Sex and regional differences in myocardial plasticity in aortic stenosis are revealed by 3D model machine learning

Aims: Left ventricular hypertrophy (LVH) in aortic stenosis (AS) varies widely before and after aortic valve replacement (AVR), and deeper phenotyping beyond traditional global measures may improve risk stratification. We hypothesized that machine learning derived 3D LV models may provide a more sensitive assessment of remodelling and sex-related differences in AS than conventional measurements.

Methods and results: One hundred and sixteen patients with severe, symptomatic AS (54% male, 70 ± 10 years) underwent cardiovascular magnetic resonance pre-AVR and 1 year post-AVR. Computational analysis produced co-registered 3D models of wall thickness, which were compared with 40 propensity-matched healthy controls. Preoperative regional wall thickness and post-operative percentage wall thickness regression were analysed, stratified by sex. AS hypertrophy and regression post-AVR was non-uniform-greatest in the septum with more pronounced changes in males than females (wall thickness regression: -13 ± 3.6 vs. -6 ± 1.9%, respectively, P < 0.05). Even patients without LVH (16% with normal indexed LV mass, 79% female) had greater septal and inferior wall thickness compared with controls (8.8 ± 1.6 vs. 6.6 ± 1.2 mm, P < 0.05), which regressed post-AVR. These differences were not detectable by global measures of remodelling. Changes to clinical parameters post-AVR were also greater in males: N-terminal pro-brain natriuretic peptide (NT-proBNP) [-37 (interquartile range -88 to -2) vs. -1 (-24 to 11) ng/L, P = 0.008], and systolic blood pressure (12.9 ± 23 vs. 2.1 ± 17 mmHg, P = 0.009), with changes in NT-proBNP correlating with percentage LV mass regression in males only (ß 0.32, P = 0.02).

Conclusion: In patients with severe AS, including those without overt LVH, LV remodelling is most plastic in the septum, and greater in males, both pre-AVR and post-AVR. Three-dimensional machine learning is more sensitive than conventional analysis to these changes, potentially enhancing risk stratification.

Clinical trial registration: Regression of myocardial fibrosis after aortic valve replacement (RELIEF-AS); NCT02174471. https://clinicaltrials.gov/ct2/show/NCT02174471.