Abstract 16405: Long-Term Biological Pacemaker Activity Created by Percutaneous TBX18 Gene Transfer
Background: Minimally-invasive TBX18 gene transfer creates physiologically-relevant biological pacemaker (BioP) activity for at least 2 weeks in pigs with complete heart block, providing evidence for therapeutic somatic reprogramming in a clinically-relevant disease model (Hu et al, Sci Trans Med 2014). It remains unknown how long biological pacemaker activity is maintained after TBX18 gene transfer.
Hypothesis: We tested whether TBX18 gene transfer could create sustained BioP activity beyond two weeks.
Methods: Adenoviral vectors expressing either TBX18 (n=3) or GFP (n=2) as a control were delivered into the high right ventricular septum via injection catheters (NOGA™ Myostar). Rate and rhythm were followed continuously for one month by implanted telemetry, and backup device utilization was quantified by serial pacemaker interrogations. Physical activity was measured by a built-in accelerometer.
Results: BioP activity was evident in TBX18-transduced animals and persisted at least for 4 weeks. At week 4, maximal heart rate (HR,101±8 vs. 65±3bpm, p<0.05), daytime HR (79±4 vs. 53±1bpm, p<0.05), and electronic pacemaker utilization (82±3 vs. 6±3%, p<0.05) were higher in TBX18-transduced animals compared to GFP controls. Mean HR was borderline higher in TBX18-transduced animals compared to GFP controls (HR=70±7 vs. 51±1bpm, p=0.11) as was night-time HR (70±5 vs. 51±0bpm, p=0.07). Mean daily activity tends to be greater in TBX18-transduced group (394±18 vs. 339±12 A.U, p=0.11). There were no significant differences of ventricular arrhythmia incidence between the two groups during 4 week follow-up. Cardiac enzymes, liver function, renal function, and systemic inflammatory markers remained unchanged in both groups during follow-up.
Conclusions: TBX18 gene transfer can create stable BioP activity for at least 4 weeks, suggesting a potential long-term BioP effect after adenoviral gene transfer.
Author Disclosures: Y. Hu: None. J. Dawkins: None. H. Cho: None. E. Marbán: None. E. Cingolani: None.
- © 2014 by American Heart Association, Inc.