Clinical Focus

  • Advanced Heart Failure and Transplant Cardiology

Academic Appointments

Professional Education

  • Board Certification: American Board of Pediatrics, Pediatric Cardiology (2016)
  • Board Certification: American Board of Pediatrics, Pediatrics (2019)
  • Medical Education: Medical College of Georgia Registrar (2009) GA
  • Residency: University of Tennessee Health Science Center Pediatric Residency (2012) TN
  • Fellowship: Nicklaus Childrens Hospital Pediatric Cardiology Fellowship (2015) FL
  • Fellowship: Stanford University Pediatric Cardiology Fellowship (2016) CA

All Publications

  • A prospective multicenter feasibility study of a miniaturized implantable continuous flow ventricular assist device in smaller children with heart failure. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Almond, C. S., Davies, R., Adachi, I., Richmond, M., Law, S., Tunuguntla, H., Mao, C., Shaw, F., Lantz, J., Wearden, P. D., Jordan, L. C., Ichord, R. N., Burns, K., Zak, V., Magnavita, A., Gonzales, S., Conway, J., Jeewa, A., Freemon, D. '., Stylianou, M., Sleeper, L., Dykes, J. C., Ma, M., Fynn-Thompson, F., Lorts, A., Morales, D., Vanderpluym, C., Dasse, K., Patricia Massicotte, M., Jaquiss, R., Mahle, W. T. 2024


    There is no FDA-approved left ventricular assist device (LVAD) for smaller children permitting routine hospital discharge. Smaller children supported with LVADs typically remain hospitalized for months awaiting heart transplant-a major burden for families and a challenge for hospitals. We describe the initial outcomes of the Jarvik 2015, a miniaturized implantable continuous flow LVAD, in the NHLBI-funded Pumps for Kids, Infants, and Neonates (PumpKIN) study, for bridge-to-heart transplant.Children weighing 8 to 30 kg with severe systolic heart failure and failing optimal medical therapy were recruited at 7 centers in the United States. Patients with severe right heart failure and single-ventricle congenital heart disease were excluded. The primary feasibility endpoint was survival to 30 days without severe stroke or non-operational device failure.Of 7 children implanted, the median age was 2.2 (range 0.7, 7.1) years, median weight 10 (8.2 to 20.7) kilograms; 86% had dilated cardiomyopathy; 29% were INTERMACS profile 1. The median duration of Jarvik 2015 support was 149 (range 5 to 188) days where all 7 children survived including 5 to heart transplant, 1 to recovery, and 1 to conversion to a paracorporeal device. One patient experienced an ischemic stroke on day 53 of device support in the setting of myocardial recovery. One patient required ECMO support for intractable ventricular arrhythmias and was eventually transplanted from paracorporeal biventricular VAD support. The median pump speed was 1600 RPM with power ranging from 1-4 Watts. The median plasma free hemoglobin was 19, 30, 19 and 30 mg/dL at 7, 30, 90 and 180 days or time of explant, respectively. All patients reached the primary feasibility endpoint. Patient-reported outcomes with the device were favorable with respect to participation in a full range of activities. Due to financial issues with the manufacturer, the study was suspended after consent of the eighth patient.The Jarvik 2015 LVAD appears to hold important promise as an implantable continuous flow device for smaller children that may support hospital discharge. The FDA has approved the device to proceed to a 22-subject pivotal trial. Whether this device will survive to commercialization remains unclear because of the financial challenges faced by industry seeking to develop pediatric medical devices. (Supported by NIH/NHLBI HHS Contract N268201200001I, 02954497).

    View details for DOI 10.1016/j.healun.2024.02.003

    View details for PubMedID 38713124

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


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

    View details for DOI 10.1097/MAT.0000000000002023

    View details for PubMedID 37556563

  • 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

  • Expanding Use of the HeartMate 3 Ventricular Assist Device in Pediatric and Adult Patients within the Advanced Cardiac Therapies Improving Outcomes Network (ACTION). The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation O'Connor, M. J., Shezad, M., Ahmed, H., Amdani, S., Auerbach, S. R., Bearl, D. W., Butto, A., Byrnes, J. W., Conway, J., Dykes, J. C., Glass, L., Lantz, J., Law, S., Monge, M. C., Morales, D. L., Parent, J. J., Peng, D. M., Ploutz, M. S., Puri, K., Shugh, S., Shwaish, N. S., VanderPluym, C. J., Wilkens, S., Wright, L., Zinn, M. D., Lorts, A. 2023


