Ventricular arrhythmia substrate distribution and its relation to sympathetic innervation in nonischemic cardiomyopathy patients

Chen, H.S.; Jungen, C.; Kimura, Y.; Dibbets-Schneider, P.; Piers, S.R.; Androulakis, A.F.A.; Geest, R.J.V.; Geus-Oei, L.F. de; Scholte, A.J.H.A.; Lamb, H.J.; Jongbloed, M.R.M.; Zeppenfeld, K.

doi:doi:10.1016/j.jacep.2022.07.006

BACKGROUND Nonischemic cardiomyopathy patients referred for catheter ablation of ventricular arrhythmias (VAs) typically have either inferolateral (ILS) or anteroseptal (ASS) VA substrate locations, with poorer outcomes for ASS. Sympathetic denervation is an important determinant of arrhythmogenicity. Its relation to nonischemic fibrosis in general and to the different VA substrates is unknown.OBJECTIVES This study sought to evaluate the association between VA substrates, myocardial fibrosis, and sympa-thetic denervation. METHODS Thirty-five patients from the Leiden Nonischemic Cardiomyopathy Study, who underwent electroanatomic voltage mapping and iodine-123 metaiodobenzylguanidine imaging between 2011 and 2018 were included. Late gadolinium-enhanced cardiac magnetic resonance data were collected when available. The relation between global cardiac sympathetic innervation and area-weighted unipolar voltage (UV) as a surrogate for diffuse fibrosis was evalu-ated. For regional...Show moreBACKGROUND Nonischemic cardiomyopathy patients referred for catheter ablation of ventricular arrhythmias (VAs) typically have either inferolateral (ILS) or anteroseptal (ASS) VA substrate locations, with poorer outcomes for ASS. Sympathetic denervation is an important determinant of arrhythmogenicity. Its relation to nonischemic fibrosis in general and to the different VA substrates is unknown.OBJECTIVES This study sought to evaluate the association between VA substrates, myocardial fibrosis, and sympa-thetic denervation. METHODS Thirty-five patients from the Leiden Nonischemic Cardiomyopathy Study, who underwent electroanatomic voltage mapping and iodine-123 metaiodobenzylguanidine imaging between 2011 and 2018 were included. Late gadolinium-enhanced cardiac magnetic resonance data were collected when available. The relation between global cardiac sympathetic innervation and area-weighted unipolar voltage (UV) as a surrogate for diffuse fibrosis was evalu-ated. For regional analysis, patients were categorized as ASS or ILS. The distribution of low UV, sympathetic denervation, and late gadolinium enhancement (LGE) scar were compared using the 17-segment model.RESULTS Median area-weighted UV was 12.3 mV in patients with normal sympathetic innervation and 8.7 mV in patients with sympathetic denervation. Global sympathetic denervation correlated with diffuse myocardial fibrosis (R = 0.53; P = 0.02). ILS (n = 13) matched with low UV, sympathetic denervation, and LGE scar in all patients, whereas ASS (n = 11) matched with low UV in all patients, with LGE scar in 63% (P = 0.20), but with sympathetic denervation in only 27% of patients (P = 0.0002).CONCLUSIONS Global cardiac sympathetic denervation is related to fibrosis in nonischemic cardiomyopathy patients with VA. The mismatch between regional fibrosis and preserved innervation for ASS may contribute to a VA substrate difficult to control by catheter ablation. (J Am Coll Cardiol EP 2022;8:1234-1245)(c) 2022 by the American College of Cardiology Foundation.Show less

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Ventricular arrhythmia substrate distribution and its relation to sympathetic innervation in nonischemic cardiomyopathy patients