Beth Kaufman

All Publications

• Race and Socioeconomic Bias in Pediatric Cardiac Transplantation. JACC. Heart failure Amdani, S., Conway, J., Kleinmahon, J., Auerbach, S., Hsu, D., Cousino, M. K., Kaufman, B., Alejos, J., Cruz, J. H., Lee, H. Y., Rudraraju, R., Kirklin, J. K., Asante-Korang, A. 2023; 11 (1): 19-26

  Abstract

  To date, no studies evaluated implicit bias among clinicians caring for children with advanced heart failure.This study aims to evaluate implicit racial and socioeconomic bias among pediatric heart transplant clinicians.A cross-sectional survey of transplant clinicians from the Pediatric Heart Transplant Society was conducted between June and August 2021. The survey consisted of demographic questions along with explicit and validated race and socioeconomic status (SES) implicit association tests (IATs). Implicit and explicit biases among survey group members were studied and associations were tested between implicit and explicit measures.Of 500 members, 91 (18.2%) individuals completed the race IAT and 70 (14%) completed the SES IAT. Race IAT scores indicated moderate levels of implicit bias (mean = 0.33, d = 0.76; P < 0.001; ie, preference for White individuals). SES IAT scores indicated strong implicit bias (mean = 0.52, d = 1.53; P < 0.001; ie, preference for people from upper SES). There were weak levels of explicit race and wealth bias. There was a strong level of explicit education bias (mean = 5.22, d = 1.19; P < 0.001; ie, preference for educated people). There were nonsignificant correlations between the race and the SES IAT and explicit measures (P > 0.05 for all).As observed across other health care disciplines, among a group of pediatric heart transplant clinicians, there is an implicit preference for individuals who are White and from higher SES, and an explicit preference for educated people. Future studies should evaluate how implicit biases affect clinician behavior and assess the impact of efforts to reduce such biases.

  View details for DOI 10.1016/j.jchf.2022.08.021

  View details for PubMedID 36599545

• The Prevalence and Association of Exercise Test Abnormalities With Sudden Cardiac Death and Transplant-Free Survival in Childhood Hypertrophic Cardiomyopathy Conway, J., Min, S., Villa, C., Weintraub, R. G., Nakano, S. J., Godown, J., Kathyrn, A., Richmond, M. E., Kaufman, B. D., Lal, A. K., Balaji, S., Power, A., Gardin, L., Kantor, P. F., Parent, J. J., Aziz, P. F., Jefferies, J. L., Papaz, T., Jeewa, A., Benson, L. N., Russell, M. W., Whitehall, R. LIPPINCOTT WILLIAMS & WILKINS. 2022

  View details for Web of Science ID 000890856903075

• The Prevalence and Association of Exercise Test Abnormalities with Sudden Cardiac Death and Transplant-Free Survival in Childhood Hypertrophic Cardiomyopathy. Circulation Conway, J., Min, S., Villa, C., Weintraub, R. G., Nakano, S., Godown, J., Tatangelo, M., Armstrong, K., Richmond, M., Kaufman, B., Lal, A. K., Balaji, S., Power, A., Baez Hernandez, N., Gardin, L., Kantor, P. F., Parent, J. J., Aziz, P. F., Jefferies, J. L., Dragulescu, A., Jeewa, A., Benson, L., Russell, M. W., Whitehill, R., Rossano, J., Howard, T., Mital, S. 2022

  Abstract

  BACKGROUND: Hypertrophic cardiomyopathy (HCM) can be associated with an abnormal exercise response. In adults with HCM, an abnormal exercise stress test is predictive of heart failure outcomes. Our goal was to determine if an abnormal exercise response is associated with adverse outcomes in pediatric HCM patients.METHODS: In an international cohort study with 20 centers, phenotype-positive children with primary HCM <18 years at diagnosis were included. Abnormal exercise response was defined as a blunted blood pressure response, and new or worsened ST-T wave segment changes or complex ventricular ectopy. Sudden cardiac death (SCD) events were defined as a composite of SCD and aborted sudden cardiac arrest. Using Kaplan-Meier survival, competing outcomes, and Cox regression analyses, we analyzed the association of an abnormal exercise test with transplant and SCD event-free survival.RESULTS: Of 724 eligible patients, 630 underwent at least one exercise test. There were no major differences in clinical characteristics between those with or without an exercise test. The median age at exercise testing was 13.8yrs (IQR 4.7yrs); 78% were male, 39% were receiving beta-blockers. 175 (28%) had an abnormal test. Patients with an abnormal test had more severe septal hypertrophy, higher left atrial diameter z-scores, higher resting LV outflow tract gradient, and higher frequency of myectomy compared to those with a normal test (p<0.05). Compared to those with a normal test, an abnormal test was independently associated with a lower 5-year transplant-free survival (97% vs. 88% respectively, p=0.005). Those with exercise-induced ischemia were most likely to experience all-cause death or transplant [Hazard ratio (HR) 4.86, CI 1.69-13.99], followed by those with an abnormal blood pressure response (HR 3.19, CI 1.32-7.71). Exercise-induced ischemia was also independently associated with lower SCD event-free survival (HR 3.32, CI 1.27-8.70). Exercise-induced ectopy was not associated with survival.CONCLUSIONS: Exercise abnormalities are common in childhood HCM. An abnormal exercise test was independently associated with lower transplant-free survival especially in those with an ischemic or abnormal blood pressure response with exercise. Exercise-induced ischemia was also independently associated with SCD events. These findings argue for routine exercise testing in childhood HCM as part of ongoing risk assessment.

  View details for DOI 10.1161/CIRCULATIONAHA.122.062699

  View details for PubMedID 36335467

• Risk Factors and Outcomes of Sudden Cardiac Arrest in Pediatric Heart Transplant Recipients. American heart journal Hollander, S. A., Barkoff, L., Giacone, H., Adamson, G. T., Kaufman, B. D., Motonaga, K. S., Dubin, A. M., Chubb, H. 2022

  Abstract

  Sudden cardiac arrest (SCA) is a prevailing cause of mortality after pediatric heart transplant (HT) but remains understudied. We analyzed the incidence, outcomes, and risk factors for SCA at our center.Retrospective review of all pediatric HT patients at our center from 1/1/2009-9/1/2021. SCA was defined as an abrupt loss of cardiac function requiring cardiopulmonary resuscitation and/or mechanical circulatory support (MCS). Events that occurred in the setting of limited resuscitative wishes, or while on MCS were excluded. Patient characteristics and risk factors were analyzed.Fourteen of 254 (6%) experienced SCA at a median of 3 (1, 4) years post-HT. Seven (50%) events occurred out-of-hospital. Eleven (79%) died from their initial event, 2 (18%) after failure to separate from extracorporeal membrane (ECMO). In univariate analysis, black race, younger donor age, prior acute cellular rejection (ACR) episode, pacemaker and/or ICD in place, and pre-mortem diagnosis of allograft vasculopathy were associated with SCA (P=0.003-0.02). In multivariable analysis, history of ACR, younger donor age, and black race retained significance. [OR=6.3, 95% CI: 1.6-25.4, P=0.01], [OR=0.9, 95% CI: 0.8-1, P=0.04], and [OR=7.3, 95% CI: 1.1-49.9, P=0.04], respectively. SCA occurred in 3 patients with a functioning ICD or pacemaker, which failed to restore a perfusing rhythm.SCA occurs relatively early after pediatric HT and is usually fatal. Half of events happen at home. Those who received younger donors, have a history of ACR, or are of black race are at increased risk. ICDs/pacemakers may offer limited protection.

  View details for DOI 10.1016/j.ahj.2022.06.003

  View details for PubMedID 35705134

• Current Practices in Treating Cardiomyopathy and Heart Failure in Duchenne Muscular Dystrophy (DMD): Understanding Care Practices in Order to Optimize DMD Heart Failure Through ACTION. Pediatric cardiology Villa, C., Auerbach, S. R., Bansal, N., Birnbaum, B. F., Conway, J., Esteso, P., Gambetta, K., Hall, E. K., Kaufman, B. D., Kirmani, S., Lal, A. K., Martinez, H. R., Nandi, D., O'Connor, M. J., Parent, J. J., Raucci, F. J., Shih, R., Shugh, S., Soslow, J. H., Tunuguntla, H., Wittlieb-Weber, C. A., Kinnett, K., Cripe, L. 1800

  Abstract

  Cardiac disease has emerged as a leading cause of mortality in Duchenne muscular dystrophy in the current era. This survey sought to identify the diagnostic and therapeutic approach to DMD among pediatric cardiologists in Advanced Cardiac Therapies Improving Outcomes Network. Pediatric cardiology providers within ACTION (a multi-center pediatric heart failure learning network) were surveyed regarding their approaches to cardiac care in DMD. Thirty-one providers from 23 centers responded. Cardiac MRI and Holter monitoring are routinely obtained, but the frequency of use and indications for ordering these tests varied widely. Angiotensin converting enzyme inhibitor and aldosterone antagonist are generally initiated prior to onset of systolic dysfunction, while the indications for initiating beta-blocker therapy vary more widely. Seventeen (55%) providers report their center has placed an implantable cardioverter defibrillator in at least 1 DMD patient, while 11 providers (35%) would not place an ICD for primary prevention in a DMD patient. Twenty-three providers (74%) would consider placement of a ventricular assist device (VAD) as destination therapy (n=23, 74%) and three providers (10%) would consider a VAD only as bridge to transplant. Five providers (16%) would not consider VAD at their institution. Cardiac diagnostic and therapeutic approaches vary among ACTION centers, with notable variation present regarding the use of advanced therapies (ICD and VAD). The network is currently working to harmonize medical practices and optimize clinical care in an era of rapidly evolving outcomes and cardiac/skeletal muscle therapies.

