Comparison of percutaneous device closure versus surgical closure of peri-membranous ventricular septal defects: A systematic review and meta-analysis.

BACKGROUND: While percutaneous device closure (PDC) is a first-line therapy for isolated muscular ventricular septal defects (mVSD), surgery is still the preferred approach for peri-membranous ventricular septal defects (pmVSD). OBJECTIVE: We sought to compare the outcomes of percutaneous versus open surgical closure of pmVSDs. METHODS: PubMed, Cochrane Library, and Web of Science databases were searched through October 15, 2014 for English language studies comparing outcomes of PDC with surgical closure of pmVSDs. Study quality, publication bias, and heterogeneity were assessed. A meta-analysis of selected studies was performed using a random effects model. Comparison was done for early (<1 month) safety and efficacy outcomes. RESULTS: Seven studies with a total of 3,134 patients (PDC = 1,312, surgery = 1,822) were identified. Patients in the PDC group were older than those treated surgically (mean age 12.2 vs. 5.5 years, respectively). In six out of seven studies, the mean VSD size was found to be comparable between the treatment arms (PDC 4.9 mm vs. surgery 6.0 mm). Males represented 52% of patients in either group. Follow-up ranged from 5 to 42 months. No significant differences were observed between PDC vs. surgery in terms of procedural success rate [relative risk (RR): 1.00, confidence interval (CI): 0.99-1.00; P = 0.67]. Combined safety end points for major complications (early death/reoperation/permanent pacemaker) were similar in both groups (RR: 0.55, CI: 0.23-1.35; P = 0.19) as were as other outcomes like post-procedure significant residual shunt (RR: 0.69, CI: 0.29-1.68; P = 0.41), significant valvular (aortic/tricuspid) regurgitation (RR: 0.70, CI: 0.26-1.86; P = 0.47), and advanced heart block (RR: 0.99, CI: 0.46-2.14; P = 0.98). The need for blood transfusion (RR: 0.02, CI: 0.00-0.05; P < 0.001) and duration of hospital stay [standard mean difference (SMD) -2.17 days, CI: -3.12 to -1.23; P < 0.001] were significantly reduced in the PDC group. CONCLUSION: Percutaneous closure of pmVSD when performed in a selected subgroup of patients is associated with similar procedural success rate without increased risk of significant valvular regurgitation or heart block when compared with surgical closure.

Efficacy and safety of transulnar coronary angiography and interventions--a single center experience.

OBJECTIVES: To evaluate the efficacy and long-term safety of transulnar approach in complex coronary interventions. BACKGROUND: The success rate of transulnar approach in complex coronary interventions and its long-term safety remains to be proven. METHODS: We conducted a retrospective chart review of patients undergoing transulnar coronary angiography and interventions at our institution from January 2004 through July 2009. Primary endpoint of the study was the success rate of the procedure. Secondary endpoints were major bleeding, local vascular and neurological complications, cerebrovascular accident (CVA)/transient ischemic attack (TIA), myocardial infarction (MI), all-cause mortality, and major adverse cardiovascular events (MACE) rate that was a composite of MI, CVA/TIA, and all-cause mortality. RESULTS: Of 81 patients undergoing transulnar approach, 41 (50.6%) patients underwent intervention on 65 lesions. Twelve percent of the interventions were performed on coronary bypass grafts and 9.2% on the left main coronary artery. Success rates for transulnar access, coronary angiography, and coronary/bypass graft interventions were 93.8%, 100%, and 92.6%, respectively. Follow-up data was available on 71 patients at short term (30 days) and 58 patients at long term (1 year). At 30-day follow-up, vascular complication rate was 2.8 %. At 1-year follow-up, there were no residual deficits from vascular or neurological complications associated with the index procedure and the overall MACE rate was 3.4%. CONCLUSION: In this first study evaluating long-term safety and feasibility of transulnar coronary angiography and complex coronary interventions, we conclude that transulnar approach appears to be safe and effective.

Development and validation of a risk calculator for prediction of cardiac risk after surgery.

