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

Abstract

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.

Keywords: ECG; arrhythmia; cardiac magnetic resonance imaging; hypertrophic cardiomyopathy; repolarization; sarcomere; sudden cardiac death.

Structured Graphical Abstract

Figure 1

Mean diastolic FA and ECV correlation with JTc interval in SARC+LVH− and HCM. (A) Mean diastolic FA across groups. (B) Correlation between mean diastolic FA and JTc duration in pre-hypertrophic variant carriers. (C) Mean ECV across groups. (D) Correlation between mean ECV and JTc duration in HCM patients. ECV, extracellular volume; FA, fractional anisotropy; JTc, J point → T wave tangential line, corrected for heart rate; HCM, hypertrophic cardiomyopathy; SARC+LVH, pre-hypertrophic sarcomeric variant carriers.

Figure 2

Microstructural abnormalities detected using DT-CMR in both SARC+LVH− and overt HCM are associated with prolongation of repolarization parameters linked to arrhythmic risk (main illustration). DT-CMR, diffusion tensor cardiac magnetic resonance imaging; HCM, hypertrophic cardiomyopathy; SARC+LVH−, pre-hypertrophic sarcomeric variant carriers.

Figure 3

QTc interval, QTc dispersion, and JTc interval across groups. JTc, J point → T wave tangential line, corrected for heart rate; QTc, Q wave → T wave tangential line, corrected for heart rate.

Figure 4

Receiver operator characteristic curve—diagnostic ability of JTc interval in discriminating SARC+LVH− from healthy controls. JTc, J point → T wave tangential line, corrected for heart rate; SARC+LVH−, pre-hypertrophic sarcomeric variant carriers.