  View details for DOI 10.1007/s00246-021-02807-7

  View details for PubMedID 35024902

• Advance Care Planning Preferences for Adolescents With Cardiac Disease. Pediatrics Hansen, K., Edwards, L. A., Yohannes, K., Luong, R., Lin, A., Long, J., Halpern-Felsher, B., Cohen, H., Kaufman, B. D. 1800

  Abstract

  BACKGROUND AND OBJECTIVES: Adolescents with cardiac disease are at risk for life-changing complications and premature death. The importance of advance care planning (ACP) in adults with congenital heart disease and in pediatric patients with HIV and cancer has been demonstrated. ACP preferences of adolescents with heart disease have not been evaluated. We describe ACP preferences of adolescents with heart disease and compare with those of their caregivers.METHODS: Outpatient adolescents aged 12 to 18 years with heart failure, cardiomyopathy, heart transplantation, or who were at risk for cardiomyopathy, as well as their caregivers, completed self-administered questionnaires which evaluated participants' opinions regarding content and timing of ACP discussions, preferences for end-of-life communication, and emotional responses to ACP.RESULTS: Seventy-eight adolescents and 69 caregivers participated, forming 62 adolescent-caregiver dyads. Adolescents and caregivers reported that adolescent ACP discussions should occur early in the disease course (75% and 61%, respectively). Adolescents (92%) wanted to be told about terminal prognosis, whereas only 43% of caregivers wanted the doctor to tell their child this information. Most adolescents (72%) and caregivers (67%) anticipated that discussing ACP would make the adolescent feel relieved the medical team knew their wishes. Most caregivers (61%) believed that adolescents would feel stress associated with ACP discussions, whereas only 31% of adolescents anticipated this.CONCLUSIONS: Adolescents and their caregivers agree that ACP should occur early in disease course. There are discrepancies regarding communication of prognosis and perceived adolescent stress related to ACP discussions. Facilitated conversations between patient, caregiver, and providers may align goals of care and communication preferences.

  View details for DOI 10.1542/peds.2020-049902

  View details for PubMedID 34984466

• Response by Mital et al to Letter Regarding Article, "A Validated Model for Sudden Cardiac Death Risk Prediction in Pediatric Hypertrophic Cardiomyopathy". Circulation Mital, S., Armstrong, K. R., Butts, R. J., Conway, J., Fan, S., Gardin, L., Kantor, P. F., Kaufman, B., Lafreniere-Roula, M., Miron, A., Richmond, M. E., Rossano, J. W., Russell, M. W., Villa, C., Weintraub, R. G., PRIMaCY Investigators 2021; 143 (11): e788–e789

  View details for DOI 10.1161/CIRCULATIONAHA.120.051632

  View details for PubMedID 33720772

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

  Abstract

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

  View details for DOI 10.1016/j.jpainsymman.2021.01.125

  View details for PubMedID 33910026

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

  Abstract

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

  View details for DOI 10.1016/j.healun.2020.08.002

  View details for PubMedID 33032871

• A Validated Model for Sudden Cardiac Death Risk Prediction in Pediatric Hypertrophic Cardiomyopathy. Circulation Miron, A., Lafreniere-Roula, M., Fan, C. S., Armstrong, K. R., Dragulescu, A., Papaz, T., Manlhiot, C., Kaufman, B., Butts, R. J., Gardin, L., Stephenson, E. A., Howard, T. S., Aziz, P. F., Balaji, S., Beausejour Ladouceur, V., Benson, L. N., Colan, S. D., Godown, J., Henderson, H. T., Ingles, J., Jeewa, A., Jefferies, J. L., Lal, A. K., Mathew, J., Jean-St-Michel, E., Michels, M., Nakano, S. J., Olivotto, I., Parent, J. J., Pereira, A. C., Semsarian, C., Whitehill, R. D., Wittekind, S. G., Russell, M. W., Conway, J., Richmond, M. E., Villa, C., Weintraub, R. G., Rossano, J. W., Kantor, P. F., Ho, C. Y., Mital, S. 2020

  Abstract

  Background: Hypertrophic cardiomyopathy (HCM) is the leading cause of sudden cardiac death (SCD) in children and young adults. Our objective was to develop and validate a SCD risk prediction model in pediatric HCM to guide SCD prevention strategies. Methods: In an international multi-center observational cohort study, phenotype-positive patients with isolated HCM <18 years at diagnosis were eligible. The primary outcome variable was the time from diagnosis to a composite of SCD events at 5-year follow-up: SCD, resuscitated sudden cardiac arrest (SCA), and aborted SCD, i.e. appropriate shock following primary prevention ICD. Competing risk models with cause-specific hazard regression were used to identify and quantify clinical and genetic factors associated with SCD. The cause-specific regression model was implemented using boosting, and tuned with ten repeated four-fold cross-validations. The final model was fitted using all data with the tuned hyperparameter value that maximizes the c-statistic, and its performance was characterized using c-statistic for competing risk models. The final model was validated in an independent external cohort (SHaRe, n=285). Results: Overall, 572 patients met eligibility criteria with 2855 patient-years of follow-up. The 5-year cumulative proportion of SCD events was 9.1% (14 SCD, 25 resuscitated SCA, 14 aborted SCD). Risk predictors included age at diagnosis, documented non-sustained ventricular tachycardia, unexplained syncope, septal diameter z-score, LV posterior wall diameter z-score, LA diameter z-score, peak LV outflow tract (LVOT) gradient, and presence of a pathogenic variant. Unlike adults, LVOT gradient had an inverse association, and family history of SCD had no association with SCD. Clinical and clinical/genetic models were developed to predict 5-year freedom from SCD. Both models adequately discriminated patients with and without SCD events with a c-statistic of 0.75 and 0.76 respectively and demonstrated good agreement between predicted and observed events in the primary and validation cohorts (validation c-statistic 0.71 and 0.72 respectively). Conclusions:Our study provides a validated SCD risk prediction model with over 70% prediction accuracy and incorporates risk factors that are unique to pediatric HCM. An individualized risk prediction model has the potential to improve the application of clinical practice guidelines and shared decision-making for ICD insertion. Clinical Trial Registration:URL: https://clinicaltrials.gov Unique Identifier: NCT04036799.

  View details for DOI 10.1161/CIRCULATIONAHA.120.047235

  View details for PubMedID 32418493

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

  Abstract

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

  View details for DOI 10.1016/j.athoracsur.2019.12.088

  View details for PubMedID 32151575

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

  Abstract

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

  View details for DOI 10.1097/MAT.0000000000001092

  View details for PubMedID 31789655

• 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

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

  View details for DOI 10.1111/petr.13335

  View details for Web of Science ID 000459211900020

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

  Abstract

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

  View details for PubMedID 30734422

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

  Abstract

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

  View details for DOI 10.1111/petr.13643

  View details for PubMedID 31891211

• Palliative care in pediatric heart failure and transplantation. Current opinion in pediatrics Kaufman, B. D., Cohen, H. J. 2019

  Abstract

  Advanced heart failure in children is characterized by dynamic clinical trajectories, uncertainty of prognosis, and intermittent need for difficult decision-making, often related to novel therapeutic interventions with uncertain impact on quality of life. This review will examine the current role of palliative care to support this unique population.Pediatric heart failure patients commonly die in ICUs with high burden of invasive therapies together with end of life care needs. In addition, several studies advocate for integration of palliative care early in disease trajectory, not only focused on end of life care. Many advocate for the core tenets of palliative care (symptom management, communication of prognosis, and advanced care planning) to be provided by the primary cardiology team, with consultation by pediatric palliative care specialists. There is also a consensus that palliative care training should be incorporated into pediatric advanced heart disease training programs.Palliative care is an important component of pediatric heart failure care. Research and quality improvement efforts are needed to determine the most effective palliative care interventions for children with advanced heart disease. Provision of palliative care is an essential component of training for pediatric heart failure and transplant specialists.

  View details for DOI 10.1097/MOP.0000000000000799

  View details for PubMedID 31335747

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

  Abstract

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

  View details for PubMedID 30536852

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

  View details for Web of Science ID 000528619407085

• When a Child Becomes Terminal: Discrepant Adolescent and Parent Perspectives on Discussing a Terminal Prognosis With Adolescents With Cardiomyopathy, Heart Failure, and Heart Transplant Hansen, K., Edwards, L. A., Luong, R., Yohannes, K., Halpern-Felsher, B., Cohen, H., Kaufman, B. LIPPINCOTT WILLIAMS & WILKINS. 2018

  View details for Web of Science ID 000528619400075

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

  View details for DOI 10.1111/petr.13181

  View details for Web of Science ID 000433590800012

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

  Abstract

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

  View details for PubMedID 29635728

• Pediatric Cardiology Provider Attitudes About Palliative Care: A Multicenter Survey Study PEDIATRIC CARDIOLOGY Balkin, E., Kirkpatrick, J. N., Kaufman, B., Swetz, K. M., Sleeper, L. A., Wolfe, J., Blume, E. D. 2017; 38 (7): 1324–31

  Abstract

  While availability of palliative care consultation for children with advanced heart disease increases, little is known about cardiologist attitudes towards palliative care. We sought to describe perspectives of cardiologists regarding palliative care and to characterize their perceived competence in palliative care concepts. A cross-sectional survey of pediatric cardiologists and cardiac surgeons from 19 pediatric medical centers was performed. Overall response rate was 31% (183/589). Respondents had a median of 18 years of experience since medical school (range 2-49) and most practiced at academic centers (91%). Sixty-percent of respondents felt that palliative care consultations occur "too late" and the majority (85%) agreed that palliative care consultations are helpful. Barriers to requesting palliative care consultation were most frequently described as "referring to palliative care services too early will undermine parents' hope" (45%) and "concern that parents will think I am giving up on their child" (56%). Only 33% of cardiologists reported feeling "very" or "moderately" competent in prognosticating life expectancy while over 60% felt competent caring for children with heart disease around end of life, and nearly 80% felt competent discussing goals of care and code status. Greater perceived competence was associated with subspecialty (heart failure/intensivist vs. other) (OR 3.6, 95% CI 1.6-8.1, p = 0.003) and didactic training (OR 6.27, 95% CI 1.8-21.8, p = 0.004). These results underscore the need for further training in palliative care skills for pediatric cardiologists. Enhancing palliative care skills among cardiologists and facilitating partnership with subspecialty palliative care teams may improve overall care of children with advanced heart disease.

