Claude Le Feuvre

The Common 866G>A Variant in the Promoter of UCP2 Is Associated With Decreased Risk of Coronary Artery Disease in Type 2 Diabetic Men

OBJECTIVE—Uncoupling protein 2 (UCP2) is a physiological downregulator of reactive oxygen species generation and plays an antiatherogenic role in the vascular wall. A common variant in the UCP2 promoter (−866G>A) modulates mRNA expression, with increased expression associated with the A allele. We investigated association of this variant with coronary artery disease (CAD) in two cohorts of type 2 diabetic subjects. RESEARCH DESIGN AND METHODS—We studied 3,122 subjects from the 6-year prospective Non–Insulin-Dependent Diabetes, Hypertension, Microalbuminuria, Cardiovascular Events, and Ramipril (DIABHYCAR) Study (14.9% of CAD incidence at follow-up). An independent, hospital-based cohort of 335 men, 52% of whom had CAD, was also studied. RESULTS—We observed an inverse association of the A allele with incident cases of CAD in a dominant model (hazard risk 0.88 [95% CI 0.80–0.96]; P = 0.006). Similar results were observed for baseline cases of CAD. Stratification by sex confirmed an allelic association with CAD in men, whereas no association was observed in women. All CAD phenotypes considered—myocardial infarction, angina pectoris, coronary artery bypass graft (CABG), and sudden death—contributed significantly to the association. Results were replicated in a cross-sectional study of an independent cohort (odds ratio 0.47 [95% CI 0.25–0.89]; P = 0.02 for a recessive model). CONCLUSIONS—The A allele of the −866G>A variant of UCP2 was associated with reduced risk of CAD in men with type 2 diabetes in a 6-year prospective study. Decreased risk of myocardial infarction, angina pectoris, CABG, and sudden death contributed individually and significantly to the reduction of CAD risk. This association was independent of other common CAD risk factors.

Treatment of severe mitral regurgitation caused by ischemic papillary muscle dysfunction: Indications for coronary angioplasty

The aim of this study was to evaluate the prognosis and functional outcome of mitral regurgitation caused by ischemic papillary muscle dysfunction with respect to treatment, and to determine the role of coronary angioplasty in this context. Thirty patients with severe ischemic mitral regurgitation were followed up for 33 +/- 3 months. Thirteen patients were treated medically (group I) and 17 patients underwent surgery or angioplasty (group II). The 3-year survival was 59.5% (45.6% in group I and 70.2% in group II). Angioplasty was only used in paroxysmal mitral regurgitation caused by papillary muscle ischemia. This technique resulted in spectacular immediate results in three patients with pulmonary edema caused by mitral regurgitation during myocardial ischemia. Surgical correction of mitral regurgitation should be considered without delay if angioplasty is not feasible or if the regurgitation is permanent or severe. Widening the indications of surgery or angioplasty should result in an improvement of the prognosis of these high-risk patients.

Drug insight: antithrombotic therapy after percutaneous coronary intervention in patients with an indication for anticoagulation.

Antiplatelet therapy with aspirin and clopidogrel is standard care following revascularization by percutaneous coronary intervention with stent insertion. This so-called dual therapy is recommended for up to 4 weeks after intervention for bare-metal stents and for 6–12 months after intervention for drug-eluting stents. Although it is estimated that 5% of patients undergoing percutaneous coronary intervention require long-term anticoagulation because of an underlying chronic medical condition, continuing treatment with triple therapy (warfarin, aspirin and clopidogrel) increases the risk of bleeding. In most patients triple antithrombotic therapy seems justified for a short period of time. In some patients, however, a more considered judgment based on absolute need for triple therapy, risk of bleeding and risk of stent thrombosis is required, but the optimum antithrombotic treatment for these patients who require long-term anticoagulation has not been defined. This Review summarizes the existing literature concerning antithrombotic therapy and makes recommendations for initiation and duration of triple therapy in the small proportion of patients already receiving anticoagulant therapy who require percutaneous coronary intervention.

