[Cardiac arrest following treatment with non-cardiologic QT-interval-increasing medications].
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Bendroflumethiazide↗
Biomedical subjects
Hanne Elming
Publications and source records attributed to Hanne Elming.
New antiarrhythmic agents for atrial fibrillation and atrial flutter.
Atrial fibrillation is the most common sustained cardiac arrhythmia and is a frequent reason for antiarrhythmic therapy. Existing antiarrhythmic drugs have important side effects and presently the therapy to maintain sinus rhythm is not superior to a strategy of controlling excessive heart rate. This review summarises current strategies to improve antiarrhythmic therapy for atrial fibrillation. The most important strategies are: i) to develop drugs without proarrhythmic effects--development of drugs devoid of QT prolonging potential is the main strategy; ii) multiple channel-blocking drugs--inspired by the efficacy of amiodarone, several drugs are being developed that have similar electrophysiological properties as amiodarone, but without the extracardiac side effects; iii) drugs that act exclusively in the atria--the atria contain specific potassium channels, and several drugs that act only on these channels are in development; and iv) antiarrhythmic therapy without effects on ion channels--inhibition of the renin-angiotensin system and steroid therapy has been shown to have some effect in the treatment of atrial fibrillation. Many drugs are in development and the therapeutic scenario for treatment of atrial fibrillation may change quickly.
Animals↗
A benefit-risk assessment of class III antiarrhythmic agents.
The prevalence of arrhythmia in the population is increasing as more people survive for longer with cardiovascular disease. It was once thought that antiarrhythmic therapy could save life, however, it is now evident that antiarrhythmic therapy should be administrated with the purpose of symptomatic relief. Since many patients experience a decrease in physical performance as well as a diminished quality of life during arrhythmia there is still a need for antiarrhythmic drug therapy. The development of new antiarrhythmic agents has changed the focus from class I to class III agents since it became evident that with class I drug therapy the prevalence of mortality is considerably higher. This review focuses on the benefits and risks of known and newer class III antiarrhythmic agents. The benefits discussed include the ability to maintain sinus rhythm in persistent atrial fibrillation patients, and reducing the need for implantable cardioverter defibrillator shock/antitachycardia therapy, since no class III antiarrhythmic agents have proven survival benefit. The risks discussed mainly focus on pro-arrhythmia as torsade de pointes ventricular tachycardia.
Amiodarone↗
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.
Aged↗
Does conversion and prevention of atrial fibrillation enhance survival in patients with left ventricular dysfunction? Evidence from the Danish Investigations of Arrhythmia and Mortality ON Dofetilide/(DIAMOND) study.
BACKGROUND: Atrial fibrillation is a common arrhythmia in patients with left ventricular dysfunction associated with increased morbidity and mortality. The present study investigated the potential of dofetilide to restore and maintain sinus rhythm in patients with left ventricular dysfunction, which might reduce mortality and hospitalizations. METHODS AND RESULTS: In the Danish Investigations of Arrhythmia and Mortality ON Dofetilide (DIAMOND) studies, 506 patients were in atrial fibrillation (AF) or atrial flutter (AFl) at baseline. Over the course of study, cardioversion occurred in 148 (59%) dofetilide- and 86 (34%) placebo-treated patients. In these patients, the probability of maintaining sinus rhythm for 1 year was 79% with dofetilide versus 42% with placebo ( P < 0.001). Dofetilide had no effect on all-cause mortality, but restoration and maintenance of sinusrhythm (independent of study treatment) was associated with a significant reduction in mortality (risk ratio [RR], 0.44; 95% CI, 0.30 to 0.64; P < 0.0001). In addition, dofetilide therapy was associated with a significantly lower risk ratio versus placebo for either all-cause (RR, 0.70; 95% CI, 0.56 to 0.89; P < or = 0.005) or congestive heart failure (RR, 0.69; 95% CI, 0.51 to 0.93; P < or = 0.02) rehospitalization. CONCLUSIONS: Dofetilide is safe and increases the probability of obtaining and maintaining sinus rhythm in patients with structural heart disease. The present study suggests that restoration of sinus rhythm--on placebo or dofetilide--is associated with improved survival.
Anti-Arrhythmia Agents↗
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.
Anti-Arrhythmia Agents↗
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.
Angiotensin-Converting Enzyme Inhibitors↗
[Why is QT interval interesting?].
A prolonged Q-T interval is generally associated with increased risk of ventricular arrhythmias, like torsade de pointes, and death. It has recently become apparent that not only antiarrhythmic drugs such as sotalol and Kinidin, but also a variety of nonantiarrhythmic drugs, like certain antihistamines, antimicrobial drugs, psychiatric drugs, and cisapride, may induce prolongation of the Q-T interval and torsade de pointes. Special concern should be drawn to the co-administration of drugs that interfere with the metabolism and elimination of these drugs, such as ketoconazole. Patients with congenital long Q-T syndrome, patients with heart disease, with hypokalaemia or hypomagnesaemia, and women have an increased risk. Every sign on dizziness or syncope should be regarded as a warning sign of possible arrhythmia in patients treated with drugs that potentially prolong the Q-T interval. Measurement of the Q-T interval before and during treatment is generally recommended in high-risk patients.
Anti-Arrhythmia Agents↗
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↗
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.
Cardiovascular Diseases↗
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↗