In this scientific statement from the American Heart Association, experts in the field of cardiomyopathy (heart muscle disease) in children address 2 issues: the most current understanding of the ...causes of cardiomyopathy in children and the optimal approaches to diagnosis cardiomyopathy in children. Cardiomyopathies result in some of the worst pediatric cardiology outcomes; nearly 40% of children who present with symptomatic cardiomyopathy undergo a heart transplantation or die within the first 2 years after diagnosis. The percentage of children with cardiomyopathy who underwent a heart transplantation has not declined over the past 10 years, and cardiomyopathy remains the leading cause of transplantation for children >1 year of age. Studies from the National Heart, Lung, and Blood Institute-funded Pediatric Cardiomyopathy Registry have shown that causes are established in very few children with cardiomyopathy, yet genetic causes are likely to be present in most. The incidence of pediatric cardiomyopathy is ≈1 per 100 000 children. This is comparable to the incidence of such childhood cancers as lymphoma, Wilms tumor, and neuroblastoma. However, the published research and scientific conferences focused on pediatric cardiomyopathy are sparcer than for those cancers. The aim of the statement is to focus on the diagnosis and classification of cardiomyopathy. We anticipate that this report will help shape the future research priorities in this set of diseases to achieve earlier diagnosis, improved clinical outcomes, and better quality of life for these children and their families.
Basic fluid dynamic principles were used to derive a theoretical model of optimum cardiovascular allometry, the relationship between somatic and cardiovascular growth. The validity of the predicted ...models was then tested against the size of 22 cardiovascular structures measured echocardiographically in 496 normal children aged 1 day to 20 yr, including valves, pulmonary arteries, aorta and aortic branches, pulmonary veins, and left ventricular volume. Body surface area (BSA) was found to be a more important determinant of the size of each of the cardiovascular structures than age, height, or weight alone. The observed vascular and valvar dimensions were in agreement with values predicted from the theoretical models. Vascular and valve diameters related linearly to the square root of BSA, whereas valve and vascular areas related to BSA. The relationship between left ventricular volume and body size fit a complex model predicted by the nonlinear decrease of heart rate with growth. Overall, the relationship between cardiac output and body size is the fundamental driving factor in cardiovascular allometry.
Pediatric Cardiomyopathies Lee, Teresa M; Hsu, Daphne T; Kantor, Paul ...
Circulation research,
2017-September-15, Volume:
121, Issue:
7
Journal Article
Peer reviewed
Open access
Pediatric cardiomyopathies are rare diseases with an annual incidence of 1.1 to 1.5 per 100 000. Dilated and hypertrophic cardiomyopathies are the most common; restrictive, noncompaction, and mixed ...cardiomyopathies occur infrequently; and arrhythmogenic right ventricular cardiomyopathy is rare. Pediatric cardiomyopathies can result from coronary artery abnormalities, tachyarrhythmias, exposure to infection or toxins, or secondary to other underlying disorders. Increasingly, the importance of genetic mutations in the pathogenesis of isolated or syndromic pediatric cardiomyopathies is becoming apparent. Pediatric cardiomyopathies often occur in the absence of comorbidities, such as atherosclerosis, hypertension, renal dysfunction, and diabetes mellitus; as a result, they offer insights into the primary pathogenesis of myocardial dysfunction. Large international registries have characterized the epidemiology, cause, and outcomes of pediatric cardiomyopathies. Although adult and pediatric cardiomyopathies have similar morphological and clinical manifestations, their outcomes differ significantly. Within 2 years of presentation, normalization of function occurs in 20% of children with dilated cardiomyopathy, and 40% die or undergo transplantation. Infants with hypertrophic cardiomyopathy have a 2-year mortality of 30%, whereas death is rare in older children. Sudden death is rare. Molecular evidence indicates that gene expression differs between adult and pediatric cardiomyopathies, suggesting that treatment response may differ as well. Clinical trials to support evidence-based treatments and the development of disease-specific therapies for pediatric cardiomyopathies are in their infancy. This compendium summarizes current knowledge of the genetic and molecular origins, clinical course, and outcomes of the most common phenotypic presentations of pediatric cardiomyopathies and highlights key areas where additional research is required.
