Search

Background. Our knowledge regarding the epidemiology of pediatric cardiomyopathy is based on large national population studies reporting an annual incidence of 1 case per 100,000 children, with a higher incidence observed in infancy and among selected populations. The aim here is to document the epidemiology of pediatric cardiomyopathy in a Mediterranean population. Methods. Children younger than 18 years of age living on the Mediterranean island of Crete, Greece, who have been evaluated since the establishment of tertiary pediatric cardiology services (2002–2022) were included in this retrospective study. Results. A total of 40 children were included, corresponding to an average annual incidence of pediatric cardiomyopathy of 1.59 cases (95% CI: 1.4–2.3) and a prevalence of 26 cases per 100,000 children. In decreasing order of frequency, most cases corresponded to dilated (50%), followed by hypertrophic (42.5%), arrhythmogenic (5%), and restrictive (2.5%) cardiomyopathy. An etiology was identified in 40%, including a genetic diagnosis in 22.5%. Conclusions. The incidence of pediatric cardiomyopathy in the Mediterranean island of Crete is higher compared with that reported previously for other Caucasian populations. Further study is needed to investigate the exact prevalence and specific genetic factors associated with the epidemiology of pediatric cardiomyopathy in Mediterranean populations. [ABSTRACT FROM AUTHOR]

Background. Our knowledge regarding the epidemiology of pediatric cardiomyopathy is based on large national population studies reporting an annual incidence of 1 case per 100,000 children, with a higher incidence observed in infancy and among selected populations. The aim here is to document the epidemiology of pediatric cardiomyopathy in a Mediterranean population. Methods. Children younger than 18 years of age living on the Mediterranean island of Crete, Greece, who have been evaluated since the establishment of tertiary pediatric cardiology services (2002–2022) were included in this retrospective study. Results. A total of 40 children were included, corresponding to an average annual incidence of pediatric cardiomyopathy of 1.59 cases (95% CI: 1.4–2.3) and a prevalence of 26 cases per 100,000 children. In decreasing order of frequency, most cases corresponded to dilated (50%), followed by hypertrophic (42.5%), arrhythmogenic (5%), and restrictive (2.5%) cardiomyopathy. An etiology was identified in 40%, including a genetic diagnosis in 22.5%. Conclusions. The incidence of pediatric cardiomyopathy in the Mediterranean island of Crete is higher compared with that reported previously for other Caucasian populations. Further study is needed to investigate the exact prevalence and specific genetic factors associated with the epidemiology of pediatric cardiomyopathy in Mediterranean populations.

Cardiomyopathies are a heterogeneous group of myocardial diseases representing the first cause of heart transplantation in children. Diagnosing and classifying the different phenotypes can be challenging, particularly in this age group, where cardiomyopathies are often overlooked until the onset of severe symptoms. Cardiovascular imaging is crucial in the diagnostic pathway, from screening to classification and follow-up assessment. Several imaging modalities have been proven to be helpful in this field, with echocardiography undoubtedly representing the first imaging approach due to its low cost, lack of radiation, and wide availability. However, particularly in this clinical context, echocardiography may not be able to differentiate from cardiomyopathies with similar phenotypes and is often complemented with cardiovascular magnetic resonance. The latter allows a radiation-free differentiation between different phenotypes with unique myocardial tissue characterization, thus identifying the presence and extent of myocardial fibrosis. Nuclear imaging and computed tomography have a complementary role, although they are less used in daily clinical practice due to the concern related to the use of radiation in pediatric patients. However, these modalities may have some advantages in evaluating children with cardiomyopathies. This paper aims to review the strengths and limitations of each imaging modality in evaluating pediatric patients with suspected or known cardiomyopathies. [ABSTRACT FROM AUTHOR]

Pediatric cardiomyopathies (CM) are rare and challenging to diagnose due to the complex and mixed phenotypes. With the advent of next-generation sequencing (NGS), variants in several genes associated with CM have been identified, such as Troponin C (TnC), encoded by the TNNC1 gene. De novo variants in TNNC1 have been associated with different types of CM, including dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). The American College of Medical Genetics and Genomics recently added TNNC1 to their recommended list of genes for reporting secondary findings. In this study, we report a de novo variant, c.100G > C (p.Gly34Arg) in the TNNC1 gene identified in three siblings with a diagnosis of severe DCM causing infant death for one of the siblings and stillbirth in the other two pregnancies. The identification of the same de novo variant in all affected siblings is suggestive of germline mosaicism in this family. [ABSTRACT FROM AUTHOR]

TAF1A , a gene encoding a TATA-box binding protein involved in ribosomal RNA synthesis, is a candidate gene for pediatric cardiomyopathy as biallelic TAF1A variants were reported in two families with affected individuals. Here, we report a third family with two siblings who presented with infantile restrictive cardiomyopathy and carried biallelic missense variants in TAF1A (NM_001201536.1:c.1021G>A p.(Gly341Arg) and c.781A>C p.(Thr261Pro)). Additional shared clinical features in the siblings included feeding intolerance, congenital leukoencephalopathy, ventriculomegaly and concern for primary immunodeficiency. The first-born sibling passed away at 6 months of age due to complications of hemophagocytic lymphohistiocytosis (HLH) whereas the second sibling underwent cardiac transplantation at 1 year of age and is currently well. We compare the clinical and molecular features of all the TAF1A associated cardiomyopathy cases. Our study adds evidence for the gene-disease association of TAF1A with autosomal recessive pediatric cardiomyopathy. [ABSTRACT FROM AUTHOR]

