Continuous electrocardiography for detecting atrial fibrillation beyond 1 year after stroke in primary care.

BACKGROUND AND PURPOSE: The diagnostic benefit of using continuous ECG (cECG) for poststroke atrial fibrillation (AF) screening in a primary care setting is unclear. We aimed to assess the diagnostic yield from screening patients who previously had a stroke with a 7-day Holter monitor. METHODS: Patients older than 49 years, naive to AF, with an ischaemic stroke over 1 year before enrolment were included. In a primary care setting, all patients were screened for AF using pulse palpation, 12-lead ECG and 7-day Holter monitoring. Further, NT-proBNP was determined at baseline. RESULTS: 7-day Holter monitoring uncovered AF in 17 of 366 patients (4.6% (95% CI 2.7 to 7.3)). The number needed to screen was 22 patients (14-37). 12-lead ECG uncovered AF in 3 patients (0.82% (95% CI 0.17 to 2.4)), and 122 patients had irregular pulse during pulse palpation (33.5% (95% CI 28.7 to 38.2)). When using 7-day Holter monitoring as reference standard, the sensitivity of pulse palpation and 12-lead ECG was 47% (95% CI 23% to 72%) and 18% (95% CI 4% to 43%). High levels (≥400 pg/mL) of NT-proBNP versus low levels (≤200 pg/mL) were not associated with AF in the univariate analysis nor when adjusted for age (OR 2.4 (95% CI 0.5 to 8.4) and 1.6 (95% CI 0.3 to 6.0)). CONCLUSIONS: A relevant proportion of patients with stroke more than 1 year before inclusion were diagnosed with AF through 7-day Holter monitoring. Given the low sensitivities of pulse palpation and 12-lead ECG, additional cECG may be considered during poststroke primary care follow-up.

The weight lowering effect of sibutramine and its impact on serum lipids in cardiovascular high risk patients with and without type 2 diabetes mellitus - an analysis from the SCOUT lead-in period.

BACKGROUND: Obesity, type 2 diabetes mellitus (T2D) and unhealthy blood lipid profile are strongly associated with the risk of developing cardiovascular disease (CVD). We examined whether blood lipid changes with short term administration of the weight lowering drug, sibutramine and lifestyle modification in obese and overweight high-risk patients was associated with T2D status at screening. METHODS: The Sibutramine Cardiovascular OUTcomes (SCOUT) trial included obese and overweight patients at increased risk of cardiovascular events. All patients received guidance on diet and exercise plus once-daily 10 mg sibutramine during the 6-week, single blind lead-in period. Multivariable regression models were used to investigate factors associated with changes in lipid levels during the first four weeks of treatment. RESULTS: A total of 10 742 patients received at least one dose of sibutramine during the 6-week lead-in period of SCOUT. After four weeks, patients experienced mean reductions in low density lipoprotein (LDL-C) 0.19 mmol/L, high density lipoprotein (HDL-C) 0.019 mmol/L, very low density lipoprotein (VLDL-C) 0.08 mmol/L, total cholesterol (TC) 0.31 mmol/L and triglycerides 0.24 mmol/L (p < 0.0001 for each). Four week changes in LDL-C, HDL-C and total cholesterol for patients without vs. with T2D were: LDL-C:-0.25 mmol/L vs. -0.18 mmol/L, P = 0.0004; HDL-C: -0.03 mmol/L vs. -0.02 mmol/L, P = 0.0014; total cholesterol: -0.37 mmol/l vs. -0.29 mmol/l, P = 0.0009. Multivariable regression analysis showed that similar decreases in body mass index (BMI) affected lipid changes differently according to diabetes status. A 1 kg/m2 decrease in BMI in patients with T2D was associated with -0.09 mmol/L in LDL-C (P < 0.0001) and -0.01 mmol/L in HDL-C (P = 0.0001) but larger changes of -0.16 mmol/L LDL-C and -0.03 mmol/L in HDL-C (P < 0.0001 for both) in patients without T2D. CONCLUSION: Short term weight management with sibutramine therapy in obese or overweight high-risk patients induced significant mean reductions for all lipids. Those without T2D benefited most. Patients with hyperlipidaemia and the less obese patients also had greater falls in LDL-C and TC during weight loss. The trial is registered at ClinicalTrial.gov number: NCT00234832.

