Identification of functional phenotypes and determinants of effort intolerance in patients with heart failure: insights from a combined echocardiography and cardiopulmonary stress protocol.

BACKGROUND. Combining cardiopulmonary exercise test (CPET) and exercise stress echocardiography (ESE) allows non-invasive evaluation of cardiac function, hemodynamics, and arterial-venous oxygen content difference (AVO2diff) during different exercise stages: rest, low-load, anaerobic threshold, and peak effort. The aim of the study was to characterize patients with heart failure and preserved, mid-range and reduced ejection fraction (HFpEF, HFmrEF and HFrEF, respectively). METHODS. We studied 106 consecutive subjects (age 62.3±11 years; 74% male): 30 healthy controls, 20 HFpEF, 22 HFmrEF and 34 HFrEF patients (groups age- and sex-matched). Left ventricular (LV) volumes, ejection fraction (EF), elastance, global longitudinal strain (GLS), E/E’, oxygen consumption (VO2), and AVO2diff were measured in all effort stages. RESULTS. HFmrEF revealed features intermediate between HFrEF and HFpEF, with the exception of AVO2diff. In all groups, AVO2diff gradually increased from rest to reach plateau at the AT (p<0.0001 within groups), with the lowest peak values reported in HFmrEF (controls: 21.1±7.1 mL/dL, HFpEF: 15.6±5.3 mL/dL, HFmrEF: 13.3±4.2 mL/dL, HFrEF: 17.8±9.6 mL/dL; p=0.005 between groups). Peak VO2 was reduced in HF patients compared to controls (HFpEF: 16.7±3.8 mL/min/kg, HFmrEF: 16.6±4.7 mL/min/kg, HFrEF:15.1±4.4 mL/min/kg, controls: 24.8±6.4 mL/min/kg; p<0.0001 between groups). At multivariable analysis, peak parameters were the most significant independent predictors of peak VO2: heart rate, elastance, GLS, systemic vascular resistance and AVO2diff (R2=0.92, p<0.0001). The parameters that significantly distinguished HF groups from each other and controls were elastance and GLS at AT and at peak (all p