BACKGROUND: Perioperative myocardial infarction or cardiac arrest is associated with significant morbidity and mortality. The Revised Cardiac Risk Index is currently the most commonly used cardiac risk stratification tool; however, it has several limitations, one of which is its relatively low discriminative ability. The objective of the present study was to develop and validate a predictive cardiac risk calculator. METHODS AND RESULTS: Patients who underwent surgery were identified from the American College of Surgeons' 2007 National Surgical Quality Improvement Program database, a multicenter (>250 hospitals) prospective database. Of the 211 410 patients, 1371 (0.65%) developed perioperative myocardial infarction or cardiac arrest. On multivariate logistic regression analysis, 5 predictors of perioperative myocardial infarction or cardiac arrest were identified: type of surgery, dependent functional status, abnormal creatinine, American Society of Anesthesiologists' class, and increasing age. The risk model based on the 2007 data set was subsequently validated on the 2008 data set (n=257 385). The model performance was very similar between the 2007 and 2008 data sets, with C statistics (also known as area under the receiver operating characteristic curve) of 0.884 and 0.874, respectively. Application of the Revised Cardiac Risk Index to the 2008 National Surgical Quality Improvement Program data set yielded a relatively lower C statistic (0.747). The risk model was used to develop an interactive risk calculator. CONCLUSIONS: The cardiac risk calculator provides a risk estimate of perioperative myocardial infarction or cardiac arrest and is anticipated to simplify the informed consent process. Its predictive performance surpasses that of the Revised Cardiac Risk Index.

Circadian, daily, and seasonal distributions of ventricular tachyarrhythmias in patients with implantable cardioverter-defibrillators.

This study investigated the circadian, daily, and seasonal distributions of ventricular arrhythmias in patients with new implantable cardioverter-defibrillator placement at Creighton University Medical Center from January 2000 to December 2004. The incidence and distribution of ventricular tachyarrhythmias as recorded by implantable cardioverter-defibrillators were analyzed with respect to season, month, day of the week, and average daily temperature. Data from 154 consecutive patients (mean age 67 +/- 14 years; 78% men, 71% with ischemic heart disease [IHD], mean left ventricular ejection fraction 34 +/- 15%) were analyzed. During a mean follow-up of 35 +/- 19 months, a total of 1,055 episodes of spontaneously terminated ventricular tachycardia (VT) and 612 episodes of VT or ventricular fibrillation with appropriate device therapy occurred. Distributions in the incidence of VT and VT or ventricular fibrillation receiving appropriate therapy were similar in patients with IHD and non-IHD. Spontaneously terminated VT and appropriately treated VT or ventricular fibrillation episodes occurred with the greatest incidence in the winter months and the lowest incidence in summer, spring, and fall. A linear regression between the number of episodes and the average daily temperature showed a greater likelihood of the 2 events occurring on cooler days, irrespective of the cause of cardiac disease. A weekly distribution was also observed, with the greatest proportion of episodes occurring on Fridays and the lowest on Saturdays and Sundays. A bimodal circadian distribution was present, with the greatest peak occurring from 8 a.m. to 1 p.m. and a smaller peak occurring from 5 p.m. to 10 p.m. In conclusion, the occurrence of ventricular tachyarrhythmias appears to follow circadian, daily, and seasonal distributions that are similar in patients with IHD and non-IHD. The incidence inversely correlates with average daily temperatures.

Intensive smoking cessation intervention reduces mortality in high-risk smokers with cardiovascular disease.

PURPOSES: To compare an intensive smoking cessation intervention against usual care in hospitalized high-risk smokers with acute cardiovascular disease. METHODS: A total of 209 hospitalized smokers were randomized to the intensive intervention (n = 109) or to usual care (n = 100). Usual care consisted only of counseling and printed educational material provided prior to hospital discharge. Intensive treatment consisted of a minimum of 12 weeks of behavior modification counseling and individualized pharmacotherapy provided at no cost to the participant. Smoking status in all subjects was confirmed biochemically (ie, by measuring expired carbon monoxide) at 3, 6, 12, and 24 months after randomization. Outcomes included point prevalence and continuous abstinence smoking cessation rates, hospitalizations, and all-cause mortality. RESULTS: At each follow-up interval, point prevalence and continuous abstinence smoking cessation rates were significantly greater in the intensive-treatment group compared to the usual-care group. At 24 months, continuous abstinence smoking cessation rates were 33% in the intensive-treatment group and 9% in the usual-care group (p < 0.0001). Over the 2-year follow-up period, 41 patients in the usual-care group were hospitalized compared to 25 patients in the intensive-treatment group (relative risk reduction [RRR], 44%; 95% confidence interval [CI], 16 to 63%; p = 0.007). The all-cause mortality rate was 2.8% in the intensive-treatment group and 12.0% in the usual-care group (RRR, 77%; 95% CI, 27 to 93%; p = 0.014). The absolute risk reduction in mortality was 9.2% with a number needed to treat of 11. CONCLUSION: Hospitalized smokers, especially those with cardiovascular disease, should undergo treatment with a structured intensive cessation intervention. The duration of the initial treatment should be 3 months.