There are limited data that can explain the earlier penetrance and the different expressivity of pediatric cardiomyopathy (pCM) compared to adult-onset cardiomyopathy (aCM). In addition, the relationship between genotype and pCM results is poorly described. We compared the genotypes between a cohort of aCM and a cohort of pCM to propose hypotheses on the earlier penetrance and expressivity of pCM. Finally, we report how genetic testing was used to guide genetic counseling in pCM. 253 pCM (<18 years old) and 1466 aCM patients were sequenced on a panel of 67 cardiomyopathy genes. Risk factors for death and heart transplantation were analyzed. In pCM, the variant of interest (VOI) yield was 53.7 % including 24.2 % carrying two VOI. De novo variants represented 11 % of VOI in pCM and 50 % in restrictive pCM. An age at diagnosis younger than 1 year (HR = 2.07, p = 0.029), restrictive phenotype (HR = 2.87, p = 0.03) and the presence of two VOI (HR = 2.97, p = 0.001) were independent risk factors for death or heart transplantation. In comparison with aCM, pCM patients harbored more frequently two VOI (p = 0.02), or de novo variants (p = 4.10−13). In addition, the distribution of VOI was different in aCM and pCM. Genotyping of pCM improved genetic counseling in families and led to ten prenatal-diagnosis. Conclusions: Genetic testing provides clues for earlier penetrance of pCM. The presence of two VOI in children with CM is a risk factor for severe and early cardiac events. • Carrying 2 variants and an age of onset before 1 year old are risk factors associated with severe outcomes in pCM • pCM patients harbored a different spectrum of genes and variants compare to adult cardiomyopathies cohorts • A higher rate of patients carrying 2 or de novo variants, and specific genetic spectrum could explain pediatric onset of CM [ABSTRACT FROM AUTHOR]

Clinical genetic testing is increasingly being utilized to establish a molecular diagnosis to help manage children with cardiomyopathy and to assess the risk of cardiomyopathy among family members. However, as evidence and guidelines evolve, variant classification can change with the potential to impact counseling and family screening. The main purpose of this study was to investigate whether variants in cardiomyopathy genes previously interpreted by clinical genetic testing laboratories would be reclassified under current guidelines for the interpretation of sequence variants. In 211 children enrolled in the Pediatric Cardiomyopathy Registry, we compared the results of previous clinical genetic testing with the results of research testing in 37 cardiomyopathy genes. The mean time difference between initial testing and reinterpretation was 7 years. Using the 2015 American College of Medical Genetics and Genomics guidelines for the interpretation of sequence variants, we found that 18 % of the tested population had a change in variant classification. Ninety-two percent of the initial classifications were performed before the publication of the guidelines, with 82 % of reclassifications resulting in a variant downgrade. Most of these were changes from the pathogenic or likely pathogenic category to a variant of uncertain significance. Reclassification frequency was similar across types of cardiomyopathy. Our results highlight that a portion of variants get downgraded, and periodic reinterpretation of genetic testing results is necessary for all types of cardiomyopathy—particularly for variant interpretations prior to 2015. Importantly, variant reclassification has potential impact on the clinical management of at-risk patients. • Genetic variants from clinical genetic testing results can be reclassified. • Results older than 2015 or from racial/ethnic minorities should be verified. • Downgrading variants can have implications for clinical care. [ABSTRACT FROM AUTHOR]

OBJECTIVES This exploratory mixed-methods study explored the barriers to physical activity, daily physical activity and submaximal exercise capacity among children with and at risk for cardiomyopathy and children with atrial septal defects. METHODS The study followed a convergent parallel mixed methodology design. Semi-structured interviews explored physical activity barriers. Seven-day accelerometry assessed moderate-to-vigorous physical activity, and an intermittent cardiopulmonary exercise test measured submaximal exercise capacity. RESULTS Twenty children, including 5 with cardiomyopathy (n=2 females, 14.2 ± 2.7 years old), 7 who were genotype-positive phenotype-negative for cardiomyopathy (n=5 females, 10.6 ± 3.3 years old) and 8 with atrial septal defects (n=4 females, 9.4 ± 3.8 years old) were recruited. Children with cardiomyopathy reported disease-specific physical activity barriers, while children who were genotype-positive phenotype-negative perceived barriers related to lack of time, parent support or activity motivation. The average daily moderate-to-vigorous physical activity was less than the recommended 60-minutes/day (n=20, mean 48.1 ± 18.0 minutes). Children with cardiomyopathy participated a median of 141.2 [interquartile range (IQR): 98.8) minutes of light-intensity physical activity and a median of 55.6 (IQR: 34.6) minutes of moderate-to-vigorous physical activity. The average submaximal exercise capacity was low (n=16, 25.2 ± 5.7 mL/kg/min). Estimated submaximal exercise capacity, including metabolic equivalent (4.5 ± 3.1 METs), respiratory exchange ratio (median = 1.0, IQR: 0.09) and ratings of perceived exertion (median = 7, IQR: 5) at peak exercise suggest that children with cardiomyopathy appear to have the exercise capacity to participate in low-to-moderate intensity activities. CONCLUSIONS These novel data suggest that a diagnosis of cardiomyopathy may not preclude children from participating in a healthy, active lifestyle. However, they perceive disease-specific physical activity barriers and may require support to optimize their level of participation for optimal health.

