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

Abstract

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.

Figure 1:

Study population Derivation of the study population and control group after exclusions is shown.

Figure 2:

Sex-specific differences in prevalence and transmitral gradients in patients with extensive MAC and MV dysfunction (A) The prevalence by sex of extensive MAC with mitral valve dysfunction, defined as a transmitral gradient of ≥3 mmHg, is shown, with women significantly outnumbering men (67%). In (B), the distribution of the transmitral gradient by sex is shown, with men predominating at lower gradients (≤5 mmHg) and women at higher gradients (>5 mmHg).

Figure 3:

Spline analysis of sex-specific impact of the transmitral gradient on all-cause mortality in extensive MAC with MV dysfunction In exploratory spline survival analysis the adjusted hazard ratio of death relative to the control group progressively increases at higher transmitral gradients for both women and men. However, for women the HR does not become significantly greater than 1 until a gradient between 8 and 9 mmHg, while for men it does so between 5 and 6 mmHg. Survival was adjusted for age, sex, and common MAC-associated comorbidities (diabetes, hypertension, CAD and CKD).