Sex Differences in Extensive Mitral Annular Calcification With Associated Mitral Valve Dysfunction

Mitral annular calcification (MAC)-related mitral valve (MV) dysfunction is an increasingly recognized entity, which confers a high burden of morbidity and mortality. Although more common among women, there is a paucity of data regarding how the phenotype of MAC and the associated adverse clinical implications may differ between women and men. A total of 3,524 patients with extensive MAC and significant MAC-related MV dysfunction (i.e., transmitral gradient ≥3 mm Hg) were retrospectively analyzed from a large institutional database, with the goal of defining gender differences in clinical and echocardiographic characteristics and the prognostic importance of MAC-related MV dysfunction. We stratified patients into low- (3 to 5 mm Hg), moderate- (5 to 10 mm Hg), and high- (≥10 mm Hg) gradient groups and analyzed the gender differences in phenotype and outcome. The primary outcome was all-cause mortality, assessed using adjusted Cox regression models. Women represented the majority (67%) of subjects, were older (79.3 ± 10.4 vs 75.5 ± 10.9 years, p <0.001) and had a lower burden of cardiovascular co-morbidities than men. Women had higher transmitral gradients (5.7 ± 2.7 vs 5.3 ± 2.6 mm Hg, p <0.001), more concentric hypertrophy (49% vs 33%), and more mitral regurgitation. The median survival was 3.4 years (95% confidence interval 3.0 to 3.6) among women and 3.0 years (95% confidence interval 2.6 to 4.5) among men. The adjusted survival was worse among men, and the prognostic impact of the transmitral gradient did not differ overall by gender. In conclusion, we describe important gender differences among patients with MAC-related MV dysfunction and show worse adjusted survival among men; although, the adverse prognostic impact of the transmitral gradient was similar between men and women.

Introduction

Mitral annular calcification (MAC) occurs secondary to dystrophic calcification of the mitral annulus and has been shown to be an independent predictor of cardiovascular events, including atrial fibrillation (AF),^1,2 myocardial infarction,³ and cardiovascular death.^3,4 MAC-related mitral valve (MV) dysfunction is caused by the encroachment of annular calcium onto the valve leaflets, resulting in restricted annular dynamics and decreased leaflet mobility and can lead to mitral stenosis and often, concomitant mitral regurgitation (MR). The transmitral gradient represents an integrative measure of the hemodynamic impact of MAC-related MV dysfunction and offers independent prognostic information,^5,6 with markedly increased mortality at higher gradients. MAC is traditionally viewed as a female-predominant disease, and it is increasingly recognized that MAC-related MV dysfunction is more common among women.^7,8 However, gender differences in the prevalence and natural history of MAC-related MV dysfunction and in the prognostic implications of the transmitral gradient remain poorly understood. An improved understanding of such differences may allow A more precise risk assessment and stratification, which in turn has important implications for patient selection for the expanding array of therapeutic options in this population.⁹ This study aimed to define the important differences in clinical characteristics, echocardiographic phenotypes, and clinical outcomes between women and men with MAC and MV dysfunction. We hypothesized that although MAC and MV dysfunction are more prevalent in women, the outcomes would be similarly affected by the presence of hemodynamically significant MAC across both genders.