Effect of omega-3 fatty acid supplementation on the arachidonic acid:eicosapentaenoic acid ratio.

STUDY OBJECTIVES: To determine the baseline arachidonic acid:eicosapentaenoic acid (AA:EPA) ratio in patients with coronary artery disease and healthy subjects, and whether supplementation of omega-3 fatty acids, administered as fish oil capsules, affects this ratio. DESIGN: Prospective, open-label trial. SETTING: University-affiliated cardiology clinic. SUBJECTS: Thirty patients with stable coronary artery disease (CAD) and 30 healthy subjects. INTERVENTION: All participants received omega-3 fatty acids 1.5 g/day for 4 weeks, followed by 3 g/day for an additional 4 weeks. MEASUREMENTS AND MAIN RESULTS: For each participant, a lipid profile was determined at baseline and after 4 weeks of treatment with each dose. Other laboratory results analyzed were serum AA:EPA ratios, high-sensitivity C-reactive protein (hs-CRP) levels, and blood glucose levels. Mean +/- SD baseline AA:EPA ratios were 39.6 +/- 19.0 in healthy subjects and 23.7 +/- 12.5 in patients with CAD. These ratios decreased significantly in both groups after treatment with 1.5 g/day of omega-3 fatty acids: 9.0 +/- 4.2 in healthy subjects and 10.3 +/- 8.8 in patients with CAD. After treatment with 3 g/day, the ratios were further reduced: 5.1 +/- 3.2 in healthy subjects and 4.9 +/- 2.6 in patients with CAD. Supplementation with omega-3 fatty acids did not significantly affect hs-CRP, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, or blood glucose levels. Triglyceride levels were not reduced in patients with CAD but were significantly decreased in healthy subjects (by 20% decrease with omega-3 fatty acids 1.5 g/day and by 32% decrease with 3 g/day). CONCLUSION: Treatment with omega-3 fatty acids significantly reduced AA:EPA ratios in both healthy subjects and in patients with stable CAD. The treatment had no effect on hs-CRP levels in either group, and it reduced triglyceride levels in healthy subjects but not in patients with CAD.

Meta-analysis: inhibition of renin-angiotensin system prevents new-onset atrial fibrillation.

BACKGROUND: Epidemiologic studies suggest that inhibition of renin-angiotensin system with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may prevent development of atrial fibrillation (AF). OBJECTIVE: The objective of the study was to assess if there is significant indication for using angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in the prevention of new-onset AF and to identify the target patient population. METHODS: PubMed and Cochrane clinical trials database were searched from 1980 through March 2005 together with the review of citations. Nine randomized controlled human trials reporting the prevention of new-onset AF by inhibition of renin-angiotensin system were identified. Information about study design, follow-up, intervention, population, outcomes, and methodology quality was extracted. RESULTS: The mean follow-up of the studies ranged from 6 months to 6.1 year. The pooled estimate using random effects model was 0.82 (95% CI 0.70-0.97) for prevention of new-onset AF and 0.61 (95% CI 0.46-0.83) for primary prevention of AF. The angiotensin-converting enzyme inhibitors (0.75, 95% CI 0.57-0.99) had greater protective effect than angiotensin receptor blockers (0.81, 95% CI 0.62-1.06). Patients with heart failure benefited the most (0.57, 95% CI 0.37-0.89). The test for heterogeneity between studies was significant. There was no consistent visual or statistical evidence of publication bias. CONCLUSION: The use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers had an overall effect of 18% risk reduction in new-onset AF across the trials and 43% risk reduction in patients with heart failure.

Randomized, double-blind, crossover comparison of amlodipine and valsartan in african-americans with hypertension using 24-hour ambulatory blood pressure monitoring.

