Myocardial Entropy and Risk Predictors in Hypertrophic Cardiomyopathy: An Analysis From the NHLBI HCM Registry

Abstract

Background: Entropy, a novel measure of myocardial tissue heterogeneity by cardiovascular magnetic resonance imaging, may have clinical value in patients with hypertrophic cardiomyopathy (HCM). We aimed to investigate the associations of entropy with risk predictors in HCM, using the National Heart, Lung, and Blood Institute HCM Registry.

Methods: Entropy values were calculated using the probability distribution of pixel signal intensities of the left ventricular (LV) myocardium on the late gadolinium enhancement (LGE) short-axis stack images. Entropy values were correlated with demographic, genetic, imaging, and serum biomarkers as well as ambulatory Holter recordings and the European Society of Cardiology risk score of sudden cardiac death at 5 years.

Results: Among 1736 patients with HCM, LV entropy demonstrated significant associations with sarcomere mutations, history of ventricular tachycardia, atrial fibrillation, and elevation of cTnT (cardiac troponin T) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels (P<0.001). Furthermore, LV entropy demonstrated an association with increased maximal LV wall thickness, LGE presence and extent, higher extracellular volume, left atrial area and function, myocardial strain (P<0.001), and was positively correlated with higher values of the European Society of Cardiology risk score (P<0.001). In the subgroup of patients without LGE (n=858), entropy values remained significantly associated with a history of ventricular tachycardia, increased maximal wall thickness, decreased myocardial strain, and the European Society of Cardiology risk score (P<0.05 for all). In both the whole cohort and in patients without LGE, LV entropy was the strongest predictor of ventricular tachycardia on Holter (odds ratio [95% CI] 1.59 [1.33-1.90]; 1.87 [1.28-2.74] respectively, P<0.001 for both).

Conclusions: In patients with HCM, LV entropy demonstrated associations with clinical, imaging, and biological predictors of adverse outcomes independent of LGE presence and was the strongest predictor of ventricular tachycardia on Holter.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01915615.

Keywords: cardiomyopathy, hypertrophic; death, sudden, cardiac; entropy; gadolinium; tachycardia, ventricular.

Figure 1:. Myocardial entropy by Cardiovascular Magnetic Resonance

After loading the whole short axis LGE PSIR stack and corresponding contours, Mass Research Software provides the “Multi Slice Pixel Intensity Histogram” and automatically calculates the mean LV entropy value for the whole stack. * LGE = Late Gadolinium Enhancement; PSIR = Phase Sensitive Inversion Recovery; LV = Left Ventricular

Figure 2:. ESC guidelines- based Sudden Cardiac Death 5-year risk according to LV entropy tertiles

Significant increase in mean 5-year SCD risk across entropy tertiles, from 4.2 (3.0 – 5.9) in Tertile 1, to 4.7 (3.4 – 6.6) in Tertile 2 and 5.0 (3.5 – 7.3) in Tertile 3 (p<0.001). The reference line at 6%, demonstrates the “High Risk” threshold, according to ESC guidelines. * ESC = European Society of Cardiology; LV = Left Ventricular; SCD = Sudden Cardiac Death;