Left ventricular afterload and myocardial fibrosis in patients with severe symptomatic Aortic Stenosis: a multimodality study

Left ventricular (LV) adaptation to increased afterload in patients with aortic stenosis (AS) is not only determined by valve obstacle but also by arterial impedance. As a compensatory response to maintain wall stress, LV remodeling occurs with myocardial changes that include fibrosis beyond hypertrophy. The impact of aortic stiffness, as a component of vascular load, to this adaptation remains poorly characterized. To assess the role of aortic stiffness, using aortic distensibility (AD) as a surrogate marker, in the myocardial tissue adaptation of the LV in patients with severe AS. Single-centre, prospective study of 158 patients with severe symptomatic aortic stenosis (mean age 71±8 years; 50% male) undergoing surgical aortic valve replacement (SAVR) between 2019 and 2022. Patients with prior cardiomyopathy, significant aortic regurgitation, or other severe valve disease were excluded. All underwent transthoracic echocardiography and cardiac magnetic resonance (CMR) within 3 months before and after SAVR. Septal myocardial biopsies were harvested during surgery and analysed for myocardial fibrosis (MF) using Masson’s trichrome histochemistry. QuPath™ algorithm was applied for automatic MF quantification. Aortic dimensions were measured on cine CMR images at pulmonary artery bifurcation level in three-chamber and coronal left ventricular outflow tract views for the ascending aorta, and in the four-chamber view for the descending aorta. AD before and after SAVR was inferred. Valvulo-arterial impedance (Zva) and relative valve load (RVL) were also calculated. The correlation between AD and MF, as non-invasively assessed by CMR and at histopathology, was determined. 128 patients with complete study were included (median age 73 years [69–77]; 48% male). Median AD was 1.4 [0.7–2.2] × 10−3 mmHg−1, median Zva was 4.59 mmHg/mL/m² [3.76–5.14], and RVL was 13.5 mL/m² [10.9–16.7]. Pre-operative CMR native T1 value was 1051 [1027–1071]ms; extracellular volume (ECV) fraction: 23.6 ± 4.8%. Non-ischemic late gadolinium enhancement (LGE) was present in 67% of patients, with a LGE percentage of 4.1% [1.6–6.9]. MF area was quantified at 1398163 [713204–3116924] µm², representing a median proportion of 12 [6–20]%. No significant correlations were found between AD and tissue characterization at CMR: T1 mapping (ρ= –0.183, p=0.044), LGE percentage (ρ=–0.192, p=0.079); ECV (ρ=–0.022, p=0.810). Similarly, AD showed no correlation with histological MF (ρ=–0.080, p=0.411, ρ=–0.129, p=0.185, for absolute area and proportion, respectively). Zva and RVL also showed no significant associations with either CMR tissue parameters or MF. In patients with classical severe symptomatic AS, myocardial tissue characterization at both pre-operative CMR and histology was unrelated to indexes of LV afterload. Additional factors determining tissue remodeling beyond the valve obstacle and arterial impedance are to be supposed.