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Objective: Atrial fibrillation (AF) induces electrical and ionic remodeling of the atria. We investigated whether AF-induced remodeling alters the electrophysiological and anti-fibrillatory effects of class I (flecainide) and class III (d-sotalol, ibutilide) anti-arrhythmic drugs., Methods: In 9 goats, the effects of flecainide (6 mg/kg) and d-sotalol (6 mg/kg) on atrial electrophysiology were measured both before and after 48 h of electrically induced AF. During a 1-h infusion period the atrial effective refractory period (AERP) and conduction velocity (CV) were measured both during slow and rapid pacing (interval 400 and 200 ms). In 8 other goats, the rate-dependent effects of ibutilide (0.12 mg/kg) on AERP were determined., Results: The effects of flecainide on atrial conduction and refractoriness were not altered after 48 h of AF. At a dose of 6 mg/kg flecainide reduced the CV200 by 19+/-5% in normal atria and by 21+/-9% after 48 h of AF (p=0.20). The AERP200 was prolonged by 10+/-6% and 8+/-7%, respectively (p=0.40). In contrast, the effect of d-sotalol on atrial refractoriness was markedly diminished. During control d-sotalol prolonged the AERP400 by 17+/-6% compared to only 6+/-5% after 2 days of AF (p<0.01). Also ibutilide lost much of its class III effect on the AERP by electrical remodeling (from 15 to 5%; p<0.05). The loss of class III action was less pronounced at rapid heart rates., Conclusions: AF-induced atrial electrical remodeling in the goat did not modulate the action of flecainide on atrial conduction and refractoriness. In contrast, the class III effects of d-sotalol and ibutilide on the atria were strongly reduced after 2 days of AF. The prolongation of QT-duration was not affected.

Background: The optimal pharmacologic means to restore and maintain sinus rhythm in patients with atrial fibrillation remains controversial., Methods: In this double-blind, placebo-controlled trial, we randomly assigned 665 patients who were receiving anticoagulants and had persistent atrial fibrillation to receive amiodarone (267 patients), sotalol (261 patients), or placebo (137 patients) and monitored them for 1 to 4.5 years. The primary end point was the time to recurrence of atrial fibrillation beginning on day 28, determined by means of weekly transtelephonic monitoring., Results: Spontaneous conversion occurred in 27.1 percent of the amiodarone group, 24.2 percent of the sotalol group, and 0.8 percent of the placebo group, and direct-current cardioversion failed in 27.7 percent, 26.5 percent, and 32.1 percent, respectively. The median times to a recurrence of atrial fibrillation were 487 days in the amiodarone group, 74 days in the sotalol group, and 6 days in the placebo group according to intention to treat and 809, 209, and 13 days, respectively, according to treatment received. Amiodarone was superior to sotalol (P<0.001) and to placebo (P<0.001), and sotalol was superior to placebo (P<0.001). In patients with ischemic heart disease, the median time to a recurrence of atrial fibrillation was 569 days with amiodarone therapy and 428 days with sotalol therapy (P=0.53). Restoration and maintenance of sinus rhythm significantly improved the quality of life and exercise capacity. There were no significant differences in major adverse events among the three groups., Conclusions: Amiodarone and sotalol are equally efficacious in converting atrial fibrillation to sinus rhythm. Amiodarone is superior for maintaining sinus rhythm, but both drugs have similar efficacy in patients with ischemic heart disease. Sustained sinus rhythm is associated with an improved quality of life and improved exercise performance., (Copyright 2005 Massachusetts Medical Society.)

The aim of this study was to investigate the long-term efficacy and safety of electrophysiologic study (EPS)-guided sotalol administration combined with implantable cardioverter defibrillators (ICD) for ventricular tachyarrhythmias (VTA). This study enrolled 92 patients with both structural heart disease and sustained VTA. Sotalol was administered to 57 patients, and its efficacy was assessed by EPS. Long-term treatment was continued in combination with ICD in 31 patients (57%) whose VTA was no longer inducible (responder group) and in 16 patients whose VTA remained inducible (nonresponder group). The long-term outcomes were compared among the responder group, the nonresponder group, and 35 ICD recipients untreated with antiarrhythmic drugs (ICD-only group). During a mean follow-up of 44 +/- 33 months, the recurrence of VTA was not significantly different between all patients treated with sotalol (30%) and patients in the ICD-only group (46%). However, the recurrence of VTA was significantly lower in the responder (13%) than in the nonresponder (63%) or the ICD-only groups (46%). There was no significant difference in VTA recurrence between the nonresponder and the ICD-only groups. One patient each in the responder and the ICD-only groups died suddenly, and all-cause mortality was similar in the three groups. The incidence of inappropriate ICD discharges was less in the sotalol than in the ICD-only groups. No patient had to discontinue long-term sotalol treatment because of the adverse effects. In conclusion, sotalol reduced VTA recurrence in the responding patients and inappropriate ICD discharge. EPS may predict the efficacy of sotalol for VTA recurrence.

Background: Many patients with paroxysmal atrial fibrillation (AF) become refractory to antiarrhythmic drugs (AADs). Early studies suggested that linear catheter ablation in the right atrium may provide sufficient substrate modification to reestablish therapeutic efficacy of previously ineffective AADs., Methods: This prospective before-after multicenter trial evaluated the safety and effectiveness of hybrid therapy that included right atrial catheter ablation coupled with a regimen of previously ineffective AADs on AF episode frequency and symptoms in drug refractory patients with paroxysmal AF. A standard linear lesion set (lateral, septal, isthmus) was used in all subjects. AF episode frequency, clinical arrhythmia symptoms, condition-specific (AFSS) and global health-related quality of life (SF-36) were assessed prior to ablation and at 6 months., Results: Ninety-three subjects, refractory to an average 2.9 AADs at baseline, qualified for inclusion and underwent right atrial catheter ablation. Eighty-four subjects (90%) provided 6 month AF episode frequency data which demonstrated a significant decrease compared to baseline (3.4 vs. 9.5, p < 0.0001). Forty-nine subjects (58%) were considered a clinical success by virtue of achieving a pre-specified target level episode frequency reduction of 50% or greater. Substantial and statistically significant improvements were realized almost uniformly for all measured arrhythmia symptoms as well as for both quality of life measures. The incidence of major complications was 5.4%., Conclusions: The addition of right atrial catheter ablation to a regimen of previously ineffective AADs is associated with a significant reduction in the frequency, duration and severity of AF episodes and symptoms.

Aims: Atrial fibrillation (AF) shortens the atrial action potential and the atrial refractory period. These changes promote persistence of AF. Pharmacological prolongation of atrial action potential duration (APD) may therefore help to prevent recurrent AF. In addition to prolonging APD, sodium channel blockers may prevent AF by inducing post-repolarization refractoriness (PRR). We studied whether two antiarrhythmic drugs (sotalol, flecainide) prolong APD or induce PRR in the fibrillating human atrium., Methods: In 12 patients with persistent AF (11 male, 58 +/- 5 yrs, 27 +/- 7 months duration of AF), we recorded monophasic action potentials from the right atrial appendage and inferior right atrium at baseline and 15 minutes after intravenous administration of sotalol (1.5 mg/kg) or flecainide (2 mg/kg). APD and effective refractory periods (ERP) were determined., Results: Both drugs prolonged APD90 during AF (flecainide from 109 +/- 7 ms to 137 +/- 10 ms, sotalol from 108 +/- 6 ms to 131 +/- 8 ms, both p < 0.05 vs. baseline). Sotalol prolonged ERP in parallel to APD (from 119 +/- 8 ms to 139 +/- 8 ms, p < 0.05). Flecainide induced PRR by prolonging ERP more than APD90 (from 134 +/- 9 ms to 197 +/- 28 ms, p < 0.05 vs. baseline and vs. sotalol)., Conclusions: Flecainide and sotalol prolong the atrial action potential during atrial fibrillation in humans. In addition, flecainide induces atrial PRR. These electrophysiological effects may reduce AF recurrences and prevent their persistence.

