Anticoagulation with otamixaban and ischemic events in non-ST-segment elevation acute coronary syndromes: the TAO randomized clinical trial.

IMPORTANCE: The optimal anticoagulant for patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) managed with an invasive strategy remains controversial. OBJECTIVE: To compare the clinical efficacy and safety of otamixaban, a novel intravenous direct factor Xa inhibitor, with that of unfractionated heparin plus downstream eptifibatide in patients with NSTE-ACS undergoing a planned early invasive strategy. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, active-controlled superiority trial that enrolled 13,229 patients with NSTE-ACS and a planned early invasive strategy, at 568 active sites in 55 countries and conducted between April 2010 and February 2013. A planned interim analysis was conducted for otamixaban dose selection. INTERVENTIONS: Eligible participants were randomized to otamixaban (bolus and infusion, at 1 of 2 doses) or unfractionated heparin plus, at the time of percutaneous coronary intervention, eptifibatide. The otamixaban dose selected at interim analysis was an intravenous bolus of 0.080 mg/kg followed by an infusion of 0.140 mg/kg per hour. MAIN OUTCOMES AND MEASURES: The primary efficacy outcome was the composite of all-cause death or new myocardial infarction through day 7. RESULTS: Rates of the primary efficacy outcome were 5.5% (279 of 5105 patients) randomized to receive otamixaban and 5.7% (310 of 5466 patients) randomized to receive unfractionated heparin plus eptifibatide (adjusted relative risk, 0.99 [95% CI, 0.85-1.16]; P = .93). There were no differences for the secondary end points, including procedural thrombotic complications. The primary safety outcome of Thrombosis in Myocardial Infarction major or minor bleeding through day 7 was increased by otamixaban (3.1% vs 1.5%; relative risk, 2.13 [95% CI, 1.63-2.78]; P < .001). Results were consistent across prespecified subgroups. CONCLUSIONS AND RELEVANCE: Otamixaban did not reduce the rate of ischemic events relative to unfractionated heparin plus eptifibatide but did increase bleeding. These findings do not support the use of otamixaban for patients with NSTE-ACS undergoing planned early percutaneous coronary intervention. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01076764.

The relationship between resistant hypertension and arterial stiffness.

OBJECTIVES: With growing awareness of arterial stiffness (AS) in the past 10 years, it was realized that resistant hypertension (RH) and AS share the same associated conditions such as older age, isolated systolic hypertension (HT), obesity, chronic kidney disease (CKD), and so on. Until now, there is no study investigating the role of AS in RH. In our study we aimed to determine whether there is an association between RH and AS. METHODS: Among 87 patients enrolled in this study, 30 were resistant hypertensives (Group 1), 29 were controlled hypertensives (Group 2), and 28 were normotensives (Group 3). Arterial stiffness was measured by both applanation tonometry and echocardiography; augmentation index, pulse wave velocity (PWV), aortic strain, and aortic distensibility were recorded in each patient. Diastolic function parameters were also assessed. RESULTS: In resistant hypertensive group, augmentation index and PWV were significantly higher than Group 2 and Group 3 (P = .03 and P < .01). Aortic strain and aortic distensibility parameters were significantly lower in RH group (P < .01 and P < .01). Arterial stiffness parameters were similar among Group 2 and Group 3. Among diastolic function parameters, left atrial volume index and left ventricular mass index significantly differ between groups. These two parameters were significantly lower in control group (P < .01 and P = .02) whereas similar in Group 1 and Group 2. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels were significantly different between groups as expected. When the correlation between two methods of AS was analyzed, a significant strong inverse correlation was found between echocardiographic and tonometric parameters. CONCLUSION: Arterial stiffness was found to be associated with RH. The inconsistency of this association in controlled hypertensives suggests a possible role of AS in RH pathogenesis. This study also showed that aortic strain and distensibility correlate well with the PWV which is the gold standard in the assessment of AS. This finding is important for the evaluation of AS more commonly in daily practice as echocardiography is a more feasible device than applanation tonometry.

[Coronary invasive procedures in women]. / Kadinlarda koroner invaziv girisimler.

Cardiovascular diseases are the most common etiology in women deaths worldwide. Despite this fact, coronary artery disease is usually known as a disease of men, and its importance in women health is not emphasized so much. In many registries, it has been shown that, female patients are opposed to less coronary invasive procedures than men. The reasons of this conservative strategy in women are, the older age, the more advanced coronary atherosclerosis at the time of diagnosis and smaller coronary arteries. Because of these factors, female patients are also prone to more complication rates than men. Until a few years ago, there had been little knowledge about gender related differences in diagnosis and management of coronary artery disease. In many of the large angiographic trials, most of the female patients were excluded from the studies, because of age and small coronary vessels. But now, with growing awareness of gender related differences in management of coronary artery disease, more female patients are included in trials, and more post-hoc analysis about gender factor are made.

