Ishidoya, Y. | bioRxiv Science

bioRxiv2025

Antitachycardia Pacing is More Effective When Delivered to the Left Bundle Branch Area Compared to the Right Ventricle in a Pre-clinical Model of Ischemic Ventricular Tachycardia

BackgroundAnti-tachycardia pacing (ATP) delivered from implantable cardioverter defibrillators (ICDs) provides critically timed pacing pulses to terminate ventricular tachycardia (VT). Physiological pacing through left bundle branch area (LBBA) pacing has emerged as a clinically relevant alternative to induce synchronous activation of the ventricles. The main objective of this study was to compare the efficacy and safety of ATP delivered to an LBBA lead and a conventional RV lead. MethodsUsing a preclinical animal model (n=7), pacing leads were implanted in the RV apex and LBBA and connected to ICDs. The left anterior descending artery was occluded for two hours to cause an ischemia-reperfusion injury (IRI). Four days following IRI, VT episodes were induced using programmed electrical stimulation (PES), and burst ATP therapy was delivered to the RV or LBBA leads for each VT episode. ResultsVT was induced 80 times, with a mean VT cycle length (VT CL) of 180.0{+/-}30.0 ms. ATP delivered to the LBBA terminated VT more often than RV ATP (70.2% vs 47.3%, P = 0.04), and there was no significant difference in negative outcomes of VT acceleration or VF induction. Activation sequences from the basket catheter were determined for the pre-therapy VT and captured ATP beats, and correlation coefficients were computed to the activation sequences during ATP delivery. The number of ATP pulses required for the activation sequences to correlate with the captured ATP pattern rather than the pre-therapy VT pattern was lower for LBBA ATP compared to RV ATP (4.1 vs. 5.1 beats, P = 0.04). Successful LBBA ATP demonstrated earlier and more frequent Purkinje activations preceding myocardial activation than successful RV ATP. ConclusionImproved performance of LBBA ATP compared to RV ATP provides further incentive for the wide use of LBBA leads in patients who need cardiac electrotherapy.

bioengineering↗

bioRxiv2022

A Canine Model of Chronic Ischemic Heart Failure

BackgroundThere is a paucity of novel therapeutics for chronic heart failure (HF). Preclinical large animal models of chronic HF are crucial to translating fundamental discoveries. Canine models of ischemic cardiomyopathy are frequently utilized but are severely limited by competing needs to both induce sufficient muscle injury which results in an appropriately severe degree of left ventricular dysfunction yet to also minimize early mortality. MethodsTwenty-eight healthy adult dogs (30{+/-}4 kg, 15/28 male) underwent thoracotomy procedures followed by one of three types of left anterior descending (LAD) coronary artery ligations: Simple LAD (proximal and distal LAD ligation), LAD and Lateral (proximal and distal LAD, distal first diagonal, and proximal first obtuse marginal), and Total LAD Devascularization (TLD including the proximal and distal LAD, proximal aspects of the first, second, and third diagonals, and proximal aspects of first and second epicardial right ventricular branches of the LAD). Invasive and non-invasive hemodynamics were followed until attainment of chronic severe HF, which was achieved when left ventricular ejection fraction (LVEF) was <40% and N-terminal prohormone B-type Natriuretic peptide (NT-proBNP) >900 pmol/L, both for two consecutive measurements. ResultsOverall post-ligation early mortality (within 48 h of coronary ligation) was 18% (n=5/28), and the overall survival rate at 5 weeks post-ligation was 68% (n=19/28). At post-ligation week 1, LVEF was acutely reduced in all animals, from 54{+/-}4 to 38{+/-}1%, p<0.001. Beyond week 1, systolic function recovered over 3-4 weeks and then slowly declined as the left ventricle dilated and both systolic and diastolic function worsened. The magnitude of the initial decline in LVEF predicted ultimate HF development. Dogs with Simple LAD and LAD plus Lateral had excellent and limited survival at 48 hours (100% and 47%, respectively), yet the second group more likely developed chronic HF at 9 - 14 weeks (50% versus 57%, respectively). Dogs with TLD had both improved survival at 48 hours (90%) and excellent development of chronic HF (100%). ConclusionsBy focusing on the LAD only and limiting collateral flow to it by ligating all side branches, optimal survival and attainment of chronic ischemic HF can be achieved in the canine heart.

developmental biology↗