Late-Gadolinium Enhancement Interface Area and Electrophysiological Simulations Predict Arrhythmic Events in Patients With Nonischemic Dilated Cardiomyopathy
Clinical Electrophysiology: Imaging
This study sought to investigate whether shape-based late gadolinium enhancement (LGE) metrics and simulations of re-entrant electrical activity are associated with arrhythmic events in patients with nonischemic dilated cardiomyopathy (NIDCM).
The presence of LGE predicts life-threatening ventricular arrhythmias in NIDCM; however, risk stratification remains imprecise. LGE shape and simulations of electrical activity may be able to provide additional prognostic information.
Cardiac magnetic resonance (CMR)-LGE shape metrics were computed for a cohort of 156 patients with NIDCM and visible LGE and tested retrospectively for an association with an arrhythmic composite endpoint of sudden cardiac death and ventricular tachycardia. Computational models were created from images and used in conjunction with simulated stimulation protocols to assess the potential for re-entry induction in each patient’s scar morphology. A mechanistic analysis of the simulations was carried out to explain the associations.
During a median follow-up of 1,611 (interquartile range: 881 to 2,341) days, 16 patients (10.3%) met the primary endpoint. In an inverse probability weighted Cox regression, the LGE–myocardial interface area (hazard ratio [HR]: 1.75; 95% confidence interval [CI]: 1.24 to 2.47; p = 0.001), number of simulated re-entries (HR: 1.40; 95% CI: 1.23 to 1.59; p < 0.01) and LGE volume (HR: 1.44; 95% CI: 1.07 to 1.94; p = 0.02) were associated with arrhythmic events. Computational modeling revealed repolarization heterogeneity and rate-dependent block of electrical wavefronts at the LGE–myocardial interface as putative arrhythmogenic mechanisms directly related to the LGE interface area.
The area of interface between scar and surviving myocardium, as well as simulated re-entrant activity, are associated with an elevated risk of major arrhythmic events in patients with NIDCM and LGE and represent novel risk predictors.
1. "Dilated cardiomyopathy". Circ Arrhythm Electrophysiol 2013;6:228-237.
2. "Association of fibrosis with mortality and sudden cardiac death in patients with nonischemic dilated cardiomyopathy". JAMA 2013;309:896-908.
3. "Defibrillator implantation in patients with nonischemic systolic heart failure". N Engl J Med 2016;375:1221-1230.
4. "Risk stratification for arrhythmic sudden cardiac death: identifying the roadblocks". Circulation 2011;123:2423-2430.
5. "Outcome in dilated cardiomyopathy related to the extent, location, and pattern of late gadolinium enhancement". J Am Coll Cardiol Img 2019;12:1645-1655.
6. "Left ventricular entropy is a novel predictor of arrhythmic events in patients with dilated cardiomyopathy receiving defibrillators for primary prevention". J Am Coll Cardiol Img 2019;7:1177-1184.
7. "Mortality and sudden cardiac death risk stratification using the noninvasive combination of wide QRS duration and late gadolinium enhancement in idiopathic dilated cardiomyopathy". Circ Arrhythm Electrophysiol 2018;11:e006233.
8. "Nonischemic left ventricular scar as a substrate of life-threatening ventricular arrhythmias and sudden cardiac death in competitive athletes". Circ Arrhythm Electrophysiol 2016;9:e004229.
9. "Scar shape analysis and simulated electrical instabilities in a non-ischemic dilated cardiomyopathy patient cohort". PLoS Comput Biol 2019;15:e1007421.
10. "Computational tools for modeling electrical activity in cardiac tissue". J Electrocardiol 2003;36:69-74.
11. "Myocardial electrical propagation in patients with idiopathic dilated cardiomyopathy". J Clin Invest 1993;92:122-140.
12. "Factors promoting conduction slowing as substrates for block and reentry in infarcted hearts". Biophys J 2019;117:1-14.
13. "Percolation as a mechanism to explain atrial fractionated electrograms and reentry in a fibrosis model based on imaging data". Heart Rhythm 2016;13:1536-1543.
14. "Fibrosis microstructure modulates reentry in non-ischemic dilated cardiomyopathy: Insights from imaged guided 2D computational modelling". Front Physiol 2018;9:1832.
15. "Infarct tissue heterogeneity by magnetic resonance imaging identifies enhanced cardiac arrhythmia susceptibility in patients with left ventricular dysfunction". Circulation 2007;115:2006-2014.
16. "Cardiovascular magnetic resonance to predict appropriate implantable cardioverter defibrillator therapy in ischemic and nonischemic cardiomyopathy patients using late gadolinium enhancement border zone: comparison of four analysis methods". Circ Cardiovasc Imaging 2017;10:e006105.
17. "Whole human heart histology to validate electroanatomical voltage mapping in patients with non-ischaemic cardiomyopathy and ventricular tachycardia". Eur Heart J 2018;39:2867-2875.
18. "Mean entropy predicts implantable cardioverter-defibrillator therapy using cardiac magnetic resonance texture analysis of scar heterogeneity". Heart Rhythm 2019. S1547-S1571.
19. "Arrhythmia risk stratification of patients after myocardial infarction using personalized heart models". Nat Commun 2016;7:1-8.
20. "3D electrophysiological modeling of interstitial fibrosis networks and their role in ventricular arrhythmias in non-ischemic cardiomyopathy". IEEE Trans Biomed Eng 2020;67:3125-3133.