Preclinical study of the efficacy of the VVF34 composition for chemical myocardial ablation

Background: Ventricular arrhythmias (VA) remain a leading cause of cardiovascular mortality. Existing ablation methods, including radiofrequency ablation (RFA), have limitations related to the depth and homogeneity of the lesion created. Objective: The objective of this study was to experimentally assess the efficacy of a new method on controlled chemical myocardial ablation using the VVF34 composition. Methods: The study was conducted on rats (n = 60) and minipigs (n = 6). The histological dynamics and dose-dependent fibrosis formation in response to intramuscular administration of VVF34 (0.1; 0.2 and 0.3 ml) were studied in rats. Intramyocardial injection under fluoroscopic guidance using a Myostar catheter was tested in minipigs, and the safety of the procedure was assessed using echocardiography and electrocardiography. Results: VVF34 has been shown to induce dose-dependent formation of a sharply marginated zone. A low dose (0.1 ml) proved to be optimal, resulting in the formation of dense fibrosis with minimal inflammation, while elevating the dose caused destructive necrosis. To create extended ablation lines, it was appropriate to use a series of injections spaced at least 3 mm. The intramyocardial injection procedure was safe, did not have a proarrhythmic effect, and did not impair cardiac contractility. Conclusion: Chemical ablation with VVF34 composition is a promising alternative to existing approaches and enables to create controlled homogeneous deep fibrotic lesions, opening up new possibilities for the treatment of resistant ventricular arrhythmias.