Unique Aspects of Hypertrophic Cardiomyopathy in Children.

Hypertrophic cardiomyopathy (HCM) is a primary heart muscle disease characterized by left ventricular hypertrophy that can be asymptomatic or with presentations that vary from left ventricular outflow tract obstruction, heart failure from diastolic dysfunction, arrhythmias, and/or sudden cardiac death. Children younger than 1 year of age tend to have worse outcomes and often have HCM secondary to inborn errors of metabolism or syndromes such as RASopathies. For children who survive or are diagnosed after 1 year of age, HCM outcomes are often favourable and similar to those seen in adults. This is because of sudden cardiac death risk stratification and medical and surgical innovations. Genetic testing and timely cardiac screening are paving the way for disease-modifying treatment as gene-specific therapies are being developed.

Uncertain benefit of statins in pediatric heart transplant recipients: A PHTS analysis.

BACKGROUND: Cardiac allograft vasculopathy (CAV) is a leading cause of graft failure in pediatric heart transplant recipients (HTRs). Early statin use has been shown to reduce CAV incidence and all-cause mortality in adult HTRs. We sought to evaluate the contemporary prevalence and trends of statin use in pediatric HTRs and the association between statin use with CAV development and graft failure. METHODS: Patients aged <17 years at the time of primary heart transplant who survived to ≥3 years without CAV were identified from the Pediatric Heart Transplant Society database (2001-2018). Statin use in the first 3 years posttransplant was defined as consecutive, intermediate, or absent. Kaplan-Meier survival, multivariable modeling, and propensity score-matched analyses evaluated associations between statin use and CAV incidence and graft survival, with subanalyses performed on subjects aged ≥10 years at transplant. RESULTS: Among 3,485 (of which 1,086 aged ≥10 years) HTRs, 584 (17%) received consecutive statin therapy, 647 (19%) received intermediate use, and 2,254 (65%) received no statin therapy. Statin use varied widely between sites, with increasing use in the ≥10-year-old cohort over time. By multivariate analysis, statin use was not associated with graft loss. Consecutive statin use was also not associated with graft survival or freedom from CAV development when compared to absent statin use in unmatched or propensity-matched analyses. CONCLUSIONS: While statins remain commonly utilized in pediatric HTRs, early consecutive statin therapy did not decrease CAV incidence or graft loss. The differing effects of statins on CAV development and progression in pediatric vs adult HTRs suggest differing risk and mediating factors and require further study.

Prospective examination of HLA sensitization after VAD implantation in children and adults.

BACKGROUND: Ventricular assist devices (VADs) have improved survival to heart transplantation (HTx). However, VADs have been associated with development of antibodies against human leukocyte antigen (HLA-Ab) which may limit the donor pool and decrease survival post-HTx. Since HLA-Ab development after VAD insertion is poorly understood, the purpose of this prospective single-center study was to quantify the incidence of and evaluate risk factors for HLA-Ab development across the age spectrum following VAD implantation. METHODS: Adult and pediatric patients undergoing VAD placement as bridge to transplant or transplant candidacy between 5/2016 and 7/2020 were enrolled. HLA-Ab were assessed pre-VAD and at 1-, 3-, and 12-months post-implant. Factors associated with HLA-Ab development post-VAD implant were explored using univariate and multivariate logistic regression. RESULTS: 15/41 (37%) adults and 7/17 (41%) children developed new HLA-Ab post-VAD. The majority of patients (19/22) developed HLA-Ab within two months of implant. New class I HLA-Ab were more common (87% adult, 86% pediatric). Prior pregnancy was strongly associated with HLA-Ab development in adults post-VAD (HR 16.7, 95% CI 1.8-158, p = 0.01). Of the patients who developed new HLA-Ab post-VAD, in 45% (10/22) the HLA-Ab resolved while in 55% (12/22) the HLA-Ab persisted. CONCLUSION: More than one-third of adult and pediatric VAD patients developed new HLA-Ab early after VAD implant with the majority having class I antibodies. Prior pregnancy was strongly associated with post-VAD HLA-Ab development. Further studies are needed to predict regression or persistence of HLA-Ab developed post-VAD, to understand modulation of individuals' immune responses to sensitizing events, and to determine whether transiently detected HLA-Ab post-VAD recur and have long-term clinical impact post-heart transplantation.

Ex situ heart perfusion for optimization of pediatric donor organ utilization: Attitudes and perceptions.

BACKGROUND: Children with heart failure have the highest mortality while awaiting transplantation. Ex situ heart perfusion (ESHP), a method for continuous perfusion of the donor heart, has the potential to improve access to transplant by increasing travel distance between donor and recipient. An adult ESHP device is currently available, but as of yet there is no pediatric device. The aim of this study was to evaluate current knowledge of ESHP among pediatric heart transplant practitioners, define potential barriers, and identify uses of this novel technology. METHODS: An electronic survey was developed to assess perspectives of international pediatric heart transplant stakeholders (n = 68) on ESHP. Select questions were analyzed to evaluate for associations between groups of respondents and patterns of response. RESULTS: Most respondents were familiar but <10% had clinically utilized ESHP. There was optimism that ESHP could decrease waitlist mortality. Respondents were concerned about potential device malfunction and lack of long-term outcomes. There were no differences found in terms of ESHP familiarity among age groups, practitioner center volume, country of work, or discipline. CONCLUSIONS: ESHP has the potential to expand the pediatric heart donor pool and decrease waitlist mortality. More education on outcomes and risks/benefits is needed in order to promote widespread adoption.

