Ibutilide to expedite ED therapy for recent-onset atrial fibrillation flutter

OBJECTIVE: Ibutilide is a type III antiarrhythmic agent approved for the pharmacologic conversion of atrial fibrillation (AF) and atrial flutter (AFl). Previous studies conducted outside the ED setting have demonstrated conversion rates of 60% to 80%. This response has been highest in patients with recent-onset AF-AFl. These observations and the 4-hour half-life of ibutilide suggest that it may be an excellent drug with which to treat AF-AFl in the ED. The purpose of the study was to examine the efficacy and safety of ibutilide in terminating AF-AFl in patients who present to the ED with symptoms of less than 3 days' duration, neither angina nor heart failure, and no comorbid conditions that require admission. METHODS: Among 36 enrolled patients, the admission electrocardiogram demonstrated AF in 26 and AFl in 10. Ibutilide 1 mg was administered intravenously for 10 minutes. If sinus rhythm was not present 10 minutes after the infusion concluded, a second infusion of 1 mg was given. Successful conversion was defined as restoration of sinus rhythm within 1 hour after the last dose of ibutilide. RESULTS: Sixteen (61.5%) of 26 patients with AF and 9 (90%) of 10 patients with AFl converted to sinus rhythm (overall conversion rate=69%). The mean time to arrhythmia termination was 19+/-9 minutes. The mean stay in the ED was 16.2 hours. No significant complications occurred. CONCLUSION: We conclude that ibutilide is an excellent therapy option for restoring sinus rhythm in the ED. Its use may obviate the need for admission, avoid the risks and inconveniences of general anesthesia to perform electrical cardioversion, and reduce the ED length of stay in selected patients with recent-onset atrial arrhythmias.     

Ibutilide-induced long QT syndrome and torsade de pointes

Ibutilide is a class III antiarrhythmic agent used for the termination of atrial fibrillation and atrial flutter. It mainly affects membrane potassium currents and prolongs the cardiac action potential. This effect is reflected as QT interval prolongation on the surface electrocardiogram. Like other drugs that affect potassium currents, ibutilide is prone to induce a malignant ventricular tachycardia, torsade de pointes. We report four cases of torsade de pointes after administration of ibutilide for pharmacologic cardioversion of atrial fibrillation and atrial flutter; three of these cases required direct current cardioversion for termination of torsade de pointes. All four patients were female. We discuss the risk factors for development of ibutilide-induced torsade de pointes.     

伊布利特转复房颤110例的疗效分析

目的探讨伊布利特药物复律心房颤动的疗效和安全性,并分析影响转复成功率的因素。方法回顾性分析2009年1月至2011年6月期间110例使用伊布利特行药物复律的心房颤动患者的临床资料。结果 65例患者转复为窦性心律,成功率59.1%;转复组在年龄、合并器质性心脏病的比率、心房颤动发作持续时间及左房内径等方面均小于未转复组,差异有统计学意义(P均<0.05);4例在用药过程中发生频发室性早搏;2例发生非持续性尖端扭转性室速(TdP);所有患者均未出现血流动力学不稳定及其他严重不良反应。结论伊布利特转复心房颤动疗效肯定,转复成功率与年龄、合并器质性心脏病、心房颤动发作持续时间和左房内径等因素有关。用药期间有发生TdP的可能,做好用药期间的监护可以显著减少这一不良反应的发生。     

Ibutilide for treatment of atrial fibrillation in the emergency department

The purpose of this study was to assess the efficacy and safety of ibutilide, a class III antiarrhythmic drug, for acute treatment of atrial fibrillation (AF) in the emergency department (ED) setting. A retrospective analysis was done reviewing all patients with AF who received ibutilide in the ED in a university hospital setting. A total of 22 patients received ibutilide. Another 24 patients who received rate control drugs only served as a control group. Of the 22 patients who received ibutilide, 14 (64%) converted to sinus rhythm. The mean (SD) rate of AF was 137 (24) bpm and the mean QTc interval immediately after conversion to sinus rhythm was 420 (28) ms. There were no complications. In the rate control group 7 patients (29%) converted to sinus rhythm (p<0.05, compared with ibutilide). The mean rate of AF was 126 (26) bpm (p = ns, compared with ibutilide) and the mean QTc interval in those who converted was 377 (28) ms (p<0.05, compared with ibutilide). One patient developed severe bradycardia. Ibutilide is effective for conversion of recent onset AF in patients presenting to the ED and there is a low rate of complications from ibutilide in this setting.     

