Natural history of moderate aortic stenosis and predictors for mortality: Systematic review and meta-analysis

Although the current guidelines advocate imaging surveillance for moderate aortic stenosis (AS), recent studies suggest a worse prognosis associated with moderate AS than previously reported. Considering the recent paradigm shift in AS management, the risk/benefit profile of aortic valve replacement (AVR) for moderate AS needs to be re-evaluated. Herein, we conducted meta-analyses of natural history and risk predictors in patients with moderate AS. PubMed and EMBASE were searched through May 2022 to identify studies that investigated the natural history of patients with moderate AS. Meta-analyses with random effects model were conducted. Our analysis included 20 observational studies which enrolled a total of 11,114 patients with moderate AS. The rate of all-cause death was 11.0 [95 % confidence interval (CI), 7.6-14.4] per 100 patients per year. Surgical or transcatheter AVR occurred at a rate of 8.5 (95 % CI, 6.2-10.8; I², 98.9 %) per 100 patients per year. Occurrence of AVR during follow-up [hazard ratio (HR) (95 % CI) = 0.56 (0.42-0.75), p < 0.001] and early AVR for moderate AS [HR (95 % CI) = 0.47 (0.25-0.90), p = 0.02] were associated with significantly lower all-cause mortality, while left ventricular ejection fraction <50 % [HR (95 % CI) = 1.84 (1.33-2.57), p = 0.0003] and symptomatic status [HR (95 % CI) = 1.52 (1.32-1.75), p < 0.0001] were associated with increased all-cause mortality. Sex difference was not related to all-cause mortality. Our meta-analysis suggested that moderate AS was associated with high mortality, especially in low left ventricular systolic function or symptomatic patients. In addition, significant portion of the patients underwent AVR during follow-up.