Irvine, Calif., Jan. 22, 2026 — Researchers from the University of California, Irvine, and Jefferson Health in Philadelphia have unveiled crucial differences in the structural and functional aspects of mitral valve stenosis, a condition that narrows the heart valve, impeding blood flow. These findings, published in the Journal of the American Heart Association, could revolutionize diagnostic and treatment strategies for a growing number of patients.
The study employed advanced 3D ultrasound imaging and patient-specific laboratory modeling to differentiate stenosis caused by mitral annular calcification (MAC) from the rheumatic form, which currently informs many diagnostic standards. This revelation suggests that existing methods may mischaracterize MAC-related stenosis, potentially impacting clinical decisions.
Understanding Mitral Valve Stenosis
Mitral valve stenosis affects a significant portion of the population, with MAC impacting an estimated 8 to 15 percent, particularly among older adults, those with chronic kidney disease, and individuals with a history of chest radiation. Despite its prevalence, MAC-related stenosis has been assessed using rheumatic heart disease frameworks, which may not account for its unique characteristics.
“For decades, mitral stenosis has been assessed using a one-size-fits-all approach,” said Arash Kheradvar, senior co-author and 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.”
Innovative Research Methodology
The research team adopted a two-phase approach. Initially, they analyzed 3D transesophageal echocardiography data from 70 patients, comparing healthy mitral valves with those affected by MAC-related and rheumatic stenosis. In the second phase, they used 3D printing to create silicone models of these valves, which were then evaluated in a heart flow simulator to understand the impact of valve geometry on blood flow and pressure.
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,” noted Gregg Pressman, senior co-author and Jefferson Health professor of medicine. “That mismatch between anatomy and hemodynamics helps explain why conventional thresholds can fail in this population.”
Implications for Clinical Practice
The findings have significant implications for clinical practice. The researchers caution against using rheumatic-based diagnostic thresholds for MAC-related mitral stenosis and advocate for the development of disease-specific criteria and management guidelines. This detailed understanding of structural and flow characteristics could also guide future transcatheter and surgical therapies tailored for MAC-related stenosis.
Beyond its impact on the mitral valve, MAC is recognized as a marker of broader cardiovascular risk, associated with adverse outcomes such as stroke and increased mortality. This underscores the importance of accurate diagnosis and tailored treatment strategies.
Future Directions and Acknowledgments
The study’s first author, Mohammad Saber Hashemi, now an assistant professor at Kansas State University, along with co-authors Peter Abdelmaseeh and Atif Nehvi from Jefferson Health, contributed to this groundbreaking research. The work was supported by the National Institutes of Health and the National Science Foundation.
Founded in 1965, the University of California, Irvine is a leading research institution, known for its academic excellence and innovation. It is part of the prestigious Association of American Universities and is ranked among the top 10 public universities in the United States. For more information, visit www.uci.edu.
