Clinical Focus

  • Single Ventricle Heart Disease
  • Mechanical Circulatory Support
  • Heart Failure
  • Heart Transplantation
  • Advanced Heart Failure and Transplant Cardiology

Academic Appointments

Administrative Appointments

  • Additional Ventures Endowed Directorship, Comprehensive Single Ventricle Program (2020 - Present)

Boards, Advisory Committees, Professional Organizations

  • Member, International Society of Heart and Lung Transplantation (2015 - Present)
  • Member, National Pediatric Cardiology Quality Improvement Collaborative (2020 - Present)
  • Member, Advanced Cardiac Therapies Improving Outcomes Network (2020 - Present)
  • Member, Fontan Outcomes Network (2022 - Present)
  • Member, American Society for Artificial Internal Organs (2023 - Present)

Professional Education

  • Fellowship: Stanford University (2015) CA
  • Senior Fellowship, Stanford University, Pediatric Heart Failure/Transplant (2015)
  • Board Certification: American Board of Pediatrics, Pediatric Cardiology (2014)
  • Fellowship, Stanford University, Pediatric Cardiology (2014)
  • Chief Residency, UCSF, Pediatrics (2011)
  • Board Certification: American Board of Pediatrics, Pediatrics (2010)
  • Residency, UCSF, Pediatrics (2010)
  • Medical Education: University of California at San Francisco School of Medicine (2006) CA
  • MD, UCSF (2006)
  • MPH, UC Berkeley, Epidemiology and Biostatistics (2005)
  • Bachelor of Arts, Stanford University (2001)

Clinical Trials

  • Inhaled Tissue Plasminogen Activator for Acute Plastic Bronchitis Not Recruiting

    Plastic bronchitis (PB) is a rare, most often pediatric disease characterized by the formation of obstructive airway casts primarily composed of fibrin. There is presently no FDA-approved pharmacotherapy for PB, but acute exacerbations of the illness are often treated with inhaled tissue plasminogen activator (tPA). To date, this is done somewhat anecdotally because there has been no safety or efficacy testing of this treatment. In addition, there is presently no reliable surrogate marker of adverse drug events. Nevertheless, in the absence of inhaled tPA treatment, PB-induced respiratory distress can be severe, often warranting urgent or emergent bronchoscopy for cast removal, or can sometimes result in respiratory failure. As such there is a significant unmet need for safety and efficacy testing of inhaled tPA and for biomarkers of drug response. Objectives and Endpoints: The objectives of this protocol are to: 1) test the safety and efficacy of an inhaled tPA regimen in children with PB; and 2) identify potential candidate biomarkers of inhaled tPA drug response. Safety endpoints will consist of the development of new, active bleeding that is systemic and/or pulmonary and/or new hematuria (defined as gross hematuria). Secondary endpoints of efficacy will also be measured (e.g., frequency of cast production). Urine and blood will also be collected for the development of potential biomarkers of inhaled tPA drug response. Funding source- FDA OOPD

    Stanford is currently not accepting patients for this trial. For more information, please contact Melissa Jenkins, 650-736-6588.

    View full details

All Publications

  • Mortality and morbidity after combined heart and liver transplantation in the failing Fontan: An updated dual center retrospective study. Clinical transplantation Vaikunth, S. S., Ortega-Legaspi, J. M., Conrad, D. R., Chen, S., Daugherty, T., Haeffele, C. L., Teuteberg, J., Mclean, R., MacArthur, J. W., Woo, Y. J., Maeda, K., Ma, M., Nasirov, T., Hoteit, M., Hilscher, M. B., Wald, J., Mandelbaum, T., Olthoff, K. M., Abt, P. L., Atluri, P., Cevasco, M., Mavroudis, C. D., Fuller, S., Lui, G. K., Kim, Y. Y. 2024; 38 (4): e15302


    As the adult Fontan population with Fontan associated liver disease continues to increase, more patients are being referred for transplantation, including combined heart and liver transplantation.We report updated mortality and morbidity outcomes after combined heart and liver transplant in a retrospective cohort series of 40 patients (age 14 to 49 years) with Fontan circulation across two centers from 2006-2022.The 30-day, 1-year, 5-year and 10-year survival rate was 90%, 80%, 73% and 73% respectively. Sixty percent of patients met a composite comorbidity of needing either post-transplant mechanical circulatory support, renal replacement therapy or tracheostomy. Cardiopulmonary bypass time > 283 min (4.7 h) and meeting the composite comorbidity were associated with mortality by Kaplan Meier analysis.Further study to mitigate early mortality and the above comorbidities as well as the high risk of bleeding and vasoplegia in this patient population is warranted.

    View details for DOI 10.1111/ctr.15302

    View details for PubMedID 38567883

  • Summary of a Consensus Conference on Heart-Liver Transplantation. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons Kobashigawa, J., VanWagner, L. B., Hall, S., Emamaullee, J., Entwistle, J. W., Ganger, D., Gebel, H., Jeevanandam, V., Kaldas, F., Kilic, A., Kittleson, M., Kushwaha, S., Kwong, A., Lui, G. K., Motayagheni, N., Patel, J., Patel, N., Pereira, N., Potter, L., Sani, M., Schiano, T. D., Shingina, A. 2023


    Patients with severe heart disease may have co-existing liver disease from various causes. The incidence of combined heart-liver transplant (CHLT) is increasing as more patients with congenital heart disease survive to adulthood and develop advanced heart failure with associated liver disease from chronic right-sided heart or Fontan failure. However, the criteria for CHLT have not been established. To address this unmet need, a virtual consensus conference was organized on June 10, 2022, endorsed by the American Society of Transplantation. The conference represented a collaborative effort by experts in cardiothoracic and liver transplantation from across the United States to assess interdisciplinary criteria for liver transplantation in the CHLT candidate, surgical considerations of CHLT, current allocation system that generally results in the liver following the heart for CHLT, and the optimal post-CHLT management. The conference served as a forum to unify criteria between the different specialties and to forge a pathway for patients who may need dual organ transplantation. Due to the continuing shortage of available donor organs, ethical issues related to multi-organ transplantation were also debated. The findings and consensus statements are presented.

    View details for DOI 10.1016/j.ajt.2023.12.002

    View details for PubMedID 38072122

  • Research gaps in pediatric heart failure: defining the gaps and then closing them over the next decade. Journal of cardiac failure Amdani, S., Auerbach, S. R., Bansal, N., Chen, S., Conway, J., Da Silva, J. P., Deshpande, S. R., Hoover, J., Lin, K., Miyamoto, S., Puri, K., Price, J., Spinner, J., White, R., Rossano, J. W., Bearl, D. W., Cousino, M. K., Catlin, P., Hidalgo, N. C., Godown, J., Kantor, P., Masarone, D., Peng, D. M., Rea, K. E., Schumacher, K., Shaddy, R., Shea, E., Tapia, H. V., Valikodath, N., Zafar, F., Hsu, D. 2023


    Given the numerous opportunities and the wide knowledge gap in pediatric HF, an international group of pediatric HF experts with diverse backgrounds were invited and tasked with identifying research gaps in each pediatric HF domain that scientists and funding agencies need to focus on over the next decade (Visual Take Home Graphic).

