Mitochondrial disorders often affect several organs, but symptoms are more likely to be evident in organs like the heart that are most dependent on oxidative metabolism — the use of oxygen to convert sugars to energy.
But while the diagnosis and treatment of cardiac problems related to mitochondrial disease is advancing, it still falls short of what both children and adults need, an opinion piece states.
Gregory Enns, a professor of pediatrics and medical genetics at Stanford University’s Lucile Packard Children’s Hospital, based his article on a review of cardiac and other conditions thought to be associated with mitochondrial disease, and current knowledge of cardiac involvement in these illnesses. His report, “Pediatric mitochondrial diseases and the heart,” published in Current Opinion in Pediatrics, calls for more research and testing to address this problem.
People with mitochondrial diseases and cardiac problems often have cardiomyopathy, or heart muscles that don’t work as intended, or conduction defects, which are abnormal cardiac electrical impulses — or both.
Advances in diagnostic tools and approaches, and the development of non-invasive gene sequencing techniques, have made it possible to identify new genetic mutations associated with mitochondrial disorders, as well as syndromes linked to mitochondrial dysfunction.
Cardiovascular magnetic resonance (CMR) imaging has shown promise in diagnosing mitochondrial cardiac disease in adults, Enns writes. The new approach has the potential to identify subtle structural changes in the heart, giving it an advantage over standard cardiac echo.
Previous studies show that CMR can differentiate cardiac involvement between patients with Kearns–Sayre syndrome or chronic progressive external ophthalmoplegia (CPEO) and patients with MELAS,. The implication of this research is that CMR could be an important asset in the diagnostic process.
As of now, no approved therapies exist for mitochondrial diseases. But some primary and secondary mitochondrial disorders with cardiac involvement have improved in response to different cofactors — including coenzyme Q10 (CoQ10), riboflavin, and thiamine — depending on a patient’s needs and specific mitochondrial deficiency. More trials are necessary to confirm the therapeutic potential of this approach, Enns says.
A number of treatments under investigation may also hold promise for mitochondrial disorders.
Therapies designed to increase levels of glutathione — an important antioxidant compound — have been shown to improve symptoms of primary and secondary mitochondrial disorders. But they do not appear to benefit people with mitochondrial cardiac dysfunction.
Benzalip (benzafibrate), an approved cholesterol drug, has shown promise against cardiac symptoms in preclinical-trial studies. It is currently in a Phase 2 clinical trial (NCT02398201) in the United Kingdom as a potential therapy for mitochondrial disorders.
Finally, heart transplants and implanted ventricular assist devices show promise in treating cardiomyopathies in patients with mitochondrial disorders. In fact, defibrillators that regulate heartbeats have reduced rates of sudden cardiac arrest in patients with Barth syndrome or Kearns–Sayre syndrome. A ventricular assist device is a mechanical pump that supports heart function and blood flow in people with weakened hearts.
“Cardiomyopathy and conduction defects are the primary cardiac manifestations of mitochondrial disease in the heart,” Enns wrote. “As our understanding of underlying pathophysiology [mechanisms] of mitochondrial disorders continues to improve, there is an increased likelihood that improved treatments for these devastating conditions will be developed, but rigorously designed clinical trials are needed.”
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