Conversion of recent-onset atrial fibrillation or flutter with ibutilide after amiodarone has failed

OBJECTIVE: To evaluate whether ibutilide can convert atrial fibrillation or flutter in patients in whom amiodarone has failed. DESIGN AND SETTING: Clinical study in a university hospital intensive care unit (ICU). PATIENTS: Twenty-six patients were studied, in whom atrial fibrillation or flutter persisted for a maximum of 6 h at maximum. Patients were monitored continuously during the arrhythmia. Medical conversion was necessary due to symptomatic or hemodynamic causes. INTERVENTIONS: All patients initially received amiodarone (150 mg i.v.) and after 2 h of persistent arrhythmia ibutilide (1 mg or, without success and body weight > 70 kg, 2 mg i.v.). Before the administration of ibutilide 1 g magnesium was administered, and high normal levels of potassium serum levels were achieved (4.5-5.0 mmol/l). RESULTS. After amiodarone atrial flutter persisted in 73% and atrial fibrillation in 27% of patients. After ibutilide the QT interval was prolonged from 327 +/- 61 to 387 +/- 62 ms. The QTc interval increased from 456 +/-32 to 461 +/- 66 ms. Conversion to normal sinus rhythm was achieved in 22 of 27 of cases. Nonsustained torsade de pointes tachycardia was seen in three patients (11%). No patient showed sustained ventricular tachycardia. Patients with proarrhythmic effects were characterized by a decreased left ventricular function. CONCLUSIONS: In ICU patients ibutilide led to conversion to sinus rhythm in 81.5% of patients in whom amiodarone was unsuccessful. Nonsustained tachycardias were seen in 11%; sustained ventricular tachycardia was not seen. Ibutilide seems to be well suitable for conversion of recent onset atrial fibrillation or flutter and had no severe side effects in this study population.     

Efficacy and safety of ibutilide for the conversion of monomorphic atrial tachycardia

BACKGROUND: Ibutilide is a class III antiarrhythmic drug, frequently used for conversion of atrial fibrillation and flutter. We studied the efficacy of ibutilide for acute conversion of monomorphic atrial tachycardia (monoAT) in a prospective, open label study in the intensive care unit of a cardiological clinic. METHODS: We examined 49 episodes of monoAT in 38 patients (19 men/19 women). Thirty-three patients (87%) suffered from structural heart disease. Twenty-three episodes occurred while on antiarrhythmic therapy with class I or III drugs. Patients with prolonged QT interval (except for patients with pretreatment with class III drugs), hypokalemia, left ventricular failure, and recent myocardial infarction were excluded. All patients received one or two doses of 1 mg ibutilide fumarate under continuous rhythm monitoring. RESULTS: Conversion to sinus rhythm occurred in 19 episodes (38.8%), in 6 episodes (12.2%) after the first dose. Conversion rate was significantly higher in patients with a short history of symptoms (66.6% vs 28.6%; P < 0.05), of documented arrhythmia (0.13 (0/5.7) vs 2.6 (0.38/23.5) months, median (interquartile range); P < 0.03), higher atrial rate (272 +/- 49 vs 207 +/- 36 beats/min (means +/- SD); P < 0.004), or without preexisting antiarrhythmic therapy (53.8% vs 21.7%; P < 0.02). No differences in conversion rates were found regarding gender, age, body mass index, left ventricular function, left atrial diameter, or underlying disease. In three episodes torsade de pointes occurred after ibutilide (6.1%), requiring defibrillation in two cases (4.1%). CONCLUSIONS: Ibutilide can be used for conversion of monoAT with a similar efficacy as for atrial fibrillation, but with a considerably lower efficacy compared to typical atrial flutter.     