  View details for PubMedID 28664445

• Non-cardiac targets to treat heart failure in children: Anemia, Exercise, Nutrition, Proceedings from the 4th International Conference on Cardiomyopathy in Children, Bethesda, May 17, 2017 PROGRESS IN PEDIATRIC CARDIOLOGY Kaufman, B. D., Dennis, K., Tierney, S. E. 2017; 46: 7–10

  View details for DOI 10.1016/j.ppedcard.2017.07.003

  View details for Web of Science ID 000426221300003

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

  Abstract

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

  View details for DOI 10.1161/CIRCULATIONAHA.115.016520

  View details for PubMedID 28119383

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

  Abstract

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

  View details for DOI 10.1111/petr.12857

  View details for PubMedID 27891727

• Pediatric Cardiologist Attitudes About Palliative Care Balkin, E., Wolfe, J., Kirkpatrick, J., Swetz, K., Blume, E., Kaufman, B. ELSEVIER SCIENCE INC. 2017: 358–59

  View details for DOI 10.1016/j.jpainsymman.2016.12.114

  View details for Web of Science ID 000397118300139

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

  Abstract

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

  View details for DOI 10.1016/j.jpainsymman.2016.12.334

  View details for PubMedID 28063864

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

  Abstract

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

  View details for PubMedID 28712678

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

  Abstract

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

  View details for PubMedID 29019615

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

  Abstract

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

  View details for DOI 10.1097/MAT.0000000000000356

  View details for PubMedID 26919182

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

  Abstract

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

  View details for DOI 10.1016/j.hrthm.2016.02.014

  View details for Web of Science ID 000376334800016

  View details for PubMedID 26945851

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

  Abstract

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

  View details for DOI 10.1016/j.healun.2016.03.020

  View details for Web of Science ID 000376951900004

  View details for PubMedID 27197773

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

  Abstract

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

  View details for DOI 10.1016/j.healun.2015.06.006

  View details for PubMedID 26210751

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

  Abstract

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

  View details for DOI 10.1111/petr.12574

  View details for Web of Science ID 000362580100018

  View details for PubMedID 26250489

• Maintenance steroid use at 30 days post-transplant and outcomes of pediatric heart transplantation: A propensity matched analysis of the Pediatric Heart Transplant Study database JOURNAL OF HEART AND LUNG TRANSPLANTATION Auerbach, S. R., Kukreja, M., Gilbert, D., Bastardi, H., Feingold, B., Knecht, K., Kaufman, B. D., Brown, R. N., Miyamoto, S. D. 2015; 34 (8): 1066-1072

  Abstract

  Maintenance steroid (MS) use in pediatric heart transplantation is variable. The purpose of this study was to evaluate the impact of MS use on graft outcomes.All patients <18 years old in the Pediatric Heart Transplant Study database at the time of first heart transplant between 1993 and 2011 who survived ≥30 days post-transplant and were from centers with a protocolized approach to MS use were included (N = 2,178). Patients were grouped by MS use at 30 days post-transplant as MS+ or MS- (no MS use). Propensity score analysis was used to generate matched groups of MS+ and MS- patients based on pre-transplant and peri-transplant factors. Kaplan-Meier survival analysis was used to compare freedom from graft loss, graft loss secondary to rejection, rejection, rejection with severe hemodynamic compromise (RSHC), malignancy, and infection between groups.Of patients, 1,393 (64%) were MS+ and 785 (36%) were MS-. There were 315 MS- patients who had propensity matched MS+ controls. Kaplan-Meier estimates showed no difference in graft loss (p = 0.9) or graft loss secondary to rejection (p = 0.09). At 1 year post-transplant, there was no difference in freedom from rejection (p = 0.15) or malignancy (p = 0.07), but there was lower freedom from RSHC and infection in the MS- group (p = 0.05 and p = 0.02, respectively).MS use at 30 days post-transplant was not associated with enhanced graft survival after pediatric heart transplant. MS- patients had a higher incidence of RSHC and infection. These risks should be taken into consideration when determining MS use for pediatric recipients of heart transplants.

  View details for DOI 10.1016/j.healun.2015.03.003

  View details for Web of Science ID 000358183600009

• Maintenance steroid use at 30 days post-transplant and outcomes of pediatric heart transplantation: A propensity matched analysis of the Pediatric Heart Transplant Study database. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Auerbach, S. R., Kukreja, M., Gilbert, D., Bastardi, H., Feingold, B., Knecht, K., Kaufman, B. D., Brown, R. N., Miyamoto, S. D. 2015; 34 (8): 1066-72

  Abstract

  Maintenance steroid (MS) use in pediatric heart transplantation is variable. The purpose of this study was to evaluate the impact of MS use on graft outcomes.All patients <18 years old in the Pediatric Heart Transplant Study database at the time of first heart transplant between 1993 and 2011 who survived ≥30 days post-transplant and were from centers with a protocolized approach to MS use were included (N = 2,178). Patients were grouped by MS use at 30 days post-transplant as MS+ or MS- (no MS use). Propensity score analysis was used to generate matched groups of MS+ and MS- patients based on pre-transplant and peri-transplant factors. Kaplan-Meier survival analysis was used to compare freedom from graft loss, graft loss secondary to rejection, rejection, rejection with severe hemodynamic compromise (RSHC), malignancy, and infection between groups.Of patients, 1,393 (64%) were MS+ and 785 (36%) were MS-. There were 315 MS- patients who had propensity matched MS+ controls. Kaplan-Meier estimates showed no difference in graft loss (p = 0.9) or graft loss secondary to rejection (p = 0.09). At 1 year post-transplant, there was no difference in freedom from rejection (p = 0.15) or malignancy (p = 0.07), but there was lower freedom from RSHC and infection in the MS- group (p = 0.05 and p = 0.02, respectively).MS use at 30 days post-transplant was not associated with enhanced graft survival after pediatric heart transplant. MS- patients had a higher incidence of RSHC and infection. These risks should be taken into consideration when determining MS use for pediatric recipients of heart transplants.

  View details for DOI 10.1016/j.healun.2015.03.003

  View details for PubMedID 25980572

• The Use of Pediatric Ventricular Assist Devices in Children's Hospitals From 2000 to 2010: Morbidity, Mortality, and Hospital Charges. Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies Mansfield, R. T., Lin, K. Y., Zaoutis, T., Mott, A. R., Mohamad, Z., Luan, X., Kaufman, B. D., Ravishankar, C., Gaynor, J. W., Shaddy, R. E., Rossano, J. W. 2015; 16 (6): 522-8

  Abstract

  The use of ventricular assist devices has increased dramatically in adult heart failure patients. However, the overall use, outcome, comorbidities, and resource utilization of ventricular assist devices in pediatric patients have not been well described. We sought to demonstrate that the use of ventricular assist devices in pediatric patients has increased over time and that mortality has decreased.A retrospective study of the Pediatric Health Information System database was performed for patients 20 years old or younger undergoing ventricular assist device placement from 2000 to 2010.None.Four hundred seventy-five pediatric patients were implanted with ventricular assist devices during the study period: 69 in 2000-2003 (era 1), 135 in 2004-2006 (era 2), and 271 in 2007-2010 (era 3). Median age at ventricular assist device implantation was 6.0 years (interquartile range, 0.5-13.8), and the proportion of children who were 1-12 years old increased from 29% in era 1 to 47% in era 3 (p = 0.002). The majority of patients had a diagnosis of cardiomyopathy; this increased from 52% in era 1 to 72% in era 3 (p = 0.003). Comorbidities included arrhythmias (48%), pulmonary hypertension (16%), acute renal failure (34%), cerebrovascular disease (28%), and sepsis/systemic inflammatory response syndrome (34%). Two hundred forty-seven patients (52%) underwent heart transplantation and 327 (69%) survived to hospital discharge. Hospital mortality decreased from 42% in era 1 to 25% in era 3 (p = 0.004). Median hospital length of stay increased (37 d [interquartile range, 12-64 d] in era 1 vs 69 d [interquartile range, 35-130] in era 3; p < 0.001) and median adjusted hospital charges increased ($630,630 [interquartile range, $227,052-$853,318] in era 1 vs $1,577,983 [interquartile range, $874,463-$2,280,435] in era 3; p < 0.001). Factors associated with increased mortality include age less than 1 year (odds ratio, 2.04; 95% CI, 1.01-3.83), acute renal failure (odds ratio, 2.1; 95% CI, 1.26-3.65), cerebrovascular disease (odds ratio, 2.1; 95% CI, 1.25-3.62), and extracorporeal membrane oxygenation (odds ratio, 3.16; 95% CI, 1.79-5.60). Ventricular assist device placement in era 3 (odds ratio, 0.3; 95% CI, 0.15-0.57) and a diagnosis of cardiomyopathy (odds ratio, 0.5; 95% CI, 0.32-0.84), were associated with decreased mortality. Large-volume centers had lower mortality (odds ratio, 0.55; 95% CI, 0.34-0.88), lower use of extracorporeal membrane oxygenation, and higher charges.The use of ventricular assist devices and survival after ventricular assist device placement in pediatric patients have increased over time, with a concomitant increase in resource utilization. Age under 1 year, certain noncardiac morbidities, and the use of extracorporeal membrane oxygenation are associated with worse outcomes. Lower mortality was seen at larger volume ventricular assist device centers.