Prognostic importance of change in QRS duration over time associated with left ventricular dysfunction in patients with congestive heart failure: the DIAMOND study.

BACKGROUND: The prognostic importance reported for QRS duration in patients with heart failure (HF) and left ventricular dysfunction varies. No prior study has investigated the prognostic importance of change in QRS duration over time. METHODS AND RESULTS: The Danish Investigations and Arrhythmia ON Dofetilide (DIAMOND) study randomized 1518 patients with HF to dofetilide (class III antiarrhythmic drug) or placebo. All patients had left ventricular dysfunction. QRS duration was systematically measured at randomization and every 3 months after that. During 10 years of follow-up, 1324 (89%) of the patients died. QRS duration increased from baseline by 1.36 ms (95% confidence interval [CI]: -0.26 to -2.98; P = .1) after 12 months and by 3.65 ms (CI: 0.22-7.07; P = .04) after 24 months. QRS duration measured at baseline was not of prognostic significance after multivariable adjustment (adjusted hazard ratio [HR] 1.01, CI: 0.99-1.04; P = .2 per 10-ms increment in QRS duration). The adjusted relative risk associated with a 10-ms increase in QRS duration over time was 2% (HR 1.02, CI: 1.01-1.04; P = .03). A 10-ms increment in QRS 12 months after randomization was associated with a HR of 1.05 (CI: 1.00-1.09; P = .03). CONCLUSIONS: In patients with left ventricular dysfunction and HF, QRS duration increased over time and the increase was associated with increasing mortality.

Risk factors and predictors of Torsade de pointes ventricular tachycardia in patients with left ventricular systolic dysfunction receiving Dofetilide.

The purpose of this study was to identify risk factors of Torsade de pointes (TdP) ventricular tachycardia in patients medicated with a class III antiarrhythmic drug (dofetilide) and left ventricular systolic dysfunction with heart failure (HF) or recent myocardial infarction (MI). The 2 Danish Investigations of Arrhythmia and Mortality on Dofetilide (DIAMOND) studies enrolled patients with HF (DIAMOND-HF) or MI (DIAMOND-MI) and left ventricular systolic dysfunction. The present analysis includes only patients treated solely with dofetilide. The incidence of TdP was 2.1% (32 of 1,511). Twenty-five of the incidences occurred in the DIAMOND-HF study and 7 cases in the DIAMOND-MI study (p = 0.0015). TdP was more frequent in women than in men (47% vs 28%, p = 0.02). Risk factors for developing TdP were female gender (odds ratio 2.2, 95% confidence interval [CI] 1.0 to 5.0), MI within 8 weeks (odds ratio 0.3, 95% CI 0.1 to 0.7), being in New York Heart Association class III or IV (odds ratio 3.2, 95% CI 1.2 to 8.6), and baseline QTc duration (odds ratio 1.14, 95% CI 1.00 to 1.30) per 10 ms. Women with chronic HF, QTc duration >400 ms. and New York Heart Association class III or IV had a risk of TdP of 10%, whereas no TdP episodes were observed in patients with QTc duration <400 ms. In conclusion, severity of HF, female gender, and QTc duration make it possible to identify patients with a high risk of early TdP when treated with dofetilide. Patients with recent MI less often had TdP compared with patients with chronic HF.

Differential prognostic importance of QRS duration in heart failure and acute myocardial infarction associated with left ventricular dysfunction.

BACKGROUND/AIMS: Studies of the prognostic importance of QRS duration in patients with heart failure (HF) have shown conflicting results and few studies have estimated the importance after myocardial infarction (MI). METHODS: The Danish Investigations and Arrhythmia ON Dofetilide (DIAMOND) study randomised 3028 patients to dofetilide (class III antiarrhythmic) or placebo. The study consisted of two almost identical trials conducted simultaneously. One trial included 1518 patients with chronic HF and the other trial 1510 patients with a recent MI. All patients had left ventricular dysfunction. Dofetilide did not influence mortality in either trial. QRS duration was systematically measured at randomisation and was available in 2972 patients. RESULTS: Over a 10 year observation period 1037 (70%) patients in the MI study and 1324 (87%) in the HF study died. In the MI study, risk of death increased 6% for each 10 ms increase in QRS duration (HR=1.06/10 ms increase in QRS (CI=1.04-1.09), p<0.0001) whereas QRS duration had no influence in the HF study after multivariable adjustment. The difference between HF and MI was significant (p<0.0004 for interaction). CONCLUSION: QRS duration predicts death in patients with left ventricular dysfunction who have suffered MI. In patients with HF QRS duration is not predictive of mortality.