There is wide variability in the timing of heart transplant (HTx) after pediatric VAD implant. While some centers wait months before listing for HTx, others accept donor heart offers within days of VAD surgery. We sought to determine if HTx within 30 days versus ≥ 30 after VAD impacts post-HTx outcomes. Children on VAD pre-HTx were extracted from the Pediatric Heart Transplant Study database. The primary endpoints were post-HTx length of hospital stay (LOS) and one-year survival. Confounding was addressed by propensity score weighting using inverse probability of treatment. Propensity scores were calculated based on age, blood type, primary cardiac diagnosis, decade, VAD type, and allosensitization status. A total of 1064 children underwent VAD prior to HTx between 2000 to 2018. Most underwent HTx ≥ 30 days post-VAD (70%). Infants made up 22% of both groups. Patients ≥ 12 years old were 42% of the < 30 days group and children 1 to 11 years comprised 47% of the ≥ 30 days group (p < 0.001). There was no difference in the prevalence of congenital heart disease vs. cardiomyopathy (p = 0.8) or high allosensitization status (p = 0.9) between groups. Post-HTx LOS was similar between groups (p = 0.11). One-year survival was lower in the < 30 days group (adjusted mortality HR 1.76, 95% CI 1.11-2.78, p = 0.016). A longer duration of VAD support prior to HTx is associated with a one-year survival benefit in children, although questions of patient complexity, post-VAD complications and the impact on causality remain. Additional studies using linked databases to understand these factors will be needed to fully assess the optimal timing for post-VAD HTx. [ABSTRACT FROM AUTHOR]

Cardiomyopathy is a risk factor for poor prognosis in pediatric patients with mitochondrial disease. However, other risk factors including genetic factors related to poor prognosis in mitochondrial disease has yet to be fully elucidated. Between January 2004 and September 2019, we enrolled 223 consecutive pediatric mitochondrial disease patients aged <18 years with a confirmed genetic diagnosis, including 114 with nuclear gene mutations, 89 patients with mitochondrial DNA (mtDNA) point mutations, 11 with mtDNA single large-scale deletions and 9 with chromosomal aberrations. Cardiomyopathy at baseline was observed in 46 patients (21%). Hazard ratios (HR) and 95% confidence intervals (CI) were calculated for all-cause mortality. Over a median follow-up of 36 months (12–77), there were 85 deaths (38%). The overall survival rate was significantly lower in patients with cardiomyopathy than in those without (p < 0.001, log-rank test). By multivariable analysis, left ventricular (LV) hypertrophy (HR = 4.6; 95% CI: 2.8–7.3), neonatal onset (HR = 2.9; 95% CI: 1.8–4.5) and chromosomal aberrations (HR = 2.9; 95% CI: 1.3–6.5) were independent predictors of all-cause mortality. Patients with LV hypertrophy with neonatal onset and/or chromosomal aberrations had higher mortality (100% in 21 patients) than those with LV hypertrophy alone (71% in 14 patients). In pediatric patients with mitochondrial disease, cardiomyopathy was common (21%) and was associated with increased mortality. LV hypertrophy, neonatal onset and chromosomal aberrations were independent predictors of all-cause mortality. Prognosis is particularly unfavorable if LV hypertrophy is combined with neonatal onset and/or chromosomal aberrations. • Cardiomyopathy is related to poor prognosis in pediatric mitochondrial disease patients. • However, other risk factors including genetic factors related to poor prognosis has yet to be fully elucidated. • We assessed the prognosis and genetic background of cardiomyopathy in 223 pediatric mitochondrial disease patients. • Cardiomyopathy was common (22%) and was associated with increased mortality. • Left ventricular (LV) hypertrophy, neonatal onset and chromosomal aberrations were independent predictors of mortality. • Prognosis is particularly unfavorable if LV hypertrophy is combined with neonatal onset and/or chromosomal aberrations. [ABSTRACT FROM AUTHOR]

Pediatric patients on the waiting list for heart transplantation incur the highest risk of death for any organ transplantation. Berlin Heart EXCOR provides a reliable support as a bridge to heart transplantation or recovery for all pediatric age groups. We report the first successful experience of Berlin Heart EXCOR mechanical circulatory support and heart transplantation in pediatric patients in Saudi Arabia. The purpose of this report is to highlight the clinical events and share lessons learned from this endeavor. [ABSTRACT FROM AUTHOR]

Endomyocardial biopsy (EMB) is a well-known diagnostic tool for the investigation and treatment of myocardial diseases and remains the gold standard for the diagnosis of myocarditis. Due to its invasiveness, with a complication rate ranging from 1 to 15%, its role in the diagnostic work-up of pediatric heart failure is not well established. The aim of this review is to define the role of EMB as diagnostic technique in the work up of children presenting with severe left ventricular dysfunction with the support of our center experience.

