Impact of cardiovascular involvement on the clinical course of paediatric mitochondrial disorders

Area of Science:

• Pediatric Cardiology
• Rare Diseases
• Mitochondrial Genetics

Background:

• Primary mitochondrial disorders (PMD) are rare genetic conditions causing progressive multi-organ failure.
• Cardiovascular involvement (CVI) is a known complication in pediatric PMD, but its prevalence, presentation, and prognostic impact require further elucidation.

Purpose of the Study:

• To investigate the age-related prevalence, clinical characteristics, and prognostic significance of cardiovascular involvement in a pediatric cohort diagnosed with primary mitochondrial disorders.

Main Methods:

• Retrospective analysis of 86 pediatric patients diagnosed with PMD over two decades at a tertiary referral center.
• Detailed assessment of cardiovascular involvement, including cardiac imaging, clinical presentation, and adverse events.
• Statistical analysis to determine predictors of outcome and mortality.

Main Results:

• Cardiovascular involvement was identified in 36% of pediatric PMD patients, frequently presenting in early childhood and sometimes as the initial sign of the disorder.
• Common cardiac manifestations included hypertrophic, non-compaction, and dilated cardiomyopathies, as well as pulmonary arterial hypertension. Males and patients with Barth, TMEM70, and MELAS syndromes showed higher CVI prevalence.
• Adverse cardiac events occurred in 19% of patients with CVI, and overall mortality was significantly higher in those with cardiovascular involvement (45.1% vs 21.8%).

Conclusions:

• Cardiovascular involvement is a significant complication in pediatric primary mitochondrial disorders, impacting prognosis and often manifesting early in life.
• The specific etiology of PMD influences cardiovascular outcomes, highlighting the need for individualized management strategies for heart failure and sudden death prevention.