Enoxaparin versus unfractionated heparin with fibrinolysis for ST-elevation myocardial infarction.

BACKGROUND: Unfractionated heparin is often used as adjunctive therapy with fibrinolysis in patients with ST-elevation myocardial infarction. We compared a low-molecular-weight heparin, enoxaparin, with unfractionated heparin for this purpose. METHODS: We randomly assigned 20,506 patients with ST-elevation myocardial infarction who were scheduled to undergo fibrinolysis to receive enoxaparin throughout the index hospitalization or weight-based unfractionated heparin for at least 48 hours. The primary efficacy end point was death or nonfatal recurrent myocardial infarction through 30 days. RESULTS: The primary end point occurred in 12.0 percent of patients in the unfractionated heparin group and 9.9 percent of those in the enoxaparin group (17 percent reduction in relative risk, P<0.001). Nonfatal reinfarction occurred in 4.5 percent of the patients receiving unfractionated heparin and 3.0 percent of those receiving enoxaparin (33 percent reduction in relative risk, P<0.001); 7.5 percent of patients given unfractionated heparin died, as did 6.9 percent of those given enoxaparin (P=0.11). The composite of death, nonfatal reinfarction, or urgent revascularization occurred in 14.5 percent of patients given unfractionated heparin and 11.7 percent of those given enoxaparin (P<0.001); major bleeding occurred in 1.4 percent and 2.1 percent, respectively (P<0.001). The composite of death, nonfatal reinfarction, or nonfatal intracranial hemorrhage (a measure of net clinical benefit) occurred in 12.2 percent of patients given unfractionated heparin and 10.1 percent of those given enoxaparin (P<0.001). CONCLUSIONS: In patients receiving fibrinolysis for ST-elevation myocardial infarction, treatment with enoxaparin throughout the index hospitalization is superior to treatment with unfractionated heparin for 48 hours but is associated with an increase in major bleeding episodes. These findings should be interpreted in the context of net clinical benefit. (ClinicalTrials.gov number, NCT00077792.).

Evaluation of serum anti-cardiolipin and oxidized low-density lipoprotein levels in chronic periodontitis patients with essential hypertension.

BACKGROUND: The aim of the present study was to investigate whether chronic periodontitis caused the elevated levels of anti-cardiolipin antibodies (anti-CL) and oxidized low-density lipoprotein (oxLDL) in subjects with essential hypertension. METHODS: Seventy-two subjects were categorized as healthy controls, subjects with essential hypertension and periodontal health (healthy-hypertension group), subjects with essential hypertension and gingivitis (gingivitis-hypertension group), or subjects with essential hypertension and chronic periodontitis (periodontitis-hypertension group). Individuals with essential hypertension who had been taking antihypertensive medication > or =2 years were included in the present study. The presence of supragingival plaque, bleeding on probing (BOP), probing depth (PD), and clinical attachment level were recorded, and blood samples were collected. Serum immunoglobulin M (IgM) and immunoglobulin G (IgG) anti-CL and oxLDL levels were assessed by enzyme-linked immunosorbent assay. For IgM and IgG anti-CL assays, positive tests were defined as > or =15 IgM phospholipid units and > or =10 IgG phospholipid units, respectively. RESULTS: The mean IgM anti-CL level and the prevalence of subjects positive for IgM anti-CL were significantly higher in the periodontitis-hypertension group compared to the other groups (P = 0.001). No significant differences were observed in the mean IgG anti-CL and oxLDL levels or in the number of subjects positive for IgG anti-CL and positive for IgM or IgG anti-CL among the study groups. The Pearson correlation analysis revealed positive correlations between IgM anti-CL levels and supragingival plaque, BOP, and PD scores. CONCLUSIONS: Chronic periodontitis might play a causal role in the elevated serum levels of anti-CL antibodies in individuals with essential hypertension. These elevated anti-CL levels that are due to chronic periodontitis might contribute to an increased risk for atherosclerosis in individuals with essential hypertension.

Sodium bicarbonate, N-acetylcysteine, and saline for prevention of radiocontrast-induced nephropathy. A comparison of 3 regimens for protecting contrast-induced nephropathy in patients undergoing coronary procedures. A single-center prospective controlled trial.