The ACMG/AMP variant classification framework was intended for highly penetrant Mendelian conditions. While it is appreciated that clinically relevant variants exhibit a wide spectrum of penetrance, accurately assessing and expressing the pathogenicity of variants with lower penetrance can be challenging. The vinculin (VCL) gene illustrates these challenges. Model organism data provide evidence that loss of function of VCL may play a role in cardiomyopathy and aggregate case‐control studies suggest low penetrance. VCL loss of function variants, however, are rarely identified in affected probands and therefore there is a paucity of family studies clarifying the clinical significance of individual variants. This study, which aggregated data from >18,000 individuals who underwent gene panel or exome testing for inherited cardiomyopathies, identified 32 probands with VCL loss‐of‐function variants and confirmed enrichment in probands with dilated cardiomyopathy (odds ratio [OR] = 9.01; confidence interval [CI] = 4.93–16.45). Our data revealed that the majority of these individuals (89.5%) had pediatric onset of disease. Family studies demonstrated that heterozygous loss of function of VCL alone is insufficient to cause cardiomyopathy but that these variants do contribute to disease risk. In conclusion, VCL loss‐of‐function variants should be reported in a diagnostic setting but need to be clearly distinguished as having lower penetrance. [ABSTRACT FROM AUTHOR]

Aim: The aim of the study was to assess predictors of outcome in patients hospitalized for dilated cardiomyopathy (DCM) and severe left ventricular dysfunction. Patients & methods: 83 pediatric patients hospitalized for heart failure due to DCM with coexistent left ventricular dysfunction were enrolled.Results: Overall, 5-year survival free from heart transplantation was 69.8%. Normalization of left ventricular function was achieved in 39.8% of patients during follow-up: younger age, less necessity of inotropic support and other than idiopathic DCM predicted left ventricular function, while familial history for cardiac disease or sudden death and inotropic support during hospitalization were associated with poorer outcome.Conclusion: Almost 40% of patients with DCM experienced a complete normalization of cardiac function. Outcome was extremely variable according to the type of DCM. [ABSTRACT FROM AUTHOR]

Successful therapy in a cohort with early onset Danon disease (DD) highlights the potential importance of earlier disease recognition. We present experience from the largest National Pediatric Center in Russia for cardiomyopathy patients. This report focuses on identification of early clinical features of DD in the pediatric population by detailed pedigree analysis and review of medical records. Nine patients (3 females) were identified with DD at the Russian National Medical Research Center of Children's Health ("National Pediatric Center") aged birth to 16 years. At presentation/evaluation: all patients had left ventricular hypertrophy (LVH), ECG features of Wolff-Parkinson-White (WPW), and an increase in hepatic enzymes (particularly lactate dehydrogenase (LDH)); three had marked increase in NT-proBNP; two had HCM with impaired LV function; one had LVH with LV noncompaction; five had arrhythmia with paroxysmal supraventricular and/or ventricular tachycardia. Two teenagers died at ages 16–17 from refractory heart failure and two underwent heart transplantation. All patients were found to have a pathogenic/likely pathogenic variant in the LAMP2 gene, six patients had no family history and a de novo evolvement was documented in 4/6 of those available for genetic tested. Retrospective review related to family background and earlier clinical evaluations revealed a definitive or highly suspicious family history of DD in 3, early clinical presentation with cardiac abnormalities (ECG, echo) in 3, and cerebral, hepatic and/or neuromuscular symptoms in 5. Abnormalities were detected 9,5 months to 5,8 years, median 3,5 years prior to referral to the National Pediatric Center. The earliest clinical manifestations of Danon disease occur in the first 12 years of life with symptoms of skeletal muscle and cerebral disease, raised hepatic enzymes, and evidence of cardiac disease on ECG/echo. • Danon disease develops in patients of both sexes, despite the X-linked variant of inheritance. • Pediatric red flags for early diagnosis are: intracellular enzyme elevation in blood tests which are associated with Wolff-Parkinson-White-like patterns on ECG and myocardial hypertrophy. • The positive Phase 1 study results of Danon gene therapy treatment makes early diagnosis in children particularly important and might help to avoid the typically rapid progression of Danon disease that leads to patients requiring heart transplantation. [ABSTRACT FROM AUTHOR]

Pediatric cardiomyopathies are rare. The disease can be a chronic, debilitating illness and is often progressive. There are many unknowns related to the heritability of cardiomyopathy, acute risks of disease, disease progression, and treatment efficacy that are unique to this population. These disease-related confounders may be important determinants of quality of life for PCM patients and families. Few studies have evaluated health-related quality of life and its determinants in pediatric cardiomyopathy patients. In this review, we will describe the epidemiology and natural history of pediatric cardiomyopathy and outcomes in these patients. We will highlight the clinical and scientific utility of health-related quality of life assessments in pediatric patients with cardiomyopathy and describe the screening tools that are currently in use and their potential roles in improving outcomes in pediatric patients living with cardiomyopathy. Finally, we will suggest potential, disease specific, modifiers of health-related quality of life in pediatric cardiomyopathy patients that may serve as a focus for clinical care and future research endpoints. [ABSTRACT FROM AUTHOR]

Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a heritable cardiomyopathy characterized by fibro-fatty replacement of right ventricular myocardium. Diagnostic criteria, established in 1994 and modified in 2010, are based on predominately adult manifestations of ARVC/D. The goal of this paper is to review a single-center experience with pediatric ARVC/D and propose modifications of current diagnostic criteria to appropriately include pediatric ARVC/D. We identified 16 pediatric cases of ARVC/D from our tertiary care center. Patient demographics, presentation, course, genetic testing, and family history were reviewed. Sixteen patients were diagnosed with ARVC/D through the modified diagnostic criteria, genetic testing, and pathology. Five patients had positive family histories. Five patients presented with cardiac arrest, and six were found to have ventricular tachycardia. Two patients presented with heart failure. Six autopsies, six explanted hearts, and three biopsies found massive fibro-fatty infiltration of the right ventricular wall. Six patients underwent heart transplantation, and two have received automatic implantable cardioverter defibrillator. Two patients had identifiable genetic mutations previously noted in the literature. One patient had a novel mutation of a known ARVC/D gene. Many pediatric patients do not meet the current ARVC/D diagnostic criteria, resulting in delays in diagnosis and treatment. The current criteria need further revision to encompass pediatric manifestations of ARVC/D. In our opinion, pathological and clinical findings alone are sufficient for accurate diagnosis of pediatric ARVC/D. Creating modified pediatric criteria would facilitate prompt diagnosis and management of ARVC/D and facilitate structured research with the goal of improving outcomes. [ABSTRACT FROM AUTHOR]

Cardiomyopathy is the leading diagnosis for pediatric heart transplantation in children over 1 year of age. The majority of these patients usually have dilated cardiomyopathy. Children with hypertrophic and restrictive types of cardiomyopathy comprise less than 20% of the total children transplanted. Hypertrophic cardiomyopathy is the smallest subgroup to receive a cardiac transplant (6%). The mean age at listing in the Pediatric Heart Transplant Study (PHTS) was 7.6 years; however, 39% were infants listed at a mean of 3.2 ± 2.8 months of age. A patient with hypertrophic cardiomyopathy older than 1 year had low waitlist mortality and survival after transplant was no different than dilated or non-cardiomyopathy patients. The infant subgroup had the poorest overall survival with waitlist mortality of 33%, within a few months after listing. Restrictive cardiomyopathy is the rarest type of cardiomyopathy (2–5%) but accounts for 11% of children transplanted with cardiomyopathy in PHTS. Survival after listing in infants < 1 year of age with either hypertrophic or restrictive cardiomyopathy was poor, 50% at 1 year compared with 80% in infants with dilated cardiomyopathy. The mean age at listing for restrictive patients in PHTS was 8.1 years, 81% were transplanted and 9% died waiting (40% of pre-transplant deaths were infants < 1 year). The 1 and 5 year survival was 89 and 77%, similar to other cardiomyopathy patients and better than non-cardiomyopathy patients. Risk factors and clinical profiles leading to listing are discussed. [ABSTRACT FROM AUTHOR]

Ventricular assist device ( VAD) support induces reverse remodeling of failing myocardium that leads to occasional functional recovery of the adult heart. While there have been numerous clinical reports in adult patients with end-stage cardiomyopathy, little is known about reverse remodeling in children, which has increasing clinical potential with the recent expansion of pediatric VADs in the setting of static organ supply for heart transplantation. Pediatric myocardium also promises theoretical advantages for recovery over adult myocardium due to its greater abundance of cardiac progenitor cells. To identify potential targets of future studies, we conducted a literature review with two aims: (i) to summarize clinical cases of pediatric patients who exhibited cardiac recovery following VAD support; and (ii) to analyze genetic changes in pediatric myocardium induced by VAD support compared with those observed in adult patients. Several clinical series of pediatric VAD cases report that small proportions of their cohorts were weaned off from device support, but a lack of information about the etiology and support duration of these patients limits the ability to determine whether they represent reverse remodeling of myocardial structure or just recovery from acute illness. A comparison of pediatric and adult gene expression changes with VAD support reveals approximately 40% of genes to be oppositely regulated, indicating that the pediatric genetic response is distinct. These observations highlight a necessity to better understand reverse remodeling specific to pediatric myocardium, which is crucial to improving clinical strategies for bridge-to-recovery in children. [ABSTRACT FROM AUTHOR]

Heart failure remains a significant contributor to morbidity and mortality in pediatric patients with congenital and acquired heart diseases. However, there are several new promising therapies for acute and chronic heart failures including the development of new pediatric specific ventricular assist devices. There remains a need for collaborative research including the creation of a large-scale registry of pediatric heart failure, increased utilization of genetic testing, and an improved understanding of the optimal model of disease management that maximizes quality care. [ABSTRACT FROM AUTHOR]

Cardiomyopathy (CM) in children shares some features with cardiomyopathy in adults but also has many important unique features. Heretofore, genetic testing panels, testing strategies, and treatment recommendations have largely been based on studies in adult populations. In general, CMs in children are much more likely to be genetic and to have extracardiac manifestations that should be medically addressed. Therefore, genetic testing in children with CM is an essential part of their initial evaluation and the ongoing care of the child and family. CMs in children are more genetically heterogeneous, and many of the genes that are rare causes of CM in children are not currently included in testing panels, and future genetic testing is likely to increasingly utilize more comprehensive approaches such as whole exome/whole genome sequencing with focused analysis of all the genes that can cause CM in children. [ABSTRACT FROM AUTHOR]

Coronary and congenital heart malformations contribute to and overlap with clinical cardiomyopathy. As cellular mechanisms and gene associations are better understood, overlap is becoming apparent between cardiomyopathies such as left ventricular non-compaction, hypertrophic cardiomyopathy and congenital heart disease. In current studies and registries, patients with clinical overlap are excluded limiting our understanding of the synergy of disease. We review contributing lesions and discuss genetic contributions to overlapping disease. [ABSTRACT FROM AUTHOR]