STUDY OBJECTIVE: To compare the efficacy of amlodipine and valsartan in African-American patients with hypertension using ambulatory blood pressure monitoring (ABPM). DESIGN: Prospective, randomized, double-blind, crossover comparison study. SETTING: University-affiliated cardiac center clinic. PATIENTS: Twenty African-Americans (12 men, 8 women), with a history of uncomplicated hypertension (blood pressure > 140/90 mm Hg). INTERVENTION: Patients were randomized to receive amlodipine 5 or 10 mg/day or valsartan 80 or 160 mg/day for 8-10 weeks, depending on response. Dosages were titrated to achieve a blood pressure of 140/90 mm Hg or below. For patients whose blood pressures were not controlled, hydrochlorothiazide 12.5 mg/day was added to their regimens. Patients then underwent 24-hour ABPM. After an intervening washout period during which baseline blood pressure was reestablished, patients received the other treatment. MEASUREMENTS AND MAIN RESULTS: Mean +/- SD baseline blood pressure before the two ABPM periods were 155 +/- 12/100 +/- 8 mm Hg and 156 +/- 11/101 +/- 9 mm Hg, respectively. Fifteen (75%) patients achieved goal blood pressure with amlodipine and 14 (70%) with valsartan (p=0.62). Final daily dosages were as follows: amlodipine 5 mg in nine patients, 10 mg in five patients, and 10 mg plus hydrochlorothiazide in six patients; valsartan 80 mg in nine patients, 160 mg in four patients, and 160 mg plus hydrochlorothiazide in seven patients. Ambulatory blood pressure monitoring was not completed in three patients due to adverse effects: headache and dizziness (one patient each, amlodipine and valsartan) and hyperkalemia (one patient, valsartan). Four patients (20%) in each treatment group had drug-related adverse effects. Results of ABPM including averages for 24-hour, daytime, nighttime, first 4 hours, and last 8 hours, and trough:peak ratios were not significantly different between the amlodipine- and valsartan-based treatments. CONCLUSION: Based on both clinic blood pressure measurements and ABPM data, amlodipine and valsartan produced similar reductions in blood pressure in African-American patients with uncomplicated hypertension.

Aldosterone inhibition reduces the risk of sudden cardiac death in patients with heart failure.

Sudden cardiac death (SCD) accounts for over 450,000 deaths annually in the USA. Sudden death is estimated to account for approximately 50% of all deaths from cardiovascular causes. Total cardiac mortality has decreased from 728,115 in 1989 to 719,456 in 1999 but the percentage of deaths that are sudden has actually increased from 38% to 47%. Prevention of SCD in patients with risk factors is a high priority for public health professionals. Aldosterone has been shown to be associated with myocardial inflammation, endothelial dysfunction and fibrosis. There is evidence from clinical trials suggesting the role of aldosterone inhibition in prevention of SCD. We reviewed the potential mechanisms and discuss the clinical implications of Randomised ALdactone Evaluation Study (RALES) and Eplerenone Neurohormonal Efficacy and Survival Study (EPHESUS). The use of aldosterone receptor blockers had an overall effect of 21% risk reduction in SCD. Appropriate monitoring and counselling is essential while using either of the aldosterone inhibitors.

Early versus late surgical intervention or medical management for infective endocarditis: a systematic review and meta-analysis.

OBJECTIVE: Infective endocarditis is associated with high morbidity and mortality and optimal timing for surgical intervention is unclear. We performed a systematic review and meta-analysis to compare early surgical intervention with conservative therapy in patients with infective endocarditis. METHODS: PubMed, Cochrane, EMBASE, CINAHL and Google-scholar databases were searched from January 1960 to April 2015. Randomised controlled trials, retrospective cohorts and prospective observational studies comparing outcomes between early surgery at 20 days or less and conservative management for infective endocarditis were analysed. RESULTS: A total of 21 studies were included. OR of all-cause mortality for early surgery was 0.61 (95% CI 0.50 to 0.74, p<0.001) in unmatched groups and 0.41 (95% CI 0.31 to 0.54, p<0.001) in the propensity-matched groups (matched for baseline variables). For patients who had surgical intervention at 7 days or less, OR of all-cause mortality was 0.61 (95% CI 0.39 to 0.96, p=0.034) and in those who had surgical intervention within 8-20 days, the OR of mortality was 0.64 (95% CI 0.48 to 0.86, p=0.003) compared with conservative management. In propensity-matched groups, the OR of mortality in patients with surgical intervention at 7 days or less was 0.30 (95% CI 0.16 to 0.54, p<0.001) and in the subgroup of patients who underwent surgery between 8 and 20 days was 0.51 (95% CI 0.35 to 0.72, p<0.001). There was no significant difference in in-hospital mortality, embolisation, heart failure and recurrence of endocarditis between the overall unmatched cohorts. CONCLUSION: The results of our meta-analysis suggest that early surgical intervention is associated with significantly lower risk of mortality in patients with infective endocarditis.

Prognostic value of the Duke Treadmill Score in diabetic patients.

