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Christian Torp-Pedersen

Publications and source records attributed to Christian Torp-Pedersen.

81 records · Page 5Linked to original sources
PubMed2002

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.

Aged↗
PubMed2002

Rationale and design of the carvedilol or metoprolol European trial in patients with chronic heart failure: COMET.

In large clinical trials both carvedilol and metoprolol have been shown to reduce mortality and morbidity in patients with chronic heart failure. Carvedilol is an adrenoceptor antagonist, which inhibits beta(1)-, beta(2)-, and alpha(1)-adrenergic receptors. Carvedilol has additional metabolic and antioxidant properties. Metoprolol is a selective antagonist of beta(1)-adrenergic receptors. The carvedilol or metoprolol European trial (COMET) is the first study to investigate whether beta-blocking agents with differing pharmacological profiles exert different effects on morbidity and mortality in patients with chronic heart failure. 3029 patients from 15 different European countries were enrolled into COMET and will be followed until 1020 fatal events have been observed, unless the data and safety monitoring committee (DSMC) recommends early termination. The target dose for carvedilol is 25 mg bid and for metoprolol tartrate 50 mg bid. This manuscript outlines the rationale, design and possible outcomes of COMET.

Adrenergic beta-Antagonists↗
PubMed2002

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.

Adrenergic beta-Antagonists↗
PubMed2002

The prognostic accuracy of different QT interval measures.

BACKGROUND: The QT intervals accuracy for predicting arrhythmic death varies between studies, possibly due to differences in the selection of the lead used for measurement of the QT interval. The purpose of this study was to analyze the prognostic accuracy of all known ways to select the lead. METHODS AND RESULTS: Three institutions that used different methods for measuring QT intervals provided their QT databases. They included more than 3500 twelve-lead surface ECGs. The data represented low- and high-risk patients of the normal population (survivors vs dead from cardiovascular causes), acute myocardial infarction (survivors versus death from all causes) and remote myocardial infarction (with vs without a history of ventricular arrhythmia). The prognostic accuracy was defined as the area under the Receiver Operator Curve (ROC-area). The most accurate standard leads were I and aVL and the least accurate was AVR. The most accurate precordial lead was V4. The prognostic accuracy of the longest QT interval was higher than for any standard lead. The prognostic accuracy of the mean of the three longest QT intervals was equal to or slightly lower than for the longest QT interval. CONCLUSIONS: The highest prognostic accuracy is obtained with the longest QT interval. The accuracies of the lead selection methods are so different that it can explain a substantial part of the differences between otherwise similar studies in the literature. We recommend the use of the mean value of the three longest QT intervals.

Adult↗
PubMed2002

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.

Journal Article↗
PubMed2002

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.

Action Potentials↗
PubMedDate not supplied

Prolonged local forearm hyperinsulinemia induces sustained enhancement of nitric oxide-dependent vasodilation in healthy subjects.

Systemic hyperinsulinemia induces enhancement of endothelium-dependent vasodilation of healthy subjects. During systemic infusion of insulin, endothelium-dependent vasodilation may be improved through a decrease in the concentration of free fatty acids. To explore the direct effect of continued insulin on the vascular endothelium, the authors infused insulin in the brachial artery for 4 h and measured the effect on endothelium-dependent vasodilation in the human forearm. Thirty-six experiments were performed in healthy subjects, mean age 47.7 +/- 1.1 years. Endothelium-dependent and -independent vasodilatation was studied during intra-arterial infusion of serotonin and sodium nitroprusside (SNP), respectively. Forearm blood flow was measured by plethysmography. Intra-arterial insulin was infused for 240 min at a constant rate and blood flow was measured hourly during stimulation of endothelium-dependent and -independent vasodilation.N(G)-monomethyl-L-arginine (L-NMMA) was coinfused to test the degree of nitric oxide (NO)-mediated vasodilation. Insulin infusion for 60 min enhanced serotonin-induced vasodilation by 37% compared to vehicle, p = .016. This increase was maintained for 4 h and was blocked by L-NMMA. The SNP response was increased by insulin but the increment was inhibited by L-NMMA. Four hours of local forearm hyperinsulinemia causes a sustained increase in endothelium dependent vasodilation in resistance vessels, which is mediated by NO.

Aged↗
PubMedDate not supplied

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.

Anti-Arrhythmia Agents↗