    BACKGROUND: We report current outcomes in patients supported with the HeartMate 3 ventricular assist device in a multicenter learning network.METHODS: The Advanced Cardiac Therapies Improving Outcomes Network database was queried for HeartMate 3 implants between 12/2017 - 5/2022. Clinical characteristics, post-implant course, and adverse events were collected. Patients were stratified according to body surface area (<1.4 m2, 1.4-1.8 m2, and >1.8 m2) at device implantation.RESULTS: During the study period, 170 patients were implanted with the HeartMate 3 at participating network centers, with median age 15.3 years; 27.1% were female. Median body surface area was 1.68 m2; the smallest patient was 0.73 m2 (17.7 kg). Most (71.8%) had a diagnosis of dilated cardiomyopathy. With a median support time of 102.5 days, 61.2% underwent transplantation, 22.9% remained supported on device, 7.6% died, and 2.4% underwent device explantation for recovery; the remainder had transferred to another institution or transitioned to a different device type. The most common adverse events included major bleeding (20.8%) and driveline infection (12.9%); ischemic and hemorrhagic stroke were encountered in 6.5% and 1.2% of patients, respectively. Patients with body surface area <1.4 m2 had a higher incidence of infection, renal dysfunction, and ischemic stroke.CONCLUSIONS: In this updated cohort of predominantly pediatric patients supported with the HeartMate 3 ventricular assist device, outcomes are excellent with <8% mortality on device. Device-related adverse events including stroke, infection, and renal dysfunction were more commonly seen in smaller patients, highlighting opportunities for improvements in care.

    View details for DOI 10.1016/j.healun.2023.06.015

    View details for PubMedID 37419295

  • Contemporary care and outcomes of critically ill children with clinically diagnosed myocarditis. Journal of cardiac failure Peng, D. M., Kwiatkowski, D. M., Lasa, J. J., Zhang, W., Banerjee, M., Mikesell, K., Joong, A., Dykes, J. C., Tume, S. C., Niebler, R. A., Teele, S. A., Klugman, D., Gaies, M. G., Schumacher, K. R. 2023


    PURPOSE: To describe contemporary management and outcomes in children with myocarditis admitted to the cardiac intensive care unit (CICU) and to identify characteristics associated with mortality.METHODS: All patients in the Pediatric Cardiac Critical Care Consortium (PC4) registry from 8/2014-6/2021 diagnosed with myocarditis were included. Univariable analyses and multivariable logistic regression evaluated factors associated with in-hospital mortality.RESULTS: There were 847 CICU admissions for myocarditis in 51 centers. Median age was 12 years (IQR 2.7-16). In-hospital mortality occurred in 53 patients (6.3%) and 60 (7.1%) had cardiac arrest during the admission. Mechanical ventilation was required in 339 patients (40%) and mechanical circulatory support (MCS) in 177 (21%): extracorporeal membrane oxygenation (ECMO)-only in 142 (16.7%), ECMO-to-ventricular assist device (VAD) in 20 (2.4%), extracorporeal cardiac resuscitation (eCPR) in 43 (5%), VAD-only in 15 (1.8%) patients. MCS was associated with in-hospital mortality; 20.3% receiving MCS died compared to 2.5% without MCS (p<0.001). Mortality was similar between ECMO-only, ECMO-to-VAD, and VAD-only groups. Median time from CICU admission to ECMO was 2.0 hours (IQR 0-9.4) and to VAD was 9.9 days (IQR 6.3-16.8). Time to MCS was not associated with mortality. In multivariable modeling of patient characteristics, smaller body surface area (BSA) and low eGFR were independently associated with mortality, and after including critical therapies, mechanical ventilation or ECMO were independent predictors of mortality.CONCLUSION: This contemporary cohort of children admitted to the CICU with myocarditis frequently received high-resource therapies however, most patients survived to hospital discharge and rarely received VAD. Smaller patient size, acute kidney injury, and receipt of mechanical ventilation or ECMO were independently associated with mortality.

    View details for DOI 10.1016/j.cardfail.2023.04.010

    View details for PubMedID 37150502

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


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

    View details for DOI 10.1097/MAT.0000000000001861

    View details for PubMedID 37071761

  • The Fontan immunophenotype and post-transplant outcomes in children: A multi-institutional study. Pediatric transplantation Mantell, B. S., Azeka, E., Cantor, R. S., Carlo, W. F., Chrisant, M., Dykes, J. C., Hoffman, T. M., Kirklin, J. K., Koehl, D., L'Ecuyer, T. J., McAllister, J. M., Prada-Ruiz, A. C., Richmond, M. E. 2023: e14456


