BNP and Survival in Degenerative Mitral Regurgitation

Study Questions:

Is there an association between B-type natriuretic peptide (BNP) activation and mortality among patients with degenerative mitral regurgitation (MR)?


A cohort of 1,331 patients with MR due to mitral valve prolapse or flail at one of four tertiary medical centers (68% at one center; and 14%, 9%, and 9%, respectively, at the three others) during 2001 through 2013 were followed if the patient also had BNP assessed at the time of echocardiography. MR was assessed semi-quantitatively (on a scale of 1-4) using echocardiography/Doppler. BNP was expressed as a BNP ratio (the ratio of the BNP value to an upper-limit-of-normal based on patient age, sex, and the specific assay used). Patients were considered to have undergone initial mitral surgery if surgery was performed within 3 months of the echocardiogram. Patients who did not undergo surgery within 3 months of the echocardiogram were classified as having undergone initial medical therapy. Clinicians caring for the patients were not blinded to BNP results. The primary endpoint was all-cause mortality; secondary endpoints were mortality under medical therapy and mortality after surgery.


Mean patient age was 64 ± 15 years, 66% were male, mean ejection fraction was 64 ± 9%, mean regurgitant volume was 67 ± 31 ml, and mean Charlson comorbidity index was 1.09 ± 1.76. Median BNP ratio was 1.01 (interquartile range [IQR], 0.42-2.36). Overall, BNP ratio was an independent predictor of mortality (hazard ratio [HR], 1.33 [1.15-1.54]; p < 0.0001), although absolute BNP was not (p = 0.43). Among 770 patients (58%) initially treated medically (of whom 52% had severe MR), BNP ratio was an independent and incremental predictor of mortality after diagnosis (HR, 1.61 [1.34-1.93]; p < 0.0001); higher BNP activation was associated with higher mortality (p < 0.0001). All subgroups, particularly severe MR, incurred similar excess mortality with BNP activation. Among 561 patients (42%) who underwent initial surgical treatment (of whom 82% had severe MR), BNP activation was not associated with excess long-term mortality (p = 0.23).


The authors concluded that BNP ratio is a powerful, independent, and incremental predictor of long-term mortality among patients with degenerative MR who do not undergo surgery within 3 months. They suggest that BNP ratio should be incorporated into the routine clinical assessment of patients with degenerative MR.


Although BNP has been associated with worse outcomes among patients with aortic stenosis or with MR, prospective, randomized studies are lacking. Apart from a lack of methodologic detail in this manuscript, limitations associated with this retrospective, observational study raise concern. Severe (4+) or even moderate-to-severe (3+) MR were not inclusion criteria; clinicians were not blinded to BNP results; adequacy of medical follow-up was not defined; and conservatively managed patients included 51% with dyspnea and 19% with atrial fibrillation, respectively, Class I and potentially Class IIa indications for intervention. As with prior studies, this study fails to provide a compelling argument for including BNP in timing intervention for MR.

Clinical Topics: Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Valvular Heart Disease, Aortic Surgery, Cardiac Surgery and VHD, Interventions and Imaging, Interventions and Structural Heart Disease, Echocardiography/Ultrasound, Mitral Regurgitation

Keywords: Aortic Valve Stenosis, Biological Markers, Cardiac Surgical Procedures, Diagnostic Imaging, Echocardiography, Heart Valve Diseases, Mitral Valve Insufficiency, Mitral Valve Prolapse, Mortality, Natriuretic Peptide, Brain

< Back to Listings