A small study led by researchers at Johns Hopkins Medicine, published on July 25th in Nature Cardiovascular Research, has uncovered how obesity affects muscle structure in patients with a specific type of heart failure known as heart failure with preserved ejection fraction (HFpEF).
HFpEF makes up more than half of all heart failure cases globally.
In the United States alone, it accounts for over 3.5 million cases. Initially, this form of heart disease was linked to high blood pressure, which led to excess muscle growth (hypertrophy) to counteract the pressure.
Over the last 20 years, HFpEF has been increasingly found in patients with severe obesity and diabetes. Despite the prevalence of HFpEF, effective treatments are scarce.
Developing therapies is challenging due to a lack of studies on human heart tissue to determine the exact abnormalities. Given the high hospitalization and death rates among HFpEF patients (30-40% over five years), understanding the underlying causes is crucial.
“HFpEF is a complex syndrome involving multiple organs,” says Dr. David Kass, the lead investigator and Professor of Medicine at Johns Hopkins University School of Medicine. “We call it heart failure because the symptoms are similar to those in patients with weakened hearts.
However, in HFpEF, the heart’s contraction appears normal, but heart failure symptoms persist. Traditional heart failure drugs haven’t worked well for HFpEF, but success has been seen with drugs used to treat diabetes and obesity.”
One such drug is an SGLT2 inhibitor (sodium glucose transporter 2 inhibitor), used to treat diabetes. This is currently the only evidence-based drug for HFpEF that not only improves symptoms but also reduces long-term rehospitalization and mortality rates.
Another drug, a GLP1-receptor agonist used for weight loss, has shown promise in improving HFpEF symptoms. Ongoing studies are examining whether it can also reduce mortality and hospitalizations for HF. These drugs have shown effectiveness not only in diabetes but also in HFpEF.
In the study, the research team examined small muscle tissue samples from 25 patients diagnosed with varying degrees of HFpEF caused by diabetes and obesity.
They compared these samples to heart tissue from 14 organ donors with normal hearts. The muscle tissue was examined using an electron microscope, which provides a detailed view of the muscle structure at a very high magnification.
Dr. Mariam Meddeb, a cardiovascular disease specialist at Johns Hopkins University School of Medicine, explains, “The electron microscope allows us to magnify the image 40,000 times, giving a clear picture of the muscle cell’s inside, such as mitochondria, the energy power plants, and sarcomeres, the units of muscle fiber that generate force.”
The researchers discovered significant abnormalities in the muscle tissue of the most obese patients with HFpEF.
Their mitochondria were swollen, pale, and disrupted, with many fat droplets, and their sarcomeres appeared damaged. These issues were not linked to whether the patient had diabetes and were less severe in patients who were less obese.
“These findings will aid those developing animal models of HFpEF by showing what to look for at the microscopic level,” notes Dr. Kass. “It also raises the important question of whether reducing obesity with various drug therapies will reverse these muscle abnormalities and improve HFpEF outcomes.”
The study’s findings enhance our understanding of HFpEF and highlight the impact of obesity on heart disease. They also provide a target for developing therapies to benefit the millions of HFpEF patients.
Other contributors to the study from Johns Hopkins include Navid Koleini, Mohammad Keykhaei, Seoyoung Kwon, Celia Aboaf, Mohamed Lehar, Kavita Sharma, and Virginia S. Hahn.
If you care about heart health, please read studies about top 10 foods for a healthy heart, and how to eat right for heart rhythm disorders.
For more health information, please see recent studies about how to eat your way to cleaner arteries, and salt and heart health: does less really mean more?
The research findings can be found in Nature Cardiovascular Research.
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