Effect of diabetes mellitus on the development of left ventricular contractile dysfunction in women with heart failure and preserved ejection fraction

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome with sex-specific pathophysiology. Estrogen deficiency is believed to be responsible for the development of HFpEF in women. However, estrogen deficiency does not seem to be completely responsible for the differences in HFpEF prevalence between sexes. While diabetes mellitus (DM) frequently coexists with HFpEF in women and is associated with worse outcomes, the changes in myocardial contractility among women with HFpEF and the DM phenotype is yet unknown. Therefore, we aimed to investigate sex-related differences in left ventricular (LV) contractility dysfunction in HFpEF comorbid with DM. METHODS: A total of 224 patients who underwent cardiac cine MRI were included in this study. Sex-specific differences in LV structure and function in the context of DM were determined. LV systolic strains (global longitudinal strain [GLS], circumferential strain [GCS] and radial strain [GRS]) were measured using cine MRI. The determinants of impaired myocardial strain for women and men were assessed. RESULTS: The prevalence of DM did not differ between sexes (p > 0.05). Despite a similar LV ejection fraction, women with DM demonstrated a greater LV mass index than women without DM (p = 0.023). The prevalence of LV geometry patterns by sex did not differ in the non-DM subgroup, but there was a trend toward a more abnormal LV geometry in women with DM (p = 0.072). The magnitudes of systolic strains were similar between sexes in the non-DM group (p > 0.05). Nevertheless, in the DM subgroup, there was significant impairment in women in systolic strains compared with men (p < 0.05). In the multivariable analysis, DM was associated with impaired systolic strains in women (GLS [β = 0.26; p = 0.007], GCS [β = 0.31; p < 0.001], and GRS [β = −0.24; p = 0.016]), whereas obesity and coronary artery disease were associated with impaired systolic strains in men (p < 0.05). CONCLUSIONS: Women with DM demonstrated greater LV contractile dysfunction, which indicates that women with HFpEF comorbid with DM have a high-risk phenotype of cardiac failure that may require more aggressive and personalized medical treatment.