Refereed journal article or data article (A1)

Adenoviral intramyocardial VEGF-D(ΔNΔC) gene transfer increases myocardial perfusion reserve in refractory angina patients: a phase I/IIa study with 1-year follow-up




List of AuthorsHartikainen J, Hassinen I, Hedman A, Kivela A, Saraste A, Knuuti J, Husso M, Mussalo H, Hedman M, Rissanen TT, Toivanen P, Heikura T, Witztum JL, Tsimikas S, Yla-Herttuala S

PublisherOXFORD UNIV PRESS

Publication year2017

JournalEuropean Heart Journal

Journal name in sourceEUROPEAN HEART JOURNAL

Journal acronymEUR HEART J

Volume number38

Issue number33

Start page2547

End page2555

Number of pages9

ISSN0195-668X

DOIhttp://dx.doi.org/10.1093/eurheartj/ehx352


Abstract
Aims We evaluated for the first time the effects of angiogenic and lymphangiogenic AdVEGF-D-Delta N Delta C gene therapy in patients with refractory angina.Methods and results Thirty patients were randomized to AdVEGF-D-Delta N Delta C (AdVEGF-D) or placebo (control) groups. Electromechanical NOGA mapping and radiowater PET were used to identify hibernating viable myocardium where treatment was targeted. Safety, severity of symptoms, quality of life, lipoprotein(a) [Lp(a)] and routine clinical chemistry were measured. Myocardial perfusion reserve (MPR) was assessed with radiowater PET at baseline and after 3- and 12-months follow-up. Treatment was well tolerated. Myocardial perfusion reserve increased significantly in the treated area in the AdVEGF-D group compared with baseline (1.00 +/- 0.36) at 3 months (1.31 +/- 0.46, P = 0.045) and 12 months (1.44 +/- 0.48, P = 0.009) whereas MPR in the reference area tended to decrease (2.05 +/- 0.69, 1.76 +/- 0.62, and 1.87 +/- 0.69; baseline, 3 and 12 months, respectively, P = 0.551). Myocardial perfusion reserve in the control group showed no significant change from baseline to 3 and 12 months (1.26 +/- 0.37, 1.57 +/- 0.55, and 1.48 +/- 0.48; respectively, P = 0.690). No major changes were found in clinical chemistry but anti-adenovirus antibodies increased in 54% of the treated patients compared with baseline. AdVEGF-D patients in the highest Lp(a) tertile at baseline showed the best response to therapy (MPR 0.94 +/- 0.32 and 1.76 +/- 0.41 baseline and 12 months, respectively, P = 0.023).Conclusion AdVEGF-D-Delta N Delta C gene therapy was safe, feasible, and well tolerated. Myocardial perfusion increased at 1 year in the treated areas with impaired MPR at baseline. Plasma Lp(a) may be a potential biomarker to identify patients that may have the greatest benefit with this therapy.


Last updated on 2021-24-06 at 08:57