Pathogenesis of mitral annular calcification – the consequence of comorbidities or left ventricular mechanics?
C Engelsgaard, A Haujir, A P Diederichsen, J S Lindholt, P Kumarathurai, K A Oevrehus, V Poulsen, P Pellikka, M A Clavel, J S DahlAbstract
Aims
- Mitral annular calcification (MAC) is common in the general population, especially among women and patients with left ventricular (LV) pressure overload conditions, which may increase stress onto the mitral valve inducing the calcification process. The pathogenesis of MAC is presumed multifactorial, but remains poorly understood. Women display a different LV response to pressure overload compared to men, but this association has rather not been thoroughly investigated.
Methods and results
- The DANCAVAS pilot study included 1422 randomly selected individuals from the general population aged 60-75 years to undergo a computed tomography (CT)-based screening program. After the exclusion of patients due to prior mitral valve surgery (n=2) and patients with missing echocardiographic data (n=957), 463 individuals were included in this substudy. They were stratified according to MAC severity based on mitral valve calcification (MVC) score assessed by CT. MAC was found in 165 (32.6%) patients with MVC scores <100 AU in 20.7%, 100-400 AU in 8.2% and >400 AU in 6.7%. While MAC was most prevalent in men, women presented with higher MVC scores and severe MAC on echocardiography. Patients with MAC were elderly with cardiovascular risk factors. Concentric LV geometry with smaller LV cavities and higher relative wall thickness assessed by echocardiography were highly associated with MAC (p<0.001). From multivariate analyses, relative wall thickness and the mechanical load on the mitral valve (i.e. StressMV = (systolic blood pressure + aortic mean gradient)/(π x [LV end-systolic diameter/2]2)) strongly associated with MAC (standard deviation-adjusted OR 28.8, 95% CI [15.6;53.5] and 2.97 [2.25;3.91], respectively) and MAC severity (10.9 [7.74;15.5] and 2.98 [2.33;3.82], respectively). The predictive performance was high with area under curve (AUC) of 0.78 [0.74;0.82] by including StressMV in the model of age, sex and cardiovascular comorbidity (p<0.001). However, relative wall thickness had distinctive importance (AUC 0.96 [0.94;0.98], p<0.001) regardless of sex.
Conclusion
- MAC is common in the general population with the highest prevalence among men. LV geometry and the pressure on the mitral valve are crucial factors in the pathogenesis of MAC, and sex-specific differences in LV response to pressure overload may elucidate why more extensive grades of MAC mainly affect women.MVC and Relative wall thicknessMVC and StressMV