Long-term Antiarrhythmic Therapy Research Articles

New possibilities of antiarrhythmic therapy of atrial fibrillation: A review

Atrial fibrillation (AF) is the most common heart rhythm disorder. According to current recommendations, the treatment of AF includes 3 main directions: "A" – the appointment of anticoagulant therapy with an increased risk of thromboembolic complications, "B" – control of arrhythmia symptoms, choice of a strategy for rhythm control or control of ventricular contractions, "C" – treatment of concomitant diseases and correction of risk factors. The rhythm control strategy includes performing cardioversion, prescribing long-term antiarrhythmic therapy, or performing radiofrequency catheter ablation. According to the latest recommendations of 2020, antiarrhythmic drugs of IC and III classes are currently used for pharmacological cardioversion of AF and long-term retention of sinus rhythm. The choice of a specific antiarrhythmic drug is based on its safety and effectiveness. â-Blockers, non-dihydropyridine calcium channel blockers and digoxin are used to control CHS. The results of modern research have significantly expanded our understanding of the molecular mechanisms underlying various forms of AF. Currently, the search for new drugs is actively underway that will allow preventing the development of AF and its progression at the molecular level.

Atrial Arrhythmias in Adults with Fontan Palliation.

Single ventricle physiology is a rare form of congenital heart disease and was, historically, a uniformly lethal condition. However, the atriopulmonary Fontan operation, and its successive iterations, the lateral tunnel and extracardiac conduit Fontan, became the fundamental approach to treating single ventricle heart disease. Over time, dysrhythmias are some of the most common complications with Fontan physiology, compounding morbidity and mortality. Atrial arrhythmias are prevalent in the Fontan population and occur in about 15-60% of patients with Fontan palliation, increasingly with age. Diagnosing atrial arrhythmias in patients with Fontan palliation may be challenging because of low voltage amplitudes arising from myopathic atrial tissue making it difficult to clearly assess atrial depolarization on surface electrocardiograms (ECG), vague symptoms not suggestive of tachyarrhythmia, or atrial arrhythmia with ventricular rates below 100beats per minute. Intra-atrial reentrant tachycardia (IART) is the most common type of supraventricular tachycardia in adults with Fontan palliation. Acute management of atrial arrhythmias in patients with Fontan palliation involves prompt assessment of a patient's hemodynamic stability, anticoagulation and thrombosis risk, systemic ventricular function, and risk of sedation or anesthesia if needed. Long-term management of atrial arrhythmias is often multifactorial and may include long-term anti-arrhythmic therapy, permanent pacing, and ablation. The best approach for the management of atrial arrhythmias in adults with Fontan palliation is patient-specific and involves collaboration between congenital electrophysiologists, adult congenital cardiologists, and the patient.

Tyrosine kinase inhibitor-associated ventricular arrhythmias: a case series and review of literature.

Tyrosine kinase inhibitors (TKIs) have been increasingly used as first-line therapy in hematologic and solid-organ malignancies. Multiple TKIs have been linked with the development of cardiovascular complications, especially atrial arrhythmias, but data on ventricular arrhythmias (VAs) is scarce. Herein we describe five detailed cases of VAs related to TKI use in patients with varied baseline cardiovascular risk factors between 2019 and 2022 at three centers. Individual chart review was conducted retrospectively. Patient ages ranged from 43 to 83years. Three patients were on Bruton's TKI (2 ibrutinib and 1 zanubrutinib) at the time of VAs; other TKIs involved were afatinib and dasatinib. Three patients had a high burden of non-sustained ventricular tachycardia (NSVT) requiring interventions, whereas two patients had sustained VAs. While all patients in our case series had significant improvement in VA burden after TKI cessation, two patients required new long-term antiarrhythmic drug therapy, and one had an implantable defibrillator cardioverter (ICD) placed due to persistent VAs after cessation of TKI therapy. One patient reinitiated TKI therapy after control of arrhythmia was achieved with antiarrhythmic drug therapy. Given the expanding long-term use of TKIs among a growing population of cancer patients, it is critical to acknowledge the association of TKIs with cardiovascular complications such as VAs, to characterize those at risk, and deploy preventive and therapeutic measures to avoid such complications and interference with oncologic therapy. Further efforts are warranted to develop monitoring protocols and optimal treatment strategies for TKI-induced VAs.

