• Genetic landscape
• Heart transplantation
• Pediatric cardiomyopathy

• Humans
• Genetic Testing/methods
• Female
• Male
• Cardiomyopathies/genetics
• Cardiomyopathies/diagnosis
• Child
• Adolescent
• Cohort Studies
• Child, Preschool
• Infant
• Adult

• cardiomyocytes
• cardiovascular health
• echocardiography
• infantile dilated cardiomyopathy
• pathogenesis
• pediatric dilated cardiomyopathy
• pediatric heart failure

• R01 HL167133 NHLBI NIH HHS

• Cardiomyopathy
• Children
• Clinical characteristics
• Outcome
• Risk factor

• Child
• Humans
• Retrospective Studies
• Genetic Profile
• Cardiomyopathies/genetics
• Cardiomyopathy, Hypertrophic
• Cardiomyopathy, Restrictive/complications
• Cardiomyopathy, Restrictive/genetics
• Cardiomyopathy, Dilated/genetics

• 81974030 the National Natural Science Foundation of China
• NCRCCHD-2021-KP-01 the Key Grant from the National Clinical Research Center for Child Health and Disorders
• cstc2021jcyj-bshX0056 the Science and Technology Foundation of Chongqing, China

• blood vessel distribution
• direct assist device
• finite element model
• main and secondary assist area
• optimal assist method

• Humans
• Heart Failure
• Heart-Assist Devices/adverse effects
• Heart
• Heart Ventricles

• Cardiomyopathy
• Child
• Genetic
• Sarcomeric cardiomyopathy

• Child
• Humans
• Infant
• Child, Preschool
• Retrospective Studies
• Mutation
• Cardiomyopathy, Dilated/diagnostic imaging
• Cardiomyopathy, Dilated/genetics
• Genetic Profile
• Genetic Association Studies
• Cardiomyopathy, Hypertrophic/diagnostic imaging
• Cardiomyopathy, Hypertrophic/genetics
• Phenotype
• Genetic Testing

• ancestry
• bioinformatics
• clinical interpretation
• exome
• heart
• infant
• molecular diagnosis
• variant

Background  Hypocalcemia is a rare reversible cause of dilated cardiomyopathy in pediatric population. Myocarditis is another more frequent cause of cardiomyopathy with overlapping presenting features. Cardiac magnetic resonance imaging (CMRI) is a vital modality capable of tissue characterization for the evaluation of cardiomyopathy. The present study is the first attempt to determine if any specific characteristics on CMR exist in patients with hypocalcemic dilated cardiomyopathy.

Methods  A retrospective analysis of 10 cases of hypocalcemic dilated cardiomyopathy (August 2012–August 2019), among which CMRI of nine patients were analyzed. Patients were categorized in to three categories; category 1 defined as absence of edema and late gadolinium enhancement (LGE), category 2 having edema only, and category 3 with presence of both edema and LGE. A diagnosis of myocarditis was considered if both edema and LGE were present.

Results  The mean age of the cohort was 5.5 ± 3.3 months. The mean ejection fraction of the cohort was 20.5 ± 6.85% that improved significantly to 35.22 ± 9.3% at the time of discharge. Five of nine patients had no edema or LGE (category 1), whereas two patients each were categorized into category 2 and 3. All cases in category 1 had normalized ventricular function on follow-up. One patient in category 2 had normal ejection fraction and one was lost to follow-up. Out of the two patients in category 3, there was one mortality and another was lost to follow-up. Of the six patients at follow-up (19 ± 11.0 months), the mean left ventricle ejection fraction improved to 56.5 ± 6.1%.

Conclusion  Hypocalcemic dilated cardiomyopathy has a favorable outcome on rapid initiation of treatment. CMR can be utilized for further prognostication of these patients. Absence of edema and LGE predicts a good outcome, whereas presence of LGE and/or edema either indicates a worse prognosis or an underlying coexistent myocarditis warranting an early myocardial biopsy.

