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

• Published in: Circulation (New York, N.Y.) Vol. 146; no. 7; pp. 506 - 518
• Main Authors: Rosch, Sebastian, Kresoja, Karl-Patrik, Besler, Christian, Fengler, Karl, Schöber, Anne Rebecca, von Roeder, Maximilian, Lücke, Christian, Gutberlet, Matthias, Klingel, Karin, Thiele, Holger, Rommel, Karl-Philipp, Lurz, Philipp
• Format: Journal Article
• Language: English
• Published: United States 16.08.2022
• Subjects: Hand Strength - physiology; Heart Failure - diagnostic imaging; Heart Failure - therapy; Humans; Prospective Studies; Stroke Volume - physiology; Ventricular Function, Left - physiology; heart failure, diastolic; fibrosis; hemodynamics
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/CIRCULATIONAHA.122.059280

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 ( =0.019) and end-systolic volumes ( =0.001) than the LVEF 50% to 60% cohort; stroke volume ( =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; =0.018). Pressure-volume loop analyses demonstrated higher baseline LV contractility (end-systolic elastance, 1.85 vs 1.33 mm Hg/mL; <0.001) and passive diastolic stiffness (β constant, 0.032 versus 0.018; =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; =0.005). During handgrip exercise, patients with LVEF >60% had higher increases in end-systolic elastance (1.85 versus 0.82 mm Hg/mL; =0.023), attenuated increases in indexed end-systolic volume (-1 versus 7 mL/m²; <0.004), and more exaggerated increases in LV filling pressures (8 vs 5 mm Hg; =0.023). LV stroke volume decreased in the LVEF >60% cohort ( =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.