Propafenone-Induced Torsade de Pointes: Cross-Reactivity with Quinidine

A 77-year-oid/emale with new onset atrial fibrillation occurring in the absence of structural heart disease developed torsade de pointes during therapy with quinidine bisulfate 500 mg orally every 8 hours. Ten days after quinidine therapy had been discontinued she developed torsade de pointes while receiving propafenone 300 mg orally every 8 hours. This case demonstrates that propafenone may be associated with torsade de pointes and suggests a cross-reactivity between this effect and prior occurrence of torsade de pointes on Class IA antiarrhythmic drug therapy.     

The safety and efficacy of ibutilide in children and in patients with congenital heart disease

BACKGROUND: The safety and efficacy of ibutilide in the cardioversion of atrial flutter and atrial fibrillation in children and in patients with congenital heart disease (CHD) is unknown. METHODS: Data from 19 patients (age 6 months to 34 years, median 16 years) who received ibutilide for atrial flutter or atrial fibrillation between 1996 and 2005 was retrospectively reviewed. There were 15 patients with CHD (14 had prior heart surgery); four children had normal heart structure. RESULTS: There were 74 episodes of atrial flutter and four episodes of atrial fibrillation (median episodes per patient was one, range 1-31). Ibutilide converted 55 of all the episodes (71%). Ibutilide was successful during its first-ever administration in 12 of 19 patients (63%). Fourteen episodes in six patients required electrical cardioversion after ibutilide failed. There were no episodes of symptomatic bradycardia. One patient went into torsade de pointes and one patient had nonsustained ventricular tachycardia. CONCLUSION: With careful monitoring, ibutilide can be an effective tool in selected patients for cardioversion of atrial flutter.     

Long QT syndrome induced by cordaron and quinidine

The article presents an observation of a 63-year-old female patient suffering from arterial hypertension, coronary artery disease complicated by a persistent form of atrial fibrillation during 1.5 months, and hereditary Minkowski-Chauffard hemolytic anemia. Treatment with cordaron proved to be ineffective, while oral administration of quinidin in a dose of 1 gr (0.2 gr five times a day) led to restoration of sinus rhythm. However, long QT interval syndrome complicated by ventricular tachycardic paroxysms of torsade de pointes type developed; later it transformed into ventricular fibrillation.     

Poster Session 2-1: Pharmacological and Cellular Therapy Monday, April 3, 2006, 4:00–5:30pm

Prof. Yuji Nakazato ¹ , Masayuki Yasuda ¹ , Hiroto Tsuchiya ¹ , Akitoshi Sasaki ¹ , Takashi Tokano ¹ , Hiroyuki Daida ^{1   1} Cardiology, Juntendo University, Tokyo, Japan
The purpose of this study is to clarify the efficacy and safety of bepridil for persistent atrial fibrillation (AF). Method: Bepridil (100-200mg/day) was administered to 159 patients (141 males, mean age 58 years) with persistent AF. The effects of conversion and maintenance of sinus rhythm were evaluated. If sinus restoration was not obtained until 3 months observation, DC cardioversion was performed. Results: In 87 of 159 patients (55%), sinus rhythm was restored within an average 2.1 months following administration of bepridil. 74 of those 87 patients (85%) have been maintained in sinus rhythm for the average follow-up of 16 months. The 31 out of remaining 72 patients failed pharmacological conversion and performed DC cardioversion. All of the patients restored sinus rhythm, and 18 of them (58%) maintained sinus rhythm for an average of 20 months. Although ECG revealed significant prolongation of QT interval from 0.38/0.03 to 0.42/0.06 sec, QTc was unchanged and no serious adverse complications including torsade de pointes were recognized. Conclusion: Bepridil is clinically safe and useful with favorable efficacy for conversion and maintenance of sinus rhythm in patients with persistent AF.     

