Drug-induced post-repolarization refractoriness as an antiarrhythmic principle and its underlying mechanism.

AIMS: We hypothesized that amiodarone (AM), unlike d-sotalol (DS) (a 'pure' Class III agent), not only prolongs the action potential duration (APD) but also causes post-repolarization refractoriness (PRR), thereby preventing premature excitation and providing superior antiarrhythmic efficacy. METHODS AND RESULTS: We tested this hypothesis in 31 patients with inducible ventricular tachycardia (VT) during programmed stimulation with the use of the 'Franz' monophasic action potential (MAP) catheter with simultaneous pacing capability. We determined the effective refractory period (ERP) for each of three extrastimuli (S2-S4) and the corresponding MAP duration at 90% repolarization (APD90), both during baseline and on randomized therapy with either DS (n = 15) or AM (n = 16). We defined ERP > APD90 as PRR and ERP < APD90 as 'encroachment' on repolarization. A revised computer action potential model was developed to help explain the mechanisms of these in-vivo human-heart phenomena. Encroachment but not PRR was present in all patients at baseline and during DS treatment (NS vs. baseline), and VT was non-inducible in only 2 of 15 DS patients. In contrast, in 12 of 16 AM patients PRR was present (P < 0.001 vs. baseline), and VT was no longer inducible. Our model (with revised sodium channel kinetics) reproduced encroachment and drug-induced PRR. CONCLUSION: Both, AM and DS, prolonged APD90 but only AM produced PRR and prevented encroachment of premature extrastimuli. Our computer simulations suggest that PRR is due to altered kinetics of the slow inactivation of the rapid sodium current. This may contribute to the high antiarrhythmic efficacy of AM.

Adjuvant antiarrhythmic therapy in patients with implantable cardioverter defibrillators.

The risk of sudden cardiac death from ventricular fibrillation or ventricular tachycardia in patients with cardiomyopathy related to structural heart disease has been favorably impacted by the wide adaptation of implantable cardioverter defibrillators (ICDs) for both primary and secondary prevention. Unfortunately, after ICD implantation both appropriate and inappropriate ICD therapies are common. ICD shocks in particular can have significant effects on quality of life and disease-related morbidity and mortality. While not indicated for primary prevention of ICD therapies, beta-blockers and antiarrhythmic drugs are a cornerstone for secondary prevention of them. This review will summarize our current understanding of adjuvant antiarrhythmic drug therapy in ICD patients. The review will also discuss the roles of nonantiarrhythmic drug approaches that are used in isolation and in combination with antiarrhythmic drugs to reduce subsequent risk of ICD shocks.

[Atrial fibrillation after coronary artery bypass surgery: possibilities of prevention].

Atrial fibrillation occurs as a frequent complication after cardiac interventions. It can be found in 5% of all surgical patients, and it is far more common in cardiac (10% - 65% of patients) than in non-cardiac procedures. In a number of patients it remains asymptomatic, but may be accompanied by very severe symptoms of hypotension, heart failure, syncope, systemic or pulmonary embolism, perioperative myocardial infarction, cerebrovascular insult and increased operative mortality. Patients whose postoperative course is complicated by atrial fibrillation require longer hospitalization. Possible predisposing factors of this arrhythmia are numerous and are associated with surgery, extensive coronary heart disease and revascularization, and preoperative diseases. According to the recommendations of the European Society of Cardiology orally applied beta-blocker, amiodarone and sotalol can be used for prophylaxis of atrial fibrillation. Following the recommendations, treatment of postoperative atrial fibrillation should include beta-blockers, amiodarone, and in patients with heart failure and left ventricular dysfunction, digoxin. Due to the increased risk of stroke, an anticoagulant protection is necessary. Many studies have been conducted with results supporting the prophylactic use of amiodarone and beta-blockers, while the treatment with new agents such as magnesium, statins, omega-3 fatty acids and inhibitors of the renin-angiotensin-aldosterone system is still being investigated.

Long-term omega-3 polyunsaturated fatty acid supplementation reduces the recurrence of persistent atrial fibrillation after electrical cardioversion.

