009. The mean age at hospitalization was 7 years. The majority of patients demonstrated moderate or severe left ventricular dysfunction on initial echocardiogram (80%) and/or the need for intravenous inotropes within 7 days of hospital admission (69%). Five patients (6%) died, and 15 (18%) were transplanted in the initial hospitalization. At 1 year, 11/71 (15%) had died, and 27/71 (38%) were transplanted. The overall freedom from death, transplantation, or rehospitalization at 1 year following admission was 21%. Fractional shortening, left ventricular ejection fraction, serum cholesterol, uric acid, mixed venous saturation, and atrial filling pressures were all predictive of death or transplantation during the initial hospitalization. Left ventricular ejection fraction was predictive of death or transplantation at 1 year.The first hospitalization for dilated cardiomyopathy marks a period of high risk for clinical decline, end stage heart failure, and the need for cardiac transplantation. Echocardiographic function and hemodynamic and serum measurements may aid in predicting outcomes. Despite medical management, most patients will be rehospitalized and/or require cardiac transplantation within 1 year of admission.

  View details for DOI 10.1161/CIRCHEARTFAILURE.111.964510

  View details for Web of Science ID 000313578100013

  View details for PubMedID 22570362

• Randomized controlled trial of acupuncture for prevention of radiation-induced xerostomia among patients with nasopharyngeal carcinoma CANCER Meng, Z., Garcia, M. K., Hu, C., Chiang, J., Chambers, M., Rosenthal, D. I., Peng, H., Zhang, Y., Zhao, Q., Zhao, G., Liu, L., Spelman, A., Palmer, J. L., Wei, Q., Cohen, L. 2012; 118 (13): 3337-3344

  Abstract

  Xerostomia (dry mouth) after head/neck radiation is a common problem among cancer patients, and available treatments are of little benefit. The objective of this trial was to determine whether acupuncture can prevent xerostomia among head/neck patients undergoing radiotherapy.A randomized, controlled trial among patients with nasopharyngeal carcinoma was conducted comparing acupuncture to standard care. Participants were treated at Fudan University Shanghai Cancer Center, Shanghai, China. Forty patients were randomized to acupuncture treatment and 46 to standard care. Patients were treated 3×/wk on the same days they received radiotherapy. Subjective measures included the Xerostomia Questionnaire and MD Anderson Symptom Inventory-Head and Neck (MDASI-HN). Objective measures were unstimulated and stimulated whole salivary flow rates. Patients were followed for 6 months after the end of radiotherapy.Xerostomia Questionnaire scores for acupuncture were statistically significantly lower than for controls starting in week 3 through the 6 months (P = .003 at week 3, all other P < .0001), with clinically significant differences as follows: week 11, relative risk (RR) 0.63 (95% confidence interval [CI], 0.45-0.87); 6 months, RR 0.38 (95% CI, 0.19-0.76). Similar findings were seen for MDASI-HN scores. Group differences emerged as early as 3 weeks into treatment for saliva (unstimulated whole salivary flow rate, P = .0004), with greater saliva flow in the acupuncture group at week 7 (unstimulated whole salivary flow rate, P < .0001; stimulated whole salivary flow rate, P = .002) and 11 (unstimulated whole salivary flow rate, P < .02; stimulated whole salivary flow rate, P < .03) and at 6 months (stimulated whole salivary flow rate, P < .003).Acupuncture given concurrently with radiotherapy significantly reduced xerostomia and improved quality of life.

  View details for DOI 10.1002/cncr.26550

  View details for Web of Science ID 000305389500019

  View details for PubMedID 22072272

• Perioperative management of the morbidly obese adolescent with heart failure undergoing bariatric surgery PEDIATRIC ANESTHESIA Maxwell, B. G., Ingrande, J., Rosenthal, D. N., Ramamoorthy, C. 2012; 22 (5): 476-482

  Abstract

  The incidence and prevalence of adolescent obesity and adolescent heart failure are increasing, and anesthesiologists increasingly will encounter patients with both conditions. A greater understanding of the physiologic challenges of adolescent heart failure as they relate to the perioperative stressors of anesthesia and bariatric surgery is necessary to successfully manage the perioperative risks faced by this growing subpopulation. Here, we present a representative case of a morbidly obese adolescent with heart failure who underwent a laparoscopic bariatric operation and review the limited available literature on perioperative management in this age group. Specifically, we review evidence and offer recommendations related to preoperative evaluation, venous thromboembolism prophylaxis, positioning, induction, airway management, monitoring, anesthetic maintenance, ventilator management, and adverse effects of the pneumoperitoneum, rhabdomyolysis, and postoperative care.

  View details for DOI 10.1111/j.1460-9592.2012.03824.x

  View details for Web of Science ID 000302540900011

  View details for PubMedID 22385267

• Is There a Rote for Cardiac Resynchronization Therapy in Pediatric Pulmonary Hypertension? 32nd Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation / Meeting of the ISHLT Academy - Core Competencies in Mechanical Circulatory Support Motonaga, K. S., MIYAKE, C. Y., Punn, R., Rosenthal, D. N., Feinstein, J. A., Dubin, A. M. ELSEVIER SCIENCE INC. 2012: S29–S29

  View details for Web of Science ID 000302207900059

• Complement Fixation by C1q vs MFI: Detection of Clinically Relevant Antibodies 32nd Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation / Meeting of the ISHLT Academy - Core Competencies in Mechanical Circulatory Support Castleberry, C. D., Chin, C., Rosenthal, D., Bernstein, D., HOLLANDER, S. A., Tyan, D. ELSEVIER SCIENCE INC. 2012: S139–S140

  View details for Web of Science ID 000302207900392

• Use of the Impella 5.0 as a bridge from ECMO to implantation of the HeartMate II left ventricular assist device in a pediatric patient PEDIATRIC TRANSPLANTATION Hollander, S. A., Reinhartz, O., Chin, C., Yeh, J., Maeda, K., Mallidi, H., Bernstein, D., Rosenthal, D. 2012; 16 (2): 205-206

  View details for DOI 10.1111/j.1399-3046.2011.01578.x

  View details for Web of Science ID 000300709600022

  View details for PubMedID 21923883

• End-Stage Renal Disease and Cardiomyopathy in Children: Cardiac Effects of Renal Transplantation TRANSPLANTATION Lal, A. K., de Biasi, A. R., Alexander, S., Rosenthal, D. N., Sutherland, S. M. 2012; 93 (2): 182-187

  Abstract

  The occurrence and progression of cardiomyopathy is well known in patients with end-stage renal disease (ESRD). However, the feasibility of renal transplantation in the setting of cardiac dysfunction and the effect of renal transplantation on this progression remain poorly studied in pediatric patients.A single-center, retrospective review of pediatric renal transplants between January 1, 2001, and December 31, 2010, was conducted. Six children with ESRD and severe systolic dysfunction underwent renal transplantation. Clinical data were collected and compared for the pretransplant, peritransplant, and posttransplant periods.Nutritional support, dialysis, and chronic kidney disease and heart failure therapy led to improved cardiac function before transplantation (ejection fraction 28.8%±9.6% vs. 44.4%±11.5%; fractional shortening 12.7%±5.1% vs. 23.6%±6.2%); however, normal systolic function was not achieved before transplantation in any patient. After transplantation, two patients had normalization of systolic function by hospital discharge, while the systolic function of the remaining four patients normalized during the first posttransplant year. Mean ejection fraction 1 year posttransplant was 22 units greater than before transplant. All patients experienced excellent allograft function in the peritransplant period. Mean estimated creatinine clearance 1 year posttransplant was 93.2±33.3 mL/min/1.73 m(2).Renal transplantation can be performed safely in children with ESRD and severe systolic dysfunction. After transplantation, systolic function continues to improve and may reach normal levels during the first posttransplant year. The presence of severe systolic dysfunction in pediatric dialysis patients should not deter referral for renal transplantation.

  View details for DOI 10.1097/TP.0b013e31823be7f8

  View details for PubMedID 22146314

• Outcomes of Children Implanted with Ventricular Assist Devices in the United States: Analysis of the Interagency Registry for Mechanical Circulatory Support (INTERMACS) Morales, D. L., Lowry, A. W., Epstein, D. J., Rosenthal, D. N., Chen, J. M., Almond, C. S., Wearden, P. D., Naftel, D. C., Kirklin, J. K., Blume, E. D. LIPPINCOTT WILLIAMS & WILKINS. 2011

  View details for Web of Science ID 000299738702229

• Characteristics and Outcome After Hospitalization for Acute Right Heart Failure in Patients With Pulmonary Arterial Hypertension CIRCULATION-HEART FAILURE Haddad, F., Peterson, T., Fuh, E., Kudelko, K. T., Perez, V. D., Skhiri, M., Vagelos, R., Schnittger, I., Denault, A. Y., Rosenthal, D. N., Doyle, R. L., Zamanian, R. T. 2011; 4 (6): 692-699

  Abstract

  Although much is known about the risk factors for poor outcome in patients hospitalized with acute heart failure and left ventricular dysfunction, much less is known about the syndrome of acute heart failure primarily affecting the right ventricle (acute right heart failure).By using Stanford Hospital's pulmonary hypertension database, we identified consecutive acute right heart failure hospitalizations in patients with PAH. We used longitudinal regression analysis with the generalized estimating equations method to identify factors associated with an increased likelihood of 90-day mortality or urgent transplantation. From June 1999 to September 2009, 119 patients with PAH were hospitalized for acute right heart failure (207 episodes). Death or urgent transplantation occurred in 34 patients by 90 days of admission. Multivariable analysis identified a higher respiratory rate on admission (>20 breaths per minute; OR, 3.4; 95% CI, 1.5-7.8), renal dysfunction on admission (glomerular filtration rate <45 mL/min per 1.73 m2; OR, 2.7; 95% CI, 1.2-6.3), hyponatremia (serum sodium ≤136 mEq/L; OR, 3.6; 95% CI, 1.7-7.9), and tricuspid regurgitation severity (OR, 2.5 per grade; 95% CI, 1.2-5.5) as independent factors associated with an increased likelihood of death or urgent transplantation.These results highlight the high mortality after hospitalizations for acute right heart failure in patients with PAH. Factors identifiable within hours of hospitalization may help predict the likelihood of death or the need for urgent transplantation in patients with PAH.

  View details for DOI 10.1161/CIRCHEARTFAILURE.110.949933

  View details for PubMedID 21908586

• Berlin Heart EXCOR Pediatric ventricular assist device Investigational Device Exemption study: Study design and rationale AMERICAN HEART JOURNAL Almond, C. S., Buchholz, H., Massicotte, P., Ichord, R., Rosenthal, D. N., Uzark, K., Jaquiss, R. D., Kroslowitz, R., Kepler, M. B., Lobbestael, A., Bellinger, D., Blume, E. D., Fraser, C. D., Bartlett, R. H., Thiagarajan, R., Jenkins, K. 2011; 162 (3): 425-U41

  Abstract

  Currently, there are no Food and Drug Administration-approved devices available that can provide long-term mechanical circulatory support to smaller children with severe heart failure as a bridge to heart transplant (HT). In recent years, the Berlin Heart EXCOR Pediatric ventricular assist device (VAD) has emerged as a potential treatment option. Systematic data on the safety and efficacy of the EXCOR are limited.The Investigational Device Exemption (IDE) clinical study is designed to evaluate the safety and probable benefit of the EXCOR to support regulatory review of the device under the Humanitarian Device Exemption regulation. The study design and rationale are reviewed in light of the well-described challenges inherent in small population studies.The Berlin Heart EXCOR IDE clinical study is a prospective, multicenter, single-arm, clinical cohort study. Children aged 0 to 16 years with severe heart failure (Interagency Registry for Mechanically Assisted Circulatory Support profile 1 or 2) due to 2-ventricle heart disease and actively listed for HT comprise the primary study cohort. The control population is a propensity-matched retrospective cohort of children supported with extracorporeal membrane oxygenation, the only bridge device available to smaller children before the EXCOR. The primary efficacy end point is survival to heart transplantation or recovery. The primary safety end point is the incidence of serious adverse events as defined by pediatric Interagency Registry for Mechanically Assisted Circulatory Support criteria. The study will enroll a total of 48 subjects in 2 cohorts based on body surface area (cohort 1 <0.7 m(2), cohort 2 0.7-1.5 m(2)) and is powered to show safety superiority to a prespecified performance goal of 0.25 serious adverse events per day of support. Children ineligible for the primary cohort will still have access to the device in a third compassionate-use cohort where adverse event data will be collected for additional safety characterization of the device.The Berlin Heart IDE clinical study will be the first bridge-to-HT VAD study designed exclusively for children. It is anticipated that the study will provide important information on the safety and efficacy of the Berlin Heart EXCOR Pediatric in children while providing valuable lessons into the design and conduct of future VAD studies in children.