    View details for DOI 10.1016/j.cardfail.2023.08.026

    View details for PubMedID 38065308

  • Maternal Diabetes and Cardiovascular Health in the Offspring. Pediatric cardiology Jodah, R., Arunamata, A., Kipps, A. K., Chen, S., Stauffer, K. J., Selamet Tierney, E. S. 2023


    Pulse wave velocity (PWV) has been explored to predict cardiovascular health in adults. Less is known about neonatal PWV. We evaluated the association between arterial stiffness of neonates of mothers (NoM) with diabetes and childhood health.Neonatal brachial-femoral PWV (bfPWV) was measured after birth and neonates followed for a median of 5.2 years [1 month-6.6 years]. 36 pregnant women with pregestational diabetes mellitus PGDM (n= 12), gestational diabetes mellitus (GDM) (n = 13), and controls (n= 11) were enrolled. Neonates were similar in weight, gestational age, and delivery mode. 26 neonates had follow-up data including weight, height and blood pressure.More mothers with PGDM had poor glycemic control compared to mothers with GDM (83% vs. 8%; p =0.0002). PWV was higher in NoM with PGDM than controls (3.4± 0.5 vs. 2.6±0.8 m/s; p= 0.04). At follow-up, children of mothers with diabetes (n= 16) had higher weight percentile (78.5 ± 27.9 vs 49.5± 34.6%; p= 0.02) and diastolic blood pressure (DBP) (68± 13.6 vs 57.3± 4.3mmHg; p=0.01) than controls (n = 10). No correlation emerged between neonatal PWV and childhood body mass index (BMI) or maternal HbA1c. Results suggest maternal diabetes affect neonatal arterial stiffness and childhood blood pressure; however, the mechanism is unclear. The long-term implications of these findings warrant further investigation.

    View details for DOI 10.1007/s00246-023-03333-4

    View details for PubMedID 37930377

  • Combined Heart Liver Transplantation in the Patients with Advanced Liver Disease and/or Hepatocellular Carcinoma: Why Can't Liver Pull the Heart? American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons Shingina, A., Bansal, N., Cedars, A., Chen, S., Daugherty, T., Emamaullee, J., Ganger, D., Ge, J., Heller, T., Hughes, D., Kay, J., Ortega Legaspi, J., Menachem, J., Montenovo, M., Sack, J., Reardon, L., Schiano, T., Simpson, K., Teuteberg, J., Tompkins, R., Vodkin, I., Wu, F., Lui, G. 2023

    View details for DOI 10.1016/j.ajt.2023.10.008

    View details for PubMedID 37839708

  • 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


    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

  • Morbidity and Mortality in Adult Fontan Patients After Heart or Combined Heart-Liver Transplantation. Journal of the American College of Cardiology Lewis, M. J., Reardon, L. C., Aboulhosn, J., Haeffele, C., Chen, S., Kim, Y., Fuller, S., Forbess, L., Alshawabkeh, L., Urey, M. A., Book, W. M., Rodriguez, F., Menachem, J. N., Clark, D. E., Valente, A. M., Carazo, M., Egbe, A., Connolly, H. M., Krieger, E. V., Angiulo, J., Cedars, A., Ko, J., Jacobsen, R. M., Earing, M. G., Cramer, J. W., Ermis, P., Broda, C., Nugaeva, N., Ross, H., Awerbach, J. D., Krasuski, R. A., Rosenbaum, M. 2023; 81 (22): 2161-2171


    An increasing number of adult Fontan patients require heart transplantation (HT) or combined heart-liver transplant (CHLT); however, data regarding outcomes and optimal referral time remain limited.The purpose of this study was to define survivorship post-HT/CHLT and predictors of post-transplant mortality, including timing of referral, in the adult Fontan population.A retrospective cohort study of adult Fontan patients who underwent HT or CHLT across 15 centers in the United States and Canada was performed. Inclusion criteria included the following: 1) Fontan; 2) HT/CHLT referral; and 3) age ≥16 years at the time of referral. Date of "failing" Fontan was defined as the earliest of the following: worsening fluid retention, new ascites, refractory arrhythmia, "failing Fontan" diagnosis by treating cardiologist, or admission for heart failure.A total of 131 patients underwent transplant, including 40 CHLT, from 1995 to 2021 with a median post-transplant follow-up time of 1.6 years (Q1 0.35 years, Q3 4.3 years). Survival was 79% at 1 year and 66% at 5 years. Survival differed by decade of transplantation and was 87% at 1 year and 76% at 5 years after 2010. Time from Fontan failure to evaluation (HR/year: 1.23 [95% CI: 1.11-1.36]; P < 0.001) and markers of failure, including NYHA functional class IV (HR: 2.29 [95% CI: 1.10-5.28]; P = 0.050), lower extremity varicosities (HR: 3.92 [95% CI: 1.68-9.14]; P = 0.002), and venovenous collaterals (HR: 2.70 [95% CI: 1.17-6.20]; P = 0.019), were associated with decreased post-transplant survival at 1 year in a bivariate model that included transplant decade.In our multicenter cohort, post-transplant survival improved over time. Late referral after Fontan failure and markers of failing Fontan physiology, including worse functional status, lower extremity varicosities, and venovenous collaterals, were associated with post-transplant mortality.

    View details for DOI 10.1016/j.jacc.2023.03.422

    View details for PubMedID 37257951

  • Clinical Outcomes of Adult Fontan-Associated Liver Disease and Combined Heart-Liver Transplantation. Journal of the American College of Cardiology Lewis, M. J., Reardon, L. C., Aboulhosn, J., Haeffele, C., Chen, S., Kim, Y., Fuller, S., Forbess, L., Alshawabkeh, L., Urey, M. A., Book, W. M., Rodriguez, F., Menachem, J. N., Clark, D. E., Valente, A. M., Carazo, M., Egbe, A., Connolly, H. M., Krieger, E. V., Angiulo, J., Cedars, A., Ko, J., Jacobsen, R. M., Earing, M. G., Cramer, J. W., Ermis, P., Broda, C., Nugaeva, N., Ross, H., Awerbach, J. D., Krasuski, R. A., Rosenbaum, M. 2023; 81 (22): 2149-2160


    The impact of Fontan-associated liver disease (FALD) on post-transplant mortality and indications for combined heart-liver transplant (CHLT) in adult Fontan patients remains unknown.The purpose of this study was to assess the impact of FALD on post-transplant outcomes and compare HT vs CHLT in adult Fontan patients.We performed a retrospective-cohort study of adult Fontan patients who underwent HT or CHLT across 15 centers. Inclusion criteria were as follows: 1) Fontan; 2) HT/CHLT referral; and 3) age ≥16 years at referral. Pretransplant FALD score was calculated using the following: 1) cirrhosis; 2) varices; 3) splenomegaly; or 4) ≥2 paracenteses.A total of 131 patients (91 HT and 40 CHLT) were included. CHLT recipients were more likely to be older (P = 0.016), have a lower hemoglobin (P = 0.025), require ≥2 diuretic agents pretransplant (P = 0.051), or be transplanted in more recent decades (P = 0.001). Postmatching, CHLT demonstrated a trend toward improved survival at 1 year (93% vs 74%; P = 0.097) and improved survival at 5 years (86% vs 52%; P = 0.041) compared with HT alone. In patients with a FALD score ≥2, CHLT was associated with improved survival (1 year: 85% vs 62%; P = 0.044; 5 years: 77% vs 42%; P = 0.019). In a model with transplant decade and FALD score, CHLT was associated with improved survival (HR: 0.33; P = 0.044) and increasing FALD score was associated with worse survival (FALD score: 2 [HR: 14.6; P = 0.015], 3 [HR: 22.2; P = 0.007], and 4 [HR: 27.8; P = 0.011]).Higher FALD scores were associated with post-transplant mortality. Although prospective confirmation of our findings is necessary, compared with HT alone, CHLT recipients were older with higher FALD scores, but had similar survival overall and superior survival in patients with a FALD score ≥2.

