Presentation description

Background: Chronic heart failure (HF) affects millions worldwide with limited treatment options. cBIN1 gene therapy addresses these deficits by stabilizing T-tubules and restoring calcium cycling efficiency, both of which are impaired in chronic HF. This study investigates whether cBIN1 gene therapy leads to improved hemodynamic function in a preclinical model with chronic HF induced by myocardial infarction.

Methods: After ligation of the left anterior descending artery, the models were implanted with telemetry transmitters. Left ventricular pressure (LVP) was monitored continuously by a pressure catheter, and the data collected were analyzed. When ejection fraction (EF) declined to <40% the canines were endocardially injected with saline (n=3 control) or AAV9-cBIN1 (n=1 treatment). Mean pre-treatment and post-treatment (5-6 weeks after injection) values for end-diastolic pressure (EDP), end-systolic pressure (ESP), peak upslope and downslope of LVP (±dP/dt), and contractility index (ctrI) were compared between groups.

Results: The cBIN1 treatment group showed hemodynamic improvements compared to the controls, including reduced EDP (-Δ4% vs +Δ11%), increased ESP (+Δ2% vs. -Δ5%), decreased -dP/dt (-Δ1% vs. +Δ12%), and less severe decreases in +dP/dt (-Δ6% vs. -Δ15%) and ctrI (-Δ9% vs. -Δ15%).

Conclusion: These preliminary results suggest that cBIN1 gene therapy may help the hemodynamic problems associated with chronic HF. Further studies with larger sample sizes are needed.