  View details for DOI 10.1016/j.ahj.2011.05.026

  View details for Web of Science ID 000294447400003

  View details for PubMedID 21884857

• The impact of heart failure severity at time of listing for cardiac transplantation on survival in pediatric cardiomyopathy JOURNAL OF HEART AND LUNG TRANSPLANTATION Larsen, R. L., Canter, C. E., Naftel, D. C., Tressler, M., Rosenthal, D. N., Blume, E. D., Mahle, W. T., Yung, D., Morrow, W. R., Orav, E. J., Wilkinson, J. D., Towbin, J. A., Lipshultz, S. E. 2011; 30 (7): 755-760

  Abstract

  The survival benefit of heart transplantation in adult heart failure is greatest for the sickest patients and negligible for patients not requiring inotropic or mechanical support. We hypothesized a similar survival benefit of heart transplantation for childhood cardiomyopathies with heart failure.A merged data set of children registered in both the Pediatric Cardiomyopathy Registry and the Pediatric Heart Transplant Study was used to assess differences in mortality before and after transplant in patients with different levels of heart failure severity. Severity was scored 2 if mechanical ventilatory or circulatory support was required, 1 if intravenous inotropes were required, or 0 if no support was required.For 332 eligible children, 12-month mortality after listing was 9% for those with a severity score of 0 (n = 105), 16% with a score of 1 (n = 118), and 26% with a score of 2 (n = 109; p = 0.002) with a 3%, 8%, and 20% mortality with severity scores at listing of 0, 1, and 2, respectively, occurring before transplant. Patients listed with a score of 0 frequently deteriorated: 50% received an allograft or died before transplant with severity scores of 1 or 2. The risk of deterioration increased with previous surgery (relative risk, 3.84; p = 0.03) in the short-term and with lower left ventricular mass z-score at time of presentation (relative risk, 1.74; p = 0.003) in the longer-term.Pediatric cardiomyopathy patients who require high levels of support receive a survival benefit from heart transplantation that is not shared by patients not requiring intravenous inotropic or mechanical support.

  View details for DOI 10.1016/j.healun.2011.01.718

  View details for Web of Science ID 000291898800003

  View details for PubMedID 21419658

  View details for PubMedCentralID PMC3110638

• Cardiomyopathy and heart failure in children: anesthetic implications PEDIATRIC ANESTHESIA Rosenthal, D. N., Hammer, G. B. 2011; 21 (5): 577-584

  Abstract

  The purpose of this article is to provide a brief but systematic overview of heart failure and cardiomyopathy in children and the anesthetic management of these patients. We will begin with disease definitions and descriptions of the disorders. Our review will include the epidemiology and etiology of the more prevalent underlying causes of heart failure, the principal pathophysiology of the specific cardiomyopathies, as well as the common therapies in use today in both inpatient and outpatient settings. Important implications for anesthetic management will be highlighted.

  View details for DOI 10.1111/j.1460-9592.2011.03561.x

  View details for PubMedID 21481080

• Cardiac resynchronization therapy in pediatric heart failure PROGRESS IN PEDIATRIC CARDIOLOGY Hollander, S. A., Rosenthal, D. N. 2011; 31 (2): 111–17

  View details for DOI 10.1016/j.ppedcard.2011.02.008

  View details for Web of Science ID 000213525200008

• Implementation of a Comprehensive Interdisciplinary Care Coordination of Infants and Young Children on Berlin Heart Ventricular Assist Devices JOURNAL OF CARDIOVASCULAR NURSING Staveski, S. L., Avery, S., Rosenthal, D. N., Roth, S. J., Wright, G. E. 2011; 26 (3): 231-238

  Abstract

  Young children supported on a ventricular assist device (VAD) can have prolonged hospitalizations awaiting heart transplantation. The adult VAD literature demonstrates that comprehensive programs optimize transplantation outcomes. The goal of this intervention was to create an interdisciplinary program to optimize care coordination and delivery in young children requiring a VAD.This study was a case review.We have supported 8 infants and young children with Berlin Heart VAD. These children's hospitalizations have been more complex than those of our older VAD patients, and they have required intensive care for prolonged periods. An interdisciplinary group evaluated our practices and identified areas for potential improvement. The focus group from our intensive care unit introduced multiple interventions to optimize interdisciplinary care coordination and consistency of practice. These included (1) interdisciplinary care guidelines for chronically, critically ill patients; (2) institution of a primary cardiovascular intensive care unit (CVICU) physician and nurse practitioner system; (3) introduction of a psychological intervention for families to minimize the impact of their extended CVICU stay; (4) implementation of early jejunal feeds; (5) a focused developmental and rehabilitation protocol, 6) implementation of a structured approach to minimizing blood transfusions; (7) increased structure for our interdisciplinary rounds to optimize team communication; (8) comprehensive nursing education including wound care, anticoagulation management, and laboratory draws; and (9) a protocol for off-unit rehabilitative/developmental interventions. These changes in both practice and approach for young VAD patients have also been of benefit to other chronically, critically ill children in the CVICU, as well as to our CVICU team.Comprehensive interdisciplinary care coordination and standardized practice can be achieved in the critical care setting for complex pediatric heart failure patients who require long-term VAD support.

  View details for DOI 10.1097/JCN.0b013e3181f29a2e

  View details for Web of Science ID 000289404100010

  View details for PubMedID 21099697

• GENETIC DETERMINANTS OF DRAMATIC IMPROVEMENT IN LEFT VENTRICULAR FUNCTION IN PATIENTS WITH HEART FAILURE 60th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) / I2 Summit / ACCF/Herman K. Gold Young Investigator's Award in Molecular and Cellular Cardiology Perez, M. V., Pavlovic, A., Wheeler, M. T., Dewey, F. E., Bernstein, D., Fowler, M. B., Robbins, R. C., Quertermous, T., Chan, K., Absher, D., Ho, M., Cretti, E., Southwick, A., Rosenthal, D., Myers, R. M., Heidenreich, P., Garrett, L., Sedehi, D., Kao, D., Salisbury, H., Ashley, E. A. ELSEVIER SCIENCE INC. 2011: E2041–E2041

  View details for Web of Science ID 000291695102046

• Electrical Dyssynchrony in Pediatric Pulmonary Arterial Hypertension 31st Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation (ISHLT) Hill, A. C., Maxey, D. M., Siehr, S. L., Rosenthal, D. N., Dubin, A. M., Feinstein, J. A. ELSEVIER SCIENCE INC. 2011: S224–S225

  View details for Web of Science ID 000288924300670

• Longitudinal Hemodynamic Changes in Pediatric Patients with Severe Pulmonary Arterial Hypertension (PAH) on Prostanoid Therapy 31st Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation (ISHLT) Siehr, S. L., Ivy, D., Miller-Reed, K., Ogawa, M., Rosenthal, D., Feinstein, J. A. ELSEVIER SCIENCE INC. 2011: S72–S72

  View details for Web of Science ID 000288924300198

• MRI Evaluation of the Right Ventricle in Pediatric Pulmonary Arterial Hypertension 31st Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation (ISHLT) Blalock, S. E., Ogawa, M., Chan, F., MAXEY, D., Rosenthal, D. N., Feinstein, J. A. ELSEVIER SCIENCE INC. 2011: S81–S81

  View details for Web of Science ID 000288924300224

• Clinical usefulness of a novel C1q assay to detect immunoglobulin G antibodies capable of fixing complement in sensitized pediatric heart transplant patients JOURNAL OF HEART AND LUNG TRANSPLANTATION Chin, C., Chen, G., Sequeria, F., Berry, G., Siehr, S., Bernstein, D., Rosenthal, D., Reinhartz, O., Tyan, D. 2011; 30 (2): 158-163

  Abstract

  Donor-specific antibodies (DSA) against human leukocyte antigens complicate transplantation with the potential for acute antibody-mediated rejection (AMR). Complement-fixing antibodies are required to initiate the complement cascade. Not all DSAs, however, can fix complement.A novel C1q assay was developed to detect the sub-set of immunoglobulin G (IgG) antibodies capable of fixing complement. Sera from 18 pediatric heart transplant patients were analyzed for DSAs using a Luminex platform (Luminex Inc, Austin, TX) and commercially available single-antigen bead assay kits. Biopsy specimens were assessed for AMR using histopathologic criteria and immunohistochemical staining.During the study period, 5 patients had AMR; of these, 2 were C1q virtual crossmatch positive (VXM+) and had persistent C1q DSAs after transplant, and 3 were C1q VXM- but antibody developed immediately after transplant. A positive C1q assay in the immediate post-transplant period had a positive predictive value (PPV) of 100% and a negative predictive value (NPV) of 100%, with 100% sensitivity and 100% specificity (Fisher exact p = 0.001). Of 11 patients who were IgG VXM+, 5 had AMR; the IgG VXM had a PPV of 45% and NPV of 100%, with 100% sensitivity and 54% specificity (Fisher exact p = 0.101).The C1q assay can detect a sub-set of antibodies capable of fixing complement and predicts AMR early after transplant. Avoiding only the donor antigens that would be recognized by the C1q assay may accelerate time to transplant by expansion of the donor pool and potentially allows transplantation of previously "incompatible" organs.

  View details for DOI 10.1016/j.healun.2010.08.020

  View details for Web of Science ID 000286545200008

  View details for PubMedID 20951058

• Bridging children of all sizes to cardiac transplantation: The initial multicenter North American experience with the Berlin Heart EXCOR ventricular assist device JOURNAL OF HEART AND LUNG TRANSPLANTATION Morales, D. L., Almond, C. S., Jaquiss, R. D., Rosenthal, D. N., Naftel, D. C., Massicotte, M. P., Humpl, T., Turrentine, M. W., Tweddell, J. S., Cohen, G. A., Kroslowitz, R., Devaney, E. J., Canter, C. E., Fynn-Thompson, F., Reinhartz, O., Imamura, M., Ghanayem, N. S., Buchholz, H., Furness, S., Mazor, R., Gandhi, S. K., Fraser, C. D. 2011; 30 (1): 1-8

  Abstract

  Beginning in 2000 and accelerating in 2004, the Berlin Heart EXCOR (Berlin Heart Inc Woodlands, TX) became the first pediatric-specific ventricular assist device (VAD) applied throughout North America for children of all sizes. This retrospective study analyzed the initial Berlin Heart EXCOR pediatric experience as a bridge to transplantation.Between June 2000 and May 2007, 97 EXCOR VADs were implanted in North America at 29 different institutions. The analysis is limited to 73 patients (75%) from 17 institutions, for which retrospective data were available.Median age and weight at VAD implant were 2.1 years (range, 12 days-17.8 years) and 11 kg (range, 3-87.6 kg), respectively. The primary diagnoses were dilated cardiomyopathy in 42 (58%), congenital heart disease in 19 (26%), myocarditis in 7 (10%), and other cardiomyopathies in 5 (7%). Pre-implant clinical condition was critical cardiogenic shock in 38 (52%), progressive decline in 33 (45%), or other in 2 (3%). Extracorporeal membrane oxygenation was used as a bridge to EXCOR in 22 patients (30%). Device selection was left VAD (LVAD) in 42 (57%) and biventricular assist devices (BiVAD) in 31 (43%). The EXCOR bridged 51 patients (70%) to transplant and 5 (7%) to recovery. Mortality on the EXCOR was 23% (n = 17) overall, including 35% (11 of 31) in BiVAD vs 14% (6 of 42) in LVAD patients (p = 0.003). Multivariate analysis showed younger age and BiVAD support were significant risk factors for death while on the EXCOR.This limited but large preliminary North American experience with the Berlin Heart EXCOR VAD as a bridge to cardiac transplantation for children of all ages and sizes points to the feasibility of this approach. The prospective investigational device evaluation trial presently underway will further characterize the safety and efficacy of the EXCOR as a bridge to pediatric cardiac transplantation.

  View details for DOI 10.1016/j.healun.2010.08.033

  View details for Web of Science ID 000286287000001

  View details for PubMedID 21145473

• Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS)-Defined Morbidity and Mortality Associated With Pediatric Ventricular Assist Device Support at a Single US Center The Stanford Experience CIRCULATION-HEART FAILURE Stein, M. L., Robbins, R., Sabati, A. A., Reinhartz, O., Chin, C., Liu, E., Bernstein, D., Roth, S., Wright, G., Reitz, B., Rosenthal, D. 2010; 3 (6): 682-688

  Abstract

  The use of ventricular assist devices (VADs) to bridge pediatric patients to heart transplantation has increased dramatically over the last 15 years. In this report, we present the largest US single-center report of pediatric VAD use to date. We present detailed descriptions of morbidity and mortality associated with VAD support, using standard Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) criteria for pediatrics to facilitate the comparison of these results to other studies.We retrospectively identified 25 patients younger than 18 years with 27 episodes of mechanical circulatory support using VADs as bridge to heart transplantation from January 1998 to December 2007. Survival to transplant for the entire cohort was 74%. The most common major morbidities, as defined by INTERMACS criteria for a pediatric population, were respiratory failure, major localized infections, major bleeding events, hepatic dysfunction, and right heart failure. Major neurological events occurred in 48% of the study population. The median time to the first occurrence of an adverse event was less than 14 days for respiratory failure, right heart failure, major localized infection, and major bleeding. Patients who died before transplantation had significantly more adverse events per day of support than did those who were successfully transplanted. Episodes of major bleeding, tamponade, acute renal failure, respiratory failure, and right heart failure were all associated with increased risk of mortality.INTERMACS criteria can be successfully used to analyze pediatric VAD outcomes. These data serve as a baseline for future studies of VAD support in children and indicate good survival rates but considerable morbidity.