BACKGROUND: The Duke Treadmill Score (DTS) is an established clinical tool for risk stratification of coronary artery disease. We sought to assess the prognostic value of the DTS in diabetics compared with nondiabetics in this study. METHODS: We studied 100 diabetics and 202 age- and sex-matched nondiabetic controls without known coronary artery disease risk stratified by DTS and followed for a median duration of 6.6 years. The association between DTS and primary, secondary outcomes, composite events, and rate of coronary angiography was tested. RESULTS: Survival free from cardiac death, nonfatal myocardial infarction, congestive heart failure, or early and late revascularization was 89%, 54%, and 13%, respectively, in the low-, intermediate-, and high-risk categories of diabetic group (P < .0001), and 91%, 57%, and 17%, respectively, in the low- to high-risk groups of nondiabetics (P < .0001). During follow-up, diabetics had more secondary events (P = .011) and coronary angiography (P < .001) compared with nondiabetics. The DTS was a strong independent predictor of composite events in both diabetics (P < .001) and nondiabetics (P < .001). A significant number of diabetics were classified as intermediate risk and had a significantly higher incidence of coronary angiography (87.5% vs 70.8%, P = .032) and late revascularizations (35.4% vs 15.3%, P = .011) within this risk group compared with nondiabetics. Survival free from major adverse cardiac events differed significantly across the 3 Duke risk groups for diabetics (P = .002) but not for controls (P = .07). Survival free from composite events differed significantly across the 3 Duke risk groups for both diabetics and nondiabetics (P < .0001). Overall, diabetics had higher rates of major adverse cardiac events, composite events (P = .011), and coronary angiography (P < .001) than nondiabetics. The DTS is a strong predictor of survival free of composite events in both groups by multivariate analysis. CONCLUSIONS: The DTS predicted survival free from MACE and composite events equally well in patients with and without diabetes.

Antiplatelet drug resistance: not ready for prime time.

Antiplatelet drug therapy reduces vascular events in a wide range of patients. Although antiplatelet drug resistance is becoming well documented, a universal definition has not been established. This lack and the lack of standardized measures of platelet function make estimation of the prevalence of antiplatelet drug resistance difficult. Mounting evidence suggests that antiplatelet drug resistance is associated with adverse clinical outcomes, which have been assessed in patients with coronary artery disease, myocardial infarction, cerebrovascular disease, and peripheral vascular disease. Patients with antiplatelet drug resistance have significantly more vascular events than patients without such resistance. However, there are no guidelines for the treatment of antiplatelet drug resistance. Although point-of-care platelet-function testing makes screening for resistance feasible, routine screening should not be standard practice until data regarding the management of antiplatelet drug resistance are available.

Low high-density lipoprotein cholesterol is associated with impaired endothelial function in Asian Indians.

This study was designed to assess the relationship between plasma lipid levels and endothelial function in Asian Indians without cardiovascular risk factors living in the United States. While traditional risk factors do not account for the increased incidence of coronary heart disease (CHD) in Asian Indians, low high-density lipoprotein (HDL) cholesterol, elevated triglycerides, elevated lipoprotein (a), and insulin resistance are consistently found in Asian Indians with CHD. Endothelial function was measured in 86 healthy Asian Indians (mean age 33 years) free of cardiac risk factors with LDL levels<160 mg/dL. Subjects were divided into two groups on the basis of HDL levels (low HDL<40 mg/dL and normal HDL-40 mg/dL). Endothelial function during reactive hyperemia was significantly impaired in Asian Indians in the low HDL group. After covariate adjustment, NTG-induced brachial vasodilation was not different between patients in the two HDL groups. These data indicate that low HDL is associated with endothelial dysfunction in this population.

Probable hydrochlorothiazide-induced myopericarditis: first case reported.

Hydrochlorothiazide has never been reported as a reason for myopericarditis. An African American female, with past history of hypertension, coronary artery disease, and sulfa allergy, presented with indolent onset and retrosternal chest pain which was positional, pleuritic, and unresponsive to sublingual nitroglycerin. Her medications included hydrochlorothiazide (HCTZ) which was started three months ago for uncontrolled hypertension. Significant laboratory parameters included erythrocyte sedimentation rate (ESR) of 47 mm/hr and peak troponin of 0.26 ng/mL. Transthoracic echocardiogram (TTE) revealed preserved ejection fraction with no segmental wall motion abnormalities; however, it showed moderate pericardial effusion without tamponade physiology. We hypothesize that this myopericarditis could be due to HCTZ allergic reaction after all other common etiologies have been ruled out. There is a scarcity of the literature regarding HCTZ as an etiology for pericardial disease, with only one case reported as presumed hydrochlorothiazide-induced pericardial effusion. Management involves discontinuation of HCTZ and starting anti-inflammatory therapy.