Abstract: Tremendous advances have been made in understanding the basic cellular mechanisms of hypertrophy and heart failure. Powerful new tools, such as targeted gene manipulation in the mouse, have provided great insight into the complex cross-talk between different signaling pathways regulating cardiac function and remodeling. New levels of complexity are being uncovered, e.g. regulation of gene expression by micro-RNAs and histone modification. However, many of the models used to study these processes may not accurately recapitulate the cardiac stresses experienced by patients with congenital heart disease. There has been a very "left ventricular-centric" bias in this field, whereas many congenital heart disease patients have abnormal hemodynamics affecting the right ventricle (e.g. tetralogy of Fallot, L-TGA, hypoplastic left heart). Developing a better understanding of the similarities and differences between left and right ventricular hypertrophy and failure will be critically important, as common therapeutics which are effective in left ventricular failure are often not effective in the failing right ventricle. [Copyright &y& Elsevier]

Abstract: Substantial numbers of children with cardiomyopathy are now surviving into adulthood, making it essentially a chronic disease. As a chronic condition, it may be best treated through comprehensive, multidisciplinary treatment programs. Such programs have improved health outcomes and reduced costs in managing other pediatric chronic diseases and heart failure in adults, but the treatment and cost implications of programs for managing pediatric cardiomyopathy are unknown. We investigated the treatment and cost implications of establishing such programs by reviewing cost-effectiveness studies of similar programs, estimating the current inpatient costs of this diagnosis, and interviewing experts in the field about the need and desirability of these programs. According to our findings, comprehensive pediatric heart failure programs do exist, but they have not been evaluated or even described in the literature. Consensus among experts in the field is that comprehensive chronic care programs are highly desirable, and similar programs have reported tremendous cost savings through early and intensive management: the return on investment has been as high as 22 to 1. Another study reported that mean length of stay decreased from 83.9 to 10.6 days, mean annual admissions decreased from 2796 to 1622, and median hospital charges decreased from $26.1 million to $14.6 million. In conclusion, limited experience and strong circumstantial evidence suggest that, despite substantial costs, comprehensive multidisciplinary pediatric heart failure programs would be cost-effective and beneficial to patients, families, and institutions alike. [Copyright &y& Elsevier]

Abstract: Pediatric cardiomyopathies are heterogeneous groups of serious disorders of the heart muscle and are responsible for significant morbidity and mortality among children who have the disease. While enormous improvements have been made in the treatment and survival of children with congenital heart disease, parallel strides have not been made in the outcomes for cardiomyopathies. Thus, ancillary therapies, such as nutrition and nutritional interventions, that may not cure but may potentially improve cardiac function and quality of life, are imperative to consider in children with all types of cardiomyopathy. Growth failure is one of the most significant clinical problems of children with cardiomyopathy with nearly one-third of children with this disorder manifesting some degree of growth failure during the course of their illness. Optimal intake of macronutrients can help improve cardiac function. In addition, several specific nutrients have been shown to correct myocardial abnormalities that often occur with cardiomyopathy and heart failure. In particular, antioxidants that can protect against free radical damage that often occurs in heart failure and nutrients that augment myocardial energy production are important therapies that have been explored more in adults with cardiomyopathy than in the pediatric population. Future research directions should pay particular attention to the effect of overall nutrition and specific nutritional therapies on clinical outcomes and quality of life in children with pediatric cardiomyopathy. [Copyright &y& Elsevier]

Abstract: Although there has been substantial progress in the treatment of cardiomyopathy in children, the field is still evolving and many of the important aspects of cardiomyopathy care remain uncertain. As a result of this uncertainty, parents and health care professionals are often faced with difficult decisions that raise serious ethical concerns. We identify and discuss some of these challenges within the framework of ethics and medical decision making. We address several common issues: (1) Who makes decisions in the case of children and adolescents with cardiomyopathy, and how are these made? (2) How should the effect of a treatment be weighed against consideration of the impact of the treatment on the child''s quality of life? (3) How should the limitations of treatment effectiveness and the impact on scarce resources be addressed in children with cardiomyopathy, and (4) What is the role of a pediatric bioethics committee in facilitating decision-making related to cardiomyopathy in children? The patient''s health care team must be able to identify and address the ethical considerations that arise in the setting of a child with a disease that has a high risk of progressing towards transplant and possibly an early death. Physicians and other health care professionals who care for children with pediatric cardiomyopathy often face questions related to deciding who should be involved with medical decision making, balancing acute physiologic benefits with considerations of the patient''s quality of life and understanding how the concept of futility applies in an otherwise aggressive treatment setting. To aid clinicians with these challenges, we discuss the role of an ethics consultation in the management process of a child with cardiomyopathy. [Copyright &y& Elsevier]

Summary: Pediatric cardiomyopathy (PCM) represents a group of rare and heterogeneous disorders that often results in death. While there is a large body of literature on adult cardiomyopathy, all of the information is not necessarily relevant to children with PCM. About 40% of children who present with symptomatic cardiomyopathy are reported to receive a heart transplant or die within the first two years of life. In spite of some of the advances in the management of PCM, the data shows that the time to transplantation or death has not improved during the past 35 years. Coenzyme Q10 is a vitamin-like nutrient that has a fundamental role in mitochondrial function, especially as it relates to the production of energy (ATP) and also as an antioxidant. Based upon the biochemical rationale and a large body of data on patients with adult cardiomyopathy, heart failure, and mitochondrial diseases with heart involvement, a role for coenzyme Q10 therapy in PCM patients is indicated, and preliminary results are promising. Additional studies on the potential usefulness of coenzyme Q10 supplementation as an adjunct to conventional therapy in PCM, particularly in children with dilated cardiomyopathy, are therefore warranted. [Copyright &y& Elsevier]

