BACKGROUND: The short-term clinical impact of intramyocardial gene transfer (GT) of the angiogenic protein vascular endothelial growth factor-2 (VEGF-2) has been previously reported to significantly reduce Canadian Cardiovascular Society (CCS) angina class and to prolong exercise treadmill test (ETT) time. We describe the safety and long-term events (>1 year) in consecutive, nonrandomized, patients who received intramyocardial VEGF-2. METHODS: Thirty patients with intractable CCS class III or IV angina and no options for revascularization underwent direct intramyocardial GT of VEGF-2 naked DNA via limited thoracotomy at total doses of 0.2, 0.8, or 2.0 mg. Patients were followed for clinical events after 1 year by hospital records, follow-up visits or telephone contact. Due to one perioperative death, 29 patients were followed. RESULTS: At a mean follow-up of 751 +/- 102.5 days (range 459-959) there were four deaths (13.8%), five myocardial infarctions (MIs) (17.2%), and seven revascularization procedures (24.1%). There were 15 hospitalizations in 12 patients. At the end of the follow-up period no patient (0%) had CCS class IV angina, 3 patients (11.5%) had class III angina, and 23 (88.5%) had class I to II angina. There were two new diagnoses of cancer. CONCLUSION: Transthoracic intramyocardial injection of VEGF-2 is associated with an improvement of symptoms of angina in the majority of patients beyond the first year of treatment. Major clinical events such as death, MI, and repeat revascularization are uncommon during the first year but more frequent after 1 year at a rate consistent with the severity of underlying disease in this population with advanced atherosclerosis. The majority of events were the result of progression of disease in areas of the heart remote from the site of GT. A large randomized trial is planned to determine the efficacy of intramyocardial VEGF-2 injections in inoperable patients.
BACKGROUND: The short-term clinical impact of intramyocardial gene transfer (GT) of the angiogenic protein vascular endothelial growth factor-2 (VEGF-2) has been previously reported to significantly reduce Canadian Cardiovascular Society (CCS) angina class and to prolong exercise treadmill test (ETT) time. We describe the safety and long-term events (>1 year) in consecutive, nonrandomized, patients who received intramyocardial VEGF-2. METHODS: Thirty patients with intractable CCS class III or IV angina and no options for revascularization underwent direct intramyocardial GT of VEGF-2 naked DNA via limited thoracotomy at total doses of 0.2, 0.8, or 2.0 mg. Patients were followed for clinical events after 1 year by hospital records, follow-up visits or telephone contact. Due to one perioperative death, 29 patients were followed. RESULTS: At a mean follow-up of 751 +/- 102.5 days (range 459-959) there were four deaths (13.8%), five myocardial infarctions (MIs) (17.2%), and seven revascularization procedures (24.1%). There were 15 hospitalizations in 12 patients. At the end of the follow-up period no patient (0%) had CCS class IV angina, 3 patients (11.5%) had class III angina, and 23 (88.5%) had class I to II angina. There were two new diagnoses of cancer. CONCLUSION: Transthoracic intramyocardial injection of VEGF-2 is associated with an improvement of symptoms of angina in the majority of patients beyond the first year of treatment. Major clinical events such as death, MI, and repeat revascularization are uncommon during the first year but more frequent after 1 year at a rate consistent with the severity of underlying disease in this population with advanced atherosclerosis. The majority of events were the result of progression of disease in areas of the heart remote from the site of GT. A large randomized trial is planned to determine the efficacy of intramyocardial VEGF-2 injections in inoperable patients.
Authors: Artavazd Tadevosyan; George Vaniotis; Bruce G Allen; Terence E Hébert; Stanley Nattel Journal: J Physiol Date: 2011-12-19 Impact factor: 5.182
Authors: Duncan J Stewart; Michael J B Kutryk; David Fitchett; Michael Freeman; Nancy Camack; Yinghua Su; Anthony Della Siega; Luc Bilodeau; Jeffrey R Burton; Guy Proulx; Sam Radhakrishnan Journal: Mol Ther Date: 2009-04-07 Impact factor: 11.454
Authors: Michael G Katz; Anthony S Fargnoli; Andrew P Kendle; Roger J Hajjar; Charles R Bridges Journal: Ann Thorac Surg Date: 2016-01-20 Impact factor: 4.330