    View details for DOI 10.1016/j.jacc.2023.03.421

    View details for PubMedID 37257950

  • Outcomes After Development of Ventricular Arrhythmias in Single Ventricular Heart Disease Patients With Fontan Palliation. Circulation. Arrhythmia and electrophysiology Giacone, H. M., Chubb, H., Dubin, A. M., Motonaga, K. S., Ceresnak, S. R., Goodyer, W. R., Hanish, D., Trela, A. V., Boramanand, N., Lencioni, E., Boothroyd, D., Graber-Naidich, A., Wright, G., Haeffele, C., Hollander, S. A., McElhinney, D. B., Ma, M., Hanley, F. L., Chen, S. 2023: e011143


    With the advent of more intensive rhythm monitoring strategies, ventricular arrhythmias (VAs) are increasingly detected in Fontan patients. However, the prognostic implications of VA are poorly understood. We assessed the incidence of VA in Fontan patients and the implications on transplant-free survival.Medical records of Fontan patients seen at a single center between 2002 and 2019 were reviewed to identify post-Fontan VA (nonsustained ventricular tachycardia >4 beats or sustained >30 seconds). Patients with preFontan VA were excluded. Hemodynamically unstable VA was defined as malignant VA. The primary outcome was death or heart transplantation. Death with censoring at transplant was a secondary outcome.Of 431 Fontan patients, transplant-free survival was 82% at 15 years post-Fontan with 64 (15%) meeting primary outcome of either death (n=16, 3.7%), at a median 4.6 (0.4-10.2) years post-Fontan, or transplant (n=48, 11%), at a median of 11.1 (5.9-16.2) years post-Fontan. Forty-eight (11%) patients were diagnosed with VA (90% nonsustained ventricular tachycardia, 10% sustained ventricular tachycardia). Malignant VA (n=9, 2.0%) was associated with younger age, worse systolic function, and valvular regurgitation. Risk for VA increased with time from Fontan, 2.4% at 10 years to 19% at 20 years. History of Stage 1 surgery with right ventricular to pulmonary artery conduit and older age at Fontan were significant risk factors for VA. VA was strongly associated with an increased risk of transplant or death (HR, 9.2 [95% CI, 4.5-18.7]; P<0.001), with a transplant-free survival of 48% at 5-year post-VA diagnosis.Ventricular arrhythmias occurred in 11% of Fontan patients and was highly associated with transplant or death, with a transplant-free survival of <50% at 5-year post-VA diagnosis. Risk factors for VA included older age at Fontan and history of right ventricular to pulmonary artery conduit. A diagnosis of VA in Fontan patients should prompt increased clinical surveillance.

    View details for DOI 10.1161/CIRCEP.122.011143

    View details for PubMedID 37254747

  • High Prevalence of Abnormal Hemoglobin A1c in the Adolescent and Young Adult Fontan Population. Pediatric cardiology Woo, J. P., Romfh, A., Levin, G., Norris, J., Han, J., Grover, M., Chen, S. 2023


    Little is known about diabetes risk in adolescents and young adults with Fontan palliation. We sought to understand the prevalence of abnormal hemoglobin A1c (HbA1c) in the adolescent and young adult population with Fontan palliation. Between 2015 and 2021, 78 Fontan patients > 10 years of age were seen in our single ventricle clinic; 66 underwent screening with HbA1c. 50% of the study cohort (n = 33) had HbA1c ≥ 5.7%; 2% (n = 1) had HbA1c ≥ 6.5%. There was no correlation between BMI and HbA1c, with no difference in the prevalence of overweight or obesity (BMI ≥ 85th percentile) between those with and without abnormal HbA1c (31% versus 27%, p = 0.69). While 20% of the cohort had a family history of diabetes, there was no difference in family history between those with and without abnormal HbA1c (21% versus 19%, p = 0.85). There were no differences in other risk factors and characteristics (race, glomerular filtration rate, liver function, liver elastography, hematocrit, and years from Fontan surgery) between those with and without abnormal HbA1c. Our results highlight the importance of recognizing that abnormal HbA1c is highly prevalent in the Fontan population. Whether abnormal HbA1c in this population correlates with atherosclerotic cardiovascular disease in adulthood is not known. The mechanism for an abnormal HbA1c in the adolescent and young adult Fontan population remains unclear and further studies are needed.

    View details for DOI 10.1007/s00246-023-03139-4

    View details for PubMedID 36943450

    View details for PubMedCentralID 4859356

  • 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


    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

  • The development and efficacy of a paediatric cardiology fellowship online preparatory course. Cardiology in the young Motonaga, K. S., Sacks, L., Olson, I., Balasubramanian, S., Chen, S., Peng, L., Feinstein, J. A., Silverman, N. H., Hanley, F. L., Axelrod, D. M., Krawczeski, C. D., Arunamata, A., Kwiatkowski, D. M., Ceresnak, S. R. 2022: 1-6


    BACKGROUND: The transition from residency to paediatric cardiology fellowship is challenging due to the new knowledge and technical skills required. Online learning can be an effective didactic modality that can be widely accessed by trainees. We sought to evaluate the effectiveness of a paediatric cardiology Fellowship Online Preparatory Course prior to the start of fellowship.METHODS: The Online Preparatory Course contained 18 online learning modules covering basic concepts in anatomy, auscultation, echocardiography, catheterisation, cardiovascular intensive care, electrophysiology, pulmonary hypertension, heart failure, and cardiac surgery. Each online learning module included an instructional video with pre-and post-video tests. Participants completed pre- and post-Online Preparatory Course knowledge-based exams and surveys. Pre- and post-Online Preparatory Course survey and knowledge-based examination results were compared via Wilcoxon sign and paired t-tests.RESULTS: 151 incoming paediatric cardiology fellows from programmes across the USA participated in the 3 months prior to starting fellowship training between 2017 and 2019. There was significant improvement between pre- and post-video test scores for all 18 online learning modules. There was also significant improvement between pre- and post-Online Preparatory Course exam scores (PRE 43.6 ± 11% versus POST 60.3 ± 10%, p < 0.001). Comparing pre- and post-Online Preparatory Course surveys, there was a statistically significant improvement in the participants' comfort level in 35 of 36 (97%) assessment areas. Nearly all participants (98%) agreed or strongly agreed that the Online Preparatory Course was a valuable learning experience and helped alleviate some anxieties (77% agreed or strongly agreed) related to starting fellowship.CONCLUSION: An Online Preparatory Course prior to starting fellowship can provide a foundation of knowledge, decrease anxiety, and serve as an effective educational springboard for paediatric cardiology fellows.