  View details for DOI 10.1161/CIRCHEARTFAILURE.109.918672

  View details for PubMedID 20807863

• Outpatient management of pediatric heart failure. Heart failure clinics O'Connor, M. J., Rosenthal, D. N., Shaddy, R. E. 2010; 6 (4): 515-?

  Abstract

  The management of heart failure in children is becoming a specialized discipline within pediatric cardiology. Unlike the treatment of heart failure in adults, for which an extensive body of literature supports current treatment regimens, management of heart failure in children is largely guided by extrapolation from adult studies and expert opinion. This review focuses on the current state-of-the-art with respect to the outpatient management of heart failure in children.

  View details for DOI 10.1016/j.hfc.2010.05.007

  View details for PubMedID 20869651

• Cardiac Findings in Congenital Muscular Dystrophies PEDIATRICS Finsterer, J., Ramaciotti, C., Wang, C. H., Wahbi, K., Rosenthal, D., Duboc, D., Melacini, P. 2010; 126 (3): 538-545

  Abstract

  Cardiac involvement (CI) in congenital muscular dystrophies (CMDs) has been only rarely investigated so far. By means of a systematic literature search we reviewed the literature about CI in CMD and found that CI is apparently absent in Ullrich CMD or CMD with integrin deficiency and only mild in Bethlem CMD. CI in merosin deficiency includes dilated cardiomyopathy and systolic dysfunction. CI in dystroglycanopathies seems most prevalent among all CMDs and includes dilated cardiomyopathy, systolic dysfunction, and myocardial fibrosis in Fukuyama CMD. Among the nonspecified dystroglycanopathies, CI manifests as dilated cardiomyopathy, hypertrophic cardiomyopathy (CMP) or systolic dysfunction. With CMD type 1C, as well as with limb-girdle muscular dystrophy 2I, up to half of the patients develop dilated cardiomyopathy. In rigid-spine syndrome, predominantly the right heart is affected secondary to thoracic deformity. In patients who carry LMNA mutations, CI may manifest as dilated cardiomyopathy, hypertrophic cardiomyopathy, or fatal ventricular arrhythmias. Overall, CI in patients with CMD varies considerably between the different CMD types from absent or mild CI to severe cardiac disease, particularly in merosin deficiency, dystroglycanopathies, and laminopathies. Patients with CMD with CI require regular cardiologic surveillance so that severe, treatable cardiac disease is not overlooked.

  View details for DOI 10.1542/peds.2010-0208

  View details for Web of Science ID 000281535700017

  View details for PubMedID 20679303

• Outcomes of Children With Restrictive Cardiomyopathy Listed for Heart Transplant: A Multi-institutional Study JOURNAL OF HEART AND LUNG TRANSPLANTATION Zangwill, S. D., Naftel, D., L'Ecuyer, T., Rosenthal, D., Robinson, B., Kirklin, J. K., Stendahl, G., Dipchand, A. I. 2009; 28 (12): 1335-1340

  Abstract

  Restrictive cardiomyopathy (RCM) in children often has a progressive nature, with a high risk of clinical deterioration and death. Heart transplantation (HTx) is a widely accepted therapy that offers long-term survival, but criteria for and outcomes after listing have not been well defined.A multi-institutional, prospective, event-driven data registry of 3,147 patients aged < 18 years listed for HTx from January 1993 to December 2006 was used to assess risk factors and survival of 145 listed RCM patients.Mean age at listing was 8.1 years, with 44% listed as United Network of Organ Sharing status 1, 33% on inotropic support, 10% on a ventilator, and 5% on mechanical support. At 1 year, 82% of these patients survived to HTx, whereas 9% died waiting. Univariate risk factors for death while waiting included younger age (p < 0.001), ventilator dependence (p < 0.001), status 1 (p < 0.001), and inotrope usage (p < 0.001). Use of multiple support devices at listing (ventilator, extracorporeal membrane oxygenation, ventricular assist device, intraaortic balloon pump) was also an important risk factor for early phase death while waiting (relative risk; 9.01, p < 0.0001). Survival after listing was 63% at 10 years and compared favorably with survival for non-cardiomyopathy patients (p = 0.01).Children with RCM awaiting HTx have a generally low waitlist mortality and reasonable overall survival. Children requiring mechanical support and infants had a significantly higher risk of death while waiting. Further study is warranted to identify factors important in determining the optimal timing of listing in children with RCM before the need for inotropic or mechanical support.

  View details for DOI 10.1016/j.healun.2009.06.028

  View details for Web of Science ID 000272943500017

  View details for PubMedID 19783176

• Acute Effects of Single-site Pacing from the Left and Right Ventricle on Ventricular Function and Ventricular-Ventricular Interactions in Children with Normal Hearts CONGENITAL HEART DISEASE Friedberg, M. K., Dubin, A. M., Van Hare, G. F., McDaniel, G., Niksch, A., Rosenthal, D. N. 2009; 4 (5): 356-361

  Abstract

  We studied, as a physiological benchmark, acute effects of right ventricular (RV) apical, RV outflow, and left ventricular (LV) pacing in children with normal cardiac function on LV and RV function and ventricular-ventricular interactions.The design of the study was a prospective, acute intervention.The study was conducted in a tertiary care electrophysiology laboratory. Population and Methods. Seven children (mean +/- SD, 12 +/- 4 years) were paced after accessory pathway ablation, at baseline (AOO), and with atrioventricular pacing (DOO) from the RV apex, RV outflow, and left ventricle.Right ventricular dP/dT(max) and RV dP/dT(neg) (high-fidelity transducer-tipped catheters, Millar Instruments, Houston, TX, USA), cardiac index (Fick), blood pressure, and QRS duration were measured at each pacing condition. Intra- and interventricular mechanical dyssynchrony, systolic- and diastolic peak tissue velocities, and isovolumic acceleration were recorded by tissue Doppler imaging at the lateral mitral, septal, and tricuspid annuli at each condition. Results at each pacing condition were compared by repeated-measures analysis of variance. Results. Pacing prolonged QRS duration, causing electrical dyssynchrony (86 +/- 19 ms [baseline], 141 +/- 44 ms [RV apex], 121 +/- 18 ms [RV outflow], and 136 +/- 34 ms [LV], P < .01). Right ventricular outflow pacing caused LV intraventricular delay (63 +/- 52 vs. 12 +/- 7 ms, P < .05). Right ventricular apical pacing caused interventricular delay (61 +/- 29 vs. 25 +/- 18 ms, P < .05). There were no significant changes in blood pressure, cardiac index, RV dp/dT(max), RV dP/dT(neg), regional tissue velocities, or isovolumic acceleration during any of the pacing conditions, indicating preserved ventricular function and hemodynamics. No important ventricular-ventricular interactions were seen.In children with normal cardiac anatomy and function, single-site RV apical, RV outflow, and LV pacing induce electromechanical dyssynchrony without significantly changing ventricular function or hemodynamics, or adversely affecting ventricular-ventricular interactions.

  View details for DOI 10.1111/j.1747-0803.2009.00327.x

  View details for Web of Science ID 000207893900007

  View details for PubMedID 19740190

• Right ventricular resynchronization: Moving beyond proof of concept HEART RHYTHM Dubin, A. M., Rosenthal, D. N. 2009; 6 (6): 857-859

  View details for DOI 10.1016/j.hrthm.2009.03.010

  View details for Web of Science ID 000266658800022

  View details for PubMedID 19467516

• Pacing-Induced Electromechanical Ventricular Dyssynchrony Does Not Acutely Influence Right Ventricular Function and Global Hemodynamics in Children with Normal Hearts JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY Friedberg, M. K., Dubin, A. M., Van Hare, G. F., McDaniel, G. M., Niksch, A., Rosenthal, D. N. 2009; 20 (5): 539-544

  Abstract

  Right ventricular (RV) pacing may be detrimental to ventricular function. However, the acute effects of electromechanical dyssynchrony on RV function are not well characterized in children. We studied acute effects of electromechanical dyssynchrony, induced by RV apical and RV outflow pacing, in children with normal hearts, evaluating electromechanical synchrony, hemodynamic response, and RV function.Seventeen children (mean +/- SD, 12 +/- 4 years) with normal cardiac structure/function were paced after accessory pathway ablation, at baseline (AOO), and with AV pacing (DOO) from the RV apex and RV outflow. QRS duration was determined from surface ECG. Intra- and interventricular mechanical dyssynchrony and regional ventricular function were determined using tissue Doppler imaging. Global RV systolic and diastolic functions were assessed by RV dP/dT(max) and RV dP/dT(neg) using pressure-tipped transducers. Regional RV function was assessed by tissue Doppler imaging. Cardiac index (CI) and blood pressures were measured.RV apical and outflow pacing induced significant electromechanical dyssynchrony manifested by lengthening of the QRS duration, increased LV intraventricular delay (49 +/- 34 ms, 53 +/- 43 ms, respectively, P < 0.001), and increased interventricular delay (60 +/- 29 ms, 55 +/- 37 ms, P < 0.0001) versus AOO pacing. However, there was no change in blood pressure, CI, RV dp/dT(max), RV dP/dT(neg), or regional tissue Doppler velocities, indicating preserved hemodynamics and preserved global and regional RV systolic and diastolic function.In children with normal cardiac function and structure, pacing-induced electromechanical dyssynchrony did not acutely affect RV systolic and diastolic function and did not acutely alter global hemodynamics. Therefore, electromechanical dyssynchrony may only be an important therapeutic target in the setting of decreased RV function.

  View details for DOI 10.1111/j.1540-8167.2008.01354.x

  View details for Web of Science ID 000265409900012

  View details for PubMedID 19017336

• A Novel Non-Invasive Method of Estimating Pulmonary Vascular Resistance in Patients With Pulmonary Arterial Hypertension JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY Haddad, F., Zamanian, R., Beraud, A., Schnittger, I., Feinstein, J., Peterson, T., Yang, P., Doyle, R., Rosenthal, D. 2009; 22 (5): 523-529

  Abstract

  The assessment of pulmonary vascular resistance (PVR) plays an important role in the diagnosis and management of pulmonary arterial hypertension (PAH). The main objective of this study was to determine whether the noninvasive index of systolic pulmonary arterial pressure (SPAP) to heart rate (HR) times the right ventricular outflow tract time-velocity integral (TVI(RVOT)) (SPAP/[HR x TVI(RVOT)]) provides clinically useful estimations of PVR in PAH.Doppler echocardiography and right-heart catheterization were performed in 51 consecutive patients with established PAH. The ratio of SPAP/(HR x TVI(RVOT)) was then correlated with invasive indexed PVR (PVRI) using regression and Bland-Altman analysis. Using receiver operating characteristic curve analysis, a cutoff value for the Doppler equation was generated to identify patients with PVRI > or = 15 Wood units (WU)/m2.The mean pulmonary arterial pressure was 52 +/- 15 mm Hg, the mean cardiac index was 2.2 +/- 0.6 L/min/m2, and the mean PVRI was 20.5 +/- 9.6 WU/m2. The ratio of SPAP/(HR x TVI(RVOT)) correlated very well with invasive PVRI measurements (r = 0.860; 95% confidence interval, 0.759-0.920). A cutoff value of 0.076 provided well-balanced sensitivity (86%) and specificity (82%) to determine PVRI > 15 WU/m2. A cutoff value of 0.057 increased sensitivity to 97% and decreased specificity to 65%.The novel index of SPAP/(HR x TVI(RVOT)) provides useful estimations of PVRI in patients with PAH.

  View details for DOI 10.1016/j.echo.2009.01.021

  View details for PubMedID 19307098

• Exercise Capacity Is Decreased in Children With Chronic Right Ventricular Pacing and Congenital Complete Heart Block 58th Annual Scientific Session of the American-College-of-Cardiology Axelrod, D., Rosenthal, D. N., Chin, C., Obayashi, D., Kazmucha, J., Hanisch, D., Dubin, A. M. ELSEVIER SCIENCE INC. 2009: A359–A359

  View details for Web of Science ID 000263864201488

• WHO IS DOING WELL? A TYPOLOGY OF NEWLY HOMELESS ADOLESCENTS JOURNAL OF COMMUNITY PSYCHOLOGY Milburn, N., Liang, L., Lee, S., Rotheram-Borus, M. J., Rosenthal, D., Mallett, S., Lightfoot, M., Lester, P. 2009; 37 (2): 135-147

  Abstract

  There is growing evidence to support developing new typologies for homeless adolescents. Current typologies focus on the risks associated with being homeless, with less consideration of the positive attributes of homeless adolescents. The authors examined both risk and protective factors in a sample of newly homeless adolescents. Using cluster analysis techniques, they identified three distinct clusters of newly homeless adolescents: those who are protected and doing relatively well while out of home with more protective than risk factors, those who are at-risk, and those who are risky with more risk than protective factors. Over half (51.9%) of these newly homeless adolescents were in the protected cluster. This typology has implications for the design and implementation of services and interventions for newly homeless adolescents to reconnect them with stable housing situations.

