Mechanisms of Exercise Intolerance in Heart Failure with Reduced Ejection Fraction: Influence of COPD

Abstract

IntroductionExercise intolerance is a hallmark of heart failure with reduced ejection fraction (HFrEF) resulting from a variety of factors including comprised oxygen delivery. A common comorbidity of HFrEF is chronic obstructive pulmonary disease (COPD), which is independently associated with reduced exercise tolerance and cardiac output (Q) as well as peripheral dysfunction similar to HFrEF. It is currently unknown if HFrEF and coexisting COPD (HFrEF+COPD) exhibit worsened exercise tolerance and whether the mechanisms thereof are similar to HFrEF alone. We hypothesized that patients with HFrEF+COPD demonstrate further reductions in peak VO2 and workload subsequent to a lower peak Q and arterio‐mixed venous O2 content difference (C(a‐v)O2) compared to HFrEF alone.MethodsHFrEF+COPD (n=16) and HFrEF (n=17) (age: 57±7 vs 54±6 yrs; EF%: 20±5 vs 21±5; height: 173±7 vs 174±7 cm; weight: 88±14 vs 86±17 kg; all p>0.18) underwent peak exercise testing during right heart catheterization. At rest and peak exercise, invasive hemodynamic, cardiac pressures, and arterial pressures were performed. Heart rate and oxygen uptake (VO2) were measured at rest and peak exercise via 12‐lead ECG and metabolic measurement system, respectively. Convective oxygen delivery was calculated as Q multiplied by CaO2.ResultsPeak exercise VO2 and workload were lower in HFrEF+COPD compared to HFrEF (7.0±1.9 vs. 9.9±2.7 mL/min/kg; 34±7 vs. 45±12 watts; both p<0.01). At peak exercise, Q and stroke volume were lower in HFrEF+COPD than HFrEF (4.8±1.3 vs. 7.0±3.0 L/min; 52±16 vs. 75±28 mL; both p<0.01). Significant relationships existed between delta VO2 and Q (peak exercise minus resting) in HFrEF+COPD and HFrEF (r=0.84 and r=0.89; both p<0.01); however, HFrEF+COPD had a significantly lower slope (p=0.02). Peak exercise C(a‐v)O2 was not different between HFrEF+COPD and HFrEF (12.9±2.3 vs. 12.8±2.6 mL/dL; p=0.89). No differences were present in heart rate or hemoglobin at peak exercise (p>0.73). Delta VO2 and C(a‐v)O2 was significantly related for HFrEF+COPD (r=0.68; p<0.01), but not HFrEF (r=0.14, p=0.57). At peak exercise, HFrEF+COPD had lower convective oxygen delivery (845±239 vs. 1230±517 mL/min; p<0.01).ConclusionsPatients with HFrEF and concurrent COPD demonstrate worsened exercise tolerance compared to HFrEF resulting from reduced oxygen delivery. These data suggest HFrEF with COPD exhibit more severe central and peripheral abnormalities than HFrEF alone.Support or Funding InformationNHLBI RO1 HL126638This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.