Periodic breathing during incremental exercise predicts mortality in patients with chronic heart failure evaluated for cardiac transplantation

Objectives We hypothesized that exercise-related periodic breathing (EPB) would be associated with poor prognosis in advanced chronic heart failure (CHF). Background Patients with CHF might present instability of the ventilatory control system characterized by cyclic waxing and waning of tidal volume (periodic breathing [PB]). This condition is associated with several deleterious circulatory and neuro-endocrine responses; in fact, PB in awake and asleep patients has been identified as an independent risk factor for cardiac death. During exercise, however, the prognostic value of PB is still unknown in CHF patients awaiting heart transplantation. Methods Eighty-four patients with established CHF (65 male, 19 female) were submitted to clinical evaluation, echocardiogram, ventricular scintigraphy, determination of resting serum norepinephrine levels, and an incremental cardiopulmonary exercise test on cycle ergometer. Patients were followed for up to 49.7 months (median = 15.3), and 26 patients (30.9%) died during this period. Results Twenty-five of 84 patients presented EPB (29.7%). The following variables were related to mortality according to Kaplan-Meier and univariate Cox regression analysis: EPB (p = 0.004), New York Heart Association class (p = 0.04), serum norepinephrine (p = 0.06), peak oxygen uptake (ml·min−1·kg−1 and % predicted; P = 0.085 and P = 0.10, respectively), slope of the ratio of change in minute ventilation to change in carbon dioxide output during exercise (p = 0.10), and scintigraphic left ventricular ejection fraction (p = 0.10). Cox multivariate analysis identified EPB as the only independent variable for cardiac death prediction (p = 0.007). Therefore, EPB alone was associated with a 2.97-fold increase in risk of death in this population (95% confidence INTERVAL = 1.34 to 6.54). Conclusions Exercise-related periodic breathing independently predicts cardiac mortality in CHF patients considered for heart transplantation.