Early markers of left ventricular dysfunction in asymptomatic patients with mixed aortic valve disease and preserved left ventricular ejection fraction

Abstract Background Risk stratification in patients with mixed aortic valve disease (MAVD), defined as the coexistence of aortic stenosis (AS) and aortic regurgitation (AR) is challenging, and indication for aortic valve replacement (AVR) currently relies only on the presence of symptoms or left ventricular ejection fraction (LVEF) 50%. Purpose To assess the association with outcome of early markers of LV dysfunction, such as global longitudinal strain (GLS), and LV diastolic dysfunction, in a large cohort of asymptomatic patients with significant MAVD (≥ moderate AS and ≥ moderate AR) and preserved LVEF (50%). Methods A total of 605 patients (65 ± 16 years, 55% male) with significant MAVD were included and categorized into three groups: (1) No LV dysfunction (n=110), defined as the absence of LV abnormalities or only limited to LV mass index greater than 115 g/m2 in men and 95 g/m2 in women; (2) LV diastolic dysfunction (n=188), defined by the presence of at least two of the following: E/e’ ratio 14, TR velocity 2.8 m/s, left atrial volume index (LAVI) 34 ml/m2 or atrial fibrillation; and (3) LV-systolic dysfunction (n=307), in case of LV-GLS worse than -16% (Figure 1). In case multiple abnormalities were present, patients were classified based on the most severe category. The study outcome was all-cause mortality. Results Over a median follow-up of 7.4 (IQR, 4.5-11) years, 199 patients (33%) died, and 437 (72%) underwent AVR. Patients with No LV dysfunction were younger, more often male, had higher prevalence of bicuspid aortic valve (BAV), and better eGFR. These patients also had higher prevalence of moderate MAVD, less right ventricular dysfunction, and less significant tricuspid regurgitation (TR) when compared to patients with LV diastolic and LV systolic dysfunction. Unadjusted 10-year survival was the highest in patients with No LV dysfunction (86%), followed by those with LV diastolic (69%) and systolic (56%) dysfunction (p0.001) (Figure 2A). Patients with No LV dysfunction underwent AVR less frequently during follow-up than those with LV systolic dysfunction (66% vs.79%, p0.001). Both LV diastolic (HR 2.303; 95%CI 1.099–4.828;p=0.027) and systolic (HR 2.611; 95%CI 1.295–5.267; p=0.007) dysfunction were independently associated with mortality compared to those without LV dysfunction, after adjustment for age, coronary artery disease, diabetes, hypertension, smoking, eGFR 60 ml/min/1.73m², AVR as a time-dependent covariate, BAV, MAVD severity, TAPSE 17 mm, and significant TR. Adjusted 10-year survival remained highest in patients with No LV dysfunction (89%) versus those with LV diastolic (77%) and systolic (70%) dysfunction (p0.001) (Figure 2B). Conclusion In asymptomatic patients with significant MAVD and preserved LVEF, the presence of LV diastolic and/or systolic dysfunction was independently associated with worse long-term survival and may help identify those patients at high risk who could benefit from earlier intervention.