A recent study conducted by researchers from Johns Hopkins Medicine, published on July 25th in Nature Cardiovascular Research, has unveiled the effects of obesity on the muscle structure in patients with heart failure with preserved ejection fraction (HFpEF).
The Journal of Cardiac Failure notes that HFpEF accounts for more than half of all heart failure cases globally. In the U.S., it represents over 3.5 million cases. Historically, HFpEF was linked to high blood pressure, causing excess muscle growth (hypertrophy) to manage the increased pressures. However, in the last two decades, the prevalence of HFpEF has risen among patients with severe obesity and diabetes, as reported by the Journal of the American College of Cardiology. Despite this, there remains a scarcity of effective treatments for HFpEF, partly due to a shortage of studies on human heart tissue that pinpoint the exact abnormalities. Given the high hospitalization and mortality rates associated with HFpEF—30-40% within five years—gaining a deeper understanding of its root causes is crucial.
David Kass, M.D., Professor of Medicine at the Johns Hopkins University School of Medicine and lead investigator of the study, explains, “HFpEF is a complex syndrome that involves abnormalities across several organs. Although it’s termed heart failure due to symptom similarities with other forms of heart failure where the heart muscle is weak, in HFpEF, the heart’s pumping action is normal yet symptoms of heart failure persist. Previous standard heart failure medications have been ineffective in treating HFpEF, but recent successes have been seen with drugs originally designed for diabetes and obesity.”
Specifically, an SGLT2 inhibitor (sodium glucose transporter two inhibitor), a drug for diabetes, is the only evidence-based medication for HFpEF that has shown improvements in symptoms and significant reductions in long-term hospital readmissions and mortality rates. Additionally, the GLP1-receptor agonist, a weight loss medication, has shown promise in alleviating HFpEF symptoms, with ongoing studies investigating potential impacts on mortality and hospital admissions. These drugs, originally developed for diabetes, have also proven beneficial for HFpEF.
In their research, the Johns Hopkins team collected a small sample of muscle tissue from 25 patients diagnosed with varying degrees of HFpEF due to diabetes and obesity. They compared this with heart tissue from 14 organ donors with normal hearts. The tissue was examined under an electron microscope, which provides a high-magnification view of muscle structure.
Mariam Meddeb, M.D., MS, a cardiovascular disease specialist at Johns Hopkins involved in the study, said, “Using an electron microscope allows us to magnify images up to 40,000 times, offering an exceptionally detailed view of the muscle cell’s ultrastructure, such as mitochondria, the energy powerhouses, and sarcomeres, the muscle fiber units.”
The study identified significant ultrastructural abnormalities, especially in the tissue of the most obese patients with HFpEF. These included swollen, pale, disrupted mitochondria, abundant fat droplets, and frayed sarcomeres. Interestingly, these abnormalities were independent of diabetes and were less pronounced in less obese patients.
“These findings are pivotal for those developing animal models of HFpEF, as they clarify the specific microscopic changes one aims to replicate,” notes Dr. Kass. “It also poses an important question: can reducing obesity, which is currently being targeted with various drug therapies, reverse these ultrastructural changes and thereby improve outcomes for HFpEF patients?”
This study advances our understanding of HFpEF and elucidates the significant impact of obesity on heart disease, offering a new target for therapeutic interventions to benefit the vast number of patients suffering from HFpEF.
More information: Biykem Bozkurt et al, Heart Failure Epidemiology and Outcomes Statistics: A Report of the Heart Failure Society of America, Journal of Cardiac Failure. DOI: 10.1016/j.cardfail.2023.07.006
Journal information: Journal of Cardiac Failure Provided by Johns Hopkins Medicine