BACKGROUND: Several protective therapies have been developed to prevent contrast-induced nephropathy (CIN). We aimed to investigate the efficacy of sodium bicarbonate by comparing 2 other regimens, including combination of N-acetylcysteine (NAC) plus sodium chloride and sodium chloride alone, to prevent CIN in patients undergoing cardiovascular procedures. METHODS: We prospectively enrolled 264 patients who were scheduled for cardiovascular procedures and had a baseline creatinine level >1.2 mg/dL. The patients were assigned 1 of 3 prophylactic regimens: infusion of sodium bicarbonate, sodium chloride, sodium chloride plus oral NAC (600 mg bid). Contrast-induced nephropathy was defined as an increase in serum creatinine level >25% or 0.5 mg/dL after 48 hours. RESULTS: There were no significant differences among groups regarding baseline demographic properties and nephropathy risk factors. The change in creatinine clearance was significantly better in the sodium bicarbonate group than other 2 groups (P = .007). The incidence of CIN was significantly lower in the sodium bicarbonate group (4.5%) compared with sodium chloride alone (13.6%, P = .036) and tended to be lower than in the combination group (12.5%, P = .059). After adjusting the Mehran nephropathy risk score, the risk of CIN significantly reduced with sodium bicarbonate compared with sodium chloride alone (adjusted risk ratio 0.29, P = .043). CONCLUSIONS: Hydration with sodium bicarbonate provides better protection against CIN than the sodium chloride infusion does alone. Combination therapy of NAC plus sodium chloride did not offer additional benefit over hydration with sodium chloride alone.

Effect of enoxaparin versus unfractionated heparin in diabetic patients with ST-elevation myocardial infarction in the Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment-Thrombolysis In Myocardial Infarction study 25 (ExTRACT-TIMI 25) trial.

BACKGROUND: Patients with diabetes mellitus (DM) are at higher risk for complications after ST-elevation myocardial infarction (STEMI) than patients without DM. Potent antithrombotic therapies may offer particular benefit for these high-risk patients and must be balanced against the potential for increased bleeding. METHODS: We performed a prospectively planned analysis of efficacy and safety in patients with DM among 20,479 patients with STEMI treated with fibrinolysis and randomized to a strategy of enoxaparin (up to 8 days) or unfractionated heparin (UFH) (48 hours) in ExTRACT-TIMI 25. RESULTS: Patients with DM (n = 3060) were older and more likely to be women and to present with heart failure (P < .0001 for each) than those without DM. After adjustment for the TIMI Risk Score, sex, and renal function, patients with DM were at 30% higher risk for death or myocardial infarction (MI) by 30 days (OR(adj) 1.29, 95% CI 1.14-1.46). Among patients with DM, the enoxaparin strategy reduced mortality (9.5% vs 11.8%, relative risk [RR] 0.81, 95% CI 0.66-0.99), death/MI (13.6% vs 17.1%, RR 0.80; 95% CI 0.67-0.94), and death/MI/urgent revascularization (16.0% vs 19.7%, RR 0.81, 95% CI 0.70-0.94). The enoxaparin strategy was associated with a trend toward higher major bleeding (2.6% vs 1.6%, RR 1.63, 95% CI 0.99-2.69). Taking efficacy and safety into account, the enoxaparin strategy offered superior net clinical benefit (death/MI/major bleed, 14.8% vs 18.0%, RR 0.83, 95% CI 0.70-0.97) compared with UFH in patients with DM. CONCLUSIONS: In a subgroup analysis, a reperfusion strategy including enoxaparin significantly improved outcomes compared with UFH among high-risk STEMI patients with DM undergoing fibrinolysis.

[Interventional therapy indications in the elderly - are they different?] / Yaslilarda girisimsel tedavi endikasyonlari - fark var mi?

The prevalance of cardiovascular disease increases with age and cardiovascular disease is the leading cause of death in adults >75 years of age. However many trials have excluded older patients. So we don't have randomized trials but only limited subgroup analysis or registries for older patients. In general the indications for intervention and revascularization are not different in elderly patients. But complex co-morbidities, significant physical or cognitive disabilities can change our decision. Complex Coronary anatomy and the complications of the procedure is high in older patients. Long term mortality is similar in patients treated with Coronary artery bypass graft surgery or percutaneous coronary intervention, but re-intervention is higher in coronary intervention group. Invazive approach is superior to conservative treatment even in very elderly patients with acute coronary syndrome. We need randomized trials including mainly older patients in this era.

Efficacy and Safety of Adding Ezetimibe to Statin Therapy Among Women and Men: Insight From IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial).

