Different Mitochondrial Myopathies Are Associated With Distinct Cardiac Phenotypes in Patients

Patricia Silva, PhD avatar

by Patricia Silva, PhD |

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Researchers at the University Hospital Münster and the Robert-Bosch-Krankenhaus in Germany recently revealed that patients with different mitochondrial myopathies can exhibit different disease related cardiac phenotypes. The study was recently published in the Journal of Cardiovascular Magnetic Resonance and is entitled “Characteristic cardiac phenotypes are detected by cardiovascular magnetic resonance in patients with different clinical phenotypes and genotypes of mitochondrial myopathy.

Mitochondrial myopathies correspond to a group of inherited diseases that result from a defect in mitochondrial genes, causing muscular complications in different organ systems. Mitochondria are the energy factories within the cells and their dysfunction can cause impairment in cellular energy metabolism. Several syndromes have been defined within mitochondrial myopathies, such as chronic progressive external ophthalmoplegia (CPEO), Kearns-Sayre syndrome (KSS), mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) and myoclonic epilepsy with ragged-red fibers (MERRF). All these syndromes have a progressive course linked to different degrees of neurological and muscular disability.

Previous studies using echocardiography and electrocardiography (ECG) showed that patients with mitochondrial myopathy experience cardiac abnormalities, varying from conduction anomalies and arrhythmias (irregular heartbeat) to hypertrophic or dilated cardiomyopathy, a disorder that affects the heart muscle (myocardium) making it weaker and less able to efficiently pump blood throughout the body. Recently, patients with CPEO/KSS and MELAS were reported to exhibit characteristic patterns of cardiac involvement by using cardiovascular magnetic resonance (CMR), a highly sensitive tool for the identification of myocardial abnormalities including tissue damage by late gadolinium enhancement (LGE).

In the study, researchers assessed the prevalence and pattern of cardiac anomalies in patients with mitochondrial myopathies and analyzed the diagnostic value of CMR. The team investigated the hypothesis that different neuromuscular mitochondrial myopathy syndromes are linked to different cardiac disease phenotypes.

The team analyzed 64 patients with mitochondrial myopathies (median age of 50 years old) and 25 matched healthy controls (median age of 52 years old) using CMR. Patients were divided according to their neuromuscular phenotype and genotype into: a) CPEO/KSS (33 patients), b) MELAS/-like (11 patients), c) MERRF (3 patients), and d) other non-specific mitochondrial myopathy forms (17 patients).

Researchers found that 53% of the patients (34 out of 64) had at least one abnormal CMR finding, including impaired heart left ventricular (LV) ejection-fraction (less than 60%) and unexplained LV hypertrophy. Patients with mitochondrial myopathies were found to have significantly higher LV maximal wall thickness and concentricity in comparison to control individuals. CPEO/KSS patients in particular exhibited an intramural LGE pattern in the basal LV inferolateral wall and a tendency for concentric remodeling. MELAS/-like patients, in turn, had the highest frequency of cardiac disease among the patients analyzed, a concentric LV hypertrophy and a unique, focally accentuated LGE equally distributed among the different LV segments. Patients with MERRF and non-specific mitochondrial myopathies had no specific CMR findings.

The team concluded that cardiac involvement is frequent in patients with mitochondrial myopathies, and that two distinct cardiac patterns could be found in patients with KSS/CPEO and MELAS/-like. Researchers suggest that pathological CMR findings are superior and have an added diagnostic value for cardiomyopathy in comparison to ECG and cardiac serum biomarkers. The finding of valuable diagnostic tools for cardiac conditions is essential for a timely initiation of appropriate treatment and it may result in better patient prognosis.