Beware! Changes in leg muscle blood vessels may be the earliest warning sign of heart failure

Compiled by: Gong Zixin

Researchers at the University of Toronto's Institute of Biomedical Engineering have made an important discovery: studying blood flow in leg muscles may be able to detect cardiovascular disease earlier than traditional standardized tests, creating the possibility of early treatment and good prognosis.

Heart failure with preserved ejection fraction (HFpEF) is a common and challenging disease affecting millions of people worldwide, accounting for more than half of all heart failure cases, and its prevalence continues to increase, but diagnosis often occurs at a late stage when treatment is limited.

Left ventricular wall thickening, left atrial enlargement, and chamber hemodynamic abnormalities are late phenotypes of this silent, slowly progressive disease and are easily detected on routine echocardiography. However, early tissue changes associated with HFpEF, such as microvascular dysfunction, interstitial fibrosis, and myocardial stiffening, are more difficult to diagnose.

While medical imaging has improved the ability to detect specific problems with the heart, such as hardening or scarring of heart tissue, these tests often miss early signs of problems elsewhere in the body.

In fact, previous research suggests that poor blood flow regulation in the leg muscles may precede similar changes in the heart and may even explain symptoms such as fatigue or difficulty exercising.

"This study provides important clues on how we can detect HFpEF before irreversible damage to the heart occurs," said Hai-Ling Margaret Cheng, a professor at the University of Toronto's Institute of Biomedical Engineering and a senior researcher on the project.

"Our study suggests that changes in the blood vessels of the leg muscles may be an earlier and more easily detectable warning sign of the disease."
To explore this idea, the team used a special type of steady-state blood pool magnetic resonance imaging to track how blood vessels responded to pressure. Their findings are published in the journal Discovery Medicine.

The researchers tested this approach in a preclinical model of diabetes-induced HFpEF, focusing on changes in blood flow to the heart and leg muscles. They found that in people with diabetes, problems with blood flow regulation in the leg muscles occurred months earlier than similar problems in the heart. This suggests that leg muscles may provide a better location to capture early HFpEF.

Representative cardiac images during different intervals of normoxic-hypercapnic-recovering normoxic gas stimulation in control rats and diabetic rats of both sexes "The findings suggest that by looking at blood flow in the legs, problems can be identified sooner than focusing only on the heart," said lead researcher Sadi Loai, a Ph.D. in biomedical engineering at the University of Toronto. "This could have major implications for how we diagnose and treat heart failure." The researchers emphasize that the next step will be to test human patients with risk factors for HFpEF and determine if the current MRI platform can indeed identify the disease earlier than traditional diagnostic methods.

“Our ultimate goal is to not only open the door to earlier diagnosis when the disease is treatable, but also to provide new directions for treating this increasingly prevalent disease that has become the most common form of heart failure.”

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