Irvine, Calif., Jan. 22, 2026 — University of California, Irvine and Philadelphia-based Jefferson Health researchers have identified fundamental structural and functional differences between two major causes of mitral valve stenosis. This narrowing restricts blood flow through the heart. The findings challenge current diagnostic approaches and may help clinicians tailor treatment decisions for a growing patient population.
The study, published in the Journal of the American Heart Association , combined 3D ultrasound heart imaging with patient-specific laboratory modeling to show that stenosis caused by mitral annular calcification, or MAC, is different in terms of structure and blood flow dynamics from rheumatic mitral stenosis, the form on which many current diagnostic standards are based.
The researchers found that using diagnostics developed for rheumatic disease may underestimate or mischaracterize MAC-related mitral stenosis, potentially affecting clinical decision-making and treatment selection.
Mitral annular calcification affects an estimated 8 to 15 percent of the general population and is more common in older adults, patients with chronic kidney disease, and individuals with a history of chest radiation.
Despite its prevalence, mitral stenosis associated with mitral valve disease has not been well-characterized. It's often assessed using frameworks developed for rheumatic heart disease, though there are significant differences between the two, particularly in valve structure and blood flow constraints.
"For decades, mitral stenosis has been assessed using a one-size-fits-all approach," said senior co-author of the study 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 team used a two-phase strategy. First, they analyzed 3D transesophageal echocardiography data from 70 patients, making detailed measurements to compare healthy mitral valves with valves affected by MAC-related and rheumatic mitral stenosis.
In the second phase, researchers used 3D printing to create patient-specific silicone models representing healthy, rheumatic and MAC-affected valves. They evaluated these models in a heart flow simulator that replicates conditions inside the human heart. This controlled approach helped isolate how valve geometry alters blood flow and pressure gradients –factors that can be difficult to disentangle in routine clinical imaging.
Compared with rheumatic mitral stenosis, MAC-related stenosis demonstrated:
· Smaller overall valve dimensions and reduced valve volume.
· Distinct leaflet motion and apically displaced hinge points.
· Disproportionately high pressure gradients across the valve.
· Greater kinetic energy loss during blood flow.
· Unique flow behavior despite a relatively larger geometric orifice area.
"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 senior co-author Gregg Pressman, Jefferson Health professor of medicine. "That mismatch between anatomy and hemodynamics helps explain why conventional thresholds can fail in this population."
The findings have immediate implications for clinical practice. The researchers emphasize that clinicians should use caution when applying rheumatic-based diagnostic thresholds to patients with MAC-related mitral stenosis and highlight the need for disease-specific diagnostic criteria and management guidelines.
The detailed structural and flow characterization may also inform future transcatheter and surgical therapies tailored for MAC-related stenosis. Many interventional strategies were developed with rheumatic disease in mind and may not fully account for the distinct anatomy and hemodynamics seen in calcification-driven stenosis.
Beyond its impact on the mitral valve, MAC is also recognized as a marker of broader cardiovascular risk and has been associated with adverse outcomes, including stroke and increased mortality.
The study's first author, Mohammad Saber Hashemi, who conducted this work as a postdoctoral scholar at UC Irvine, is now an assistant professor at Kansas State University. Other co-authors include Peter Abdelmaseeh and Atif Nehvi, both from Jefferson Health. This research was partially supported by the National Institutes of Health (National Heart, Lung, and Blood Institute) and the National Science Foundation.
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