Sympathetic innervation pattern in NICM patients with ventricular tachycardia -anteroseptal versus inferolateral substrates-
Authors: Jungen C , Chen HS , Kimura Y , Dibbets-Schneider P , Piers SRD , Androulakis AFA , Van Der Geest RJ , De Geus-Oei LF , Scholte AJH , Lamb HJ , Jongbloed MRM , Zeppenfeld K 
Published: May 2021

Abstract

Funding Acknowledgements
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation - Projektnummer 447558597)

Background
Among patients with non-ischemic cardiomyopathy (NICM) two dominant ventricular tachycardia (VT) substrate locations, namely anteroseptal (AS) and inferolateral (IL), have been identified. The poor outcome after catheter ablation of AS substrates (ASS) compared to IL substrates (ILS) has been attributed to its deep intramural location. However, region specific tissue charateristics, including sympathetic innervation, as important determinant of arrhythmogeneity, may also contribute to the outcome disparity.

Aim
To evaluate the association between regional sympathetic denervation, myocardial fibrosis and VT substrates according to two dominant VT substrate locations.

Methods
Twenty-nine patients from the ‘Leiden Nonischemic Cardiomyopathy Study’, who underwent electroanatomical substrate mapping and radiofrequency catheter ablation (RFCA), LGE-CMR and 123-I-MIBG imaging between 2011-2018 were included. The 16-segment model was used to describe the distribution of endocardial low unipolar voltage (UV &lt;25th IQR) (=electroanatomical surrogate for fibrosis), the location of abnormal local electrograms and VT related sites (= surrogate for VT substrate) and the presence of LGE. Regional cardiac sympathetic innervation was determined by 123-I-MIBG imaging and analyzed according to the 16-segment model. Regions with sympathetic denervation were correlated with low UV areas, VT substrate location and LGE. Patients were categorized according to the dominant VT substrate location in ASS or ILS.

Results
Ten patients had a dominant ASS, 12 patients a dominant ILS and 1 patient had ASS and ILS; 6 patients had other VT substrate locations. All but one patient with ASS and one with ILS also showed corresponding low UV (=surrogate for fibrosis) in segments with VT substrates. Eight patients with IL VT substrates but only 4 with AS substrates showed corresponding LGE in the VT related segments. All patients with inferolateral VT substrates showed sympathetic denervation in IL segments (100% matching segments), but only 3/11 (27%) with anteroseptal substrates had sympathetic denervation in AS segments (P = 0.0002). UV was not significantly different between matching (VT substrate and denervation) and not matching ASS segments (5.74 ± 2.69 mV vs. 4.64 ± 1.85 mV, P = 0.78) and between matching ASS and ILS segments (5.74 ± 2.69 mV vs. 7.61 ± 2.91, P = 0.43). LGE location was matching with sympathetic denervation in all patients with ILS but only in 33% of patients with ASS.

Conclusion
Despite low endocardial UV (=surrogate for fibrosis) for AS and IL segments harboring VT substrates, regional sympathetic denervation coincided with fibrosis only for IL VT substrates. The mismatch between regional fibrosis and preserved innervation for AS VT substrates may contribute to a VT substrate difficult to control by RFCA.