  View details for DOI 10.1097/PCC.0000000000000401

  View details for PubMedID 25850863

• The Use of Pediatric Ventricular Assist Devices in Children's Hospitals From 2000 to 2010: Morbidity, Mortality, and Hospital Charges PEDIATRIC CRITICAL CARE MEDICINE Mansfield, R. T., Lin, K. Y., Zaoutis, T., Mott, A. R., Mohamad, Z., Luan, X., Kaufman, B. D., Ravishankar, C., Gaynor, J. W., Shaddy, R. E., Rossano, J. W. 2015; 16 (6): 522-528

  Abstract

  The use of ventricular assist devices has increased dramatically in adult heart failure patients. However, the overall use, outcome, comorbidities, and resource utilization of ventricular assist devices in pediatric patients have not been well described. We sought to demonstrate that the use of ventricular assist devices in pediatric patients has increased over time and that mortality has decreased.A retrospective study of the Pediatric Health Information System database was performed for patients 20 years old or younger undergoing ventricular assist device placement from 2000 to 2010.None.Four hundred seventy-five pediatric patients were implanted with ventricular assist devices during the study period: 69 in 2000-2003 (era 1), 135 in 2004-2006 (era 2), and 271 in 2007-2010 (era 3). Median age at ventricular assist device implantation was 6.0 years (interquartile range, 0.5-13.8), and the proportion of children who were 1-12 years old increased from 29% in era 1 to 47% in era 3 (p = 0.002). The majority of patients had a diagnosis of cardiomyopathy; this increased from 52% in era 1 to 72% in era 3 (p = 0.003). Comorbidities included arrhythmias (48%), pulmonary hypertension (16%), acute renal failure (34%), cerebrovascular disease (28%), and sepsis/systemic inflammatory response syndrome (34%). Two hundred forty-seven patients (52%) underwent heart transplantation and 327 (69%) survived to hospital discharge. Hospital mortality decreased from 42% in era 1 to 25% in era 3 (p = 0.004). Median hospital length of stay increased (37 d [interquartile range, 12-64 d] in era 1 vs 69 d [interquartile range, 35-130] in era 3; p < 0.001) and median adjusted hospital charges increased ($630,630 [interquartile range, $227,052-$853,318] in era 1 vs $1,577,983 [interquartile range, $874,463-$2,280,435] in era 3; p < 0.001). Factors associated with increased mortality include age less than 1 year (odds ratio, 2.04; 95% CI, 1.01-3.83), acute renal failure (odds ratio, 2.1; 95% CI, 1.26-3.65), cerebrovascular disease (odds ratio, 2.1; 95% CI, 1.25-3.62), and extracorporeal membrane oxygenation (odds ratio, 3.16; 95% CI, 1.79-5.60). Ventricular assist device placement in era 3 (odds ratio, 0.3; 95% CI, 0.15-0.57) and a diagnosis of cardiomyopathy (odds ratio, 0.5; 95% CI, 0.32-0.84), were associated with decreased mortality. Large-volume centers had lower mortality (odds ratio, 0.55; 95% CI, 0.34-0.88), lower use of extracorporeal membrane oxygenation, and higher charges.The use of ventricular assist devices and survival after ventricular assist device placement in pediatric patients have increased over time, with a concomitant increase in resource utilization. Age under 1 year, certain noncardiac morbidities, and the use of extracorporeal membrane oxygenation are associated with worse outcomes. Lower mortality was seen at larger volume ventricular assist device centers.

  View details for DOI 10.1097/PCC.0000000000000401

  View details for Web of Science ID 000358289700004

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

  Abstract

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

  View details for DOI 10.1016/j.healun.2014.10.007

  View details for PubMedID 25538014

• Adrenergic receptor genotype influences heart failure severity and ß-blocker response in children with dilated cardiomyopathy. Pediatric research Reddy, S., Fung, A., Manlhiot, C., Selamet Tierney, E. S., Chung, W. K., Blume, E., Kaufman, B. D., Goldmuntz, E., Colan, S., Mital, S. 2015; 77 (2): 363-369

  Abstract

  Adrenergic receptor (ADR) genotypes are associated with heart failure (HF) and β-blocker response in adults. We assessed the influence of ADR genotypes in children with dilated cardiomyopathy (DCM).Ninety-one children with advanced DCM and 44 with stable DCM were genotyped for three ADR genotypes associated with HF risk in adults: α2cdel322-325, β1Arg389, and β2Arg16. Data were analyzed by genotype and β-blocker use. Mean age at enrollment was 8.5 y.One-year event-free survival was 51% in advanced and 80% in stable DCM. High-risk genotypes were associated with higher left ventricular (LV) filling pressures, higher systemic and pulmonary vascular resistance, greater decline in LV ejection fraction (P < 0.05), and a higher frequency of mechanical circulatory support while awaiting transplant (P = 0.05). While β-blockers did not reduce HF severity in the overall cohort, in the subset with multiple high-risk genotypes, those receiving β-blockers showed better preservation of cardiac function and hemodynamics compared with those not receiving β-blockers (interaction P < 0.05).Our study identifies genetic risk markers that may help in the identification of patients at risk for developing decompensated HF and who may benefit from early institution of β-blocker therapy before progression to decompensated HF.

  View details for DOI 10.1038/pr.2014.183

  View details for PubMedID 25406899

  View details for PubMedCentralID PMC4298011

• Procollagen type III amino-terminal propeptide: a serum biomarker of left ventricular remodelling in paediatric dilated cardiomyopathy CARDIOLOGY IN THE YOUNG Kaufman, B. D., Videon, N., Zhang, X., Harris, M. A., Shaddy, R. E., Goldmuntz, E. 2015; 25 (2): 228-236

  Abstract

  Procollagen type III amino-terminal propeptide is a collagen III cleavage product released in blood. The serum levels of this propeptide in adults with dilated cardiomyopathy are associated with cardiac remodelling and prognosis. The utility of procollagen type III amino-terminal propeptide as a biomarker in paediatric dilated cardiomyopathy is unknown.This was a prospective, longitudinal study of children with dilated cardiomyopathy and changes in procollagen type III amino-terminal propeptide. The serum level of propeptide was measured serially, compared with paediatric normal values, and correlated with clinical status and left ventricular size and function on echocardiograms and cardiac magnetic resonance imaging.Procollagen type III amino-terminal propeptide was measured serially in 149 samples from 39 patients, age 9.0±6.4 years, followed up for 16.8±16.3 months. Procollagen type III amino-terminal propeptide in dilated cardiomyopathy was higher than in normal children. On multivariate analyses, procollagen type III amino-terminal propeptide had a positive correlation with left ventricular dilation, left ventricular end-diastolic diameter index (p<0.0001), and left ventricular end-diastolic diameter Z-score (p=0.0003), and a negative correlation with shortening fraction changes over time (p=0.001). Patients with myocarditis (n=12) had higher procollagen type III amino-terminal propeptide values than those with idiopathic dilated cardiomyopathy (n=20).Procollagen type III amino-terminal propeptide increases with left ventricular dilation and decreases with improvement in systolic function in paediatric dilated cardiomyopathy, indicating a role as a biomarker of cardiac remodelling in children. The diagnostic utility of procollagen type III amino-terminal propeptide to differentiate myocarditis from idiopathic dilated cardiomyopathy warrants further investigation.

  View details for DOI 10.1017/S1047951113001820

  View details for Web of Science ID 000349387000005

  View details for PubMedID 24192074

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

  Abstract

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

  View details for DOI 10.1016/j.healun.2014.08.019

  View details for PubMedID 25307622

  View details for PubMedCentralID PMC4278954

• Cardiomyopathy Phenotypes and Outcomes for Children With Left Ventricular Myocardial Noncompaction: Results From the Pediatric Cardiomyopathy Registry. Journal of cardiac failure Jefferies, J. L., Wilkinson, J. D., Sleeper, L. A., Colan, S. D., Lu, M. n., Pahl, E. n., Kantor, P. F., Everitt, M. D., Webber, S. A., Kaufman, B. D., Lamour, J. M., Canter, C. E., Hsu, D. T., Addonizio, L. J., Lipshultz, S. E., Towbin, J. A. 2015

  Abstract

  Left ventricular noncompaction (LVNC) is a distinct form of cardiomyopathy characterized by hypertrabeculation of the left ventricle. The LVNC phenotype may occur in isolation or with other cardiomyopathy phenotypes. Prognosis is incompletely characterized in children.According to diagnoses from the National Heart, Lung, and Blood Institute-funded Pediatric Cardiomyopathy Registry from 1990 to 2008, 155 of 3,219 children (4.8%) had LVNC. Each LVNC patient was also classified as having an associated echocardiographically diagnosed cardiomyopathy phenotype: dilated (DCM), hypertrophic (HCM), restrictive (RCM), isolated, or indeterminate. The time to death or transplantation differed among the phenotypic groups (P = .035). Time to listing for cardiac transplantation significantly differed by phenotype (P < .001), as did time to transplantation (P = .015). The hazard ratio for death/transplantation (with isolated LVNC as the reference group) was 4.26 (95% confidence interval [CI] 0.78-23.3) for HCM, 6.35 (95% CI 1.52-26.6) for DCM, and 5.66 (95% CI 1.04-30.9) for the indeterminate phenotype. Most events occurred in the 1st year after diagnosis.LVNC is present in at least 5% of children with cardiomyopathy. The specific LVNC-associated cardiomyopathy phenotype predicts the risk of death or transplantation and should inform clinical management.

