Digital Poster 10: Myocardial Strain by Feature Tracking Cardiovascular Magnetic Resonance in Sarcomeric Positive Hypertrophic Cardiomyopathy with Cardiac Myosin-binding Protein C Mutation: A Long-Term Follow-up Study

Mutations in the cardiac myosin-binding protein C (MYBPC3) gene are commonly seen in hypertrophic cardiomyopathy (HCM) and result in a variable phenotypic expression, ranging from a gene positive, phenotype negative (G+P-) state to classical asymmetric left ventricular hypertrophy (LVH) (G+P+). Abnormal myocardial strain by feature tracking CMR (FT-CMR) is frequently detected in G+P+ HCM and is associated with a poorer cardiac outcome, although studies to-date have been contradictory whether it is deranged also in sarcomere gene mutation carriers without overt LVH (G+P- or subclinical HCM). Furthermore, its progression over time is uncertain in both P+ and P- HCM states. We therefore aimed to assess two-dimensional global circumferential (GCS), radial (GRS), and longitudinal (GLS) strain of the left ventricle (LV) by FT-CMR over time in G+P+ and G+P- HCM.

Methods:

In this prospective study, 6 MYBPC3 G+P+, 7 MYBPC3 G+P- HCM patients, and 6 G- normal volunteers (NV) underwent 3T CMR at baseline and a minimum of 6 years later.  CMR protocol included LV and RV functional mass assessments, and LGE. FT-CMR was quantitated for GCS, GRS and GLS. LGE involvement was quantitated and expressed as number of segments involved in a 17 segment AHA model. Statistical analyses comprised of Mann-Whitney U test, Kruscal Wallis test and paired t-test.

Results:

Median follow-up duration was 8 years (IQR 2 years). GCS, GRS and GLS were similarly impaired at baseline (BL) in the G+P+ and G+P- groups (BL GCS G+P+ -16.4 ±3.1, BL GCS G+P- -18.8 ±1.6; BL GRS G+P+ 28.4 ±10.4, BL GRS G+P- 29.6 ±4.3; BL GLS G+P+ -9.8 ±3.8, BL GLS G+P- -11.8 ±3.4; p>0.05 for all 3 comparisons) and were lower compared with the NV GCS, GRS and GLS parameters at BL. Both HCM groups exhibited a numerical reduction in GCS and GRS FT tracking parameters over time (F/U GCS G+P+ -15.7 ±3.1, F/U GCS G+P- -14.2 ±2.1; F/U GRS G+P+ 26.2 ±10.1, F/U GRS G+P- 24.0 ±7.3), but this only reached statistical significance in the G+P- group (GCS p=0.009, GRS p=0.025). While GLS in the G+P- group was similarly reduced over time, in contrast this reduction was not observed in the G+P+ group (F/U GLS G+P+ -10.8 ±4.0, F/U GLS G+P- -10.5 ±2.6). There was quantitative increase in LGE over time in the G+P+ group (mean of 6.8 LGE segments per patient (pp) increasing to 7.7 segments pp, p=0.071), and in the G+P- group (mean: 0 to 0.4 segments pp respectively, p=0.1). There were no LGE in NV at either baseline or follow-up.

Conclusion:

Impairments in GCS, GRS and GLS were demonstrated at baseline in MYBPC3 gene positive patients with and without left ventricular hypertrophy. These abnormalities worsened over time, regardless of phenotype. Impaired LV myocardial strain despite normal LV wall thickness could imply subclinical pathological processes of impaired myocardial energetics and/or increased interstitial fibrosis that worsen over time even in patients with no overt left ventricular hypertrophy.