Myocardial disarray and fibrosis across hypertrophic cardiomyopathy stages associate with ECG markers of arrhythmic risk

Aims Myocardial disarray, an early feature of hypertrophic cardiomyopathy (HCM) and a substrate for ventricular arrhythmia, is poorly characterized in pre-hypertrophic sarcomeric variant carriers (SARC+LVH−). Using diffusion tensor cardiac magnetic resonance (DT-CMR) we assessed myocardial disarray and fibrosis in both SARC+LVH− and HCM patients and evaluated the relationship between microstructural alterations and electrocardiographic (ECG) parameters associated with arrhythmic risk. Methods and results Sixty-two individuals (24 SARC+LVH−, 24 HCM, and 14 matched controls) were evaluated with multi-parametric CMR including stimulated echo acquisition mode DT-CMR, and blinded quantitative 12-lead ECG analysis. Mean diastolic fractional anisotropy (FA) was reduced in HCM compared with SARC+LVH− and controls (0.49 ± 0.05 vs. 0.52 ± 0.04 vs. 0.53 ± 0.04, P = 0.009), even after adjustment for differences in extracellular volume (ECV) (P = 0.038). Both HCM and SARC+LVH− had segments with significantly reduced diastolic FA relative to controls (54 vs. 25 vs. 0%, P = 0.002). Multiple repolarization parameters were prolonged in HCM and SARC+LVH−, with corrected JT interval (JTc) being most significant (354 ± 42 vs. 356 ± 26 vs. 314 ± 26 ms, P = 0.002). Among SARC+LVH−, JTc duration correlated negatively with mean diastolic FA (r = −0.6, P = 0.002). In HCM, the JTc interval showed a stronger association with ECV (r = 0.6 P = 0.019) than with mean diastolic FA (r = −0.1 P = 0.72). JTc discriminated SARC+LVH− from controls [area under the receiver operator curve 0.88, confidence interval 0.76–1.00, P < 0.001], and in HCM correlated with the European Society of Cardiology HCM sudden cardiac death risk score (r = 0.5, P = 0.014). Conclusion Low diastolic FA, suggestive of myocardial disarray, is present in both SARC+LVH− and HCM. Low FA and raised ECV were associated with repolarization prolongation. Myocardial disarray assessment using DT-CMR and repolarization parameters such as the JTc interval demonstrate significant potential as markers of disease activity in HCM.