  View details for DOI 10.1016/j.cardfail.2015.06.381

  View details for PubMedID 26164213

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

  Abstract

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

  View details for DOI 10.1111/petr.12347

  View details for Web of Science ID 000344360500006

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

  Abstract

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

  View details for DOI 10.1111/petr.12347

  View details for PubMedID 25174602

• Thrombotic events in critically ill children with myocarditis CARDIOLOGY IN THE YOUNG Lin, K. Y., Kerur, B., Witmer, C. M., Beslow, L. A., Licht, D. J., Ichord, R. N., Kaufman, B. D. 2014; 24 (5): 840-847

  Abstract

  Children with myocarditis have multiple risk factors for thrombotic events, yet the role of antithrombotic therapy is unclear in this population. We hypothesised that thrombotic events in critically ill children with myocarditis are common and that children with myocarditis are at higher risk for thrombotic events than children with non-inflammatory dilated cardiomyopathy.This is a retrospective chart review of all children presenting to a single centre cardiac intensive care unit with myocarditis from 1995 to 2008. A comparison group of children with dilated cardiomyopathy was also examined. Antithrombotic regimens were recorded. The primary outcome of thrombotic events included intracardiac clots and any thromboembolic events.Out of 45 cases with myocarditis, 40% were biopsy-proven, 24% viral polymerase chain reaction-supported, and 36% diagnosed based on high clinical suspicion. There were two (4.4%) thrombotic events in the myocarditis group and three (6.7%) in the dilated cardiomyopathy group (p = 1.0). Neither the use of any antiplatelet or anticoagulation therapy, use of intravenous immune globulin, presence of any arrhythmia, nor need for mechanical circulatory support were predictive of thrombotic events in the myocarditis, dilated cardiomyopathy, or combined groups.Thrombotic events in critically ill children with myocarditis and dilated cardiomyopathy occurred in 6% of the combined cohort. There was no difference in thrombotic events between inflammatory and non-inflammatory cardiomyopathy groups, suggesting that the decision to use antithrombotic prophylaxis should be based on factors other than the underlying aetiology of a child's acute decompensated heart failure.

  View details for DOI 10.1017/S1047951113001145

  View details for Web of Science ID 000346331200009

  View details for PubMedID 24016733

  View details for PubMedCentralID PMC3950243

• Hypoalbuminemia and poor growth predict worse outcomes in pediatric heart transplant recipients PEDIATRIC TRANSPLANTATION Castleberry, C., White-Williams, C., Naftel, D., Tresler, M. A., Pruitt, E., Miyamoto, S. D., Murphy, D., Spicer, R., Bannister, L., Schowengerdt, K., Gilmore, L., Kaufman, B., Zangwill, S. 2014; 18 (3): 280-287

  Abstract

  Children with end-stage cardiac failure are at risk of HA and PG. The effects of these factors on post-transplant outcome are not well defined. Using the PHTS database, albumin and growth data from pediatric heart transplant patients from 12/1999 to 12/2009 were analyzed for effect on mortality. Covariables were examined to determine whether HA and PG were risk factors for mortality at listing and transplant. HA patients had higher waitlist mortality (15.81% vs. 10.59%, p = 0.015) with an OR of 1.59 (95% CI 1.09-2.30). Survival was worse for patients with HA at listing and transplant (p ≤ 0.01 and p = 0.026). Infants and patients with congenital heart disease did worse if they were HA at time of transplant (p = 0.020 and p = 0.028). Growth was poor while waiting with PG as risk factor for mortality in multivariate analysis (p = 0.008). HA and PG are risk factors for mortality. Survival was worse in infants and patients with congenital heart disease. PG was a risk factor for mortality in multivariate analysis. These results suggest that an opportunity may exist to improve outcomes for these patients by employing strategies to mitigate these risk factors.

  View details for DOI 10.1111/petr.12239

  View details for Web of Science ID 000333807400015

  View details for PubMedID 24646199

• Impact of congenital heart disease on outcomes of pediatric heart-lung transplantation PEDIATRIC TRANSPLANTATION Keeshan, B. C., Goldfarb, S. B., Lin, K. Y., Kreindler, J. L., Kaufman, B. D., Gaynor, J. W., Shaddy, R. E., Rossano, J. W. 2014; 18 (2): 204-210

  Abstract

  HLT is reserved for children with cardiopulmonary disease not amendable to alternative therapies. Children with CHD with or without ES may be considered for HLT. Outcomes of HLT in this population are not well described. To test the hypothesis that CHD without ES is associated with worse graft survival and identify factors associated with poor outcome, a retrospective analysis of the UNOS database was performed. One hundred and seventy-eight pediatric HLTs were performed between 1987 and 2011. CHD was the diagnosis in 65 patients, of which 34 had CHD without ES. Patients with CHD without ES had decreased patient survival (median 1.31 yr) compared with CHD with ES (4.80 yr, p = 0.05). On multivariable analysis, the following were associated with graft failure: CHD without ES (adjusted HR 1.69, 95% CI 1.09-2.62), younger age (1.04, 1.01-1.08), pretransplant mechanical ventilation (1.75, 1.01-3.06), pretransplant ECMO (3.07, 1.32-7.12), pretransplant PRAs (1.53, 1.06-2.20), and transplant era (1.85, 1.16-2.94). In children with CHD who require HLT, underlying physiology influences outcomes. Those without ES have a worse prognosis. The diagnosis of CHD without ES and preoperative factors may inform decisions in a complex patient population.

  View details for DOI 10.1111/petr.12208

  View details for Web of Science ID 000330740100019

  View details for PubMedID 24373099

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

  Abstract

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

  View details for DOI 10.1016/j.jacc.2013.07.100

  View details for Web of Science ID 000328073000002

  View details for PubMedID 24076489

• Pediatric heart transplantation from donors with depressed ventricular function: an analysis of the United Network of Organ Sharing Database. Circulation. Heart failure Rossano, J. W., Lin, K. Y., Paridon, S. M., Zhang, X., Gaynor, J. W., Kaufman, B. D., Shaddy, R. E. 2013; 6 (6): 1223-1229

  Abstract

  Wait-list mortality for children awaiting heart transplantation remains high. Potential donor hearts with depressed ventricular function are often declined. We aimed to test the hypothesis that pediatric heart transplant recipients of grafts with depressed ventricular function would have comparable survival with those with normal function.A retrospective study was performed for pediatric heart transplants from the United Network of Organ Sharing Database from October 26, 1999, to June 30, 2011. Patients were grouped based on accepted donor left ventricular ejection fraction (LVEF): normal function (LVEF ≥55%), mildly depressed function (LVEF 45%-54%), or moderately-to-severely depressed function (LVEF <45%). During the study period, there were 3672 pediatric heart transplants; 3306 (90%) had a LVEF reported. Ventricular function was mildly depressed in 245 (7%) and moderately-to-severely depressed in 172 (5%). Patients receiving grafts with moderately-to-severely depressed function were more likely to be younger and weigh less (P<0.001 for both) than those receiving grafts with normal function. Median graft survival from accepted donors with normal ventricular function (10.6 years) was similar to survival from accepted donors with mildly depressed ventricular function (9.7 years; P=0.24) and from accepted donors with moderately-to-severely depressed ventricular function (9.1 years; P=0.13). On propensity-matched analysis, donor ventricular function was not associated with graft survival.The use of donors with depressed ventricular function is uncommon in pediatric heart transplantation (<15% of all transplants), yet graft survival does not differ significantly from accepted donors with normal ventricular function. Hearts from donors with depressed ventricular function may be considered in selected patients.

  View details for DOI 10.1161/CIRCHEARTFAILURE.112.000029

  View details for PubMedID 23985431

• Adult and pediatric perspectives on heart retransplant. World journal for pediatric & congenital heart surgery Kaufman, B. D., Jessup, M. 2013; 4 (1): 75-79

  Abstract

  At the Ethics of the Heart II: Ethical and Policy Challenges in Congenital Heart Disease Conference, March 16-17, 2012 in Philadelphia, Pennsylvania, one of the sessions focused on the issues related to end-stage heart failure in patients with congenital heart disease including utilizing the therapy of heart transplantation. This article will summarize the session related to repeat heart transplant that was based on discussion of actual patient cases, two adults and one pediatric, presented, respectively, by an adult and a pediatric heart transplant specialist. Outcome data related to retransplant for both adult and pediatric heart transplant populations are reviewed. The complicated ethical issues related to considerations of beneficence versus nonmalfeasance by a medical care team for an individual patient, patient autonomy related to adherence, and obligations to society to fairly allocate the scarce precious resource of donor organs are discussed.

  View details for DOI 10.1177/2150135112469972

  View details for PubMedID 23799759

• Ethical considerations related to the use of mechanical support in congenital heart disease. World journal for pediatric & congenital heart surgery Rossano, J. W., Kaufman, B. D., Rame, J. E. 2013; 4 (1): 70-74

  Abstract

  Heart failure frequently complicates congenital heart disease (CHD) in children and adults. In patients with end-stage disease, mechanical circulatory support may improve survival, quality of life, and serve as bridge to cardiac transplantation. There are many ethical issues surrounding the use of mechanical circulatory support in patients with CHD including the use of prospective and randomized trials, proper oversight of new therapies, and transparency in reporting. Additionally, there are ethical considerations relevant to the greater society as these therapies are highly resource intensive in a resource-limited society. This article will review the burden of disease of heart failure in patients with CHD, the challenges of mechanical circulatory support and heart transplantation, and the ethical considerations and problems that arise for this population.

