Impact of Pulmonary Vascular Resistances in Heart Transplantation for Congenital Heart Disease

Congenital heart disease is one of the major diagnoses in pediatric heart transplantation recipients of all age groups. Assessment of pulmonary vascular resistance in these patients prior to transplantation is crucial to determine their candidacy, however, it is frequently inaccurate because of their abnormal anatomy and physiology. This problem places them at significant risk for pulmonary hypertension and right ventricular failure post transplantation. The pathophysiology of pulmonary vascular disease in children with congenital heart disease depends on their pulmonary blood flow patterns, systemic ventricle function, as well as semilunar valves and atrioventricular valves structure and function. In our review we analyze the pathophysiology of pulmonary vascular disease in children with congenital heart disease and end-stage heart failure, and outline the state of the art pre-transplantation medical and surgical management to achieve reverse remodeling of the pulmonary vasculature by using pulmonary vasodilators and mechanical circulatory support

Progressive left ventricular remodeling for predicting mortality in children with dilated cardiomyopathy: The Pediatric Cardiomyopathy Registry

BACKGROUND: Pediatric dilated cardiomyopathy often leads to death or cardiac transplantation. We sought to determine whether changes in left ventricular (LV) end-diastolic dimension (LVEDD), LV end-diastolic posterior wall thickness, and LV fractional shortening (LVFS) over time may help predict adverse outcomes. METHODS AND RESULTS: We studied children up to 18 years old with dilated cardiomyopathy, enrolled between 1990 and 2009 in the Pediatric Cardiomyopathy Registry. Changes in LVFS, LVEDD, LV end-diastolic posterior wall thickness, and the LV end-diastolic posterior wall thickness:LVEDD ratio between baseline and follow-up echocardiograms acquired ≈1 year after diagnosis were determined for children who, at the 1-year follow-up had died, received a heart transplant, or were alive and transplant-free. Within 1 year after diagnosis, 40 (5.0%) of the 794 eligible children had died, 117 (14.7%) had undergone cardiac transplantation, and 585 (73.7%) had survived without transplantation. At diagnosis, survivors had higher median LVFS and lower median LVEDD CONCLUSIONS: Progressive deterioration in LV contractile function and increasing LV dilation are associated with both early and continuing mortality in children with dilated cardiomyopathy. Serial echocardiographic monitoring of these children is therefore indicated. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00005391

Genetic causes of cardiomyopathy in children: First results from the Pediatric Cardiomyopathy Genes Study

Background Pediatric cardiomyopathy is a genetically heterogeneous disease with substantial morbidity and mortality. Current guidelines recommend genetic testing in children with hypertrophic, dilated, or restrictive cardiomyopathy, but practice variations exist. Robust data on clinical testing practices and diagnostic yield in children are lacking. This study aimed to identify the genetic causes of cardiomyopathy in children and to investigate clinical genetic testing practices. Methods and Results Children with familial or idiopathic cardiomyopathy were enrolled from 14 institutions in North America. Probands underwent exome sequencing. Rare sequence variants in 37 known cardiomyopathy genes were assessed for pathogenicity using consensus clinical interpretation guidelines. Of the 152 enrolled probands, 41% had a family history of cardiomyopathy. Of 81 (53%) who had undergone clinical genetic testing for cardiomyopathy before enrollment, 39 (48%) had a positive result. Genetic testing rates varied from 0% to 97% between sites. A positive family history and hypertrophic cardiomyopathy subtype were associated with increased likelihood of genetic testing

Mechanical Circulatory Support of the Critically Ill Child Awaiting Heart Transplantation

The majority of children awaiting heart transplantation require inotropic support, mechanical ventilation, and/or extracorporeal membrane oxygenation (ECMO) support. Unfortunately, due to the limited pool of organs, many of these children do not survive to transplant. Mechanical circulatory support of the failing heart in pediatrics is a new and rapidly developing field world-wide. It is utilized in children with acute congestive heart failure associated with congenital heart disease, cardiomyopathy, and myocarditis, both as a bridge to transplantation and as a bridge to myocardial recovery. The current arsenal of mechanical assist devices available for children is limited to ECMO, intra-aortic balloon counterpulsation, centrifugal pump ventricular assist devices, the DeBakey ventricular assist device Child; the Thoratec ventricular assist device; and the Berlin Heart. In the spring of 2004, five contracts were awarded by the National Heart, Lung and Blood Institute to support preclinical development for a range of pediatric ventricular assist devices and similar circulatory support systems. The support of early development efforts provided by this program is expected to yield several devices that will be ready for clinical trials within the next few years. Our work reviews the current international experience with mechanical circulatory support in children and summarizes our own experience since 2005 with the Berlin Heart, comparing the indications for use, length of support, and outcome between these modalities