BACKGROUND: IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) showed that adding the nonstatin ezetimibe to statin therapy further reduced cardiovascular events in patients after an acute coronary syndrome. In a prespecified analysis, we explore results stratified by sex. METHODS AND RESULTS: In IMPROVE-IT, patients with acute coronary syndrome and low-density lipoprotein cholesterol of 50 to 125 mg/dL were randomized to placebo/simvastatin 40 mg or ezetimibe/simvastatin 10/40 mg. They were followed up for a median of 6 years for the primary composite of cardiovascular death, myocardial infarction, hospitalization for unstable angina, coronary revascularization ≥30 days, and stroke. Among 18 144 patients in IMPROVE-IT, 4416 (24%) were women. At 12 months, the addition of ezetimibe to simvastatin significantly reduced low-density lipoprotein cholesterol from baseline compared with simvastatin monotherapy in men and women equally (absolute reduction, 16.7 mg/dL in men and 16.4 mg/dL in women). Women receiving ezetimibe/simvastatin had a 12% risk reduction over those receiving placebo/simvastatin for the primary composite end point (hazard ratio, 0.88; 95% confidence interval, 0.79-0.99) compared with a 5% reduction for men (hazard ratio, 0.95; 95% confidence interval, 0.90-1.01; P=0.26 for interaction). When the total number of primary events was considered, women had an 18% reduction with the addition of ezetimibe (relative risk, 95% confidence interval, 0.81; 0.71-0.94) and men had a 6% reduction (relative risk, 0.94; 95% confidence interval, 0.87-1.02; P=0.08 for interaction). The addition of ezetimibe did not increase the rates of safety events in either women or men. CONCLUSIONS: IMPROVE-IT demonstrated that the benefit of adding ezetimibe to statin is present in both women and men, with a good safety profile supporting the use of intensive, combination, lipid-lowering therapy to optimize cardiovascular outcomes. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00202878.

Usefulness of preprocedural soluble CD40 ligand for predicting restenosis after percutaneous coronary intervention in patients with stable coronary artery disease.

CD40-CD40 ligand interaction is involved in the inflammatory pathogenesis of atherosclerosis but clinical data about its role in stent restenosis are still limited. We investigated the effect of preprocedural CD40 ligand (sCD40L) on stent restenosis. We enrolled 36 patients (mean age 61.4 +/- 8.5 years) with stable angina who underwent successful stent implantation. Control angiograms were performed in all patients after 6 months. Plasma sCD40L and high-sensitive C-reactive protein levels were measured before stent implantation and at 1 and 6 months after the procedure. Angiographically proven restenosis rate was 27.8%. Plasma sCD40L levels were significantly higher (preprocedural 0.74 +/- 0.79) and more prolonged in patients with stent restenosis compared with patients without stent restenosis (0.02 +/- 0.22 ng/ml, p < 0.001). According to receiver-operator characteristic analysis, sCD40L > 0.41 ng/ml was the best distinguished parameter between patients with and without restenosis. At the multivariate logistic regression analysis, preprocedural sCD40L was an independent predictor (RR 39.4, 95% confidence interval 4.05 to 383.8, p = 0.002) of stent restenosis after adjusting for confounding variables, including diabetes, reference vessel diameter, lesion length, stent diameter, stent length, and baseline high-sensitive C-reactive protein. Sensitivity, specificity, and positive and negative predictive values and likelihood ratio of preprocedural sCD40L levels in stent restenosis were 78%, 92%, 78%, 92%, and 9.37%, respectively. In conclusion, enhanced inflammation of plaque (increased sCD40L) before percutaneous coronary intervention may increase the rate of stent restenosis. Increased preprocedural sCD40L level is an independent predictor of stent restenosis. We can use this marker for the assessment of risk stratification before planning stent implantation.

The effect of raloxifene on cardiac autonomic regulation in osteoporotic women.

