Exercise ventilatory inefficiency is an independent predictor of mortality in patients with pulmonary arterial hypertension

Abstract

Rationale: An excessive ventilatory (V´E) response to CO₂ output (V´CO₂) during incremental exercise is a strong prognosticator in cardiovascular diseases. The role of ΔV´E/ΔV'CO₂ to predict mortality in pulmonary arterial hypertension (PAH), however, remains to be demonstrated. Objective: To investigate the value of increased ΔV'E/ΔV'CO₂ as a negative prognostic marker in PAH. Methods: 80 patients with PAH who underwent a ramp-incremental cardiopulmonary exercise test (CPET) were followed-up for 5 yrs. ΔV'E/ΔV'CO₂ slope was calculated to the respiratory compensation point (ΔV'E/ΔV'CO_2(start-RCP)) or to peak exercise (ΔV'E/ΔV'CO_{2(start-PEAK)}). Results: 14 patients (17.5 %) died of PAH-related causes. Compared to survivors, deceased patients were younger and had lower peak O₂ uptake, O₂ pulse, and oxyhemoglobin saturation but, regardless the method of calculation, higher ΔV'E/ΔV'CO₂ (p<0.05). None of the other variables (including the six-minute walking distance) was related to mortality (p>0.05). The best cutoff to death prediction was higher for ΔV'E/ΔV'CO_{2(start-PEAK)} (>55) than ΔV'E/ΔV'CO_2(start-RCP) (>45). An univariate analysis revealed that the former variable was superior to the later on this regard (p= 0.004 vs. 0.02).In fact, a multiple regression analysis showed that resting heart rate (hazard ratio (95% CI)= 1.04 (1.00-1.08); p=0.03) and ΔV'E/ΔV'CO_{2(start-PEAK)} (1.04 (1.01-1.07); p= 0.006) were the only independent predictors of mortality. Conclusions: A resting variable (heart rate) and an effort-independent marker of ventilatory inefficiency (ΔV'E/ΔV'CO_{2(start-PEAK)}) are clinically-useful markers of poor prognosis in patients with PAH.