    BACKGROUND: Patients after Fontan palliation represent a growing pediatric population requiring heart transplant (HTx) and often have lymphopenia (L) and/or hypogammaglobinemia that may be exacerbated by protein-losing enteropathy (PLE, P). The post-HTx effects of this altered immune phenotype are not well studied.METHODS: In this study of the Pediatric Heart Transplant Society Registry, 106 Fontan patients who underwent HTx between 2005 and 2018 were analyzed. The impact of lymphopenia and PLE on graft survival, infection, rejection, and malignancy was analyzed at 1 and 5years post-HTx.RESULTS: The following combinations of lymphopenia and PLE were noted: +L+P, n=37; +L-P, n=23; -L+P, n=10; and -L-P, n=36. Graft survival between the groups was similar within the first year after transplant (+L+P: 86%, +L-P: 86%, -L+P: 87%, -L-P: 89%, p=.9). Freedom from first infection post-HTx was greatest among -L-P patients compared to patients with either PLE, lymphopenia, or both; with a 22.1% infection incidence in the -L-P group and 41.4% in all others. These patients had a significantly lower infection rate in the first year after HTx (+L+P: 1.03, +L-P: 1, -L+P: 1.3, -L-P: 0.3 infections/year, p<.001) and were similar to a non-single ventricle CHD control group (0.4 infections/year). Neither freedom from rejection nor freedom from malignancy 1 and 5years post-HTx, differed among the groups.CONCLUSIONS: Fontan patients with altered immunophenotype, with lymphopenia and/or PLE, are at increased risk of infection post-HTx, although have similar early survival and freedom from rejection and malignancy. These data may encourage alternative immunosuppression strategies and enhanced monitoring for this growing subset of patients.

    View details for DOI 10.1111/petr.14456

    View details for PubMedID 36591863

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


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

    View details for DOI 10.1016/j.jpainsymman.2022.11.014

    View details for PubMedID 36417945

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


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

    View details for DOI 10.1111/petr.14421

    View details for PubMedID 36303275

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


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

    View details for DOI 10.1016/j.healun.2022.08.027

    View details for PubMedID 36210265

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


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

    View details for DOI 10.1016/j.athoracsur.2022.05.067

    View details for PubMedID 35835207

  • 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

  • Expanded cardiovascular phenotype of Myhre syndrome includes tetralogy of Fallot suggesting a role for SMAD4 in human neural crest defects. American journal of medical genetics. Part A Cappuccio, G., Brunetti-Pierri, N., Clift, P., Learn, C., Dykes, J. C., Mercer, C. L., Callewaert, B., Meerschaut, I., Spinelli, A. M., Bruno, I., Gillespie, M. J., Dorfman, A. T., Grimberg, A., Lindsay, M. E., Lin, A. E. 1800


    Tetralogy of Fallot (ToF) can be associated with a wide range of extracardiac anomalies, with an underlying etiology identified in approximately 10% of cases. Individuals affected with Myhre syndrome due to recurrent SMAD4 mutations frequently have cardiovascular anomalies, including congenital heart defects. In addition to two patients in the literature with ToF, we describe five additional individuals with Myhre syndrome and classic ToF, ToF with pulmonary atresia and multiple aorto-pulmonary collaterals, and ToF with absent pulmonary valve. Aorta hypoplasia was documented in one patient and suspected in another two. In half of these individuals, postoperative cardiac dysfunction was thought to be more severe than classic postoperative ToF repair. There may be an increase in right ventricular pressure, and right ventricular dysfunction due to free pulmonic regurgitation. Noncardiac developmental abnormalities in our series and the literature, including corectopia, heterochromia iridis, and congenital miosis suggest an underlying defect of neural crest cell migration in Myhre syndrome. We advise clinicians that Myhre syndrome should be considered in the genetic evaluation of a child with ToF, short stature, unusual facial features, and developmental delay, as these children may be at risk for increased postoperative morbidity. Additional research is needed to investigate the hypothesis that postoperative hemodynamics in these patients may be consistent with restrictive myocardial physiology.

    View details for DOI 10.1002/ajmg.a.62645

    View details for PubMedID 35025139

  • 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

  • Characteristics and Outcomes of Pediatric Patients With a Ventricular Assist Device Presenting to the Emergency Department. Pediatric emergency care Pokrajac, N., Cantwell, L. M., Murray, J. M., Dykes, J. C. 2021