  View details for DOI 10.1002/jcop.20283

  View details for Web of Science ID 000263381900001

  View details for PubMedCentralID PMC2824440

• C1q and Desensitization with IVIG: Use of a Novel HLA Complement Fixing Antibody Detection Technique To Guide Desensitization Therapy for Pediatric Heart Transplantation. Chin, C., Chen, G., Vayntrub, T., Siehr, S., Rosenthal, D., Reinhartz, O., Bernstein, D., Tyan, D. WILEY-BLACKWELL PUBLISHING, INC. 2009: 653

  View details for Web of Science ID 000265068801682

• The Impact of Heart Failure Severity at Time of Listing for Cardiac Transplantation on Short and Long Term Stability with Pediatric Cardiomyopathy Larsen, R., Naftel, D. C., Rosenthal, D. N., Blume, E. D., Mahle, W. T., Yung, D., Morrow, W., Orav, E., Wilkinson, J., Towbin, J. A., Lipshultz, S. E., Canter, C. E. LIPPINCOTT WILLIAMS & WILKINS. 2008: S963–S964

  View details for Web of Science ID 000262104503573

• Evaluation of Polymorphisms in Candidate Genes in the Dramatic Response to Pharmacologic Therapy of Heart Failure Basic Cardiovascular Sciences Conference Wheeler, M. T., Pavlovic, A., Dewey, F., Perez, M., Absher, D., Ho, M. Y., Cretti, E., Southwick, A., Rosenthal, D. N., Bernstein, D., Myers, R. M., Heidenreich, P. A., Fowler, M. B., Robbins, R. C., Ashley, E. A. LIPPINCOTT WILLIAMS & WILKINS. 2008: E64–E65

  View details for Web of Science ID 000258845200165

• Overrepresentation of neuronal development pathways in heart failure patients who dramatically responded to pharmaceutical therapy 12th Annual Scientific Meeting of the Heart-Failure-Society-of-America Pavlovic, A., Perez, M., Absher, D., Wheeler, M., Ho, M., Dewey, R., Cretti, L., Southwick, A., Rosenthal, D., Bernstein, D., Myers, R. M., Heidenreich, P., Fowler, M. B., Robbins, R., Ashley, E. CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS. 2008: S41–S41

  View details for Web of Science ID 000258565100129

• Does size matter? Clinical applications of scaling cardiac size and function for body size CIRCULATION Dewey, F. E., Rosenthal, D., Murphy, D. J., Froelicher, V. F., Ashley, E. A. 2008; 117 (17): 2279-2287

  Abstract

  Extensive evidence is available that cardiovascular structure and function, along with other biological properties that span the range of organism size and speciation, scale with body size. Although appreciation of such factors is commonplace in pediatrics, cardiovascular measurements in the adult population, with similarly wide variation in body size, are rarely corrected for body size. In this review, we describe the critical role of body size measurements in cardiovascular medicine. Using examples, we illustrate the confounding effects of body size. Current cardiovascular scaling practices are reviewed, as are limitations and alternative relationships between body and cardiovascular dimensions. The experimental evidence, theoretical basis, and clinical application of scaling of various functional parameters are presented. Appropriately scaled parameters aid diagnostic and therapeutic decision making in specific disease states such as hypertrophic cardiomyopathy and congestive heart failure. Large-scale studies in clinical populations are needed to define normative relationships for this purpose. Lack of appropriate consideration of body size in the evaluation of cardiovascular structure and function may adversely affect recognition and treatment of cardiovascular disease states in the adult patient.

  View details for DOI 10.1161/CIRCULATIONAHA.107.736785

  View details for PubMedID 18443249

• Subclinical late cardiac toxicity in childhood cancer survivors - Impact on self-reported health CANCER Cox, C. L., Rai, S. N., Rosenthal, D., Phipps, S., Hudson, M. M. 2008; 112 (8): 1835-1844

  Abstract

  The authors analyzed how self-reported health and self-reported modified New York Heart Association (NYHA) cardiac function scores were related to cardiac systolic function, cardiac risk factors, and cancer treatment history in childhood cancer survivors who reported no symptoms of cardiac disease.Long-term survivors of pediatric cancer who were treated between 1971 and 1995 (current ages, 16-39.7 years) underwent noninvasive clinical and laboratory cardiac risk evaluation and responded to selected subscales of the Medical Outcomes Study 36-item Short Form Health Survey. Results were compared with survivor history of anthracycline therapy alone or with radiotherapy (n=127 patients; mean, 10 years after diagnosis) versus no anthracycline therapy (n=32 patients; mean, 11 years after diagnosis).Sex, current age, highest school grade completed, race, age at diagnosis, diagnostic group, years off therapy, fractional shortening (FS), heart rate, and smoking status were found to be independently predictive of self-reported health. Interaction between female sex and higher low-density lipoprotein values and between diagnosis and abnormal FS variably predicted low reported vitality and low reported modified New York Heart Association (NYHA) scores. Echocardiographic findings, cardiac risk factors, and treatment history explained 13% to 28% of the variance in perceived health and self-reported modified NYHA scores.Systolic function and cardiac risk factors were linked to lower self-reported health and NYHA scores even in the absence of clinically evident cardiotoxicity.

  View details for DOI 10.1002/cncr.23378

  View details for Web of Science ID 000255018900024

  View details for PubMedID 18311782

• Right ventricular function in cardiovascular disease, part I - Anatomy, physiology, aging, and functional assessment of the right ventricle CIRCULATION Haddad, F., Hunt, S. A., Rosenthal, D. N., Murphy, D. J. 2008; 117 (11): 1436-1448

  View details for DOI 10.1161/CIRCULATIONAHA.107.653576

  View details for Web of Science ID 000254065200011

  View details for PubMedID 18347220

• Pneumatic paracorporeal ventricular assist device in infants and children: Initial Stanford experience 27th Annual Meeting of the International-Society-for-Heart-and-Lung-Transplantation Malaisrie, S. C., Pelletier, M. P., Yun, J. J., Sharma, K., Timek, T. A., Rosenthal, D. N., Wright, G. E., Robbins, R. C., Reitz, B. A. ELSEVIER SCIENCE INC. 2008: 173–77

  Abstract

  Mechanical circulatory support with the Berlin Heart EXCOR pediatric ventricular assist device (VAD) has been used successfully in Europe for children with cardiac failure. Eighty-seven devices have been placed in North America through February 2007. We describe our single-center experience in 8 children.Eight children (ages 4 to 55 months), with median weight of 9.6 kg and body surface area of 0.48 m(2), received the Berlin Heart VAD as a bridge to transplantation. All patients were in cardiogenic shock requiring multiple inotropes. Primary diagnoses were idiopathic dilated cardiomyopathy (n = 4), congenital heart disease (n = 3) and restrictive cardiomyopathy (n = 1). After device insertion, all patients were treated with an anti-coagulant (heparin or coumadin) and one or more platelet inhibitors (aspirin with clopidogrel or dipyridamole).Five patients received support with a left ventricular assist device (LVAD) and 3 with a biventricular device (BiVAD). Duration of support ranged from 2 to 234 days (median 57 days). Five patients (63%) were successfully bridged to transplantation; of these, 4 were discharged home and 1 died from early graft failure. Five patients developed post-operative neurologic events. Of these 5 events, 4 could be explained by embolism or hemorrhage. Device exchange was performed in 4 patients in the intensive care unit.In selected children, the Berlin Heart VAD can be used as a bridge to transplantation. In contrast to the published European experience, neurologic events occur frequently. Anti-coagulation and platelet inhibition strategies continue to evolve. Device exchange is technically feasible at the bedside and should be considered at the earliest visualization of thrombus formation.

  View details for DOI 10.1016/j.healun.2007.11.567

  View details for Web of Science ID 000253258800005

  View details for PubMedID 18267223

• Monitoring for cardiovascular disease in survivors of childhood cancer: Report from the cardiovascular disease task force of the children's oncology group PEDIATRICS Shankar, S. M., Marina, N., Hudson, M. M., Hodgson, D. C., Adams, M. J., Landier, W., Bhatia, S., Meeske, K., Chen, M. H., Kinahan, K. E., Steinberger, J., Rosenthal, D. 2008; 121 (2): E387-E396

  Abstract

  Curative therapy for childhood cancer has improved significantly in the last 2 decades such that, at present, approximately 80% of all children with cancer are likely to survive > or = 5 years after diagnosis. Prevention, early diagnosis, and treatment of long-term sequelae of therapy have become increasingly more significant as survival rates continue to improve. Cardiovascular disease is a well-recognized cause of increased late morbidity and mortality among survivors of childhood cancer. The Children's Oncology Group Late Effects Committee and Nursing Discipline and Patient Advocacy Committee have recently developed guidelines for follow-up of long-term survivors of pediatric cancer. A multidisciplinary task force critically reviewed the existing literature to evaluate the evidence for the cardiovascular screening recommended by the Children's Oncology Group guidelines. In this review we outline the clinical manifestations of late cardiovascular toxicities, suggest modalities and frequency of monitoring, and address some of the controversial and unresolved issues regarding cardiovascular disease in childhood cancer survivors.

  View details for DOI 10.1542/peds.2007-0575

  View details for Web of Science ID 000252877600058

  View details for PubMedID 18187811

• Outcomes of children with restrictive cardiornyopathy listed for heart transplant: A multi-institutional study 28th Annual Meeting of the International-Society-for-Heart-and-Lung-Transplantation Zangwill, S. D., Naftel, D., L'Ecuyer, T., Rosenthal, D., Robinson, B., Kirklin, J., Stendabl, G., Dipchand, A. I. ELSEVIER SCIENCE INC. 2008: S188–S189

  View details for Web of Science ID 000253342300354

• Midterm results of resynchronization therapy in pediatrics: Do we need new guidelines? Dubin, A. M., Collins, K. K., Van Hare, G. F., Reddy, V. M., Hanisch, D., Chiesa, N., Rosenthal, D. N. LIPPINCOTT WILLIAMS & WILKINS. 2007: 664

  View details for Web of Science ID 000250394303073

• Carvedilol for children and adolescents with heart failure - A Randomized controlled trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Shaddy, R. E., Boucek, M. M., Hsu, D. T., Boucek, R. J., Canter, C. E., Mahony, L., Ross, R. D., Pahl, E., Blume, E. D., Dodd, D. A., Rosenthal, D. N., Burr, J., LaSalle, B., Holubkov, R., Lukas, M. A., Tani, L. Y. 2007; 298 (10): 1171-1179

  Abstract

  Although beta-blockers improve symptoms and survival in adults with heart failure, little is known about these medications in children and adolescents.To prospectively evaluate the effects of carvedilol in children and adolescents with symptomatic systemic ventricular systolic dysfunction.A multicenter, randomized, double-blind, placebo-controlled study of 161 children and adolescents with symptomatic systolic heart failure from 26 US centers. In addition to treatment with conventional heart failure medications, patients were assigned to receive placebo or carvedilol. Enrollment began in June 2000 and the last dose was given in May 2005 (each patient received medication for 8 months).Patients were randomized in a 1:1:1 ratio to twice-daily dosing with placebo, low-dose carvedilol (0.2 mg/kg per dose if weight <62.5 kg or 12.5 mg per dose if weight > or =62.5 kg), or high-dose carvedilol (0.4 mg/kg per dose if weight <62.5 kg or 25 mg per dose if weight > or =62.5 kg) and were stratified according to whether each patient's systemic ventricle was a left ventricle or not.The primary outcome was a composite measure of heart failure outcomes in patients receiving carvedilol (low- and high-dose combined) vs placebo. Secondary efficacy variables included individual components of this composite, echocardiographic measures, and plasma b-type natriuretic peptide levels.There was no statistically significant difference between groups for the composite end point based on the percentage of patients who improved, worsened, or were unchanged. Among 54 patients assigned to placebo, 30 improved (56%), 16 worsened (30%), and 8 were unchanged (15%); among 103 patients assigned to carvedilol, 58 improved (56%), 25 worsened (24%), and 20 were unchanged (19%). The rates of worsening were lower than expected. The odds ratio for worsened outcome for patients in the combined carvedilol group vs the placebo group was 0.79 (95% CI, 0.36-1.59; P = .47). A prespecified subgroup analysis noted significant interaction between treatment and ventricular morphology (P = .02), indicating a possible differential effect of treatment between patients with a systemic left ventricle (beneficial trend) and those whose systemic ventricle was not a left ventricle (nonbeneficial trend).These preliminary results suggest that carvedilol does not significantly improve clinical heart failure outcomes in children and adolescents with symptomatic systolic heart failure. However, given the lower than expected event rates, the trial may have been underpowered. There may be a differential effect of carvedilol in children and adolescents based on ventricular morphology.clinicaltrials.gov Identifier: NCT00052026.

