Exploring the mechanisms responsible for reduced systolic function in high-gradient aortic stenosis

Objective: To characterise the mechanics responsible for the reduced ejection fraction (rEF) in high-gradient severe aortic stenosis (AS).

Methods: 21 patients with high-gradient severe AS (aortic valve area (AVA) <1.0 cm² and mean gradient (MG) >40 mm Hg) were included. They included 9 patients with rEF (EF <50%) and 12 with preserved ejection fraction (pEF) (EF >50%). Valve area and MG were assessed echocardiographically, and myocardial fibrosis was quantified using MRI. Load-independent measures of intrinsic contractility was assessed with pressure-volume haemodynamics.

Results: 80% of the cohort was female, with a mean age of 64 years. Patients were matched for age, sex and body surface area. Load-independent contractile function was similar between the rEF and pEF groups: preload recruitable stroke work slope (101 vs 112 mm Hg; p=0.65), end-systolic pressure-volume relationship slope (1.91 vs 1.28 mmHg/mL; p=0.07) and Starling Contractile Index slope (3.47 vs 7.96 mm Hg/mL/s; p=0.31). End-systolic wall stress and valvuloarterial impedance were higher in cases with rEF (150 vs 83.5 N/cm²; p<0.01 and 4.8 vs 3.4 mm Hg/mL; p=0.05), driven by higher degrees of valvular stenosis (valve area 0.46 vs 0.78 cm²; p<0.01). The rEF group was more symptomatic (New York Heart Association 3.3 vs 2.3; p=0.02), with higher pulmonary pressures (50 vs 30 mm Hg; p=0.04) and more fibrosis (24% vs 13% of left ventricular mass; p=0.03).

Conclusion: The pathophysiological problem in patients with high-gradient AS with rEF relates to an excessively increased afterload due to more severe valvular stenosis, with preserved intrinsic contractile function. Myocardial fibrosis in the rEF group did not translate into worse muscle function.