• Disparities
• Genetic testing
• Hypertrophic cardiomyopathy
• Pediatrics

We report on a 36-year-old man with cerebellar-extrapyramidal syndrome and severe heart failure because of dilated cardiomyopathy of unknown origin. Dysarthria and cardiac arrhythmia began at early childhood (4 years of age). Brain MRI (28 years of age) demonstrated severe cerebellar atrophy. At the age 32, he presented with dysarthria, ataxia, dystonia, and tremor of the right hand, bilateral slowed neural conduction in the visual pathways, and decreased mental acuity. At the age of 33 years, the patient underwent cardiac transplantation because of severe dilated cardiomyopathy. In the TPP1 gene, biallelic variants were identified: previously reported p.(Leu13Pro) and novel p.(Tyr508Cys) variant. Additionally, hemizygous novel missense variant in the ABCD1 gene was inherited from the mother p.(Arg17His). Normal very-long-chain fatty acids (VLCFA) levels both in patient and his mother excluded ABCD1 mutation as the pathogenic one. Tripeptidyl peptidase 1 (TPP1) activity was reduced (8,8 U/mg protein/h; reference range: 47.4 ± 10.7). In light microscopy the biopsy specimens obtained from explanted heart showed severe myocyte hypertrophy with perinuclear vacuolization with inclusions. Electron microscopy revealed absence of lipofuscin accumulation, no ultrastructural curvilinear profiles, fingerprint bodies, or granular osmiophilic deposits (GRODs) in lysosomes. As described here, the patient presents clinical symptoms observed in benign forms of ceroid lipofuscinosis type 2 (CLN2) and simultaneously some features of autosomal recessive spinocerebellar ataxia type 7 (SCAR7), which is also caused by mutations in the TPP1 gene.

• Advanced heart disease
• Cardiology
• Palliative care
• Pediatric

• genotype
• hypertrophic cardiomyopathy

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.

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 (P=0.005 and P=0.03, respectively). A molecular cause was identified in an additional 21% of the 63 children who did not undergo clinical testing, with positive results identified in both familial and idiopathic cases and across all phenotypic subtypes.

A definitive molecular genetic diagnosis can be made in a substantial proportion of children for whom the cause and heritable nature of their cardiomyopathy was previously unknown. Practice variations in genetic testing are great and should be reduced. Improvements can be made in comprehensive cardiac screening and predictive genetic testing in first‐degree relatives. Overall, our results support use of routine genetic testing in cases of both familial and idiopathic cardiomyopathy.

URL: https://www.clinicaltrials.gov; Unique identifier: NCT01873963.

• exome
• heart failure
• infant
• molecular
• mutation

• heart failure reduced ejection fraction (HFrEF)
• ivabradine
• omecamtiv mecarbil
• pediatric heart failure
• sacubitril/valsartan

• cardiomyopathy
• consanguinity
• exome
• founder mutation
• genome
• pediatrics

• Adolescent
• Adult
• Aged
• Cardiomyopathy, Hypertrophic/blood
• Cardiomyopathy, Hypertrophic/diagnosis
• Cardiomyopathy, Hypertrophic/epidemiology
• Child
• Child, Preschool
• Cohort Studies
• Cross-Sectional Studies
• Female
• Humans
• Infant
• Infant, Newborn
• Male
• Middle Aged
• Prevalence
• Young Adult

• AHA Scientific Statements
• cardiomyopathies
• child
• genetics
• heart failure
• heart transplantation
• sudden death

• Adolescent
• American Heart Association
• Cardiomyopathies/classification
• Cardiomyopathies/diagnosis
• Cardiomyopathies/epidemiology
• Cardiomyopathies/genetics
• Child
• Genetic Testing/standards
• Humans
• Registries/standards
• United States/epidemiology

• ALPK3
• cardiomyopathy
• dilated
• hypertrophic

The RASopathies are a class of developmental disorders caused by germline mutations in the RAS-mitogen-activated protein kinase (MAPK) pathway. Hypertrophic cardiomyopathy (HCM) has been frequently described in children with RASopathy, but only a minority of patients have received formal genotyping. The purpose of this study was to evaluate the genetic basis and clinical outcome of pediatric patients with RASopathy-associated HCM.

We retrospectively reviewed the mutation spectrum and clinical outcome of all the patients with RASopathy derived from 168 pediatric HCM cases referred to our institution between January 2012 and July 2018.

A heterozygous missense mutation in one of known RASopathy genes was identified in 46 unrelated children with HCM. Mutations in the PTPN11 gene were the most prevalent (19/46); this was followed by mutations in RAF1 (11/46), KRAS (5/46), RIT1 (4/46), BRAF (3/46), SOS1 (2/46), HRAS (1/46), and SHOC2 (1/46). Moreover, two compound heterozygous missense mutations in the LZTR1 gene were identified in one patient with the Noonan syndrome phenotype and HCM. The median age at the diagnosis of HCM was 3.0 months (range 0 months to 8.1 years). Twenty-one of the patients had significant left ventricular outflow tract obstruction and 32 had concomitant congenital heart disease. Three patients with a mutation in exon 13 of the PTPN11 gene died of cardiac failure at the ages of 3.0, 3.5, and 6.0 months. The remaining 44 patients were alive after an average follow-up time of 3.9 years (0.5 to 17.1 years, median 2.9 years) from the initial diagnosis of HCM, including 5 patients with spontaneous regression of their cardiac hypertrophy.

