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.

[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.

A mandatory modification in extracorporeal biventricular assist device (BIVAD) implantation: intercostal tunnel application: a case report.

In this case, our patient was a heart transplant candidate connected to a respiratory system. An extracorporeal biventricular assist device (BIVAD) was the only option in order to bridge to transplantation. In routine procedures, it is recommended that Berlin Heart Excor cannulas be removed through the subfascial subcostal tunnel. As the severely dilated right ventricle compressed the apex of the left ventricle, which was also dilated to the mid-back zone of the left hemithorax, the whole length of the Extracorporeal BIVAD apical cannula had to remain within the thorax; however, the cannula was removed from the body by creating a tunnel at the 7th intercostal space. In the long-term follow-up, this compulsory modification has proven to be safe and effective.

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 effects of chronic usage of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on contrast-induced nephropathy in low-risk patients [corrected].

OBJECTIVE: There is conflicting data about the role of renin- angiotensin- aldosterone system (RAAS) blockers in contrast-induced nephropathy (CIN) pathophysiology. In this study, we aimed to investigate the effects of chronic usage of RAAS blocker drugs on development of CIN in low risk patients. METHODS: Study was designed as a prospective cohort study. A total of 295 patients were enrolled in the study. Study population was consisted of three subgroups according to prior usage of RAAS blockers: no RAAS blocker group (n=95), angiotensin-converting enzyme inhibitor (ACEI) group (n=106), angiotensin receptor blocker (ARB) group (n=94). CIN was defined as an increase of ≥25% in creatinine over the baseline value or 0.5 mg/dL rise within 48-72 h of angiography. Mehran score was calculated for each patient. Baseline variables and percentage of CIN were compared with ANOVA, Mann-Whitney U, Kruskal-Wallis and Pearson Chi-square tests between groups. In order to determine the independent predictors of CIN, binary logistic regression analyses were performed. RESULTS: CIN occurred in 18 patients (17.0%) in the ACEI group, 17 patients (18.1%) in ARB group and 7 patients (7.4%) in the no RAAS group. CIN occurrence was significantly higher in RAAS than no RAAS group (17.5% vs. 7.4%, p=0.01). Chronic RAAS blocker administration was an independent predictor of CIN (OR=2.69; 95% CI: 1.025-7.067; p=0.04). Mehran score was the only other independent predictor for CIN (OR=1.15; 95% CI: 1.019-1.310; p=0.02). CONCLUSION: In patients with near normal renal functions who are undergoing elective coronary procedure, chronic usage of ACEI and ARB increases the risk of CIN.

An observational study to evaluate factors responsible and actions taken for hypertensive patients who are not at blood pressure goal: i-target Goal Study.

To evaluate the percentage of hypertensive patients who could achieve target blood pressure (TBP) according to the guidelines in the context of recommended measures and the factors responsible for failure. A total of 589 hypertensive patients (59.0% female; mean age: 57.7 ± 10.4 years) were assessed twice for TBP achievement based on 2007 ESH/ESC guidelines and the investigators' view, in addition to the recommended measures and possible causes of failure in hypertension management in this national multi-center (n = 99), non-interventional observational study. Only 29.5% of the patients at the first visit and 46.8% at the second visit achieved the TBP levels specified by the guidelines. However, the investigators' evaluation indicated a higher achievement rate at the first (43.5%) as well as the second (69.1%) visit when compared with the guideline-based assessments (P < 0.001). The primary reasons identified by the investigators for the failure to reach TBP were non-compliance with dietary recommendations (61.6%) at the first visit and non-compliance with treatment (63.92%) at the second visit. Recommendations for lifestyle were the most commonly identified treatment plan by the investigators at both visits (62.9% and 66.1%, respectively). Although more patients achieved the TBP levels specified by the guidelines for the second visit compared with the first, effective blood pressure control was achieved only in 29.5% of our patients. Interestingly, the investigators had a more optimistic view about their patients' control of hypertension, which may have contributed to a poor achievement of TBP.