Transesophageal echocardiography before cardioversion of recurrent atrial fibrillation: does absence of previous atrial thrombi preclude the need of a repeat test?

BACKGROUND: Atrial fibrillation (AF) is a recurrent problem that frequently requires repeat cardioversion. Transesophageal echocardiography (TEE) is indicated before cardioversion in patients who are underanticoagulated (warfarin therapy <3 weeks or international normalized ratio [INR] <2.0). It remains uncertain if TEE should be repeated in underanticoagulated patients who had no atrial thrombi detected by previous TEE. Methods and results From January 1996 to June 2001, 76 patients (43 men, 33 women; mean age, 68.8 +/- 10.4 years) who were underanticoagulated and had no atrial thrombi in previous TEE underwent repeat TEE before cardioversion of recurrent AF. The duration of recurrent AF at the time of the second TEE was 5.1 +/- 9.3 months (1 day to 4 years). The underlying diseases included coronary artery disease (n = 30), hypertension (n = 22), valvular heart diseases (n = 8), dilated cardiomyopathy (n = 4), hypertrophic cardiomyopathy (n = 2), and others (n = 10). Eight (10.5%) patients (2 men, 6 women; mean age, 68.6 +/- 6.6 years) were found to have intra-atrial thrombi on the second TEE. Of these 8 patients, 3 had coronary artery disease, 1 had hypertension, 2 had dilated cardiomyopathy, 1 had hypertrophic cardiomyopathy, and 1 had AF of unknown cause. The duration of recurrent AF in patients with and without thrombi was not significantly different (3.6 +/- 4.7 versus 5.3 +/- 9.7 months, P =.22). Of the 8 patients with intra-atrial thrombi on the second TEE, 5 had been taking warfarin for 3 to 4 weeks but had subtherapeutic INR and 3 were taking aspirin only. Compared with patients without intra-atrial thrombi, patients with intra-atrial thrombi had lower ejection fraction (32.5% +/- 18.1% versus 49.9% +/- 14.1%, P =.015), slower left atrial appendage empty velocity (0.22 +/- 0.08 versus 0.41 +/- 0.17 m/s, P <.01), and higher prevalence of spontaneous echo contrast (87.5%) than in patients without intra-atrial thrombi (19.1%, P <.05) but similar left atrial size (49.5 +/- 5.3 versus 47.3 +/- 7.1 mm, P =.15). Cardioversion was cancelled in all patients with atrial thrombi. CONCLUSIONS: In underanticoagulated patients, repeat TEE is necessary before cardioversion of recurrent AF even if the previous TEE showed no atrial thrombi.

Acetylcysteine in the prevention of contrast-induced nephropathy after coronary angiography.

BACKGROUND: Contrast-induced nephropathy (CIN) after coronary angiography is associated with increased morbidity and mortality rates. Preliminary studies with N-acetylcysteine (NAC) have found conflicting results in the prevention of CIN in patients undergoing coronary angiography. This study was designed to evaluate the efficacy and safety of NAC in the prevention of CIN in patients undergoing coronary angiography. METHODS: This study was prospective, randomized, double-blind, and placebo-controlled. Patients referred for elective coronary angiography with a baseline creatinine clearance level <50 mL/min and serum creatinine >1.2 mg/dL were randomly assigned to 1500 mg NAC or placebo, starting the evening before angiography and given every 12 hours for 4 doses. The primary study end point was the development of CIN, which was defined as an increase of >0.5 mg/dL or an increase of > or =25% in serum creatinine over baseline within 48 hours of angiography. Secondary end points included changes in serum creatinine and blood urea nitrogen, requirement of dialysis, side effects of study medication, hospital length of stay, and hospital charges. RESULTS: CIN occurred in 8.2% (4/49) of patients taking NAC and 6.4% (3/47) of patients taking placebo. Changes in BUN and serum creatinine from baseline were not significantly different in the two treatment groups. Baseline BUN and volume of contrast were the only independent predictors of CIN. More patients with diabetes had development of CIN (5/43; 12%) compared with nondiabetic patients (2/52; 4%), but the difference was not significant (P =.15). The incidence of CIN in diabetic patients was not different in the two treatment groups. No patient with development of CIN required dialysis. Side effects (mostly gastrointestinal) occurred in 16% of patients taking NAC and in none of the patients taking placebo. Length of stay and hospital charges were not different between the treatment groups. CONCLUSIONS: In patients with reduced renal function undergoing elective coronary angiography, NAC does not reduce the risk of CIN.

