Association of Physiological Reserve Obtained from Cardiopulmonary Exercise Testing and Frailty with All-Cause Mortality in Patients on Hemodialysis

Key Points This study analyzed the prognostic value of reserves obtained from cardiopulmonary exercise testing in patients on hemodialysis. Each reserve (cardiac, autonomic, and muscular) was associated with mortality, with muscle reserve having the highest prognostic accuracy. Patients with physical frailty also had a fairly good prognosis if their physiological reserve is preserved by exercise testing. Background Potential impairment of exercise capacity is prevalent even in patients undergoing hemodialysis without frailty. Cardiopulmonary exercise testing (CPET) can detect physiological reserves, such as cardiopulmonary, muscle, and autonomic function. We hypothesized that these indices could accurately determine the prognosis of patients on hemodialysis and analyzed them on the basis of their relationship to frailty. Methods In this two-center prospective cohort study of patients on hemodialysis from Japan, patients underwent CPET and physical assessment to evaluate peak oxygen uptake (peak VO 2 , indicator of exercise capacity), peak work rate (WR, indicator of muscle function), ventilatory equivalent for carbon dioxide (VE/VCO 2 ) slope (indicator of cardiac reserve), heart rate reserve (indicator of chronotropic incompetence), and frailty phenotype. Survival was followed up for up to 5 years. Results Data from 189 patients (median [interquartile range] age: 71 [62–77] years) were analyzed. All CPET indicators showed a consistent nonlinear relationship with all-cause mortality after adjustment: for peak VO 2 , hazard ratio (HR), 0.79 (95% confidence interval [CI], 0.71 to 0.88), P < 0.001; for peak WR, HR, 0.95 (95% CI, 0.93 to 0.97), P < 0.001; for VE/VCO 2 slope, HR, 1.09 (95% CI, 1.05 to 1.13), P < 0.001; and for heart rate reserve, HR, 0.96 (95% CI, 0.93 to 0.99), P = 0.02. Frailty phenotype was associated with mortality after adjustment (HR, 1.73 [95% CI, 1.06 to 2.81], P = 0.03); however, this association was not statistically significant in the model after adding peak VO 2 ( P = 0.41). Furthermore, in both subgroups with and without frailty, CPET measures were significantly associated with mortality risk (peak VO 2 , peak WR, and VE/VCO 2 slope: P < 0.05). The peak VO 2 (Δ area under the curve, 0.09; 95% CI, 0.02 to 0.16) or the peak WR (Δ area under the curve, 0.09; 95% CI, 0.02 to 0.15) most significantly improved the prognostic accuracy. Conclusions Results showed the fragile aspect of the frailty phenotype in the hemodialysis population and the superior ability of CPET to indicate death risk complementing that aspect.