Postoperative atrial fibrillation is a common complication after open heart surgery; it increases morbidity, hospital stay, and costs. In an analysis of 8 large cardiac surgery trials totaling 20,193 patients, the incidence of postoperative atrial fibrillation was estimated to be 26% and ranged from 17% to 35%. We reviewed the results of 52 studies published between 1966 and 2003 that evaluated pharmacologic strategies to prevent postoperative atrial fibrillation in nearly 10,000 patients undergoing open heart operations. Supraventricular tachyarrhythmias, including atrial fibrillation, after open heart operations occurred in 29% of patients who did not receive prophylactic drugs, compared with 12% in patients who received intravenous followed by oral amiodarone, 15% in those given sotalol, 16% in those given oral amiodarone, and 19% in those given beta-blockers. Pharmacologic strategies and regimens aimed at preventing postoperative atrial fibrillation are necessary to optimize the postoperative care of patients undergoing open heart operations. Although no strategy has consistently been shown to be superior to another, the most effective approach to preventing postoperative atrial fibrillation likely involves multiple interventions. In the absence of contraindications, all patients should receive beta-blocker therapy before and after the operation. For patients with 1 or more risk factors for postoperative atrial fibrillation, regimens consisting of either sotalol (beta-blocker with class III antiarrhythmic properties) alone or beta-blockers in combination with amiodarone seem to be the safest, most effective pharmacologic strategies for preventing postoperative atrial fibrillation.

This prospective, randomized, single-blinded, placebo-controlled study compared the efficacy and safety of sotalol and propafenone when used for long-term prevention of atrial fibrillation. For the long-term maintenance of normal sinus rhythm, propafenone seems to be more effective than sotalol.

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.

Supraventricular tachycardia is the most common clinically significant fetal tachycardia. The diagnosis is usually made at routine sonographic workup during the second-third trimester of pregnancy. Treatment goals are cardioversion to sinus rhythm and reversal of cardiac dysfunction. We describe a case of fetal supraventricular tachycardia diagnosed at 24 weeks of gestation. The first-line treatment was oral maternal digoxin and sotalol. This therapy was not sufficient for complete control of the tachycardia. Hence, second-line treatment with digoxin and flecainide was started and successfully achieved conversion to sinus rhythm. No adverse maternal side effects were noted during the 14 weeks of therapy. A normal male infant was delivered at elective cesarean section performed for obstetric indications at 38 weeks of gestation. A persistent junctional reciprocating tachycardia with a ventriculo-atrial/atrioventricular ratio > 1 was diagnosed following delivery at transesophageal electrophysiological study. At the age of 8 months the child is on therapy with sotalol (4 mg/kg/day) and flecainide (3 mg/kg/day) and is in good clinical conditions.

Objectives: This prospective, randomized, double-blind, placebo-controlled study compared the efficacy and safety of amiodarone and sotalol in the prevention of atrial fibrillation (AF) following open heart surgery., Background: The incidence of supraventricular arrhythmias following open heart surgery ranges from 20% to 40%, with AF being the most common. Both amiodarone and sotalol have been shown to be effective in reducing postoperative arrhythmias, but no direct comparison of these agents has been conducted., Methods: A total of 160 patients were randomized, of whom 134 underwent coronary artery bypass graft surgery (CABG) alone, 17 underwent CABG and concomitant aortic valve replacement surgery (AVR), 9 underwent AVR only, and 1 patient's surgery was canceled. Patients with signs or symptoms of congestive heart failure (CHF), ejection fraction < or =30%, estimated creatinine clearance <30 mL/min, or serum creatinine > or =2.5 mg/dL were excluded. Patients were randomized to receive either sotalol 80 mg 2 times per day (n = 76) or intravenous amiodarone 15 mg/kg over 24 hours followed by oral amiodarone 200 mg 3 times per day (n = 83). Study drug was started at the time of surgery and continued for 7 days or until discharge, whichever came first., Results: AF occurred in 17% of patients randomized to amiodarone and 25% of the patients randomized to sotalol (P =.21). However, the duration of AF was significantly shorter in amiodarone-treated patients (169 +/- 224 min) compared to sotalol treated patients (487 +/- 505 min; P =.04). In a subgroup analysis, the incidence of AF in patients undergoing AVR or CABG with AVR was significantly less with amiodarone (1/15, 7%) compared to sotalol (9/11, 82%) (P <.001). Blood pressure was lower immediately after surgery with amiodarone but comparable to sotalol at 24 hours. Of the hemodynamic indices measured, only stroke volume was significantly lower in patients randomized to sotalol at 24 hours (P =.035)., Conclusions: Amiodarone and sotalol share similar efficacy and safety in reducing postoperative AF. Hemodynamic effects were similar between both drugs at 24 hours, with the exception that stroke volume was lower in sotalol-treated patients. In patients undergoing more complex surgery, postoperative AF occurred more frequently with sotalol than with amiodarone.

Background: Of the antiarrhythmic agents currently marketed in Canada, 5 are commonly used to treat atrial fibrillation (AF). The impact of contraindications, warnings and precautions for the use of these drugs in patients with AF is not known. We evaluated the proportion of patients with AF for whom contraindications, warnings and/or precautions might limit the use of these commonly prescribed drugs and the proportion of patients actually receiving antiarrhythmic drugs despite the presence of contraindications and/or warnings., Methods: A total of 723 patients with electrocardiographically confirmed, new-onset paroxysmal AF who were enrolled in the Canadian Registry of Atrial Fibrillation were used in this analysis. The 1996 Compendium of Pharmaceuticals and Specialties was used to obtain contraindications, warnings and precautions for use of 5 antiarrhythmic drugs: flecainide, quinidine, sotalol, amiodarone and propafenone. Proportions of patients with contraindications, warnings and/or precautions for use of any of these drugs owing to comorbid conditions or concomitant drug therapy were calculated, regardless of whether the drugs had been prescribed. We then calculated the proportion of patients taking each antiarrhythmic drug at 3 months despite contraindications and/or warnings., Results: At baseline, when conditions for contraindications and warnings were combined, 414 (57%), 235 (33%), 327 (45%), 285 (39%) and 272 (38%) patients had restrictions for the use of flecainide, quinidine, sotalol, amiodarone and propafenone respectively. Among 465 patients actually taking these medications at 3-month follow-up, 33.3% (2/6), 83.3% (40/48), 36.4% (92/253), 64.1% (25/39) and 34.5% (41/119) respectively had contraindications and/or warnings against their use. The burden of comorbid disease among patients with AF was noteworthy: 404 (56%) had structural heart disease, which included 227 (31%) with ischemic heart disease, 158 (22%) with left ventricular systolic dysfunction and 106 (15%) with heart failure., Interpretation: The high burden of comorbid disease and concomitant drug use in a large proportion of patients with AF limits the suitability of existing antiarrhythmic drugs. Over one-third of patients with new-onset AF received antiarrhythmic drugs despite the presence of contraindications or warnings. Although such restrictions may not preclude the use of these drugs, the results demonstrate the need for new antiarrhythmic drugs with fewer limitations.