BACKGROUND: Persistent atrial fibrillation (AF) is associated with a high risk of recurrence after electrical cardioversion. OBJECTIVE: We examined if long-term supplementation with omega-3 polyunsaturated fatty acids in fish oils commenced >1 month prior to electrical cardioversion and continued thereafter reduces recurrence of persistent AF. METHODS: This was an open-label, randomized study of 178 patients with persistent AF >1-month duration. Participants were assigned to control group (n = 87) or omega-3 group (6 g/d fish oil; n = 91) and underwent cardioversion 1 month later. Concurrent antiarrhythmic use of sotalol or amiodarone was permitted. Fish oil was continued till return of persistent AF or a maximum of 1 year. Intention-to-treat analysis was performed for the primary end point defined as the recurrence of persistent AF. RESULTS: Mean duration of fish oil intake was 56 days precardioversion and a total of 242 days in follow-up. Eicosapentaenoic acid and docosahexaenoic acid, the active components of fish oils, were 1.8-fold and 2.1-fold higher, respectively, in the omega-3 group compared with controls at the time of cardioversion (P <.001). At 90 days, 38.5% of the patients receiving omega-3 fatty acid supplement had AF recurrence compared with 77.5% of the controls (hazard ratio [omega-3 vs control] 0.38; 95% confidence interval 0.27-0.56; P <.001). Omega-3 intake was associated with a significant reduction in AF recurrence with or without concurrent antiarrhythmic drugs. CONCLUSIONS: Omega-3 polyunsaturated fatty acid supplementation commenced >1 month prior to electrical cardioversion and continued thereafter reduces the recurrence of persistent AF. Randomized controlled trials on long-term fish oil supplementation are needed to confirm these findings.

Augmenting maintenance of sinus rhythm in the control of atrial fibrillation by antiarrhythmic drug combinations.

In recent years, a major development in the treatment of atrial fibrillation (AF) is the use of catheter ablation, and a significant number of patients may benefit from this mode of therapy. On a global scale, it may not be feasible to deal with most patients solely on the basis of ablation. Therefore, it is likely that much of the therapy for AF will continue to rely on antiarrhythmic agents for maintaining sinus rhythm. For many years, amiodarone and sotalol have been the dominant antiarrhythmic agents, with amiodarone being the most effective antiarrhythmic in suppressing AF; however, amiodarone use is limited due to concerns of end-organ toxicity. Upstream therapies, such as statins, fish oil, angiotensin converting enzyme (ACE) inhibitors, and angiotensin receptor blockers may also provide additive efficacy to these and other membrane-active antiarrhythmics. In recent years, a number of new agents are being developed and the first successful congener of amiodarone, dronedarone, has been shown to be effective in controlling AF and reducing cardiovascular hospitalization. This paper explores the possibility of augmenting the extent of controlling AF by combining multiple potent antiarrhythmic agents old and new.

Pharmacologic prophylaxis of postoperative atrial fibrillation in patients undergoing cardiac surgery: beyond beta-blockers.

Postoperative atrial fibrillation (POAF) is a frequent complication of cardiac surgery that increases patient morbidity, length of stay, and hospital costs. A substantial body of evidence exists evaluating various pharmacologic and nonpharmacologic methods to decrease the occurrence of POAF in an effort to decrease its burden on the health care system. Evidence-based guidelines support the use of beta-blockers as standard prophylaxis of POAF in patients undergoing cardiac surgery. Traditional prophylactic therapy for POAF targets the sympathetic nervous system, refractory period, and atrial conduction. However, associations between the development of POAF and the inflammatory process, oxidative stress, and atrial remodeling have prompted the investigation of novel therapies targeting these processes. To evaluate the role of pharmacologic strategies beyond beta-blockers in the prevention of POAF, we conducted a search of the PubMed database to identify studies published from 1950-February 2009. Emphasis was placed on how these therapies could be used in patients intolerant to beta-blockers or as additive therapy in high-risk patients. We found that sufficient evidence exists to recommend the use of amiodarone, sotalol, and possibly magnesium as monotherapy in patients unable to take beta-blockers or as add-on therapy for the prevention of POAF. Currently, available evidence does not support the use of propafenone, procainamide, digoxin, thiazolidinediones, triiodothyronine, or calcium channel blockers in the prevention of POAF. Preliminary evidence suggests that dofetilide, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins), nonsteroidal antiinflammatory drugs, corticosteroids, omega-3 fatty acids, ascorbic acid, N-acetylcysteine, and sodium nitroprusside may be effective in preventing POAF. Additional large-scale, adequately powered clinical studies are needed to determine the benefit of these agents before they can be considered for routine use.