A systematic review and meta-analysis comparing radiofrequency catheter ablation with medical therapy for ventricular tachycardia in patients with ischemic and non-ischemic cardiomyopathies.

In patients with cardiomyopathy, radiofrequency catheter ablation (CA) for ventricular tachycardia (VT) is an adjunctive and alternative treatment option to long-term anti-arrhythmic drug therapy. We sought to compare CA with medical therapy for the management of VT in patients with ischemic and non-ischemic cardiomyopathies. MEDLINE, Cochrane, and ClinicalTrials.gov databases were evaluated for relevant studies. Eleven studies with 2126 adult patients were included (711 in CA, 1415 in medical therapy). In the randomized controlled trial (RCT) analysis, CA reduced risk of recurrent VT (risk ratio (RR) 0.79 [95% CI 0.67 to 0.93], p = 0.005), ICD shocks (RR 0.64 [95% CI 0.45 to 0.89] p = 0.008), and cardiac hospitalizations (RR 0.76 [95% CI 0.63 to 0.92] p = 0.005). There was no difference in all-cause mortality (RR 0.94, p = 0.71). In combined RCT and observational study analysis, there was a trend for reduction in all-cause mortality (RR 0.75 [95% CI 0.55 to 1.02] p = 0.07). In subgroup analysis of studies with mean left ventricular ejection fraction (LVEF) < 35%, CA demonstrated reduction in mortality (RR 0.71, p = 0.004), ICD shocks (RR 0.63, p = 0.03), VT recurrence (RR 0.76, p = 0.004), and cardiac hospitalizations (RR 0.75, p = 0.02). The subgroup of early CA prior to ICD shocks demonstrated reduction in ICD shocks (RR 0.57, p < 0.001) and VT recurrence (RR 0.74, p = 0.01). CA for VT demonstrated a lower risk of VT recurrence, ICD shocks, and hospitalization in comparison to medical therapy. The subgroups of early CA and LVEF < 35% demonstrated better outcomes.

Медикаментозная кардиоверсия пароксизмальной фибрилляции предсердий у больных пожилого и старческого возраста на догоспитальном этапе

Atrial fibrillation (AF) is the most common heart rhythm disorder requiring treatment and is associated with an increased rate of hospitalization and death. When choosing the tactics of restoring and maintaining sinus rhythm in most patients with AF paroxysm without pronounced organic heart damage, the drug of choice is propafenone, which has a high level of safety and efficacy. The use of the drug within the framework of a «pill in a pocket» by the patient himself, intravenously in a day hospital of an outpatient medical institution or by an ambulance team allows stopping AF paroxysm in most patients at the prehospital stage. Propafenone is also the drug of choice for inpatient sinus rhythm restoration and for long-term antiarrhythmic therapy in a wide range of patients with AF.

Antiarrhythmic drug therapy after atrial fibrillation ablation: data of the ESC-EHRA registry

Aim. Catheter ablation (CA) is an effective approach for rhythm control in atrial fibrillation (AF), however antiarrhythmic therapy (AAT) remains important. There is a lack of data about long-term AAT use after CA. This study evaluates AAT after CA for AF.Material and methods. In 2012-2016, EURObservational Research Programme of Atrial Fibrillation Ablation Long-Term (EORP AFA L-T) registry was conducted, which included 476 Russian patients (57,1% — men; mean age — 57,1±8,7 years). The follow-up after CA was 12 months (available in 81,9% of patients). The use of AAT was evaluated prior to hospitalization, during hospitalization for CA, as well as at 3, 6 and 12 months of follow-up.Results. Prior to CA, 439 (92,2%) patients received AAT During CA, 459 (96,4%) patients were treated with AAT. After CA, AAT was used by 463 (97,3%), 370 (94,8%), and 307 (78,7%) patients at 3, 6 and 12 months of follow-up, respectively. There was no arrhythmia recurrence in 187 (47,9%) subjects. Among these patients, 40 (21,4%) received class IC or III AAT. The peak of AAT use was found for class IC agents within 3 months after CA (P&lt;0,05), while for other drugs this trend was not observed. There were no factors associated with AAT usage in patients without arrhythmia recurrence after CA. A positive correlation of arrhythmia non-recurrence with a minimum number of previously used antiarrhythmic agents was revealed (RR=0,85; 95% CI 0,73-0,98; P=0,03).Conclusion. The frequency of AAT use after AF ablation is significantly reduced. However, there is a cohort of patients without documented arrhythmia recurrence still receiving AAT, which requires special attention of physicians. There were no clinical predictors of continued AAT in subjects without arrhythmia recurrence.