  View details for DOI 10.1177/2150135112469040

  View details for PubMedID 23799758

• Why should we care about ethical and policy challenges in congenital heart disease? World journal for pediatric & congenital heart surgery Kirkpatrick, J. N., Kaufman, B. 2013; 4 (1): 7-9

  Abstract

  Congenital heart disease (CHD) affects 1% of infants worldwide, and approximately 90% of children with serious CHD who have access to surgery survive to adulthood. Particularly as this population ages, there are unique ethical and policy challenges pertaining to this diverse population of children and adults, which also serve as a paradigm for other chronic diseases. A unique forum to discuss these issues occurred at the University of Pennsylvania in Philadelphia on March 16 to 17, 2012, and was entitled "Ethics of the Heart: Ethical and Policy Challenges in Adult and Pediatric Congenital Heart Disease." The conference convened a multidisciplinary panel of nationally known experts in the fields of Pediatric Congenital Heart Disease, Adult Congenital Heart Disease, and Bioethics to identify and discuss the most important ethical issues in CHD through talks, panel discussions, and one-on-one interviews in six topic areas: genetic testing, transitions of care from pediatric to adult CHD, transplantation and mechanical circulatory support, research and development in CHD, the social and personal costs of success in treating CHD, and end-of-life considerations. This article is an introduction to the topics discussed.

  View details for DOI 10.1177/2150135112454666

  View details for PubMedID 23799747

• Ethics Priorities in Adult Congenital Heart Disease PROGRESS IN CARDIOVASCULAR DISEASES Kirkpatrick, J. N., Kim, Y. Y., Kaufman, B. D. 2012; 55 (3): 266-273

  Abstract

  The success of modern therapies in congenital heart disease has produced a large and growing population of adults with congenital heart disease as a chronic condition. Such success increasingly raises a host of ethical issues, from resource utilization to end of life decision-making. The importance of a multidisciplinary approach to the care of adult congenital heart disease (ACHD) patients has been emphasized for some time, but addressing the challenges in this population requires a broad range of ethical expertise as well. This paper is based on a conference entitled "Ethical and Policy Challenges in Pediatric and Adult Congenital Heart Disease" held in March of 2012. Herein, we present a compilation of the ethics priorities in ACHD discussed at the conference, including ethical aspects of clinical care, ethics research and policy development in the areas of providing clinical care for challenging ACHD patients, improving transitions from pediatric to adult healthcare systems, advance care planning, and addressing costs.

  View details for DOI 10.1016/j.pcad.2012.10.004

  View details for Web of Science ID 000312433100005

  View details for PubMedID 23217430

• Incidence of and Risk Factors for Sudden Cardiac Death in Children With Dilated Cardiomyopathy A Report From the Pediatric Cardiomyopathy Registry JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Pahl, E., Sleeper, L. A., Canter, C. E., Hsu, D. T., Lu, M., Webber, S. A., Colan, S. D., Kantor, P. F., Everitt, M. D., Towbin, J. A., Jefferies, J. L., Kaufman, B. D., Wilkinson, J. D., Lipshultz, S. E. 2012; 59 (6): 607-615

  Abstract

  The purpose of this study was to establish the incidence of and risk factors for sudden cardiac death (SCD) in pediatric dilated cardiomyopathy (DCM).The incidence of SCD in children with DCM is unknown. The ability to predict patients at high risk of SCD will help to define who may benefit most from implantable cardioverter-defibrillators.The cohort was 1,803 children in the PCMR (Pediatric Cardiomyopathy Registry) with a diagnosis of DCM from 1990 to 2009. Cumulative incidence competing-risks event rates were estimated. We achieved risk stratification using Classification and Regression Tree methodology.The 5-year incidence rates were 29% for heart transplantation, 12.1% non-SCD, 4.0% death from unknown cause, and 2.4% for SCD. Of 280 deaths, 35 were SCD, and the cause was unknown for 56. The 5-year incidence rate for SCD incorporating a subset of the unknown deaths is 3%. Patients receiving antiarrhythmic medication were at higher risk of SCD (hazard ratio: 3.0, 95% confidence interval: 1.1 to 8.3, p = 0.025). A risk stratification model based on most recent echocardiographic values had 86% sensitivity and 57% specificity. Thirty of 35 SCDs occurred in patients who met all these criteria: left ventricular (LV) end-systolic dimension z-score >2.6, age at diagnosis younger than 14.3 years, and the LV posterior wall thickness to end-diastolic dimension ratio <0.14. Sex, ethnicity, cause of DCM, and family history were not associated with SCD.The 5-year incidence rate of SCD in children with DCM is 3%. A risk stratification rule (86% sensitivity) included age at diagnosis younger than 14.3 years, LV dilation, and LV posterior wall thinning. Patients who consistently meet these criteria should be considered for implantable cardioverter-defibrillator placement.

  View details for DOI 10.1016/j.jacc.2011.10.878

  View details for Web of Science ID 000300196500009

  View details for PubMedID 22300696

  View details for PubMedCentralID PMC3280885

• Unusual cardiac "masses" in a newborn with infantile pompe disease. JIMD reports Swarr, D. T., Kaufman, B., Fogel, M. A., Finkel, R., Ganesh, J. 2012; 5: 17-20

  Abstract

  Glycogen storage disease type II (OMIM #232300), or Pompe disease, may present in the newborn period with moderate-to-severe biventricular hypertrophy with or without left ventricular outflow tract obstruction that typically leads to death from cardiorespiratory failure in the first year of life. Glycogen deposition tends to be uniform, and is only occasionally accompanied by patchy areas of fibrosis. Here, we present an infant identified with biventricular hypertrophy and cardiac masses by prenatal ultrasound. Postnatal molecular studies did not support the diagnosis of tuberous sclerosis in this case. Additional evaluation for infantile hypertrophic cardiomyopathy confirmed the diagnosis of Pompe disease. We discuss whether the "cardiac masses," which brought this infant to medical attention and facilitated an early diagnosis of Pompe disease, may represent an unusual manifestation of GSD type II or the coincidental occurrence of an unrelated disease process.

  View details for DOI 10.1007/8904_2011_85

  View details for PubMedID 23430912

  View details for PubMedCentralID PMC3509919

• Invasive fungal infections in pediatric heart transplant recipients: Incidence, risk factors, and outcomes PEDIATRIC TRANSPLANTATION Zaoutis, T. E., Webber, S., Naftel, D. C., Chrisant, M. A., Kaufman, B., Pearce, F. B., Spicer, R., Dipchand, A. I. 2011; 15 (5): 465-469

  Abstract

  There are limited data on the incidence or risk factors for IFI in pediatric heart transplant recipients. The purpose of this study was to describe the incidence and types of IFI, to determine risk factors for outcomes of IFI, and to assist in decision-making concerning the need for prophylactic strategies in pediatric heart transplant recipients. Data from a multi-institutional registry of 1854 patients transplanted between 01/93 and 12/04 were analyzed to determine risk factors and outcomes of children with IFI post-heart transplantation. One hundred and thirty-nine episodes of IFI occurred in 123 patients and made up 6.8% of the total number of post-transplant infections. IFI was most commonly attributed to yeast (66.2%), followed by mold (15.8%) and Pneumocystis jiroveci (13%). Ninety percent of the yeast infections were caused by Candida spp., and Aspergillus spp. was causative in 82% of the mold infections. There was a significantly increased risk of fungal infection associated with pretransplant invasive procedures (e.g., ECMO, prior surgery, VAD, mechanical ventilation) with an incremental risk with increasing numbers of invasive procedures (early phase 0 vs. 1, RR 1.3; 0 vs. 3, RR 2.3; p<0.001). In multivariate analysis, previous surgery (p=0.05) and mechanical support at transplantation (p=0.01) remained significant. Forty-nine percent of recipients with IFI died, all within six months post-transplant. Invasive fungal infections are uncommon in pediatric heart transplant recipients. Risk and mortality are highest in the first six months post-transplant especially in patients with previous surgery and those requiring mechanical support. Prophylactic strategies for high-risk patients should be considered and warrants further study.

  View details for DOI 10.1111/j.1399-3046.2010.01415.x

  View details for Web of Science ID 000292908600010

  View details for PubMedID 21108712

• Troponin I levels from donors accepted for pediatric heart transplantation do not predict recipient graft survival JOURNAL OF HEART AND LUNG TRANSPLANTATION Lin, K. Y., Sullivan, P., Salam, A., Kaufman, B., Paridon, S., Hanna, B. D., Spray, T. L., Weber, J., Shaddy, R. 2011; 30 (8): 920-927

  Abstract

  Troponin I is often obtained during the evaluation of a potential transplant donor heart. It is not clear whether elevations in donor troponin I levels predict adverse outcomes and should thus preclude acceptance of a donor heart. This study examined whether troponin I levels from donors accepted for pediatric heart transplantation predicted graft failure.Deidentified data on heart transplants performed in recipients aged < 21 years between April 2007 and April 2009 was provided by the Organ Procurement and Transplantation Network. Donor troponin I level and recipient outcomes, including survival without retransplantation (graft survival), were examined for statistical correlation.Overall graft survival in 839 heart transplants was 81% at 2 years. At least 1 troponin I level was recorded in 657 donors before transplant, with a median value of 0.1 ng/ml (range, 0-50 ng/ml). Troponin I level and graft status were not correlated (p = 0.74). A receiver operating characteristic curve showed no association between troponin I and graft status (area under the curve, 0.51; p = 0.98). Graft survival did not differ significantly (p = 0.60) among quartiles of troponin I levels (<0.04, 0.04-<0.1, 0.1-<0.35, ≥ 0.35 ng/ml). A troponin I level ≥ 1 ng/ml was found in 74 transplanted donor hearts; graft survival was not associated with troponin I ≥ 1 (80%) vs < 1 (80%) at 2 years (p = 0.93). Troponin I values were not associated with post-transplant hospital length of stay (r = -0.06; p = 0.10).In donor hearts accepted for pediatric heart transplantation, troponin I elevation before procurement is not associated with increased graft failure. The significance of elevated troponin I levels, which occurs in many heart donors, remains unclear and should therefore be considered in the context of other clinical information.

