A flattening oxygen consumption trajectory phenotypes disease severity and poor prognosis in patients with heart failure with reduced, mid-range, and preserved ejection fraction

In heart failure (HF), a flattening oxygen consumption (VO₂ ) trajectory during cardiopulmonary exercise test (CPET) reflects an acutely compromised cardiac output. We hypothesized that a flattening VO₂ trajectory is helpful in phenotyping disease severity and prognosis in HF with either reduced (HFrEF), mid-range (HFmrEF), or preserved (HFpEF) ejection fraction.

Overall, 319 HF patients (198 HFrEF, 80 HFmrEF, and 41 HFpEF) underwent CPET. A flattening VO₂ trajectory was tracked and defined as an inflection of VO₂ linearity as a function of work rate with a second slope downward inflection >35% extent of the first one. Peak VO₂ , the minute ventilation/carbon dioxide production (VE/VCO₂ ) slope, and the presence of exercise oscillatory ventilation (EOV) were also determined. Pulmonary artery systolic pressure (PASP) and tricuspid annular plane systolic excursion (TAPSE) were measured by echocardiography. A flattening VO₂ occurred in 92 patients (28.8%). PASP and TAPSE at rest were significantly higher and lower (P < 0.001), respectively. The primary outcome was the combination of all-cause death, heart transplantation and left ventricular assist device implantation. The secondary outcome was the primary outcome plus hospitalization for cardiac reasons. In the multivariate model including peak VO₂ , VE/VCO₂ slope, EOV and VO₂ trajectory, a flattening VO₂ trajectory and EOV were retained in the regression for primary (X² = 35.78, and 36.36, respectively; P < 0.001) and secondary (X² = 12.45 and 47.91, respectively; P < 0.001) outcomes.

Results point to a flattening VO₂ trajectory as a likely new and strong predictor of events in HF with any ejection fraction. Given the relation of right-sided cardiac dysfunction to pulmonary hypertension, this oxygen pattern might suggest a real-time decrease in pulmonary blood flow to the left heart.