Aortic Stenosis: New Insights in Diagnosis, Treatment, and Prevention

Abstract

Aortic stenosis (AS) is one of the most common valvular heart diseases and the number of patients with AS is expected to increase globally as the older population is growing fast. Since the majority of patients are elderly, AS is no longer a simple valvular heart disease of left ventricular outflow obstruction but is accompanied by other cardiac and comorbid conditions. Because of the significant variations of the disease, identifying patients at high risk and even earlier detection of patients with AS before developing symptomatic severe AS is becoming increasingly important. With the proven of efficacy and safety of transcatheter aortic valve replacement (TAVR) in the severe AS population, there is a growing interest in applying TAVR in those with less than severe AS. A medical therapy to reduce or prevent the progression in AS is actively investigated by several randomized control trials. In this review, we will summarize the most recent findings in AS and discuss potential future management strategies of patients with AS.

Keywords: Artificial intelligence; Prognosis; Transcatheter aortic valve replacement.

Figure 1. Longitudinal change of AS and LV hemodynamics between sexes. Longitudinal analysis using splines within mixed linear models is shown with mean and 95% confidence interval for AS and LV hemodynamics until developing AVA ≤1.0 cm² in a total of 927 patients.

AS = aortic stenosis; AVA= aortic valve area; LV = left ventricular; LVEF = left ventricular ejection fraction; MG = mean pressure gradient; peak V = peak velocity; SV = stroke volume. With permission from Ito S, Miranda WR, Nkomo VT, Lewis BR, Oh JK. Sex differences in LV remodeling and hemodynamics in aortic stenosis: sex-specific criteria for severe stenosis? JACC Cardiovasc Imaging 2022;15:1175-89.

Figure 2. The pathophysiology of AS. The pathophysiology of AS is summarized. Initiation phase: endothelial injury facilitates the infiltration of oxidized lipids and inflammatory cells into the valve and the release of proinflammatory mediators. These trigger the very early stages of valve calcification. The propagation phase: these proinflammatory processes subsequently induce VICs to undergo osteogenic differentiation via several different mechanisms, including the binding of receptor activator of nuclear kappa B ligand to receptor activator of nuclear kappa B. Differentiated cells within the aortic valve first lay down a collagen matrix and other bone-related proteins causing valvular thickening and stiffening before producing calcium. Additionally, apoptotic remnants of some VICs and inflammatory cells create a nidus for apoptosis-mediated calcification. Calcification of the valve induces compliance mismatch, resulting in increased mechanical stress and injury. This results in further calcification via osteogenic differentiation and apoptosis. Hence, a self-perpetuating cycle of calcification, valve injury, apoptosis, and osteogenic activation is established that drives the propagation phase of the disease.

ACE = angiotensin-converting enzyme; AS = aortic stenosis; VIC = valvular interstitial cell. With permission from Pawade TA, Newby DE, Dweck MR. Calcification in aortic stenosis: the skeleton key. J Am Coll Cardiol 2015;66:561-77.