Effectiveness of the Cox Maze-IV Procedure in Cardiac Surgery Patients With Atrial Fibrillation

Aim Analyzing a 5-year experience of surgical treatment of cardiosurgical patients with atrial fibrillation (AF).Material and methods The study analyzed results of surgical treatment with extracorporeal circulation in 132 patients with AF who underwent the Maze-IV procedure using a radiofrequency ablator with transmurality feedback from 2013 through 2018.Results Two fatal outcomes were observed in the study group. These outcomes took place in the early postoperative period and were associated with progressive acute heart failure in patients with repeated surgery for mitral valve restenosis. 61.2% of the patients had no AF. Recurrent AF was observed during the first three years after surgery in association with withdrawal of the antiarrhythmic medication, which confirmed a need for long-term antiarrhythmic therapy. Analysis of risk factors for AF relapse identified significant predictors, including left ventricular dilatation larger than 5.5 cm at baseline and more than two-year duration of a history of arrhythmias.Conclusion The Maze-IV procedure proved an effective and safe method of surgical treatment in AF patients with acquired heart defects and ischemic heart disease, which allowed maintaining sinus rhythm in 61.2% of patients for 5 years. Preventive amiodarone saturation reduced the risk of AF relapse by 24.2 % (p=0.038) and incidence of postoperative arrhythmic complications by 34.9 % (p=0.008) in cardiosurgical patients.

Pharmacokinetics and electrophysiological effects of sotalol hydrochloride in horses.

Arrhythmias in horses may require long-term anti-arrhythmic therapy. Unfortunately, oral anti-arrhythmic drugs for use in horses are currently scarce. In human patients and small animals, sotalol, a β-blocker with class III anti-arrhythmic properties, is often used for long-term treatment. To determine the pharmacokinetics of sotalol at multiple oral dosages in unfasted horses, as well as the effects on electro- and echocardiographic measurements, right atrial and ventricular monophasic action potential (MAP) and effective refractory period (ERP). Placebo controlled, double-blinded experiment. Six healthy, unfasted Warmblood horses were given either 0, 2, 3 or 4 mg/kg bodyweight (bwt) sotalol orally (PO) twice daily (bid) for 9 days in a randomised cross-over design. Echocardiography and surface electrocardiography were performed and plasma concentrations of sotalol and right atrial and right ventricular MAPs and ERPs were determined at steady-state conditions. Statistical analysis was performed using a repeated measures univariate analysis with post hoc Bonferroni corrections. Calculated mean steady-state plasma concentrations determined by nonlinear mixed-effect modelling were 287 (range 234-339), 409 (359-458) and 543 (439-646) ng/mL for 2, 3 and 4 mg/kg bwt sotalol PO bid respectively. Sotalol significantly increased the QT interval and ERPs, but, despite increasing plasma concentrations, higher dosages did not result in a progressive increase in QT interval or ERPs. Echocardiographic and other electrocardiographic measurements did not change significantly. MAP durations at 90% repolarisation were not significantly different during sotalol treatment. Besides transient local sweating, no side effects were noted. Study size and ad libitum feeding of hay. Sotalol at a dose of 2, 3 and 4 mg/kg bwt PO bid increases the QT interval and ERP and might be a useful drug for long-term anti-arrhythmic therapy in horses.