Pediatric and adult dilated cardiomyopathy represent distinct pathological entities

Pediatric dilated cardiomyopathy (DCM) is the most common indication for heart transplantation in children. Despite similar genetic etiologies, medications routinely used in adult heart failure patients do not improve outcomes in the pediatric population. The mechanistic basis for these observations is unknown. We hypothesized that pediatric and adult DCM comprise distinct pathological entities, in that children do not undergo adverse remodeling, the target of adult heart failure therapies. To test this hypothesis, we examined LV specimens obtained from pediatric and adult donor controls and DCM patients. Consistent with the established pathophysiology of adult heart failure, adults with DCM displayed marked cardiomyocyte hypertrophy and myocardial fibrosis compared with donor controls. In contrast, pediatric DCM specimens demonstrated minimal cardiomyocyte hypertrophy and myocardial fibrosis compared with both age-matched controls and adults with DCM. Strikingly, RNA sequencing uncovered divergent gene expression profiles in pediatric and adult patients, including enrichment of transcripts associated with adverse remodeling and innate immune activation in adult DCM specimens. Collectively, these findings reveal that pediatric and adult DCM represent distinct pathological entities, provide a mechanistic basis to explain why children fail to respond to adult heart failure therapies, and suggest the need to develop new approaches for pediatric DCM

Human polyomaviruses in children undergoing transplantation, United States, 2008-2010

Immunocompromised patients are at risk for disease caused by infection by some polyomaviruses. To define the prevalence of polyomaviruses in children undergoing transplantation, we collected samples from a longitudinal cohort and tested for the 9 known human polyomaviruses. All were detected; several were present in previously unreported specimen types

Differences in Presentation and Outcomes between Children with Familial Dilated Cardiomyopathy and Children with Idiopathic Dilated Cardiomyopathy: A Report from the Pediatric Cardiomyopathy Registry Study Group

Research comparing the survival of children with familial dilated cardiomyopathy (FDCM) to that of children with idiopathic dilated cardiomyopathy (IDCM) has produced conflicting results

Improved outcomes of pediatric dilated cardiomyopathy with utilization of heart transplantation

AbstractObjectivesWe studied the outcomes of pediatric patients diagnosed with dilated cardiomyopathy (DCM) and their relation to epidemiologic and echocardiographic variables at the time of presentation.BackgroundThe outcome of pediatric DCM patients ranges from recovery to a 50% to 60% chance of death within five years of diagnosis. The impact of heart transplantation and other emerging therapies on the outcomes of pediatric DCM patients is uncertain.MethodsWe performed a retrospective study of the outcomes in 91 pediatric patients diagnosed with DCM from 1990 to 1999. Routine therapy included use of digoxin, diuretics, angiotensin-converting enzyme inhibitors, and heart transplantation.ResultsAt the time of last follow-up, 11 patients (12%) had died without transplantation; 20 (22%) underwent transplantation; 27 (30%) had persistent cardiomyopathy; and 33 (36%) had recovery of left ventricular systolic function. Overall actuarial one-year survival was 90%, and five-year survival was 83%. However, actuarial freedom from “heart death” (death or transplantation) was only 70% at one year and 58% at five years. Multivariate analysis found age <1 year (hazard ratio 7.1), age >12 years (hazard ratio 4.5), and female gender (hazard ratio 3.0) to be significantly associated with a greater risk of death or transplantation and a higher left ventricular shortening fraction at presentation (hazard ratio 0.92), with a slightly decreased risk of death or transplantation.ConclusionsPediatric DCM patients continue to have multiple outcomes, with recovery of left ventricular systolic function occurring most frequently. Utilization of heart transplantation has led to improved survival after the diagnosis of pediatric DCM