Effects of intravenous dofetilide on induction of atrioventricular re-entrant tachycardia.

OBJECTIVE: To assess the efficacy and safety of intravenous dofetilide in preventing induction of atrioventricular re-entrant tachycardia. DESIGN: A multicentre, open, dose ranging trial. Fifty one patients with electrically inducible atrioventricular re-entrant tachycardia were allocated to one of five doses of dofetilide (1.5, 3, 6, 9, and 15 microgram/kg), two thirds of the dofetilide dose being given over a 15 minute loading period and the remainder over a 45 minute maintenance period. MAIN OUTCOME MEASURE: Responders were defined as patients in whom dofetilide prevented reinduction of atrioventricular re-entrant tachycardia at the end of the infusion. RESULTS: Intravenous dofetilide had no effect on tachycardia inducibility at the two lower doses (1.5 and 3 microgram/kg) but prevented the reinduction of tachycardia at the three higher doses (6, 9, and 15 microgram/kg) at a rate of 36% (11/31). There was a clear relation between plasma dofetilide concentrations and efficacy (p = 0.009). In non-responders, dofetilide increased the cycle length of induced atrioventricular re-entrant tachycardia. Dofetilide increased the atrial and ventricular effective refractory periods, as well as the antegrade and retrograde effective refractory period of the accessory pathway. Treatment related side effects were reported in four patients, one with a new sustained incessant supraventricular tachycardia. CONCLUSIONS: Dofetilide shows promise as an agent for the prevention of atrioventricular re-entrant tachycardia in patients without structural heart disease.

[Dofetilide to patients with heart failure and left ventricular dysfunction]. / Dofetilid til patienter med hjerteinsufficiens og dårligt fungerende venstre ventrikel.

INTRODUCTION: Dofetilide, a new class III antiarrhythmic drug, was tested for its ability to reduce mortality and morbidity in patients with congestive heart failure and left ventricular dysfunction. METHODS: In 34 Danish centers, 1518 patients with NYHA class III or IV heart failure and wall motion index of the left ventricle < or = 1.2 (ejection fraction < or = 35%) were randomized to receive dofetilide or placebo in a double blind study. The dose of dofetilide was adjusted to renal function and the QT interval. Patients were monitored continuously with ekg during the first three days in the study. Minimum follow up was one year. RESULTS: Dofetilide did not affect mortality. Hospitalizations for worsening of heart failure were reduced significantly, hazard ratio 0.75 (0.63-0.89) Dofetilide effectively converted atrial fibrillation to sinus rhythm. After one year, 61% of patients with atrial fibrillation had converted on dofetilide and 33% on placebo (p < 0.001). DISCUSSION: Dofetilide can be used to convert atrial fibrillation to sinus rhythm and to maintain sinus rhythm in patients with congestive heart failure and left ventricular dysfunction. Dofetilide does not affect mortality.

Effect of dofetilide in patients with recent myocardial infarction and left-ventricular dysfunction: a randomised trial.

BACKGROUND: Arrhythmias cause much morbidity and mortality after myocardial infarction, but in previous trials, antiarrhythmic drug therapy has not been convincingly effective. Dofetilide, a new class III agent, was investigated for effects on all-cause mortality and morbidity in patients with left-ventricular dysfunction after myocardial infarction. METHODS: In 37 Danish coronary-care units, 1510 patients with severe left-ventricular dysfunction (wall motion index < or = 1.2, corresponding to ejection fraction < or = 0.35) were enrolled in a randomised, double-blind study comparing dofetilide (n=749) with placebo (n=761). The primary endpoint was all-cause mortality. Secondary endpoints included cardiac and arrhythmic mortality and total arrhythmic deaths. Analyses were by intention to treat. FINDINGS: No significant differences were found between the dofetilide and placebo groups in all-cause mortality (230 [31%] vs 243 [32%]), cardiac mortality (191 [26%] vs 212 [28%]), or total arrhythmic deaths (129 [17%] vs 140 [18%]). Atrial fibrillation or flutter was present in 8% of the patients at study entry. In these patients, dofetilide was significantly better than placebo at restoring sinus rhythm (25 of 59 vs seven of 56; p=0.002). There were seven cases of torsade de pointes ventricular tachycardia, all in the dofetilide group. INTERPRETATION: In patients with severe left-ventricular dysfunction and recent myocardial infarction, treatment with dofetilide did not affect all-cause mortality, cardiac mortality, or total arrhythmic deaths. Dofetilide was effective in treating atrial fibrillation or flutter in this population.

