Relevance of sympathetic innervation and myocardial substrate for ventricular arrhythmogenesis in patients with non-ischemic cardiomyopathy
Final Report Abstract
During the funding period, the applicant was able to gain new insights into the influence of sympathetic innervation on the development of ventricular arrhythmias (VA) in patients with non-ischemic cardiomyopathy (NICM). The analysis of global and regional sympathetic innervation using nuclear medicine 123I-MIBG imaging, of myocardial scar using late gadolinium enhancement (LGE) in cardiac MRI, of endomyocardial voltage as surrogate for fibrosis in interventional mapping and of VA-related substrate in catheter ablation and the relation of these parameters yielded the following results: (1) It has been shown for the first time that global cardiac sympathetic denervation correlates with weighted unipolar voltage as a surrogate parameter for diffuse cardiac fibrosis. In addition, a difference in regional fibrosis and sympathetic denervation was found for patients with inferolateral in comparison to those with anteroseptal substrate: in patients with inferolateral substrate, the areas of VA-related substrate, regional scar and regional sympathetic denervation coincided, whereas in patients with anteroseptal substrate, the VA -related area did not exhibit local scar or local denervation. This imbalance and the anteroseptal preservation of innervation could be a reason for the higher recurrence rates for patients undergoing VA catheter ablation of anteroseptal substrate. (2) Furthermore, it could be shown that in NICM patients who don’t have LGE in the cardiac MRI, the extent of regional denervation is relevant for the occurrence of VA. In these patients, a regional denervation of ≥7 segments was shown to correlate with the occurrence of VA in the disease course. This correlation was not present for NICM patients who had LGE in the cardiac MRI. In summary, the relationship between global denervation and fibrosis, the relevance of the localization of denervation and a connection between the extent of regional denervation and the probability of VA occurrence in the further disease course in NICM patients could be shown for the first time. On basis of these results, an improved risk stratification in NICM patients could be carried out. This can optimize therapeutical decisions and lead to a more personalized patient care in clinical routine.
Publications
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Sympathetic innervation pattern in NICM patients with ventricular tachycardia -anteroseptal versus inferolateral substrates-. EP Europace, 23(Supplement_3).
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.
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Ventricular Arrhythmia Substrate Distribution and Its Relation to Sympathetic Innervation in Nonischemic Cardiomyopathy Patients. JACC: Clinical Electrophysiology, 8(10), 1234-1245.
Chen, H. Sophia; Jungen, Christiane; Kimura, Yoshitaka; Dibbets-Schneider, Petra; Piers, Sebastiaan R.; Androulakis, Alexander F.A.; van der Geest, Rob. J.; de Geus-Oei, Lioe-Fee; Scholte, Arthur J.H.A.; Lamb, Hildo J.; Jongbloed, Monique R.M. & Zeppenfeld, Katja