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.

The association of beta-fibrinogen 455 G/A gene polymorphism with left atrial thrombus and severe spontaneous echo contrast in atrial fibrillation.

OBJECTIVE: The role of coagulation parameters left atrial thrombus formation in atrial fibrillation has not been investigated before. We aimed to investigate the association between the beta-fibrinogen gene polymorphism or glycoprotein IIIa gene polymorphism and presence of left atrial (LA) thrombus or spontaneous echo contrast (SEC) in patients with atrial fibrillation (AF). METHODS: Forty-seven patients with AF, in whom transesophageal echocardiography was performed, were included to this cross-sectional observational study. Patients were divided in two groups; those with LA thrombus (n=24) were assigned to group 1 and those without thrombus in group 2 (n=23). DNA analysis was conducted to determine gene polymorphism in all patients. Mann-Whitney U test or Chi-square tests were used for statistical analysis. RESULTS: There were no significant differences between groups regarding to demographic and clinical characteristics. The frequency of beta-fibrinogen 455 G/A polymorphism was higher (37.5%) in group 1 as compared to group 2 (15.1%) but it did not reach statistical difference (p=0.23). When we added patients with severe SEC in the study group (patients with severe SEC and/or thrombus n=27) the difference (44.40%-10%) reached the statistical difference (p=0.01). Glycoprotein IIIa Pl A1/A2 polymorphism was not different between groups with (p=0.82) or without SEC (p=0.73). CONCLUSION: In patients with atrial fibrillation, beta-fibrinogen 455 G/A gene polymorphism is associated with the presence of left atrial thrombus and severe SEC. Beta-fibrinogen 455 G/A gene polymorphism may be a promising marker for the prediction of thromboembolism risk in patients with atrial fibrillation.

[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.

Comparison of site-reported and core laboratory-reported creatine kinase-MB values in non-ST-segment elevation acute coronary syndrome (from the international trial SYNERGY).

The effect of nonstandardized creatine kinase (CK)-MB assays on the assessment of myocardial infarction (MI) end points in multicenter international trials has not been evaluated. We compared the site-reported and corresponding core laboratory CK-MB measures from 5 countries participating in the Superior Yield of the New Strategy of Enoxaparin, Revascularization, and Glycoprotein IIb/IIIa Inhibitors (SYNERGY) trial. Samples for CK-MB were collected locally, with corresponding samples sent to a core laboratory at enrollment and after recurrent ischemic events, percutaneous coronary intervention, or coronary artery bypass grafting. The measured values were compared to the reported assay upper limits of normal (ULN) used at the site (or core laboratory for the core laboratory samples). The CK-MB results were available locally and from the core laboratory for 913 patients, constituting 4,693 time-matched laboratory values. The agreement between the core and site laboratory CK-MB/ULN ratio was moderate (concordance correlation coefficient 0.45) and varied considerably by geographic location and site. The CK-MB values were elevated (>or=2 times the ULN) by the core laboratory but normal (<2 times the ULN) by local standards in 708 instances (15%). There were 162 MI end points according to the core laboratory values versus 91 MI end points using the site-reported CK-MB data (kappa statistic 0.48). Compared with patients with no MI by the core or site laboratory values, patients with MI, as determined by both the core and the site laboratories, had significantly lower unadjusted 1-year survival rates (80.6% vs 93.5%, p <0.0001). Patients with MI, as determined by the core laboratory but not by the site laboratory, showed a trend toward a lower 1-year survival rate (89.8% vs 93.5%, p = 0.20). In conclusion, a substantial variation in CK-MB ratios and MI outcomes between the site and core laboratory data was observed in the SYNERGY trial. More MI outcomes were identified by the core laboratory, and patients with MI as defined by core laboratory data had lower 1-year survival, making these events potentially clinically important.

Assessment of aortic stiffness and ventricular functions in familial Mediterranean fever.