    View details for DOI 10.1017/S1047951122003626

    View details for PubMedID 36440543

  • Fontan-associated liver disease after heart transplant. Pediatric transplantation Griffiths, E. R., Lambert, L. M., Ou, Z., Shaaban, A., Rezvani, M., Carlo, W. F., Schumacher, K. R., DiPaola, F., O'Connor, M. J., Nandi, D., Zangwill, S., McCulloch, M. A., Friedland-Little, J. M., West, S. C., Lee, T. M., Alejos, J. C., Chen, S., Molina, K. M. 2022: e14435


    BACKGROUND: Fontan associated liver disease (FALD) potentially impacts Fontan patients undergoing heart transplant. This multi-center study sought to identify pre-transplant risk factors and characterize any post-transplant liver recovery in those patients undergoing heart-alone transplant.METHODS: Review of Fontan patients at 12 pediatric institutions who underwent heart transplant between 2001-2019. Radiologists reviewed pre and post-transplant liver imaging for fibrosis. Laboratory, pathology and endoscopy studies were reviewed.RESULTS: 156 patients underwent transplant due to decreased ventricular function (49%), protein losing enteropathy (31%) or plastic bronchitis (10%); median age at transplant was 13.6 years (interquartile range IQR 7.8, 17.2) with a median of 9.3 years (IQR 3.2, 13.4) between the Fontan operation and transplant. Few patients had pre-transplant endoscopy (18%), and liver biopsy (19%). There were 31 deaths (20%). The median time from transplant to death was 0.5 years (95% Confidence Interval CI 0.0, 3.6). The five-year survival was 73% (95% CI 64%, 83%). Deaths were related to cardiac causes in 68% (21/31) and infection in 6 (19%). A pre-transplant elevation in bilirubin was a predictor of death. Higher platelet levels were protective. Immediate post-transplant elevations in creatinine, AST, ALT, and INR were predictive of death. Advanced liver fibrosis identified on ultrasound, computed tomography, or magnetic resonance imaging was not predictive of death. Liver imaging suggested some improvement in liver congestion post-transplant.CONCLUSIONS: Elevated bilirubin, but not fibrosis on liver imaging, was associated with post-heart transplant mortality in Fontan patients in this multicenter retrospective study. Additionally, heart transplant may alter the progression of FALD.

    View details for DOI 10.1111/petr.14435

    View details for PubMedID 36380561

  • 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


    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

  • Subcutaneous Treprostinil Improves Surgical Candidacy for Next Stage Palliation in Single Ventricle Patients With High-Risk Hemodynamics. Seminars in thoracic and cardiovascular surgery Sullivan, R. T., Handler, S. S., Feinstein, J. A., Ogawa, M., Liu, E., Ma, M., Hopper, R. K., Norris, J., Hollander, S. A., Chen, S. 2022


    Single ventricle (SV) patients with pulmonary vascular disease (SV-PVD) are considered poor surgical candidates for Glenn or Fontan palliation. Given limited options for Stage 1 (S1) and Stage 2 (S2) SV patients with SV-PVD, we report on the use of subcutaneous treprostinil (TRE) to treat SV-PVD in this population. This single-center, retrospective cohort study examined SV patients who were not candidates for subsequent surgical palliation due to SV-PVD and were treated with TRE. The primary outcome was ability to progress to the next surgical stage; secondary outcomes included changes in hemodynamics after TRE initiation. Between 3/2014 and 8/2021, 17 SV patients received TRE for SV-PVD: 11 after S1 and 6 after S2 (median PVR 4.1 [IQR 3.2-4.8] WU*m2, and 5.0 [IQR 1.5-6.1] WU*m2, respectively). Nine of eleven (82%) S1 progressed to S2, and 2 (18%) underwent heart transplant (HTx). Three of six (50%) S2 progressed to Fontan, 1 underwent HTx and 2 are awaiting Fontan on TRE. TRE significantly decreased PVR in S1 patients with median post-treatment PVR of 2.0 (IQR 1.5-2.6) WU*m2. TRE can allow for further surgical palliation in select pre-Fontan patients with SV-PVD, obviating the need for HTx. Improvement in PVR was significant in S1 patients and persisted beyond discontinuation of therapy for most patients.

    View details for DOI 10.1053/j.semtcvs.2022.07.011

    View details for PubMedID 35931345

  • Fatal nocardiosis infection in a pediatric patient with an immunodeficiency after heart re-transplantation. Pediatric transplantation Mai, D. H., Sedler, J., Weinberg, K., Bernstein, D., Schroeder, A., Mathew, R., Chen, S., Lee, D., Dykes, J. C., Hollander, S. A. 2022: e14344


    BACKGROUND: Nocardia infections are rare opportunistic infections in SOT recipients, with few reported pediatric cases. Pediatric patients with single ventricle congenital heart defects requiring HT may be more susceptible to opportunistic infections due to a decreased T-cell repertoire from early thymectomy and potential immunodeficiencies related to their congenital heart disease. Other risk factors in SOT recipients include the use of immunosuppressive medications and the development of persistent lymphopenia, delayed count recovery and/or lymphocyte dysfunction.METHODS: We report the case of a patient with hypoplastic left heart syndrome who underwent neonatal congenital heart surgery (with thymectomy) prior to palliative surgery and 2 HTs.RESULTS: After developing respiratory and neurological symptoms, the patient was found to be positive for Nocardia farcinica by BAL culture and cerebrospinal fluid PCR. Immune cell phenotyping demonstrated an attenuated T and B-cell repertoire. Despite antibiotic and immunoglobulin therapy, his symptoms worsened and he was subsequently discharged with hospice care.CONCLUSION: Pediatric patients with a history of congenital heart defects who undergo neonatal thymectomy prior to heart transplantation and a long-term history of immunosuppression should undergo routine immune system profiling to evaluate for T- and B-cell deficiency as risk factors for opportunistic infection. Such patients could benefit from long-term therapy with TMP/SMX for optimal antimicrobial prophylaxis, with desensitization as needed for allergies. Disseminated nocardiosis should be considered when evaluating acutely ill SOT recipients, especially those with persistent lymphopenia and known or suspected secondary immunodeficiencies.