Aims: In patients with persistent atrial fibrillation (AF), the efficacy and safety of two anti-arrhythmic drugs in preventing the recurrence of AF after successful direct current (DC) cardioversion was prospectively assessed in a multi-centre double-blind, placebo-controlled, randomised trial using daily trans-telephonic monitoring., Methods and Results: 1182 patients with persistent AF were prospectively enrolled, 848 patients were successfully cardioverted and then randomised to either sotalol (383 patients), quinidine plus verapamil (377 patients) or placebo (88 patients). The primary outcome parameter was AF recurrence or death. All patients received an event recorder (Tele-ECG) and had to record and transmit via telephone at least one ECG per day during follow-up. The mean follow-up period was 266 days. A total of 191,103 Tele-ECGs were recorded and transmitted. The primary outcome parameter (AF recurrence of any kind or death) was observed in 572 patients (67%) in whom at least one episode of AF recurrence was documented during follow-up, in 348 patients (41%) AF recurrence was persistent. The recurrence rates after one year for any AF were 83% for placebo, 67% for sotalol and 65% for quinidine plus verapamil, the latter being statistically superior to placebo but not different from sotalol. The recurrence rates for the secondary outcome parameter persistent AF were 77%, 49% and 38%, respectively. Quinidine plus verapamil was significantly superior to placebo and to sotalol. About 95% of all AF recurrences were initially detected in the daily Tele-ECG, about 70% of all AF recurrences occurred completely asymptomatic. Adverse events on sotalol and quinidine plus verapamil were comparable with the exception that all torsade de pointes tachycardias occurred on sotalol., Conclusion: Anti-arrhythmic treatment after DC cardioversion of persistent AF significantly decreases the recurrence rates of persistent AF compared to placebo with superiority of quinidine plus verapamil compared to sotalol. Symptoms were not reliable as clinical surrogates to detect episodes of AF.

Background and Purpose: Pharmacological treatment of atrial fibrillation (AF) is limited by induction of malignant ventricular arrhythmias. Developing new drugs, a promising strategy is a more specific treatment of the atria. Muscarinic potassium current (IK[ACh]) is predominantly expressed in supraventricular tissue and mediates the induction of vagus-induced AF. The authors investigated the profile of representative class III drugs in respect to their effect on IK(ACh)., Methods: In rat atrial myocytes, IK(ACh) was activated by acetylcholine (ACh) measured with the whole-cell voltage clamp method. Drugs used: selective IKs blocker chromanole 293B (Cro); IKr blockers sotalol (Sot), dofetilide (Dof), ibutilide (Ibu), and terikalant (Ter). Data are expressed as mean values +/- standard deviation (SD)., Results: ACh-induced IK(ACh) density was 73 +/- 9 pA/pF (n= 9). IK(ACh) was almost completely desensitized in the presence of 50 micro M Ter, Ibu, or Dof. IC(50) of IK(ACh) inhibition by the three drugs was 0.9, 2.8, and 4.2 micro M (Dof, Ibu, and Ter, respectively). Receptor-independent GTP-gamma-S-induced IK(ACh) was sensitive to Ter, Ibu, and Dof as well. Sot is known to be a weak inhibitor of IKr. Inhibition of IK(ACh) by Sot was much less potent (IC(50) = 35.5 micro M) than inhibition by the high-affinity IKr blockers Ter, Ibu, and Dof. Superfusion of the cells with the IKs blocker Cro showed no desensitization of IK(ACh). Applied via the patch pipette (< 40 min) none of the class III drugs were effective., Conclusion: The results indicate inhibition of IK(ACh) and IKr but not IKs to be of similar mechanism (direct ion channel inhibition from the external side of the membrane). Potent desensitization of muscarinic potassium current could be of clinical relevance especially in patients with vagus-induced AF.

We describe a 53-year-old man with recurrent syncopal events and a malignant family history who was treated for 13 years with sotalol drug therapy with no further occurrence of Brugada syndrome symptoms. Genetic testing revealed that he carried a Brugada syndrome sodium channel SCN5A mutation (4189delT). This finding suggests that sotalol may be of therapeutic benefit in such patients.

Introduction: The atrial fibrillation is a severe and frequent disease, which influences greatly the patients' quality of life. Only a few Hungarian studies exist which discuss the physicians' own experiences in its treatment., Aim: The description of the experiences acquired in an internal medicine department with cardiological profile during the treatment based on the actual guidelines and the review of the results of one year follow-up., Method: Retrospective analysis of the data of patients treated with atrial fibrillation between 1 january 1999 and 31 december 2001 and a one year follow-up was performed. The age, gender, success in cardioversion, the antiarrhythmic therapy at the discharge and the modification in it during the first year were evaluated., Results: During the 3 years long period 1115 patients with atrial fibrillation were admitted (53.9% female, 46.1% male, the mean age was 72.0 +/- 10.4 years), 391 of whom were discharged with sinus rhythm. In 193 cases (49%) a spontaneous cardioversion was observed. 120 electrical (31%) and 78 pharmacological (20%) cardioversions were performed. The electrical form was carried out in 42 cases with acute atrial fibrillation (in 36 of them successfully) and in 100 cases as an elective procedure, in 84 successfully. Pharmacological cardioversion was made in 39 acute cases with the administration of propafenone (in 29 ones successfully) and in 57 elective cases with quinidine + beta-blocker + magnesium (in 49 ones successfully). For the maintenance of sinus rhythm in the 38.8% of cases amiodarone, 24.0% propafenone, 19.9% sotalol, 10.7% beta-blocker, 0.8% quinidine, 0.5% prajmaline was administered, and 5.1% of the patients didn't receive any special treatment. During the one year follow-up from the 391 patients 261 remained on sinus rhythm, in 81 cases (21%) the return of the atrial fibrillation was diagnosed (in 57 of them a successful cardioversion was performed again), 11 patients (3%) died and 38 (9%) were lost for observation. At the time of the one year control 57.8% of patients treated with amiodarone, 61.7% of those treated with propafenone, 67.9% with sotalol and 35.7% with beta-blocker remained on sinus rhythm. The amiodarone was omitted in 17 cases because of its side effects., Conclusions: The treatment of the atrial fibrillation has to be performed individually taking into account the guidelines, the comorbidity, the time of the beginning of rhythm disorder, the patients' present other drugs and the former antiarrhythmic therapy. A continuous and consistent follow-up of these patients is crucial.

In this study, high-risk patients with hypertrophic cardiomyopathy were treated with an implantable defibrillator. Long-term follow-up analysis showed the efficacy of implantable defibrillator therapy, with patients having an appropriate device intervention at a rate of 11%/year, thereby preventing sudden death in an Australian population.

Objectives: The purpose of this study was to evaluate the efficacy of various antiarrhythmic drugs at prolonging the QT interval into the normal range and preventing ventricular arrhythmias in patients with short QT syndrome., Background: Short QT syndrome is a recently described genetic disease characterized by short QT interval, high risk of sudden death, atrial fibrillation, and short refractory periods., Methods: Six patients with short QT syndrome, five of whom had received an implantable cardioverter-defibrillator (ICD) and one child, were tested with different antiarrhythmic drugs, including flecainide, sotalol, ibutilide, and hydroquinidine, to determine whether they could prolong the QT interval into the normal range and thus prevent symptoms and arrhythmia recurrences., Results: Class IC and III antiarrhythmic drugs did not produce a significant QT interval prolongation. Only hydroquinidine administration caused a QT prolongation, which increased from 263 +/- 12 ms to 362 +/- 25 ms (calculated QT from 290 +/- 13 ms to 405 +/- 26 ms). Ventricular programmed stimulation showed prolongation of ventricular effective refractory period to > or =200 ms, and ventricular fibrillation was no longer induced., Conclusions: The ability of quinidine to prolong the QT interval has the potential to be an effective therapy for short QT patients. This is particularly important because these patients are at risk of sudden death from birth, and ICD implant is not feasible in very young children.