Detection of coronary restenosis by exercise electrocardiography thallium-201 perfusion imaging and coronary angiography in asymptomatic patients after percutaneous transluminal coronary angioplasty

Noninvasive detection of restenosis in patients remaining asymptomatic after percutaneous transluminal coronary angioplasty (PTCA) remains a major clinical problem. The value of exercise electrocardiography (ECG) and exercise-redistribution thallium-201 single-photon emission computed tomography (SPECT) in detecting restenosis in such patients remains uncertain. Discordances between these tests and coronary angiography is a common situation. We studied 179 consecutive patients remaining asymptomatic after successful PTCA (208 vessels), who underwent 6 +/- 2 months of exercise ECG, SPECT, and coronary angiography. We sought to assess the diagnostic value of the noninvasive tests compared with coronary angiography, and identify the determinants of discordances between the tests. Restenosis (diameter stenosis >50%) was detected in 39% of patients and in 37% of vessels. The overall sensitivity, specificity, and accuracy for exercise ECG and SPECT in detecting restenosis in individual vessels were, respectively, 53% versus 63% (p = 0.06), 59% versus 77% (p = 0.0001), and 57% versus 72% (p = 0. 0001). On multivariate analysis, positive exercise ECG was associated with higher heart rate response (p = 0.02), incomplete revascularization (p = 0.004), and angiographic restenosis (p = 0. 03), whereas positive SPECT was associated with incomplete revascularization (p = 0.02), infarct-related artery PTCA (p = 0.01), and angiographic restenosis (p = 0.0001). Accuracies of the 2 tests were not significantly different in patients with incomplete revascularization or PTCA of an infarct-related vessel. Overall, SPECT is more accurate than exercise ECG in detecting asymptomatic restenosis. Nevertheless, incomplete revascularization and PTCA of an infarct-related artery could cause reversible perfusion defects regardless of restenosis, reducing the diagnostic value of SPECT in such patients.

Silent myocardial ischemia screening in patients with diabetes mellitus

The prevalence of diabetes mellitus is fairly increasing, especially in the developing countries. Diabetes is a major cardiovascular risk factor; it often leads to severe cardiovascular complications, and coronary artery disease (CAD) is the main cause of death in diabetic patients. Silent myocardial ischemia (SMI) is more frequent in diabetic patients. The progress made in detection and treatment of CAD allows reconsidering the screening of SMI, in the hope that early CAD diagnosis leads to a more effective therapy and the decrease of cardiovascular complications and mortality. However, the benefit of systematic SMI screening remains discussed. Current guidelines recommend screening SMI in asymptomatic diabetic patients selected for high cardiovascular risk (i.e. with two or more other cardiovascular risk factors, or peripheral or carotid arterial disease, or proteinuria). ECG stress test can be recommended in first intention if maximal heart rate can be achieved. For patient with inconclusive ECG stress test, myocardial scintigraphy seems more accurate than stress echocardiography. Coronary angiogram should be performed in case of positive stress test. Further evaluations of systematic screening have to be conducted on broad randomized trial.

Comparison of short- and long-term outcomes of coronary angioplasty in patients with and without diabetes mellitus and with and without hemodialysis

In-hospital and long-term outcomes after coronary angioplasty in 28 dialysis diabetic and 84 dialysis nondiabetic patients were compared with clinical outcomes after coronary angioplasty in 28 nondialysis diabetic and 84 nondialysis, nondiabetic patients matched according to clinical and angiographic characteristics. The rate of angiographic success in diabetic dialysis patients was high and similar in the 4 groups. The risk of 4-year cardiac death and nonfatal myocardial infarction was higher in dialysis diabetics than in dialysis nondiabetics (odds ratio [OR] 1.88, 95% confidence interval [CI] 1.01 to 2.75, p <0.05), nondialysis diabetics (OR 4.27, 95% CI 2.87 to 5.67, p <0.008), and nondialysis nondiabetics (OR 5.2, 95% CI 4.17 to 6.23, p <0.0001).

Assessment of reversible dyssynergic segments after acute myocardial infarction : Dobutamine echocardiography versus thallium-201 single photon emission computed tomography

Only a moderate degree of concordance has been reported between stress-redistribution-reinjection thallium-201 single photon emission computed tomography (SPECT) and dobutamine echocardiography for the identification of myocardial viability after acute myocardial infarction. SPECT with rest-reinjection performed 4 hours after exercise testing and digitized two-dimensional (2-D) ultrasound reconstruction of the left ventricle at baseline and after low-dose dobutamine (5 to 10 microg/kg/min) infusion were compared in 50 patients > or = 8 days (12 +/- 7 days) after acute myocardial infarction. Five patients were excluded because of technically inadequate echocardiograms. Both SPECT and dobutamine echocardiography were assessed in a 16-segment model and interpreted in the remaining 45 patients. Digitized 2-D reconstruction of the left ventricle in each wall motion was scored from 1 (normal) to 4 (dyskinesia). Myocardial viability was identified on ultrasound wall-motion improvement of one or more grades from baseline to echocardiography performed > or = 30 days (60 +/- 41 days) after systematic revascularization procedure of the infarct-related artery. Reversible defect under thallium-201 SPECT and wall-motion improvement under dobutamine echocardiography were concordant in 163 (69 percent) of the 235 baseline dyssynergic segments and in 30 (67 percent) patients. Myocardial viability was identified after angioplasty (n=37) or surgery (n=8) in 29 patients and 109 segments. Positive and negative predictive values per patient in the diagnosis of myocardial viability were 86 percent and 57 percent, respectively, for stress thallium-201 SPECT with reinjection, and 100 percent and 62 percent for dobutamine echocardiography. Positive and negative predictive values per segment were 80 percent and 69 percent for the isotopic method and 91 percent and 70 percent for dobutamine echocardiography. We conclude that dobutamine echocardiography and stress thallium-201 SPECT with reinjection have similar accuracies to identify myocardial viability after acute myocardial infarction, with excellent positive but relatively low negative predictive values.

