VE/VCO2 slope is associated with abnormal resting haemodynamics and is a predictor of long‐term survival in chronic heart failure

Abstract

Patients with chronic heart failure (CHF) present with exercise-induced hyperpnea, but its pathophysiological mechanism has not been thoroughly investigated. We aimed to determine the relationship between exercise-induced hyperpnea, resting haemodynamic measurements and the validity of ventilatory response (V(E)/V(CO(2)) slope) as a mortality predictor in CHF patients. Ninety-eight CHF patients (90M/8F) underwent a symptom-limited treadmill cardiopulmonary exercise test (CPET). Right heart catheterization and radionuclide ventriculography were performed within 72 h of CPET. Twenty-seven patients died from cardiac causes during 20+/-6 months follow-up. Non-survivors had a lower peak oxygen consumption (V(O(2)p)), (16.5+/-4.9 vs. 20.2+/-6.1, ml/kg/min, p=0.003), a steeper V(E)/V(CO(2)) slope (34.8+/-8.3 vs. 28.9+/-4.8, p<0.001) and a higher pulmonary capillary wedge pressure (PCWP) (19.5+/-8.6 vs. 11.7+/-6.5 mm Hg, p=0.008) than survivors. By multivariate survival analysis, the V(E)/V(CO(2)) slope as a continuous variable was an independent prognostic factor (chi(2): 8.5, relative risk: 1.1, 95% CI: 1.03-1.18, p=0.004). Overall mortality was 52% in patients with V(E)/V(CO(2)) slope > or =34 and 18% in those with V(E)/V(CO(2)) slope <34 (log rank: 18.5, p<0.001). In a subgroup of patients (V(O(2)p): 10-18 ml/kg/min), V(E)/V(CO(2)) slope was a significant predictor of mortality (relative risk: 6.2, 95% CI: 1.7-22.2, p=0.002). Patients with high V(E)/V(CO(2)) slope had higher resting PCWP (19.9+/-9.1 vs. 11.3+/-5.7 mmHg, p<0.001) and V(E)/V(CO(2)) slope correlated significantly with PCWP (r: 0.57, p<0.001). The V(E)/V(CO(2)) slope, as an index of ventilatory response to exercise, improves the risk stratification of CHF patients. Interstitial pulmonary oedema may be a pathophysiological mechanism of inefficient ventilation during exercise in these patients.