  View details for Web of Science ID 000249374200022

  View details for PubMedID 17848651

• Right ventricular mechanical dyssynchrony in children with hypoplastic left heart syndrome JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY Friedberg, M. K., Silverman, N. H., Dubin, A. M., Rosenthal, D. N. 2007; 20 (9): 1073-1079

  Abstract

  Mechanical dyssynchrony predicts response to cardiac resynchronization therapy in adults with heart failure. Children with hypoplastic left heart syndrome (HLHS) are susceptible to right ventricular (RV) failure; however, mechanical dyssynchrony has not been studied in this population with newly available methodologies. We investigated RV mechanical dyssynchrony in children with HLHS using vector velocity imaging.We used vector velocity imaging to quantify the SD of time to peak velocity, strain, and strain rate among 6 RV segments to define intraventricular RV synchrony in 16 children with HLHS and RV and left ventricular (LV) synchrony in 16 healthy age-matched control subjects. We further investigated relations between QRS duration and mechanical dyssynchrony and between mechanical dyssynchrony and systolic function.Children with HLHS had significant RV mechanical dyssynchrony versus LV and RV control subjects (strain 37 +/- 35 vs 8 +/- 8 milliseconds, P = .003 [LV], 9 +/- 11 milliseconds, P = .005 [RV]; strain rate 31 +/- 37 vs 10 +/- 13 milliseconds, P = .04 [LV], 14 +/- 15 milliseconds, P = .09 [RV]). There was no significant relationship between QRS duration and mechanical dyssynchrony and no obvious relation between the degree of mechanical dyssynchrony and the RV fractional area of change.Children with HLHS have RV mechanical dyssynchrony unrelated to surface electrocardiographic QRS duration. This may contribute to RV dysfunction and may indicate the usefulness of cardiac resynchronization therapy in this population.

  View details for DOI 10.1016/j.echo.2007.02.015

  View details for Web of Science ID 000249454900007

  View details for PubMedID 17566698

• Noninvasive evaluation of late anthracycline cardiac toxicity in childhood cancer survivors JOURNAL OF CLINICAL ONCOLOGY Hudson, M. M., Rai, S. N., Nunez, C., Merchant, T. E., Marina, N. M., Zalamea, N., Cox, C., Phipps, S., Pompeu, R., Rosenthal, D. 2007; 25 (24): 3635-3643

  Abstract

  PURPOSEl: Childhood cancer survivors treated with anthracyclines and cardiac radiation are at risk for late-onset cardiotoxicity. The purpose of this study was to delineate the relationship between clinical factors and abnormalities of noninvasive cardiac testing (NICT).Participants were recruited from a long-term follow-up clinic. Study measures comprised physical examination, laboratory evaluation, echocardiogram, and ECG. Mean fractional shortening (FS) and afterload were compared for survivors who did (at risk [AR]) and did not (no risk [NR]) receive potentially cardiotoxic modalities, and with values expected for comparable age- and sex-matched controls.The 278 study participants (mean age, 18.1 years; median age, 16.8 years; range, 7.5 to 39.7 years) included 223 survivors AR for cardiotoxicity after treatment with anthracyclines (median dose +/- standard deviation [SD], 202 +/- 109 mg/m(2)) and/or cardiac radiation. Mean FS (+/- SD) was lower for AR (0.33 +/- 0.06) compared with NR survivors (0.36 +/- 0.05; P = .004) and normative controls (0.36 +/- 0.04; P < .001). Mean afterload (+/- SD) was higher for AR (58 +/- 21 g/cm(2)) compared with NR survivors (46 +/- 15 g/cm(2); P < .001) and normative controls (48 +/- 13 g/cm(2); P < .001). The distribution of FS and afterload among NR survivors did not differ from that of controls. After adjustment for age group at diagnosis and time since completion of therapy, anthracycline dose predicted decline in distribution of FS (P < .001) and increase in distribution of afterload (P < .001). Treatment with anthracycline doses >or= 100 mg/m(2) increased the risk of abnormal NICT; survivors who received >or= 270 mg/m(2) had a 4.5-fold excess risk of abnormal NICT (95% CI, 2.1 to 9.6) compared with controls.Childhood cancer survivors treated with anthracycline doses >or= 270 mg/m(2) are at greatest risk for abnormalities of FS and afterload.

  View details for DOI 10.1200/JCO.2006.09.7451

  View details for Web of Science ID 000249415900015

  View details for PubMedID 17704413

• Children with cardiomyopathy: complications after noncardiac procedures with general anesthesia PEDIATRIC ANESTHESIA Kipps, A. K., Ramamoorthy, C., Rosenthal, D. N., Williams, G. D. 2007; 17 (8): 775-781

  Abstract

  Children with cardiomyopathy (CM) often undergo procedures that require general anesthesia (GA) but little is known about anesthesia-related adverse events or postprocedural outcomes.After approval, all children with CM who underwent nonopen heart surgical procedures and/or diagnostic imaging under GA at a tertiary children's hospital during January 2002 to May 2005 were identified from a clinical database. Based on their preprocedure fractional shortening (FS) on echocardiogram, systemic ventricular dysfunction was categorized as mild (FS 23-28%), moderate (FS 16-22%), or severe (FS < 16%) and those with normal (FS > 28%) were excluded from review.Twenty-six patients underwent 34 procedures under GA, of whom 13 (38%) had mild or moderate ventricular dysfunction and 21 (62%) had severe dysfunction. Common procedures included pacer/defibrillator placement (43%) and imaging studies (18%). Eighteen complications were noted in 12 patients. Fifteen (83%) complications occurred in patients with severe ventricular dysfunction. One patient with severe ventricular dysfunction died (3% mortality). Hypotension requiring inotropic support was the most frequent complication (61%). Children with severe ventricular dysfunction often required hospital support pre- and postprocedure with 67% requiring intensive care. Hospital stay was longer for patients with severe ventricular dysfunction compared with children with mild or moderate ventricular dysfunction (P = 0.006).The 30-day mortality rate was low but complications were common, especially in patients with severe ventricular dysfunction. For these patients, we recommend early consideration of perioperative intensive care support to optimize cardiovascular therapy and monitoring.

  View details for DOI 10.1111/j.1460-9592.2007.02245.x

  View details for Web of Science ID 000247582600007

  View details for PubMedID 17596222

• Mechanical dyssynchrony in children with systolic dysfunction secondary to cardiomyopathy: A Doppler tissue and vector velocity imaging study JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY Friedberg, M. K., Silverman, N. H., Dubin, A. M., Rosenthal, D. N. 2007; 20 (6): 756-763

  Abstract

  Mechanical dyssynchrony is common in adults with heart failure and its presence predicts response to cardiac resynchronization therapy. However, mechanical dyssynchrony and its quantification by echocardiography have not been extensively studied in children with cardiomyopathy. We investigated mechanical dyssynchrony in children with systolic dysfunction secondary to cardiomyopathy using Doppler tissue imaging (DTI) and vector velocity imaging (VVI).We used DTI and VVI to quantify mechanical dyssynchrony in 22 children with systolic dysfunction secondary to cardiomyopathy and in 25 healthy control subjects. We analyzed DTI results corrected for cardiac dimensions and evaluated correlation between electrical and mechanical dyssynchrony and between mechanical dyssynchrony and systolic function.DTI and VVI revealed significant mechanical dyssynchrony among children with cardiomyopathy. Intraventricular and interventricular delays as defined by DTI, and the SD of time to peak velocity, strain, and strain rate as defined by VVI were 2 to 3 times higher in patients with cardiomyopathy as compared with control subjects. There was no significant relationship between electrical and mechanical dyssynchrony.Children with systolic dysfunction secondary to cardiomyopathy have mechanical dyssynchrony, unrelated to electrical dyssynchrony, which can be measured by recent echocardiographic techniques including DTI and VVI. Children with cardiomyopathy and mechanical dyssynchrony are potential candidates for cardiac resynchronization therapy.

  View details for DOI 10.1016/j.echo.2006.11.007

  View details for Web of Science ID 000247090900012

  View details for PubMedID 17543748

• Right ventricular mechanical dyssynchrony in children with hypoplastic left heart syndrome: A target for cardiac resynchronization therapy? Friedberg, M. K., Silverman, N. H., Dubin, A. M., Rosenthal, D. N. ELSEVIER SCIENCE INC. 2007: 257A

  View details for Web of Science ID 000244651801499

• Indications for heart transplantation in pediatric heart disease - A scientific statement from the American Heart Association Council on Cardiovascular Disease in the Young; the Councils on Clinical Cardiology, Cardiovascular Nursing, and Cardiovascular Surgery and Anesthesia; and the Quality of Care and Outcomes Research Interdisciplinary Working Group CIRCULATION Canter, C. E., Shaddy, R. E., Bernstein, D., Hsu, D. T., Chrisant, M. R., Kirklin, J. K., Kanter, K. R., Higgins, R. S., Blume, E. D., Rosenthal, D. N., Boucek, M. M., Uzark, K. C., Friedman, A. H., Young, J. K. 2007; 115 (5): 658-676

  Abstract

  Since the initial utilization of heart transplantation as therapy for end-stage pediatric heart disease, improvements have occurred in outcomes with heart transplantation and surgical therapies for congenital heart disease along with the application of medical therapies to pediatric heart failure that have improved outcomes in adults. These events justify a reevaluation of the indications for heart transplantation in congenital heart disease and other causes of pediatric heart failure.A working group was commissioned to review accumulated experience with pediatric heart transplantation and its use in patients with unrepaired and/or previously repaired or palliated congenital heart disease (children and adults), in patients with pediatric cardiomyopathies, and in pediatric patients with prior heart transplantation. Evidence-based guidelines for the indications for heart transplantation or retransplantation for these conditions were developed.This evaluation has led to the development and refinement of indications for heart transplantation for patients with congenital heart disease and pediatric cardiomyopathies in addition to indications for pediatric heart retransplantation.

  View details for DOI 10.1161/CIRCULATIONAHA.106.180449

  View details for Web of Science ID 000244000800018

  View details for PubMedID 17261651

• Noninvasive assessment of pulmonary arterial capacitance by echocardiography JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY Friedberg, M. K., Feinstein, J. A., Rosenthal, D. N. 2007; 20 (2): 186-190

  Abstract

  Pulmonary arterial capacitance (PAC) has been associated with right ventricular (RV) workload and mortality in pulmonary hypertension, but is not routinely evaluated in children. We investigated whether PAC can be estimated noninvasively by echocardiography.We retrospectively determined PAC in 31 children with pulmonary hypertension, using echocardiography, and compared the results with those obtained at cardiac catheterization.PAC derived from echocardiography was similar to that derived from catheterization (mean +/- SD 1.16 +/- 1.0 vs 1.10 +/- 0.95 mL(3) x mm Hg(-1), P = not significant) and the two correlated well (r = 0.74, P < .0001). There was a highly significant polynomial relationship between PAC and RV anterior wall thickness indexed to body surface area (R(2) = 0.54, P < .0001), but not between pulmonary vascular resistance and RV wall thickness. Pulmonary vascular resistance and PAC did not correlate.Echocardiography can reliably estimate PAC, which strongly correlates with RV hypertrophy, a surrogate for RV work.

  View details for DOI 10.1016/j.echo.2006.08.009

  View details for PubMedID 17275705

• Percutaneous translurninal coronary angioplasty in a two-month old with coronary stenosis presenting as congenital cardiomyopathy: Acute results and intermediate follow-up CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Cheng, C. W., Lee, D. P., Rosenthal, D. N., Feinstein, J. A. 2006; 68 (4): 632-636

  Abstract

  Congenital or nonsurgically acquired obstructive coronary artery disease in infancy is exceedingly rare, and previous reports of catheter-based therapies in very young patients have been solely in patients having undergone arterial switch or other cardiovascular surgical procedures. We describe a previously unreported cause for ventricular dysfunction and heart failure in an infant, isolated congenital circumflex coronary artery stenosis, and successful treatment with percutaneous transluminal coronary angioplasty. Technical considerations, immediate results, and 3-year follow-up are provided.