(1) The treatment aims in atrial fibrillation are to reduce patients' symptoms and to prevent both embolism and deterioration of any underlying heart disease. Therapy consists of anticoagulant or antiplatelet drugs, treatment of any underlying heart disease, and heart rate control. (2) Digoxin, betablockers, diltiazem and verapamil slow the heart rate but rarely restore sinus rhythm. Amiodarone, disopyramide, flecainide, quinidine and sotalol can be used to prevent relapse of atrial fibrillation after electrical cardioversion, but they all have potentially serious adverse effects. New trials of antiarrhythmic treatments have been published since our last review of this subject. (3) In one trial in 403 patients, amiodarone was more effective than sotalol and propafenone in restoring and maintaining sinus rhythm. After 15 months of follow-up, there were fewer strokes among patients treated with amiodarone, but there was no difference between the three drugs in the overall incidence of cardiovascular events. (4) A clinical trial with 4060 patients compared rhythm control (mainly with amiodarone, sotalol or propafenone; sometimes combined with electrical cardioversion) and rate control (with digoxin, betablocker, diltiazem or verapamil; systematically combined with anticoagulant therapy). The antiarrhythmic treatment restored sinus rhythm in more than half the patients in the long term. But rhythm control did not reduce the risk of death or serious cardiovascular events during a mean follow-up period of 3.5 years. Rhythm control caused more adverse events than rate control; subgroup analyses (weak evidence) suggest that rhythm control may also have caused more deaths among patients over 65 and among patients with coronary heart disease. (5) In another trial, electrical cardioversion followed by antiarrhythmic therapy (mainly sotalol) sustainably restored sinus rhythm in more than one-third of 522 patients. But, compared with rate control treatment plus anticoagulant therapy, rhythm control did not reduce the risk of cardiovascular events, and was associated with a larger number of serious adverse cardiac effects. (6) Other recent trials confirm the risk of serious adverse effects, including severe arrhythmia with sotalol (especially at the start of treatment), and adverse thyroid and pulmonary effects with amiodarone. (7) Combined radiofrequency ablation and cardiac stimulation improved symptoms in some patients with incapacitating atrial fibrillation who had not responded to other treatments. However, this approach carries a risk of serious adverse effects, and its impact on the risk of cardiovascular events and death is not known. (8) In practice, an attempt should be made to restore sinus rhythm with amiodarone and/or electrical cardioversion, in symptomatic, recent or paroxysmal atrial fibrillation in patients under 65 who have no signs or symptoms of coronary heart disease. In other situations, rate control is the first-line option, using digoxin, betablockers (other than sotalol) or calcium channel blockers (diltiazem or verapamil). Whatever the option, treatment must be combined with anticoagulant or antiplatelet therapy, and with treatment of any underlying heart disease.

Background: Atrial fibrillation (AF) frequently occurs after cardiac surgical procedures, and beta-blockers, sotalol, and amiodarone may reduce the frequency of AF after open heart surgery. This pilot trial was designed to test whether each of the active oral drug regimens is superior to placebo for prevention of postoperative AF and whether there are differences in favor of 1 of the preventive strategies., Methods and Results: We conducted a randomized, double-blinded, placebo-controlled trial in which patients undergoing cardiac surgery in the absence of heart failure and without significant left ventricular dysfunction (n = 253; average age, 65 +/- 11 years) received oral amiodarone plus metoprolol (n = 63), metoprolol alone (n = 62), sotalol (n = 63), or placebo (n = 65). Patients receiving combination therapy (amiodarone plus metoprolol) and those receiving sotalol had a significantly lower frequency of AF (30.2% and 31.7%; absolute difference, 23.6% and 22.1%; odds ratios [OR], 0.37 [95% CI, 0.18 to 0.77, P <.01 vs placebo] and 0.40 [0.19 to 0.82, P =.01 vs placebo]) compared with patients receiving placebo (53.8%). Treatment with metoprolol was associated with a 13.5% absolute reduction of AF (P =.16; OR, 0.58 [0.29 to 1.17]. Treatment effects did not differ significantly between active drug groups. Adverse events including cerebrovascular accident, postoperative ventricular tachycardia, nausea, and dyspepsia, in hospital death, postoperative infections, and hypotension, were similar among the groups. Bradycardia necessitating dose reduction or drug withdrawal occurred in 3.1% (placebo), 3.2% (combined amiodarone and metoprolol; P =.65 vs placebo), 12.7% (sotalol; P <.05 vs placebo), and 16.1% (metoprolol; P <.05 vs placebo). Patients in the placebo group had a nonsignificantly longer length of hospital stay as compared with the active treatment groups (13.1 +/- 8.9 days vs 11.3 +/- 7; P =.10), with no significant difference between the active treatment groups., Conclusions: Oral active prophylaxis with either sotalol or amiodarone plus metoprolol may reduce the rate of AF after cardiac surgery in a population at high risk for postoperative AF. Treatment with metoprolol alone resulted in a trend to a lower risk for postoperative AF.

Atrioventricular reciprocating tachycardia (AVRT) using an accessory pathway is the most common supraventricular tachycardia observed in infancy and childhood. There is a general agreement to treat children older than 5 years who are on a potentially long-term antiarrhythmic agent with radiofrequency catheter ablation. Atenolol, a relatively long-acting and cardioselective beta-adrenoceptor blocker, has been used to control the various types of supraventricular tachycardia in children and adults. There are few reports on the use of atenolol in children <5 years old with AVRT. This retrospective study reports our experience in 22 children <5 years old (median age, 20 months) who received atenolol monotherapy between 1995 and 2001 for treatment of AVRT. AVRT was confirmed in 17 patients by transvenous or transesophageal electrophysiologic study and in 5 patients by documented preexcitation on electrocardiograms. In nine patients atenolol was the first antiarrhythmic drug given. In 15 of the 22 patients (68%) therapy with atenolol was considered successful. The average effective dose of atenolol in these 15 patients was 1.2 +/- 0.3 mg/kg/day. During a median follow-up of 41 months (8-74 months), atenolol had been discontinued in 10 patients and no further attacks of tachycardia occurred except in 1 patient. In no case did the drug have to be withdrawn for adverse effects. In conclusion, this retrospective study shows that atenolol as a monotherapy is efficient and relatively safe in the long-term treatment of AVRT in young children. Atenolol can be recommended as a first-line treatment option for the management of AVRT in infants and young children.

In the post-AFFIRM era, treatment of AF has become the treatment of symptoms. In some patients, this will be simple rate control, but there remain a significant cohort of patients in whom rate control alone does not give acceptable symptom relief. In this group, antiarrhythmic therapy still has a role, and the AFFIRM trial indicates that this therapeutic strategy is without significant deleterious effect on mortality. The choice of antiarrhythmic agent must be individualized according to underlying cardiac pathologies and comorbidities, however. Most recently, the introduction of dofetilide has widened the therapeutic options in patients with severe heart disease, and the Canadian Trial of Atrial Fibrillation indicated the superior efficacy of amiodarone at low doses. The release/ development of newer Class III antiarrhythmic agents may offer hope for the benefits of amiodarone without the serious adverse effects with long-term therapy.