OBJECTIVE: There are suggestive data that raloxifene may have favorable effects on the arterial systems in postmenopausal women and thereby lowering the incidence of future adverse cardiovascular events. Reduction of heart rate variability appears to be a marker for identifying subjects with an increased risk for cardiac mortality, particularly in patients after myocardial infarction and in elderly people. Although there are conflicting data with regard to the effects of estrogen and progesterone on heart rate variability in postmenopausal women, the impact of raloxifene treatment on heart rate variability is fully unknown. STUDY DESIGN: Forty-three osteoporotic postmenopausal women were recruited in a prospective, randomized, and placebo-controlled 6-month study. Of these women, 23 received raloxifene hydrocloride, 60 mg once daily, whereas 20 women received alendronate, 10 mg daily. Time and frequency domains of heart rate variability were measured at baseline and at 3 months and 6 months of the treatment. RESULTS: Time domain indices of heart rate variability, mean RR, and SD of all beat-to-beat intervals remained identical within the groups at the end of treatment. The square root of the mean of the sum of squares of successive RR intervals, a sensitive index of parasympathetic activity, tended to increase with raloxifene. Frequency domain indices of heart rate variability were as follows: low-frequency power of heart rate variability tended to stay the same, compared with the baseline values in both treatment regimens. High-frequency power of heart rate variability increased significantly in the raloxifene group (P = .039) at 3 months, and this significance persisted at the end of the treatment. A nonsignificant decrease was observed in the alendronate group. Accordingly, the low-frequency power/high-frequency power ratio, an index of sympathovagal balance, decreased significantly by the raloxifene treatment (P = .028) at 3 months and persisted at 6 months. There was no significant change in low-frequency power/high-frequency power ratio of patients taking alendronate. CONCLUSION: Raloxifene seems to have a positive effect on cardiac autonomic regulation in postmenopausal osteoporotic women. This observation could at least partially explain the reduced cardiovascular events in the subset of women with increased cardiovascular risk in the Multiple Outcomes of Raloxifene Evaluation trial. However, the results of ongoing studies should be awaited to have a conclusion of its effects on the cardiovascular system.

Are complex coronary lesions more frequent in patients with diabetes mellitus?

BACKGROUND: Coronary atherosclerotic burden is excessive in diabetic patients. Diabetes mellitus (DM) is an independent predictor for both death and myocardial infarction. It is not known whether the prevalence of complex coronary lesions, such as bifurcation and ostial lesions, is different in diabetics from nondiabetics. OBJECTIVE: The aim of present study was to investigate the prevalence of these lesions in patients with DM. METHODS: One thousand fourteen consecutive patients (mean age 61.3+/-10.7 years) were investigated. Coronary angiograms were examined for bifurcation and ostial lesions using a digital quantitative system. Patients were classified as diabetic (n=281) or nondiabetic (n=733). RESULTS: Patient mean age, and rates of hypertension and hyperlipidemia were significantly higher in the diabetic group than in the nondiabetic group (P<0.0001), although smoking was significantly lower (P=0.001). Reasons for coronary angiography and treatment were comparable between the two groups. The prevalence of bifurcation lesions and ostial lesions was significantly greater in the diabetic group than in the nondiabetic group (9.8% versus 4.3% [P=0.001] and 38.4% versus 29.2% [P=0.003] in the diabetic group versus the nondiabetic group). The presence of DM and greater age were found to be independent predictors for bifurcation lesions (OR=2.27 [P=0.004] and OR=1.03 [P=0.01], for DM and age, respectively) and ostial lesions (OR=1.40 [P=0.027] and OR=1.02 [P=0.001], for DM and age, respectively) in multivariate analysis. CONCLUSIONS: Complex coronary lesions such as bifurcation and ostial lesions were significantly more common in diabetic patients than in nondiabetic patients. Greater age and the presence of DM were independent predictors for these complex lesions. These results may help to explain the poor prognosis of coronary artery disease among diabetic patients.

Cardioversion under the guidance of transesophageal echochardiograhy in persistent atrial fibrillation: results with low molecular weight heparin.

BACKGROUND: Transesophageal echocardiography (TEE) guided cardioversion to restoration of sinus rhythm is a therapeutic option in patients with atrial fibrillation (AF). Anticoagulation at the time of and after cardioversion is necessary to prevent formation of new thrombus during atrial stunning period. We aimed to evaluate the efficacy and safety to TEE guided cardioversion with low molecular weight heparin (LMWH) in patients with atrial fibrillation. METHODS: We followed up 208 patients with persistent AF (mean age: 65.5+/-10.2 years) who were attempted TEE guided cardioversion. LMWH were used as an anticoagulant and warfarin therapy was continued. RESULTS: Cardioversion were performed in 183 patients. Sinus rhythm restored in 144 patients (78.7%). Mean follow up duration was 155 days. No cardiac death occurred. In the early follow up period (within 30 day) one thromboembolic event (0.54%) occurred in a patient who was cardioverted. Two patients who had not been cardioverted because of left atrial thrombus presented embolic stroke, one in early and another in late follow up period. All embolic complications occurred in patients who had been taking warfarin and whose INR level was subtherapeutic at the time of stroke. Sinus rhythm was maintained in 64% and total hemorrhagic complications occurred in 4.8% of the patients in long-term follow-up. CONCLUSION: TEE guided cardioversion with a short-term anticoagulation protocol using low molecular weight heparin is a safe and effective method in restoring and maintaining sinus rhythm and enables us to make earlier cardioversion in atrial fibrillation.

