Predictors of Major Adverse Cardiovascular Events in Patients With Moderate Aortic Stenosis: Implications for Aortic Valve Replacement

Abstract

Background: Although the prognosis and management of severe aortic stenosis has been extensively studied, the risk stratification and outcomes of patients with moderate aortic stenosis remain elusive. Methods: This study included 674 patients from the Cleveland Clinic Health System with moderate aortic stenosis (aortic valve area, 1–1.5 cm 2 ; mean gradient, 20–40 mm Hg; and peak velocity <4 m/s) and an NT-proBNP (N-terminal pro-B-type natriuretic peptide) level within 3 months of index diagnosis. The primary outcome of major adverse cardiovascular events (defined as the composite outcome of progression to severe aortic stenosis requiring aortic valve replacement, heart failure hospitalization, or death) was extracted from the electronic medical record. Results: The mean age was 75.3±12 years, and 57% were men. During a median follow-up of 316 days, the composite end point occurred in 305 patients. There were 132 (19.6%) deaths, 144 (21.4%) heart failure hospitalizations, and 114 (16.9%) patients underwent aortic valve replacement. Elevated NT-proBNP (1.41 [95% CI, 1.01–1.95]; P =0.048), diabetes (1.46 [95% CI, 1.08–1.96]; P =0.01), elevated averaged mitral valve E/e′ ratio (hazard ratio, 1.57 [95% CI, 1.18–2.10]; P <0.01), and presence atrial fibrillation at the time of index echocardiogram (hazard ratio, 1.83 [95% CI, 1.15–2.91]; P =0.01) were each independently associated with an increased hazard for the composite outcome and when taken collectively, each of these factors incrementally increased risk. Conclusions: These results further elucidate the relatively poor short-medium term outcomes and risk stratification of patients with moderate aortic stenosis, supporting randomized trials assessing the efficacy of transcatheter aortic valve replacement in this population.

Letter by Velders et al Regarding Article “Predictors of Major Adverse Cardiovascular Events in Patients With Moderate Aortic Stenosis: Implications for Aortic Valve Replacement”

“…A specification of handling the latter generally lacks in research, though is pivotal to give risk estimates a clinical meaning, for example, when analyzing components of a composite end point. We support this using examples from Howard et al 1 and suggest potentially interesting extensions.…”

“…We congratulate Howard and colleagues 1 with their important contribution to current knowledge on the prognosis of moderate aortic stenosis regarding major adverse cardiovascular events. They analyzed predictors and estimated the cumulative incidence of the composite end point major adverse cardiovascular event but also investigated its components.…”

A Multimodal Video-Based AI Biomarker for Aortic Stenosis Development and Progression

“…11,30,31 However, a challenge in personalizing patient follow-up is the marked variability in the progression rates of patients within similar Doppler-adjudicated severity stages. [32][33][34][35] Traditional risk factors, such as hypercholesterolemia, smoking, kidney dysfunction, and elevated natriuretic peptide levels, lack specificity for AS, 15,36 while alternative Doppler-derived indices require skilled acquisition and modifications to the scanning protocols. 36,37 Deep learning-enhanced, 2-dimensional echocardiography with DASSi aims to bridge this gap by providing a Dopplerindependent AS severity metric that can be computed from any portable or standard echocardiogram.…”

“…[32][33][34][35] Traditional risk factors, such as hypercholesterolemia, smoking, kidney dysfunction, and elevated natriuretic peptide levels, lack specificity for AS, 15,36 while alternative Doppler-derived indices require skilled acquisition and modifications to the scanning protocols. 36,37 Deep learning-enhanced, 2-dimensional echocardiography with DASSi aims to bridge this gap by providing a Dopplerindependent AS severity metric that can be computed from any portable or standard echocardiogram. Trained to detect generalizable features associated with the severe AS phenotype, 16 DASSi maintains its prognostic value across the spectrum of AS stages, identifying individuals who do not meet traditional criteria for severe AS, yet exhibit fast rates of progression.…”

Response by Majmundar et al to Letter Regarding Article, “Predictors of Major Adverse Cardiovascular Events in Patients With Moderate Aortic Stenosis: Implications for Aortic Valve Replacement”

“…However, it is paramount to acknowledge the inherent limitations associated with drawing causal inference conclusions from observational cohort data. In light of this, we approached our presented retrospective cohort study 3 with judiciousness, opting not to explicitly test hypotheses pertaining to treatment effects. Instead, we underscored the importance of our findings in guiding the design of future randomized controlled trials.…”