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Background: Primary mitochondrial disorders (PMD) are rare conditions resulting in progressive multi-organ failure. Cardiovascular involvement (CVI) has been reported in paediatric patients. However, its age-related prevalence, clinical presentation and prognostic impact are unresolved. We detailed CVI in a cohort of children diagnosed with PMD over two decades at a tertiary referral centre., Results: We enrolled 86 PMD patients (M/F = 30/56; mean age 6.4 ± 8.58 years). CVI was detected in 31 patients (36%), with mean age at onset of 5.7 ± 7.8 years including the pre- and neonatal phase in 14, often representing the first sign of PMD (42% of those with CVI). Heart disease resulted more common in males and in children with specific aetiologies (Barth, TMEM70 and MELAS syndromes). Hypertrophic, non-compaction and dilated cardiomyopathies were the prevalent disorders, although pulmonary arterial hypertension was also found. Adverse cardiac events (heart failure, resuscitated cardiac arrest, ICD/PM implantation, sudden death) occurred in 19% of children with CVI over a follow-up period of 5.4 ± 4.3 years. All-cause mortality was higher in patients with CVI compared to those without CVI (45.1% vs 21.8%; p < 0.01); female sex, age at onset < 5 years, acute heart failure at presentation and diabetes also proved independent predictors of outcome., Conclusion: Cardiovascular involvement occurred in over one-third of children diagnosed with PMD, often at a very early age, and was associated with adverse prognosis. Final outcome of PMD-related CVI was influenced by the specific underlying aetiology, suggesting the need for tailored management of heart failure and sudden death prevention.

Due to their rare prevalence and marked heterogeneity, pediatric cardiomyopathies (CMPs) are little known and scarcely reported. We report the etiology, clinical profile and outcome of a consecutive cohort of children diagnosed with CMP and followed at Meyer Children's Hospital over a decade. We retrospectively reviewed patients consecutively referred from May 2008 to May 2019 for pediatric onset CMP (<18 years). Heart disease caused by arrhythmic disorders, toxic agents, rheumatic conditions and maternal disease were excluded. We enrolled 110 patients (65 males), diagnosed at a median age of 27 [4–134] months; 35% had an infant onset (<1 year of age). A positive family history was more often associated with childhood-onset (38.8%). Hypertrophic cardiomyopathy (HCM; 48 patients) was the most frequent phenotype, followed by dilated cardiomyopathy (DCM; 35 patients). While metabolic and idiopathic etiologies were preponderant in infants, metabolic and sarcomeric diseases were most frequent in the childhood-onset group. Major adverse cardiac events (MACE) occurred in 31.8% of patients, including hospitalization for acute heart failure in 25.5% of patients, most commonly due to DCM. Overall, the most severe outcomes were documented in patients with metabolic diseases. In a consecutive cohort of pediatric patients with CMP, those with infantile onset and with a metabolic etiology had the worst prognosis. Overall, MACE occurred in 41% of the entire population, most commonly associated with DCM, inborn errors of metabolism and genetic syndromes. Systematic NGS genetic testing was critical for etiological diagnosis and management. • Children with CMP with infantile onset and with a metabolic etiology had the worst prognosis. • MACE is most commonly associated with DCM, inborn errors of metabolism and genetic syndromes. • NGS genetic testing was pivotal to reach an etiological diagnosis and guide management. [ABSTRACT FROM AUTHOR]