Influence of diabetes and diabetes-gender interaction on the risk of death in patients hospitalized with congestive heart failure.

OBJECTIVES: The purpose of this study was to investigate the influence of diabetes on long-term mortality in a large cohort of patients hospitalized with heart failure (HF). BACKGROUND: Diabetes is common in HF patients, but information on the prognostic effect of diabetes is sparse. METHODS: The study is an analysis of survival data comprising 5,491 patients consecutively hospitalized with new or worsening HF and screened for entry into the Danish Investigations of Arrhythmia and Mortality on Dofetilide (DIAMOND). Screening, which included obtaining an echocardiogram in 95% of the patients, took place at Danish hospitals between 1993 and 1995. The follow-up time was five to eight years. RESULTS: A history of diabetes was found in 900 patients (16%), 41% of whom were female. Among the diabetic patients, 755 (84%) died during follow-up, compared with 3,200 (70%) among the non-diabetic patients, resulting in a risk ratio (RR) of death in diabetic patients of 1.5 (95% confidence interval [CI] 1.4 to 1.6, p < 0.0001). In a multivariate analysis, the RR of death in diabetic patients was 1.5 (CI 1.3 to 1.76, p < 0.0001), but a significant interaction between diabetes and gender was found. Diabetes increased the mortality risk more in women than in men, with the RR for diabetic men being 1.4 (95% CI 1.3 to 1.6, p < 0.0001) and 1.7 for diabetic women (95% CI 1.4 to 1.9, p < 0.0001). The effect of diabetes on mortality was similar in patients with depressed and normal left ventricular systolic function. CONCLUSIONS: Diabetes is a potent, independent risk factor for mortality in patients hospitalized with HF. The excess risk in diabetic patients appears to be particularly prominent in females.

Effect of dofetilide on QT dispersion and the prognostic implications of changes in QT dispersion for patients with congestive heart failure.

AIMS: Drug-induced changes in QT dispersion may be a way of detecting harmful repolarisation abnormalities for patients receiving antiarrhythmic drugs affecting ventricular repolarisation. METHODS AND RESULTS: In 463 congestive heart failure (CHF) patients enrolled in the Danish Investigations Of Arrhythmia and Mortality On Dofetilide-CHF (DIAMOND-CHF) study, both pre-treatment and on-treatment day 2-6 QT dispersion was available from standard 12-lead ECGs. Patients were randomised in a double-blind manner to receive either placebo or dofetilide, a new class III antiarrhythmic drug. During a median follow-up of 19 months (minimum 1 year), 179 patients (39%) died (135 patients from cardiac causes). Changes in QT dispersion did not predict all-cause or cardiac mortality for patients treated with dofetilide in multivariate survival analysis (Risk ratio: 1.02, 95% confidence interval: 0.97-1.08, P>0.4). This finding was independent of pre-treatment QT dispersion. Dofetilide caused a small QT dispersion increment of 8 ms, not different from the changes seen in the placebo group (3 ms). CONCLUSION: For patients with CHF and reduced left ventricular systolic function, changes in QT dispersion following treatment with dofetilide do not predict all-cause or cardiac mortality. The dofetilide-induced QT dispersion changes are small and comparable to those seen in placebo treated patients.

Congestive heart failure with preserved left ventricular systolic function after acute myocardial infarction: clinical and prognostic implications.

AIMS: To characterise the prevalence, in-hospital complications, management, and long-term outcome of patients with congestive heart failure but preserved left ventricular systolic function after acute myocardial infarction. METHODS: 3166 consecutive patients screened for entry in the Bucindolol Evaluation in Acute Myocardial Infarction Trial with definite acute myocardial infarction and echocardiographic assessment of left ventricular systolic function were included between 1998 and 1999 in this prospective observational study. Main outcome measures were occurrences of in-hospital complications and all cause mortality. RESULTS: Congestive heart failure was seen during hospitalisation in 1464 patients (46%), 717 patients had preserved left ventricular systolic function (wall motion index > or =1.3 corresponding to ejection fraction > or =0.40), and 732 patients had systolic dysfunction (wall motion index <1.3). One year mortality in patients with no heart failure, heart failure with preserved systolic function, and heart failure with systolic dysfunction were 6, 22 and 35%, P<0.0001. Unadjusted risk of death from all causes associated with heart failure and preserved systolic function was 3.3 (95% CI 2.8-4.0), and after adjustment for baseline characteristics and left ventricular systolic function in multivariate Cox proportional hazards analysis the risk was 2.1 (95% CI 1.7-2.6), P<0.0001. CONCLUSIONS: Congestive heart failure is frequently present in patients with preserved left ventricular systolic function, and is associated with increased risk of in-hospital complications and death following acute myocardial infarction.

