Chronotropic and neurohumoral markers for the evaluation of functional capacity in patients with impaired left ventricular function.

INTRODUCTION Brain natriuretic peptide (BNP) levels correlate with functional capacity in patients with heart failure. Autonomic dysfunction and baro-chemo reflex balance play a role in conditioning exercise tolerance and chronotropic competence in heart failure. In this study we examined the relationship between N-terminal pro-brain natriuretic peptide (NT-pro-BNP) and heart rate (HR) response during cardiopulmonary exercise testing and the ability of those two markers to detect low functional class patients. METHODS We studied 100 patients (age 59 +/- 13 yrs) with heart failure and left ventricular ejection fraction 35 +/- 9% who underwent treadmill cardiopulmonary exercise testing using the Dargie protocol. HR response was assessed by the chronotropic response index (CRI), which is calculated using the formula CRI = (peak HR - rest HR) /(220 - age - rest HR) x 100 (%). Blood samples for NT-pro-BNP assessment were taken before exercise. RESULTS The overall peak VO2 achieved was 18 +/- 5 ml/kg/mm and CRI was 70 +/- 26% (normal value >80%). CRI correlated both with peak VO2 (r = 0.50, p < 0.001) and VE/VCO2 (r = -0.24, p < 0.05). Peak VO2 correlated strongly with NT-pro-BNP (r = -0.77, p < 0.001). NT-pro-BNP values >335 pg/ml showed 83% sensitivity and 76% specificity for detecting peak VO2 values <20 ml/kg/mm (AUC=86%, p < 0.001). CRI values >79% showed 70% sensitivity and 60% specificity for detecting peak VO2 values <20 ml/kg/mm (AUC=72%, p < 0.001). CRI correlated well with NT-pro-BNP at rest (r = -0.31, p < 0.001). CONCLUSIONS In patients with heart failure, CR1 correlates significantly with both functional capacity derived from cardiopulmonary exercise testing and NT-pro-BNP levels. These findings may support the use of CR1 as a simple noninvasive marker of heart failure severity.