Amiodarone versus sotalol for the treatment of atrial fibrillation after open heart surgery: the Reduction in Postoperative Cardiovascular Arrhythmic Events (REDUCE) trial.

OBJECTIVES: This prospective, randomized, double-blind, placebo-controlled study compared the efficacy and safety of amiodarone and sotalol in the prevention of atrial fibrillation (AF) following open heart surgery. BACKGROUND: The incidence of supraventricular arrhythmias following open heart surgery ranges from 20% to 40%, with AF being the most common. Both amiodarone and sotalol have been shown to be effective in reducing postoperative arrhythmias, but no direct comparison of these agents has been conducted. METHODS: A total of 160 patients were randomized, of whom 134 underwent coronary artery bypass graft surgery (CABG) alone, 17 underwent CABG and concomitant aortic valve replacement surgery (AVR), 9 underwent AVR only, and 1 patient's surgery was canceled. Patients with signs or symptoms of congestive heart failure (CHF), ejection fraction < or =30%, estimated creatinine clearance <30 mL/min, or serum creatinine > or =2.5 mg/dL were excluded. Patients were randomized to receive either sotalol 80 mg 2 times per day (n = 76) or intravenous amiodarone 15 mg/kg over 24 hours followed by oral amiodarone 200 mg 3 times per day (n = 83). Study drug was started at the time of surgery and continued for 7 days or until discharge, whichever came first. RESULTS: AF occurred in 17% of patients randomized to amiodarone and 25% of the patients randomized to sotalol (P =.21). However, the duration of AF was significantly shorter in amiodarone-treated patients (169 +/- 224 min) compared to sotalol treated patients (487 +/- 505 min; P =.04). In a subgroup analysis, the incidence of AF in patients undergoing AVR or CABG with AVR was significantly less with amiodarone (1/15, 7%) compared to sotalol (9/11, 82%) (P <.001). Blood pressure was lower immediately after surgery with amiodarone but comparable to sotalol at 24 hours. Of the hemodynamic indices measured, only stroke volume was significantly lower in patients randomized to sotalol at 24 hours (P =.035). CONCLUSIONS: Amiodarone and sotalol share similar efficacy and safety in reducing postoperative AF. Hemodynamic effects were similar between both drugs at 24 hours, with the exception that stroke volume was lower in sotalol-treated patients. In patients undergoing more complex surgery, postoperative AF occurred more frequently with sotalol than with amiodarone.

Amiodarone vs. sotalol as prophylaxis against atrial fibrillation/flutter after heart surgery: a meta-analysis.

BACKGROUND: The incidence of supraventricular arrhythmias remains high following open-heart surgery. The most common of these arrhythmias are atrial fibrillation and flutter (AFF), for which treatment is not well defined. Recent studies have focused on prophylactically treating patients in an attempt to reduce postoperative AFF. Several studies have shown that sotalol and amiodarone are both effective in reducing AFF following heart surgery. However, no studies have been done comparing both drugs. METHODS: A meta-analysis was done to compare the efficacy of sotalol and amiodarone after bypass graft surgery. Randomized controlled trials were included if patients were clearly monitored, and the incidence of AFF was noted. Ten studies were included in the final analysis. RESULTS: Both amiodarone and sotalol were more effective than placebo treatment in reducing the incidence of postoperative AFF. However, when the data were pooled, no differences were noted between amiodarone and sotalol for efficacy (sotalol, - 21.5%; 95% confidence interval [CI], - 28.3 to - 14.6; amiodarone, - 14.1%; CI, - 20.1 to - 8.1), length of stay (sotalol, - 0.13 d; CI, - 0.33 to 0.07 d; amiodarone, - 0.18; CI, - 0.38 to 0.02 d), or adverse drug reactions causing drug termination (sotalol, 9.7%; CI, 0.086 to 19.3; amiodarone, 1.95%; CI, - 0.48 to 4.38). CONCLUSIONS: This data would suggest that either drug could be used in a prophylactic regimen to reduce the incidence of AFF following heart surgery.

Esmolol versus diltiazem in atrial fibrillation following coronary artery bypass graft surgery.

