{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T04:16:06Z","timestamp":1792556166500,"version":"4.5.0"},"reference-count":35,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T00:00:00Z","timestamp":1657065600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004092","name":"Kuopion Yliopistollinen Sairaala","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004092","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The phase I KAT301 trial investigated the use of intramyocardial adenoviral vascular endothelial growth factor\u2010D<jats:sup>\u0394N\u0394C<\/jats:sup> (AdVEGF\u2010D) gene therapy (GT) to alleviate symptoms in refractory angina (RA) patients. In KAT301, 30 patients with RA were randomized to AdVEGF\u2010D or the control group in 4:1 ratio. The treatment was found to be feasible, increasing myocardial perfusion and reducing angina symptoms at 1\u2010year follow\u2010up. 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\u2010D GT increases the risk of ventricular arrhythmias in patients treated for RA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analyzed non\u2010invasive risk predictors of ventricular arrhythmias from 12\u2010lead electrocardiography (ECG) as well as heart rate variability (HRV) and the incidence of arrhythmias from 24\u2009h ambulatory ECG at baseline and 3 and 12\u2009months after the GT. In addition, we analyzed the incidence of new\u2010onset arrhythmias and pacemaker implantations during 8.2\u00a0years (range 6.3\u201310.4\u00a0years) of follow\u2010up.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found no significant increase in arrhythmias, including supraventricular and ventricular ectopic beats, atrial fibrillation, non\u2010sustained ventricular tachycardias, and life\u2010threatening tachycardias, nor changes in the non\u2010invasive risk predictors of ventricular arrhythmias in the AdVEGF\u2010D treated patients. Instead, we found a significant improvement in the very low and high\u2010frequency bands of HRV suggestive of improved cardiac autonomic regulation after GT.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In conclusion, our results suggest that AdVEGF\u2010D GT does not predispose to arrhythmias and might improve HRV metrics.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jgm.3437","type":"journal-article","created":{"date-parts":[[2022,6,25]],"date-time":"2022-06-25T02:13:20Z","timestamp":1656123200000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Intramyocardial adenoviral vascular endothelial growth factor\u2010D<sup>\u2206N\u2206C<\/sup> gene therapy does not induce ventricular arrhythmias"],"prefix":"10.1002","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9590-0105","authenticated-orcid":false,"given":"Aleksi J.","family":"Leikas","sequence":"first","affiliation":[{"name":"Heart Center Kuopio University Hospital  Kuopio Finland"},{"name":"A.I. Virtanen Institute for Molecular Sciences University of Eastern Finland  Kuopio Finland"},{"name":"Gene Therapy Unit Kuopio University Hospital  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iiro","family":"Hassinen","sequence":"additional","affiliation":[{"name":"Heart Center Kuopio University Hospital  Kuopio Finland"},{"name":"Mikkeli Central Hospital  Mikkeli Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antti","family":"Kivel\u00e4","sequence":"additional","affiliation":[{"name":"Heart Center Kuopio University Hospital  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antti","family":"Hedman","sequence":"additional","affiliation":[{"name":"Heart Center Kuopio University Hospital  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Mussalo","sequence":"additional","affiliation":[{"name":"Imaging Center Kuopio University Hospital  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7593-2708","authenticated-orcid":false,"given":"Seppo","family":"Yl\u00e4\u2010Herttuala","sequence":"additional","affiliation":[{"name":"Heart Center Kuopio University Hospital  Kuopio Finland"},{"name":"A.I. 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