Prognostic importance of exercise brain natriuretic peptide in asymptomatic degenerative mitral regurgitation

The exercise Doppler echocardiographic stress test can be of interest in the management of asymptomatic patients with primary mitral regurgitation (MR). The resting brain natriuretic peptide (BNP) level is a good surrogate marker of the consequences of MR and is a powerful predictor of outcome. The incremental prognostic value of BNP response during exercise is unknown. We aimed to identify the determinants of exercise BNP level and to evaluate its prognostic value in asymptomatic patients with primary MR.

Comprehensive resting and exercise transthoracic Doppler echocardiography was performed in 113 consecutive asymptomatic patients with moderate to severe degenerative MR and preserved left ventricular (LV) function. Blood samples were collected both at rest and during exercise. The BNP level significantly increased from rest to exercise (P < 0.0001). The independent determinants of exercise BNP were resting E/Ea ratio (P = 0.043), indexed left atrial volume (P = 0.022), and exercise LV global longitudinal strain (P = 0.001). There was a significant graded relationship between increasing BNP level at exercise (according to tertiles) and increased incidence of cardiac events (death, heart failure, mitral valve surgery driven by symptoms, or LV dilatation/dysfunction onset) (1 year, 11 ± 5% vs. 14 ± 6% vs. 43.5 ± 9%; 2 years, 21 ± 7% vs. 40 ± 8% vs. 67 ± 9%; in tertiles 1, 2 and 3, respectively). On multivariable analysis, after adjustment for demographic and echocardiographic data and for resting BNP level, exercise BNP remained significantly associated with increased risk of cardiac events during the follow-up (hazard ratio 2.8 and 3.4, P = 0.041 and 0.023, for tertiles 2 and 3, as compared with tertile 1).

In asymptomatic patients with primary MR, exercise BNP level provides incremental prognostic value beyond what is achieved by demographic and echocardiographic data and resting BNP level. Patients with elevated exercise BNP should be considered at high risk of reduced cardiac event-free survival.