  View details for DOI 10.1016/j.healun.2011.02.011

  View details for Web of Science ID 000293038800010

  View details for PubMedID 21489812

  View details for PubMedCentralID PMC3129377

• Immunologic considerations in heart transplantation for congenital heart disease. Current cardiology reviews Kaufman, B. D., Shaddy, R. E. 2011; 7 (2): 67-71

  Abstract

  Children and adults with congenital heart disease (CHD) can require interventions that result in immunologic alterations that are different than those seen in patients with cardiomyopathies. Patients with CHD can be exposed to heart surgeries, blood products, valved and non-valved allograft tissue, and mechanical circulatory support, all of which can alter the immunologic status of these patients. This change in immunologic status is most commonly manifested as the development of anti-human leukocyte antigen (HLA) antibodies. This review will delineate a) the causes of anti-HLA anti-body production (often referred to as allosensitization); b) preventive strategies for anti-HLA antibody production before transplantation; c) treatment strategies for those patients who develop anti-HLA antibodies before transplantation; d) consequences of HLA allosensitization after transplantation; and e) treatment of HLA allosensitization and antibody-mediated rejection after transplantation.

  View details for DOI 10.2174/157340311797484204

  View details for PubMedID 22548029

  View details for PubMedCentralID PMC3197091

• Idebenone in Friedreich ataxia cardiomyopathy-results from a 6-month phase III study (IONIA) AMERICAN HEART JOURNAL Lagedrost, S. J., Sutton, M. S., Cohen, M. S., Satou, G. M., Kaufman, B. D., Perlman, S. L., Rummey, C., Meier, T., Lynch, D. R. 2011; 161 (3): 639-?

  Abstract

  Friedreich ataxia (FRDA) is commonly associated with hypertrophic cardiomyopathy, but little is known about its frequency, severity, or treatment. In this 6-month randomized, double-blind, controlled study, we sought to determine whether idebenone improves cardiac measures in FRDA.Seventy pediatric subjects were treated either with idebenone (450/900 mg/d or 1,350/2,250 mg/d) or with placebo. Electrocardiograms (ECGs) were assessed at each visit, and echocardiograms, at baseline and week 24.We found ECG abnormalities in 90% of the subjects. On echocardiogram, 81.4% of the total cohort had left ventricular (LV) hypertrophy, as measured by increased LV mass index-Dubois, and the mean ejection fraction (EF) was 56.9%. In linear regression models, longer PR intervals at baseline were marginally associated with longer GAA repeat length (P = .011). Similarly, GAA repeat length did not clearly predict baseline EF (P = .086) and LV mass by M-mode (P = .045). Left ventricular mass index, posterior wall thickness, EF, and ECG parameters were not significantly improved by treatment with idebenone. Some changes in echocardiographic parameters during the treatment phase correlated with baseline status but not with treatment group.Idebenone did not decrease LV hypertrophy or improve cardiac function in subjects with FRDA. The present study does not provide evidence of benefit in this cohort over a 6-month treatment period.

  View details for DOI 10.1016/j.ahj.2010.10.038

  View details for Web of Science ID 000288156400032

  View details for PubMedID 21392622

• Brain-type natriuretic peptide correlates with right heart pressures in a cross section of pediatric heart transplant patients PEDIATRIC TRANSPLANTATION Hall, E. K., Glatz, A. C., Quartermain, M. D., Ravishankar, C., Kaufman, B., Cohen, M. S., Hanna, B. D., Goldberg, D. J. 2011; 15 (1): 70-74

  Abstract

  Serum brain-type natriuretic peptide level (BNP) correlates with hemodynamic parameters measured during cardiac catheterization in adult patients with heart failure. We sought to describe the relationship of BNP with invasive hemodynamic measurements and cellular rejection in children following OHT. Children undergoing catheterization for OHT surveillance had simultaneous measurement of BNP. A total of 62 subjects were studied. The median BNP was 171 pg/mL (range 19-1130). There were significant positive correlations between BNP and mean PAP (R=0.33, p=0.009), RVSP (R=0.25, p=0.05), RVEDP (R=0.29, p=0.02), and mean RAP (R=0.39, p=0.002). Rejection grade varied from 0 to 3A (58 patients < ISHLT 3A and four patients ≥ ISHLT 3A). There was no significant difference in BNP based on cellular rejection grade. In a cohort of pediatric patients after heart transplantation, BNP correlates with direct measurements of right-sided pressures, but not with other hemodynamic measurements, time from transplant or rejection grade. This suggests that BNP may have a complimentary role in the monitoring of children following heart transplantation.

  View details for DOI 10.1111/j.1399-3046.2010.01421.x

  View details for Web of Science ID 000286329400018

  View details for PubMedID 21199206

• Ventricular assist device-associated anti-human leukocyte antigen antibody sensitization in pediatric patients bridged to heart transplantation JOURNAL OF HEART AND LUNG TRANSPLANTATION O'Connor, M. J., Menteer, J., Chrisant, M. R., Monos, D., Lind, C., Levine, S., Gaynor, J. W., Hanna, B. D., Paridon, S. M., Ravishankar, C., Kaufman, B. D. 2010; 29 (1): 109-116

  Abstract

  Ventricular assist devices (VAD) are associated with the formation of antibodies to anti-human leukocyte antigens (HLA) or sensitization. The incidence and effects of VAD-associated anti-HLA sensitization have not been well studied in the pediatric population.A retrospective review of all patients undergoing VAD implant at our institution from 1998 to 2008 was performed. Panel reactive antibody (PRA) results before VAD implant, after VAD implant, and after orthotopic heart transplantation (OHT) were recorded. Patients who became sensitized (PRA for class I and/or II immunoglobulin G antibodies >or= 10%) on VAD support were compared with non-sensitized patients with regard to demographics, diagnosis, device type, and blood product exposure on VAD support. Outcomes after OHT were also compared between groups.VAD support was initiated in 20 patients (median age, 14.4 years), with 75% survival to OHT or recovery. PRA data before and after VAD implant were available for 17 patients. VAD-associated sensitization developed in 35% of recipients. There were no differences between those sensitized in association with VAD support and non-sensitized patients with regard to age, gender, diagnosis, device type, extracorporeal membrane oxygenation use, or blood product exposure on VAD support. Black race predicted sensitization on VAD (p = 0.02). There were no differences in survival or rejection between groups.VAD therapy was associated with the development of anti-HLA sensitization in 35% of recipients. Black race predicted sensitization, but there were no differences in overall survival or outcomes after OHT.

  View details for DOI 10.1016/j.healun.2009.08.028

  View details for Web of Science ID 000273795500019

  View details for PubMedID 20123248

• Outcomes of Children With Cardiomyopathy Listed for Transplant: A Multi-institutional Study JOURNAL OF HEART AND LUNG TRANSPLANTATION Dipchand, A. I., Naftel, D. C., Feingold, B., Spicer, R., Yung, D., Kaufman, B., Kirklin, J. K., Atlain-Rooney, T., Hsu, D. 2009; 28 (12): 1312-1321

  Abstract

  Dilated (DCM), restrictive (RCM), and hypertrophic (HCM) cardiomyopathies (CM) in children have varying clinical courses and therapeutic options. Heart transplantation (HTx) offers a chance for long-term survival; but outcomes after listing have not been well defined.A multi-institutional registry of 3,147 patients listed for HTx (January 1993-December 2006) was used to compare outcomes of 1,320 children with CM (42%) and 1,827 with non-CM (58%) etiologies. Comparisons were made between sub-groups: 1,098 DCM (83%), 145 RCM (11%), and 77 HCM (6%).CM patients had a waitlist mortality of 17% vs 32% for non-CM patients (p < 0.0001), with no difference between the CM sub-groups. Risk factors were younger age, black race (relative risk [RR], 1.65; p = 0.009), mechanical ventilation (RR, 3.17; p < 0.001), and extracorporeal membrane oxygenation (RR, 2.16; p < 0.001). Ten-year survival after listing was 66% for CM vs 53% for non-CM (p < 0.0001). HCM and RCM patients aged < 1 year at the time of listing had the highest waitlist mortality and the lowest overall survival. CM patients had a better 10-year survival after HTx (68% vs 61%, p < 0.0001). Risk factors for death early after HTx included mechanical ventilation at HTx (RR, 3.07; p < 0.001), longer ischemic time (RR, 1.27; p = 0.01), and earlier era (RR, 1.77; p = 0.002). Late risk factors included black race (RR, 3.01; p < 0.001), HCM or RCM (RR, 1.93; p = 0.007), and older age (RR, 1.9; p < 0.001).Children with CM have a lower waitlist mortality and better survival post-HTx than children with a non-CM diagnosis. DCM patients have the best and HCM or RCM patients aged younger than 1 year have the worst overall outcomes.

