Bente Brendorp

Long-term survival in patients hospitalized with congestive heart failure: relation to preserved and reduced left ventricular systolic function

AIMSnThe purpose of this study was to evaluate the influence of left ventricular systolic function on the survival in a large consecutive cohort of patients hospitalized with congestive heart failure and to determine how left ventricular systolic function interacts with co-morbid conditions in terms of prognosis.nnnMETHODS AND RESULTSnAnalysis of survival data from 5491 patients admitted for new or worsening heart failure to 34 departments of cardiology or internal medicine in Denmark from 1993-1996 was carried out. A standardized echocardiogram was available for 95% of the patients, and left ventricular systolic function was estimated using wall motion index score. Follow-up time was 5-8 years. Patients with preserved systolic function were older, more frequently female, and had less evidence of ischemia than patients with systolic dysfunction. After 1 year, 24% of the patients had died. Low wall motion index was a potent independent predictor of death (risk ratio for one unit increase, 0.60 (0.56-0.64)), and was of greater prognostic significance in younger patients and patients with a history of myocardial ischemia. However, even in patients with preserved systolic function, mortality was high (1 year mortality, 19%).nnnCONCLUSIONnIn hospitalized heart failure patients, particularly in younger patients with ischemic heart disease, mortality risk is inversely related to left ventricular systolic function.

QT Dispersion Has No Prognostic Information for Patients With Advanced Congestive Heart Failure and Reduced Left Ventricular Systolic Function

Background —QT dispersion is a potential prognostic marker of tachyarrhythmic events and death, but it is unclear whether this applies to patients with congestive heart failure (CHF). Methods and Results —Of the 1518 patients with advanced CHF and left ventricular dysfunction enrolled in the Danish Investigations of Arrhythmia and Mortality on Dofetilide-CHF (Diamond-CHF) study, a baseline ECG was available in 1319 patients. Of these, QT dispersion could be measured in 703 patients. During a median follow-up of 18 months (minimum 1 year), 285 patients (41%) died. The median QT dispersion was 70 ms (34/155 ms [5%/95% percentiles]), with no difference between survivors and nonsurvivors. Survival analysis revealed no prognostic information derived from QT dispersion regarding all-cause mortality (risk ratio 1.00, 95% CI 1.00 to 1.00;P =0.74), cardiac mortality (risk ratio 1.00, 95% CI 1.00 to 1.01;P =0.55), or cardiac arrhythmic mortality (risk ratio 1.00, 95% CI 0.99 to 1.01;P =0.38). Conclusions —QT dispersion has no prognostic value regarding all-cause mortality, cardiac mortality, or cardiac arrhythmic mortality for patients with advanced CHF and reduced left ventricular systolic function.

QTc interval in the assessment of cardiac risk.

In the United States alone 300,000-400,000 people die of sudden cardiac death every year. Much of this mortality is assumed to be caused by ventricular tachyarrhythmias. Prolonged QTc reflect cardiac repolarization prolongation and/or increased repolarization inhomogenity known to be associated with increased risk of arrhythmias. The paper gives a review of the possibilities to assess the risk of ventricular arrhythmia and/or cardiac death from QTc. Prolonged QTc may hold independent prognostic importance for mortality in common diseases as ischemic heart disease and diabetes mellitus where as the prognostic importance in heart failure and arterial hypertension is more uncertain. In more rare diseases as the inborn long QT syndrome the QT interval gives not only important hint to the diagnosis but the magnitude also provides information on prognosis. QTc has probably no independent prognostic importance in hypertrophic cardiomyopathy or in the arrhythmogenic right ventricular disease. The degree of QTc prolonging during treatment with QTc prolonging drugs is prognostic for the risk of ventricular arrhythmia in form of torsade de pointes and QTc prolonging drugs should probably not be prescribed for patients with a QTc greater than 460 ms and withdrawn if QTc exceeds 500 ms during treatment. Data from the DIAMOND study suggest that QTc can be used to point out those heart failure patients who will benefit from antiarrhythmic 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 ☆

BACKGROUNDnElevated 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).nnnMETHODSnIn 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.nnnRESULTSnDuring 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.nnnCONCLUSIONSnResting 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.

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

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.

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.

The incomplete Bucindolol Evaluation in Acute myocardial infarction Trial (BEAT)

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.

Dofetilide: a class III anti-arrhythmic drug for the treatment of atrial fibrillation

Dofetilide is a class III anti-arrhythmic drug that has been approved for the treatment of atrial fibrillation. Two clinical studies, which enrolled 996 patients, demonstrated pharmacological conversion to sinus rhythm to occur in 30% of patients. Following pharmacological or electrical conversion, median time to relapse exceeded one year. Two large clinical studies that enrolled 3028 patients have been performed in high-risk patients with severe heart failure and large myocardial infarctions. The outcomes of these studies were neutral with respect to survival and demonstrated the safety of dofetilide. After pharmacological or electrical conversion of atrial fibrillation to sinus rhythm in these studies, the probability of remaining in sinus rhythm during the following year was 75%. Dofetilide has a single significant side effect: risk of developing torsade de pointes ventricular tachycardia. Therefore, dosage must be carefully adjusted to the length of QTc interval, calculated creatinine clearance and the presence of heart failure or recent infarction. In addition, treatment must be initiated in hospital with three days of continuous telemetry. Dofetilide can be co-administered with digoxin and β-blockers. Other anti-arrhythmic drugs, as well as drugs that interfere with the renal elimination or the metabolism of dofetilide, must be avoided. Dofetilide is an option when persistent atrial fibrillation is a clinical problem. In the setting of severe heart failure and large myocardial infarctions, only amiodarone and dofetilide have proven safety and dofetilide is a strong candidate for first choice treatment when the aim is to achieve sinus rhythm.

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

BackgroundObesity, 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.MethodsThe 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.ResultsA 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.ConclusionShort 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.

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

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).