OBJECTIVE: To investigate systolic and diastolic ventricular functions, aortic elastic properties and the presence of pericardial effusion in familial Mediterranean fever (FMF) patients. METHODS: A case-controlled, cross-sectional study was performed on 44 FMF patients and 27 controls. Subjects with hypertension, diabetes mellitus and hyperlipidemia were excluded. Left and right ventricular functions were measured using echocardiography including two-dimensional, M-mode, and conventional Doppler as well as pulsed wave tissue Doppler imaging (TDI). Aortic elasticity was analyzed using M-mode tracing guided by the two-dimensional echocardiography. Statistical analysis was performed using Mann Whitney U, Spearman rho correlation and Fisher's exact tests. RESULTS: Age, sex, body mass index, smoking status and lipids were comparable in patients and controls (p>0.05). None of the subjects had pericarditis and/or pericardial effusion. Aortic wall properties were similar between groups (p>0.05). The TDI parameters of mitral lateral annulus revealed significantly lower Em/Am ratios in patients compared to controls [1.77 (0.6-3.4) vs. 1.79 (0.9-4.8), p=0.02]. Mitral flow propagation velocity was significantly lower in patients than healthy subjects [63 (39-100) vs. 74 (40-94) cm/s, p=0.008]. Tricuspid annular plane systolic excursion (TAPSE) was significantly reduced in FMF group than in controls [2 (1.3-2.5) vs. 2.5 (1.7-3.2) cm; p<0.001]. Eight of the patients and one control had impaired TAPSE (<2 cm; p=0.025). There was no difference regarding right ventricular diastolic dysfunction (RVDD) as assessed by using standard Doppler echocardiography (p>0.05). However, pronounced RVDD was observed in FMF patients documented by TDI (Em/Am<1; 19 patients vs. 0 controls, p<0.001). CONCLUSION: Subclinical myocardial involvement is present in a cohort of relatively young FMF patients who were also free of classical cardiovascular risk factors. Pericardium and aorta seem to be spared during attack free periods of FMF.

Ventricular diastolic function of ankylosing spondylitis patients by using conventional pulsed wave Doppler, myocardial performance index and tissue Doppler imaging.

OBJECTIVE: The aim of this study was to evaluate ventricular functions by using standard Doppler echocardiography (SDE), myocardial performance index (MPI), and pulsed wave tissue Doppler imaging (PW-TDI) in patients with ankylosing spondylitis (AS) and healthy controls. METHODS: Forty-nine AS patients (38 +/- 11 years, 25 M/24 F) and 33 controls (36 +/- 9 years, 17 M/16 F) were studied. Two-dimensional, M-Mode, SDE, PW-TDI echocardiography examinations were performed. Spinal mobility was assessed by the Bath ankylosing spondylitis metrology index (BASMI) measurement. Patients were also evaluated using the Bath ankylosing spondylitis functional index (BASFI) and the Bath ankylosing spondylitis disease activity index (BASDAI). RESULTS: Four control subjects and six AS patients met the left ventricular (LV) diastolic dysfunction (DD) criteria by using conventional Doppler echocardiography (p > 0.05). However, using PW-TDI method 22 patients in the AS group and six subjects in the control group were diagnosed to have LV DD (Em/Am < 1). Pseudonormalized pattern was present in 16 AS patients and two control subjects. Correlation analysis revealed significant moderate negative correlations between Em/Am and BASMI, age and body mass index (p < 0.05; r =-0.3, -0.6, and -0.4, respectively). No correlation was observed between Em/Am and disease duration, BASFI, BASDAI, CRP, and ESR. We could not detect any right ventricular function involvement either by conventional or by recently introduced echocardiography methods. The risk of developing LV DD was found to be 3.7 times higher in AS patients. CONCLUSION: When sensitive echocardiographic Doppler techniques such as MPI, TDI-derived MPI, and PW-TDI are utilized, DD can be detected in a significant proportion of patients with AS without cardiovascular (CV) disease which may contribute CV mortality in these patients.

