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B-Type Natriuretic Peptide Clinical Activation in Aortic Stenosis
Open accessAbstract
Objectives This study was conducted to define the association between serum B-type natriuretic peptide (BNP) activation and survival after the diagnosis of aortic stenosis (AS).Background In AS, the link between BNP levels and clinical outcome is in dispute. Failure to account for the normal shifting of BNP ranges with aging in men and women, not using hard endpoints (survival), and not enrolling large series of patients have contributed to the uncertainty.Methods A program of prospective measurement of BNP levels with Doppler echocardiographic AS assessment during the same episode of care was conducted. BNP ratio (measured BNP/maximal normal BNP value specific to age and sex) >1 defined BNP clinical activation.Results In 1,953 consecutive patients with at least moderate AS (aortic valve area 1.03 ± 0.26 cm(2); mean gradient 36 ± 19 mm Hg), median BNP level was 252 pg/ml (interquartile range: 98 to 592 pg/ml); BNP ratio 2.46 (interquartile range 1.03 to 5.66); ejection fraction (EF) 57% ± 15%, and symptoms present in 60% of patients. After adjustment for all survival determinants, BNP clinical activation (BNP ratio >1) independently predicted mortality after diagnosis (p < 0.0001; hazard ratio [HR]: 1.91; 95% CI: 1.55 to 2.35) and provided incremental power to the survival predictive model (p < 0.0001). Eight-year survival was 62 ± 3% with normal BNP levels, 44 ± 3% with BNP ratio of 1 to 2 (adjusted HR: 1.49; 95% CI: 1.17 to 1.90), 25 ± 4% with BNP ratio of 2 to 3 (adjusted HR: 2.12; 95% CI: 1.63 to 2.75), and 15 ± 2% with BNP ratio of ≥3 (adjusted HR: 2.43; 95% CI: 1.94 to 3.05). This strong link to survival was confirmed in asymptomatic patients with normal EF (adjusted HR: 2.35 [95% CI: 1.57 to 3.56] for BNP clinical activation and 2.10 [95% CI: 1.32 to 3.36] for BNP ratio of 1 to 2, 2.25 [95% CI: 1.31 to 3.87] for BNP ratio of 2 to 3, 3.93 [95% CI: 2.40 to 6.43] for BNP ratio of ≥3). Aortic valve replacement was associated with survival improved by a similarly high margin (p = 0.54) with BNP ratio of <2 (HR: 0.68; 95% CI: 0.52 to 0.89; p = 0.003) or BNP ratio of >2 (HR: 0.56; 95% CI: 0.47 to 0.66; p < 0.0001).Conclusions In this large series of patients with AS, BNP clinical activation was associated with excess long-term mortality incrementally and independently of all baseline characteristics. Higher mortality with higher BNP clinical activation, even in asymptomatic patients, emphasizes the importance of appropriate clinical interpretation of BNP levels in managing patients with AS.
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“Previous studies showed that elevated levels of brain natriuretic peptide, cardiac troponin, and galectin-3 are correlated with all-cause mortality in individuals with CAVS.6,7,8,9,10”
From Aortic valve-specific genes dysregulated in calcific aortic valve stenosis as potential biomarkers and therapeutic targets (2025) · cites this paper as [8]
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“A BNP ratio of >1 was found to be a powerful independent predictor of mortality in AS, even in patients with asymptomatic AS187.”
From Calcific aortic stenosis (2016) · cites this paper as [187]
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Metadata
- Authors
- Clavel, M.-A., Malouf, J., Michelena, H. I., Suri, R. M., Jaffe, A. S., Mahoney, D. W., & Enriquez-Sarano, M.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- Enriquez-Sarano, Maurice
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2014-05
- Volume
- 63
- Issue
- 19
- Pages
- 2016-2025
- ISSN
- 0735-1097 (ISSN-L)
- OpenAlex
- W56250199
- Cited by
- 226
- References
- 48
- Citations by year
- 2026: 15 · 2025: 19 · 2024: 10 · 2023: 20 · 2022: 19 · 2021: 16 · 2020: 29 · 2019: 19 · 2018: 17 · 2017: 24 · 2016: 17 · 2015: 15 · 2014: 5
- FWCI
- 13.90
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Corpus Université Laval (Université Laval) (submittedVersion)
- Funders
- Canadian Institute of Health Research
- Abbott Diagnostics
- Edwards Lifesciences
- St. Jude Medical
- Sorin Group
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Valve Diseases and Treatments
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Aortic Disease and Treatment Approaches
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Keywords
- brain natriuretic peptide, aortic stenosis, mortality prediction, survival after diagnosis, asymptomatic aortic stenosis, ejection fraction, Doppler echocardiography, prognostic factors, heart failure risk stratification, heart failure hospitalization, heart failure mortality, heart failure readmission
- MeSH terms
- Aged, Aged, 80 and over, Aortic Valve Stenosis, Female, Follow-Up Studies, Humans, Male, Middle Aged, Pilot Projects, Prospective Studies, Time Factors, Cohort Studies, Biomarkers, Survival Rate, Natriuretic Peptide, Brain
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