Angiotensin Converting Enzyme and Angiotensin II Type 1 Receptor Polymorphisms in Patients with Coronary Aneurysms

BACKGROUND: Conflicting results have been reported regarding the association of gene polymorphisms in the renin-angiotensin system (RAS) with different aspects of coronary artery disease (CAD), such as myocardial infarction, neointimal hyperplasia or coronary artery vasomotion. Since previous studies have linked angiotensin II to aneurysmal disease, our study hypothesis was that RAS gene polymorphisms may be associated with aneurysm remodeling in response to CAD. METHODS: The study population was selected from a series of 3862 consecutive patients who underwent coronary angiography in our institution. One hundred and thirteen consecutive patients with at least one coronary aneurysm (CA) were compared to 226 randomized control patients without CA. DNA was extracted from white blood cells. The angiotensin-converting enzyme (ACE) I/D and angiotensin type 1 receptor (AT1-R) A/C polymorphisms were detected using previously published techniques. RESULTS: The distributions of the three ACE genotypes were similar in both groups: CA: 13%, 46%, and 41% for II, ID, and DD respectively; controls: 18%, 41%, and 41% for II, ID, and DD respectively, p = 0.45. The distributions of the three AT1-R genotypes were also similar in both groups: CA: 54%, 41%, and 5% for AA, AC, and CC respectively; controls: 55%, 33%, and 12%, for AA, AC, and CC respectively, p = 0.08. CONCLUSION: Our results provide further information on the role of RAS polymorphisms on specific mechanisms implicated in CAD. Although an activated RAS may theoretically promote aneurysm formation, the 2 RAS polymorphisms analyzed in this study are not associated with this process in coronary arteries

021: Clopidogrel low response and correlation between the different tests: light transmission aggregometry, VerifyNow-P2Y12 and V ASP

BackgroundClopidogrel low response correlates with poor prognosis after percutaneous coronary intervention (PCI). Many biological tests are currently available to test the clopidogrel response. However, the presence of any correlation between the different tests is today poorly reported.MethodsIn this prospective study, clopidogrel response was assessed in 100 consecutive patients. All patients were tested between 18h and 24h after a600mg clopidogrel loading dose using 3 different tests: light transmission aggregometry with 10μmol ADP (LTA, results expressed as platelet inhibition percentage), VerifyNow-P2Y12 (VN, results expressed as PRU) and vasodilatator stimulated phosphoprotein (VASP, results expressed as IRP). Patients under chronic clopidogrel therapy were excluded.ResultsThe mean platelet inhibition percentage, PRU value and IRP value were 38.5±13% by LTA, 178±89 PRU by VN and 52±21% by VASP. When results were analyzed as continuous variables, there was a good correlation between the different tests: LTA/VN (R2=0,642, p<0,001), LTA/VASP (R2=0,409, p<0,001) and VN/VASP (R2=0,616, p<0,001). However, when results were analyzed as pre-specified cut-off points to define patients as “low or good responders” (according to the literature: 50% for LTA, 235 PRU for VN and 50% IRP for VASP), only 47% of the patients were defined as “good” or “low responders” by the 3 tests. Altogether, 33% of the patients were defined as “low responders” by only 1 test, 20% by 2 tests and only 16% by the 3 tests.ConclusionIf the correlation between the different tests is good when results are analyzed as continuous variables, each individual is rarely (less than 50%) defined as “low or good responder” by all the 3 tests when recognized cut-off values are used. In that way, a sole test might not be sufficient to manage antiplatelet therapy in an individual patient

A common variant of endothelial nitric oxide synthase (Glu298Asp) is associated with collateral development in patients with chronic coronary occlusions

BACKGROUND: Experimental studies support an important role for endothelial nitric oxide synthase (eNOS) in the regulation of angiogenesis. In humans, a common polymorphism exists in the eNOS gene that results in the conversion of glutamate to aspartate for codon 298. In vitro and in vivo studies have suggested a decreased NOS activity in patients with the Asp(298 )variant. We hypothesized that a genetic-mediated decreased eNOS activity may limit collateral development in patients with chronic coronary occlusions. METHODS: We selected 291 consecutive patients who underwent coronary angiography and who had at least one chronic (>15 days) total coronary occlusion. Collateral development was graded angiographically using two different methods: the collateral flow grade and the recipient filling grade. Genomic DNA was extracted from white blood cells and genotyping was performed using previously published techniques. RESULTS: Collateral development was lower in patients carrying the Asp(298 )variant than in Glu-Glu homozygotes (collateral flow grade: 2.64 ± 0.08 and 2.89 ± 0.08, respectively, p = 0.04; recipient filling grade: 3.00 ± 0.08 and 3.24 ± 0.07, respectively, p = 0.04). By multivariable analysis, three variables were independently associated with the collateral flow grade: female gender, smoking, and the Asp(298 )variant (p = 0.03) while the Asp(298 )variant was the sole variable independently associated with the recipient filling grade (p = 0.03). CONCLUSION: Collateral development is lower in patients with the Asp(298 )variant. This may be explained by the decreased NOS activity in patients with the Asp(298 )variant. Further studies will have to determine whether increasing eNOS activity in humans is associated with coronary collateral development