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.

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.

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.

Percutaneous coronary intervention in a patient with a single right coronary artery: A case report and review of the literature.

The present report discusses a case of successful percutaneous coronary intervention to abnormally originating circumflex and diagonal arteries arising from the right sinus of Valsalva in a patient with a single right coronary artery. The incidence of this rare abnormality, frequency of atherosclerosis and interventional procedures in this group of patients are discussed, and a review the literature is presented.

Effects of carvedilol therapy on arrhythmia markers in patients with congestive heart failure.

The aim of this study was investigate the effects of carvedilol therapy on ventricular repolarization characteristics as assessed by QT dispersion (QTd) and heart rate variability (HRV) in patients with heart failure. Thirty-one patients with heart failure (mean age, 63.9 years) were included in the study. Carvedilol was administered in addition to standard therapy for CHF at a dose of 6.25 mg/day and uptitrated to the maximum tolerated dose. Control group consisted of 14 patients with heart failure (mean age, 69.4 years) who could not take carvedilol due to several reasons. All patients were followed-up 6 months. QT dispersion (QTd), and corrected QTd (QTcd) values were calculated at baseline and at the end of follow-up. Time domain and frequency domain heart rate variability analysis were performed with ambulatory Holter ECG. Mean carvedilol dose was 23.9 +/- 13.9 mg. Significant reductions were observed in the QTd (P = 0.016) and QTcd (P = 0.001) with carvedilol therapy, whereas QTd (P = 0.47) and QTcd (P = 0.43) did not change significantly in the control group. The QT maximum value did not change significantly but the QT minimum value (P = 0.03) was significantly increased after carvedilol therapy. Although the mean SDANN value was improved (P = 0.039), other HRV parameters such as mean SDNN (P = 0.32), rMSSD (P = 0.74), and the LF/HF ratio (P = 0.35) did not change significantly after carvedilol therapy. This prospective controlled study shows that carvedilol therapy decreased QT dispersion and improved ventricular repolarization characteristics but did not change autonomic dysfunction in patients with heart failure.

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.

Influence of carvedilol on serum digoxin levels in heart failure: is there any gender difference?

OBJECTIVE: The activity of the human cytochrome P450 and P-glycoprotein (P-gp) changes according to gender. The present study evaluated the effect of gender on the influence of carvedilol on serum digoxin levels in patients with heart failure. METHODS: Twenty-four patients (12 female and 12 male) with New York Heart Association class II-III heart failure were included in the study. Patients were taking oral digoxin (0.0625-0.25 mg, once a day) and were administered oral carvedilol (6.25 mg, two times daily) for 7 days. RESULTS: In the male group, carvedilol led to statistically significant increases in the area under the concentration time curve to 16 h (AUC(0-16h)) and the peak concentration (C(max)) for digoxin, with no change in time to peak (t(max))(AUC(0-16h)= 24.1+/-9.2 ng.h/ml vs. 15.4+/-5.8 ng.h/ml, p<0.001, C(max)=2.2+/-1.0 ng/ml vs. 1.6+/-0.6 ng/ml, p<0.01, t(max)=2.4+/-2.2 h vs. 2.1+/-1.0 h, p>0.05). In the female group, carvedilol administration did not cause statistically significant change in the AUC(0-16h), C(max), or t(max) for digoxin (p>0.05). In the male group, carvedilol resulted in a significant increase in the AUC(0-16h) and C(max) for digoxin compared with the female group (AUC(0-16h)=24.1+/- 9.2ng.h/ml vs. 17.0+/-6.8 ng.h/ml, C(max)=2.2+/-1.0 ng/ml vs. 1.5+/-0.6 ng/ml, p<0.05, respectively). CONCLUSION: Men seem to have a higher activity relative to women for the drug efflux transporter P-gp. Our results suggest that carvedilol will cause drug interaction with digoxin following the inhibition of P-gp-mediated transcellular transport of digoxin in males.

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.