Functional characteristics of coronary vasomotor function following intramyocardial gene therapy with naked DNA encoding for vascular endothelial growth factor165.

Vascular endothelial growth factor (VEGF) is a potent angiogenic factor. VEGF gene therapy improves perfusion of ischemic myocardium in experimental models and possibly in patients with end-stage coronary artery disease. In addition to its proliferative and migratory effect on endothelial cells, it also activates and up-regulates endothelial nitric oxide synthase (eNOS). Therefore, the authors investigated coronary endothelium-dependent vasodilatation in patients before and after VEGF gene therapy. The effect of intracoronary acetylcholine infusion on coronary diameter was assessed at baseline and after 3 months follow-up in patients with end-stage coronary artery disease treated with VEGF gene and in controls scheduled for elective percutaneous transluminal coronary angioplasty (PTCA) (acetylcholine test at diagnostic angiography and before a subsequently scheduled PTCA). Five out of six VEGF patients experienced a reduction in anginal complaints. Angiographic evidence for improved collateral filling was evident in two out of six patients. The vasoconstrictive response to acetylcholine was partly converted into dilatation. In contrast, the acetylcholine response in control patients remained vasoconstrictive. In conclusion, VEGF gene therapy has an important beneficial effect on the functional characteristics of the myocardial vascular network. Therefore, this therapy can potentially play an important role in all stages of the atherosclerotic process.

Long-term safety of intracoronary haemodynamic assessment for deferral of angioplasty in intermediate coronary stenoses: a 5-year follow-up.

BACKGROUND: Intracoronary flow and pressure measurements can be used for evaluating intermediate lesions. Studies focussing on short- and medium-term results demonstrated its safety. Long-term results are, however, not available. OBJECTIVE: The goal of this study was to assess the long-term safety and clinical implications of decision making for intermediate coronary stenosis based on intra-coronary haemodynamic measurements. METHODS AND RESULTS: In this prospective study, 61 patients with an intermediate coronary stenosis were included between January 1994 and December 1998. In these patients either coronary flow reserve or fractional flow reserve was measured. Death, target vessel revascularization, myocardial infarction, unstable angina and cerebrovascular accident were considered as major adverse cardiac events. The patients were followed during 5.5 (1.8) years for the occurrence of major adverse cardiac events (MACE). Although many patients presented with complaints, only 19.7% experienced a MACE in the follow-up period. CONCLUSION: Intracoronary measurements of CFR and FFR can be routinely used for objective clinical decision making in intermediate coronary stenoses. The low 5-year event rate supports conservative treatment strategy when cut-off values are implemented.

Treatment synergy of silicon carbide-coated stenting and abciximab for complex coronary artery lesions: clinical results of a single-center study.

BACKGROUND: The aim of this study was to evaluate the combination of a silicon carbide-coated stent with the periprocedural use of abciximab in patients with type B2/C lesions. The study was a prospective cohort study and was conducted at the University Medical Center of Groningen. METHODS: Elective percutaneous transluminal coronary angioplasty was performed in a total of 44 patients. All had lesions with type B2/C characteristics and most were relatively small, tortuous and calcified. The involved vessel segment was stented. Silicon carbide-coated stents were used in combination with periprocedural abciximab. The main outcome measures were cardiac death, target vessel revascularization, myocardial infarction, and cerebrovascular accident. RESULTS: At 6 months of follow-up, only 4 patients had a major adverse cardiac event. Three patients had undergone target vessel revascularization and 1 patient had suffered from a cerebrovascular accident. Sixteen patients underwent re-angiography 6 months after the initial procedure. The average stenosis at 6 months was 15% with a minimal lumen diameter of 2.4 mm. CONCLUSIONS: A 9% major adverse cardiac event rate and a 7% target vessel revascularization rate at 6 months in type B2/C lesions were recorded. Further investigation on the use of this specific treatment combination is warranted.

Restenosis after percutaneous coronary intervention is associated with the angiotensin-II type-1 receptor 1166A/C polymorphism but not with polymorphisms of angiotensin-converting enzyme, angiotensin-II receptor, angiotensinogen or heme oxygenase-1.

OBJECTIVES: The renin-angiotensin system (RAS) is thought to play a major role in the pathophysiology of de-novo restenotic lesions and in-stent restenosis after percutaneous coronary intervention (PCI). Heme oxygenase-1 (HO-1), is thought to beneficially influence these processes. We examined the effect of pharmacologic as well as genetic RAS interactions on restenosis in a large population of consecutive patients undergoing PCI, and evaluated possible gene-gene interactions in both systems. METHODS: The GENDER project is a multicenter prospective follow-up study, including 3146 patients after successful PCI. Genotyping in these patients was performed for the ACE gene insertion/deletion, the angiotensinogen 235Met/Thr, T174M and A(-6)G, the angiotensin-II type 1 receptor (AT1R) 1166A/C and T810A, the angiotensin-II type 2 receptor (AT2R) 1675G/A and 3123A polymorphisms and the length polymorphism in the HO-1 promoter region. RESULTS: A total of 3104 patients were followed for 10 months. In 2975 patients at least one of the nine genotypes could be determined. The AT1R 1166 CC genotype showed a significant association with TVR; the other polymorphisms did not. RAS-inhibitory drugs were not associated with the incidence of TVR, nor did they interact with any of the investigated polymorphisms. Patients with the ACE I/I polymorphism showed a trend towards a better outcome if they had a short number of repeats in the HO-1 promoter. This relationship was inversely present in carriers of the ACE D/D polymorphism. CONCLUSION: We could only establish a role for the AT1R 1166A/C polymorphism in restenosis after PCI. However, significant gene-gene interaction was suggested for the ACE gene and the HO-1 promotor. The RAS and HO-1 relation in restenosis merits further investigation.

Clinical impact of abciximab on long-term outcome after complex coronary angioplasty.

Glycoprotein IIb/IIIa receptor antagonists, such as abciximab, are used to reduce major adverse cardiac events (MACEs) in patients undergoing percutaneous transluminal coronary angioplasty. The goal of this study was to evaluate the administration of abciximab in relation to lesion complexity and periprocedural complications. A total of 357 patients with 435 de novo lesions were included in this study. Lesions were divided into simple (type A and type B1) and complex (type B2 and type C) lesions according to the American College of Cardiology/American Heart Association Task Force lesion complexity system. Abciximab was given to unstable complex lesions and simple lesions with a periprocedural unstable complicated course. The overall incidence of MACE during the 9-month follow-up period was 17.0%. Patients treated with abciximab had a higher lesion complexity (P < 0.001), dissections (P = 0.014), stents (P < 0.001), and vessels involved (P < 0.001). in addition, the abciximab group was characterized by a higher angina NYHA class (P = 0.005), lower TIMI flow prior to stenting (P = 0.01), and a longer total inflation time (P = 0.006). Despite these clinical differences, the occurrence of MACE within the abciximab group was slightly less than in the group without abciximab (16.2% and 17.3%, respectively). Lesion complexity was directly related to MACE in the group that did not receive abciximab (simple and stable complex lesions; P = 0.04). On the other hand, in subjects treated with abciximab, lesion complexity was not related to a higher incidence of MACE (P = 0.76). The use of abciximab equalizes the difference in outcome between simple and complex lesions. Therefore, abciximab should be advocated especially in unstable and complex percutaneous coronary interventions.