Ciprofloxacin induced acquired long QT syndrome in a patient under class III antiarrhythmic therapy.

We report one case of cardiac arrest related to ciprofloxacin administration. One female patient (aged 70 years old) developed a marked QTc prolongation (QTc = 0.62 s) within 24 hours of ciprofloxacin administration, with documented torsades de pointes and recurrent syncope that required defibrillation. The patient was under amiodarone and sotalol therapy for atrial fibrillation, with no obvious QT prolongation prior to ciprofloxacin therapy. QT prolongation and subsequent torsades de pointes appeared only after initiation of ciprofloxacin and normalized after drug discontinuation. Even though ciprofloxacin is thought to be safer than other agents in its class, it may cause QT prolongation and torsades de pointes, particularly in high risk patients with predisposing factors. Prolongation of the QT interval related to the effect of fluoroquinolones on rapid potassium channels (IKr) may result on potentially serious proarrhythmic effect, leading to torsades de pointes.

[Influence of perindopril, rosuvastatin, or omega-3 polyunsaturated fatty acids on efficacy of antirecurrence therapy with sotalol in patients with persistent atrial fibrillation].

Patients (n=187) with symptomatic persistent atrial fibrillation at the background of ischemic heart disease after restoration of sinus rhythm were randomized for treatment with sotalol 80 - 160 mg/day (n=48), or with combinations of sotalol with perindopril 4 - 8 mg/day (n=48), rosuvastatin 5 - 20 mg/day (n=45), or omega-3 polyunsaturated fatty acids containing preparation 1 g/day (n=45). After 12 months sinus rhythm was maintained in 77.6, 93.8 (p < 0.05), 86.7, and 84.4% of cases, respectively, after conduction on the average 7.9 +/- 1.6, 4.3 +/- 1.0 (p < 0.05), 6.5 +/- 1.7, 7.2 +/- 1.8 pharmacological cardioversions per 1 patient in groups of comparison, respectively. Plasma level of high sensitivity C-reactive protein was lowered by all variants of combination therapy, while anterior-posterior left atrial diameter - only under the influence of perindopril. Antiinflammatory effect of nonarrhythmic drugs is able to play substantial role in prevention of atrial fibrillation, however antiremodeling and hemodynamic effects of therapy probably possess no less important significance.

Potential proarrhythmic effect of biventricular pacing: fact or myth?

BACKGROUND: Hemodynamic improvement from biventricular pacing is well documented; however, its electrophysiologic effects have not been systematically studied. Sporadic case reports suggest a proarrhythmic effect of biventricular pacing resulting primarily in polymorphic ventricular tachycardia/ventricular fibrillation (VT/VF). OBJECTIVES: The purpose of this study was to report a series of patients in whom implantation of a biventricular system resulted in VT/VF storm with predominance of monomorphic VT. METHODS: In a retrospective analysis of all biventricular implants over a 4-year period at a single medical center, we identified 5 of 145 patients (3.4%) who developed VT/VF after they were upgraded to a biventricular system. All patients were male, age 71 +/- 8 years, with ejection fraction of 0.25 +/- 0.1. Four of five patients had ischemic cardiomyopathy. RESULTS: All patients developed incessant VT/VF within 1 week of implantation. Monomorphic VT of single morphology was noted in 3 of 5 patients, monomorphic VT of multiple morphologies in 1, and polymorphic VT/VF in 1. VT was managed by temporary discontinuation of biventricular pacing in all patients, amiodarone in 3 of 5, sotalol in 1, and beta-blocker in 1. During 11 +/- 7 months of follow-up, 4 of 5 patients remain alive and are arrhythmia-free. CONCLUSION: Biventricular pacing may result in precipitation of VT/VF storm in a minority of patients with prior history of VT/VF. This may be the first case series reporting both monomorphic and polymorphic VT after an upgrade to a system with biventricular pacing capabilities. The arrhythmias can be managed by conventional therapy and may require temporary discontinuation of left ventricular pacing. This observation is relevant to patients receiving a biventricular pacemaker without an implantable cardioverter-defibrillator backup.