The effect of long-term amiodarone administration on myocardial fibrosis and evolution of left ventricular remodeling in a porcine model of ischemic cardiomyopathy.

Amiodarone is effective in suppressing arrhythmias in heart failure patients. We investigated the effect of long-term amiodarone administration on myocardial fibrosis and left ventricular (LV) remodeling in a porcine model of ischemic cardiomyopathy. Eighteen infarcted farm pigs were randomized to receive long-term amiodarone administration for 3 months (n = 9) or conventional follow-up (n = 9). Evolution of LV remodeling over 3 months post-myocardial infarction was examined at tissue level (myocyte size, myocardial fibrosis and vascular density assessed by whole-field digital histopathology), organ level (LV structure and function assessed by echocardiography), and systemic level (BNP and MMP-9 levels). Long-term administration of the standard anti-arrhythmic doses of amiodarone was not associated with adverse effects on myocardial fibrosis and other features of adverse cardiac remodeling. This favorable safety profile suggests that long-term anti-arrhythmic therapy with amiodarone warrants further clinical investigation in the subpopulation of heart failure patients with significantly increased burden of arrhythmias.

Reduced progression of atrial fibrillation in hypertensive patients with long-term treatment of propafenone

In recent years, progress has been made in the study of the natural history of atrial fibrillation (AF) - that, from the stage of having no clinical manifestations, to the final stage, which is an irreversible arrhythmia, is associated with the development of serious cardiovascular complications. Most AF patients steadily progress in persistent or permanent form, but the risk factors and predictors of progression of the arrhythmia is not clearly defined. There is little research done on the effect of long-term antiarrhythmic therapy on the progression of AF. Objective. To evaluate the progression of arrhythmias in patients with arterial hypertension (AH) with paroxysmal AF in the treatment of propafenone (propanorm) compared to treatment with bisoprolol (Concor) in the long-term prospective study. Materials and methods. The study included 62 patients with essential hypertension aged 45 to 63 years. Patients were randomized into 2 groups: 32 patients in group 1 for storing heart rate propafenone took a daily dose of 450 mg, 30 patients in group 2 to control ventricular rate was appointed bisoprolol. Prospective monitoring of patients was carried out from 2011 to 2015, the progression of the arrhythmia was considered: increase in the frequency of paroxysms of arrhythmia in the last 3 months, the appearance of long-term persistent AF episodes or persistent AF. Results. In 14 (44%) patients in group 1 and 20 (67%) - group 2 5 years of observation, it was noted increase in the frequency and duration of AF episodes. The average value of arrhythmia progression into a more stable form of 9.3% per year in patients receiving propafenone, and 11.5% - bisoprolol (p=0.007). Keeping the treatment of sinus rhythm propafenone in a daily dose of 450 mg contributed to a significant reduction of the left atrium anteroposterior size from 43±3 to 36±3 mm (p=0.03). In the treatment with bisoprolol anteroposterior size of the left atrium was not significantly changed and amounted to 44±3 and 43±3 mm respectively. Portability of propafenone antiarrhythmic therapy was comparable with that of bisoprolol. No severe or serious side effects were observed in patients during the long-term prospective study. Conclusion. The five-year propafenone treatment of hypertensive patients with paroxysmal AF can reduce the progression of AF in a more stable form compared with bisoprolol therapy.

Catheter ablation of supraventricular tachyarrhythmia after extracardiac Fontan surgery