URL: http://www.clinicaltrials.gov. Unique identifiers: NCT02549664 and NCT01912534.
Abstract Background Multicenter longitudinal objective data for survival into adulthood of patients who have undergone Fontan procedures are lacking. Objectives This study sought to describe ...transplant-free survival and explore relationships between laboratory measures of ventricular performance and functional status over time. Methods Exercise testing, echocardiography, B-type natriuretic peptide, functional health assessment, and medical history abstraction were repeated 9.4 ± 0.4 years after the Fontan Cross-Sectional Study (Fontan 1) and compared with previous values. Cox regression analysis explored risk factors for interim death or cardiac transplantation. Results From the original cohort of 546 subjects, 466 were contacted again, and 373 (80%) were enrolled at 21.2 ± 3.5 years of age. Among subjects with paired testing, the percent predicted maximum oxygen uptake decreased (69 ± 14% vs. 61 ± 16%; p < 0.001; n = 95), ejection fraction decreased (58 ± 11% vs. 55 ± 10%; p < 0.001; n = 259), and B-type natriuretic peptide increased (median interquartile range 13 7 to 25 pg/mol vs. 18 9 to 36 pg/mol; p < 0.001; n = 340). At latest follow-up, a lower Pediatric Quality of Life Inventory physical summary score was associated with poorer exercise performance (R2 adjusted = 0.20; p < 0.001; n = 274). Cumulative complications since the Fontan procedure included additional cardiac surgery (32%), catheter intervention (62%), arrhythmia treatment (32%), thrombosis (12%), and protein-losing enteropathy (8%). Since Fontan 1, 54 subjects (10%) have received a heart transplant (n = 23) or died without transplantation (n = 31). The interval risk of death or/cardiac transplantation was associated with poorer ventricular performance and functional health status assessed at Fontan 1, but it was not associated with ventricular morphology, the subject’s age, or the type of Fontan connection. Conclusions Interim transplant-free survival over 12 years in this Fontan cohort was 90% and was independent of ventricular morphology. Exercise performance decreased and was associated with worse functional health status. Future interventions might focus on preserving exercise capacity. (Relationship Between Functional Health Status and Ventricular Performance After Fontan—Pediatric Heart Network; NCT00132782 )
Abstract Background 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. Methods and Results 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. Conclusions 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.
A Cross-Sectional Study of Exercise Performance During the First 2 Decades of Life After the Fontan Operation Stephen M. Paridon, Paul D. Mitchell, Steven D. Colan, Richard V. Williams, Andrew ...Blaufox, Jennifer S. Li, Renee Margossian, Seema Mital, Jennifer Russell, Jonathan Rhodes, for the Pediatric Heart Network Investigators Exercise testing in a large group of Fontan survivors was performed, and clinical factors influencing exercise performance were assessed. Ramp cycle ergometry with metabolic cart measurements was performed on 411 subjects (mean age 12.4 ± 3.2 years). Peak oxygen consumption (VO2 ) was decreased at 65% of predicted for age and gender. Peak VO2 at ventilatory anaerobic threshold was better preserved at 78% of predicted than peak VO2 . Higher O2 pulse was associated with better exercise performance.
Cancer diagnostics and therapies have improved steadily over the last few decades, markedly increasing life expectancy for patients at all ages. However, conventional and newer anti-neoplastic ...therapies can cause short- and long-term cardiotoxicity. The clinical implications of this cardiotoxicity become more important with the increasing use of cardiotoxic drugs. The implications are especially serious among patients predisposed to adverse cardiac effects, such as youth, the elderly, those with cardiovascular comorbidities, and those receiving additional chemotherapies or thoracic radiation. However, the optimal strategy for preventing and managing chemotherapy-induced cardiotoxicity remains unknown. The routine use of neurohormonal antagonists for cardioprotection is not currently justified, given the marginal benefits and associated adverse events, particularly with long-term use. The only United States Food and Drug Administration and European Medicines Agency approved treatment for preventing anthracycline-related cardiomyopathy is dexrazoxane. We advocate administering dexrazoxane during cancer treatment to limit the cardiotoxic effects of anthracycline chemotherapy.
PDF