Purpose of Review: This review describes the latest developments in the clinical usage of class III antiarrhythmics. It also discusses some new studies providing insight into the mechanism of action of these drugs., Recent Findings: New data suggest that amiodarone is one of the most effective drugs for management of ventricular as well as supraventricular tachyarrhythmias. As over the years we have learned to deal with the toxic side effects of this drug, the risk of bradyarrhythmias requiring placement of a pacemaker is becoming more significant. Sotalol was approved for treatment of atrial fibrillation and atrial flutter (AF). It was also found to be effective in management of postoperative AF. Dofetilide has been approved for the conversion and maintenance of sinus rhythm in AF; its role in ventricular arrhythmias remains unclear. Data are emerging regarding clinical efficacy of azimilide and dronedarone., Summary: Management of arrhythmias in patients with structural heart disease remains a challenge. Class III antiarrhythmics are the mainstay of treatment in this group of patients.

Aim: To analyze action of digoxin and some non-digitalis drugs (beta-blockers, verapamil, amiodarone, d,l-sotalol) and their combinations on electrical activity of atria, frequency and structure of ventricular rhythm in patients with permanent atrial fibrillation., Material and Methods: One hundred patients with permanent atrial fibrillation and heart rate at rest above 80 bpm were divided into 9 treatment groups. High-resolution orthogonal Frank lead ECG was recorded before and after allocated treatment. Analysis included construction of ff-waves periodograms, histograms of RR interval, cardiointervalograms and application of autocorrelation function., Results: It was demonstrated that frequency and form (structure) of ventricular rhythm was determined not only by the state of AV conduction but also by value of basic period of ff-waves. The mechanisms of ventricular rate deceleration by investigated drugs were not identical. beta-blockers and verapamil directly slowed AV conduction without changing parameters of ff-waves and differed from each other only in action on parameters of concealed conduction in AV node. Action of digoxin in patients with ff-waves period equal to or exceeding 0,15 s was biphasic. During phase I shortening of ff-wave period (by 0.025+/-0.012 s) occurred. This was associated with increase of their concealed conduction through AV node. The latter phenomenon represented independent mechanism of ventricular rhythm deceleration. During phase II of digoxin action direct inhibition of AV conduction took place. Amiodarone and d,l-sotalol increased basic ff-waves period. This facilitated their conduction through AV node. Greater heart rate slowing effect of d,l-sotalol was attributed to its ability to augment concealed conduction. Due to their antiarrhythmic qualities amiodarone and d,l-sotalol slowed heart rate in patients with peak RR duration in the region of 0.28-0.46 s. These patients often had bi- and tri-modal structure of interval RR histogram. Changes of ventricular rhythm structure during use of various drugs were different. Action of digoxin was most whilst that of beta-blockers least favorable., Conclusion: Choice of a drug for treatment of permanent atrial fibrillation should be conducted with consideration of ff-waves periodicity, parameters of RR interval histogram, and characteristics of ventricular rhythm structure.

Purpose of Review: Atrial fibrillation, atrial flutter, AV-nodal reentry tachycardia with rapid ventricular response, atrial ectopic tachycardia, and preexcitation syndromes combined with atrial fibrillation or ventricular tachyarrhythmias are typical arrhythmias in intensive care patients. Most frequently, the diagnosis of the underlying arrhythmia is possible from the physical examination, the response to maneuvers or drugs, and the 12-lead surface electrocardiogram. In all patients with unstable hemodynamics, immediate DC-cardioversion is indicated. Conversion of atrial fibrillation to sinus rhythm is possible using antiarrhythmic drugs. Amiodarone has a conversion rate in atrial fibrillation of up to 80%. However, caution in the use of short-term administration of intravenous amiodarone in critically ill patients with recent-onset atrial fibrillation is absolutely necessary, and the duration of therapy should not exceed 24 to 48 hours. Ibutilide represents a relatively new class III antiarrhythmic agent that has been reported to have conversion rates of 50% to 70%; it seems that ibutilide is even successful when intravenous amiodarone failed to convert atrial fibrillation., Recent Findings: Newer studies compared the outcome of patients with atrial fibrillation and rhythm- or rate-control. Data from these studies (AFFIRM, RACE) clearly showed that rhythm control is not superior to rate control for the prevention of death and morbidity from cardiovascular causes. Therefore, rate-control may be an appropriate therapy in patients with recurrent atrial fibrillation after DC-cardioversion. Acute therapy of atrial flutter in intensive care patients depends on the clinical presentation. Atrial flutter can most often be successfully cardioverted to sinus rhythm with energies less than 50 joules. Ibutilide trials showed efficacy rates of 38-76% for conversion of atrial flutter to sinus rhythm compared with conversion rates of 5-13% when intravenous flecainide, propafenone, or verapamil was administered. In addition, a high dose (2 mg) of ibutilide was more effective than sotalol (1.5 mg/kg) in conversion of atrial flutter to sinus rhythm (70% versus 19%)., Summary: There is general agreement that bystander first aid, defibrillation, and advanced life support is essential for neurologic outcome in patients after cardiac arrest due to ventricular tachyarrhythmias. The best survival rate from cardiac arrest can be achieved only when (1) recognition of early warning signs, (2) activation of the emergency medical services system, (3) basic cardiopulmonary resuscitation, (4) defibrillation, (5) management of the airway and ventilation, and (6) intravenous administration of medications occurs as rapidly as possible. Public access defibrillation, which places automatic external defibrillators in the hands of trained laypersons, seems to be an ideal approach in the treatment of ventricular fibrillation. The use of automatic external defibrillators by basic life support ambulance providers or first responder in early defibrillation programs has been associated with a significant increase in survival rates. Drugs such as lidocaine, procainamide, sotalol, amiodarone, or magnesium were recommended for treatment of ventricular tachyarrhythmias in intensive care patients. Amiodarone is a highly efficacious antiarrhythmic agent for many cardiac arrhythmias, ranging from atrial fibrillation to malignant ventricular tachyarrhythmias, and seems to be superior to other antiarrhythmic agents.

Objective: To determine how well dofetilide and Betapace AF (sotalol, approved solely for atrial fibrillation and atrial flutter), with their detailed dosing and monitoring guidelines for safety, were accepted into clinical practice during the 2 calendar years after their introduction., Methods and Results: We reviewed the number of new, refill, and total prescriptions of all antiarrhythmic agents in the United States from April 2000-December 2001 to assess use of dofetilide and Betapace AF in the drug market. Both were prescribed very infrequently throughout the study period. In addition, the infrequent reported use of these drugs for patients with atrial fibrillation and flutter indicated poor acceptance of these agents by prescribing physicians. We speculated that the restricted distribution and required educational program for dofetilide, as well as the availability of generic sotalol products, may have discouraged physicians from prescribing both dofetilide and Betapace AE CONCLUSION: A common goal for both the dofetilide risk-management program and the creation of a sotalol product indicated solely for atrial fibrillation and atrial flutter was to provide safer treatment for patients with these arrhythmias. Unfortunately, limited penetration of dofetilide and Betapace AF into the U.S. market suggests that drugs without a risk-management program or detailed dosing guidelines were more likely than dofetilide or Betapace AF to be selected for treatment of atrial fibrillation and atrial flutter.

