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  6. Are Skeletal Muscles the Key to Treating Heart Failure

Are Skeletal Muscles the Key to Treating Heart Failure?

Heart failure is a growing epidemic in the United States, accounting for more than 13% of annual deaths in the population. It happens when the heart cannot distribute enough blood and oxygen to support the other organs in the body. It may still be pumping, but it’s not pumping well enough.

The most common form of heart failure, making up more than half of all cases, is Heart Failure with Preserved Ejection Fraction (HFpEF). Despite the increasing prevalence of HFpEF, especially among older women, patient prognosis is worsening and pharmaceutical trials have yet to deliver any promising results.

The main way HFpEF patients experience the disease is in their trouble sustaining physical activity, also known as exercise intolerance. Patients often struggle to perform their daily activities, wherein even simple tasks like getting dressed can take as much effort as running a race.

It was previously assumed that these physical symptoms stemmed from an issue with patients’ heart function, but a growing line of research now paints a different picture. In a recent study published May 10, 2023 in JAMA Cardiology, scientists at UC San Diego School of Medicine provide convincing evidence that HFpEF is actually a systemic, multi-organ disorder that shares characteristics with other common, difficult-to-treat, aging-related disorders.

Rather than being a problem within the cardiac tissue, HFpEF may actually be caused by issues within the skeletal muscle — the muscles we use to move our limbs and other parts of the body. More specifically, mitochondria in the muscle cells of HFpEF patients are failing to generate enough energy, and it's actually this peripheral, non-cardiac factor that is leading to their physical fatigue.

“We were struck by the magnitude of our results,” said senior author Anthony J. A. Molina, PhD, associate professor at UC San Diego School of Medicine. “The analyses make it abundantly clear that skeletal muscle mitochondrial dysfunction is a primary driver of exercise intolerance in HFpEF patients.”

The authors say this might explain why treatments that target cardiac function in HFpEFpatients have largely failed. The new findings pave the way for better treatments for patients with HFpEF, focused on recovering mitochondrial function in skeletal muscle. 

“Our findings significantly impact the development of HFpEF therapeutics and interventions, and shift the focus to peripheral, non-cardiac, targets for treatment.,” said Molina. “As promising mitochondrial therapeutics are being tested and developed, they may prove to have important applications for the treatment of HFpEF.”

— Nicole Mlynaryk