Head-up tilt table testing with low dose sublingual isosorbide dinitrate in the evaluation of unexplained syncope: a comparison with isoproterenol infusion.

OBJECTIVES: To investigate the value of head-up tilt table testing (HUTT) with low-dose isosorbide dinitrate (ISDN) in the evaluation of patients with unexplained syncope and to compare the results of HUTT with ISDN and HUTT with isoproterenol. PATIENTS AND METHODS: Forty-three patients with unexplained syncope (21 women, with a mean age of 45.4 18 years) and 18 control subjects without syncope (eight women, with a mean age of 45.8 12 years) were tilted (80 ) for 30 min (passive period). When this period was negative, 2.5 mg sublingual ISDN was administered and patients were observed for an additional 15 min (ISDN period). The first 25 patients studied (10 women, with a mean age of 46.2 18 years) were tested again after a mean period of three weeks using the isoproterenol protocol. After the passive period, intravenous isoproterenol was administered (1 to 3 g/min) to patients lying in the supine position, and they were tilted again (80 ) for 10 min (isoproterenol period). RESULTS: During the passive period, 10 of 43 patients (23%) had a positive response compared with none in the control group. Syncope was observed in another 14 patients and in two control subjects during the ISDN period. The positivity rate (sensitivity) and specificity of HUTT with low dose ISDN were 56% and 89%, respectively. Among the patients (n=25) tested with the isoproterenol protocol, 14 (56%) patients had syncope. The agreement rate between the protocols was 78.9%. CONCLUSIONS: The total positivity rate of HUTT significantly increased with the use of the low dose ISDN, while specificity remained high. Due to its simplicity and tolerability, the ISDN protocol can be chosen when the results of the passive period tilt testing are negative.

Primary stenting in a patient with acute myocardial infarction and primary antiphospholipid syndrome.

We present a patient who had recurrent coronary thrombosis due to primary antiphospholipid syndrome. The patient was treated with streptokinase during the first myocardial infarction and primary stenting during reinfarction. To our knowledge, this is the first case in which the occluded right coronary artery was treated with primary stent implantation.

Enoxaparin vs unfractionated heparin in high-risk patients with non-ST-segment elevation acute coronary syndromes managed with an intended early invasive strategy: primary results of the SYNERGY randomized trial.

CONTEXT: Enoxaparin has demonstrated advantages over unfractionated heparin in low- to moderate-risk patients with non-ST-segment elevation acute coronary syndromes (ACS) treated with a conservative strategy. OBJECTIVES: To compare the outcomes of patients treated with enoxaparin vs unfractionated heparin and to define the role of enoxaparin in patients with non-ST-segment elevation ACS at high risk for ischemic cardiac complications managed with an early invasive approach. DESIGN, SETTING, AND PARTICIPANTS: The Superior Yield of the New Strategy of Enoxaparin, Revascularization and Glycoprotein IIb/IIIa Inhibitors (SYNERGY) trial was a prospective, randomized, open-label, multicenter, international trial conducted between August 2001 and December 2003. A total of 10 027 high-risk patients with non-ST-segment elevation ACS to be treated with an intended early invasive strategy were recruited. INTERVENTIONS: Subcutaneous enoxaparin (n = 4993) or intravenous unfractionated heparin (n = 4985) was to be administered immediately after enrollment and continued until the patient required no further anticoagulation, as judged by the treating physician. MAIN OUTCOME MEASURES: The primary efficacy outcome was the composite clinical end point of all-cause death or nonfatal myocardial infarction during the first 30 days after randomization. The primary safety outcome was major bleeding or stroke. RESULTS: The primary end point occurred in 14.0% (696/4993) of patients assigned to enoxaparin and 14.5% (722/4985) of patients assigned to unfractionated heparin (odds ratio [OR], 0.96; 95% confidence interval [CI], 0.86-1.06). No differences in ischemic events during percutaneous coronary intervention (PCI) were observed between enoxaparin and unfractionated heparin groups, respectively, including similar rates of abrupt closure (31/2321 [1.3%] vs 40/2364 [1.7%]), threatened abrupt closure (25/2321 [1.1%] vs 24/2363 [1.0%]), unsuccessful PCI (81/2281 [3.6%] vs 79/2328 [3.4%]), or emergency coronary artery bypass graft surgery (6/2323 [0.3%] vs 8/2363 [0.3%]). More bleeding was observed with enoxaparin, with a statistically significant increase in TIMI (Thrombolysis in Myocardial Infarction) major bleeding (9.1% vs 7.6%, P =.008) but nonsignificant excess in GUSTO (Global Utilization of Streptokinase and t-PA for Occluded Arteries) severe bleeding (2.7% vs 2.2%, P =.08) and transfusions (17.0% vs 16.0%, P =.16). CONCLUSIONS: Enoxaparin was not superior to unfractionated heparin but was noninferior for the treatment of high-risk patients with non-ST-segment elevation ACS. Enoxaparin is a safe and effective alternative to unfractionated heparin and the advantages of convenience should be balanced with the modest excess of major bleeding.

