Cardiomyopathy is common in patients with the mitochondrial DNA m.3243A>G mutation and correlates with mutation load

Area of Science:

• Cardiology
• Genetics
• Neurology

Background:

• Mitochondrial diseases, particularly those caused by the m.3243A>G mitochondrial DNA (mtDNA) mutation, often present with neuromuscular symptoms.
• Cardiac complications, such as heart failure, can occur but are frequently diagnosed late in the disease progression.

Purpose of the Study:

• To investigate the prevalence of cardiac complications in individuals with the m.3243A>G mtDNA mutation.
• To determine if cardiac screening is warranted for all mutation carriers.

Main Methods:

• Ten m.3243A>G mutation carriers underwent echocardiography and 3 Tesla cardiac MRI.
• Muscle biopsies were analyzed for respiratory chain activity and mtDNA mutation levels.
• Results were compared to age- and gender-matched controls.

Main Results:

• All ten m.3243A>G mutation carriers exhibited abnormal cardiac function on MRI, despite normal echocardiograms.
• Sub-clinical cardiac dysfunction was universally present in the study cohort.
• The severity of cardiac dysfunction correlated with the percentage of mutant mtDNA in skeletal muscle.

Conclusions:

• Cardiac dysfunction is a common, often sub-clinical, complication in patients with the m.3243A>G mtDNA mutation.
• Prospective cardiac screening using MRI is recommended for all mutation carriers.
• Early detection of cardiac dysfunction allows for timely intervention to prevent heart failure.