Dofetilide in patients with congestive heart failure and left ventricular dysfunction. Danish Investigations of Arrhythmia and Mortality on Dofetilide Study Group.

BACKGROUND: Atrial fibrillation occurs frequently in patients with congestive heart failure and commonly results in clinical deterioration and hospitalization. Sinus rhythm may be maintained with antiarrhythmic drugs, but some of these drugs increase the risk of death. METHODS: We studied 1518 patients with symptomatic congestive heart failure and severe left ventricular dysfunction at 34 Danish hospitals. We randomly assigned 762 patients to receive dofetilide, a novel class III antiarrhythmic agent, and 756 to receive placebo in a double-blind study. Treatment was initiated in the hospital and included three days of cardiac monitoring and dose adjustment. The primary end point was death from any cause. RESULTS: During a median follow-up of 18 months, 311 patients in the dofetilide group (41 percent) and 317 patients in the placebo group (42 percent) died (hazard ratio, 0.95; 95 percent confidence interval, 0.81 to 1.11). Treatment with dofetilide significantly reduced the risk of hospitalization for worsening congestive heart failure (risk ratio, 0.75; 95 percent confidence interval, 0.63 to 0.89). Dofetilide was effective in converting atrial fibrillation to sinus rhythm. After one month, 22 of 190 patients with atrial fibrillation at base line (12 percent) had sinus rhythm restored with dofetilide, as compared with only 3 of 201 patients (1 percent) given placebo. Once sinus rhythm was restored, dofetilide was significantly more effective than placebo in maintaining sinus rhythm (hazard ratio for the recurrence of atrial fibrillation, 0.35; 95 percent confidence interval, 0.22 to 0.57; P<0.001). There were 25 cases of torsade de pointes in the dofetilide group (3.3 percent) as compared with none in the placebo group. CONCLUSIONS: In patients with congestive heart failure and reduced left ventricular function, dofetilide was effective in converting atrial fibrillation, preventing its recurrence, and reducing the risk of hospitalization for worsening heart failure. Dofetilide had no effect on mortality.

[Late ventricular potentials after myocardial infarction]. / Sene ventrikulaere potentialer efter myokardieinfarkt.

Late potentials in the QRS complex can be detected with signal-averaged electrocardiography and are associated with delayed and disorganized ventricular activation. This article reviews the technique, describes the pathophysiological basis of late potentials, and assesses the prognostic value of late potentials for subsequent development of ventricular tachyarrhythmias and sudden cardiac death in postmyocardial infarction patients.

Surgery of ventricular tachycardia and ventricular fibrillation in patients with coronary artery disease and LV-aneurysms.

In 26 patients with left ventricular aneurysm and ventricular tachycardia and/or ventricular fibrillation following myocardial infarction, coronary angiography, left ventriculography and electrophysiologic examination were performed preoperatively. Surgery in all cases consisted of aneurysmectomy and mapping-guided endocardial resection of the area found to be the arrhythmogenic center. Four patients died peroperatively or during the postoperative hospital stay. The 22 survivors were followed up for 3-48 (mean 22) months postoperatively. There were no late deaths. Repeated electrophysiologic studies were performed in 18 of the survivors. Freedom from ventricular tachycardia and fibrillation was achieved in 21 patients, 17 after surgery alone and four after combined surgical and medical treatment. The remaining patient still has ventricular tachycardia despite combined treatment.