Extracardiac total cavopulmonary connection (E-TCPC) is widely performed for single ventricle palliation, yet there is little experience with catheter ablation in this population. We hypothesized that atrial tachycardia substrates after primary E-TCPC would be similar to those in other forms of congenital heart disease and that catheter ablation could be performed effectively using a primarily transconduit approach. Catheter ablation characteristics of patients with E-TCPC from 9 centers were collected. Acute procedural success was defined as elimination of all sustained supraventricular tachyarrhythmias. Procedural complications, acute success, and recurrences were assessed. Forty-six catheter ablation procedures were performed in 36 patients. Access to the atrium was by transconduit puncture in 29 procedures (63%). The most common supraventricular tachyarrhythmia mechanism was intra-atrial reentrant tachycardia (IART) in 21 patients (58%); and for all patients with primary E-TCPC and IART, an isthmus between the atrioventricular valve annulus and the oversewn inferior vena cava was critical for maintenance of tachycardia. Overall, acute success was achieved in 38 procedures (83%). There were 8 complications, with only 1 requiring intervention (epicardial pacemaker) and none related to conduit puncture. Recurrence after the final procedure occurred in 6 patients (17%) over a median follow-up duration of 0.4 years (interquartile range 0.1-1.5 years). Catheter ablation could be performed effectively in this group of patients with E-TCPC, and the underlying IART substrate after primary E-TCPC appears to be reproducible. Catheter ablation may be a reasonable alternative to long-term antiarrhythmic therapy in this patient group.

Pharmacokinetics of intravenously and orally administered sotalol hydrochloride in horses and effects on surface electrocardiogram and left ventricular systolic function

Arrhythmias are common in horses. Some, such as frequent atrial or ventricular premature beats, may require long-term anti-arrhythmic therapy. In humans and small animals, sotalol hydrochloride (STL) is often used for chronic oral anti-arrhythmic therapy. STL prolongs repolarization and the effective refractory period in all cardiac tissues. No information on STL pharmacokinetics or pharmacodynamics in horses is available and the aim of this study was to evaluate the pharmacokinetics of intravenously (IV) and orally (PO) administered STL and the effects on surface electrocardiogram and left ventricular systolic function. Six healthy horses were given 1 mg STL/kg bodyweight either IV or PO. Blood samples to determine plasma STL concentrations were taken before and at several time points after STL administration. Electrocardiography and echocardiography were performed at different time points before and after IV STL administration.Mean peak plasma concentrations after IV and PO administration of STL were 1624 ng/mL and 317 ng/mL, respectively. The oral bioavailability was intermediate (48%) with maximal absorption after 0.94 h, a moderate distribution and a mean elimination half-life of 15.24 h. After IV administration, there was a significant increase in QT interval, but no significant changes in other electrocardiographic and echocardiographic parameters. Transient transpiration was observed after IV administration, but no adverse effects were noted after a single oral dose of 1 mg/kg STL in any of the horses. It was concluded that STL has an intermediate oral bioavailability in the horse and might be useful in the treatment of equine arrhythmias.

Clinical efficacy of antazoline in rapid cardioversion of paroxysmal atrial fibrillation -- a protocol of a single center, randomized, double-blind, placebo-controlled study (the AnPAF Study)

BackgroundRapid conversion of atrial fibrillation (AF) to sinus rhythm may be achieved by the administration of class IA, IC and III antiarrhythmic drugs or vernakalant hydrochloride. However, that treatment may be related to potential pro-arrhythmia, lack of efficacy or the exceptionally high cost of a compound used. Antazoline is a first generation antihistaminic agent with chinidin-like properties. When administered intravenously, antazoline exerts a strong antiarrhythmic effect on supraventricular arrhythmia, especially on AF, facilitating rapid conversion to sinus rhythm. Despite a relative lack of published data antazoline has been marketed in Poland and widely used in cardiology wards and emergency rooms for many years due to its efficacy, safety and rapid onset of action within minutes of administration.Methods/designA randomized, double blind, placebo-controlled, superiority clinical trial was designed to assess clinical efficacy of antazoline in rapid conversion of AF to sinus rhythm. Eligible patients will present AF lasting less than 43 hours, will be in stable cardio-pulmonary condition and will have no prior history of advanced heart failure or significant valvular disease. Long-term antiarrhythmic therapy is not considered an exclusion criterion. Subjects who fulfill selection criteria will be randomly assigned to receive intravenously either antazoline or placebo in divided doses and observed for 1.5 hours after conversion to sinus rhythm or after the last i.v. bolus. Primary end point will be the conversion of AF to sinus rhythm confirmed in an electrocardiogram (ECG) during the observation period. Secondary end points will be comprised of time to conversion and return of AF during the observation period. Special consideration will be given to the observation of any adverse events. A sample size of 80 patients was calculated based on the following assumptions: two-tailed test, a type I error of 0.01, a power of 90%, efficacy of placebo 5%, efficacy of antazoline 50% and 20% drop-out rate to fulfill the criteria of intention-to-treat analysis. Due to the presumed lack of statistical power, the secondary end points and safety endpoints will be considered exploratory.Clinical trials registryClinicalTrials.gov, NCT01527279

