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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

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 (e/co2) predicts poor prognosis in advanced CHF. Derangement of cardiopulmonary reflexes may trigger exercise hyperpnea. We assessed the relationship between cardiopulmonary reflexes and e/co2 and investigated the prognostic value of e/co2 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 o2) ≥18 mL · kg−1 · min−1 (age 56 years; left ventricular ejection fraction 28%; peak o2 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 e/co2 (ie, >34.0). During follow-up (49±22 months, >3 years in all survivors), 34 patients died (3-year survival 81%). High e/co2 (hazard ratio 4.3, P <0.0001) but not peak o2 (P =0.7) predicted mortality. In patients with high e/co2, 3-year survival was 57%, compared with 93% in patients with normal e/co2 (P <0.0001). Patients with high e/co2 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 e/co2. 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 o2 does not.