The results of clinical trials in postmyocardial infarction patients using type I antiarrhythmic drugs have been disappointing. There was optimism that IKr blockers might result in a reduction in sudden cardiac death in postinfarct population. Four trials are reviewed here, and the results are variable. The four drugs reviewed--d,l-sotalol, d-sotalol, dofetilide, and azimilide--all share IKr-blocking properties. In addition, d,l-sotalol is a beta-blocker and azimilide is an IKs blocker. The primary uses of d,l-sotalol, dofetilide, and, if approved, azimilide are currently for treatment of atrial fibrillation. Thus, the mortality trials reviewed here are primarily used as support of safety in high-risk patients, because none has achieved a mortality reduction in postinfarction patients. These trials play pivotal roles for regulatory approval of these drugs for use in atrial fibrillation.

Many patients with atrial fibrillation develop symptoms attributable to the cardiac arrhythmia itself. These symptoms may be improved either by restoring sinus rhythm or by controlling the rapid and irregular ventricular response that often accompanies this arrhythmia. One of the principal goals of therapy of atrial fibrillation management is improvement of patient symptoms; it is important to quantify these symptoms by some form of quality of life analysis. The Canadian Trial of Atrial Fibrillation (CTAF) was a multi-centre randomized clinical trial of amiodarone compared with either propafenone or sotalol in patients with recent atrial fibrillation. The quality of life (QOL) substudy of CTAF was a prospective, comprehensive assessment of quality of life of patients enrolled in CTAF. Summary measures of physical and mental health on the generic QOL scale (SF-36) improved significantly with treatment from baseline to 3 months (41.9 +/- 9.6 to 43.7 +/- 9.2, p = 0.001 for the physical component and 47.5 +/- 10.4 to 49.0 +/- 9.8, p = 0.023 for the mental component). On an arrhythmia specific scale (SCL), a significant and larger improvement was noted from baseline to 3 months in both arrhythmia symptom frequency and severity (symptom frequency from 20.4 +/- 9.4 to 16.2 +/- 9.5, symptom severity from 16.7 +/- 8.2 to 12.9 +/- 7.6, both p < 0.001). The quality of life improvements were similar in the amiodarone group compared to the sotalol or propafenone groups, both for the SF-36 and the disease-specific symptom checklist (SCL) measures. In contrast, an atrial fibrillation severity scale (AFSS) did show differences between the assigned drug therapies, which were associated with different rates of arrhythmia recurrence in the parent study. By 3 months global well-being was significantly worse for patients who had recurrent atrial fibrillation compared to those who did not (6.9 +/- 1.8 versus 7.4 +/- 1.8, p = 0.04). Similarly, symptom severity at 3 months was 11.8 +/- 7.4 for patients without recurrence, compared to 14.8 +/- 7.4 for those with recurrence ( p = 0.001). Interestingly, none of the usual clinical variables that might be perceived to be associated with quality of life, e.g., male versus female sex, age, NYHA class, beta blocker use, and ejection fraction, had much impact on subjective quality of life measures. Quality of life improves with treatment atrial fibrillation and at least some of these improvements are related to the restoration and maintenance of sinus rhythm.

Atrial fibrillation (AF) is a highly prevalent arrhythmia that is difficult to treat and generates important health care costs. One consideration in the selection of various therapeutic options is the cost of a given treatment compared to that of alternatives. The Canadian Trial of Atrial Fibrillation (CTAF) evaluated the effectiveness of sinus rhythm maintenance with amiodarone compared to propafenone or sotalol in a prospective, randomized fashion. A subsequent CTAF substudy of the medical costs associated with amiodarone vs. propafenone/sotalol found that amiodarone decreased AF-related costs. This paper reviews the results of the CTAF cost-analysis substudy in the context of other analyses in the literature of the cost effectiveness of amiodarone in AF. The costs associated with amiodarone therapy are no greater than for other sinus rhythm maintenance drugs, and for some cost categories and some patient subgroups are likely to be less, despite amiodarone's greater therapeutic efficacy. However, additional considerations are important in evaluating the clinical place of amiodarone, including its adverse effect and pharmacokinetic profile. As well, the results of recent randomized clinical trials have highlighted the limitations of sinus rhythm maintenance as a primary therapeutic objective in AF. The decision about whether and at what point to use amiodarone in a given patient requires a careful analysis of the individual case, in terms of symptomatology during AF, the response to previous treatment regimes, and risk factors for various forms of adverse drug reactions.

Early reinitiation of atrial fibrillation (ERAF) was commonly observed after successful electrical cardioversion, however, the effect of ERAF on the subsequent time course of arrhythmia recurrence remains unclear. The aim of this study was to evaluate the clinical predictors and time course of AF recurrence with respect to the occurrence of ERAF after successful cardioversion. The clinical predictors and time course of AF recurrence were prospectively evaluated in 124 patients (94 men, 30 women; mean age 65 +/- 9 years) with persistent AF (mean AF duration 36 +/- 40 months), who underwent internal cardioversion. After cardioversion, all patients received treatment with sotalol and were monitored for AF recurrence. Successful restoration of sinus rhythm was achieved in 104 (84%) of 124 patients. ERAF was observed in 28 (27%) of 104 patients in whom 26 of them were successfully treated acutely with intravenous sotalol and repeated cardioversion. After a mean follow-up of 26 months, 29 (28%) of 104 patients remained in sinus rhythm. Kaplan-Meier analysis revealed a significantly poorer outcome with regard to the recurrence of AF in patients with ERAF (hazard ratio 1.7,P = 0.03) and in those with AF for more than 3 years (hazard ratio 1.6,P = 0.03). Despite treatment with sotalol, patients with ERAF had a significantly higher AF recurrence rate within the first day (13/26 [50%] vs 12/76 [16%],P < 0.01), but not during long-term follow-up (21/26 [81%] vs 52/76 [68%],P = 0.3). In contrast, patients with AF for more than 3 years had a similar AF recurrence rate within the first day (7/29 [24%] vs 18/73 [25%],P = 1.0), but a significantly higher recurrence rate during long-term follow-up (27/29 [93%] vs 46/73 [37%],P < 0.01). In conclusion, the occurrence of ERAF and long AF duration were independent predictors for AF recurrence after successful internal cardioversion. The difference in the time course of AF recurrence in patients with ERAF from those with long AF duration suggests distinct arrhythmogenic mechanisms.

Results from clinical trials suggest that antiarrhythmic drugs (AD) can facilitate electrical cardioversion (EC) for persistent atrial fibrillation (AF) (duration >48 hours, no spontaneous termination) by suppression of immediate reinitiation of AF following the procedure. Class IC agents may increase the atrial defibrillation threshold (DFT) by significantly reducing the availability of Na+-channel for depolarization. In contrast, class III agents may decrease the atrial DFT by markedly prolonging atrial refractoriness. Among all AD, ibutilide and amoidarone have been shown to be most effective in enhancing the acute outcome of EC. In patients who are over 65 years of age at high risks of stroke (e.g., atherosclerotic cardiovascular disease, diabetes, hypertension, previous thromboembolism, etc.), the rhythm control strategy offers no survival advantage over the rate control strategy and frequently subjects patients to serious adverse effects of AD therapy. It can not be overemphasized that adequate anticoagulation (INR 2.0-3.0) with warfarin is needed regardless of whichever strategy is chosen unless there are contraindications. On the other hand, in patients who are under 65 years of age without structural heart disease or other risk factors of stroke, rhythm control can be the treatment of choice. Specifically, if a patient has failed EC alone or if the patient has characteristics (e.g., duration of AF >6 months, left atrium >50 mm, etc.) that EC could fail, AD may be given before the procedure to facilitate EC. In the subgroup of patients who are symptomatic with hypertrophic cardiomyopathy and severe diastolic dysfunction requiring maintenance of sinus rhythm to have sufficient ventricular function for optimization of cardiac output, an aggressive approach for rhythm control with amiodarone along with adequate anticoagulation with warfarin should be encouraged.