Electrophysiologic study-guided therapy with sotalol for life-threatening ventricular tachyarrhythmias.

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.

Long-term efficacy of atenolol for atrioventricular reciprocating tachycardia in children less than 5 years old.

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.

Arrhythmias in the intensive care patient.

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.

Long-term follow-up of sudden cardiac arrest survivors and electrophysiologically guided antiarrhythmic therapy.

Sudden cardiac arrest survivors have a high risk of suffering from recurrent arrhythmic events. Recent studies have shown that these patients have a significantly decreased mortality rate, if they are supplied with an implantable cardioverter/defibrillator (ICD). The aim of this study was to evaluate the long-term prognosis of patients with electrophysiologically guided antiarrhythmic drug therapy in comparison to patients with ICD. 204 consecutive survivors of sudden cardiac arrest were enrolled in this study. All patients were examined with an initial electrophysiologic study (EPS) with programmed ventricular stimulation. Patients were treated with antiarrhythmic drugs (if the inducible tachycardia was suppressed) or with the implantation of an ICD. The maximal follow-up period was 120 months, the mean period was 53.3 +/- 31.4 months (ICD) versus 60.3 +/- 35.5 months (EPS, nonsignificant). Patients with ICD showed an overall mortality rate of 14.6%, whereas EPS-guided patients had a mortality rate of 43.2% (p < 0.001). The cardiac and arrhythmogenic mortality rates were significantly lower in the ICD group (12 vs. 43%, p < 0.01, and 1 vs. 16%, p < 0.001, respectively). A reduction of the mortality risk was observed in the ICD group by up to 61% (all-cause mortality), 52% (cardiac mortality) and 97.2% (arrhythmogenic mortality). In arrhythmic event survivors with ICD, arrhythmic and overall mortality rates are significantly lower compared to patients with an EPS-guided drug therapy. In the secondary prevention of sudden cardiac death, ICD should be the first choice of antiarrhythmic therapy.

Clinical usefulness of electrophysiologic testing in patients with ventricular tachycardia and chronic chagasic cardiomyopathy treated with amiodarone or sotalol.

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.

Sotalol in treatment of pediatric cardiac arrhythmias.

BACKGROUND: There is limited experience on sotalol use in the management of childhood arrhythmias. This study reviews the results of our experience with oral sotalol for treatment and prevention of tachyarrhythmias in children. METHODS: The records of 62 patients (27 female, 35 male, mean age: 8.5+/-5.3 years) treated with sotalol for supraventricular or ventricular arrhythmias from 1994 to 1999 at our institution were reviewed. Demographic, clinical, echocardiographic, electrocardiographic (ECG), ambulatory ECG and electrophysiologic variables were collected. RESULTS: Forty-two (63.6%) patients had re-entrant supraventricular tachycardia, eight patients (12.9%) had atrial tachycardia, one patient (1.6%) had junctional ectopic tachycardia, four patients (6.5%) had ventricular tachycardia, and seven patients (11.3%) had complex ventricular arrhythmias, as evidenced by surface or ambulatory ECG records; or revealed during the electrophysiological study. The mean sotalol dose was 3.9+/-1.2 mg/kg per day. In 15.5+/-13.9 months of sotalol use 50% (n=31) had complete relief of symptoms and/or arrhythmia and 29% (n=18) had partial relief. Sotalol was ineffective in 20% (n=13). Sotalol was more effective in re-entrant type supraventricular tachycardias (P=0.012). Sotalol was the first choice in 35.5% of patients. The sotalol therapy was initiated in inpatient settings in 40.3% (25 patients). Complications due to sotalol were seen in six patients (five patients developed bradycardia/pauses, and one patient had torsades de pointes) for which the sotalol dose was modified. In patients with sick sinus syndrome, a pacemaker was implanted and in another patient sotalol was stopped. CONCLUSION: Sotalol, being an effective and safe drug particularly in children, is a good therapeutic alternative for the preventive treatment of childhood tachyarrhythmias.

Global distribution of atrial ectopic foci triggering recurrence of atrial tachyarrhythmia after electrical cardioversion of long-standing atrial fibrillation: a bi-atrial basket mapping study.