  View details for DOI 10.1002/ccd.20750

  View details for PubMedID 16969876

• Unifocalization of major aortopulmonary collaterals in single-ventricle patients 42nd Annual Meeting of the Society-of-Thoracic-Surgeons Reinhartz, O., Reddy, V. M., Petrossian, E., Suleman, S., Mainwaring, R. D., Rosenthal, D. N., Feinstein, J. A., Gulati, R., Hanley, F. L. ELSEVIER SCIENCE INC. 2006: 934–39

  Abstract

  Unifocalization of major aortopulmonary collateral arteries (MAPCAs) in pulmonary atresia with ventricular septal defect and intracardiac repair has become the standard of care. However, there are no reports addressing unifocalization of MAPCAs in single-ventricle patients. It is unknown whether their pulmonary vascular bed can be reconstructed and low enough pulmonary vascular resistance achieved to allow for superior or total cavopulmonary connections.We reviewed data on all patients with functional single ventricles and unifocalization procedures of MAPCAs. From 1997 to 2005, 14 consecutive children with various single-ventricle anatomies were operated on.Patients had a median of three surgical procedures (range, 1 to 5). Two patients had absent, all others diminutive central pulmonary arteries, with an average of 3.5 +/- 1.2 MAPCAs. Seven patients (50%) had bidirectional Glenn procedures, and 3 of these had Fontan procedures. Median postoperative pulmonary artery pressures measured 12.5 mm Hg (Glenn) and 14 mm Hg (Fontan), respectively. Six patients are alive today (46%), with 1 patient lost to follow-up. Three patients died early and 3 late after initial unifocalization to shunts. One other patient survived unifocalization, but was not considered a candidate for a Glenn procedure and died after high-risk two-ventricle repair. Another patient with right-ventricle-dependent coronary circulation died of sepsis late after Glenn.In selected patients with functional single ventricles and MAPCAs, the pulmonary vascular bed can be reconstructed sufficiently to allow for cavopulmonary connections. Venous flow to the pulmonary vasculature decreases cardiac volume load and is likely to increase life expectancy and quality of life for these patients.

  View details for DOI 10.1016/j.athoracsur.2006.03.063

  View details for PubMedID 16928512

• Comparison of the epidemiology and co-morbidities of heart failure in the pediatric and adult populations: a retrospective, cross-sectional study. BMC cardiovascular disorders Webster, G., Zhang, J., Rosenthal, D. 2006; 6: 23

  Abstract

  BACKGROUND: Heart failure is a clinical syndrome that is associated with a significant number of interventional procedures and has received a large amount of scrutiny in the adult literature; however, the epidemiology in children is less well described.METHODS: We analyzed two large, commercially available inpatient datasets collected in 1997 by the Agency for Healthcare Research and Quality: the Kids' Inpatient Database and the National Inpatient Study, accounting for 50% of the U.S. pediatric discharges and 20% of the U.S. adult discharges in 1997.RESULTS: The database contained 5,610 children and 732,752 adults with a diagnosis of HF. When compared with the adult sample, the pediatric sample showed a higher proportion with cardiac procedures (61.4% vs. 0.28%, p < 0.01), a higher prevalence of congenital heart disease (61% versus 0.3%, p < 0.01), a higher percentage of male patients (50% pediatric vs. 44% adult, p < 0.01), and a lower percentage of white patients (40.9% vs. 65.6%, p < 0.01). Children had a significantly different spectrum of co-morbidities compared with adults. There was no difference in mortality rate between children and adults (7.5% vs. 7.9%, p = NS).CONCLUSION: There are significant differences in the epidemiological profile of children and adults with heart failure. Children suffer from different types of co-morbidities and require different procedures in the hospital setting. As such, children with heart failure who are hospitalized may require significantly different facilities, management and therapeutic intervention than adults with similar symptoms.

  View details for DOI 10.1186/1471-2261-6-23

  View details for PubMedID 16725044

• Pediatric mechanical circulatory support - Challenges and opportunities CIRCULATION Rosenthal, D., Bernstein, D. 2006; 113 (19): 2266–68

  View details for DOI 10.1161/CIRCULATIONAHA.106.623488

  View details for Web of Science ID 000237551300004

  View details for PubMedID 16702485

• A novel echocardiographic Doppler method for estimation of pulmonary arterial pressures JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY Friedberg, M. K., Feinstein, F. A., Rosenthal, D. N. 2006; 19 (5): 559-562

  Abstract

  Current noninvasive methods for estimating diastolic and mean pulmonary artery pressures (PAp) in children are cumbersome and have limited accuracy. We hypothesized that systolic PAp correlates with diastolic and mean PAp, and that this correlation can be used to estimate diastolic and mean PAp from Doppler flow data.We recorded PAp in 112 patients 30 years or younger catheterized for heart failure, heart transplant, pulmonary hypertension, or congenital heart disease. We derived the relationship of systolic PAp to diastolic and mean PAp. We then applied these relations to systolic PAp measured by tricuspid regurgitation (TR) Doppler flow in a subset of 17 patients with pulmonary hypertension to predict mean and diastolic PAp, and correlated the results.An excellent linear relation was found between systolic PAp and both the diastolic and mean PAp measured at cardiac catheterization (r = 0.95, P < .0001; r = 0.98, P < .0001, respectively). The calculated diastolic PAp calculated from TR Doppler correlated well with invasive data (31 +/- 13 vs 30 +/- 11 mm Hg, respectively, not significant; r = 0.85, P < .0001) and surpassed existing methods that are based on pulmonary regurgitation for predicting diastolic PAp. Similarly, mean PAp calculated from TR Doppler flow correlated well with invasive data (r = 0.86, P < .0001).A strong linear relationship between systolic and diastolic PAp allows for easy and accurate noninvasive estimation of diastolic and mean PAp from TR Doppler flow.

  View details for DOI 10.1016/j.echo.2005.12.020

  View details for PubMedID 16644441

• Heterotopic heart transplant combined with postoperative sildenafil use for the treatment of restrictive cardiomyopathy ANNALS OF THORACIC SURGERY Al-Khaldi, A., Reitz, B. A., Zhu, H., Rosenthal, D. 2006; 81 (4): 1505-1507

  Abstract

  We report successful management of a 22-month-old child with restrictive cardiomyopathy and severe pulmonary hypertension using the heterotopic heart transplant technique. Additional lessons learned from postoperative management, including the novel use of Sildenafil (Viagra, Pfizer, NY) for controlling pulmonary arterial pressure are described.

  View details for DOI 10.1016/j.athoracsur.2005.02.069

  View details for Web of Science ID 000236239200062

  View details for PubMedID 16564308

• A novel echo-doppler method to predict diastolic and mean pulmonary artery pressures: Derivation and validation by catheterization 55th Annual Scientific Session of the American-College-of-Cardiology Friedberg, M. K., Feinstein, J. A., Rosenthal, D. N. ELSEVIER SCIENCE INC. 2006: 249A–249A

  View details for Web of Science ID 000235530401392

• Anthracyclines cause endothelial injury in pediatric cancer patients: A pilot study 37th Annual Congress of the International-Society-of-Pediatric-Oncology Chow, A. Y., Chin, C., Dahl, G., Rosenthal, D. N. AMER SOC CLINICAL ONCOLOGY. 2006: 925–28

  Abstract

  The vascular endothelium plays a central role in the regulation of arterial vasomotor tone, releasing nitric oxide for vasodilation. Endothelial-dependent vasodilation can be assessed in vivo, using high resolution ultrasound to measure changes in diameter of the brachial artery. Animal studies have demonstrated that anthracyclines can damage the endothelium and impair the vasodilatory response of arteries; however, there are no comparable data in humans. This is a pilot study assessing endothelial toxicity from anthracyclines in pediatric cancer patients.Fourteen control patients and 14 cancer patients (4 to 21 years) were studied. Cancer patients had completed chemotherapy containing no less than 300 mg/m2 of anthracyclines 2 to 60 months before study. Brachial artery diameters were measured at rest and 1 minute after blood pressure cuff occlusion. Brachial artery reactivity (BAR) was calculated as percent change between baseline and after cuff deflation measurements. Results were compared using unpaired, two-tailed t-test.Baseline characteristics, including age, percentage of females, blood pressure, and resting vessel diameters were similar between the two groups. BAR in the controls averaged 6.7% with a standard deviation (SD) of 3.3%, while BAR in patients receiving anthracyclines averaged 3.8% with an SD of 3.4%, demonstrating a significant decrease (P < .05) in vasomotor reactivity in the treated group.These results suggest that anthracyclines cause impaired endothelial function, an important and newly recognized toxicity. Since endothelial dysfunction is an early event in atherogenesis, there may be important clinical implications from these findings. Further study is required to confirm these preliminary results in a larger cohort.

  View details for DOI 10.1200/JCO.2005.03.5956

  View details for Web of Science ID 000235469700017

  View details for PubMedID 16484703

• Real-time color-flow CMR in adults with congenital heart disease JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE de la Pena, E., Nguyen, P. K., Nayak, K. S., Yang, P. C., Rosenthal, D. N., Hu, B. S., Pauly, J. M., McConnell, M. V. 2006; 8 (6): 809-815

  Abstract

  CMR is valuable in the evaluation of congenital heart disease (CHD). Traditional flow imaging sequences involve cardiac and respiratory gating, increasing scan time and susceptibility to arrhythmias. We studied a real-time color-flow CMR system for the detection of flow abnormalities in 13 adults with CHD. All 16 congenital flow abnormalities previously detected by echocardiography were visualized using color-flow CMR, including atrial septal defects (n = 4), ventricular septal defects (n = 9), aortic coarctation (n = 1), Blalock-Taussig shunt (n = 1) and Fontan shunt (n = 1). Real-time color-flow CMR can identify intra- and extra-cardiac flow abnormalities in adults with congenital heart disease.

  View details for DOI 10.1080/10976640600777728

  View details for PubMedID 17060103

• Congenital junctional ectopic tachycardia and congenital complete atrioventricular block: A shared etiology? HEART RHYTHM Dubin, A. M., Cuneo, B. F., Strasburger, J. F., Wakai, R. T., Van Hare, G. F., Rosenthal, D. N. 2005; 2 (3): 313-315

  View details for DOI 10.1016/j.hrthm.2004.11.016

  View details for Web of Science ID 000227500000019

  View details for PubMedID 15851326

• New developments in echocardiographic methods to assess right ventricular function in congenital heart disease CURRENT OPINION IN CARDIOLOGY Friedberg, M. K., Rosenthal, D. N. 2005; 20 (2): 84-88

  Abstract

  Evaluation of right ventricular (RV) function in patients with congenital heart disease (CHD) is an essential component of clinical management. The complex geometry of the RV makes this a challenging task and necessitates the use of alternative methods from those used to assess left ventricular (LV) function. Recent developments in echocardiographic techniques have enhanced our ability to accurately assess RV function. We focus this review on literature published since September 2003.In this review we survey recent literature pertaining to advances in echocardiographic techniques used in assessing RV function. These new methods use two-dimensional echocardiography, Doppler echocardiography, tissue Doppler imaging (TDI), and strain rate imaging. Doppler techniques offer unique advantages for RV function in that they are independent of geometry and relatively independent of loading conditions.Echocardiography can assess RV function in a reliable fashion in children and adults with congenital heart disease. Appropriate use of echocardiography can minimize the utilization of more invasive imaging modalities such as magnetic resonance imaging and can guide clinical decisions regarding the necessity of obtaining such imaging.

  View details for Web of Science ID 000228074200004

  View details for PubMedID 15711192

• International society for heart and lung transplantation: Practice guidelines for management of heart failure in children JOURNAL OF HEART AND LUNG TRANSPLANTATION Rosenthal, D., Chrisant, M. R., Edens, E., Mahony, L., Canter, C., Colan, S., Dubin, A., Lamour, J., Ross, R., Shaddy, R., Addonizio, L., Beerman, L., Berger, S., Bernstein, D., Blume, E., Boucek, M., Checchia, P., Dipchand, A., Drummond-Webb, J., Fricker, J., Friedman, R., Hallowell, S., Jaquiss, R., Mital, S., Pahl, E., Pearce, B., Rhodes, L., Rotondo, K., Rusconi, P., Scheel, J., Singh, T. P., Towbin, J. 2004; 23 (12): 1313-1333

  View details for Web of Science ID 000226087100001

  View details for PubMedID 15607659

• Comparison of the epidemiology and co-morbidities of heart failure in the pediatric and adult populations Webster, G., Zhang, J., Rosenthal, D. INT PEDIATRIC RESEARCH FOUNDATION, INC. 2004: 53A

  View details for Web of Science ID 000220591100319

• Use of resynchronization therapy in pediatric patients with congenital heart disease and complete heart block Rosenthal, D. N., Dubin, A. M., Geiss, D. M., Reddy, V. M., Shah, J. J., Bash, S. E., Zimmerman, F. J. ELSEVIER SCIENCE INC. 2004: 384A

  View details for DOI 10.1016/S0735-1097(04)91621-X

  View details for Web of Science ID 000189388501623

• Identifying cardiac transplant rejection in children: Diagnostic utility of echocardiography, right heart catheterization and endomyocardial biopsy data JOURNAL OF HEART AND LUNG TRANSPLANTATION Rosenthal, D. N., Chin, C., Nishimura, K., Perry, S. B., Robbins, R. C., Reitz, B., Bernstein, D., Feinstein, J. A. 2004; 23 (3): 323-329

  Abstract

  There has been a continued search for alternative diagnostic techniques that do not necessitate endomyocardial biopsy for diagnosing rejection in cardiac transplant recipients. The purpose of this study is to evaluate the role of echocardiography and hemodynamic catheterization data compared with endomyocardial biopsy results, in rejection surveillance for the pediatric heart transplant recipient.A prospective, blinded evaluation was performed utilizing echocardiographic and standard right heart catheterization parameters to predict acute rejection episodes.Forty-nine patients underwent 281 biopsies. Two groups were defined: those with Grade <2 rejection and those with grade > or =2 rejection. None of the echocardiographic variables showed significant differences between the study groups and all group data were within normal limits. Mixed venous saturation, mean right atrial pressure, right ventricular end-diastolic pressure and mean pulmonary artery pressure were found to be statistically significant between groups. Receiver-operator characteristic (ROC) curves were constructed to determine the extent to which the various parameters were clinically useful. The ROC found little clinical usefulness for all variables, including those found to be statistically significant.Differences in both echocardiographic and hemodynamic data were not clinically significant between the 2 groups of patients. Although many of the catheterization-derived parameters were statistically significant, they did not permit effective discrimination between groups. This is the only clinically relevant application of such data and may explain the conflicting previous reports. It is only through analyses such as ROC that the clinical application (or lack thereof) can be appreciated in this population.