Pulmonary Vein Isolation for the Treatment of Drug-Refractory Atrial Fibrillation in Adults with Congenital Heart Disease

Atrial fibrillation (AF) is a common arrhythmia in adults with congenital heart disease (CHD). Long-term antiarrhythmic therapy (AAT) in these patients has significant shortcomings. The safety and efficacy of pulmonary vein antrum isolation (PVAI) for the treatment of AF in CHD is presently unknown. We hypothesized that PVAI for AF in patients with CHD is effective and safe. We reviewed a prospective cohort of 4315 patients (age ≥ 18) undergoing PVAI for drug refractory AF at a single institution and identified 36 consecutive patients with CHD (single ventricle physiology, tetralogy of Fallot, coarctation of the aorta, ventricular septal defects, atrial septal defects (ASD) and cardiomyopathy resulting from anomalous origin of the left main coronary from the pulmonary artery). A second cohort of 355 consecutive patients with noncongenital structural heart disease (NSHD) (coronary artery disease, valvular heart disease, ejection fraction <50%, or prior noncongenital cardiac surgery) undergoing PVAI during the same time period was used as a control. Success was defined as freedom from AF starting two months after PVAI in the absence AAT until the end of follow-up. Partial success was defined as freedom from AF in the presence of AAT until the end of follow-up. Combined success was defined as the sum of success and partial success. We compared the outcomes with the use of propensity-score matching in the overall cohort. Patients with NSHD were older and had higher prevalence of hypertension (P < .01), diabetes (P < .01) and hyperlipidemia (P < .01). The most common CHD lesion was ASD (61%) and the most common NSHD lesion was valvular heart disease (57%). After one PVAI, success was achieved in 42% and 53% at 300 days in the CHD and NSHD groups respectively. Four-year success was achieved in 27% and 36% in the CHD and NSHD groups, respectively. There were no significant differences in the success rates between patients groups (P= .46), nor were there any differences in left atrial size or changes in ejection fraction after one or two PVAI in the respective groups. Complication rates between the CHD and NSHD groups were similar (15% vs. 11%, P= .42) except for a higher risk of vascular site complications in patients with CHD (8% vs. 1%, P < .05). PVAI is an attractive treatment modality in drug refractory AF in CHD, with combined success rates in excess of 60%. The maintenance of sinus rhythm after PVAI in CHD appears similar to that of NSHD and warrants prospective validation.

Atrial flutter after non-congenital cardiac surgery: Incidence, predictors and outcome

BackgroundAtrial arrhythmias (AAs) occur frequently after cardiac surgery. However, most authors do not differentiate postoperative atrial fibrillation (AF) from atrial flutter (AFL). Our study sought to investigate the incidence and predictors of AFL following non-congenital cardiac surgery, and the long-term outcome of this arrhythmia. Methods and resultsWe conducted an observational, retrospective, single-centre study. Among 821 patients in sinus rhythm (SR) before non-congenital cardiac surgery, AFL occurred in 42 patients (5.1%) and AF in 77 (9.4%). Independent predictors of AAs were older age (odds ratio (OR): 1.06, 95% confidence interval (CI): 1.01–1.11, p=0.02), low postoperative hemoglobin level (OR: 0.43, CI: 0.29–0.63, p<0.0001) and long cross-clamp time (OR: 1.02, CI: 1.002–1.037, p=0.03). Compared to AF patients, those with AFL were younger (67±10 versus 72±8years, p=0.005) and less likely to have valve surgery (57% versus 76%, p=0.03). After conversion to SR, of 41/42 patients with AFL, 5 (12%) developed AFL and 5 (12%) had AF within a mean follow-up of 9.6±8.4months: only 32% of patients were on long-term antiarrhythmic therapy and 5% had radiofrequency ablation of AFL in the early postoperative period. ConclusionAFL following non-congenital cardiac surgery is not frequent. Compared to patients in AF, those with AFL are younger and less likely to have valve surgery. After conversion of AFL to SR, recurrence rate of AAs is relatively low. Therefore, AFL occurring in this setting does not require systematic catheter ablation in the postoperative period.