The incomplete bucindolol evaluation in acute myocardial infarction Trial (BEAT).

UNLABELLED: The aim of this study was to evaluate the efficacy of adding the beta-blocker bucindolol to standard therapy shortly after a myocardial infarction in a high-risk population with reduced left ventricular function. METHODS: The study was planned to include 2000 patients with an enzyme confirmed myocardial infarction and severely reduced left ventricular function determined by echocardiography (corresponding to ejection fraction < or =0.35). The primary endpoint was all cause mortality and the secondary endpoints were time to first event of death, progression of heart failure or reinfarction-and the components. The study was closed early due to discontinuation of development of bucindolol by the manufacturer. Therefore, 170 patients were randomised to receive bucindolol and 173 to receive placebo. RESULTS: There were 27 deaths in the bucindolol group and 30 in the placebo group, hazard ratio of bucindolol 0.88 (95% confidence limits 0.5-1.5; P=0.6). There were 9/4 (bucindolol/placebo, P=0.16) heart failure events and 5/17 (P=0.01) reinfarctions in the bucindolol/placebo groups. CONCLUSION: Due to early closure it is unknown whether bucindolol changes mortality in high-risk post myocardial infarct patients when added to best medical therapy. The frequency of reinfarction was significantly reduced.

A benefit-risk assessment of class III antiarrhythmic agents.

With beta-blockers as the exception, increasing doubt is emerging on the value of antiarrhythmic drug therapy following a series of trials that have either shown no mortality benefit or even an excess mortality. Vaughan Williams class I drugs are generally avoided in patients with structural heart disease, and class IV drugs are avoided in heart failure. Unfortunately, arrhythmias are a growing problem due to an increase in the incidence of atrial fibrillation and sudden death. The population is becoming older and more patients survive for a longer time period with congestive heart failure, which again increases the frequency of both supraventricular as well as ventricular arrhythmias. Class III antiarrhythmic drugs act by blocking repolarising currents and thereby prolong the effective refractory period of the myocardium. This is believed to facilitate termination of re-entry tachyarrhythmias. This class of drugs is developed for treatment of both supraventricular and ventricular arrhythmias. Amiodarone, sotalol, dofetilide, and ibutilide are examples of class III drugs that are currently available. Amiodarone and sotalol have other antiarrhythmic properties in addition to pure class III action, which differentiates them from the others. However, all have potential serious adverse events. Proarrhythmia, especially torsade de pointes, is a common problem making the benefit-risk ratio of these drugs a key question. Class III drugs have been evaluated in different settings: primary and secondary prevention of ventricular arrhythmias and in treatment of atrial fibrillation or flutter. Based on existing evidence there is no routine indication for antiarrhythmic drug therapy other than beta-blockers in patients at high risk of sudden death. Subgroup analyses of trials with amiodarone and dofetilide suggest that patients with atrial fibrillation may have a mortality reduction with these drugs. However, this needs to be tested in a prospective trial. Similarly, subgroups that will benefit from prophylactic treatment with class III antiarrhythmic drugs may be found based on QT-intervals or - in the future - from genetic testing. Class III drugs are effective in converting atrial fibrillation to sinus rhythm and for the maintenance of sinus rhythm after conversion. This is currently by far the most important indication for this class of drugs. As defined by recent guidelines, amiodarone and dofetilide have their place as second-line therapy except for patients with heart failure where they are first line therapy being the only drugs where the safety has been documented for this group of high risk patients.

The immediate future for the medical treatment of atrial fibrillation.