Impact of initial clinical presentation on clopidogrel low response

SummaryBackgroundLarge interindividual variability exists in clopidogrel response. Clopidogrel low response correlates with poor prognosis after percutaneous coronary intervention. Some authors also suggest intraindividual variability over time.AimTo assess the impact of initial clinical presentation on clopidogrel low response.MethodsIn this prospective study, clopidogrel response was assessed in 100 patients. Fifty patients presenting with acute coronary syndromes (ACS group) were compared with 50 patients with stable coronary artery disease matched 1:1 for age, sex, body mass index and diabetes (stable group). All patients were tested 18–24h after a 600mg loading dose of clopidogrel using the VerifyNow-P2Y12 test (results expressed as platelet reaction units [PRUs]). Patients under chronic clopidogrel therapy or treated with glycoprotein IIb/IIIa inhibitors, bivalirudin or thrombolytics were excluded.ResultsMean age was 61±12 years in each group; 28% of patients in each group were diabetic; mean body mass index was 27.6±5.6kg/m2 in the ACS group and 27.9±5.9kg/m2 in the stable group (p=0.80). Mean PRU values were 197±81 in the ACS group and 159±94 in the stable group (p=0.03). By multivariable analysis, the ACS group was significantly associated with a higher PRU value (p=0.02). There were significantly more clopidogrel low responders (PRU value>230) in the ACS group (38% vs. 18%; p=0.04).ConclusionOur study confirms that initial clinical presentation, especially ACS, is a strong predictor of clopidogrel low response; this suggests that the evolution of coronary artery disease for one patient influences the clopidogrel response over time. These results are in accordance with recent trials showing a benefit for more aggressive antiplatelet therapy in ACS patients

934-28 Sensitivity and Specificity of Angiographic Markers for Thrombus: A Prospective Comparison with Angioscopy

The limitations of angiography for the detection of intracoronary thrombus are well recognized. Between November 1991 and July 1994, we performed 402 angioscopy procedures in 225 vessels in 202 patients, with the Image-Cath (Baxter).We performed a prospective study in 190 of these patients, who had an interpretable angioscopy performed just before PTCA to determine the sensitivity and specificity of predetermined angiographic criteria that are considered to be indicative of the presence of intracoronary thrombus. Angiographically verified thrombus was used as the gold standard for comparison. Lesions were classified on angiography (2 orthogonal views) by independent observers. The presence of an intraluminal filling defect, of overhanging edges, of haziness, or of ulceration were noted. The characteristic ulceration was not mutually exclusive of the other 3 characteristics.Of 15 filling defects on angiography 14 (93%) had thrombus on angiography; in the 23 lesions with overhanging edges 19 (83%) had thrombus on angioscopy; in the 27 ulcerated lesions 21 (78%) had angioscopic thrombus; in the 6 lesions that were hazy on angiography 5 had angioscopic thrombus.AngioscopyThrombus+Thrombus-AngiographyThrombus+4512Thrombus-4093In our model, using 5 prespecified angiographic characteristics, angiography had high specificity (89%) but relatively low sensitivity (53%) for the detection of thrombus compared to angioscopy

760-4 Initial Multicenter Experience with Therapeutic Ultrasonic Coronary Angioplasty in Patients

Therapeutic ultrasonic (195 kHz) catheters with 1.2 or 1.7 mm ball tips for coronary angioplasty have recently been developed. During the first phase of a multi-center European trial (CRUSADE) this system was evaluated in 100 patients (86% male, mean age 57 years) with symptomatic coronary artery disease or acute myocardial infarction. Lesions were located in the LAD (n = 61), CX (n = 17), and RCA (n = 22); 62% were type B or C; 11 lesions were restenotic, 19 occlusive, 9 longer than 20 mm, 37 calcified, 18 thrombotic, and 15 collateralised.ResultsThe ultrasound catheter crossed 82/100 lesions, adjunctive balloon angioplastywas needed in 98 lesions. There was no death and myocardial infarction, or CABG in the first 24 hours. There was no perforation, but 2 acute vessel closures; intimal cleft or dissection was seen in 17 lesions of which 1 required stenting. Procedural success was obtained in 93%. At 24 hours 11/100 vessels were reoccluded. At 6 months angiographic follow-up in 51 patients restenosis (&gt;50% stenosis) occured in 33%.ConclusionsTherapeutic ultrasound angioplasty is a feasible and safe new treatment modality. Adjunctive balloon angioplasty is regularly necessary. Preliminary experience suggests usefulness in lesions with visible thrombus, and undilatable or uncrossable lesions

