B-Type Natriuretic Peptide Clinical Activation in Aortic Stenosis: Impact on Long-Term Survival

Study Questions:

Is there an association between serum B-type natriuretic peptide (BNP) activation and survival among patients with aortic stenosis (AS)?


A program was conducted with prospective measurement of BNP levels and concomitant Doppler/echocardiographic assessment of AS. BNP clinical activation was defined as a BNP ratio (measured BNP/maximal normal BNP value specific to age and gender) >1.


In 1,953 consecutive patients with at least moderate AS (effective orifice area 1.03 ± 0.26 cm2, mean gradient 36 ± 19 mm Hg), BNP median was 252 (interquartile range, 98-592), BNP ratio was 2.46 (1.03-5.66), and ejection fraction (EF) was 57 ± 15%; symptoms were present in 60%. Adjusting for other survival determinants, BNP clinical activation (BNP ratio >1) independently predicted mortality after AS diagnosis (p < 0.0001, hazard ratio [HR], 1.91 [1.55-2.35]) and provided incremental power to a clinically based model to predict survival (p < 0.0001). Eight-year survival was 62 ± 3% with normal BNP, 44 ± 3% with BNP ratio 1-2 (adjusted HR, 1.49 [1.17-1.90]), 25 ± 4% with BNP ratio 2-3 (adjusted HR, 2.12 [1.63-2.75]), and 15 ± 2% with BNP ratio ≥3 (adjusted HR, 2.43 [1.94-3.05]). The statistical association with survival also was present in asymptomatic patients with normal EF (adjusted HR, 2.35 [1.57-3.56] for BNP clinical activation and 2.10 [1.32-3.36] for BNP ratio 1-2, 2.25 [1.31-3.87] for BNP ratio 2-3, and 3.93 [2.40-6.43] for BNP ratio ≥3). Aortic valve replacement was associated with similarly improved survival (p = 0.54) with BNP ratio <2 (0.68 [0.52- 0.89], p = 0.003) vs. BNP ratio >2 (0.56 [0.47-0.66], p < 0.0001).


In this large series of patients with at least moderate AS, BNP clinical activation was associated with excess long-term mortality independently of and incrementally to identified clinical characteristics. Higher mortality with higher BNP, even in asymptomatic patients, emphasizes the importance of appropriate clinical interpretation of BNP levels in managing patients with AS.


This study adds to existing literature that associates elevated BNP with adverse outcome among patients with AS, in this case indexing BNP to age and gender using data derived at the Mayo Clinic and published somewhat over 10 years ago. There is something of a conundrum in the clinical implications of the study results, in that patients with moderate AS were included along with patients with severe AS. Conventional thinking remains that less than severe AS should be associated with good clinical outcomes. Logically, any association between elevated BNP and worse survival among patients with only moderate AS could be explained by vagaries of AS quantitation (in which case the added power of BNP over AS severity might be open to question), by BNP serving as a marker of another disease, or by error in the conventional thinking. Presumably, an abnormal BNP should not result in referral for aortic valve replacement in an asymptomatic patient with only moderate AS.

Clinical Topics: Noninvasive Imaging, Echocardiography/Ultrasound

Keywords: Echocardiography, Doppler, Natriuretic Peptide, Brain

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