  View details for DOI 10.1016/S1053-2498(03)00209-2

  View details for PubMedID 15019642

• A visual approach for the accurate determination of echocardiographic left ventricular ejection fraction by medical students JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY Hope, M. D., de la Pena, E., Yang, P. C., Liang, D. H., McConnell, M. V., Rosenthal, D. N. 2003; 16 (8): 824-831

  Abstract

  Previously published reports show that there is significant intraobserver, interobserver, and interinstitutional variability in the determination of left ventricular (LV) ejection fraction (EF) by echocardiography. With the increased deployment of echocardiography (eg, handheld devices), there exists a need for developing a simple, intuitive approach for evaluating LVEF that allows a wider range of physicians to accurately and rapidly determine LVEF.We sought to create a system for assessing LVEF that relies on recognition and matching of patterns, rather than on mathematic calculations and geometric assumptions.A library of videoclips of cardiac function was compiled from 54 patients who spanned the spectrum of LVEF. LVEFs were calculated for these patients using standard echocardiographic methods, with further validation of a subsample using cardiac magnetic resonance imaging measurement of LVEF. The library of images was used to create a software tool for assessing LVEF on the basis of a "template-matching" approach. The software tool was then tested on medical students (N=13) to determine whether it enabled relatively untrained individuals to make accurate LVEF estimates.Using a template-matching approach for interpretation of echocardiograms, medical students were able to accurately estimate LVEF after only a limited introduction to echocardiography. Their LVEF estimates showed good correlation and agreement with gold standard (r = 0.88, standard square of the estimate = 6.0, limits of agreement = +12.0%, -15.6%).A new visual approach for assessing cardiac function using template matching can accurately estimate LVEF. With minimal training, medical students can make LVEF estimates that correlate well with gold standard. The application of this new approach includes allowing for the interpretation of LVEF from echocardiograms to be performed by a broader spectrum of physicians.

  View details for DOI 10.1067/S0894-7317(03)00400-0

  View details for Web of Science ID 000184604400007

  View details for PubMedID 12878991

• Electrical resynchronization - A novel therapy for the failing right ventricle CIRCULATION Dubin, A. M., Feinstein, J. A., Reddy, V. M., Hanley, F. L., Van Hare, G. F., Rosenthal, D. N. 2003; 107 (18): 2287-2289

  Abstract

  Many patients with congenital heart disease develop right ventricular (RV) failure due to anatomy and prior therapy. RV problems may include right bundle-branch block (RBBB), volume loading, and chamber enlargement. Because the failing RV may have regional dyskinesis, we hypothesized that resynchronization therapy might augment its performance.We studied 7 patients with RV dysfunction and RBBB, using a predefined pacing protocol. QRS duration, cardiac index (CI), and RV dP/dt were measured in 4 different pacing states. Atrioventricular pacing improved CI and RV dP/dtmax and decreased QRS duration as compared with atrial pacing or sinus rhythm.Atrioventricular pacing in patients with RBBB and RV dysfunction augments RV and systemic performance. RV resynchronization is a promising novel therapy for patients with RV failure.

  View details for DOI 10.1161/01.CIR.0000070930.33499.9F

  View details for PubMedID 12732607

• Epidemiology of congestive heart failure in the pediatric population Webster, G., Rosenthal, D. N. INT PEDIATRIC RESEARCH FOUNDATION, INC. 2003: 41A–42A

  View details for Web of Science ID 000181897900233

• Validation of the Doppler PR interval in the fetus JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY Rosenthal, D., Friedman, D. M., Buyon, J., Dubin, A. 2002; 15 (9): 1029-1030

  View details for DOI 10.1067/mje.2002.121438

  View details for Web of Science ID 000178119200034

  View details for PubMedID 12221431

• Carbohydrate-deficient glycoprotein syndrome-associated pericardial effusion treated with corticosteroids and salicylic acid PEDIATRIC CARDIOLOGY Feldman, B. J., Rosenthal, D. 2002; 23 (4): 469-471

  Abstract

  We describe an infant with a persistent pericardial effusion who was diagnosed with carbohydrate-deficient glycoprotein syndrome (CDGS)-Ia. She was born with mild dysmorphic features and common cardiac abnormalities. However, she re-presented at 2.5 months of age with a pericardial effusion. We decided to embark on a therapeutic trial of corticosteroids and salicylic acid therapy in an attempt to avoid pericardectomy. After 3 weeks of medical treatment the effusion resolved. This experience allows us to propose that medical management with corticosteroids and salicylic acid can be considered as an alternative to surgical therapy for CDGS-I patients with persistent pericardial effusions.

  View details for DOI 10.1007/s00246-002-1497-1

  View details for Web of Science ID 000176665700018

  View details for PubMedID 12170369

• Comparison of contrast echocardiography versus cardiac catheterization for detection of pulmonary arteriovenous malformations AMERICAN JOURNAL OF CARDIOLOGY Feinstein, J. A., Moore, P., Rosenthal, D. N., Puchalski, M., Brook, M. M. 2002; 89 (3): 281-285

  Abstract

  Because clinical diagnosis of pulmonary arteriovenous malformations (AVMs) is difficult and cardiac catheterization invasive, contrast echo has been used to aid in the diagnosis. Correlation between contrast echo and catheterization data in these patients remains poorly defined. We examined the ability to detect pulmonary AVMs by contrast echocardiography, pulmonary angiography, and pulmonary vein saturations in patients who have undergone cavopulmonary (Glenn) shunts. Pulmonary vein saturations were obtained from catheterization reports. Blinded observers reviewed angiographic and contrast echo data retrospectively in 27 patients who had undergone a Glenn shunt and in 19 controls with biventricular hearts. Contrast echo was positive in 68 of 99 lungs (69%). Angiography showed AVMs in 65 of 98 lungs (66%). Pulmonary vein desaturation was found in 13 of 45 lungs sampled (29%). Only 10 of 38 lungs with positive contrast echo had pulmonary vein desaturation, but only 1 patient had pulmonary vein desaturation without positive contrast echo. The degree of desaturation did not correlate with severity of contrast echo return; 6 of 11 patients with 3+ contrast echo studies had normal pulmonary vein saturations. In a control group of patients with biventricular hearts, only 1 of 19 (5.3%) contrast echos was weakly positive. Contrast echo correlates poorly with angiography and pulmonary vein saturation for evaluation of AVMs. Contrast echo is extremely sensitive and often positive despite normal pulmonary vein saturation. Assessment of pulmonary vein desaturation in 100% oxygen may improve its sensitivity and correlation with contrast echo. Additional studies are needed to follow patients with mildly positive contrast echo studies to enable determination of their clinical relevance.

  View details for PubMedID 11809429

• Screening for complete congenital heart block among fetuses of patients with SSA and SSB antibodies Lyell, D., Rosenthal, D., El-Sayed, Y., Druzin, M. MOSBY, INC. 2001: S188

  View details for DOI 10.1016/S0002-9378(01)80425-7

  View details for Web of Science ID 000172921000390

• Survey of current practices in use of amiodarone and implantable cardioverter defibrillators in pediatric patients with end-stage heart failure AMERICAN JOURNAL OF CARDIOLOGY Dubin, A. M., Van Hare, G. F., Collins, K. K., Bernstein, D., Rosenthal, D. N. 2001; 88 (7): 809-?

  View details for Web of Science ID 000171374300022

  View details for PubMedID 11589857

• Lipoprotein abnormalities are highly prevalent in pediatric heart transplant recipients. Pediatric transplantation Chin, C., Rosenthal, D., Bernstein, D. 2000; 4 (3): 193-199

  Abstract

  The role of hyperlipidemia in graft coronary artery disease (GCAD) is controversial although hyper-triglyceridemia is an independent risk factor. Recent studies show that 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) inhibitors decrease the incidence of GCAD in adults. The incidence of GCAD in pediatric patients is lower than in adults; it is not clear whether age-related differences in lipid metabolism account for some of this protection. This study was performed to: characterize the lipoprotein profile in children after heart transplantation; demonstrate that total cholesterol (TC) is a poor marker for underlying lipoprotein abnormalities; and to compare lipid abnormalities in patients who had been converted from cyclosporin A (CsA) to tacrolimus. Seventy-one determinations of fasting lipoprotein profiles were performed in a cohort of 28 children. Each child had at least two determinations on separate occasions. TC, low-density lipoprotein (LDL), and serum triglyceride (TG) levels were categorized as abnormal if greater than the 75th percentile for age and gender. A high-density lipoprotein (HDL) level less than the 25th percentile was considered abnormal. Immunosuppression included CsA or tacrolimus, azathioprine, and prednisone. We found that 90% of the patients studied had abnormalities of either TG or HDL. In contrast, LDL tended to be normal when adjusted for age and gender. TC was a poor indicator of any underlying abnormality in TG, LDL, or HDL. In patients converted to tacrolimus, no significant differences were found in the levels of TG, LDL or HDL compared with each patient's respective values while receiving CsA. Hence, lipoprotein abnormalities among pediatric heart transplant recipients are highly prevalent. TC is a poor screening tool in the evaluation for lipid abnormalities. Lipoprotein profiles remain statistically unchanged after conversion from CsA to tacrolimus.

  View details for PubMedID 10933319

• Outcome while awaiting heart transplantation in children: A comparison of congenital heart disease and cardiomyopathy JOURNAL OF HEART AND LUNG TRANSPLANTATION Rosenthal, D. N., Dubin, A. M., Chin, C., Falco, D., Gamberg, P., Bernstein, D. 2000; 19 (8): 751-755

  Abstract

  Outcomes for children who undergo heart transplantation differ for children with congenital heart disease as compared to those with structurally normal hearts. Similar data have not been reported for these groups of patients for the morbidity and mortality associated with waiting for a donor. We report these data.A retrospective review was performed for all pediatric patients who were listed for heart transplantation at Stanford from 1977 to 1996, comparing mortality and major morbidity for patients with congenital heart disease and those with cardiomyopathy and structurally normal hearts.There were 96 patients who met study criteria, of whom 67 were successfully transplanted. The median waiting time was 23 days. Survival at 30 days was 93% and at 90 days was 81%, with no difference between groups. Major complications were identified in 38% of patients with structurally normal hearts, vs 9% of patients with congenital heart disease (p < 0.001).Overall mortality is similar for patients with congenital heart disease and those with structurally normal hearts while listed for heart transplantation, but patients with congenital heart disease have fewer episodes of major morbidity during this time.

  View details for Web of Science ID 000089041400005

  View details for PubMedID 10967268

• Safety and utility of the routine surveillance biopsy in pediatric patients 2 years after heart transplantation JOURNAL OF PEDIATRICS Chin, C., Akhtar, M. J., Rosenthal, D. N., Bernstein, D. 2000; 136 (2): 238-242

  Abstract

  The standard for diagnosing allograft rejection after heart transplantation is the endomyocardial biopsy, but the value of routine surveillance biopsies after 2 years after transplant is controversial. The objective of this study was to determine the necessity and safety of surveillance biopsies and to correlate rejection with signs and symptoms beyond the second post-transplant anniversary in pediatric patients.We reviewed the results of 899 biopsies and coincident clinical histories in 56 pediatric patients, comprising 314 patient-years of follow-up. Patients were classified as having symptoms or not based on a blinded review of their clinical status and echocardiograms. Biopsies were classified as negative or positive with established criteria.After biopsies performed less than 2 years after transplant or as a follow-up for a positive biopsy were excluded, 481 biopsies were available for analysis, of which 20 (4%) were positive. Positive biopsies were found in 15 (3%) of 456 biopsies in patients without symptoms compared with 5 (20%) of 25 biopsies in patients with symptoms. Patients with symptoms were 6 times more likely to have a positive biopsy compared with patients without symptoms. Of the positive rejection episodes, 75% occurred in patients without symptoms.Although rejection is uncommon in pediatric patients greater than 2 years after transplant, episodes of treatable allograft rejection can occur in the absence of clinical signs and symptoms. This study emphasizes the safety of and the need to continue to perform routine surveillance biopsies in patients without symptoms, even after the second post-transplant year.