Objectives: The aim of this study was to investigate the pharmacokinetics and pharmacodynamics of sotalol in the treatment of fetal tachycardia., Background: Maternally administered, intrauterine therapy of fetal tachycardia is dependent on the transplacental passage of the antiarrhythmic agent., Methods: In a prospective study of patients treated for fetal tachycardia with sotalol, concentrations of sotalol were determined in maternal and umbilical blood and in amniotic fluid, and the relationship between these concentrations and the occurrence of conversion to sinus rhythm was investigated., Results: Eighteen fetal patients were studied, nine with atrial flutter and nine with supraventricular tachycardia. Fourteen were treated with sotalol; 13 converted to sinus rhythm, of whom 2 relapsed. There was one intrauterine death. Four patients were treated with sotalol and digoxin, of whom two were treated successfully. Mean birth weight was 3,266 g. The daily maternal sotalol dose was linearly related to the maternal plasma concentration. The mean fetal/maternal sotalol plasma concentration was 1.1 (range 0.67 to 2.87, SD 0.63), and the mean amniotic fluid/fetal blood ratio of sotalol was 3.2 (range 1.28 to 5.8, SD 1.4). The effectiveness of sotalol therapy could not be extrapolated from maternal blood levels., Conclusions: Sotalol is a potent antiarrhythmic agent in the treatment of fetal tachycardia. The placental transfer is excellent. Sotalol accumulates in amniotic fluid but not in the fetus itself. Therefore it seems that renal excretion in the fetus is efficient and greater than the oral absorption by fetal swallowing. The maternal blood level is not a reliable predictor of the chances of success of therapy. Sotalol is not associated with fetal growth restriction.

The Sotalol-Amiodarone Fibrillation Efficacy Trial (SAFE-T) is a randomized, double-blind, multicenter, placebo-controlled trial in which the effects of sotalol and amiodarone in maintaining stability of sinus rhythm are being examined in patients with persistent atrial fibrillation at 20 Veterans Affairs medical centers. The time to the occurrence of atrial fibrillation or flutter in patients with atrial fibrillation converted to sinus rhythm is the primary outcome measure, with a number of parameters as secondary end points. SAFE-T had randomized 665 patients when enrollment terminated on October 31, 2001. Follow-up of patients continued until October 31, 2002, for a maximum period of 54 months and a minimum period of 12 months for all patients.

Objectives: This study evaluated the efficacy of antiarrhythmic drugs for the treatment of atrial fibrillation (AF)., Background: The most effective and safest antiarrhythmic drug for the treatment of AF is unknown., Methods: The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study compared two treatment strategies--rate control and rhythm control--in patients with AF and risk factors for stroke or death. This substudy, performed in patients randomized to rhythm control, compared different antiarrhythmic drugs by randomly assigning the first drug treatment to: 1) amiodarone, 2) sotalol, or 3) a class I drug. The primary end point was the proportion of patients alive, in sinus rhythm, with no additional cardioversions and still taking the assigned drug at one year. Comparisons were made between patients eligible for each of three drug pairs., Results: At one year, in 222 patients randomized between amiodarone and class I agents, 62% were successfully treated with amiodarone, compared with 23% taking class I agents (p < 0.001). In 256 patients randomized between amiodarone and sotalol, 60% versus 38% were successfully treated, respectively (p = 0.002). In 183 patients randomized between sotalol and class I agents, 34% versus 23% were successfully treated, respectively (p = 0.488), although this portion of the substudy was stopped early when amiodarone was shown to be better than class I agents. Sinus rhythm was achieved in nearly 80% of patients at one-year follow-up with serial therapy. Adverse effects were common., Conclusions: Amiodarone was more effective at one year than either sotalol or class I agents for the strategy of maintenance of sinus rhythm without cardioversion.

Background and Aim of the Study: Left atrial enlargement is a risk factor for the development of atrial fibrillation (AF). Large atrial size increases thromboembolic risk and reduces the success rate of cardioversion. The study aim was to evaluate if left atrial size reduction affects cardiac rhythm in patients with chronic AF undergoing mitral valve surgery., Methods: Twenty-seven patients were analyzed prospectively. The left atrial incision was extended to the left inferior pulmonary vein. Left atrial size reduction was achieved by closure of the left atrial appendage from inside with a double running suture. The same suture plicated the left lateral atrial wall to the roof of the left pulmonary vein inflow and the inferior atrial wall. The atrial septum was plicated by placing stitches of the closing suture line across the fossa ovalis. Rhythm, neurological complications, cardioversion, anticoagulation and anti-arrhythmic medication were evaluated at one year postoperatively and at recent follow up (mean 40 +/- 15 months)., Results: At discharge, five patients (19%) were in sinus rhythm (SR). At one year postoperatively, SR was restored in 17 patients (63%), but five (19%) reported episodes of arrhythmia and AF persisted in 10 (37%). At recent follow up, four patients had died and three were lost to follow up. Among 20 patients examined, 13 (65%) had SR but six reported episodes of arrhythmia and AF persisted in seven (35%). LA diameter was significantly reduced, from 60.2 +/- 9.8 mm preoperatively to 44.5 +/- 7.0 mm at one year after surgery., Conclusion: The addition of left atrial size reduction to mitral valve surgery is technically simple, and was effective in 63% of patients with chronic AF, restoring predominant SR. In order to influence pathogenetic factors other than size, additional ablative steps may further increase the SR conversion rate. Size reduction may also improve the outcome of other ablative approaches.

Postoperative atrial fibrillation after heart surgery is frequent and may increase the length of hospital stay and costs of postoperative care of patients after heat surgery. Pharmacological and pacing interventions were evaluated in the large number of relatively small trials with often contradictory results. Conventional beta-blockers, sotalol, amiodarone and pacing were shown to be equally effective in the prevention of postoperative atrial fibrillation. Amiodarone and bi-atrial pacing were also effective in decreasing the length of hospital stay.

We present the case of 81-years old woman with diabetes mellitus and moderate hypertension who reported multiple syncope's. Cerebral and metabolic causes of syncope's were excluded and the patient was diagnosed to have sick sinus syndrome. After implantation of the cardiac pacemaker the treatment with sotalol was started. After introducing the antiarrhythmic drug the frequency of syncopes increased dramatically and blood pressure rose unusually (up to 250/140 mm Hg). Subsequently phaeochromocytoma was suspected. Laboratory data as well as computed tomography confirmed the diagnosis of left adrenal tumour. After successful surgery the blood pressure normalized and the patient recovered uneventfully. The reported cases describes the difficulties in diagnosing phaeochromocytoma in elderly people with multiple different accompanying diseases.