Endomyocardial biopsy (EMB) is a well-known diagnostic tool for the investigation and treatment of myocardial diseases and remains the gold standard for the diagnosis of myocarditis. Due to its invasiveness, with a complication rate ranging from 1 to 15%, its role in the diagnostic work-up of pediatric heart failure is not well established. The aim of this review is to define the role of EMB as diagnostic technique in the work up of children presenting with severe left ventricular dysfunction with the support of our center experience.

This article summarizes the non-sarcomere genes that result in hypertrophic cardiomyopathy that may present in childhood. While some of these forms of hypertrophic cardiomyopathy are quite rare, they are important to recognize and consider when providing genetic testing for early onset hypertrophic cardiomyopathy disease. Notably, some of these conditions have specific treatments. This review will allow pediatric cardiomyopathy specialists to consider a broad range of genetic mutations that lead to pediatric onset hypertrophic cardiomyopathy. • WediscussePediatric Hypertrophic Cardiomyopathy withnon-sarcomere gene mutations including the following conditions: Glycogen storage disease • Lysosomal (LAMP) disease • Anderson Fabry disease • Pompe Disease • RASopathy mediated hypertrophic cardiomyopathy [ABSTRACT FROM AUTHOR]

Pediatric-onset cardiomyopathies are rare yet cause significant morbidity and mortality in affected children. Genetic testing has a major role in the clinical evaluation of pediatric-onset cardiomyopathies, and identification of a variant in an associated gene can be used to confirm the clinical diagnosis and exclude syndromic causes that may warrant different treatment strategies. Further, risk-predictive testing of first-degree relatives can assess who is at-risk of disease and requires continued clinical follow-up. In this review, we seek to describe the current role of genetic testing in the clinical diagnosis and management of patients and families with the five major cardiomyopathies. Further, we highlight the ongoing development of precision-based approaches to diagnosis, prognosis, and treatment. Emerging application of genotype-phenotype correlations opens the door for genetics to guide a precision medicine-based approach to prognosis and potentially for therapies. Despite advances in our understanding of the genetic etiology of cardiomyopathy and increased accessibility of clinical genetic testing, not all pediatric cardiomyopathy patients have a clear genetic explanation for their disease. Expanded genomic studies are needed to understand the cause of disease in these patients, improve variant classification and genotype-driven prognostic predictions, and ultimately develop truly disease-preventing treatment. • Genetic testing is a key component of the diagnostic evaluation of pediatric cardiomyopathy. • Risk-predictive genetic testing of a variant found in a proband can identify at-risk family members. • Genotype-phenotype correlations illustrate the potential for genetic testing to inform prognosis. • Understanding genomic drivers opens the door to a precision medicine-based approach to care. [ABSTRACT FROM AUTHOR]

A rare case of a 6-year-old male with idiopathic familial cardiomyopathy manifesting severely restrictive physiology is reported. The patient showed congestive heart failure with dilatation of both atria with a normal ventricular cavity. A square-root configuration was revealed in the ventricular pressure tracings. His elder brother had died of hypertrophic cardiomyopathy at the age of 3 years. Endomyocardial biopsy disclosed marked disorganization of muscle bundles with hypertrophy of the myocytes and interstitial fibrosis. The patient died suddenly during hospitalization. Autopsy revealed diffuse hypertrophy of both the ventricular walls and the ventricular septum with extensive myocardial disorganization and interstitial fibrosis. These advanced myopathic changes in the myocardium may have been related to the restrictive physiology in this case. [ABSTRACT FROM AUTHOR]

Introduction: Sudden cardiac death (SCD) and early onset cardiomyopathy (CM) in the young will always lead to suspicion of an underlying genetic disorder. Incited by the rapid advances in genetic testing for disease we have revisited families, which previously tested "gene-negative" for familial predominantly pediatric CM, in hopes of finding a causative gene variant. Methods: 10 different families with non-syndromic pediatric CM or hypertrophic cardiomyopathy (HCM) with severe disease progression and/or heredity for HCM/CM related SCD with "gene-negative" results were included. The index patient underwent genetic testing with a recently updated gene panel for CM and SCD. In case of failure to detect a pathogenic variant in a relevant gene, the index patient and both parents underwent clinical (i.e., partial) exome sequencing (trio-exome) in order to catch pathogenic variants linked to the disease in genes that were not included in the CM panel. Results: The mean age at clinical presentation of the 10 index cases was 12.5 years (boys 13.4 years, n = 8; girls 9 years, n = 2) and the family history burden was 33 HCM/CM cases including 9 HCM-related SCD and one heart transplantation. In 5 (50%) families we identified a genetic variant classified as pathogenic or likely pathogenic, in accordance with the American College of Medical Genetics and Genomics (ACMG) criteria, in MYH7 (n = 2), RBM20, ALPK3, and PGM1, respectively, and genetic variants of unknown significance (VUS) segregating with the disease in an additional 3 (30%) families, in MYBPC3, ABCC9, and FLNC, respectively. Conclusion: Our results show the importance of renewed thorough clinical assessment and the necessity to challenge previous genetic test results with more comprehensive updated gene panels or exome sequencing if the initial test failed to identify a causative gene for early onset CM or SCD in children. In pediatric cardiomyopathy cases when the gene panel still fails to detect a causative variant, a trio exome sequencing strategy might resolve some unexplained cases, especially if a multisystemic condition is clinically missed. [ABSTRACT FROM AUTHOR]