Ciprofloxacin- and hypocalcemia-induced torsade de pointes triggered by hemodialysis

Torsade de pointes is a polymorphic form of ventricular tachycardia associated with prolongation of the QT interval, which may be either congenital or acquired. Etiologies for the acquired forms include drug effects, hypokalemia, hypomagnesemia, hypocalcemia, starvation, sick sinus syndrome, and atrioventricular block. We present a 76-year-old man with acute on chronic renal failure, hypocalcemia, on ciprofloxacin, and a prolonged QT interval with torsade de pointes triggered by hemodialysis. The QT prolongation was corrected by treating the hypocalcemia. Hypocalcemia and ciprofloxacin are known to independently cause prolonged QT interval and torsade de pointes; our case illustrates that dialysis can trigger torsade on a background of this risk factor combination.     

Ibutilide versus amiodarone in atrial fibrillation: a double-blinded,randomized study

OBJECTIVE: Ibutilide, a class III antiarrhythmic drug, has been shown to convert atrial fibrillation to sinus rhythm more rapidly than procainamide or sotalol. Our objective was to compare the efficacy and safety of ibutilide and amiodarone in patients after cardiac surgery. DESIGN: Prospective, randomized, double-blinded study. SETTING: Intensive care unit of a university hospital. PATIENTS: Forty adults with an onset of atrial fibrillation within 3 hrs after admission. INTERVENTIONS: Before the administration of antiarrhythmic drugs, a 24-hr Holter electrocardiograph was attached. Patients in the ibutilide group received ibutilide 0.008 mg/kg body weight over 10 mins; treatment was repeated if atrial fibrillation or flutter persisted. If sinus rhythm was not achieved within 4 hrs, amiodarone 5 mg/kg was administered over 30 mins, followed by amiodarone 15 mg/kg over 24 hrs. Patients in the amiodarone group received amiodarone 5 mg/kg over 30 mins, followed by amiodarone 15 mg/kg over 24 hrs if atrial fibrillation or flutter continued. MEASUREMENTS AND MAIN RESULTS: Within the first 4 hrs, atrial fibrillation was converted in nine of 20 patients (45%) in group ibutilide and in ten of 20 patients (50%) in group amiodarone (not significant). Mean time for conversion overall was 385 mins in group ibutilide and 495 mins in group amiodarone (not significant). In group amiodarone, the protocol was discontinued in two patients because of severe arterial hypotension. Atrial fibrillation recurred in 11 of 20 patients (55%) in group ibutilide and in seven of 20 patients (35%) in group amiodarone (not significant). Ventricular arrhythmia did not occur during the first 24 hrs of the protocol. CONCLUSIONS: Ibutilide has no significant advantage over amiodarone for the conversion of atrial fibrillation to sinus rhythm in either time to conversion or conversion overall, but severe hypotension was not seen with ibutilide.     

Sinus node functions, sinoatrial conduction, atrial conductivity after incipient paroxysms of atrial fibrillation and flutter in patients with ischemic heart disease

AIM: Prediction of the rate of recurrent paroxysms of atrial fibrillation (AF) and flutter (AFl) after the first arrhythmia episode; determination of relevant antiarrhythmic treatment. MATERIAL AND METHODS: 157 patients with ischemic heart disease (IHD) complicated by new episodes of AF and AFl entered the study. After the initial episode and 1-2 arrhythmia recurrences all the patients have undergone assessment of hemodynamics, atrial conduction of excitation, sinus node function using transesophageal pacing. The patients were divided into two groups: group 1 consisted of 42 patients having no recurrent paroxysms of AF or AFl for at least 6 months; 115 patients of group 2 had at least one episode of recurrent arrhythmia for 6 months after the first paroxysm. RESULTS: Patients of group 2 vs those of group 1 had a significantly longer first episode, more frequent occurrence of calcinosis of mitral and/or aortic valve, more serious systolic and diastolic dysfunctions and most frequent retrograde atrial excitation conduction after the first paroxysm. CONCLUSION: In detection of only disturbed intraatrial conduction in IHD patients after the first paroxysm of AF and AFl predicted are clinical recurrences of arrhythmia with the recurrence-free period more than 6 months. In retrograde atrial conduction of excitation combined with systolic and diastolic left ventricular dysfunction, sinus node dysfunction prognosis was made of more frequent episodes of AF and AFl.     