OBJECTIVES: The objective of this study was to assess the spatial distribution of atrial ectopic foci potentially triggering recurrent atrial tachyarrhythmias after electrical cardioversion of long-standing atrial fibrillation (AF). BACKGROUND: It remains unknown whether targeted ablation of atrial ectopic foci concentrated in the pulmonary veins is feasible in patients with long-standin

Correlation between the effective refractory period and activation-recovery interval calculated from the intracardiac unipolar electrogram of humans with and without dl-sotalol treatment.

In experimental studies and/or human body surface mapping, the activation-recovery interval (ARI) is used as a parameter to estimate local repolarization. However, it has not been clarified whether the ARI calculated from the intracardiac unipolar electrogram of humans reasonably represents the local effective refractory period (ERP). Measurement of ARIs at multiple ventricular sites can be helpful in assessing the dispersion of ventricular refractoriness of humans, so we examined the relationship between ERP and ARI in the control state and under treatment with dl-sotalol during clinical electrophysiologic studies (EPS). Of 19 patients, an EPS was performed in the control state in 12 and during treatment with dl-sotalol in the other 7. Quadripolar electrode catheters with an interelectrode distance of 5 mm were placed at the right atrium and in the right ventricle. Using atrial pacing, the heart rate was increased incrementally by 10 beats/min, and ERP and ARI were measured for each pacing rate. The ERP at the right ventricle was measured by single extrastimulation between the first and third distal electrodes of the catheter in the right ventricle, and the ARI was calculated from the second distal unipolar electrode of the same catheter as the interval between the minimum derivative of the intrinsic deflection and the maximum derivative of the T wave. In all patients, the unipolar electrogram was stable during the entire EPS, and 83 data points in the control group and 50 in the dl-sotalol group were analyzed. At each pacing rate, the beat-to-beat difference of ARI was less than 10 ms. As the atrial pacing rate increased, the ERP and ARI were progressively shortened, and linear regression analysis revealed an excellent correlation between ERP and ARI. At the same pacing rate, the ERP and ARI in the dl-sotalol group were longer than those in the control group, but no difference was observed in the slope (close to 1.0) and in the intercept of the regression lines between ERP and ARI. In the human ventricle, the ARI calculated from the intracardiac unipolar electrogram represents the local ERP both in the control state and under treatment with dl-sotalol. The ARI can be used as a parameter of local refractoriness and used to study the distribution of refractoriness in the human ventricle.

The effect of oral magnesium, alone or as an adjuvant to sotalol, after cardioversion in patients with persistent atrial fibrillation.

AIMS: To determine whether magnesium given orally decreases the recurrence rate of atrial fibrillation after elective direct current cardioversion of persistent atrial fibrillation. METHODS AND RESULTS: Consecutive outpatients were randomized to treatment with oral magnesium (10.3 mmol) or placebo twice daily in a double-blind fashion. Two groups were studied; magnesium study: 170 patients with atrial fibrillation persistent for >1 month, scheduled for their first direct current cardioversion. No concomitant antiarrhythmic drugs of class I or III were allowed. Sotalol and magnesium study: 131 patients with recurrence of persistent atrial fibrillation after previous direct current cardioversion, or a history of paroxysmal atrial fibrillation, treated with sotalol. Patients were followed until recurrence of atrial fibrillation or for at least 6 months. Magnesium study: at cardioversion 67 of 85 (79%) in the placebo group and 64 of 85 (75%) in the magnesium group had converted to sinus rhythm. At the end of the study, with a follow-up of 6 to 42 months, 15% of patients in the placebo group and 19% of patients in the magnesium group remained in sinus rhythm (Log rank test: P=0.37). Sotalol and magnesium study: pharmacological conversion to sinus rhythm, after oral treatment, was achieved in 34 of 131 (26%) patients. Sinus rhythm, with or without cardioversion, was restored in 89% and 85% of the patients in the placebo and magnesium groups, respectively. At the end of the study, with a follow-up of 6 to 42 months, 37% of patients in the placebo group and 30% of patients in the magnesium group remained in sinus rhythm (Log rank test: P=0.64). CONCLUSION: In patients with persistent atrial fibrillation, oral treatment with magnesium alone or as an adjuvant to sotalol, does not influence the recurrence rate of atrial fibrillation after elective cardioversion.