Researchers Look for Links Between Mitochondrial Disease and Heart Diseases

Joana Fernandes, PhD avatar

by Joana Fernandes, PhD |

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Mitochondrial DNA copy number and heart disease

Researchers have conducted a thorough review that highlights several heart diseases associated with mitochondrial disease (MD), as well as the clinical features of cardiac MD and current therapies to manage the condition.

The study, “Mitochondrial Disease And The Heart” and published in the journal Heart , was conducted by Giuseppe Limongelli, MD, PhD, and his colleagues from the Second University of Naples, Italy.

In general, mitochondrial disease refers to a group of disorders that result from abnormal energy production by mitochondria, the cell’s powerhouse, due to genetic mutations in mitochondrial DNA (mtDNA). Several organs may be affected by mitochondrial dysfunction, including the heart. Because the heart is highly dependent on the energy produced in the mitochondria, defects in mitochondrial structure and function can lead to cardiovascular diseases, including cardiomyopathies, arrhythmias and abnormalities in cardiac conduction.

Mitochondria and cardiomyopathies

According to the authors, hypertrophic cardiomyopathy is the most frequent manifestation of MD. Indeed, mutations in mtDNA can cause sporadic or maternally inherited cardiomyopathy. (Mitochondria are always inherited from the mother.)

Also, previous studies have shown that among patients carrying the m.3243A.G mutation, 38-56%  have left ventricular hypertrophy (abnormal growth), which seems to be related to mutation load. Thus, patients with high mitochondrial mutation load may be at risk of developing cardiomyopathy.

Left ventricular hypertrophy also has been found in patients with other mtDNA mutations, including several mt-tRNA genes, which are crucial to maintain protein synthesis in the mitochondria.

Mitochondria and arrhythmias

Ventricular pre-excitation and Wolff-Parkinson White (WPW) syndrome are two types of arrhythmias that seem to occur more frequently among patients with mtDNA mutations than in the general population. However, there is still little data on the prevalence of arrhythmias in MD patients.

“Sudden death is a rare event, but can occur particularly in severe childhood forms, or in asymptomatic adults carrying the m.3243A>G mutation, even with no evidence of cardiomyopathy by imaging techniques,” the study authors wrote.

Mitochondria and cardiac conduction anomalies

Anomalies in the cardiac conduction system are the main signs of Kearns-Sayre syndrome (KSS) and chronic progressive external ophthalmoplegia syndromes. Although the mechanisms by which mtDNA mutations lead to these anomalies is unknown, mutation load or different sensitivity of cardiac cell types to mitochondrial dysfunction may contribute to this phenomenon.


As different mutations may account for the variability of symptoms associated with cardiac MD, diagnosis of these diseases requires a multi-parametric approach, including laboratory tests (increased creatine kinase, transaminases, lactate/pyruvate ratio, for instance), electrocardiogram, cardiac imaging, muscle biopsy and genetic tests.

In hereditary cardiac MD (cardiomyopathies and/or arrhythmias), symptoms include learning difficulties, muscle weakness, diabetes and deafness, which should be considered “red flags” for mitochondrial disease and raise the suspicions of doctors.

“Cardiologists managing patients with MD should be aware of the different aspects of the disease, and ideally should link to a specialist team comprising neurologists, geneticists and pathologists,” the authors wrote. “The clinical investigation of a patient with suspected MD should start with a three-generation pedigree in order to detect a family history of maternal inheritance or multisystem disease.”


There is no cure for mitochondrial disorders, so treatments aim at maintaining optimal health and reducing symptoms. Because MD patients have different nutritional needs, the first-line therapy is to optimize their diets.

“Some patients may need restriction of carbohydrate, protein or fat,” the authors wrote. “Caloric supplementation, enteral feeding, limited fasting, increased meal frequency and intravenous nutrition are all potential therapeutic avenues to consider.”

Patients with evidence of myocardial involvement, should start conventional therapy with β-blockers (in the absence of AV block), ACE inhibitors (used extensively for treating hypertension) or angiotensin receptor blockers, regardless of their symptomatic status.

In more advanced stages of mitochondrial cardiomyopathy, heart transplants may be considered, but transplantation is not recommended in cases in which several organs are affected by the disease.

“Patients should be referred to physicians with the appropriate expertise in MD whenever the diagnosis is suspected. Patients with cardiac involvement should be counseled about cardiovascular complications and management,” the authors advised. “Current pharmacological strategies are incompletely effective, and large, randomized, controlled trials are required to direct future therapy,” they added.