Prognostic Value of B-Type Natriuretic Peptide in Elderly Patients With Aortic Valve Stenosis: The COFRASA–GENERAC Study

Study Questions:

Is there a relationship between elevated serum levels of the N-terminal fragment of pro–B-type natriuretic peptide (NT-proBNP) and the severity of and/or symptoms and outcome associated with aortic stenosis (AS)?


Patients ≥70 years of age with at least mild degenerative AS were prospectively enrolled in two observational studies (COhorte Française de Retrecissement Aortique du Sujet Agé [COFRASA] for asymptomatic patients, and GENEtique du Retrecissement Aortique [GENERAC] for symptomatic patients). Clinical, biological, and echocardiographic evaluations were performed at study entry. Asymptomatic patients were prospectively followed on a 6-month basis, and AS-related events (sudden death, congestive heart failure, or new-onset AS-related symptoms) were recorded.


A total of 361 patients (ages 79 ± 6 years, 230 with severe AS) were prospectively enrolled. NT-proBNP increased with the grade of AS severity and with New York Heart Association class (all p < 0.0001), albeit with substantial overlap between AS grades and functional classes. Consequently, the diagnostic value of NT-proBNP for the detection of severe symptomatic AS was only modest (area under the receiver operator curve = 0.73). At 2 years, 28 AS-related events occurred among 142 prospectively followed asymptomatic patients. NT-proBNP was associated with outcome in univariate analysis (p = 0.04), but not after adjustment for age, gender, and AS severity (p = 0.40).


The present study clearly highlights the limitations of NT-proBNP for the evaluation and management of patients with AS. These results suggest that NT-proBNP should be considered cautiously, at least as a single criterion, in the decision-making process of AS patients, especially in the elderly population.


Evaluation for intervention is indicated among symptomatic patients with severe AS. Referral for intervention is more problematic among asymptomatic patients with severe AS, because some but not all patients appear to be at risk without surgery. Some studies have associated BNP elevation with increased risk of an adverse event, usually defined as death or clinical referral for aortic valve replacement. However, with substantial overlap shown in this study between BNP level and grades of AS severity and functional classes, it seems reasonable to conclude that any discriminating power associated with BNP is not absolute. Rather, an integrative approach for surgical referral of asymptomatic patients with severe AS seems prudent, potentially weighing AS severity, left ventricular mass, functional tolerance, hemodynamic response to exercise testing, and elevation of BNP.

Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Cardiac Surgery, Heart Failure and Cardiomyopathies, SCD/Ventricular Arrhythmias, Cardiac Surgery and Arrhythmias, Cardiac Surgery and Heart Failure, Acute Heart Failure, Heart Failure and Cardiac Biomarkers

Keywords: Heart Valve Prosthesis, Biological Markers, Heart Failure, Death, Sudden, Peptide Fragments, Pregnancy, Death, Sudden, Cardiac, Hemodynamics, Corynebacterium, Natriuretic Peptide, Brain

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