Mitral annular calcification (MAC) is a common degenerative disease. It is increasingly recognized as a cause of mitral stenosis (MS), specifically in elderly patients and those who have chronic comorbidities. Although rheumatic heart disease remains the classic etiology of MS, MAC-related mitral stenosis (MAC-related MS) represents a distinct pathological entity with different functional, structural, and hemodynamic characteristics. MAC-related MS is linked with worse results and poses diagnostic challenges because standard echocardiographic assessment methods were developed mainly for rheumatic mitral stenosis (RMS). Doppler-based pressure gradient estimation and valve area calculations can be inaccurate in MAC because of complex and nonuniform flow dynamics.
The aim of this study was to systematically compare geometric and hemodynamic characteristics of MS caused by MAC vs rheumatic disease by using the normal mitral valve (NMV) as a reference. It also examined how differences in valve morphology influence transmitral flow patterns, vortex formation, energy loss, and pressure gradients independent of chamber compliance or loading conditions.
This study was conducted in two phases. A retrospective analysis of earlier acquired three-dimensional transesophageal echocardiography (TEE) datasets was performed in 70 patients, which included 22 with NMV, 26 with RMS, and 22 with severe MAC. Detailed annular, tunnel, and leaflet-tip dimensions were measured by using Philips QLAB software, which includes anteroposterior and intercommissural diameters, valve areas, tunnel length, enclosed valve volume, and orifice orientation angles. Continuous variables were reported as medians with interquartile ranges, and group comparisons were performed by using Student’s t-test or Wilcoxon rank-sum test as appropriate. Statistical significance was defined as P < 0.05 with Bonferroni correction applied for multiple comparisons. Effect sizes and power calculations showed proper statistical power for key anatomic comparisons. Representative patient datasets were used to create 3D silicone valve models of NMV, RMS, and MAC in the second phase. These models were tested in heart flow simulation under controlled conditions by using particle image velocimetry (PIV) to assess transmitral velocity profiles, vortex formation, coefficient of contraction (CoC), pressure gradients, and left ventricular (LV) flow energetics.
The echocardiographic analysis revealed profound geometric differences between MAC, MS, and RMS. The MAC valves showed significantly smaller annular anteroposterior diameter and area compared with RMS (P = 0.003 and P = 0.021, respectively), and intercommissural dimensions were similar. MAC showed a dramatic reduction in anteroposterior diameter and flow area as compared with RMS (P < 0.0001 and P = 0.002) in the valve tunnel. RMS and MAC exhibited reduced dimensions relative to NMV, with no major difference between the two (P > 0.15) at leaflet tips. MAC valves had significantly shorter tunnel length and smaller total mitral valve volume than RMS (both P < 0.0001). These findings indicate that severe functional stenosis in MAC occurs in the annulus and calcified tunnel, and RMS produces a more progressive funnel-shaped narrowing toward leaflet tips.
In vitro experiments demonstrated distinct hemodynamic consequences of these geometric differences. Despite having a larger geometric orifice area than the RMS model, the MAC valve exhibited a smaller effective orifice area and a lower coefficient of contraction (0.35 vs 0.50). MAC produced the highest peak mitral jet velocity (1.67 m/s), Reynolds number (11,200), and estimated pressure gradient (11.2 mm Hg) as compared with RMS (6.8 mm Hg) and NMV (4.4 mm Hg). A stable transmitral vortex ring was observed only in the NMV model; neither RMS nor MAC demonstrated organized vortex formation. LV flow energetics showed that MAC generated the highest kinetic energy and the greatest rate of energy dissipation throughout the cardiac cycle, which indicates inefficient flow and increased energy loss attributable to abrupt obstruction from calcific deposits and reduced intravalvular volume.
Limitations include a relatively small imaging sample size, reliance on 2D flow measurements for complex 3D dynamics, use of water instead of blood analogues, and testing of the single representative valve models that cannot capture the full heterogeneity of MAC. The study gives important insights and a framework to improve the assessment and management of MAC-related MS.
This study identifies MAC-related mitral stenosis as a unique morphological and hemodynamic phenotype, distinct from rheumatic disease. It is characterized by severe narrowing, reduced valve volume, lower contraction coefficients, increased turbulence, greater energy dissipation, and larger pressure gradients. These differences highlight the limitations of Doppler assessments used for rheumatic mitral stenosis and the necessity for specific evaluation strategies in MAC patients.
Reference: Hashemi MS, Abdelmaseeh P, Nehvi A, Pressman GS, Kheradvar A. Two Faces of Mitral Stenosis: Uncovering Structural and Hemodynamic Signatures of Rheumatic and Mitral Annular Calcification-Induced Disease. J Am Heart Assoc; 2025. doi:10.1161/JAHA.125.045018
