Excessively high end-systolic wall stress, not myocardial fibrosis, strongly predicts reduced LVEF (r = -0.83, R2 = 0.7) in severe aortic stenosis with afterload mismatch.
In severe aortic stenosis with afterload mismatch, reduced LVEF is better predicted by excessively high afterload (end-systolic wall stress) than by CMR markers of myocardial fibrosis.
Abstract Background Afterload mismatch in severe aortic stenosis (AS) is an uncommon, poorly described haemodynamic subgroup of AS. Despite the presence of systolic impairment left ventricular ejection fraction (LVEF) 50%), the transaortic gradients are maintained in the severe range (mean gradient ≥ 40 mmHg) implying that mechanisms other than true contractile dysfunction underlie the reduced LVEF.1 Proposed mechanisms include abnormal loading conditions and/or the presence of myocardial fibrosis.1,2 Purpose We hypothesized that the reduced LVEF in afterload mismatch is associated with excessively high afterload rather than myocardial fibrosis. Methods Forty-three high-gradient (mean gradient ≥ 40 mmHg) severe AS aortic valve area (AVA) 1.0 cm2 participants with and without afterload mismatch were prospectively recruited for evaluation by cardiovascular magnetic resonance (CMR) imaging. Cine images for left ventricular (LV) remodeling, function, and end-systolic wall stress (ESWS) were acquired. Pre- and post-contrast T1 mapping was used to determine the diffuse myocardial fibrosis burden and late gadolinium enhancement (LGE) imaging, for the replacement fibrosis burden. Results The cohort comprised of 23/43 patients with afterload mismatch (mean AVA 0.5 ± 0.2 cm2 with a mean gradient of 58 ± 16 mmHg and LVEF 28 ± 8 %). In 20/43 controls, the mean AVA was 0.7 ± 0.2 cm2 with a mean gradient of 54 ± 16 mmHg and LVEF 68 ± 9 %. Significant cavity dilation, LV hypertrophy and elevated ESWS were observed in afterload mismatch (LVEDVi 123 ± 32 vs. 75 ± 13 ml/m2, LVMi 100 ± 38 vs. 79 ± 23 g/m2, ESWS 268 ± 80 vs. 87 ± 21 x103 dynes/cm2). Diffuse interstitial fibrosis was higher in afterload mismatch (Native T1 time 1063 ± 22 vs. 1042 ± 34 ms, p = 0.03 and ECV 26 ± 3 vs. 24 ± 3 %, p = 0.02). Replacement fibrosis was also significantly higher in afterload mismatch (LGE mass 15 ± 10 vs. 10 ± 9 g). A significant inverse linear relationship was observed between ESWS and LVEF (r = -0.83 with 95% confidence interval -0.90 to -0.70), p 0.0001). No strong or significant associations were found between native T1 time, ECV or LGE mass and LVEF. In a simple linear regression analysis assessing LVEF prediction, R2 for ESWS was 0.7 F(1,40) = 86.2; p 0.0001 and 0.1 for T1 mapping F(1,41) = 5.7; p = 0.02), ECV F(1,30) = 3.3; p = 0.08 and LGE mass F(1,41) = 4.0; p = 0.05. Conclusion Excessively high afterload with adverse LV remodeling, high ESWS and a higher fibrosis burden was observed in afterload mismatch. High ESWS reflective of high afterload, rather than CMR markers of fibrosis, associated better with a reduced LVEF. This suggests that LV fibrosis may be a marker of a more advanced stage of disease or chronicity in severe AS rather than being directly and mechanistically responsible for the LV dysfunction observed.
Rajah et al. (2025) studied this question. Excessively high end-systolic wall stress, not myocardial fibrosis, strongly predicts reduced LVEF (r = -0.83, R2 = 0.7) in severe aortic stenosis with afterload mismatch.