  View details for Web of Science ID 000085289400023

  View details for PubMedID 10657832

• Brachial artery reactivity: A modified technique with applicability to children JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY Rosenthal, D. N., Chin, C. 1999; 12 (10): 850-852

  Abstract

  Brachial artery reactivity noninvasively tests endothelial function. Cuff pressures of 180 to 300 mm Hg have been used. These pressures are ill advised in neonatal and premature infants. We therefore evaluated the use of substantially lower occlusive pressures. Fifteen adult subjects were enrolled. One arm was occluded to 200 mm Hg, and the other arm was occluded to 40 mm Hg above the resting systolic pressure. The occlusion time was 4.5 minutes. The brachial artery was measured at baseline and 1 minute after cuff deflation. Low pressure occlusions averaged 155.7 +/- 7.8 mm Hg versus 200 mm Hg for high pressure occlusions (P <.0001). One of 15 patients with low pressure occlusions reported discomfort versus 7 of 15 with high pressure occlusions (P <.05). Brachial artery reactivity increased by 8.0% +/- 2.5% with low pressure occlusions versus 7.5% +/- 2.7% with high pressure occlusions (P = not significant). Brachial artery reactivity can be assessed at lower occlusive pressures. This may extend the applicability of the technique to children and neonates.

  View details for Web of Science ID 000083255200011

  View details for PubMedID 10511654

• QT dispersion predicts ventricular arrhythmia in pediatric cardiomyopathy patients referred for heart transplantation JOURNAL OF HEART AND LUNG TRANSPLANTATION Dubin, A. M., Rosenthal, D. N., Chin, C., Bernstein, D. 1999; 18 (8): 781-785

  Abstract

  QT dispersion has been used in stratifying risk for sudden death in adults with dilated cardiomyopathy, but its role in the pediatric population has not been delineated.We reviewed electrocardiograms in pediatric patients with dilated cardiomyopathy referred for heart transplantation, to evaluate the role of QT dispersion in predicting malignant arrhythmias in these patients. Three groups were defined: Group I (n = 13) had dilated cardiomyopathy and malignant ventricular arrhythmias, Group II (n = 13) had dilated cardiomyopathy with no ventricular arrhythmias and Group III (n = 30) consisted of normals. QT dispersion was defined as the duration of the shortest QT subtracted from that of the longest. In addition, the standard deviation of the QT intervals was calculated for each ECG, using 12 leads.QT dispersion was significantly prolonged in Group I (97 +/- 33 msec) compared to Group II (74 +/- 19 msec) and Group III (42 +/- 17 msec). QT standard deviation was also prolonged in Group I (30 +/- 11 msec) vs Group II (22 +/- 5 msec) and Group III (13 +/- 4 msec). Using a threshold value of 90 msec for QT dispersion or 25 msec for QT standard deviation, a sensitivity of 78% and a specificity of 70% was obtained for identifying patients who would subsequently develop ventricular arrhythmias.In pediatric heart transplant candidates with dilated cardiomyopathy, QT dispersion and QT standard deviation identify patients at higher risk for the development of malignant ventricular arrhythmia. This simple test can be helpful in the evaluation and management of these patients awaiting transplantation.

  View details for Web of Science ID 000082347500007

  View details for PubMedID 10512525

• Persistent cardiac dysfunction following treatment of childhood malignancy is related to cumulative anthracycline dose Rosenthal, D. N., Chin, C., Bernstein, D., Marina, N. M. INT PEDIATRIC RESEARCH FOUNDATION, INC. 1999: 29A

  View details for DOI 10.1203/00006450-199904020-00181

  View details for Web of Science ID 000079476700165

• Gender and age do not alter actuarial incidence of cardiac dysfunction following anthracycline chemotherapy of childhood malignancy Rosenthal, D. N., Chin, C., Bernstein, D., Marina, N. M. NATURE PUBLISHING GROUP. 1999: 30A–30A

  View details for Web of Science ID 000079476700166

• Outcome between listing and transplantation in pediatric heart transplant candidates: Comparison of congenital heart disease and dilated cardiomyopathy Dubin, A. M., Rosenthal, D. N., Chin, C., Falco, D. A., Gamberg, P., Bernstein, D. INT PEDIATRIC RESEARCH FOUNDATION, INC. 1999: 22A

  View details for DOI 10.1203/00006450-199904020-00135

  View details for Web of Science ID 000079476700119

• ORK1, a potassium-selective leak channel with two pore domains cloned from Drosophila melanogaster by expression in Saccharomyces cerevisiae (vol 93, pg 13256, 1996) PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Goldstein, S. A., Price, L. A., Rosenthal, D. N., Pausch, M. H. 1999; 96 (1): 318

  View details for Web of Science ID 000078004400058

• A new therapeutic approach to the fetus with congenital complete heart block: Preemptive, targeted therapy with dexamethasone OBSTETRICS AND GYNECOLOGY Rosenthal, D., Druzin, M., Chin, C., Dubin, A. 1998; 92 (4): 689-691

  Abstract

  Therapy of established congenital complete heart block in the fetus has resulted in improved survival but persistence of heart block. This exposes the infant to the morbidity of heart block, including the risk of sudden death and pacemaker implantation.A 35-year-old gravida 2, para 1, with Sjogren syndrome and a previous pregnancy complicated by congenital complete heart block presented during her second pregnancy. Intensive fetal monitoring with echocardiography was employed. Early evidence of myocardial dysfunction and dysrhythmia was found, dexamethasone therapy was initiated, and the dysfunction and dysrhythmia resolved. The pregnancy went to term without further complication.This represents a new and successful strategy to identify very early signs of myocardial disease in a fetus at high risk of congenital complete heart block, enabling targeted, preemptive therapy.

  View details for Web of Science ID 000076159900022

  View details for PubMedID 9764666

• Arrhythmias and thromboembolic complications after the extracardiac Fontan operation JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Shirai, L. K., Rosenthal, D. N., Reitz, B. A., Robbins, R. C., Dubin, A. M. 1998; 115 (3): 499-505

  Abstract

  Late morbidity and mortality after the Fontan operation are largely due to atrial arrhythmias, ventricular failure, and thrombus formation. The extracardiac Fontan procedure avoids extensive atrial manipulation and suture lines, theoretically minimizing the impetus for these events. We examined our experience with the extracardiac Fontan operation with particular attention to thromboembolism and arrhythmias.We retrospectively reviewed the medical and surgical records of all 16 patients who underwent an extracardiac Fontan operation between July 1993 and May 1996. Fifteen patients (94%) were in sinus rhythm before the operation. In the immediate postoperative period, seven (44%) had arrhythmias consisting of accelerated junctional rhythm and ectopic atrial rhythm. No associated hemodynamic compromise and no early deaths occurred. Patients were followed up for 3 to 34 months after the Fontan operation. Arrhythmias were detected in eight patients (50%) on surface electrocardiograms, and seven (44%) showed evidence of sinus node dysfunction on 24-hour Holter monitor studies. Thrombi were found in three patients (19%). All patients were asymptomatic, with no evidence of conduit obstruction by echocardiogram.The incidence of hemodynamically significant tachyarrhythmias appears to be reduced after the extracardiac Fontan operation. A significant percentage of patients have evidence of sinus node dysfunction, suggesting the presence of other surgical or nonsurgical factors responsible for this finding. Our incidence of thrombotic events is similar to previous reports with other Fontan modifications. It appears to be a reasonable option to maintain these patients on anticoagulation indefinitely.

  View details for Web of Science ID 000072718800002

  View details for PubMedID 9535435

• ORK1, a potassium-selective leak channel with two pore domains cloned from Drosophila melanogaster by expression in Saccharomyces cerevisiae PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Goldstein, S. A., Price, L. A., Rosenthal, D. N., Pausch, M. H. 1996; 93 (23): 13256-13261

  Abstract

  A K+ channel gene has been cloned from Drosophila melanogaster by complementation in Saccharomyces cerevisiae cells defective for K+ uptake. Naturally expressed in the neuromuscular tissues of adult flies, this gene confers K+ transport capacity on yeast cells when heterologously expressed. In Xenopus laevis oocytes, expression yields an ungated K(+)-selective current whose attributes resemble the "leak" conductance thought to mediate the resting potential of vertebrate myelinated neurons but whose molecular nature has long remained elusive. The predicted protein has two pore (P) domains and four membrane-spanning helices and is a member of a newly recognized K+ channel family. Expression of the channel in flies and yeast cells makes feasible studies of structure and in vivo function using genetic approaches that are not possible in higher animals.

  View details for DOI 10.1073/pnas.93.23.13256

  View details for Web of Science ID A1996VT05400105

  View details for PubMedID 8917578

  View details for PubMedCentralID PMC24080

• THROMBOSIS OF THE PULMONARY-ARTERY STUMP AFTER DISTAL LIGATION JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Rosenthal, D. N., Bulbul, Z. R., Friedman, A. H., Hellenbrand, W. E., Kleinman, C. S. 1995; 110 (5): 1563-1565

  View details for Web of Science ID A1995TG02000030

  View details for PubMedID 7475209

• Thromboembolic complications after Fontan operations. Circulation Rosenthal, D. N., Friedman, A. H., Kleinman, C. S., Kopf, G. S., Rosenfeld, L. E., Hellenbrand, W. E. 1995; 92 (9): II287-93

  Abstract

  Despite the increasing recognition of thromboembolic complications of the Fontan procedure, data characterizing such events are limited. The total cavopulmonary connection is believed to be less prone to this complication than other modifications of Fontan operations. We examined our experience with thromboembolism after Fontan operations to better characterize these events and their relation to the type of Fontan operation performed.We retrospectively identified 70 patients who underwent a Fontan operation between January 1978 and March 1994. Patients were divided into three groups: (1) total cavopulmonary connection, (2) atriopulmonary connection, and (3) conduit interposition. Fourteen patients (20%) developed a thromboembolic complication during a mean (+/- SD) follow-up of 5.2 +/- 4.7 years. The rate of thrombosis was similar in each group. The time from Fontan operation to thrombosis averaged 6.1 +/- 5.0 years. The overall rate of thromboembolic events was 3.9 per 100 patient-years. Twelve of the 14 thrombi were located within the venous circulation, 1 was in the left ventricle, and the location of 1 was undetermined. Six of the patients (43%) were asymptomatic, 3 (21%) presented with cerebrovascular events, and 5 (36%) presented with other symptoms. Thromboembolic events occurred from the perioperative period to 15 years after surgery.Thromboembolic complications occur frequently after the Fontan operation and its modifications and are a cause of significant morbidity. The time of presentation varies greatly. The rate of thrombosis appears to be similar in all modifications of the Fontan operation.

  View details for PubMedID 7586425

• THROMBOEMBOLIC COMPLICATIONS AFTER FONTAN OPERATIONS CIRCULATION Rosenthal, D. N., Friedman, A. H., Kleinman, C. S., Kopf, G. S., Rosenfeld, L. E., Hellenbrand, W. E. 1995; 92 (9): 287-293

  Abstract

  Despite the increasing recognition of thromboembolic complications of the Fontan procedure, data characterizing such events are limited. The total cavopulmonary connection is believed to be less prone to this complication than other modifications of Fontan operations. We examined our experience with thromboembolism after Fontan operations to better characterize these events and their relation to the type of Fontan operation performed.We retrospectively identified 70 patients who underwent a Fontan operation between January 1978 and March 1994. Patients were divided into three groups: (1) total cavopulmonary connection, (2) atriopulmonary connection, and (3) conduit interposition. Fourteen patients (20%) developed a thromboembolic complication during a mean (+/- SD) follow-up of 5.2 +/- 4.7 years. The rate of thrombosis was similar in each group. The time from Fontan operation to thrombosis averaged 6.1 +/- 5.0 years. The overall rate of thromboembolic events was 3.9 per 100 patient-years. Twelve of the 14 thrombi were located within the venous circulation, 1 was in the left ventricle, and the location of 1 was undetermined. Six of the patients (43%) were asymptomatic, 3 (21%) presented with cerebrovascular events, and 5 (36%) presented with other symptoms. Thromboembolic events occurred from the perioperative period to 15 years after surgery.Thromboembolic complications occur frequently after the Fontan operation and its modifications and are a cause of significant morbidity. The time of presentation varies greatly. The rate of thrombosis appears to be similar in all modifications of the Fontan operation.

  View details for Web of Science ID A1995TE55900049

• MYOCARDIAL-INFARCTION IN THE PERINATAL-PERIOD SECONDARY TO MATERNAL COCAINE ABUSE - A CASE-REPORT AND LITERATURE-REVIEW ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE Bulbul, Z. R., Rosenthal, D. N., Kleinman, C. S. 1994; 148 (10): 1092-1096

  View details for Web of Science ID A1994PX05200017

  View details for PubMedID 7921102

• GENETIC-ASPECTS OF HEART-DISEASE IN THE NEWBORN SEMINARS IN PERINATOLOGY Bulbul, Z. R., Rosenthal, D., Brueckner, M. 1993; 17 (2): 61-75

  View details for Web of Science ID A1993LD19700002

  View details for PubMedID 8327904