Differences in left ventricular mass and morphology and right ventricular function differentiate phenotype-negative sarcomere gene mutation carriers from healthy volunteers

Abstract Funding Acknowledgements Type of funding sources: None. Carriers of pathogenic DNA variants (G+) causing hypertrophic cardiomyopathy (HCM) can be identified by genetic testing, before manifestation of left ventricular hypertrophy (LVH). These G+/LVH- subjects are routinely monitored for phenotypic expression, which, alongside LVH, can include other HCM-related abnormalities, including crypts and myocardial fibrosis. Cardiovascular magnetic resonance (CMR) imaging has emerged as a valuable technique in diagnosing and follow-up of HCM. In this study, we identified clinical features of subclinical HCM in a G+/LVH- population compared to healthy subjects. We studied 33 G+ subjects with CMR and a maximal wall thickness (MWT) <13mm, and compared them to an age- and gender-matched group of 35 healthy controls (44 ± 14 vs 48 ± 10 y, p = 0.17; 11 (33%) vs 12 (34%) men, p = 0.93). The CMR imaging protocol consisted of 1) steady state free procession cine imaging, 2) 2-dimensional late gadolinium enhancement (LGE) images in the G+ patients and 3) pre-contrast T1 mapping using a modified look-locker inverse recovery sequence. We assessed CMR examinations for features of HCM. Forward logistic regression analysis was performed to determine which of the CMR characteristics were predictive of G+ status. G+ subjects had a higher MWT (10.9 ± 1.6 vs 10.2 ± 1.3 mm, p = 0.04), a similar interventricular septal wall (IVS) thickness (8.8 ± 1.6 vs 8.7 ± 1.6 mm, p = 0.85), a smaller posterior wall (PW) and a higher IVS/PW ratio (6.6 ± 1.2 vs 7.7 ± 1.3mm, p < 0.001; 1.4 ± 0.3 vs 1.1 ± 0.2, p = 0.001). Indexed left ventricular (LV) mass was significantly lower in the G+ group (Table). LV function was similar (63 ± 6 vs. 61 ± 5%, p = 0.12), but right ventricular (RV) function was higher in the G+ group. They often had a characteristic hook-shaped thickening of the basal anterior wall (7 (21%) vs 0, p < 0.004; Figure) and more frequently exhibited myocardial crypts. Midwall LGE was present in 3 (9%) G+ subjects. Native septal T1 values were elevated in G+ patients compared to controls, although mostly within the normal range (986 ± 31 vs 963 ± 28 ms, p < 0.01). Crypts, indexed LV mass and RV ejection fraction were significant predictors of G+ status in logistic regression analysis (Table). CMR demonstrates significant morphological differences between the G+/LVH- population and healthy controls. Further studies are needed to assess the prognostic significance of these morphological features. Predictors of genotype-positive status Variables G+ subjects (n = 33) Controls (n = 35) P value OR for G+ status P value Left ventricular mass/BSA (g/m²) 45 ± 7.4 53 ± 7.9 <0.001 0.86 [0.78-0.95] 0.003 Right ventricular ejection fraction (%) 58 ± 6 53 ± 4 <0.001 1.15 [1.00-1.32] 0.047 Crypts 17 (55%) 4 (11%) <0.001 9.62 [1.93-48.00] 0.006 G+: genotype-positive, OR: odds ratio Abstract Figure. CMR findings