Regional Cardiac Denervation Predicts Sustained Ventricular Arrhythmias in Nonischemic Cardiomyopathy Patients Without LGE on CMR Imaging
Christiane Jungen (Leiden University Medical Center, University Hospital Essen)
H. Sophia Chen (Leiden University Medical Center)
Adrianus P. Wijnmaalen (Leiden University Medical Center)
Petra Dibbets-Schneider (Leiden University Medical Center)
Augusto Meretta (Leiden University Medical Center)
Sebastiaan R. Piers (Leiden University Medical Center)
Yoshitaka Kimura (Leiden University Medical Center)
Lioe Fee De Geus-Oei (TU Delft - RST/Radiation, Science and Technology, Leiden University Medical Center, University of Twente)
Katja Zeppenfeld (Leiden University Medical Center)
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Abstract
BACKGROUND: In patients with nonischemic cardiomyopathy and no late gadolinium enhancement (LGE) on cardiac magnetic resonance, 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 nonischemic cardiomyopathy is unknown. METHODS: Consecutive patients from the Leiden Nonischemic Cardiomyopathy Study who underwent programmed electrical stimulation, LGE-cardiac magnetic resonance, and 123-iodine meta-iodobenzylguanidine imaging between 2011 and 2019 were included. The presence of LGE and global and regional sympathetic denervation on 123-iodine meta-iodobenzylguanidine were evaluated, and patients were followed for the 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 (median age 63 years [25th-75th interquartile range (IQR) 54-68], 79% male, left ventricular ejection fraction 36% [IQR, 27-44], 37% inducible for VA), 35 had no LGE. During 4.5±1.6 years of mean follow-up, VA occurred in 8 of 35 (23%) patients without LGE and in 18 of 40 (45%) patients with LGE. Among patients without LGE, those with VA had greater regional sympathetic denervation (median number of DS 8 [IQR, 7-10] versus 2 [IQR, 1-5], P=0.004; median ratio of DS 0.5 [IQR, 0.5-0.7] versus 0.2 [IQR, 0.1-0.4], P=0.007; median defect score 36 [IQR, 30-41] versus 18 [IQR, 14-24], P=0.01; median weighted denervation size 47 [IQR, 38-54] versus 22 [IQR, 14-30]; P=0.01). In bivariate analysis, the number of DS (hazard ratio, 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 (area under the curve, 0.83; sensitivity, 88%; specificity, 89%). Among patients with LGE, the innervation state was not associated with VA during follow-up. CONCLUSIONS: In patients with nonischemic cardiomyopathy without LGE the extent of regional denervation may contribute to risk stratification for VA.