Atrial fibrillation (AF) remains a frequent complication of cardiac surgery. The optimal treatment strategy has not been established. Retrospective studies have suggested that a primary rate-control strategy may be equivalent to a strategy that restores sinus rhythm. Fifty patients with postoperative atrial fibrillation were randomly assigned to a strategy of antiarrhythmic therapy +/- electrical cardioversion or ventricular rate control. Anticoagulation with heparin overlapped with coumadin was administered to both arms. The primary endpoint of the study was time to conversion to sinus rhythm analyzed by the Kaplan-Meier method. The effects of strategy on hospital length of stay was examined as well as the incidence of recurrent AF. This study demonstrated no significant difference between an antiarrhythmic conversion strategy (n = 27) and a rate-control strategy (n = 23) in time to conversion to sinus rhythm (11.2 +/- 3.2 vs. 11.8 +/- 3.9 hours; p = 0.8). With Cox multivariate analysis to control for the effects of age, sex, beta-blocker usage, and type of surgery, the conversion strategy showed a trend toward reducing the time from treatment to restoration of sinus rhythm (p = 0.08). The length of hospital stay was reduced in the antiarrhythmic arm compared with the rate-control strategy (9.0 +/- 0.7 vs. 13.2 +/- 2.0 days; p = 0.05). In hospital relapse rates in the antiarrhythmic arm were 30% compared with 57% in the rate-control strategy (p = 0.24). At the termination of the study, 91% of the patients in the rate-control arm were in sinus rhythm compared with 96% in the antiarrhythmic arm. In conclusion, this pilot study shows little difference between a rate-control strategy and a strategy to restore/maintain sinus rhythm. Regardless of the strategy, majority of patients will be in sinus rhythm after two months. A larger randomized, controlled study is needed to assess the impact of restoration of sinus rhythm on length of stay.

Objective: Atrial Fibrillation (AF) is a common complication of coronary artery bypass surgery reported to occur in 20-40% of patients. Sotalol alone and magnesium alone have been shown to decrease the incidence of AF. The aim of this study was to evaluate the efficacy of these two agents, alone or in combination, to reduce postoperative AF., Methods: Two hundreds and seven consecutive coronary artery bypass patients were randomized to receive sotalol alone (80 mg two times daily for five days starting from the morning of the first postoperative day), magnesium alone (1.5 g daily for six days starting in the operating room just before cardiopulmonary bypass), both pharmacological agents at the same dosages or no antiarrhythmic agents (Control group). Patients with an ejection fraction <40% were excluded., Results: The incidence of postoperative AF was 11.8% (6/51) in the sotalol group, 14.8% (8/54) in the magnesium group, 1.9% (1/52) in sotalol+magnesium group and 38% (19/50) in the control group. The differences were significant between the control group and the other three groups (sotalol, magnesium and sotalol + magnesium groups: p = 0.002, p = 0.007 and p < 0.0001 respectively), and between the sotalol + magnesium group and single drug groups (sotalol and magnesium groups: p = 0.04 and p = 0.01, respectively., Conclusion: The incidence of AF after coronary surgery was significantly reduced by the administration of sotalol alone and magnesium alone. The incidence of postoperative AF was further reduced by combining the two pharmacological agents.

Objective: To describe the prenatal management and outcome of a series of 66 fetuses with supraventricular tachycardia (SVT)., Material and Methods: The perinatal data of 66 fetuses with SVT were retrospectively studied from January 1990 to December 2000. Junctional tachycardia was found in 50 fetuses and atrial flutter was found in 16 fetuses. Two groups were studied depending on the absence (n=40) or the presence of hydrops (n=26) at the time of the diagnosis. All fetuses but one were treated prenatally via the mother. Anti-arrhythmic drugs used were: digoxin, sotalol, flecainide or amiodarone., Results: Group of fetuses with no hydrops: digoxin was used in 32 cases and allowed 26 fetuses to be converted to sinus rhythm (80%). One intra uterine death (IUD) occurred in this group. Hydropic fetuses group: nine fetuses were converted to sinus rhythm using either flecainide (n=7) or amiodarone (n=2) as first line therapy, whilst digoxin alone or in association with sotalol failed to restore sinus rhythm in all cases. After first line therapy, SVT persisted in 10 fetuses. Nine fetuses received amiodarone alone or in association with digoxin as second line therapy, five of whom were converted to sinus rhythm. Among the 18 alive neonates treated by amiodarone in utero, three presented elevated thyroid stimulating hormone at day 3-4 and required thyroid hormonal substitution therapy for 2-6 months with normal outcome.

Post-operative atrial fibrillation is very common. It is associated with increased length of ICU and hospital stay, and costs of post-operative care of patients after cardiac surgery. More then seventy trials on the pharmacological and non-pharmacological interventions were conducted since 1970's. Meta-analysis of these trials, together with detailed analysis of the largest of these trials suggested that conventional beta-blockers, sotalol, amiodarone and bi-atrial overdrive pacing are effective in prevention of post-operative atrial fibrillation. Amiodarone and bi-atrial pacing may decrease the length of hospital stay.

Introduction: This study assessed the role of electrophysiologic testing to identify therapeutic strategies for the treatment of patients with sustained ventricular tachycardia (VT) and chronic chagasic cardiomyopathy treated with amiodarone or sotalol., Methods and Results: One hundred fifteen patients [69 men (60%); mean age 52 +/- 10 years] with chagasic cardiomyopathy presenting with symptomatic VT were studied after loading with Class III antiarrhythmic drugs; 78 had a history of sustained VT, and 37 with symptomatic nonsustained VT had sustained VT induced at baseline electrophysiologic study. All but 12 patients also underwent baseline electrophysiologic study. Mean left ventricular ejection fraction was 0.49 +/- 0.14. Based on results of electrophysiologic study after loading with Class III drugs, patients were divided into three groups: group 1 (n = 23) had no sustained VT induced; group 2 (n = 45) had only tolerated sustained VT induced; and group 3 (n = 47) had hemodynamically unstable sustained VT induced. After a mean follow-up of 52 +/- 32 months, total mortality rate was 39.1%; it was significantly higher in group 3 than in groups 2 and 1 [69%, 22.2%, and 26%, respectively, P < 0.0001, hazard ratio (HR) 10.4, 95% confidence interval (CI) 3.8, 21.8]. There was no significant difference in total mortality rate between groups 1 and 2 (P = 0.40, HR 1.5, 95% CI 0.75, 4.58). Cardiac mortality and sudden cardiac death rates also were higher in group 3 patients., Conclusion: In patients with chagasic cardiomyopathy and sustained VT, electrophysiologic testing can predict long-term efficacy of Class III antiarrhythmic drugs. This may help in the selection of patients for implantable cardioverter defibrillator therapy.

Objectives: This study was designed to compare two treatment strategies in patients with atrial fibrillation(AF): rhythm-control (restoration and maintenance of sinus rhythm) and rate-control (pharmacologic or invasive rate-control and anticoagulation)., Background: Atrial fibrillation is the most common arrhythmia. It is unclear whether a strategy of rhythm- or rate-control is better in terms of mortality, morbidity, and quality of life., Methods: The Strategies of Treatment of Atrial Fibrillation (STAF) multicenter pilot trial randomized 200 patients (100 per group) with persistent AF to rhythm- or rate-control. The combined primary end point was a combination of death, cardiopulmonary resuscitation, cerebrovascular event, and systemic embolism., Results: After 19.6 +/- 8.9 months (range 0 to 36 months) there was no difference in the primary end point between rhythm-control (9/100; 5.54%/year) and rate-control (10/100; 6.09%/year; p = 0.99). The percentage of patients in sinus rhythm in the rhythm-control group after up to four cardioversions during the follow-up period (rate-control group) was 23% (0%) at 36 months. Eighteen primary end points occurred in atrial fibrillation; only one occurred in sinus rhythm (p = 0.049)., Conclusions: The STAF pilot study showed no differences between the two treatment strategies in all end points except hospitalizations. These data suggest that there was no benefit in attempting rhythm-control in these patients with a high risk of arrhythmia recurrence. It remains unclear whether the results in the rhythm-control group would have been better if sinus rhythm had been maintained in a higher proportion of patients, as all but one end point occurred during AF.