    View details for DOI 10.1111/petr.14344

    View details for PubMedID 35726843

  • Towards identifying predictors of pediatric heart only versus combined heart liver transplantation Zhang, K., Chen, S., Syed, A., Gallo, A., Esquivel, C., Bonham, A., Hollander, S. A., Ma, M., Han, J., Ebel, N. H. WILEY. 2022
  • Feasibility of Assessing Adolescent and Young Adult Heart Transplant Recipient Mental Health and Resilience Using Patient-Reported Outcome Measures JOURNAL OF THE ACADEMY OF CONSULTATION-LIAISON PSYCHIATRY Brown, T., Chen, S., Ou, Z., McDonald, N., Bennett-Murphy, L., Schneider, L., Giles, L., Molina, K., Cox, D., Hoskoppal, A., Glotzbach, K., Stehlik, J., May, L. 2022; 63 (2): 153-162
  • Children who stroke on VAD support: when is it safe to transplant and what are their outcomes? Artificial organs Thangappan, K., Haney, L. C., Riggs, K., Chen, S., Mehegan, M., VanderPluym, C., Woods, R., LaPar, D., Lorts, A., Zafar, F., Morales, D. L. 2022


    OBJECTIVE: Ventricular assist devices (VADs) increase waitlist survival, yet the risk of stroke remains notable. The purpose of this study was to analyze how strokes on VAD support impact post-transplant (post-Tx) outcomes in children.METHODS: 520 pediatric (<18 yo) heart transplant candidates listed from January 2011 to April 2018 with a VAD implant date were matched between the United Network of Organ Sharing and Pediatric Health Information System databases. Patients were divided into pre-Tx Stroke and No Stroke cohorts.RESULTS: 81% of the 520 patients were transplanted. 28% (n=146) had a pre-Tx Stroke. 59% (n=89) of the Stroke patients were transplanted at a median of 57 (IQR 17-102) days from stroke. Significantly more No Stroke cohort (90%) were transplanted (p<0.001). There was no difference in post-Tx survival between the Stroke and No Stroke cohorts (p=0.440). Time between stroke and transplant for patients who died within one year of transplant was 32.0 days (median) compared to 60.5 days for those alive > 1year (p=0.18). Regarding patients in whom time from stroke to transplant was more than 60 days, one-year survival of Stroke vs. No Stroke patients was 96% vs. 95% (p=0.811), respectively.CONCLUSION: Patients with stroke during VAD support, once transplanted, enjoy similar survival compared to No Stroke patients. We hypothesize that allowing Stroke patients more time to recover could improve post-Tx outcomes. Unfortunately, the ideal duration of time between stroke and safe transplantation could not be determined and will require more detailed and larger studies in the future.

    View details for DOI 10.1111/aor.14194

    View details for PubMedID 35132634

  • Response to JHLT-D-21-00302 "Failing Fontan - heart or heart-liver transplant: The jury is (still) out?" JOURNAL OF HEART AND LUNG TRANSPLANTATION Chen, S., Bensen, R., Hollander, S. A., Sganga, D. 2021; 40 (10): 1248-1249
  • Neurosurgical intervention in children with ventricular assist devices: A single center case series review. Paediatric anaesthesia Yu, J., Murray, J., Ramamoorthy, C., Chen, S., Lee, S., Ryan, K., Maeda, K., Navaratnam, M. 2021


    BACKGROUND: The incidence of neurological complications related to ventricular assist devices (VAD) remains high and includes life-threatening conditions such as intracranial hemorrhage or ischemic stroke. Although no definitive management guidelines exist, operative interventions may be required for major neurological injuries.AIMS: This case series describes the perioperative management of children at a single center who underwent neurosurgical procedures for major intracranial bleeds or ischemic strokes whilst on VAD support.METHODS: A database review identified all pediatric VAD patients who underwent a neurosurgical procedure for an intracranial hemorrhage or ischemic stroke from April 2014 to January 2020. Data regarding patient characteristics, preoperative medical management, intraoperative anesthetic management, and postoperative outcomes were collected using retrospective chart review.RESULTS: Ninety VADs were implanted in 78 patients. Five neurosurgical interventions were performed: 4 for intracranial hemorrhages and 1 for an ischemic stroke. All 4 patients with hemorrhages were receiving anticoagulation at the time of their event and the 3 patients on warfarin received emergent reversal with prothrombin concentrate complex and vitamin K. Three patients also received pre-procedural platelet transfusions. Two of the 5 procedures were emergent bedside external ventricular drain placements and 3 were surgical operations. All 3 patients who underwent operative procedures received invasive hemodynamic monitoring and were supported with a combination of inotropes and afterload reduction. One patient required a massive blood product transfusion. The 2 patients who underwent external ventricular drain placement had no further surgical interventions and died from the severity of their neurological injuries. All 3 patients who underwent operative procedures survived to transplantation and discharge home.CONCLUSIONS: Perioperative concerns for the anesthesiologist include VAD hemodynamic management, bleeding, VAD thrombosis, and prevention of secondary brain injury. A systematic, multidisciplinary approach to management is paramount to attain favorable outcomes.

    View details for DOI 10.1111/pan.14287

    View details for PubMedID 34478592

  • Feasibility of assessing adolescent and young adult heart transplant recipient mental health and resilience using patient-reported outcome measures. Journal of the Academy of Consultation-Liaison Psychiatry Brown, T., Chen, S., Ou, Z., McDonald, N., Bennett-Murphy, L., Schneider, L., Giles, L., Molina, K., Cox, D., Hoskoppal, A., Glotzbach, K., Stehlik, J., May, L. 2021


    BACKGROUND: Although adolescents and young adults (AYA) may be particularly prone to mental health symptoms following heart transplant, screening practices are variable. This study examined the feasibility of using patient-reported outcome (PRO) measures to assess mental health, functional status, and resiliency in post-transplant AYA patients.METHODS: Patients transplanted between ages 15-25 years at three centers completed six PRO instruments via web-based platforms: PROMIS instruments for anxiety, depression, satisfaction with social roles, and physical functioning; the Posttraumatic Stress Diagnostic Scale for DSM-V (PDS-5); and the Connor-Davidson Resilience Scale-10 (CD-RISC-10). Feasibility (completion, time to completion, and measure missingness) and PRO results were described and compared between congenital heart disease (CHD) and cardiomyopathy (CM) patients.RESULTS: Nineteen patients (median age at transplant 17.7 years [IQR 16.3,19.2 years], 84% male) were enrolled at an average of 3 ± 1.8 years post-transplant. Enrollment was 90% among eligible patients. Measure missingness were zero. The average completion time was 12 ± 15 minutes for all instruments. Timely PRO completion was facilitated by in-clinic application. The PRO results indicated that 9 patients (47%) had at least mild PTSD symptoms (≥11 points on PDS-5). Among them, 4 patients had scores >28 suggestive of probable PTSD. Two (11%) and 6 (32%) patients had anxious and depressive symptoms, respectively. The CM cohort had a higher median PDS-5 score than that of the CHD subgroup (11.0 vs 6.0; p = 0.015). Twelve (63%) had resiliency scores that were lower than the population average. No significant differences were found in PRO results between CM and CHD patients apart from the PTSD assessment.CONCLUSIONS: This novel PRO-based approach to psychiatric screening of AYA patients after transplant appears feasible for assessing mental health, functional status, and resiliency, with excellent enrollment and completion rates. These instruments characterized the burden of mental health symptoms within this AYA heart transplant cohort, with a high prevalence of PTSD symptoms. Resiliency scores were lower than in a comparison population. Electronically- administered PRO administration could facilitate more consistent mental health screening in this at-risk group.

