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

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Date
2017
Author
Hartikainen J
Hassinen I
Hedman A
Kivelä A
Saraste A
Knuuti J
Husso M
Mussalo H
Hedman M
Rissanen TT
Toivanen P
Heikura T
Witztum JL
Tsimikas S
Ylä-Herttuala S
Unique identifier
10.1093/eurheartj/ehx352
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Citation
Hartikainen J. Hassinen I. Hedman A. Kivelä A. Saraste A. Knuuti J. Husso M. Mussalo H. Hedman M. Rissanen TT. Toivanen P. Heikura T. Witztum JL. Tsimikas S. Ylä-Herttuala S. (2017). Adenoviral intramyocardial VEGF-DdeltaNdeltaC gene transfer increases myocardial perfusion reserve in refractory angina patients: a phase I/IIa study with 1-year follow-up.  EUROPEAN HEART JOURNAL, 38 (33) , 2547-2555. 10.1093/eurheartj/ehx352.
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© Authors
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CC BY http://creativecommons.org/licenses/by/4.0/
Abstract

Aims
We evaluated for the first time the effects of angiogenic and lymphangiogenic AdVEGF-DΔNΔC gene therapy in patients with refractory angina.

Methods and results
Thirty patients were randomized to AdVEGF-DΔNΔC (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-DΔNΔC 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.

Subjects
Gene therapy   Angiogenesis   Lymphangiogenesis   Therapeutic angiogenesis   PET   Safety   
URI
https://erepo.uef.fi/handle/123456789/5793
Link to the original item
http://dx.doi.org/10.1093/eurheartj/ehx352
Publisher
Oxford University Press (OUP)
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