Atrial fibrillation is the most commonly sustained cardiac arrhythmia and a common reason for mortality and morbidity. Atrial fibrillation causes disease for three reasons: i) the ventricular rate is often high, which leads to symptoms ranging from discomfort to life threatening heart failure; ii) the rhythm causes loss of atrioventricular synchrony, which reduces diastolic filling and may lead to heart failure; and iii) atrial contraction is lost leading to stagnant blood that again may lead to atrial thrombi and peripheral embolism. Thus, the treatment of atrial fibrillation is focused on the maintenance of sinus rhythm, rate control and prevention of embolism. For the maintenance of sinus rhythm, all drugs under current development are potassium channel blockers; the so-called class III anti-arrhythmic drugs. Those which have been further investigated appear to be valuable for maintenance of sinus rhythm but all carry a significant risk of pro-arrhythmia, in particular Torsade de Pointe ventricular tachycardia. Rate control has been a focus of treatment for many years and several very old drugs, including digoxin, are used for this. There is, to the author's knowledge, no current effort for evaluating new drugs for this indication. Prevention of embolism has for many years been obtained with vitamin K antagonists for which the clinical evidence is overwhelming. Previous attempts to replace vitamin K antagonists with aspirin have not been fruitful. A large number of newer anticoagulation regimes are in development, but to the author's knowledge only a single thrombin inhibitor is actively being developed for atrial fibrillation.

Prevalence, prognostic significance, and treatment of atrial fibrillation in congestive heart failure with particular reference to the DIAMOND-CHF study.

Atrial fibrillation is a growing health problem and the most common cardiac arrhythmia, affecting 5% of persons above the age of 65 years. The number of hospital discharges for atrial fibrillation has more than doubled in the past decade. It occurs very often in patients with congestive heart failure and the prevalence increases with the severity of the disease. These two conditions seem to be linked together, and congestive heart failure may either be the cause or the consequence of atrial fibrillation. The prognosis of atrial fibrillation is controversial, but studies indicate that atrial fibrillation is a risk factor in congestive heart failure patients. In the last 10-15 years, significant advances in the treatment of heart failure have improved survival, whereas effective management of atrial fibrillation in heart failure patients still awaits similar progress. Empirically, two strategies have evolved for treatment of atrial fibrillation: 1) rhythm control, which means conversion to sinus rhythm and maintenance of sinus rhythm; and 2) rate control, which means reduction of heart rate to an acceptable frequency. It is unknown whether one of these strategies is better than the other. In this review the authors discuss the prevalence, impact, and treatment of atrial fibrillation in heart failure patients.

Can antiarrhythmic drugs save lives in patients with congestive heart failure?

Although arrhythmic death is a common cause of death in patients with congestive heart failure (CHF), numerous trials involving prophylactic antiarrhythmic drug treatment have yielded few gains. To date, only beta-blockers have shown a distinct mortality-reducing effect and despite the antiarrythmic effect of gamma-blockers, results point towards causes other than the antiarrhythmic effect in obtaining this beneficial effect. Atrial fibrillation is an often-encountered arrhythmia in patients with CHF and recent trials have cast doubt on the present treatment strategy of persistently striving to obtain sinus rhythm. This paper outlines the results of the large clinical trials dealing with antiarrhythmic drug treatment in CHF patients with or without atrial fibrillation and certain subgroup analysis and future treatment possibilities are discussed.

Dofetilide: a new drug to control cardiac arrhythmia.

Atrial fibrillation (AF) is the most common cardiac arrhythmia. Mortality, and especially morbidity caused by AF, are major and growing health problems in the western world. AF is strongly associated with arterial hypertension, congestive heart failure, valvular heart disease, ischaemic heart disease, and with prevalence increasing with age. A variety of drugs have been used to terminate or prevent AF but, as many antiarrhythmic agents have the potential life-threatening pro-arrhythmia, safety problems remain. Dofetilide (Tikosyn, Pfizer), a new Vaughan Williams class III antiarrhythmic agent, has been developed and approved for the treatment of AF. In contrast to most antiarrhythmic agents, the development programme included two safety studies in high-risk patients. Dofetilide is effective and safe when an elaborate procedure for dosing is implemented. Along with amiodarone and betablockers, dofetilide is the only antiarrhythmic drug, which is recommended by guidelines for the treatment of AF in a wide range of patients.

The prognostic value of QTc interval and QT dispersion following myocardial infarction in patients treated with or without dofetilide.

