Mitochondrial Cardiomyopathy: Pathophysiology,Diagnosis, and Management

Mitochondrial disease is a heterogeneous group of multisystemic diseases that develop consequent to mutations in nuclear or mitochondrial DNA. The prevalence of inherited mitochondrial disease has been estimated to be greater than 1 in 5,000 births; however, the diagnosis and treatment of this disease are not taught in most adult-cardiology curricula. Because mitochondrial diseases often occur as a syndrome with resultant multiorgan dysfunction, they might not immediately appear to be specific to the cardiovascular system. Mitochondrial cardiomyopathy can be described as a myocardial condition characterized by abnormal heart-muscle structure, function, or both, secondary to genetic defects involving the mitochondrial respiratory chain, in the absence of concomitant coronary artery disease, hypertension, valvular disease, or congenital heart disease. The typical cardiac manifestations of mitochondrial disease—hypertrophic and dilated cardiomyopathy, arrhythmias, left ventricular myocardial noncompaction, and heart failure—can worsen acutely during a metabolic crisis. The optimal management of mitochondrial disease necessitates the involvement of a multidisciplinary team, careful evaluations of patients, and the anticipation of iatrogenic and noniatrogenic complications.In this review, we describe the complex pathophysiology of mitochondrial disease and its clinical features. We focus on current practice in the diagnosis and treatment of patients with mitochondrial cardiomyopathy, including optimal therapeutic management and long-term monitoring. We hope that this information will serve as a guide for practicing cardiologists who treat patients thus affected.Key words: Cardiomyopathies/genetics/pathology/therapy, DNA, mitochondrial/analysis/genetics, energy metabolism/physiology, electron transport/physiology, genetic predisposition to disease, heart diseases/genetics, mitochondria/physiology, mitochondrial diseases/complications/diagnosis/genetics/physiopathology/drug therapy, risk factors, ventricular dysfunction, left/geneticsThe myocardium depends on a high level of aerobic metabolism to supply blood and energy substrate to all organs of the body. The mitochondria have a key role in energy production and in the growth and regulation of cardiac bioenergetic arrangements. Specific mitochondrial diseases have been attributed to mitochondrial mutations, and cardiac involvement is frequent. However, these syndromes are generally not covered comprehensively in cardiology curricula and might not be widely recognized by practicing cardiologists who treat adults. Recent research has shown that derangements of energy metabolism are ultimately implicated in most forms of heart failure. In this review, we describe the biologic characteristics of the mitochondria and their role in cardiac bioenergetic arrangements, discuss the spectrum of mitochondrial disease, and provide a guide for practicing cardiologists to use when treating patients affected by mitochondrial crisis.