Researchers from the University of California, Irvine and Jefferson Health have identified key structural and functional differences between two major causes of mitral valve stenosis, a condition that restricts blood flow through the heart. Their findings, published in the Journal of the American Heart Association, suggest that current diagnostic methods may not accurately assess one form of the disease and could influence treatment decisions for patients.
The study combined 3D ultrasound imaging with laboratory modeling tailored to individual patients. The team compared mitral annular calcification (MAC)-related stenosis with rheumatic mitral stenosis, which has been the basis for many diagnostic standards. They found that using diagnostics developed for rheumatic disease can underestimate or mischaracterize MAC-related mitral stenosis.
Mitral annular calcification affects about 8 to 15 percent of people, especially older adults and those with chronic kidney disease or prior chest radiation. Despite its frequency, this type of mitral stenosis is often evaluated using criteria designed for rheumatic disease, even though there are important differences in valve structure and blood flow.
“For decades, mitral stenosis has been assessed using a one-size-fits-all approach,” said Arash Kheradvar, UC Irvine professor of radiological sciences, biomedical engineering and medicine. “But MAC-related stenosis behaves differently. The valve structure is different and blood flow patterns are different, and the relationship between anatomy and severity doesn’t follow the same rules.”
The researchers first analyzed 3D echocardiography data from 70 patients to compare healthy valves with those affected by both types of stenosis. Next, they used 3D printing to create silicone models representing each type and tested them in a heart simulator to see how valve shape affected blood flow and pressure.
They observed that MAC-related stenosis had smaller overall valve dimensions, distinct leaflet motion, higher pressure gradients across the valve, greater energy loss during blood flow, and unique flow behavior despite a relatively larger opening.
“What’s striking is that patients with MAC-related stenosis can appear to have a reasonably sized opening on imaging yet experience pressure gradients and energy losses that indicate much more severe obstruction,” said Gregg Pressman, Jefferson Health professor of medicine. “That mismatch between anatomy and hemodynamics helps explain why conventional thresholds can fail in this population.”
The study highlights that clinicians should be cautious when applying rheumatic-based diagnostic thresholds to MAC-related cases. It also suggests a need for new diagnostic criteria specific to this condition.
Detailed analysis from this research may help guide future surgical or catheter-based therapies for MAC-related stenosis since many existing treatments were developed based on rheumatic disease characteristics.
Beyond its effect on the heart valve itself, MAC is considered an indicator of broader cardiovascular risk linked to adverse outcomes such as stroke or increased mortality.
The study’s first author was Mohammad Saber Hashemi—now at Kansas State University—with other co-authors including Peter Abdelmaseeh and Atif Nehvi from Jefferson Health. The research received partial support from the National Institutes of Health (National Heart, Lung, and Blood Institute) and the National Science Foundation.
The University of California Irvine began in 1965 as part of the University of California system and maintains its campus in Irvine, California. As a public research institution recognized for high research activity according to its official website, UC Irvine offers undergraduate and graduate programs across various fields while engaging in international collaborations to extend its global impact.