[Electrophysiological mechanisms of atrial fibrillation]. / Atriyal fibrilasyonun elektrofizyolojik temelleri.

The electrophysiological mechanism of atrial fibrillation (AF) has been the subject of interest for almost a hundred years. The mechanism that leads to the induction of atrial fibrillation can be a single automatic focus firing impulses with high rate (e.g. pulmonary vein) as well as macro- or more frequently micro-re-entrant circuits. The focal mechanism has been recently shown to be responsible for at least a particular group of AF cases. Cellular and electrophysiological abnormalities such as partly depolarised cells, fibrosis, conduction abnormalities, shortening of the refractoriness and the increase in dispersion of refractoriness in the atrium can be the underlying factors for the genesis of atrial fibrillation. Factors such as the autonomic nervous system, aging, enlargement of the atria can modulate these electrophysiological features. AF can be maintained in the existence of particular conditions and AF itself leads to some changes in the atrium that are thought to be the base of perpetuation of fibrillation in the atria. These changes in the atrial electrophysiology and anatomy are called AF-induced atrial remodeling. Whatever it is the triggering mechanism for AF, "multiple wavelet re-entry" has been widely accepted to be the maintaining mechanism of AF. Finally, it can be considered that we are facing the different types of AF that can be induced with different mechanisms, that need special conditions to perpetuate and maintain, but present with similar findings in the electrocardiogram.

[Arrhythmia risk and noninvasive markers in hypertensive left ventricular hypertrophy]. / Hipertansiyon ve sol ventrikül hipertrofisinde ventriküler aritmi riski ve noninvaziv aritmi göstergeleri ile iliskisi.

OBJECTIVE: Several studies have evidenced that hypertensive patients with severe left ventricular hypertrophy have an increased incidence of malignant ventricular arrhythmia and sudden death. However arrhythmia risk in mild to moderate hypertrophy is uncertain. This study aims to investigate the risk of ventricular arrhythmias in hypertensive patients with mild to moderate hypertrophy and evaluate the role of noninvasive arrhythmia markers and ambulatory blood pressures. METHODS: Ninety-nine hypertensive patients (35 male, mean age 57.3 +/- 9.6) without coronary heart disease were included the study. All subjects underwent an echocardiography for measurement of LV mass index (LVMI) and were classified in two groups; hypertrophic (LVH(+) n:43) and nonhypertrophic (LVH(-) n:56). Ambulatory blood pressure monitoring, 24 hour ECG, signal averaged ECG, and 12 lead ECG were performed in each group seeking to identify the arrhythmogenic risk. RESULTS: Holter ECG showed that 20.1% patients had Lown class II and 12.1% patients had Lown class IVa-IVb arrhythmia (potentially malignant ventricular arrhythmia; PMVA). PMVA incidence was significantly higher in hypertrophic groups (20.9%) compared to nonhypertrophic groups (6.5%) (p < 0.05). Ambulatory systolic and diastolic blood pressures were similar in PMVA(+) and PMVA(-) patients. At least two parameters of ventricular late potentials were significantly higher in LVH(+) group (25.7%) compared to LVH(-) group (4.9%) (p < 0.01). HRV parameters were not different between two groups. QTcd was significantly increased in LVH(+) than in LVH(-) patients (54.1 +/- 16.7 vs. 47.5 +/- 17.7 ms) (p < 0.05) The frequency of PMVA was significantly higher in increased QTcd compared to normal QTcd (24.3%-3.4%; p < 0.01) and LP(+) patients (16.2%) compared to LP(-) patients (8.7%; p < 0.05). CONCLUSION: Our data suggest that hypertension may be associated with high risk of PMVA in patients with mild to moderate LVH particularly in presence of LP and QTcd > 50 ms. QTcd and at least 2 factors of LP were increased in mild to moderate LVH. Arrhythmogenecity does not seem to be related with autonomic dysregulation and ambulatory blood pressure level in hypertensive patients.

