We performed studies in patients with stable (n=40) and unstable (n=40) angina and healthy controls (n=20), in vitro studies in T-cells and macrophages, and studies in apolipoprotein-E-deficient (ApoE-/-) mice and human atherosclerotic carotid plaques.
This phase I open label, dose-escalating study shows that gene transfer of vascular endothelial growth factor-2 naked deoxyribonucleic acid by direct myocardial injection by way of thoracotomy in patients with Canadian Cardiovascular Society class 3 or 4 angina is feasible and safe.
Furthermore, VEGF gene therapy using adenoviral vectors showed more potential benefit in terms of the risk of serious cardiac events, ΔLVEF, and Canadian Cardiovascular Society angina class.
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.
No sustained ventricular arrhythmias, ECG evidence of infarction, or ventricular perforations were observed. phVEGF-2-transfected patients experienced reduced angina (before versus after GTx, 36.2+/-2.3 versus 3.5+/-1.2 episodes/week) and reduced nitroglycerin consumption (33.8+/-2.3 versus 4.1+/-1.5 tablets/week) for up to 360 days after GTx; reduced ischemia by electromechanical mapping (mean area of ischemia, 10.2+/-3.5 versus 2.8+/-1.6 cm(2), P=0.04); and improved myocardial perfusion by SPECT-sestamibi scanning for up to 90 days after GTx when compared with images obtained after control procedure.
Several clinical trials based on intramyocardial injection of VEGF DNA in patients with otherwise inoperable coronary artery disease and intractable angina pectoris have recently been completed.
The VEGF-2 study in no-option patients showed reduced angina, and significant improvement in perfusion and function, whereas the FGF-4 study in less severely affected patients showed promising results in some subsets.
VEGF gene transfer (GTx) was performed in 5 patients (all male, ages 53 to 71) who had failed conventional therapy; these men had angina (determined by angiographically documented coronary artery disease).
Remaining efficacy end points--including change in exercise duration (91.8 versus 3.9 seconds), functional improvement by > or =2 CCS classes (9 of 12 versus 1 of 6), and Seattle Angina Questionnaire data--all showed strong trends favoring efficacy of phVEGF2 versus placebo treatment.
Stratified medical therapy, including an IDP with linked medical therapy, is routinely feasible and improves angina in patients with no obstructive CAD.
Observation outcomes include age, sex, C-reaction protein (CRP), medical history including major risk factors for CAD, ferritin and GFR, previous angina, time between MI and coronary angiography or time to rescue (TTR), and prior treatment.Around 60 patients were included in the case group (AMI with LVA) and 133 matched patients (AMI without LVA) in the control group.
In summary, the II genotype of the ACE gene was associated with a longer period of time between the first anginal pain and the onset of myocardial infarction than the ID and DD genotypes of the ACE gene.
CRP-induced monocyte TF activity correlated with serum CRP levels in controls (P = 0.005) and ID (P = 0.007) in study 3, but not in patients with angina (P =0.84) in study 2.
The relation of the ACE and AT1R gene polymorphisms to coronary heart disease and the severity of coronary artery stenosis has now been investigated in 133 patients with myocardial infarction (MI) or angina pectoris who underwent coronary angiography and in 258 control subjects.
Inclusion criteria were hospitalization for MI, Thrombolysis In Myocardial Infarction flow 0 at coronary angiography, reperfusion within 12 h from the onset of chest pain, cardiac MRI within the first month, and a 5-days' biological follow-up with at least hs-T-Troponin and C-reactive protein (CRP).
MB is significantly associated with epicardial and microvascular endothelial dysfunction in patients with non-obstructive CAD supporting its potential role as amechanism for angina in symptomatic patients with MB.
Thirty-one patients (63.0 ± 6.4 years, 70% male) with recurrent CCS II-IV angina, despite optimal medical therapy, enrolled in the REGENT-VSEL single center, randomized, double-blinded, and placebo-controlled trial.