Mild Aortic Valve Stenosis Predicts Worse Survival after Hospital Admission for Heart Failure with Preserved Ejection Fraction

Abstract

Introduction Mild aortic stenosis (AS) and aortic sclerosis are associated with increased mortality in the general population, which may be mediated by their reflection of underlying inflammation and obesity, both risk factors for HFpEF. Hypothesis Patients with HFpEF and mild AS or aortic sclerosis constitute a distinct phenotype with worse prognosis. Methods Consecutive HFpEF patients, admitted to Mayo Clinic Rochester between 2010-2015 for treatment with intravenous diuretics, were included. Patients with more than mild AS or more than mild mitral stenosis were excluded. Mild AS was defined as an aortic peak jet velocity 1.9-2.9 m/s. Extensive valvular leaflet thickening/calcification with normal peak jet velocity (≤1.8 m/s) was classified as aortic sclerosis. All-cause mortality and death causes were registered with censoring at last contact. Results In 370 HFpEF patients (age 77±13 years; 58% women), 111 had mild AS (30%), while 104 had aortic sclerosis (28%). Patients with mild AS or aortic sclerosis were significantly older with worse renal function and a lower lean body mass. Patients with mild AS (but not aortic sclerosis) had a higher stroke volume index [41 mL/m² (34-48 mL/m²) versus 46 mL/m² (40-52 mL/m²) in controls with a normal aortic valve; age-adjusted P-value<0.001] and an increased preload-recruitable stroke work (98.1±27.3 erg.cm−³.10³ versus 91.4±26.2 erg.cm−³.10³ in controls; age-adjusted P-value = 0.021). E/e’ decreased from mild AS [20.0 (15.0-25.0)], over aortic sclerosis [17.1 (12.9-23.7)] to controls [15.7 (12.0-20.0); age-adjusted P-value<0.001 for trend]. Over 38±32 months of follow-up, 247 patients died (67%) with mortality causes retrieved in 205 cases (83%). Both mild AS [HR (95%CI) = 1.57 (1.17-2.12)] and aortic sclerosis [HR (95%CI) = 1.51 (1.11-2.05)] were associated with all-cause mortality (Figure). After adjusting for differences in baseline characteristics, the hazard of aortic sclerosis disappeared, while the hazard of increased peak jet velocity remained statistically significant [HR (95%CI) = 1.31 (1.01-1.70) per 1 m/s; P-value = 0.042]. Patients with mild AS versus a normal aortic valve had less non-HF cardiovascular mortality (2.9% versus 18.4%) and more deaths due to comorbid conditions (44.1% versus 28.9%). Conclusions Mild AS in HFpEF is associated with increased mortality and a shift from non-HF cardiovascular towards comorbidity-driven deaths. While the risk of valvular sclerosis/calcification is mediated by age and comorbidities, an elevated peak jet velocity may indicate a distinct phenotype with increased stroke volume and contractility but poor outcome. Mild aortic stenosis (AS) and aortic sclerosis are associated with increased mortality in the general population, which may be mediated by their reflection of underlying inflammation and obesity, both risk factors for HFpEF. Patients with HFpEF and mild AS or aortic sclerosis constitute a distinct phenotype with worse prognosis. Consecutive HFpEF patients, admitted to Mayo Clinic Rochester between 2010-2015 for treatment with intravenous diuretics, were included. Patients with more than mild AS or more than mild mitral stenosis were excluded. Mild AS was defined as an aortic peak jet velocity 1.9-2.9 m/s. Extensive valvular leaflet thickening/calcification with normal peak jet velocity (≤1.8 m/s) was classified as aortic sclerosis. All-cause mortality and death causes were registered with censoring at last contact. In 370 HFpEF patients (age 77±13 years; 58% women), 111 had mild AS (30%), while 104 had aortic sclerosis (28%). Patients with mild AS or aortic sclerosis were significantly older with worse renal function and a lower lean body mass. Patients with mild AS (but not aortic sclerosis) had a higher stroke volume index [41 mL/m² (34-48 mL/m²) versus 46 mL/m² (40-52 mL/m²) in controls with a normal aortic valve; age-adjusted P-value<0.001] and an increased preload-recruitable stroke work (98.1±27.3 erg.cm−³.10³ versus 91.4±26.2 erg.cm−³.10³ in controls; age-adjusted P-value = 0.021). E/e’ decreased from mild AS [20.0 (15.0-25.0)], over aortic sclerosis [17.1 (12.9-23.7)] to controls [15.7 (12.0-20.0); age-adjusted P-value<0.001 for trend]. Over 38±32 months of follow-up, 247 patients died (67%) with mortality causes retrieved in 205 cases (83%). Both mild AS [HR (95%CI) = 1.57 (1.17-2.12)] and aortic sclerosis [HR (95%CI) = 1.51 (1.11-2.05)] were associated with all-cause mortality (Figure). After adjusting for differences in baseline characteristics, the hazard of aortic sclerosis disappeared, while the hazard of increased peak jet velocity remained statistically significant [HR (95%CI) = 1.31 (1.01-1.70) per 1 m/s; P-value = 0.042]. Patients with mild AS versus a normal aortic valve had less non-HF cardiovascular mortality (2.9% versus 18.4%) and more deaths due to comorbid conditions (44.1% versus 28.9%). Mild AS in HFpEF is associated with increased mortality and a shift from non-HF cardiovascular towards comorbidity-driven deaths. While the risk of valvular sclerosis/calcification is mediated by age and comorbidities, an elevated peak jet velocity may indicate a distinct phenotype with increased stroke volume and contractility but poor outcome.