Prognostic Importance of Exercise Brain Natriuretic Peptide in Asymptomatic Chronic Organic Severe Mitral Regurgitation: An Observational Study

Abstract

Background: The optimal timing of surgery in patients with chronic organic severe mitral regurgitation (MR) continues to be debated, especially for those who are asymptomatic. The aim of the study was to determine independent and additive prognostic value of exercise brain natriuretic peptide (eBNP) in patients with severe asymptomatic MR and normal left ventricular ejection fraction (LVEF).

Methods: Two hundred twenty-three consecutive patients with severe MR defined by effective regurgitant orifice (ERO) area ≥ 40 mm² and/or residual volume ≥ 60 mL, LVEF > 60%, and normal LV end-systolic diameter < 40 mm underwent symptom limited exercise treadmill test (TMT). Echocardiography was done immediately after exercise. Data were obtained within 3 minutes of peak exercise. BNP levels were assessed before echo (after 30 minutes of supine rest) and at exercise (i.e., within the 3 minutes of the end of effort). Patients were followed up every 3 months up to 15 months for major adverse cardiac events (MACEs) (cardiovascular death, need for mitral valve surgery and hospitalization for acute pulmonary edema or heart failure).

Results: Mean age was 31.2 ± 9 years (range: 18 - 40) with majority being male (n = 153; 68%). Etiologies were rheumatic (n = 201; 90%), mitral valve prolapse (n = 17; 7.6%) and hypertrophic cardiomyopathy (n = 5; 2.4%). BNP level significantly increased from rest (65.24 ± 43.92 pg/mL; median: 43.5 pg/mL) to exercise (100.24 ± 98.24 pg/mL; median: 66.5 pg/mL; P < 0.001). Patients were divided into three tertiles according to eBNP levels (T₁ = 15 - 44; T₂ = 45 - 104; T₃ = 105 - 400). There was trend for significantly lower exercise time in T₃. During TMT, 66 (29.5%) stopped exercise due to dyspnea. They had similar resting BNP level compared with others but had significantly higher eBNP level (136 ± 109.7 pg/mL vs. 84.88 ± 90.2 pg/mL; P < 0.001). During follow-up (15 months), MACE occurred in 83 patients (37.2%): mitral valve replacement (MVR) in 59 patients (symptomatic: 43; LV dilatation or dysfunction: 9; both symptoms and dilatation/dysfunction: 7), 17 hospitalizations for congestive heart failure, five patients developing acute pulmonary edema and atrial fibrillation in remaining two patients. This was 7.6%, 35% and 69% in T₁, T₂ and T₃, respectively and had significantly higher eBNP level than without any event (165 ± 119 pg/mL vs. 57 ± 48 pg/mL; P < 0.001). Using receiver operating characteristic curve analysis, the best cut-off value of eBNP level to predict cardiac events was 90 pg/mL (sensitivity: 75%; specificity: 88.6%; positive predictive value: 79%; negative predictive value: 83.9%).

Conclusion: In asymptomatic patients, eBNP level provides incremental prognostic value beyond echocardiographic data and those with elevated eBNP should be considered at high risk for reduced event-free survival and might be considered for early MVR.

Keywords: Dilatation; Dysfunction; Effective regurgitant orifice area; Exercise brain natriuretic peptide; MACE; Mitral regurgitation; Mitral valve replacement; Receiver operating characteristic curve; Tertiles.