Emergency noninvasive external cardiac pacing

Thirty-seven critical emergency department patients underwent attempts at external cardiac pacing over an 11-month period. Indications for pacing were asystole in 16, complete heart block (CHB) in 4, sinus bradycardia in 2, nodal bradycardia in 1, atrial fibrillation with bradycardia in 2, electromechanical dissociation in 1, idioventricular rhythm (IVR) in 10, and torsades de pointes in 1. Eight patients were successfully paced with improvement in their condition. Two were in asystole, two in CHB, three in sinus rhythm or atrial fibrillation with bradycardia, and one in idioventricular rhythm. Mean systolic blood pressure rise with pacing was 95 +/- 50 mm Hg. Six of these patients were ultimately discharged from the hospital. One asystolic patient survived to discharge. Other survivors presented with either CHB or bradycardia. Of the 29 patients who did not respond to pacing, 5 survived to hospital discharge. Surviving nonresponder presenting rhythms were CHB in one patient, sinus or nodal bradycardia in two, IVR in one, and torsades de pointes in one. External cardiac pacemaking appears to be effective in hemodynamically significant bradycardia. It does not appear to be effective in most instances of asystole or IVR resulting from prolonged cardiac arrest. When applied to patients with a responsive myocardium, it may result in significant hemodynamic improvement and may be lifesaving.     

Vernakalant Hydrochloride: A NovelAtrial‐selective Agent for the Cardioversionof Recent‐onset Atrial Fibrillation in the Emergency Department

Objectives: Vernakalant is a relatively atrial‐selective antiarrhythmic agent that has been shown to successfully convert atrial fibrillation (AF) to normal sinus rhythm for some patients whose onset of dysrhythmia occurred less than 7 days previously. This study sought to evaluate the efficacy and safety of vernakalant for patients with recent‐onset AF. Methods: This was a post hoc analysis of patients with recent‐onset AF (> 3 to ≤ 48 hours) enrolled in the double‐blind, placebo‐controlled Atrial arrhythmia Conversion Trial (ACT) I and the open‐label ACT IV trials. The studies enrolled adults presenting with AF to 78 emergency departments (ED) and cardiac clinics in six countries. Patients received a 10‐minute intravenous infusion of vernakalant or placebo, followed by an additional infusion if necessary. Efficacy assessments included conversion to sinus rhythm within 90 minutes and median time to conversion. Safety evaluations included telemetry, Holter monitoring, and adverse events (AEs). Results: Of the 290 patients, 229 received vernakalant, 61 received placebo, and the overall mean age was 59 years. The vernakalant and placebo groups were similar. Of all patients given vernakalant, 136 (59.4%) converted to sinus rhythm within 90 minutes, compared with three (4.9%) placebo patients. The median time to conversion with vernakalant was 12 minutes (interquartile range = 7–24.5 minutes). Clinically significant bradycardia and hypotension were uncommon, and no cases of torsade de pointes or ventricular fibrillation occurred. Conclusions: Vernakalant rapidly converted recent‐onset AF to sinus rhythm in over half of patients, was well tolerated, and has the potential to offer an important therapeutic option for rhythm control of recent‐onset AF in the ED. ACADEMIC EMERGENCY MEDICINE 2010; 17:1175–1182 © 2010 by the Society for Academic Emergency Medicine     

Azithromycin-induced torsade de pointes

Although erythromycin frequently induces long QT interval and torsade de pointes, the newer drug, azithromycin, has rarely been reported to be associated with torsade de pointes. We report here the occurrence of a significant typical QT prolongation within a few hours after taking azithromycin which lead to torsade de pointes.     

Torsade de pointes caused by polypharmacy and substance abuse in a patient with human immunodeficiency virus

Drug-induced QT prolongation is a potentially dangerous adverse effect of some medication combinations. When QT prolongation progresses to torsade de pointes, life-threatening or fatal outcomes may result. A 57-year-old man with a history of human immunodeficiency syndrome on abacavir, nevirapine, tenofovir, voriconazole, and methadone presented to the emergency department with a chief complaint of new-onset seizures. The physical exam was unremarkable. The electrocardiogram demonstrated sinus bradycardia and a prolonged QT_c interval of 690 ms. In the emergency department, he had several episodes of torsade de pointes (TdP) and ventricular tachycardia that resolved spontaneously. These episodes were accompanied by an alteration in mentation and generalized twitching. Magnesium and amiodarone were effective in terminating the dysrhythmia. The patient had multiple risk factors for prolonged QT syndrome including human immunodeficiency virus infection, methadone therapy, and polypharmacy leading to potential drug interactions. Physicians must be aware of multidrug interactions potentiating QT prolongation and leading to torsade de pointes.     

