Risk Assessment in Pediatric Primary Cardiomyopathy—The RIKADA Study

Objectives: Cardiomyopathies (CMPs) are heterogeneous diseases with clinical presentation varying from asymptomatic to severe heart failure. The role of underlying genetic and disease modulating factors in children and adolescents is relatively unknown. This study sought to perform in-depth characterization of pediatric CMP patients and first-degree family members (FMs) as well as to assess outcome aiming to contribute to risk stratification.

Methods: Patients aged ≤18 years with a diagnosis of primary CMP and their FM including siblings and parents were prospectively enrolled. The study protocol comprised cardiac work-up with medical and family history, physical examination, 12-lead electrocardiogram, Holter monitoring, cardiopulmonary exercise testing, transthoracic echocardiography, cardiovascular magnetic resonance (CMR), laboratory, as well as genetic testing. For survival analysis, adverse events including mechanical circulatory support, heart transplantation, and all-cause death were defined as a combined end point.

Results: In total, 60 index patients with primary CMP (median age 7.8 years) and 124 FM were prospectively enrolled. Adverse events appeared in 32% of index patients and were more common in those with lower body surface area (p = 0.019), increased probrain natriuretic peptide (p < 0.001), and left ventricular dysfunction (p < 0.001) and dilation (p = 0.005). The worst prognosis was observed in patients with dilated and restrictive CMP. Genetic variants of interest (VOIs) were detected in patients (79%) and FM (67%). Increased number of VOI per patient was associated with adverse events (p = 0.021). Fifty-six per cent of FM with positive genotype were clinically unaffected, 11% were genotype and phenotype positive. Late gadolinium enhancement (LGE) from CMR was related to positive genotypes in patients (p = 0.041) and to higher grades of genetic pathogenicity in FM (p = 0.012).

Conclusion: Increased number of VOI and LGE are risk factors for adverse outcomes that should be considered for risk assessment in pediatric CMP. The combination of clinical and genetic testing facilitates early identification of at-risk individuals and contributes to patient-specific follow-up and therapy regimes.

No conflict of interest has been declared by the author(s).