PURPOSE: Atrial fibrillation (AF) is the most common arrhythmic complication following coronary artery bypass graft surgery (CABG). The efficacy and safety of esmolol and diltiazem were compared in patients with post-CABG AF. METHODS: This study was a retrospective medical record review of consecutive patients with post-CABG AF > or =15 min in duration with a ventricular rate > or =110 b.p.m. who received either i.v. esmolol (n = 59) or i.v. diltiazem (n = 48) with or without concomitant digoxin therapy at a single university-affiliated teaching hospital. Treatment success was defined as either cardioversion to sinus rhythm or a reduction in the ventricular rate to < or =90 b.p.m. at 24 h after the start of therapy. Time to treatment success and the occurrence of adverse effects were considered secondary outcomes. RESULTS: A total of 107 patients with post-CABG AF were treated with i.v. esmolol (n = 59) or i.v. diltiazem (n = 48). The mean maximum dose of esmolol and diltiazem were 115 +/- 38 microg/kg/min and 11.2 +/- 3.5 mg/h, respectively. The average duration of the esmolol and diltiazem infusions were 19.3 +/- 8.5 h and 20.1 +/- 11.3 h, respectively. Based on the combined efficacy endpoint of cardioversion or ventricular rate control, esmolol was significantly more effective than diltiazem (90% vs 77%; p = 0.038). Time to treatment success was significantly better for esmolol than diltiazem at all time points (1, 2, 4, 6, 12, and 24 h post-treatment). The overall incidence of adverse effects was 44% with esmolol and 60% with diltiazem (p = 0.04). Rates of drug discontinuance for adverse effects were significantly less for esmolol (20%) compared with diltiazem (38%) (p = 0.04). CONCLUSIONS: Esmolol is significantly more effective than diltiazem in the management of post-CABG AF. More patients converted to sinus rhythm with esmolol as compared to diltiazem. Esmolol was associated with fewer adverse effects than diltiazem, including adverse effects leading to drug discontinuance. Due to study design limitations (retrospective data collection), an adequately powered randomised, controlled trial is needed to confirm these preliminary findings.

Impact of Grapefruit Juice on the Antiplatelet Activity of Loading and Maintenance Doses of Clopidogrel in Healthy Volunteers.

BACKGROUND: Grapefruit juice impacts the metabolism of a number of drugs via inhibition of a variety of metabolic enzymes. This study evaluated the impact of grapefruit juice on the antiplatelet activity of a loading dose and 7 days of maintenance therapy with clopidogrel. METHODS: Healthy volunteers participated in two separate treatment protocols. The first protocol included a single 300 mg loading dose of clopidogrel and the second protocol included maintenance therapy with clopidogrel 75 mg given for 7 consecutive days. In both protocols, subjects were randomized to take clopidogrel with grapefruit juice or with tap water. At 6 h after the loading dose and at 6 h after the last maintenance dose of clopidogrel, a P2Y12 reaction unit (PRU) value using the VerifyNow® P2Y12 assay was determined. A PRU value > 235 was defined as high on-treatment platelet reactivity (defined as clopidogrel hyporesponse). RESULTS: Fourteen subjects completed the loading dose protocol while 17 subjects completed the maintenance dose protocol. Following administration of the loading dose, the mean PRUs with grapefruit juice and tap water were 235.2 (95% confidence interval (CI): 210.4-260.0) and 177.4 (95% CI: 141.6-213.2), respectively (P = 0.001). Following administration of the loading dose, the numbers of subjects with a PRU > 235 with grapefruit juice and tap water were 9 (64%) and 3 (21%), respectively (P = 0.05). In the maintenance dose protocol, the mean PRUs with grapefruit juice and tap water were 212.4 (95% CI: 175.8-249.0) and 186.1 (95% CI: 149.6-222.7), respectively (P = 0.059). In the maintenance dose protocol, the proportions of patients with a PRU > 235 with grapefruit juice and tap water were 9 (53%) and 4 (23%), respectively (P = 0.16). DISCUSSION: Compared to tap water, grapefruit juice significantly increased the mean PRU in patients following a 300 mg loading dose of clopidogrel. The increase in mean PRU after 7 days of a 75 mg/day maintenance dose of clopidogrel was also increased by grapefruit juice, but the magnitude of the increase was not statistically significant. The proportion of subjects with high on-treatment platelet reactivity with clopidogrel after ingestion with grapefruit juice was not significant during either the loading or maintenance dose. The results of our study are insufficient to reach a valid conclusion concerning an interaction between clopidogrel and grapefruit juice.