    OBJECTIVES: A growing number of children receive support from left ventricular assist devices (LVADs) in the outpatient setting. Unexpected complications of LVAD support occur that require emergent management, and no studies examine how pediatric LVAD patients present to the emergency department (ED). The goals of this study were (1) to describe frequency of visits, clinical characteristics, adverse events, and outcomes of LVAD-supported children treated in ED settings and (2) to evaluate for associations between specified patient outcomes and ED care location.METHODS: This was a retrospective cohort study of children in a single-center outpatient VAD program who presented to several EDs during a 10-year period. We defined adverse events according to the Advanced Cardiac Therapies Improving Outcomes Network registry guidelines. Secondary analysis evaluated for associations between specified patient outcomes (adverse events, hospitalizations, intensive care unit admissions) and ED care location (institutional vs other ED).RESULTS: Of 104 subjects with LVAD implantations during the study period, 30 (28.8%) transitioned to outpatient care. Among subjects in the outpatient VAD program, 24 (80%) of 30 had 54 visits to various EDs over 141.9 patient-months. The median age at time of ED visit was 13.5 years (range, 7.2-17.9 years). The median number of visits per subject was 1 (range, 0-6). The most common complaints on arrival to the ED were vomiting or abdominal pain (16.7%), fever (15.3%), and headache (13.9%). Seventeen adverse events occurred during 14 (25.9%) of 54 ED visits. The most common adverse events were major infection (33.3%) and right heart failure (16.7%). Hospital admission resulted from 41 (75.9%) of 54 ED visits, including 17 (41.5%) of 41 to a cardiovascular intensive care unit. Care at a nonspecialty ED was associated with a higher rate of hospitalization (93.8% vs 68.4%, P = 0.049). During the study period, 4 subjects (13.3%) died, including 1 patient on destination therapy, 1 with multisystem organ failure due to cardiogenic shock, and 2 with hemorrhagic stroke. No patient died while in the ED.CONCLUSIONS: Among subjects in a single outpatient pediatric VAD program presenting to the ED, the most common complaints were abdominal pain/vomiting, fever, and headache. The most common adverse events were major infection and right heart failure. Subjects had a high rate of ED utilization and hospital admission.

    View details for DOI 10.1097/PEC.0000000000002493

    View details for PubMedID 34225326

  • The multisystem nature of isomerism: left isomerism complicated by Abernethy malformation and portopulmonary hypertension. Cardiology in the young Ringle, M. L., Loomba, R., Dykes, J. C., Khan, D., Schidlow, D., Wernovsky, G. 2021: 1–9


    Isomerism, also referred to as "heterotaxy" is a complex set of anatomic and functional perturbations. One of the most obvious manifestations of isomerism is the disturbance of organ arrangement, such that the thoracic organs are no longer asymmetric on the left and right. We report the case of a 14-year-old female in whom exercise-induced dyspnea led to a late diagnosis of left isomerism complicated by Abernethy malformation and portopulmonary hypertension. A comprehensive evaluation revealed two anatomic left lungs and hyparterial bronchi, bilateral left atria, an interrupted inferior caval vein with azygos continuation, multiple spleens, sinus node dysfunction, hepatic hypertrophy with focal nodular hyperplasia, and absence of the portal vein. Pulmonary vasodilator therapy was initiated resulting in clinical improvement. This case exhibits unique features including a late diagnosis of isomerism with Abernethy malformation and portopulmonary hypertension. The patient's presentation, medical workup, and future treatment emphasise the importance of multidisciplinary care in children with complex multisystem disease. We review the multiple cardiac and extracardiac manifestations of isomerism.

    View details for DOI 10.1017/S1047951121000809

    View details for PubMedID 33731242

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


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

    View details for DOI 10.1016/j.healun.2021.01.010

    View details for PubMedID 33579597

  • 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

  • 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

  • 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

  • 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
  • Commentary: To BiVAD or not to BiVAD…that is the question? The Journal of thoracic and cardiovascular surgery Dykes, J. C., Maeda, K. n. 2020

    View details for DOI 10.1016/j.jtcvs.2020.01.003

    View details for PubMedID 32029209

  • 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

  • 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

  • Parental Acquisition of Echocardiographic Images in Pediatric Heart Transplant Patients Using a Handheld Device: A Pilot Telehealth Study JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY Dykes, J. C., Kipps, A. K., Chen, A., Nourse, S., Rosenthal, D. N., Tierney, E. 2019; 32 (3): 404–11
  • Long-term surveillance biopsy: Is it necessary after pediatric heart transplant? PEDIATRIC TRANSPLANTATION Peng, D. M., Ding, V. Y., Hollander, S. A., Khalapyan, T., Dykes, J. C., Rosenthal, D. N., Almond, C. S., Sakarovitch, C., Desai, M., McElhinney, D. B. 2019; 23 (1)

    View details for DOI 10.1111/petr.13330

    View details for Web of Science ID 000457579500023

  • Commentary: Improving donor size matching in pediatric heart transplantation-Moving beyond body weight. The Journal of thoracic and cardiovascular surgery Maeda, K. n., Dykes, J. C. 2019

    View details for DOI 10.1016/j.jtcvs.2019.07.026

    View details for PubMedID 31439351

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


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

    View details for PubMedID 30598367

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


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

    View details for PubMedID 30506612

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


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

    View details for PubMedID 29807009

  • 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

  • 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

  • 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

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


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

    View details for PubMedID 28734448

  • 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