BACKGROUND: Acute myocardial infarction (MI) is associated with an increased risk of death, with a 1-year mortality close to 10% in patients discharged from hospital alive. During the first year following MI, close to 50% of deaths are assumed to be due to arrhythmic events. HYPOTHESIS: The study was undertaken to determine the interaction between dofetilide treatment and pretreatment QTc interval and QT dispersion regarding mortality in patients with left ventricular (LV) dysfunction and a recent MI. METHODS: The study population consisted of 894 patients with a recent MI and LV systolic dysfunction, who were randomized to receive dofetilide or placebo. The study was a substudy of the Danish Investigations of Arrhythmia and Mortality on Dofetilide-MI (DIAMOND-MI). RESULTS: During a minimum of 1-year follow-up, 261 (29%) patients died. Baseline QTc interval did not hold any prognostic value on mortality for placebo-treated patients. When pretreatment QTc interval was <429 ms, dofetilide resulted in a 45% reduction of mortality (hazard ratio 0.55, 95% confidence limits 0.34-0.88, p<0.02) compared with placebo. When QTc interval was >429 ms, dofetilide did not influence mortality significantly. This study revealed no statistically significant relation between QT dispersion, dofetilide treatment, and mortality. CONCLUSION: In patients with a recent MI, LV dysfunction, and a short baseline QTc interval, dofetilide is associated with significant survival benefit. This benefit is not seen with a longer QTc interval. QT dispersion is not a risk factor in this population.

Importance of a history of hypertension for the prognosis after acute myocardial infarction--for the Bucindolol Evaluation in Acute myocardial infarction Trial (BEAT) study group.

BACKGROUND: Arterial hypertension is a major risk factor for cardiovascular events. The prognosis for hypertensive patients after acute myocardial infarction (MI) is uncertain because of the sparse and somewhat contradictionary data. HYPOTHESIS: Our study aimed to investigate the importance of hypertension to prognosis after an MI in patients receiving contemporary medical therapy. METHODS: We performed a retrospective study using a large register from the Bucindolol Evaluation in Acute myocardial infarction Trial (BEAT). The register comprised 3,326 patients admitted between June 1998 and August 1999 with an enzyme-verified MI to 33 Danish coronary care units. Hypertension was considered present when a previous diagnosis of hypertension was accompanied by relevant medical therapy. Survival information for all patients was obtained in January 2002. RESULTS: Of the 3,326 patients studied, 825 were hypertensive. Overall, 28.4% had died by January 2002. The unadjusted hazard ratio associated with hypertension was 1.2 (95% confidence limit [CI] 1.1-1.4, p = 0.004). Hypertensive patients were older, and after adjustment for age the hazard ratio associated with hypertension was 1.04 (CI 0.9-1.2, p = 0.6). Adjustment for further covariates did not change the result. CONCLUSION: Our study showed that after an acute MI the survival rate of patients with and without a history of hypertension was identical when they received contemporary medical therapy.

Long-term prognostic importance of resting heart rate in patients with left ventricular dysfunction in connection with either heart failure or myocardial infarction: the DIAMOND study.

BACKGROUND: Elevated resting heart rate is associated with increased mortality in a variety of cardiac diseases, but comparisons between different clinical settings are lacking. We investigated the long-term prognostic importance of resting heart rate in patients hospitalized with left ventricular dysfunction in connection with either heart failure (HF) or myocardial infarction (MI). METHODS: In the Danish Investigations and Arrhythmia ON Dofetilide (DIAMOND) study; patients with left ventricular dysfunction were randomized to Dofetilide (class III antiarrhythmic drug) or placebo. One part of the study enrolled 1518 patients with HF and another 1510 patients with MI. Mortality analyses were performed using multivariable adjusted Cox proportional hazard models. RESULTS: During 10 years of follow-up, 1076 (72%) patients with MI and 1336 (89%) patients with HF died. In multivariable adjusted models, every increment in baseline heart rate of 10 bpm was associated with an increase in mortality in both MI-patients (hazard ratio, 1.14; 95%-confidence interval (CI): 1.09-1.19; P<.0001) and HF-patients (hazard ratio, 1.10; CI: 1.06-1.15; P<.0001). The importance of resting heart rate on short-term prognosis was stronger in the MI patients compared to the HF patients (P<.0001 for interaction). There was no interaction between heart rate and beta-blockade, and inclusion of beta-blockade in the model did not change the results. CONCLUSIONS: Resting heart rate was independently associated with increased risk of overall mortality. The prognostic importance of resting heart rate is stronger in patients with MI compared to patients with HF, especially in the short term.