A 17-year-old boy with a history of dyspnea attacks and chest pain was referred to our paediatric cardiology department. Electrocardiogram at presentation showed T-wave inversion in the inferior leads. Cardiovascular magnetic resonance imaging revealed the rare diagnosis of apical hypertrophic cardiomyopathy with subendocardial late gadolinium enhancement, missed by echocardiography.

Cardiomyopathy (CMP) constitutes a group of diseases of heart muscle that lead to significant mortality and morbidity, with limited data in Africa. This study aims to describe clinical and echocardiographic (echo) patterns and short-term outcomes of Pediatric CMP. The study was carried at Gaafar Ibnauf Children's Hospital and included all children 0-18 years with an echo diagnosis of CMP. A retrospective part of the study was carried from January 2013 to 2019 and a prospective part from January to June 2019. Clinical and echo data were collected on presentation and on at least one follow up. A total of 146 patients were diagnosed with CMP during the study period. Most patients (48%) presented at 1-6 years of age, neonatal CMP was present in 4%. Familial incidence was detected in 11% of cases. Heart failure was the most common mode of presentation in 96% of patients; 65% needed hospitalisation; a third of them needed intensive care unit admission. The most common type of CMP was the dilated type (67%). Others included noncompaction CMP (19%), restrictive CMP and hypertrophic CMP (each of them in 6% of patients). Hospital mortality was 20% for the whole cohort and 100% for neonates. Other complications occurred in 21% of patients including arrhythmias, cerebrovascular accidents and end stage renal disease. Echo follow up showed that most patients (52%) remained the same, 26% worsened and 21% improved. Genetic and metabolic studies that could help to improve management and outcomes of CMP are needed., (Copyright © Sudanese Association of Pediatricians.)

The systematic development of early age talent in sports academies has led to the professionalization of pediatric sport and the sports physician need to be aware of pediatric cardiological problems. Research into the medical cardiac care and assessment of the pediatric athlete are accumulating, but specific pediatric international guidelines are not available yet and reference data for ECG and echocardiography are incomplete, in particular for the age group <12 years of age. This article is an introduction to the physiological and diagnostics specifics of the pediatric athlete. The focus lies in the differences in presentation and diagnosis between pediatric and adult athletes for the most common pathologies. Reference data for electrical and structural adaptations to intensive exercise are sparse particularly in athletes aged below 12 years old. Training related changes include decrease of resting heart rate, increase of cardiac output, ventricular cavity size, and wall thickness. Cardiac hypertrophy is less pronounced in pediatric athletes, as HR mediated cardiac output increase to endurance exercise is the dominant mechanism in peripubertal children. As in adults, the most pronounced cardiovascular adaptations appear in classical endurance sports like rowing, triathlon, and swimming, but the specifics of pediatric ECG and echocardiographic changes need to be considered., (© 2020 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

Abstract: Pediatric cardiomyopathies are extremely heterogeneous in etiology and are thus associated with variability in prognosis and response to therapy. With increasing availability of clinical diagnostic tools and research methods to molecularly characterize genetic forms of cardiomyopathy and identify viral pathogens in myocarditis, we have the opportunity to define pediatric cardiomyopathies by molecular subtype and characterize the natural history of each subtype. By understanding the natural histories of the subtypes of pediatric cardiomyopathies, we can develop biomarkers for early stages of diseases and disease progression, and lay the foundations necessary for future clinical trials for treatment and primary prevention. [Copyright &y& Elsevier]

Setting: In adults with cardiomyopathy, tissue Doppler imaging (TDI) has been shown to correlate with left ventricular filling pressures (LVFPs) and has been advocated as a surrogate to catheterization. However, this has not been validated in children., Design: This is a retrospective review of children ≤18 years old with dilated, hypertrophic, restrictive, and left ventricular noncompaction cardiomyopathy who underwent cardiac catheterization within 3 months of an echocardiogram. Spearman's correlation coefficients were calculated to assess a correlation between LVFP and mitral inflow E/A ratio, lateral mitral E/E', and septal E/E'., Results: Thirty-eight patients were included in the study; median age was 8.6 years old. The median LVFP was 19 mm Hg, median mean pulmonary artery pressure was 25 mm Hg, and median pulmonary vascular resistance index (PVRi) was 2.4 Wu. There was no significant correlation between LVFP or PVRi with lateral mitral E/E' or septal E/E'. There was a positive correlation between LVFP and mitral inflow E/A ratio (rs = 0.59, P < .01). In a subgroup analysis of patients with hypertrophic or restrictive cardiomyopathy, there was a negative correlation (rs = 0.56, P = .02) between the mean pulmonary artery pressure and septal A'., Conclusions: TDI measures of diastolic function are not reliable surrogates for LVFP, mean pulmonary artery pressures, and PVRi at catheterization in children., (© 2015 Wiley Periodicals, Inc.)