Prevalence and natural history of heart disease in adults with primary mitochondrial respiratory chain disease

Abstract

AimsThe prevalence and natural history of cardiovascular disease in adult patients with respiratory chain disease (RCD) is poorly characterized. We sought to determine the frequency and natural history of cardiac disease in patients with primary RCD.Methods and resultsThirty-two patients (37.8 ± 12.6 years) with a definite diagnosis of RCD underwent clinical examination, electrocardiography (ECG), 24 h Holter ECG, and cardiopulmonary exercise testing. Patients were classified into six different phenotypes: mitochondrial myopathy (MM; n = 8), chronic progressive ophthalmoplegia (CPEO; n = 2), chronic progressive ophthalmoplegia with myopathy (CPEO + MM; n = 12), Kearns-Sayre syndrome (KSS; n = 2), mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS; n = 7), neuropathy, ataxia, and retinitis pigmentosa (NARP; n = 1). Twenty-two patients (69) had a mitochondrial DNA mutation. Twenty-six patients (81) had evidence for cardiac involvement: ECG abnormalities (69) and cardiomyopathy (hypertrophic 19; restrictive 3; left ventricular non-compaction 3). During follow-up (4.1 ± 2.8 years), two patients with CPEO + MM developed hypertrophic cardiomyopathy and one patient with NARP developed peripartum dilated cardiomyopathy. Four patients (KSS = 2; MM = 1; MELAS = 1) developed arrhythmias or syncope requiring device therapy or invasive procedures. One patient with MM and cardiomyopathy had an orthotopic heart transplant. One patient with CPEO + MM died from respiratory failure. Freedom from all cardiovascular events at 5 years was 67 (95 CI 47.4-86.6).ConclusionAll patients with RCD should undergo careful and repeated clinical assessment to diagnose and manage cardiovascular involvement. However, life-threatening cardiovascular complications rarely occur, and the prognosis is generally favourable.