Anatomy of the isthmus: unraveling tissue composition of ventricular tachycardia diastolic pathway

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Spanish Ministry of Science and Innovation Background Unequal tissue composition of post-myocardial infarction (MI) scar (viable myocardium, fibrosis, fatty infiltration) leads to heterogeneous conduction properties and excitability. The presence of a protected diastolic, slow-conducting pathway (isthmus) is the electrophysiological landmark of post-MI reentrant ventricular tachycardia (VT). Contemporary histological studies evaluating the tissue features needed for slow, protected conduction during VT are lacking. Purpose To characterize tissue composition singularities of confirmed VT isthmuses (VTI) in a chronic MI swine model, and to compare it to non-isthmus scar (NIS). Methods One-month after a non-reperfused anterior MI, 9 Landrace X Large White pigs (4 female; 33.6±2.2 Kg) with inducible VT underwent high-density activation mapping to define the diastolic corridor. VTI was defined as part of the diastolic pathway exhibiting mid-diastolic potentials. Discrete radiofrequency applications were delivered in the vicinity of the VTI and used as tissue landmarks to guide the ex vivo isthmus localization. Tissue transverse samples (5 mm) from the labelled VTI and NIS were obtained for further histological and immunohistochemical analysis. Dense scar and border zones were analyzed. Results Compared to NIS, border zone of VTI showed significantly higher fatty infiltration (p=0.016) and dense scar displayed less Collagen I (p=0.053), Collagen III (p=0.043), and Collagen Volume Fraction (p=0.027), without differences in the overall fibrotic deposition (P=0.119). Immunohistochemical studies revealed greater vascular density (Isolectin B4-positive vessels) at VTI, compared to NIS (p=0.018). Arteries and veins at the VTI were mostly surrounded by preserved cardiomyocytes (figure 1). Viable cardiomyocytes and fibroblasts at VTI displayed higher density of Cx43 and Cx40, respectively, compared to those at NIS (p=0.022 and p=0.004, respectively), despite no differences in cTnI, SERCA2 and Vimentin expression (figure 2). Conclusion The VTI exhibits distinctive tissue features compared to NIS. Unique electrophysiological properties of the VTI may be driven by increased adipocytic deposition, vascular density and Cx43/Cx40 expression, as well as lower presence of Collagen III and Collagen Volume Fraction.