Background: The aim of the study was to document cardiovascular clinical findings, cardiac imaging and laboratory markers in children presenting with the novel multisystem inflammatory syndrome (MIS-C) associated with COVID-19 infection. Methods: A real-time internet-based survey endorsed by the Association for European Paediatric and Congenital Cardiologists (AEPC) Working Groups for Cardiac Imaging and Cardiovascular Intensive Care. Inclusion criteria was children 0-18 years admitted to hospital between February 1 and June 6, 2020 with diagnosis of an inflammatory syndrome and acute cardiovascular complications. Results: A total of 286 children from 55 centers in 17 European countries were included. The median age was 8.4 years (IQR 3.8-12.4 years) and 67% were males. The most common cardiovascular complications were shock, cardiac arrhythmias, pericardial effusion and coronary artery dilatation. Reduced left ventricular ejection fraction was present in over half of the patients and a vast majority of children had raised cardiac troponin (cTnT) when checked. The biochemical markers of inflammation were raised in majority of patients on admission: elevated CRP, serum ferritin, procalcitonin, NT-proBNP, IL-6 level and D-dimers. There was a statistically significant correlation between degree of elevation in cardiac and biochemical parameters and need for intensive care support (p <0.05). Polymerase chain reaction (PCR) for SARS-CoV-2 was positive in 33.6% while IgM and IgG antibodies were positive in 15.7% and IgG 43.6 % cases, respectively when checked. One child died in the study cohort. Conclusions: Cardiac involvement is common in children with multisystem inflammatory syndrome associated with Covid-19 pandemic. A majority of children have significantly raised levels of NT pro-BNP, ferritin, D-dimers and cardiac troponin in addition to high CRP and procalcitonin levels. Compared to adults with Covid-19, mortality in children with MIS-C is uncommon despite multi-system involvement, very elevated inflammatory markers and need for intensive care support.

Although idiopathic cardiomyopathies are prognostically important and are a common indication for cardiac transplantation in all age groups, the incidence and age distribution of idiopathic cardiomyopathies in a well-defined pediatric population have been poorly characterized. A retrospective study was carried out in Finland in 1980-1991 to obtain information on the epidemiology of childhood cardiomyopathies. The medical records of all patients aged birth to 20 years with cardiomyopathy from the five university hospitals and 16 central hospitals covering the entire country were reviewed. Moreover, data on causes of death from the Finnish National Census Bureau were examined. Of the 808 potential cases screened, 118 infants, children, and adolescents, representing an average age-specific population of 1.4 million, were definitely identified as having idiopathic cardiomyopathy. The average annual occurrence of new cases was 0.65 per 100,000 population (95% confidence interval (CI) 0.53-0.79). If the 15 cases diagnosed only after death during the 12-year study period were included, the occurrence increased to 0.74 per 100,000 population per year. Fifty-six new cases of dilated cardiomyopathy and 40 new cases of hypertrophic cardiomyopathy were diagnosed during the study period, giving average annual occurrences of 0.34/100,000/year (95% CI 0.26-0.44) and 0.24/100,000/year (95% CI 0.17-0.33) for new cases of dilated and hypertrophic cardiomyopathies, respectively. At the end of 1991, the prevalence of dilated cardiomyopathy was 2.6/100,000 (95% CI 1.8-3.6) and that for hypertrophic cardiomyopathy was 2.9/100,000 (95% CI 2.0-4.0). The number of new cases of dilated cardiomyopathy per year increased over the study period, whereas the annual occurrence of hypertrophic cardiomyopathy remained relatively constant. Marked variability was seen in occurrence among the different age groups of children with dilated cardiomyopathy, suggesting that different pathophysiologic mechanisms, and possibly etiologies, may exist in different age groups.

Our study confirms that the outcome of children with IDCM still remains poor. However, a group of patients, mainly infants, make a full recovery. Adolescent male patients as well as infants suffering from endocardial fibroelastosis with persisting symptoms of congestive heart failure after initiation of medical therapy tend to have the poorest outcome. These patients need a careful follow-up at short time intervals and, in the case of lacking response to medical treatment with resulting growth failure and/or poor quality of life, should be offered urgent heart transplantation.

Objectives We evaluated ankyrin repeat domain 1 (ANKRD1), the gene encoding cardiac ankyrin repeat protein (CARP), as a novel candidate gene for dilated cardiomyopathy (DCM) through mutation analysis of a cohort of familial or idiopathic DCM patients, based on the hypothesis that inherited dysfunction of mechanical stretch-based signaling is present in a subset of DCM patients. Background CARP, a transcription coinhibitor, is a member of the titin-N2A mechanosensory complex and translocates to the nucleus in response to stretch. It is up-regulated in cardiac failure and hypertrophy and represses expression of sarcomeric proteins. Its overexpression results in contractile dysfunction. Methods In all, 208 DCM patients were screened for mutations/variants in the coding region of ANKRD1 using polymerase chain reaction, denaturing high-performance liquid chromatography, and direct deoxyribonucleic acid sequencing. In vitro functional analyses of the mutation were performed using yeast 2-hybrid assays and investigating the effect on stretch-mediated gene expression in myoblastoid cell lines using quantitative real-time reverse transcription–polymerase chain reaction. Results Three missense heterozygous ANKRD1 mutations (P105S, V107L, and M184I) were identified in 4 DCM patients. The M184I mutation results in loss of CARP binding with Talin 1 and FHL2, and the P105S mutation in loss of Talin 1 binding. Intracellular localization of mutant CARP proteins is not altered. The mutations result in differential stretch-induced gene expression compared with wild-type CARP. Conclusions ANKRD1 is a novel DCM gene, with mutations present in 1.9% of DCM patients. The ANKRD1 mutations may cause DCM as a result of disruption of the normal cardiac stretch-based signaling.

BackgroundEpidemiology of myocarditis in childhood is largely unknown. Men are known to have a higher incidence of myocarditis than women in adults aged <50 years, but whether this is true by sex in pediatric age groups is unknown. We set out to study the occurrence and potential sex differences of myocarditis in a general pediatric population.Methods and ResultsData of all hospital admissions with myocarditis in Finland occurring in patients aged ≤15 years from 2004 to 2014 were collected from a mandatory nationwide registry. All patients with myocarditis as a primary, secondary, or tertiary cause of admission were included. Total and age‐ and sexspecific incidence rates were calculated using corresponding population data. There were 213 admissions with myocarditis in pediatric patients. Myocarditis was the primary cause of admission in 86%. The overall incidence rate of myocarditis was 1.95/100 000 person‐years. Of all patients, 77% were boys, but sex differences in incidence rates were age‐dependent. In children aged 0 to 5 years, there was no sex difference in the occurrence of myocarditis. Boys aged 6 to 10 years had a higher incidence rate compared with girls (72% boys; incidence rate ratio: 2.46; 95% confidence interval, 1.03–5.89; P=0.04). Sex difference further increased in children aged 11 to 15 years (80% boys; incidence rate ratio: 3.5; 95% confidence interval, 2.68–5.67; P<0.0001).ConclusionsMyocarditis leading to hospital admission is relatively uncommon in children, but occurrence of myocarditis increases with age. There is no sex difference in the risk of myocarditis during the first 6 years of life, but boys have a significantly higher risk at ages 6 to 15 years.