Ibutilide for pharmacological cardioversion of atrial fibrillation and flutter: impact of race on efficacy and safety

OBJECTIVE: To evaluate the racial differences in the efficacy and safety of ibutilide in patients with recent-onset (<2 weeks) atrial fibrillation and atrial flutter. METHODS: This study included 58 consecutive patients with recent-onset atrial fibrillation (n = 34) and atrial flutter (n = 24). The mean age was 65.7 +/- 14.6 years (range, 37-86 years), 47% were women (n = 27) and 34% (n = 20) were African Americans. The duration of arrhythmia ranged from 3 hours to 2 weeks. All patients had echocardiography, were on therapeutic anticoagulation, had a fairly well controlled ventricular rate, normal QTc interval on 12-lead electrocardiography, and normal serum electrolytes. Ibutilide was administered as an intravenous infusion with a maximal dose of 2 mg. RESULTS: The overall conversion rate to sinus rhythm was 66% (n = 38), with 62% (n = 21) with atrial fibrillation and 71% (n = 17) of atrial flutter. Most conversions (84%) occurred within 45 minutes of ibutilide infusion. The mean time to arrhythmia conversion was 37.4 +/- 59.8 minutes. Race had a significant impact on efficacy, with increased conversions seen in African Americans (P = 0.004) and increased nonconversion seen in whites (P = 0.02). Successful conversion was not affected by the left atrial size or the presence of valvular heart disease, hypertension, heart failure, coronary heart disease, and diabetes mellitus. QTc intervals were prolonged after drug administration, with a mean change of 24.6 milliseconds for all patients. The QTc prolongation after drug administration was greater in African Americans than in whites (27.4 vs. 23.3 milliseconds). Torsade de pointes occurred in 4 patients (3 African Americans) and was treated with intravenous magnesium sulfate and electrical cardioversion. CONCLUSION: Ibutilide used for pharmacological cardioversion of atrial fibrillation and atrial flutter is more effective in African Americans but carries a higher risk of torsade de pointes.     

Marked QT prolongation and torsades de pointes secondary to acute ischemia in an elderly man taking dofetilide for atrial fibrillation: a cautionary tale

Dofetilide has been shown to be effective and safe in maintaining sinus rhythm in patients with persistent atrial fibrillation and congestive heart failure. Because of serious side effects of an increase in the QT interval causing torsades de pointes, dofetilide must be initiated with close monitoring of the QT interval in an inpatient setting. However, little has been reported about conditions surrounding the change in QT interval after the steady state is achieved that may have implications in the safety and efficacy of the drug. We report marked QT prolongation and torsades de pointes in a setting of flash pulmonary edema resulting from acute myocardial ischemia in a patient who was being treated with dofetilide for atrial fibrillation. Our case reminds the clinicians that the adverse and proarrhythmic effects of dofetilide can occur due to changes in the arrhythmic substrate during acute severe ischemia.     

Ibutilide: a class III rapidly acting antidysrhythmic for atrial fibrillation or atrial flutter

Ibutilide is an intravenous Class III antidysrhythmic approved for the treatment of recent onset atrial fibrillation or atrial flutter. Pharmacological effect occurs within 30 min, and the efficacy approaches 40%. In contrast to DC electrical cardioversion, which requires anesthesia, pharmacologic cardioversion offers an alternative in which sedation can be avoided. Patients receiving ibutilide should be monitored for at least 4 h after completed drug administration because of a small chance of ventricular dysrhythmia, mainly torsades de pointes. Careful patient selection is the key to avoiding dysrhythmic complications. The purpose of this article is to review the mechanisms, clinical applications, potential complications, and appropriate use of ibutilide.