Characteristics of Heart Failure With Preserved Ejection Fraction Across the Range of Left Ventricular Ejection Fraction.

Abstract

Recent trial data suggest that stratification of patients with heart failure with preserved ejection fraction (HFpEF) according to left ventricular ejection fraction (LVEF) provides a means for dissecting different treatment responses. However, the differential pathophysiologic considerations have rarely been described. This prospective, single-center study analyzed consecutive symptomatic patients with HFpEF diagnosed according to the 2016 European Society of Cardiology heart failure guidelines. Patients were grouped into LVEF 50% to 60% and LVEF >60% cohorts. All patients underwent cardiac magnetic resonance imaging. Transfemoral cardiac catheterization was performed to derive load-dependent and load-independent left ventricular (LV) properties on pressure-volume loop analyses. Fifty-six patients with HFpEF were enrolled and divided into LVEF 50% to 60% (n=21) and LVEF >60% (n=35) cohorts. On cardiac magnetic resonance imaging, the LVEF >60% cohort showed lower LV end-diastolic volumes (P=0.019) and end-systolic volumes (P=0.001) than the LVEF 50% to 60% cohort; stroke volume (P=0.821) did not differ between the cohorts. Extracellular volume fraction was higher in the LVEF 50% to 60% cohort than in the LVEF >60% cohort (0.332 versus 0.309; P=0.018). Pressure-volume loop analyses demonstrated higher baseline LV contractility (end-systolic elastance, 1.85 vs 1.33 mm Hg/mL; P<0.001) and passive diastolic stiffness (β constant, 0.032 versus 0.018; P=0.004) in the LVEF >60% cohort. Ventriculo-arterial coupling (end-systolic elastance/arterial elastance) at rest was in the range of optimized stroke work in the LVEF >60% cohort but was impaired in the LVEF 50% to 60% cohort (1.01 versus 0.80; P=0.005). During handgrip exercise, patients with LVEF >60% had higher increases in end-systolic elastance (1.85 versus 0.82 mm Hg/mL; P=0.023), attenuated increases in indexed end-systolic volume (-1 versus 7 mL/m²; P<0.004), and more exaggerated increases in LV filling pressures (8 vs 5 mm Hg; P=0.023). LV stroke volume decreased in the LVEF >60% cohort (P=0.007) under exertion. Patients with HFpEF in whom LVEF ranged from 50% to 60% demonstrated reduced contractility, impaired ventriculo-arterial coupling, and higher extracellular volume fraction. In contrast, patients with HFpEF and a LVEF >60% demonstrated a hypercontractile state with excessive LV afterload and diminished preload reserve. A LVEF-based stratification of patients with HFpEF identified distinct morphologic and pathophysiologic subphenotypes.