    View details for DOI 10.1016/j.jaclp.2021.08.002

    View details for PubMedID 34438097

  • Diagnosis and Management of Myocarditis in Children: A Scientific Statement From the American Heart Association. Circulation Law, Y. M., Lal, A. K., Chen, S., Čiháková, D., Cooper, L. T., Deshpande, S., Godown, J., Grosse-Wortmann, L., Robinson, J. D., Towbin, J. A. 2021; 144 (6): e123-e135


    Myocarditis remains a clinical challenge in pediatrics. Originally, it was recognized at autopsy before the application of endomyocardial biopsy, which led to a histopathology-based diagnosis such as in the Dallas criteria. Given the invasive and low-sensitivity nature of endomyocardial biopsy, its diagnostic focus shifted to a reliance on clinical suspicion. With the advances of cardiac magnetic resonance, an examination of the whole heart in vivo has gained acceptance in the pursuit of a diagnosis of myocarditis. The presentation may vary from minimal symptoms to heart failure, life-threatening arrhythmias, or cardiogenic shock. Outcomes span full resolution to chronic heart failure and the need for heart transplantation with inadequate clues to predict the disease trajectory. The American Heart Association commissioned this writing group to explore the current knowledge and management within the field of pediatric myocarditis. This statement highlights advances in our understanding of the immunopathogenesis, new and shifting dominant pathogeneses, modern laboratory testing, and use of mechanical circulatory support, with a special emphasis on innovations in cardiac magnetic resonance imaging. Despite these strides forward, we struggle without a universally accepted definition of myocarditis, which impedes progress in disease-targeted therapy.

    View details for DOI 10.1161/CIR.0000000000001001

    View details for PubMedID 34229446

  • 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


    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

  • 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

  • Longitudinal Assessment of Right Ventricular Function in Hypoplastic Left Heart Syndrome. Pediatric cardiology Balasubramanian, S., Smith, S. N., Srinivasan, P., Tacy, T. A., Hanley, F. L., Chen, S., Wright, G. E., Peng, L. F., Punn, R. 2021


    Overall survival of patients with hypoplastic left heart syndrome (HLHS) has shown continued improvement. Right ventricular (RV) dysfunction, in the long term, adversely affects prognosis in these patients. This study examines changes in echocardiographic markers of RV function in a longitudinal cohort. We retrospectively reviewed patients with HLHS managed at our institution from 7/1994 to 1/2016. Follow-up included surgical and clinical data, and echocardiographic measures. Measures of RV function preceding and following all three stages of single ventricular palliation were collected. Freedom from transplant-free survival was assessed by Kaplan-Meier analysis. Multivariable associations with time to death or transplant were explored using the Cox proportional hazards model. A total of 120 patients with HLHS were identified. Norwood operation was performed in all patients. The probability of survival for the cohort was 71±4.4%, 69±4.5% and 66±4.7% at 1, 2 and 5years respectively after stage I Norwood operation. RV fractional area change (FAC), compared to post-Norwood was decreased at all subsequent stages with the greatest change noted post-superior cavo-pulmonary shunt from 40.7±9.3% to 31.1±8.3% (p<0.001). Similarly, tricuspid valve annular systolic excursion (TAPSE) Z-score declined from -2.9±1.3 to -9.7±1.3 (p<0.001) with a decrement at every stage of evaluation. In comparison to patients with post-Norwood RV FAC>35% and TAPSE Z-score>-5, patients with RV FAC ≤ 35% and TAPSE Z-score ≤ -5 had a significantly lower transplant-free survival (p<0.0001). In patients with HLHS undergoing staged palliation, decrement in RV function manifests longitudinally. Post-Norwood RV FAC and TAPSE Z-score appear to be early markers of poor outcome in this population.

    View details for DOI 10.1007/s00246-021-02624-y

    View details for PubMedID 33987707

  • 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


    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

  • Comparison of combined heart‒liver vs heart-only transplantation in pediatric and young adult Fontan recipients. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Sganga, D., Hollander, S. A., Vaikunth, S., Haeffele, C., Bensen, R., Navaratnam, M., McDonald, N., Profita, E., Maeda, K., Concepcion, W., Bernstein, D., Chen, S. 2020


    BACKGROUND: Indications for a heart‒liver transplantation (HLT) for Fontan recipients are not well defined. We compared listing characteristics, post-operative complications, and post-transplant outcomes of Fontan recipients who underwent HLT with those of patients who underwent heart-only transplantation (HT). We hypothesized that patients who underwent HLT have increased post-operative complications but superior survival outcomes compared with patients who underwent HT.METHODS: We performed a retrospective review of Fontan recipients who underwent HLT or HT at a single institution. Characteristics at the time of listing, including the extent of liver disease determined by laboratory, imaging, and biopsy data, were compared. Post-operative complications were assessed, and the Kaplan‒Meier survival method was used to compare post-transplant survival. Univariate regression analyses were performed to identify the risk factors for increased mortality and morbidity among patients who underwent HT.RESULTS: A total of 47 patients (9 for HLT, 38 for HT) were included. Patients who underwent HLT were older, were more likely to be on dual inotrope therapy, and had evidence of worse liver disease. Whereas ischemic time was longer for the group who underwent HLT, post-operative complications were similar. Over a median post-transplant follow-up of 17 (interquartile range: 5-52) months, overall mortality for the cohort was 17%; only 1 patient who underwent HLT died (11%) vs 7 patients who underwent HT (18%) (p = 0.64). Among patients who underwent HT, cirrhosis on pre-transplant imaging was associated with worse outcomes.CONCLUSIONS: Despite greater inotrope need and more severe liver disease at the time of listing, Fontan recipients undergoing HLT have post-transplant outcomes comparable with those of patients undergoing HT. HLT may offer a survival benefit for Fontan recipients with liver disease.

    View details for DOI 10.1016/j.healun.2020.12.008

    View details for PubMedID 33485775

  • Does liver biopsy accurately measure fibrosis in Fontan associated liver disease? A comparison of liver biopsy pre-combined heart and liver transplant and liver explant post-transplant. Clinical transplantation Vaikunth, S. S., Higgins, J. P., Concepcion, W., Haeffele, C., Wright, G. E., Chen, S., Lui, G. K., Daugherty, T. 2020: e14120


    The accuracy of liver biopsy to stage fibrosis due to Fontan associated liver disease (FALD) remains unclear. We compared results of biopsy pre-combined heart and liver transplantation (CHLT) to results of whole liver explant. Liver biopsy and explants from 15 Fontan patients (ages 16 - 49, median 28 years) were retrospectively reviewed. Staging was as follows: stage 0: no fibrosis, stage 1: pericellular fibrosis, stage 2: bridging fibrosis, stage 3: regenerative nodules. There is no stage 4. Clinical characteristics including Model of End-stage Liver Disease eXcluding INR and Varices, Ascites, Splenomegaly, and Thrombocytopenia (VAST) scores were collected, and descriptive statistics and Mann-Whitney U tests used to analyze data. All patients had biopsies with at least bridging fibrosis, and all had nodularity on explant; transjugular biopsy never overestimated fibrosis. Explant showed higher grade fibrosis (Stage 3) than pre-CHLT biopsy (Stage 2) in 6 of 15 patients and equal grade of fibrosis (Stage 3) in 9 of 15 patients. Though clinical characteristics varied significantly, VAST score was ≥ 2 in all but two patients. Transjugular liver biopsy does not overestimate and can underestimate fibrosis in Fontan patients undergoing CHLT, likely due to the patchy nature of fibrosis in FALD.

