Low-flow in aortic valve stenosis patients with reduced ejection fraction does not depend on left ventricular function

Background Patients with severe aortic stenosis (AS) and reduced left ventricular ejection fraction (LVEF) can be distinguished into high- (HG) and low-gradient (LG) subgroups. However, less is known about their characteristics and underlying (pathophysiological) hemodynamic mechanisms. Methods 98 AS patients with reduced LVEF were included. Subgroup characteristics were analyzed by a multimodal approach using clinical and histological data, next-generation sequencing (NGS) and applying echocardiography as well as cardiovascular magnetic resonance (CMR) imaging. Biopsy samples were analyzed with respect to fibrosis and mRNA expression profiles. Results 40 patients were classified as HG-AS and 58 patients as LG-AS. Severity of AS was comparable between the subgroups. Comparison of both subgroups revealed no differences in LVEF ( p = 0.1), LV mass ( p = 0.6) or end-diastolic LV diameter ( p = 0.12). Neither histological (HG: 23.2% vs. LG: 25.6%, p = 0.73) and circulating biomarker-based assessment (HG: 2.6 ± 2.2% vs. LG: 3.2 ± 3.1%; p = 0.46) of myocardial fibrosis nor global gene expression patterns differed between subgroups. Mitral regurgitation (MR), atrial fibrillation (AF) and impaired right ventricular function (MR: HG: 8% vs. LG: 24%; p < 0.001; AF: HG: 30% vs. LG: 51.7%; p = 0.03; RVSVi: HG 36.7 vs. LG 31.1 ml/m2, p = 0.045; TAPSE: HG 20.2 vs. LG 17.3 mm, p = 0.002) were more frequent in LG-AS patients compared to HG-AS. These pathologies could explain the higher mortality of LG vs. HG-AS patients. Conclusion In patients with low-flow severe aortic stenosis, low transaortic gradient and cardiac output are not primarily due to LV dysfunction or global changes in gene expression, but may be attributed to other additional cardiac pathologies like mitral regurgitation, atrial fibrillation or right ventricular dysfunction. These factors should also be considered during planning of aortic valve replacement. Graphical Abstract Comparison of patients with high-gradient (HG) and low-gradient (LG) aortic stenosis (AS) and reduced ejection fraction. Comprehensive analyses including clinical data, gene expression analyses, cardiovascular magnetic resonance (CMR) imaging as well as echocardiography were performed. AF: Atrial fibrillation, MR: mitral regurgitation, RVEF: right ventricular ejection fraction, ECV%: extracellular volume.