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Intramyocardial adenoviral vascular endothelial growth factor-D ∆N∆C gene therapy does not induce ventricular arrhythmias.
- Source :
-
The journal of gene medicine [J Gene Med] 2022 Aug; Vol. 24 (8), pp. e3437. Date of Electronic Publication: 2022 Jul 06. - Publication Year :
- 2022
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Abstract
- Background: The phase I KAT301 trial investigated the use of intramyocardial adenoviral vascular endothelial growth factor-D <superscript>ΔNΔC</superscript> (AdVEGF-D) gene therapy (GT) to alleviate symptoms in refractory angina (RA) patients. In KAT301, 30 patients with RA were randomized to AdVEGF-D or the control group in 4:1 ratio. The treatment was found to be feasible, increasing myocardial perfusion and reducing angina symptoms at 1-year follow-up. However, there is some evidence suggesting that the intramyocardial delivery route and overexpression of (vascular endothelial growth) VEGFs might induce ventricular arrhythmias. Thus, we investigated whether intramyocardial AdVEGF-D GT increases the risk of ventricular arrhythmias in patients treated for RA.<br />Methods: We analyzed non-invasive risk predictors of ventricular arrhythmias from 12-lead electrocardiography (ECG) as well as heart rate variability (HRV) and the incidence of arrhythmias from 24 h ambulatory ECG at baseline and 3 and 12 months after the GT. In addition, we analyzed the incidence of new-onset arrhythmias and pacemaker implantations during 8.2 years (range 6.3-10.4 years) of follow-up.<br />Results: We found no significant increase in arrhythmias, including supraventricular and ventricular ectopic beats, atrial fibrillation, non-sustained ventricular tachycardias, and life-threatening tachycardias, nor changes in the non-invasive risk predictors of ventricular arrhythmias in the AdVEGF-D treated patients. Instead, we found a significant improvement in the very low and high-frequency bands of HRV suggestive of improved cardiac autonomic regulation after GT.<br />Conclusions: In conclusion, our results suggest that AdVEGF-D GT does not predispose to arrhythmias and might improve HRV metrics.<br /> (© 2022 John Wiley & Sons Ltd.)
Details
- Language :
- English
- ISSN :
- 1521-2254
- Volume :
- 24
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- The journal of gene medicine
- Publication Type :
- Academic Journal
- Accession number :
- 35750637
- Full Text :
- https://doi.org/10.1002/jgm.3437