The prognostic value of aortic stenosis and aortic sclerosis in patients with heart failure with reduced ejection fraction

Abstract Background Aortic stenosis (AS) and aortic valve sclerosis (AVS) as assessed by Doppler echocardiography have been associated with adverse clinical outcomes in patients with heart failure with reduced ejection fraction (HFrEF). However, further clarification of the role of AV and AVS in the HFrEF population is warranted. Methods A total of 873 patients with stable HFrEF were included in this retrospective cohort study. At referral, the patients had a left ventricular ejection fraction (LVEF) of 45% or lower Baseline clinical and echocardiographic data were retrieved from the heart failure outpatient clinic's database, and the patients were followed through a nationwide register for the outcome of all-cause mortality. The presence of AS and AVS was assessed using Doppler-derived pressure gradients of the aortic valve (AV) from the echocardiogram. Cox-regression models were used to determine the association between AV peak gradient and mortality. Multivariable models were adjusted for demographic, clinical, and echocardiographic parameters (age, sex, diabetes (DM), ischemic heart disease (IHD), BMI, heart rate, mean arterial pressure, total cholesterol and atrial fibrillation (AF), LVEF, left atrial volume index (LAVi), left ventricular mass index (LVMi), E/e’). Results Seventy-four percent of patients were male, and mean age was 66.8 ± 11.4 years. In total, 13% had DM, 57% had IHD, 38% had NYHA III-IV, 8% had implantable cardiac device (including pacemaker, ICD, and CRT), and 15.9% had AF. Mean LVEF was 27.3 ± 9.4% with a mean LVMi of 120.2 g/m2 ± 38.2. Mean AV peak velocity was 1.4 m/s ± 0.5 and median AV peak gradient was 6.3 mmHg (IQR 4.7; 8.9). During a median follow-up of 3.3 years (IQR 1.9 – 4.7 years), 143 patients (16.4 %) reached the outcome. In univariable analysis, AV peak gradient was associated with all-cause mortality (HR 1.23 per 10 mmHg increase, 95% CI 1.05-1.44, p = 0.012). LVEF modified the prognostic value of AV peak gradient (p = 0.026 for interaction). After stratifying the population by the median value of LVEF (cut-off = 28%), AV peak gradient remained prognostic only in patients with LVEF above the median (HR 1.58 per 10 mmHg increase, 95% CI 1.30-1.91, p < 0.001), whereas AV peak gradient was not significantly associated with mortality amongst the patients with LVEF below the median level (HR 1.03 per 10 mmHg increase, 95% CI 0.83-1.37, p = 0.827). After multivariable adjustment, AV peak gradient remained an independent predictor of the outcome in patients in the higher median of LVEF (HR 1.32 per 10 mmHg increase, 95% CI 1.02-1.70, p = 0.035) (Figure 1). Conclusion Presence of AS and AVS (derived by AV peak gradient Doppler echocardiography) is an independent predictor of all-cause mortality amongst HFrEF patients. However, presence of AS and AVS only entails prognostic information amongst the HFrEF patients without severely reduced LVEF.Incidence rates of all-cause mortality