Curative catheter ablation in atrial fibrillation and typical atrial flutter: systematic review and economic evaluation

Curative catheter ablation in atrial fibrillation and typical atrial flutter: systematic review and economic evaluation

Atrial fibrillation progression and management: A 5-year prospective follow-up study

Few data on atrial fibrillation (AF) progression from the first paroxysmal episode are available. The purpose of this study was to assess the progression of AF not due to potentially reversible causes in patients treated according to current guidelines recommendations that also include catheter ablation. Among 402 screened patients with first AF, 106 patients (mean age 57.5 years) were selected and followed for 5 years. Of these patients, 54 had lone AF and 52 had comorbidities. Fifty patients (61.1% with lone AF) had no further recurrence after 5 years. The remaining 56 patients within 19 months after the first episode developed recurrent paroxysmal AF requiring long-term antiarrhythmic drug therapy, which was continued in 45 patients and was stopped because of intolerance/failure in 11 patients who underwent catheter ablation. AF became persistent in 24 of the 45 patients on antiarrhythmic drug therapy and then permanent in 16, of whom 6 had refused catheter ablation at the time of persistence. No AF recurrences or AF progression occurred after ablation. Kaplan-Meier curves demonstrated that patients with comorbidities were more likely to progress than were those with lone AF (P <.001) and that patients who underwent catheter ablation were at lower risk for progression to permanent AF than were those on antiarrhythmic drug therapy (P = .029). Age, diabetes, and heart failure (P <.001) predict final progression to permanent AF. Patients with first AF and comorbidities are at higher risk for rapid progression to permanent AF, and age, diabetes, and heart failure are independent predictors. Catheter ablation rather than antiarrhythmic drug therapy is beneficial in eliminating recurrences delaying arrhythmia progression.

Targeted pharmacological reversal of electrical remodeling after cardioversion—Rationale and design of the Flecainide Short-Long (Flec-SL) trial

Persistent atrial fibrillation (AF) causes relevant mortality and cardiovascular and noncardiovascular morbidity. Therefore, maintenance of sinus rhythm is an important clinical goal, especially when the patient is symptomatic, despite the fact that current treatment strategies are not sufficient to completely prevent recurrent AF. In addition to underlying atrial disease that predisposes to AF, AF in itself induces structural and electrical adaptations ("electrical remodeling" and "structural remodeling"). Underlying disease processes and parts of structural remodeling are not always reversible. Electrical remodeling, in contrast, is reversed by a few weeks of maintenance of sinus rhythm under experimental conditions. This corresponds to the period when most of the recurrent episodes of AF occur after cardioversion. Antiarrhythmic drugs that prolong the atrial action potential can assist in the prevention of recurrent AF by promoting the reversal of electrical remodeling. Such drugs, which are currently used over long periods after cardioversion, may only be needed until the physiological action potential duration is restored, for example, during the first few weeks after cardioversion of persistent AF. This treatment concept that we call "targeted pharmacological reversal of electrical remodeling" would limit both cost and drug-induced side effects of antiarrhythmic drug therapy after cardioversion. The Flec-SL trial, ISECTN62728743, therefore tests the main hypothesis that targeted pharmacological reversal of electrical remodeling by short-term antiarrhythmic drug therapy for 4 weeks after cardioversion is not inferior to standard long-term antiarrhythmic drug therapy for the prevention of recurrent AF after cardioversion in a parallel group, randomized, multicenter, open, blinded end point analysis design. Based on its effectiveness and pharmacokinetic profile, flecainide is used to test the study hypothesis. The trial uses daily transtelephonic electrocardiographic monitoring for all patients and will be conducted within the German Atrial Fibrillation Competence NETwork (AFNET) to facilitate inclusion of patients from electrophysiologically oriented cardiology centers, ordinary hospitals, and office-based physicians.

