Resting level of plasma brain natriuretic peptide and response to exercise as predictors of outcomes in asymptomatic patients with aortic stenosis

Abstract

Purpose: Exercise stress echocardiography is useful in the management and risk stratification of patients with asymptomatic aortic stenosis (AS). Resting brain natriuretic peptides (BNP) level is associated with increased risk of adverse events in AS patients. The incremental prognostic value of BNP response during exercise is unknown. The objectives of this study were to assess the correlates of the plasma level of BNP during exercise as well as its usefulness to predict outcomes in asymptomatic patients with AS. Methods: Resting and exercise Doppler-echocardiographic data and BNP levels were prospectively collected in 211 asymptomatic AS patients in 2 centers. Results: Plasma BNP level increased significantly from rest to exercise (65±86 to 91±111 pg/mL, p<0.0001). The factors independently related to peak-exercise BNP were systemic arterial compliance (SAC: β=-0.76±0.32, p=0.02), resting mean gradient (MG: β=0.01±0.005, p=0.04), and change in stroke volume index (SVi) during exercise (β=0.01±0.005, p=0.02). During a mean follow-up of 1.8±1.3 years, 7 patients died and 97 underwent AVR motivated by development of symptoms or LV dysfunction. Higher peak-exercise BNP level was associated with higher occurrence of adverse events (2-yrs event-free survival according to tertiles of peak-exercise BNP: T1: 84±5% vs. T2: 60±7% vs. T3: 29±6%, p<0.0001). Stenosis was slightly more severe in T2 and T3 compared to T1 (MG: 43±15 and 43±16 vs. 37±13 mmHg, respectively; p=0.03). In multivariable analysis, after adjustment for age, gender, hypertension, MG, and valvulo-arterial impedance, T2 (HR=2.3; 95% CI: 1.3-4.3; p=0.005) and T3 (HR=5.3; 95% CI: 3.0-9.6; p<0.0001) tertiles of peak-exercise BNP were powerful independent predictors of events. Further adjustment for resting BNP, exercise-induced increase in MG and SVi led to similar results (T2: HR=2.2; 95% CI: 1.2-4.2; p=0.007; and T3: HR=4.8; 95% CI: 2.5-9.3; p<0.0001). The association between highest tertiles of peak-exercise BNP and outcomes remained highly significant (p<0.0001) in both subsets of patients with low or high resting BNP (i.e. ≤ or >43 pg/mL; median value). Conclusion: This study reports that, in asymptomatic patients with AS, peak-exercise BNP level provides important incremental prognostic value beyond what is achieved by demographic and echocardiographic data, as well as resting BNP level. These findings lend support to the measurement of BNP during exercise to enhance risk stratification in asymptomatic AS.