High afterload rather than myocardial fibrosis predicts reduced ejection fraction in severe aortic stenosis with afterload mismatch

Abstract

Background Afterload mismatch (AM) refers to high-gradient (mean gradient ≥40 mm Hg) severe aortic stenosis (AS) with reduced left ventricular ejection fraction (LVEF <50%) that is hypothesised to arise from mechanisms other than true contractile impairment. The extent, pattern and functional impact of myocardial fibrosis (MF), which is associated with systolic impairment, is poorly understood in the context of AM.Methods High-gradient severe AS patients with (n=25; low ejection fraction high-gradient, LEF-HG) and without (n=33; normal ejection fraction high-gradient (NEF-HG)) reduced LVEF underwent cardiovascular MRI. Using T1 mapping, extracellular volume (ECV) fraction and late gadolinium enhancement (LGE), the extent and pattern of MF was compared between the two groups. End-systolic wall stress (ESWS) as a measure of afterload was estimated, and its relationship with LVEF was compared with that of MF and LVEF.Results Stenosis severity was worse in the LEF-HG group (aortic valve area 0.5±0.2 vs 0.7±0.2 cm2, mean gradient 55 (46–66) vs 48 (41–69) mm Hg). In the LEF-HG group, high ESWS with cavity dilation and significant hypertrophy were observed compared with the NEF-HG group. MF was present in both groups with a significantly higher burden in the LEF-HG group (T1 time 1061±22 vs 1041±33 ms, ECV 26%±3% vs 24%±3%, LGE mass 4.3 (1.7–9.3) vs 0.1 (0.06–3.39) g). The association between MF and LVEF was weak, while ESWS was strongly associated with LVEF (r −0.8, p<0.0001) and was the best predictor of LVEF in multivariate prediction analysis.Conclusions MF was present in both groups with a higher burden in those with LEF-HG AS. High ESWS, that is, afterload, rather than MF, was the strongest predictor of LVEF. While MF may not directly impact systolic function in AM, it is still an important factor to account for in AS given its association with increased mortality.