  View details for DOI 10.1016/j.healun.2009.05.019

  View details for Web of Science ID 000272943500014

  View details for PubMedID 19782592

• Wasting or Obesity at Time of Transplant Does Not Predict Pediatric Heart Transplant Outcomes: Analysis of ISHLT Pediatric Heart Transplant Registry JOURNAL OF HEART AND LUNG TRANSPLANTATION Kaufman, B. D., Chuai, S., Dobbels, F., Shaddy, R. E. 2009; 28 (12): 1273-1278

  Abstract

  Body mass index (BMI) both before and after heart transplant (HT) is used to risk stratify in adult HT. Single-center studies identify BMI as a potential predictor of outcome after HT in children; large-scale analyses in pediatric HT have not been performed.The ISHLT pediatric heart transplant registry was queried for HT recipients >2 years old between 1996 and 2006 with data for BMI percentile (BMI%ile) at HT. Survival and morbidity rates post-HT were compared between BMI%ile cohorts defined as: wasted, <5th BMI%ile; normal, 5th to 95th BMI%ile; and obese, >95th BMI%ile at HT.Data from 2,333 pediatric HT patients were available for analysis. Incidence of abnormal BMI%ile at HT was: wasted = 23% and obese = 8%. Wasting and obesity were similar in patients with congenital or cardiomyopathic diagnoses. Wasted or obese patients at HT did not differ from patients with normal BMI in survival on Kaplan-Meier or multivariate analyses. There were no significant differences in pre-, peri- or post-operative adverse events between patients with wasting or obesity and those with normal BMI%ile at HT.In contrast to adults, abnormal body mass at time of transplant was not associated with decreased survival in pediatric HT recipients. Potential pediatric transplant candidates should not be excluded based on the perception that wasting or obesity will increase the risk of adverse outcomes.

  View details for DOI 10.1016/j.healun.2009.07.020

  View details for Web of Science ID 000272943500008

  View details for PubMedID 19783177

• Assessment and management of the failing heart in children 8th International Symposium on Congenital Heart Disease Kaufman, B. D., Shaddy, R. E., Shirali, G. S., Tanel, R., Towbin, J. A. CAMBRIDGE UNIV PRESS. 2008: 63–71

  View details for Web of Science ID 000266381000008

  View details for PubMedID 19094380

• Genomic Profiling of Left and Right Ventricular Hypertrophy in Congenital Heart Disease 53rd Annual Scientific Session of the American-College-of-Cardiology Kaufman, B. D., Desai, M., Reddy, S., Osorio, J. C., Chen, J. M., Mosca, R. S., Ferrante, A. W., Mital, S. CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS. 2008: 760–67

  Abstract

  The right ventricle (RV) has a lower ability than the left ventricle (LV) to adapt to systemic load. The molecular basis of these differences is not known. We compared hypertrophy-signaling pathways between the RV and the LV in patients with congenital heart disease (CHD).Gene expression was measured using DNA microarrays in myocardium from children with CHD with LV or RV obstructive lesions undergoing surgery. The expression of 175 hypertrophy-signaling genes was compared between the LV (n=7) and the RV (n=11). Hierarchic clustering was performed.Seventeen genes (10%) were differentially expressed between the LV and the RV. Expression of genes for angiotensin, adrenergic, G-proteins, cytoskeletal, and contractile components was lower (P < .05) and expression of maladaptive factors (fibroblast growth factors, transforming growth factor-beta, caspases, ubiquitin) was higher in the RV compared with the LV (P < .05). Five of 7 LV samples clustered together. Only 4 of 11 RV samples clustered with the LV. Genes critical to adaptive remodeling correlated with the degree of LV hypertrophy but not RV hypertrophy.The transcription of pathways of adaptive remodeling was lower in the RV compared with the LV. This may explain the lower ability of the RV to adapt to hemodynamic load in CHD.

  View details for DOI 10.1016/j.cardfail.2008.06.002

  View details for Web of Science ID 000261269800008

  View details for PubMedID 18995181

• Too fat or too thin? Body habitus assessment in children listed for heart transplant and impact on outcome JOURNAL OF HEART AND LUNG TRANSPLANTATION Kaufman, B. D., Nagle, M. L., Levine, S. R., Vijaynathan, N., Hanna, B. D., Paridon, S., Ravishankar, C., Chrisant, M. K. 2008; 27 (5): 508-513

  Abstract

  Body habitus assessment (BHA), be it wasted or obese, is a useful marker of nutritional status and overall medical condition. Wasting and obesity pre-heart transplant adversely affects outcomes in adults. The utility of BHA as a prognostic factor in children post-transplant is unknown.Weight and height at listing and standard growth charts were used to determine the ideal body weight (%IBW) and percentiles for body mass index for age (BMI%) and weight-for-length (W:L%). Wasting was defined as <90%IBW and/or 120%IBW and/or >or=95th percentile BMI% or W:L%. Outcomes of cohorts based on these criteria were compared.From June 1990 to December 2006, 180 children, aged 5.81 +/- 6 years, were listed for transplant. Wasting occurred in 66 (37%) and obesity in 22 (12%) children, without differences between diagnoses of cardiomyopathy or congenital heart disease. %IBW was a prognostic factor for survival post-transplant on multivariate analysis: obese patients had a hazard ratio (HR) of 3.82 (95% confidence interval [CI] 1.81 to 8.06) compared with normal BHA (p < 0.001). Wasting had a survival advantage compared with normal BHA (HR 0.51, 95% CI 0.27 to 0.94, p = 0.032). There were no significant differences between cohorts in incidence of infections, first-year rejections or graft vasculopathy.Abnormal BHA at listing was a prognostic factor for survival post-transplant. Obese children had increased mortality, but wasting did not adversely affect post-transplant survival in our population. Body habitus assessment may risk-stratify children at listing, potentially providing a complex target for intervention.

  View details for DOI 10.1016/j.healun.2008.01.026

  View details for Web of Science ID 000255556900007

  View details for PubMedID 18442716

• RAAS gene polymorphisms influence progression of pediatric hypertrophic cardiomyopathy 77th Scientific Meeting of the American-Heart-Association Kaufman, B. D., Auerbach, S., Reddy, S., Manlhiot, C., Deng, L., Prakash, A., Printz, B. F., Gruber, D., Papavassiliou, D. P., Hsu, D. T., Sehnert, A. J., Chung, W. K., Mital, S. SPRINGER. 2007: 515–23

  Abstract

  Hypertrophic Cardiomyopathy (HCM) is a disease with variable rate of progression. Young age is an independent risk factor for poor outcome in HCM. The influence of renin-angiotensin-aldosterone (RAAS) genotype on the progression of HCM in children is unknown. Children with HCM (n = 65) were enrolled prospectively across two centers (2001-2005). All subjects were genotyped for five RAAS gene polymorphisms previously associated with LV hypertrophy (pro-LVH): AGT M235T, ACE DD, CMA-1903 A/G, AGTR1 1666 A/C and CYP11B2-344 C/T. Linear regression models, based on maximum likelihood estimates, were created to assess the independent effect of RAAS genotype on LV hypertrophy (LVH). Forty-six subjects were homozygous for <2 and 19 were homozygous for > or =2 pro-LVH RAAS polymorphisms. Mean age at presentation was 9.6 +/- 6 years. Forty children had follow-up echocardiograms after a median of 1.5 years. Indexed LV mass (LVMI) and LV mass z-scores were higher at presentation and follow-up in subjects with > or =2 pro-LVH genotypes compared to those with <2 (P < 0.05). Subjects with > or =2 pro-LVH genotypes also demonstrated a greater increase in septal thickness (IVST) and in LV outflow tract (LVOT) obstruction on follow-up (P < 0.05). On multivariate analysis, a higher number of pro-LVH genotypes was associated with a larger effect size (P < 0.05). Pro-LVH RAAS gene polymorphisms are associated with progressive septal hypertrophy and LVOT obstruction in children with HCM. Identification of RAAS modifier genes may help to risk-stratify patients with HCM.

  View details for DOI 10.1007/s00439-007-0429-9

  View details for Web of Science ID 000251143900011

  View details for PubMedID 17851694

• Failure of right ventricular adaptation in children with tetralogy of Fallot 78th Annual Scientific Session of the American-Heart-Association Reddy, S., Osorio, J. C., Duque, A. M., Kaufman, B. D., Phillips, A. B., Chen, J. M., Quaegebeur, J., Mosca, R. S., Mital, S. LIPPINCOTT WILLIAMS & WILKINS. 2006: I37–I42

  Abstract

  The left ventricle (LV) adapts to chronic hypoxia by expressing protective angiogenic, metabolic, and antioxidant genes to improve O2 delivery and energy production, and to minimize reoxygenation injury. The ability of the right ventricle (RV) to adapt to hypoxia in children with tetralogy of Fallot (TOF) is unknown.Gene expression using real-time polymerase chain reaction was measured in RV myocardium obtained during surgical repair of TOF from 23 patients: 13 cyanotic and 10 acyanotic. Results were compared between the 2 groups and correlated with age at surgery, severity of cyanosis, and early postoperative course. The cyanotic patients were younger at surgery compared with acyanotic (5+/-3 versus 9+/-4 months; P=0.01), had higher hematocrit (43+/-4 versus 38+/-3 grams/dL; P=0.004), and lower O2 saturations (84+/-4% versus 98+/-2%; (P<0.001). Cyanotic patients had a significantly lower expression of vascular endothelial growth factor (VEGF), glycolytic enzymes, and glutathione peroxidase (GPX) (P<0.05), and a higher expression of collagen (P<0.01) compared with acyanotic patients. Gene expression correlated inversely with severity of cyanosis ie, preoperative hematocrit (P<0.01) and positively with preoperative saturation (P<0.05). The relationship between gene expression and cyanosis was independent of age at surgery. Ca2+ handling genes did not correlate with the severity of hypoxia. Lower angiogenic, glycolytic, and antioxidant gene expression correlated with increasing postoperative lactate (P<0.05).The RV fails to up regulate adaptive pathways in response to increasing hypoxia in children with TOF. The implications of an early maladaptive response of the RV on long-term RV function require further investigation.

  View details for DOI 10.1161/CIRCULATIONAHA.105.001248

  View details for Web of Science ID 000238688200008

  View details for PubMedID 16820602