RASopathy-associated HCM is a heterogeneous genetic condition characterized by early-onset cardiac hypertrophy and a high prevalence of co-existing congenital heart disease, which is most frequently related to specific mutations in the PTPN11 gene. Rapidly progressive HCM, resulting in an early death, is uncommon in RASopathy patients except those with specific mutations in exon 13 of the PTPN11 gene.

• Hypertrophic cardiomyopathy
• RAS-MAPK pathway
• RASopathy

Pompe disease is an autosomal recessive lysosomal storage disorder characterized by progressive myopathy with proximal muscle weakness, respiratory muscle dysfunction, and cardiomyopathy. Its prevalence ranges between 1/9000 and 1/40,000. It is caused by compound heterozygous or homozygous mutations in the GAA gene, which encodes for the lysosomal enzyme alpha-glucosidase, required for the degrading of lysosomal glycogen.

In this study, we report the case of a Moroccan consanguineous family with hypertrophic cardiomyopathy and sudden cardiac deaths at an early age; our patient was a 7-month-old Moroccan girl. Whole exome sequencing identified the deleterious homozygous mutation c.236_246delCCACACAGTGC (p.Pro79ArgfsX13) of GAA gene leading to a post-mortem diagnosis of Pompe disease.

The identification of the genetic substrate in our patient, the daughter, confirmed the clinical diagnosis of Pompe disease and allowed us to provide appropriate genetic counseling to the family for future pregnancies.

• GAA gene
• Moroccan family
• Pompe disease
• Post-mortem diagnosis

• Cardiomyopathy
• Genetic analysis
• Genetics
• Practice resource
• Secondary findings

• Cardiomyopathy
• genetic analysis
• genetics
• practice guideline
• secondary findings

• Cardiomyopathies/genetics
• Genetic Counseling/methods
• Genetic Testing/standards
• Genetics, Medical/methods
• Genotype
• Heart Failure
• Humans
• Phenotype
• Practice Guidelines as Topic
• Societies, Medical

• P01 HL134599 NHLBI NIH HHS

• cardiomyopathy
• classification
• pediatrics

• epidemiology
• genetics
• pediatrics

• dilatation
• dilated cardiomyopathy
• family history
• genetics
• incidence
• pediatrics

Recent studies have indicated a much broader role to Vitamin D than simply the regulation of calcium metabolism alone. Vitamin D likely confers physiologically relevant pleiotropic functions that include cardioprotective and immunomodulatory effect, and its deficiency could lead to increased risk of cardiovascular disease and heart failure.

The aim of our work was to evaluate the presence of hypovitaminosis D in patients with dilated cardiomyopathy (DCMP) and to study any correlation of echocardiographic parameters with Vitamin D deficiency.

In an observational case–control hospital-based study, 56 patients diagnosed to have DCMP and 60 age-, gender-, and body mass index-matched controls who were patients of other medical illnesses were included in the study. Each subject underwent transthoracic two-dimensional guided M-mode echocardiography, and Vitamin D, parathyroid hormone (PTH), and N-terminal pro-B-type natriuretic peptide (NT-ProBNP) were assessed.

Mean 25-hydroxyvitamin D3 [25(OH) D3] levels were significantly lower (14.5 ± 7.4 ng/ml vs. 28.2 ± 12 ng/ml, P = 0.001), whereas PTH (90.5 ± 28.5 pg/ml vs. 57 ± 20.2 pg/ml, P = 0.02) and NT-proBNP levels were significantly greater in patients with DCMP than controls. In DCMP group, 24/56 patients had severe Vitamin D deficiency, whereas in control group, 10/60 patients had severe hypovitaminosis D. There was a significant negative correlation between 25(OH) D3 concentrations and left ventricular (LV) end-diastolic and LV end-systolic dimensions.

Patients with DCMP had lower Vitamin D levels than controls, and Vitamin D deficiency had a significant correlation with cardiac function. Therefore, screening for Vitamin D deficiency along with prompt treatment is recommended in patients with DCMP.