Intensive cardiovascular risk factors therapy and prevalence of silent myocardial ischaemia in patients with type 2 diabetes.

BACKGROUND Screening for silent myocardial ischaemia (SMI) is a controversial strategy undergoing intensive risk factor therapy. AIMS To assess the prevalence of SMI and coronary artery disease (CAD) in asymptomatic type 2 diabetic patients at high cardiovascular risk (two additional risk factors or more) and undergoing long-term intensive risk factor therapy and tight glycaemic control. METHODS SMI screening, using isotopic or echographic stress tests, was carried out in 122 asymptomatic type 2 diabetic patients at high cardiovascular risk and undergoing long-term intensive risk factor therapy. Coronary angiography was proposed if SMI was detected. Long-term follow-up data on death, myocardial infarction and revascularization were obtained by telephone call or clinical review. RESULTS The mean age was 65+/-6 years and 74% of patients were men. The mean duration of diabetes was 15+/-9 years. The mean number of additional risk factors was 2.9, 32% of patients had microalbuminuria and 12% had peripheral arterial disease. SMI was detected in 20 (16%) patients. Seven (6%) patients had significant CAD treated successfully by angioplasty (n=6) or bypass surgery (n=1). The positive predictive value of the non-invasive screening test for the diagnosis of significant CAD (stenosis>50%) was 39%. The event rate was very low (1.6%) at 2-year follow-up. CONCLUSION Long-term intensive risk factor therapy in high-risk patients with type 2 diabetes is associated with low prevalence of SMI and detected CAD. Optimal medical therapy and revascularization of significant CAD are associated with a low cardiovascular event rate at two years.

Cardiac events after low osmolar ionic or isosmolar nonionic contrast media utilization in the current era of coronary angioplasty.

Our study aimed to compare the isosmolar nonionic dimer iodixanol and the low osmolar ionic agent ioxaglate in the current era of percutaneous coronary intervention (PCI), using clopidogrel, enoxaparine, direct stenting, and drug eluting stent.

Efficacy and safety of 12 versus 48 months of dual antiplatelet therapy after implantation of a drug-eluting stent: the OPTImal DUAL antiplatelet therapy (OPTIDUAL) trial: study protocol for a randomized controlled trial.

BackgroundDual antiplatelet therapy with aspirin and thienopyridine is required after placement of coronary drug-eluting stents (DES) to prevent thrombotic complications. Current clinical guidelines recommend at least 6 to 12 months of treatment after a DES implantation, but it may be beneficial to apply dual antiplatelet therapy for a longer duration.Methods/designThe optimal dual antiplatelet therapy (OPTIDUAL) study aims to compare the benefits and risks of dual antiplatelet therapy applied for either 12 or 48 months. We will examine the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) in patients undergoing percutaneous coronary intervention with DES for the treatment of coronary lesions. The OPTIDUAL study is an open-label multicenter, randomized, national trial that will include 1,966 patients treated with DES. All patients will be treated with dual antiplatelet therapy for 12 months (+/− 3). Then, patients with no MACCE or major bleeding will be randomized to receive either 36 additional months of clopidogrel plus aspirin or aspirin only. The primary end-point is the combination of death from all causes, myocardial infarction, stroke and major bleeding. The secondary end points include the individual components of the primary end-point, stent thrombosis, repeat revascularization of the treated vessel and minor bleeding.DiscussionThis randomized trial is designed to assess the benefits and safety of 12 versus 48 months of dual antiplatelet therapy in patients that receive a DES. We aim to determine whether substantial prolongation of clopidogrel (a thienopyridine) after DES implantation offers an advantage over its discontinuation.Trial registrationClinicalTrials.gov Identifier: NCT00822536