title: Intramyocardial Gene Therapy Directed to Hibernating Heart Muscle Using a Combination of Electromechanical Mapping and Positron Emission Tomography.
abstract: Cardiac gene transfer for the treatment of ischemic diseases has suffered from low gene transfer efficiency and inability to target treatment genes to the ischemic myocardium. A combined method has been developed based on electromechanical mapping and radiowater PET imaging to target gene therapy to viable but ischemic and hibernating areas of the myocardium. Electromechanical NOGA mapping produces three-dimensional images of myocardium with both an electric activity map and a myocardial contractility map. These have been converted to 17-segment 2D bull's-eye maps, which were superimposed onto PET radiowater perfusion imaging maps of the myocardium. This technique was applied in a Phase I/IIa clinical trial to target gene therapy for refractory angina patients. It was found that by combining electromechanical map with PET imaging, targeting of gene therapy to hibernating ischemic myocardium can be significantly improved. Here, the methods for the identification of viable, ischemic, and hibernating myocardium for gene transfer are described, and examples of treated refractory angina patients who have benefited from the improved gene transfer method to the ischemic myocardium are presented.
authors.affiliation: 1 Heart Center, Kuopio University Hospital , Kuopio, Finland.
authors.forename: Iiro
authors.initials: I
authors.lastname: Hassinen
authors.affiliation: 1 Heart Center, Kuopio University Hospital , Kuopio, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Kivelä
authors.affiliation: 1 Heart Center, Kuopio University Hospital , Kuopio, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Hedman
authors.affiliation: 2 Turku PET Centre, Turku University Hospital , Turku, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Saraste
authors.affiliation: 2 Turku PET Centre, Turku University Hospital , Turku, Finland.
authors.forename: Juhani
authors.initials: J
authors.lastname: Knuuti
authors.affiliation: 1 Heart Center, Kuopio University Hospital , Kuopio, Finland.|3 Institute of Clinical Medicine, University of Eastern Finland , Kuopio, Finland .
authors.forename: Juha
authors.initials: J
authors.lastname: Hartikainen
authors.affiliation: 1 Heart Center, Kuopio University Hospital , Kuopio, Finland.|4 A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland , Kuopio, Finland .|5 Science Service Center and Gene Therapy Unit, Kuopio University Hospital , Kuopio, Finland.
authors.forename: Seppo
authors.initials: S
authors.lastname: Ylä-Herttuala
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000789:Angina, Unstable / Q000000981:diagnostic imaging / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D004576:Electromyography; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics / Q000627:therapeutic use; D006321:Heart / Q000000981:diagnostic imaging* / Q000503:physiopathology; D006605:Hibernation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology; D049268:Positron-Emission Tomography