Acute myocardial infarction and syncope in an 18-year-old athlete with an abnormal origin of the left coronary artery: a case report.

We report a case of acute myocardial infarction and syncope in an 18-year-old athlete during high-performance exercise. A coronary arteriography and an angiographic computed tomography scan subsequently revealed a left coronary arterial origin from the right aortic sinus along with an intramural course of the left main stem. The patient was successfully treated with surgical unroofing of the left main stem from inside the aorta. To our knowledge, this is the first report demonstrating this type of anomaly pre- and postoperatively by use of angiographic computed tomography scan in the context of acute coronary syndrome.

Acute effect of weight loss on levels of total bilirubin in obese, cardiovascular high-risk patients: an analysis from the lead-in period of the Sibutramine Cardiovascular Outcome trial.

Low levels of bilirubin are associated with an increased risk of cardiovascular adverse events. Weight reduction is known to reduce several cardiovascular risk factors, but effects on bilirubin levels have not been reported. We studied the response of weight loss therapy with sibutramine and lifestyle change on levels of total bilirubin in an overweight or obese, cardiovascular high-risk population. Data from the first 4 weeks of the lead-in period of the Sibutramine Cardiovascular Outcome study were analyzed. A total of 10 198 patients provided body weight measurements before and after 4 weeks of sibutramine treatment (10 mg daily), of whom 1059 (10.4%) gained weight, 1467 (13.7%) lost greater than 0% to 1%, 2492 (23.2%) lost greater than 1% to 2%, 2280 (21.2%) lost greater than 2% to 3%, 1498 (13.9%) lost greater than 3% to 4%, and 1402 (13.1%) lost greater than 4% of their initial weight, respectively. At screening, bilirubin concentrations were similar between weight loss groups (around 11 micromol/L, P = .7) and increased linearly as a function of weight loss. The effect was significantly more pronounced in men compared with women (P for interaction = .003). Adjusted for multiple variables, each 1% increase in weight loss was associated with 0.21-micromol/L (+/- standard error 0.027) increase in men (P < .0001) and 0.11-micromol/L (+/-0.024) increase in women (P < .0001). Short-term weight loss during administration of sibutramine in combination with diet and exercise advice is effective in increasing bilirubin levels within the reference range, with bilirubin increasing as a linear function of weight change. The effect is greater in men than in women.

Differential changes in serum uric acid concentrations in sibutramine promoted weight loss in diabetes: results from four weeks of the lead-in period of the SCOUT trial.

BACKGROUND AND AIMS: Elevated levels of serum uric acid are associated with an increased risk of cardiovascular morbidity and mortality. The response of uric acid to weight loss therapy (lifestyle plus sibutramine) in an overweight and obese cardiovascular high risk population was studied. METHODS AND RESULTS: Data from a four week single-blind lead-in period of the Sibutramine Cardiovascular OUTcomes (SCOUT) study were analyzed. 2584 patients (24%) had diabetes mellitus (DM) only, 1748 (16%) had cardiovascular disease (CVD) only and 6397 (60%) had both DM + CVD. Uric acid concentrations (mean +/- standard deviation) at screening were significantly higher among patients with CVD compared to patients without CVD (p < 0.0001): 369 +/- 86 mumol/L, 374 +/- 98 mumol/L and 342 +/- 87 mumol/L in CVD only, CVD+DM and DM only groups, respectively. During treatment uric acid decreased significantly more in patients without DM (p < 0.0001): -15.0 mumol/L (95% confidence interval -17.7;-12.4), -4.6 mumol/L (-6.2;-3.0), and -6.6 mumol/L (-8.7;-4.5) in CVD only, CVD+DM, and DM only groups, respectively. In patients who failed to lose weight, sibutramine induced lower uric acid levels, but greater weight loss and diabetes were associated with smaller falls in blood uric acid levels; decreasing fasting and urinary glucose concentrations in diabetes were associated with increases in uric acid levels. CONCLUSION: A four week daily intake of sibutramine and life style changes was associated with significant reductions in mean uric acid levels. Changes in renal glucose load in diabetes seem to counteract a potential uricosuric effect of sibutramine. TRIAL REGISTRATION: The trial is registered at ClinicalTrial.gov number: NCT00234832.