Clinical approach to vasoplegia in the transplant patient from the Pediatric Heart Transplant Society.

This manuscript outlines a clinical approach to vasoplegia incorporating the current state of knowledge regarding vasoplegia in pediatric patients immediately post-transplant and to identify modifiable factors both pre- and post-transplant that may reduce post-operative morbidity, end-organ dysfunction, and mortality. Centers participating in the Pediatric Heart Transplant Society (PHTS) were asked to provide their internal protocols and rationale for vasoplegia management, and applicable adult and pediatric data were reviewed. The authors synthesized the above protocols and literature into the following description of clinical approaches to vasoplegia highlighting areas of both broad consensus and of significant practice variation.

Clinical approach to acute cellular rejection from the pediatric heart transplant society.

BACKGROUND: Early detection of cardiac allograft rejection is crucial for post-transplant graft survival. Despite the progress made in immunosuppression strategies, acute cellular rejection remains a serious complication during and after the first post-transplant year, and there is a continued lack of consensus regarding its treatment, especially in pediatric transplant patients. METHODS: An open request was placed via the listserv to the membership of the Pediatric Heart Transplant Society (PHTS). Along with a broad literature search, numerous institutional protocols were pooled, analyzed and consolidated. A clinical approach document was generated highlighting areas of consensus and practice variation. RESULTS: The clinical approach document divides cellular rejection by International Society for Heart and Lung Transplantation grades and provides management strategies for each, including persistent cellular rejection. CONCLUSIONS: Cellular rejection treatment can be tailored to the clinical status, graft function, and the grade of cellular rejection. A case of mild and asymptomatic rejection may not require treatment, whereas a higher-grade rejection or rejection with graft dysfunction or hemodynamic compromise may require aggressive intravenous therapies, changes to maintenance immunosuppression therapy and augmented surveillance.

Waitlist Outcomes for Children With Congenital Heart Disease: Lessons Learned From Over 5000 Heart Transplant Listings in the United States.

BACKGROUND: We evaluated the impact of pediatric heart-allocation policy changes over time and the approval of the Berlin ventricular assist device (VAD) on waitlist (WL) outcomes for children with congenital heart disease (CHD). METHODS: The Scientific Registry of Transplant Recipients database was evaluated to include all children (age < 18) with CHD and cardiomyopathy (CMP) on the WL between 1999 and 2019, divided into 4 eras: Era 1 (1999-2008); Era 2 (2009-2011); Era 3 (2012-2016); and Era 4 (2016-2019). WL characteristics and survival outcomes were evaluated for patients with CHD over time and were compared to those with CMP listed currently (Era 4). RESULTS: We included 5185 children with CHD on the WL during the study period; 1999 (39%) were listed in Era 1; 693 (13%) in Era 2; 1196 (23%) in Era 3; and 1297 (25%) in Era 4. Compared to the CHD WL in eras 1 and 2, those in Era 4 were less likely to be infants (48% vs 49% vs 43%), on mechanical ventilation (30% vs 26% vs 19%), on extracorporeal membrane oxygenation (15% vs 9.7% vs 6.2%), and were more likely to be on a VAD (2.4% vs 2.2% vs 6.0%) (P < .05 for all). WL survival improved in children with CHD from Era 1 to Era 4 (P < .001). However, in Era 4, children with CHD had lower WL survival than those with CMP (P < .001). CONCLUSION: Children with CHD are increasingly being listed with less advanced heart failure, and they have had improved WL survival over time; however, WL outcomes remain inferior to those with CMP. Advances in pediatric medical and VAD therapy may improve future WL outcomes.

Ventricular Assist Device Use in Patients With Single-Ventricle Circulation.

Ventricular assist devices (VADs) are being increasingly used to support patients with congenital heart disease and single-ventricle physiology. Because of their unique anatomy and physiology, special consideration must be used to provide effective mechanical circulatory support for each individual patient. This can include alternative cannulation techniques, strategies to balance cardiac output to the systemic and pulmonary circulations from a single ventricle, or the use of continuous vs pulsatile VADs for better ventricular offloading. In this article we review the etiology of single-ventricle failure, VAD options for support, cannulation strategies, post-VAD management considerations, and outcomes at each of the 3 stages of palliation.

Temporary Veno-Venous ECMO for Acute Respiratory Illness in Pediatric Berlin Heart Patient.

We report the unique case of a 2-year-old male with severe heart failure requiring mechanical circulatory support with a left ventricular assist device, who developed adenovirus pneumonitis infection requiring veno-venous extracorporeal membrane oxygenation (ECMO) support. He progressed to acute respiratory failure and refractory hypoxemia despite intubation with maximum respiratory support. The patient was placed on ECMO with improvement in lung function over four days with subsequent successful decannulation. During the ECMO run, anticoagulation required escalation given the increased circuit surface area. Patient has since recovered and undergone heart transplantation.