Abstract 4372169: Sex Differences in Exercise-Induced Diastolic Dysfunction in Patients without Evidence of Myocardial Ischemia

Background: We studied sex differences in exercise-induced diastolic dysfunction (Ex-DD) in patients undergoing exercise stress echocardiography (ExE) without myocardial ischemia. Methods: Retrospectively, 701 patients [57±13 years, 405(58%) women] undergoing ExE who had no exercise-induced myocardial ischemia were included and followed for a median of 3.4 years for combined outcomes [death, acute coronary syndrome (ACS), cardiac hospitalization and follow-up cardiac testing]. Ex-DD was defined as presence of 2 or more abnormal Doppler-derived measures, namely e’ velocity at rest, post-exercise septal E/e’ ratio, and post-exercise tricuspid regurgitant jet velocity. Results: During follow-up, combined outcomes occurred in 133(19%) patients (9 died, 7 ACS, 40 hospitalization, and 96 repeated ischemia evaluation). There were no significant sex differences regarding clinical, demographic variables, or EF, however, men had a higher prevalence of coronary artery disease, and women had more resting DD [36(9%) vs 16(5%), p=0.042] and lower workloads. 236 (34%) patients had Ex-DD which was more prevalent in women [152(38%) vs 83(28%), p=0.009]. Survival analyses suggested that Ex-DD (HR: 1.49, 95% CI: 1.06 to 2.1), but not sex, was an independent predictor of the combined outcomes in isolation. Patients were stratified based on sex and Ex-DD (Figure1). There were significant differences regarding age, risk factor, resting and exercise echocardiographic measures such that the best profile was seen in women without Ex-DD and the worst profiles were similarly seen in men and women with Ex-DD. Survival analyses suggested that, compared to women without Ex-DD, both categories of women with Ex-DD (HR: 1.78, 95% CI: 1.12 to 2.84) and men with Ex-DD (HR: 1.89, 95% CI: 1.1 to 3.26) were associated with the outcomes, while men without Ex-DD was an intermediate group. These relationships persisted after propensity matching risk factors, pre-existing coronary artery disease and resting diastolic dysfunction. Conclusions: Women with Ex-DD and no evidence of myocardial ischemia during exercise echocardiography carry a high risk of adverse events, which is independent of traditional risk factors, comorbidities and baseline diastolic function. Future studies should focus on underlying pathophysiology and novel preventive and disease-modifying treatments for subclinical and clinically overt myocardial dysfunction in these patients.