    View details for DOI 10.1111/ctr.14120

    View details for PubMedID 33053213

  • 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


    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
  • Review of the discard and/or refusal rate of offered donor hearts to pediatric waitlisted candidates. Pediatric transplantation Schweiger, M., Everitt, M. D., Chen, S., Nandi, D., Castro, J., Gupta, D., Scheel, J., Lal, A. K., Ablonczy, L., Kirk, R., Miera, O., Davies, R. R., Dipchand, A. I. 2020: e13674


    We aimed to review current literature on the discard rate of donor hearts offered to pediatric recipients and assess geographical differences. Consequences and ways to reduce the discard rate are discussed. A systemic review on published literature on pediatric transplantation published in English since 2010 was undertaken. Additionally, a survey was sent to international OPOs with the goal of incorporating responses from around the world providing a more global picture. Based on the literature review and survey, there is a remarkably wide range of discard and/or refusal for pediatric hearts offered for transplant, ranging between 18% and 57% with great geographic variation. The data suggest that that the overall refusal rate may have decreased over the last decade. Reasons for organ discard were difficult to identify from the available data. Although the refusal rate of pediatric donor hearts seems to be lower compared to that reported in adults, it is still as high as 57% with geographic variation.

    View details for DOI 10.1111/petr.13674

    View details for PubMedID 32198804

  • 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


    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

  • The use of prothrombin complex concentrate as a warfarin reversal agent in pediatric patients undergoing orthotopic heart transplantation. Paediatric anaesthesia Sisti, D., Williams, G. D., Ding, V., Long, J., Maeda, K., Chen, S., Navaratnam, M. 2020


    BACKGROUND: Patients supported with a ventricular assist device are predisposed to severe bleeding at the time of orthotopic heart transplant due to several risk factors including anticoagulation with vitamin K antagonists. Kcentra, a four-factor prothrombin complex concentrate has been approved by the FDA for warfarin reversal in adults prior to urgent surgery. There is a lack of published data on the preoperative use of four-factor prothrombin complex concentrates in pediatric patients undergoing cardiac surgery.METHODS: This is a single center retrospective analysis of pediatric patients with a continuous flow ventricular assist device who underwent heart transplant, comparing patients who received Kcentra for anticoagulation reversal with a historical patient cohort who did not. Consecutive patients from January 2013 to December 2017 were analyzed. The primary outcome was volume of blood product transfusion prior to cardiopulmonary bypass initiation. Secondary outcomes include blood product transfusion after cardiopulmonary bypass intraoperatively and up to 24 hours postoperatively, chest tube output within 24 hours of surgery, time to extubation, incidence of thromboembolism, and post-transplant length of stay.RESULTS: From 2013 to 2017, 31 patients with continuous flow ventricular assist devices underwent heart transplant, with 27 patients included in the analysis. Fifteen patients received Kcentra compared with 12 patients who received fresh frozen plasma for anticoagulation reversal. Compared with the control group, patients who received Kcentra had less packed red blood cells, fresh frozen plasma, and platelets transfused prior to cardiopulmonary bypass initiation. The Kcentra group also received less packed red blood cells on bypass and less packed red blood cells after cardiopulmonary bypass termination. There were no differences in chest tube output, time to extubation, intensive care unit length of stay or overall hospital length of stay. Neither group had thromboembolic complications detected during the first 7 postoperative days.CONCLUSION: This small retrospective study indicates that preoperative warfarin reversal with Kcentra reduces blood product exposure in pediatric patients with ventricular assist devices undergoing heart transplant.

    View details for DOI 10.1111/pan.13839

    View details for PubMedID 32037665

  • 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
  • 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

  • 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


    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


    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

  • 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


    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

  • 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
  • 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


    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

  • Outcomes After Infections in Adolescents and Young Adults with Continuous-Flow Left Ventricular Assist Devices ASAIO JOURNAL Chen, S., Cantor, R. S., Auerbach, S., Schumacher, K., Almond, C. S., Eghtesady, P., Alejos, J., Das, B. B., Hong, B. J., Jaquiss, R. B., Kirklin, J. K., Jeewa, A. 2019; 65 (4): 380–88
  • 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

  • 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

  • Outcomes of children supported with an intracorporeal continuous-flow left ventricular assist system JOURNAL OF HEART AND LUNG TRANSPLANTATION VanderPluym, C. J., Adachi, I., Niebler, R., Griffiths, E., Fynn-Thompson, F., Chen, S., O'Connor, M. J., Machado, D., Hawkins, B., Bleiweis, M. S., Koehl, D. A., Cantor, R. S., Morales, D., Lorts, A. 2019; 38 (4): 385–93
  • 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


    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

  • 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


    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

  • Fontan-associated protein-losing enteropathy and post-heart transplant outcomes: A multicenter study JOURNAL OF HEART AND LUNG TRANSPLANTATION Schumacher, K. R., Yu, S., Butts, R., Castleberry, C., Chen, S., Edens, E., Godown, J., Johnson, J., Kemna, M., Lin, K., Lowery, R., Simpson, K., West, S., Wilmot, I., Gossett, J. G. 2019; 38 (1): 17–25
  • Outcomes of children supported with an intracorporeal continuous-flow left ventricular assist system. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation VanderPluym, C. J., Adachi, I., Niebler, R., Griffiths, E., Fynn-Thompson, F., Chen, S., O'Connor, M. J., Machado, D., Hawkins, B., Bleiweis, M. S., Koehl, D. A., Cantor, R. S., Morales, D., Lorts, A. 2018


    BACKGROUND: Since 2012, there has been growing use of the HeartWare (Medtronic, Mounds View, MN) intracorporeal continuous flow (CF) ventricular assist device (VAD) in children, despite it not being labeled for use in pediatric patients. We sought to describe the use and outcomes of children with HeartWare VADs.METHODS: We identified all patients aged < 19 years and young adults aged 19 to 30 years supported with HeartWare who were entered into the pediatric portion (Pedimacs) of the Interagency Registry for Mechanically Assisted Circulatory Support (Intermacs) and the Intermacs registries, respectively, between September 2012 and June 2017. Adverse events and outcomes were analyzed and compared.RESULTS: We identified 192 children and 247 young adult HeartWare patients. Baseline characteristics of children differed from young adults, with lower median weight of 51.5 kg (range, 13.1-162) vs 75.8 kg (range, 29.8-191; p ≤ 0.0001) and body surface area of 1.5 m2 (range, 0.6-2.9 m2) vs 1.9 m2 (range, 1.1-3.2 m2; p ≤ 0.0001) . At the time of implant, 12 children weighed < 20 kg, and 58.3% of these children had congenital heart disease compared with 11.7% in children who weighed ≥ 20 kg and 6.1% in young adults (p ≤ 0.0001). Median duration of support was 2.8 months (IQR, 1.3-6.0 months) in children and 9.7 months (IQR 4.0-19.2 months) in young adults (p ≤ 0.0001). Serious adverse events in children and young adults included infection in 27% and 44% of patients, respectively (p=0.0002), major bleeding in 23% and 23%, respectively (p = 0.9), device malfunction/pump thrombosis in 11% and 19.0%, respectively (p = 0.04), and stroke in 10% and 12%, respectively (p = 0.5). Of the children who weighed < 20 kg at time of implant, 0% had major bleeding, 16.7% had infections, and 8.3% had stroke. Overall survival was not statistically different between children and young adults, and there was no increased mortality in children who weighed < 20 kg. Rate of discharge on HeartWare was 80% in young adults vs 48% in children who weighed ≥ 20 kg and only 33% in children who weighed < 20 kg.CONCLUSIONS: Survival in children supported with HeartWare is encouraging and comparable to young adults; however, adverse events are not uncommon in children. Ongoing evaluation of the HeartWare use in children is necessary to further decrease the rate of adverse events and understand obstacles to discharge.