Percutaneous transluminal coronary rotary ablation with rotablator (European experience)

This study reports the results from 3 European centers using rotary ablation with Rotablator, a device that is inserted into the coronary artery and removes atheroma by grinding it into millions of tiny fragments. Rotary ablation was performed in 129 patients. Primary success (reduction in percent luminal narrowing greater than 20%, residual stenosis less than 50%, without complications) was achieved by rotary angioplasty alone in 73 patients (57%). An additional 38 patients (29%) had successful adjunctive balloon angioplasty. Thus primary success was achieved in 111 patients (86%) at the end of the procedure. Acute occlusion occurred in 10 patients (7.7%). Recanalization was achieved by balloon angioplasty in 7: urgent bypass grafting was undertaken in 2. Q-wave and non-Q-wave myocardial infarction occurred in 3 and 7 patients, respectively. No deaths occurred. Follow-up angiography was performed in 74 patients (60%). Restenosis, defined as the recurrence of significant luminal narrowing (greater than 50%) occurred in 17 of 37 patients (46%) who underwent rotary ablation alone, and 11 of 37 patients (30%) who had adjunctive balloon angioplasty. The overall angiographic restenosis rate was 37.8%. In conclusion, rotary ablation is technically feasible, and relatively safe i

Randomized Comparison of Eptifibatide Versus Abciximab in Primary Percutaneous Coronary Intervention in Patients With Acute ST-Segment Elevation Myocardial Infarction Results of the EVA-AMI Trial

ObjectivesThe aim of this study was to compare eptifibatide and abciximab as adjuncts to primary percutaneous coronary intervention (PCI).BackgroundThe glycoprotein (GP) IIb/IIIa receptor inhibitor abciximab as adjunct to primary PCI in patients with ST-segment elevation myocardial infarctions has been shown to reduce ischemic complications and improve clinical outcomes. So far, no trial has been performed to compare the efficacy of another GP IIb/IIIa receptor inhibitor, eptifibatide, and abciximab in primary PCI.MethodsA total of 427 patients with ST-segment elevation myocardial infarctions <12 h and planned primary PCI were randomized to double-bolus eptifibatide (n = 226) followed by a 24-h infusion or single-bolus abciximab (n = 201) followed by a 12-h infusion. In this noninferiority trial, the primary end point was the incidence of complete (≥70%) ST-segment resolution (STR) 60 min after PCI, a measure of myocardial reperfusion. The assumption was a 60% complete STR rate in the abciximab group. The noninferiority margin was set to 15%.ResultsThe incidence of complete STR at 60 min after PCI in the intention-to-treat analysis was 62.6% after eptifibatide and 56.3% after abciximab (adjusted difference: 7.1%; 95% confidence interval: 2.7% to 17.0%). All-cause mortality 6.2% versus 4.5% (p = 0.50); reinfarction 0.4% versus 3.5% (p = 0.03); target vessel revascularization 4.4% versus 6.5% (p = 0.40); the combined end point of death, nonfatal reinfarction, and target vessel revascularization 10.6% versus 10.9% (p = 0.90); stroke 0.5% versus 0.5% (p = 1.00) after 6 months; and Thrombolysis In Myocardial Infarction major bleeding complications 4.0% versus 2.0% (p = 0.20) after 30 days were observed after eptifibatide and abciximab, respectively.ConclusionsEptifibatide as an adjunct to primary PCI is equally as effective as abciximab with respect to STR. (Efficacy of Eptifibatide Compared to Abciximab in Primary Percutaneous Coronary Intervention [PCI] for Acute ST Elevation Myocardial Infarction [STEMI]; NCT00426751

Usefulness of quantitative and qualitative angiographic lesion morphology, and clinical characteristics in predicting major adverse cardiac events during and after native coronary balloon angioplasty

Major, adverse cardiac events (death, myocardial infarction, bypass surgery and reintervention) occur in 4 to 7% of all patients undergoing coronary balloon angioplasty. Prospectively collected clinical data, and angiographic quantitative and qualitative lesion morphologic assessment and procedural factors were examined to determine whether the occurrence of these events could be predicted. Of 1,442 patients undergoing balloon angioplasty for native primary coronary disease in 2 European multicenter trials, 69 had major, adverse cardiac procedural or in-hospital complications after ≥1 balloon inflation and were randomly matched with patients who completed an uncomplicated in-hospital course after successful angioplasty. No quantitative angiographic variable was associated with major adverse cardiac events in univariate and multivariate analyses. Univariate analysis showed that major adverse cardiac events were associated with the following preprocedural variables: (1) unstable angina (odds ratio [OR] 3.11; p 45 ° (OR 2.34; p 45 ° (OR 2.87; p 45 ° (OR 2.54; p < 0.006) were independent predictors of major adverse cardiac events