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Background: This study aimed to describe the current practice and results of genetic evaluation in Dutch children with dilated cardiomyopathy and to evaluate genotype-phenotype correlations that may guide prognosis., Methods: We performed a multicenter observational study in children diagnosed with dilated cardiomyopathy, from 2010 to 2017., Results: One hundred forty-four children were included. Initial diagnostic categories were idiopathic dilated cardiomyopathy in 67 children (47%), myocarditis in 23 (16%), neuromuscular in 7 (5%), familial in 18 (13%), inborn error of metabolism in 4 (3%), malformation syndrome in 2 (1%), and "other" in 23 (16%). Median follow-up time was 2.1 years [IQR 1.0-4.3]. Hundred-seven patients (74%) underwent genetic testing. We found a likely pathogenic or pathogenic variant in 38 children (36%), most often in MYH7 (n = 8). In 1 patient initially diagnosed with myocarditis, a pathogenic LMNA variant was found. During the study, 39 patients (27%) reached study endpoint (SE: all-cause death or heart transplantation). Patients with a likely pathogenic or pathogenic variant were more likely to reach SE compared with those without (hazard ratio 2.8; 95% CI 1.3-5.8, P = 0.007), while transplant-free survival was significantly lower ( P = 0.006). Clinical characteristics at diagnosis did not differ between the 2 groups., Conclusions: Genetic testing is a valuable tool for predicting prognosis in children with dilated cardiomyopathy, with carriers of a likely pathogenic or pathogenic variant having a worse prognosis overall. Genetic testing should be incorporated in clinical work-up of all children with dilated cardiomyopathy regardless of presumed disease pathogenesis.

Aims: We aimed to determine whether in children with dilated cardiomyopathy repeated measurement of known risk factors for death or heart transplantation (HTx) during disease progression can identify children at the highest risk for adverse outcome., Methods and Results: Of 137 children we included in a prospective cohort, 36 (26%) reached the study endpoint (SE: all-cause death or HTx), 15 (11%) died at a median of 0.09 years [inter-quartile range (IQR) 0.03-0.7] after diagnosis, and 21 (15%) underwent HTx at a median of 2.9 years [IQR 0.8-6.1] after diagnosis. Median follow-up was 2.1 years [IQR 0.8-4.3]. Twenty-three children recovered at a median of 0.6 years [IQR 0.5-1.4] after diagnosis, and 78 children had ongoing disease at the end of the study. Children who reached the SE could be distinguished from those who did not, based on the temporal evolution of four risk factors: stunting of length growth (-0.42 vs. -0.02 length Z-score per year, P < 0.001), less decrease in N-terminal pro-B-type natriuretic peptide (NT-proBNP) (-0.26 vs. -1.06 2log pg/mL/year, P < 0.01), no decrease in left ventricular internal diastolic dimension (LVIDd; 0.24 vs. -0.60 Boston Z-score per year, P < 0.01), and increase in New York University Pediatric Heart Failure Index (NYU PHFI; 0.49 vs. -1.16 per year, P < 0.001). When we compared children who reached the SE with those with ongoing disease (leaving out the children who recovered), we found similar results, although the effects were smaller. In univariate analysis, NT-proBNP, length Z-score, LVIDd Z-score, global longitudinal strain (%), NYU PHFI, and age >6 years at presentation (all P < 0.001) were predictive of adverse outcome. In multivariate analysis, NT-proBNP appeared the only independent predictor for adverse outcome, a two-fold higher NT-proBNP was associated with a 2.8 times higher risk of the SE (hazard ratio 2.78, 95% confidence interval 1.81-3.94, P < 0.001)., Conclusions: The evolution over time of NT-proBNP, LVIDd, length growth, and NYU PHFI identified a subgroup of children with dilated cardiomyopathy at high risk for adverse outcome. In this sample, with a limited number of endpoints, NT-proBNP was the strongest independent predictor for adverse outcome., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

A single 6-min walk test (6MWT) can be used to identify children with dilated cardiomyopathy (DCM) with a high risk of death or heart transplantation. To determine if repeated 6MWT has added value in addition to a single 6MWT in predicting death or heart transplantation in children with DCM. Prospective multicenter cohort study including ambulatory DCM patients ≥ 6 years. A 6MWT was performed 1 to 4 times per year. The distance walked was expressed as percentage of predicted (6MWD%). We compared the temporal evolution of 6MWD% in patients with and without the study endpoint (SE: all-cause death or heart transplantation), using a linear mixed effects model. In 57 patients, we obtained a median of 4 (IQR 2-6) 6MWTs per patient during a median of 3.0 years of observation (IQR 1.5-5.1). Fourteen patients reached a SE (3 deaths, 11 heart transplantations). At any time during follow-up, the average estimate of 6MWD% was significantly lower in patients with a SE compared to patients without a SE. In both patients groups, 6MWD% remained constant over time. An absolute 1% lower 6MWD% was associated with an 11% higher risk (hazard) of the SE (HR 0.90, 95% CI 0.86-0.95 p < 0.001). Children with DCM who died or underwent heart transplantation had systematically reduced 6MWD%. The performance of all patients was stable over time, so repeated measurement of 6MWT within this time frame had little added value over a single test.