• Cardiomyopathy
• Vitamin D
• heart failure

• dilated cardiomyopathy
• heart failure
• inflammation
• myocarditis
• viral myocarditis

• intellectual disability, mild
• microcephaly
• restrictive cardiomyopathy
• severe short stature

• R01 GM081519 NIGMS NIH HHS

• Cardiomyopathy
• Pediatric Cardiomyopathy Registry
• heart failure
• paediatrics
• patient registry

• Mutation
• genetic syndrome
• genetic variant
• sarcomere

• cascade screening
• metabolic
• sarcomere
• syndrome

• Dilated cardiomyopathy
• Heart transplantation
• Mechanical circulatory support

Pediatric cardiomyopathies are clinically heterogeneous heart muscle disorders that are responsible for significant morbidity and mortality. Phenotypes include hypertrophic cardiomyopathy, dilated cardiomyopathy, restrictive cardiomyopathy, left ventricular noncompaction and arrhythmogenic right ventricular cardiomyopathy. There is substantial evidence for a genetic contribution to pediatric cardiomyopathy. To date, more than 100 genes have been implicated in cardiomyopathy, but comprehensive genetic diagnosis has been problematic because of the large number of genes, the private nature of mutations, and difficulties in interpreting novel rare variants. This review will focus on current knowledge on the genetic etiologies of pediatric cardiomyopathy and their diagnostic relevance in clinical settings. Recent developments in sequencing technologies are greatly impacting the pace of gene discovery and clinical diagnosis. Understanding the genetic basis for pediatric cardiomyopathy and establishing genotype-phenotype correlations may help delineate the molecular and cellular events necessary to identify potential novel therapeutic targets for heart muscle dysfunction in children.

• Pediatric
• Mutation
• Exome sequencing
• Sarcomere

• cardiomyopathy
• echocardiography
• fetal
• noncompaction
• outcome

Carnitine is essential for the transfer of long-chain fatty acids from the cytosol into mitochondria for subsequent β-oxidation. A lack of carnitine results in impaired energy production from long-chain fatty acids, especially during periods of fasting or stress. Primary carnitine deficiency (PCD) is an autosomal recessive disorder of mitochondrial β-oxidation resulting from defective carnitine transport and is one of the rare treatable etiologies of metabolic cardiomyopathies. Patients affected with the disease may present with acute metabolic decompensation during infancy or with severe cardiomyopathy in childhood. Early recognition of the disease and treatment with L-carnitine may be life-saving. In this review article, the pathophysiology, clinical presentation, diagnosis, treatment and prognosis of PCD are discussed, with a focus on cardiac involvements.

• Cardiomyopathies
• Carnitine deficiency, primary

• Cardiomyopathy, Hypertrophic/diagnosis
• Female
• Humans
• Male

To analyze the clinical effect of extracorporeal membrane oxygenation (ECMO) in children with acute fulminant myocarditis, we retrospectively analyzed the data of five children with acute fulminant myocarditis in the intensive care unit (ICU) at the Affiliated Children’s Hospital, Zhejiang University from February 2009 to November 2012. The study group included two boys and three girls ranging in age from 9 to 13 years (median 10 years). Body weight ranged from 25 to 33 kg (mean 29.6 kg). They underwent extracorporeal membrane oxygenation (ECMO) through a venous-arterial ECMO model with an average ECMO supporting time of 89.8 h (40–142 h). Extracorporeal circulation was established in all five children. After treatment with ECMO, the heart rate, blood pressure, and oxygen saturation were greatly improved in the four children who survived. These four children were successfully weaned from ECMO and discharged from hospital machine-free, for a survival rate of 80% (4/5). One child died still dependent on the machine. Cause of death was irrecoverable cardiac function and multiple organ failure. Complications during ECMO included three cases of suture bleeding, one case of acute hemolytic renal failure and suture bleeding, and one case of hyperglycemia. During the follow-up period of 4–50 months, the four surviving children recovered with normal cardiac function and no abnormal functions of other organs. The application of ECMO in acute fulminant myocarditis, even in local centers that experience low incidence of this disease, remains an effective approach. Larger studies to determine optimal timing of placement on ECMO to guide local centers are warranted.

• Adolescent
• Child
• Extracorporeal Membrane Oxygenation
• Female
• Follow-Up Studies
• Heart Function Tests
• Humans
• Male
• Myocarditis/physiopathology
• Myocarditis/therapy
• Patient Discharge

• Cardiomyopathy, Hypertrophic/diagnosis
• Female
• Humans
• Male

• cardiomyopathy
• heart failure
• pediatric
• risk factors
• transplantation
• treatment

• Cardiomyopathies/epidemiology
• Cardiomyopathies/etiology
• Cardiomyopathies/prevention & control
• Child
• Chronic Disease
• Disease Management
• Disease Progression
• Humans
• Incidence
• Practice Guidelines as Topic
• Prevalence
• Prognosis
• Risk Factors
• United States/epidemiology

• R01 HL053392 NHLBI NIH HHS

• Dilated cardiomyopathy
• hypocalcaemia
• vitamin D deficiency

• Cardiomypathy
• Rickets