[Does the short-term mortality differ between men and women with first acute myocardial infarction?]. / Acil Servise Akut Miyokard Infarktüsü ile Ilk Kez Basvuran Kadin ve Erkeklerde 28 Günlük Sagkalim Farkli mi?

OBJECTIVE: Women with myocardial infarction (MI) have been reported to have worse short-term prognosis than men. We aimed to compare men and women with first MI regarding 28 days survival, cardiovascular (CV) risk factors, clinical findings, and the treatment in the emergency setting. METHODS: One-hundred and seventy-five consecutive patients with first MI admitted to the emergency department of our hospital within one year were included in the study. Data on admission time, CV risk factors, clinical findings and treatment options were obtained from the patient charts. Twenty-eight days after the first admission, patients were called by phone and asked information about their health status. Survival curves for men and women were compared using log rank test. RESULTS: After the exclusion of 20 cases who were lost during the follow up, 117 men and 38 women were evaluated in the study; 9.4% of the men and 10.5% of the women died within 28 days (p=0.85). Women were older (10 years), had higher prevalence of hypertension (p=0.04), diabetes (p=0.01) and stroke history (p=0.02) than men. Men had higher levels of smoking history than women (79.1%, 31.6%; p<0.001). There were no significant gender differences regarding clinical findings, time to hospital admission after chest pain onset and time to thrombolysis. Thrombolysis was applied in 35.8% of women and in 48.6% of men patients. Primary PTCA was performed in 26.4% of men and 11.4% of women patients (p=0.16). CONCLUSION: Women tended to be older and had more co-morbidities, but did not differ from men regarding clinical findings, treatment given in emergency department and short-term survival.

The association of plasma homocysteine, coronary risk factors and serum nitrite in patients with coronary artery disease, vascular syndrome x and healthy subjects.

OBJECTIVE: We evaluated the association of plasma total homocysteine (tHcy), cardiac risk factors and total nitrite in coronary artery disease (CAD) patients, cardiac syndrome X patients and in healthy subjects. METHODS: Forty two CAD, 22 cardiac syndrome X patients and 30 healthy subjects, aged 30 to 75 years were included into the study. Blood samples of tHcy, serum total nitrite and cardiac risk factors were studied appropriately. The results were compared between the groups. The independent contributions of tHcy and total nitrite to CAD and cardiac syndrome X and their interactions with cardiac risk factors were evaluated. RESULTS: After adjusting for age, median values of tHcy and total nitrite were evaluated for their skewness. Coronary artery disease patients had higher median plasma tHcy levels than cardiac syndrome X patients (p<0.001) and healthy subjects (p<0.001) and lower serum total nitrite levels than patients in the two other groups (p<0.05), respectively. Using a univariate linear regression analysis tHcy had a moderately significant positive correlation with age (beta=0.34, p=0.002) and a weakly significant inverse correlation with female gender (beta=-0.24, p=0.032). Using a partial correlation analysis by controlling for age, gender and clinical situations tHcy had a positive but moderately significant correlation with LDL cholesterol (r=0.23, p=0.01) and triglycerides (r=0.27, p=0.016). Total nitrite had a positive but weakly significant correlation with HDL cholesterol (r=0.23, p=0.04) and fibrinogen (r=0.24, p=0.03) and an inverse but moderately significant correlation with LDL cholesterol (r=-0.37,p=0.001). Using a multivariate stepwise regression analysis total nitrite was inversely and significantly associated with tHcy (beta=-0.45) in the control group. The contribution of HDL cholesterol to the association was beta=-0.45, p=0.044, R2=36.2%, HDL cholesterol with fibrinogen--beta=-0.45, p=0.05, R2=36.6% and HDL cholesterol with LDL cholesterol--beta=-0.45, p=0.05, R2=36.3%. In a forward stepwise logistic regression analysis the age adjusted odds ratio (OR) for coronary artery disease per standard deviation change in log-transformed tHcy concentration was - 0.82, p=0.013 and in total nitrite concentration was - 1.08, p=0.02. Using the same model neither tHcy nor total nitrite was associated with cardiac syndrome X (p=0.221 and p=0.112), respectively. CONCLUSION: The low nitrite levels can be a marker of endothelial dysfunction in the presence of hyperhomocysteinemia and other cardiac risk factors. Our results might support endothelial dysfunction in CAD but not in cardiac syndrome X patients.