Enhanced Ventilatory Response to Exercise in Patients With Chronic Heart Failure and Preserved Exercise Tolerance: Marker of Abnormal Cardiorespiratory Reflex Control and Predictor of Poor Prognosis

Abstract

Background —In patients with chronic heart failure (CHF) and preserved exercise tolerance, the value of cardiopulmonary exercise testing for risk stratification is not known. Elevated slope of ventilatory response to exercise (V̇ e /V̇ co 2 ) predicts poor prognosis in advanced CHF. Derangement of cardiopulmonary reflexes may trigger exercise hyperpnea. We assessed the relationship between cardiopulmonary reflexes and V̇ e /V̇ co 2 and investigated the prognostic value of V̇ e /V̇ co 2 in CHF patients with preserved exercise tolerance. Methods and Results —Among 344 consecutive CHF patients, we identified 123 with preserved exercise capacity, defined as a peak oxygen consumption (peak V̇ o 2 ) ≥18 mL · kg −1 · min −1 (age 56 years; left ventricular ejection fraction 28%; peak V̇ o 2 23.5 mL · kg −1 · min −1 ). Hypoxic and hypercapnic chemosensitivity (n=38), heart rate variability (n=34), baroreflex sensitivity (n=20), and ergoreflex activity (n=20) were also assessed. We identified 40 patients (33%) with high V̇ e /V̇ co 2 (ie, >34.0). During follow-up (49±22 months, >3 years in all survivors), 34 patients died (3-year survival 81%). High V̇ e /V̇ co 2 (hazard ratio 4.3, P <0.0001) but not peak V̇ o 2 ( P =0.7) predicted mortality. In patients with high V̇ e /V̇ co 2 , 3-year survival was 57%, compared with 93% in patients with normal V̇ e /V̇ co 2 ( P <0.0001). Patients with high V̇ e /V̇ co 2 demonstrated impaired reflex control, as evidenced by augmented peripheral ( P =0.01) and central ( P =0.0006) chemosensitivity, depressed low-frequency component of heart rate variability ( P <0.0001) and baroreflex sensitivity ( P =0.03), and overactive ergoreceptors ( P =0.003) compared with patients with normal V̇ e /V̇ co 2 . Conclusions —In CHF patients with preserved exercise capacity, enhanced ventilatory response to exercise is a simple marker of a widespread derangement of cardiovascular reflex control; it predicts poor prognosis, which peak V̇ o 2 does not.