April 25, 2026Journal of the American College of Cardiology
Calcific Aortic Stenosis
Key result
Valve narrowing and secondary LVH drive AS progression, requiring therapies targeting inflammation, fibrosis, and calcification.
Why the study?
Aortic stenosis causes major morbidity, mortality, and health economic costs, but no medical interventions currently delay or halt its progression, requiring re-evaluation of pathophysiology to develop novel therapeutic strategies.
Key Points
- The review aims to understand the pathophysiology of aortic stenosis and explore potential therapeutic strategies.
- Examined the mechanisms of aortic stenosis focusing on valve and myocardial interactions.
- Highlighted the roles of inflammation, fibrosis, and calcification in disease progression.
- Discussed comparisons with other pathological conditions to identify novel therapies.
- Identified inflammation and fibrosis as key factors in valve narrowing and left ventricular hypertrophy.
- Addressed the transition from hypertrophy to heart failure as a critical outcome of disease progression.
- Proposed potential therapeutic strategies based on shared mechanisms with other cardiovascular diseases.
Structured PICO
P
Population
Patients with calcific aortic stenosis
This review highlights the pathophysiology of calcific aortic stenosis and left ventricular hypertrophy, emphasizing the need for novel medical interventions to halt disease progression.
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
MDMilind DesaiVice-Chair, Heart Vascular & Thoracic Institute, Cleveland Clinic
“We are starting to appreciate that CAVS is not simply a passive degenerative process associated with aging but that it involves active mechanisms that may be amenable to intervention. We believe we can improve on the current commonly employed strategy of watchful waiting until patients become eligible for aortic valve replacement.”
“You need to target at-risk patients very early. Once you have calcification, then it's perhaps a different pathogenesis that may be more accelerated as opposed to the precalcification molecular changes that are occurring.”
“We still think Lp(a) is a very good target to prevent aortic valve stenosis, but not necessarily treat it once calcium deposits have been established within the valve.”
Implication
May support closer LV decompensation monitoring in AS with hypertrophy; leaves open efficacy of novel anti-inflammatory and antifibrotic therapies.
Abstract
Although aortic stenosis is a common condition associated with major morbidity, mortality, and health economic costs, there are currently no medical interventions capable of delaying or halting its progression. Re-evaluation of the underlying pathophysiology is therefore required so that novel therapeutic strategies can be developed. Aortic stenosis is characterized by progressive aortic valve narrowing and secondary left ventricular hypertrophy. Both processes are important because in combination they drive the development of symptoms and adverse events that characterize the latter stages of the disease. In this review, the authors examine the pathophysiology of aortic stenosis with respect to both the valve and the myocardium. In particular, the authors focus on the role of inflammation, fibrosis, and calcification in progressive valve narrowing and then examine the development of left ventricular hypertrophy, its subsequent decompensation, and the transition to heart failure. Finally the authors discuss potential therapeutic strategies on the basis of similarities aortic stenosis shares with other pathological conditions.
Discussion
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Cite This Study
Dweck et al. (2012) conducted a review in Calcific Aortic Stenosis. Aortic stenosis progression is driven by valve narrowing and secondary left ventricular hypertrophy, highlighting the need for novel therapies targeting inflammation, fibrosis, and calcification.