Regional cardiac denervation predicts sustained ventricular arrhythmias in non-ischemic cardiomyopathy patients without LGE on CMR imaging

Abstract Background In patients with non-ischemic cardiomyopathy (NICM) and no late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR), risk prediction for the occurrence of sustained ventricular arrhythmias (VA) is challenging. Global and regional sympathetic denervation has been associated with VA in patients with ischemic cardiomyopathy. Its prognostic relevance in NICM is unknown. Purpose To assess the risk prediction of sympathetic denervation for the occurrence of VA in NICM patients without LGE. Methods Consecutive patients from the ‘Leiden Nonischemic Cardiomyopathy Study’, who underwent programmed electrical stimulation, LGE-CMR and 123I- MIBG imaging between 2011-2018 were included. The presence of LGE and global and regional sympathetic denervation on 123I- MIBG was evaluated and patients were followed for occurrence of VA. Global denervation was assessed using the heart-to-mediastinum ratio. Regional denervation was evaluated by calculating the number of denervated segments (DS), the ratio of DS, the summed defect score and the weighted denervation size. Results Of 75 included patients (63 years [52-68], 79% male, LVEF 36% [27-44], 37% inducible for VA) 35 had no LGE. During 4.5±1.6 years follow-up, VA occurred in 8/35 (23%) patients without LGE and in 18/40 (45%) patients with LGE. Among patients without LGE, those with VA had greater regional sympathetic denervation (number of DS 8 [8-10] vs. 2 [1-5], P=0.004; ratio of DS 0.5 [0.5-0.7] vs. 0.2 [0.1-0.4], P=0.007; defect score 36 [31-41] vs. 18 [14-24], P=0.01; weighted denervation size 47 [39-53] vs. 22 [16-30], P=0.01). In univariable analysis the number of DS (HR 1.25, 95% CI 1.06–1.46, P=0.006) was associated with the occurrence of VA in patients without LGE. Denervation of ≥ 7 segments identified patients without LGE at risk for VA (AUC: 0.83, sensitivity: 88%; specificity: 89%). Among patients with LGE, innervation state was not associated with VA during follow-up. Conclusions In NICM patients without LGE the extent of regional denervation may contribute to risk stratification for VA.Graphical Abstract