    View details for PubMedID 30391197

  • Outcomes After Infections in Adolescents and Young Adults with Continuous-Flow Left Ventricular Assist Devices. ASAIO journal (American Society for Artificial Internal Organs : 1992) Chen, S. n., Cantor, R. S., Auerbach, S. n., Schumacher, K. n., Almond, C. S., Eghtesady, P. n., Alejos, J. n., Das, B. B., Hong, B. J., Jaquiss, R. n., Kirklin, J. K., Jeewa, A. n. 2018


    Infections in adult ventricular assist device patients increase subsequent mortality and stroke risk. Less is known about outcomes after infections in younger patients, where diabetes and obesity, risk factors associated with poor outcomes, are less prevalent. The purpose of this study was to examine outcomes after infections in adolescents and young adults with continuous-flow left ventricular assist devices (VAD) bridged to transplant. From Pediatric Interagency Registry for Mechanically Assisted Circulatory Support and Interagency Registry for Mechanical Circulatory Support registries, we identified patients aged 12-29 years with continuous-flow VADs implanted as bridged to transplant from September 2012 to March 2016. The primary predictor variable was first reported infection. The primary outcome was death on VAD support; secondary outcome was clinical stroke. Kaplan-Meier and Cox proportional hazard methods were used to compare outcomes between patients before or without infection and patients after infection. Ninety-two adolescents (12-18 years of age) and 224 young adults (19-29 years of age) with 3,748 patient-months of follow-up were included. Adolescents were smaller (body surface area 1.7 vs. 2.0 m, p < 0.01) and implanted at higher Interagency Registry for Mechanical Circulatory Support profiles (p = 0.005); there were no differences in diabetes and obesity, and survival on VAD was similar (p = 0.22). Among adolescents but not young adults, mortality increased after infection (hazard ratio 8.2, 95% confidence interval 1.6-42.6, p = 0.01). In contrast, stroke risk increased after infection in young adults (hazard ratio 3.1, 95% confidence interval 1.3-7.6, p = 0.01) but not in adolescents. Despite similar underlying risk factors, adolescents have increased mortality after infections, whereas young adults have increased strokes after infections. Both pre- and postimplant factors likely contribute to the discrepancy in outcomes between the two age cohorts.

    View details for PubMedID 29762230

  • 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


    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


    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

  • 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


    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

  • 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)


    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

  • 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


    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

  • 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


    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


    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

  • 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


    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

  • 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


    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

  • 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


    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

  • 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


    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


    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 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


    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

  • 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


    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

  • 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


    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

  • Feasibility of neonatal pulse wave velocity and association with maternal hemoglobin a1c. Neonatology Chen, S., Chetty, S., Lowenthal, A., Evans, J. M., Vu, C., Stauffer, K. J., Lyell, D., Selamet Tierney, E. S. 2015; 107 (1): 20-26


    Use of non-invasive peripheral arterial tonometry to assess arterial stiffness has not been studied in neonates. Perinatal factors impact childhood vascular health, but the effect in neonates remains to be examined.To examine the feasibility of pulse wave velocity (PWV) among healthy term neonates, and to evaluate the effects of perinatal factors on neonatal PWV.Pregnant women with singleton gestation presenting for routine care were enrolled. Postnatally, PWV measurements of their neonates were obtained using an arterial tonometer. A variability index was calculated for each PWV measurement. Intra- and inter-observer reproducibility were illustrated with Bland-Altman plots. Medical records were reviewed. Relationships between neonatal PWV and perinatal factors were examined.PWV measurements were attempted in 76 neonates and successfully obtained in 67 (88%). Using PWV measurements with a variability index ≤0.25 (48 neonates), the intra-class coefficient was 0.69. The mean differences (limits of agreement) for intra- and inter-rater reproducibility were 0.02 (-3.64 to 3.60) and 0.34 (-2.23 to 2.39), respectively. Median neonatal PWV was 2.80 m/s (range 0.60-8.40). Neonates of mothers with HgbA1c ≥6% had significantly higher PWV than neonates of mothers with HgbA1c <6% (4.12 m/s, 95% CI 3.22-5.02, vs. 2.78 m/s, 95% CI 2.28-3.28, p = 0.02).Neonatal PWV using peripheral arterial tonometry is feasible and reproducible when using measurements with a variability index ≤0.25. Neonates of mothers with increased HgbA1c had higher PWV, suggesting an effect of maternal hyperglycemia on neonatal vasculature. The long-term implications of this finding warrant further investigation. © 2014 S. Karger AG, Basel.

    View details for DOI 10.1159/000366467

    View details for PubMedID 25301402

  • 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


    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

  • 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


    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

  • How useful are B-type natriuretic peptide measurements for monitoring changes in patent ductus arteriosus shunt magnitude? JOURNAL OF PERINATOLOGY Chen, S., Tacy, T., Clyman, R. 2010; 30 (12): 780-785


    Although B-type natriuretic peptide (BNP) concentrations seem to be useful for detecting the presence of patent ductus arteriosus, there is no information about their usefulness for monitoring changes in PDA shunt magnitude.We performed a retrospective analysis of paired BNP-echocardiogram measurements (obtained from infants (24 to 32 weeks gestation) with clinical suspicion of PDA).Individual BNP concentrations (n=146, from 88 infants) were significantly related to shunt magnitude at the time of measurement and had good discriminating power for detecting a moderate-or-large shunt (area under receiver-operator characteristic curves (ROC-AUC)=0.85). In total, 36 infants had serial BNP-echocardiogram pairs (n=91) measured during their hospitalization. Changes (either increases or decreases) in BNP concentrations over time had only fair discriminating power (ROC-AUC=0.76) for detecting increases or decreases, respectively, in shunt magnitude.The high degree of variability in the BNP measurements made them less useful for monitoring changes in magnitude.

    View details for DOI 10.1038/jp.2010.47

    View details for Web of Science ID 000284693200004

    View details for PubMedID 20376057

  • Prenatal diagnosis of primary pulmonary hypoplasia in fraternal twins ULTRASOUND IN OBSTETRICS & GYNECOLOGY Chen, S., Ursell, P. C., Adatia, I., Hislop, A. A., Giannikopoulos, P., Hornberger, L. K. 2010; 35 (1): 113–16


    Primary pulmonary hypoplasia is a rare, usually lethal, condition presenting only after birth without other congenital abnormalities. We describe the first case of fraternal twins diagnosed prenatally with primary pulmonary hypoplasia. Both had diffuse hypoplasia of the pulmonary arteries initially identified by fetal echocardiography and confirmed at autopsy following termination. These cases permit examination of the histopathology of this disease in the fetal stage of development.

    View details for DOI 10.1002/uog.7520

    View details for Web of Science ID 000273679800018

    View details for PubMedID 20033995