Prevalence and determinants of asymmetric septal hypertrophy (ASH) in diseases of left ventricular hypertrophy (LVH)

To determine the prevalence of asymmetric septal hypertrophy (ASH) across health and in diseases associated with left ventricular hypertrophy (LVH), including hypertrophic cardiomyopathy (HCM).

We analysed two complementary datasets. First, a large UK Biobank healthy reference cohort (n = 4020) was used to model demographic determinants of septal-to-lateral wall thickness ratio (SLR) and to provide the reference group for age-, sex-, and body surface area-adjusted comparisons. Second, a multi-cohort clinical CMR dataset included 1655 subjects comprising local healthy volunteers, athletes, patients with hypertension, aortic stenosis, Fabry disease, amyloid light chain (AL) amyloidosis, amyloid transthyretin (ATTR) amyloidosis, and HCM. LVH was defined by maximum wall thickness (MWT) ≥15 mm and asymmetry defined as SLR≥1.3. Left ventricular morphology was classified as normal, asymmetric remodelling (SLR≥1.3; MWT<15 mm), symmetric hypertrophy (SLR<1.3; MWT≥15 mm) or ASH (SLR≥1.3; MWT≥15 mm). ASH was highly prevalent in HCM (61%) but was also observed in ATTR amyloidosis (37%), AS (26%), and AL amyloidosis (23%). In the healthy reference cohort, a higher septal-to-lateral ratio was independently associated with older age, female sex, and larger body surface area (P < 0.001). After adjustment for these demographic factors, only HCM retained a clinically meaningful excess in septal asymmetry (ΔSLR = +0.27; P < 0.001). In contrast, the apparent asymmetry in non-HCM cohorts was partly explained by demographic variation. After adjustment, only HCM showed a clinically meaningful excess in SLR, whereas other disease cohorts showed either no material difference or small negative differences relative to healthy controls.

ASH is a common but non-specific finding in diseases associated with LVH. Septal asymmetry increases with age and body-size and is more pronounced in women. After adjusting for age, sex, and body-size, disproportionate septal asymmetry was most characteristic of HCM.