Early versus late atrial fibrillation after atrial flutter ablation.

Radiofrequency catheter ablation of atrial flutter (AFl) has high initial success with a 10-15% recurrence. Atrial fibrillation (AFib) after radiofrequency catheter ablation of AFl can occur but may be transient (lasting no more than four weeks). Of one hundred seventeen consecutive patients studied, one hundred and four consecutive patients with sustained, symptomatic AFl, as the predominant rhythm disturbance (some of whom had transient pre-ablation AFib), referred for radiofrequency catheter ablation, had clinical follow-up. All had evidence for successful AFl ablation. Patients were followed prospectively. Over a mean follow-up of 28 months, 28 patients developed AFib after ablation of AFl [12 early AFib (<2 months) and 16 late AFib (>2 months)]. Seven of 12 (58%) patients in the early onset group reverted to normal sinus rhythm; none required long-term antiarrhythmic therapy. Only one (8%) developed permanent AFib. No patient in the late onset group remained in sinus rhythm without an antiarrhythmic drug. Three (19%) developed permanent AFib despite therapy among those with late onset AFib. Two (17%) patients with early onset AFib reverted to normal sinus rhythm with treatment versus 5 (31%) in the late onset group. Finally, only 2 patients (17%) with paroxysmal/persistent episodes of Afib from the early onset group stayed in normal sinus rhythm despite therapy, while 8 patients (50%) with paroxysmal/persistent AFib episodes from the late onset group required therapy to maintain normal sinus rhythm. Early onset AFib after ablation of AFl is likely to be transient and self-limited. Late onset AFib after ablation of AFl can persist and require chronic therapy.

Effect of atrial septal pacing on P-wave duration dispersion and atrial late potentials in patients with paroxysmal atrial fibrillation

Atrial fibrillation (AF) is a common type of arrhythmia and its incidence increases with aging. Long-term antiarrhythmic drug therapy was usually used for the maintenance of sinus rhythm in patients with paroxysmal AF. However, many patients with paroxysmal AF experience AF recurrence in the long term. 1 Fuchs T. Podrid P.J. Pharmacologic therapy for revision of atrial fibrillation and maintenance of sinus rhythm. in: Falk R.H. Podrid P.J. Atrial Fibrillation: Mechanism and Management. Raven Press, New York1992: 253-254 Google Scholar Nonpharmacologic therapies have been investigated, including maze surgery, internal defibrillators, catheter ablation, and pacemakers. 2 Barold S.S. The role of cardiac pacing in the prevention of atrial fibrillation. Cardiol Rev. 1992; 4: 353-365 Crossref Scopus (4) Google Scholar Chronic atrial pacing was known to be associated with a lower incidence of AF in patients with sick sinus syndrome. 3 Andersen H.R. Thussen L. Bagger J.P. Vesterlund T. Thomsen P.E.B. Prospective randomised trial of atrial versus ventricular pacing in sick sinus syndrome. Lancet. 1992; 344: 1523-1528 Abstract Scopus (423) Google Scholar Recently, atrial septal pacing has been reported to be effective in preventing AF recurrence. 4 Spencer W. Zhu D.W.X. Markowitz T. Badruddin S.M. Zoghbi W.A. Atrial septal pacing A method for pacing both atria simultaneously. PACE. 1992; 20: 2739-2745 Crossref Scopus (61) Google Scholar , 5 Katsivas A. Manolis A.G. Lazaris E. Vassilopoulos C. Louvros N. Atrial septal pacing to synchonize atrial depolarization in patients with delayed interatrial conduction. PACE. 1992; 21: 2220-2225 Crossref Scopus (59) Google Scholar , 6 Bailin S.J. Johnson W.B. Hoyt R. A prospective randomized trial of Bachmann’s bundle pacing for the prevention of atrial fibrillation (abstr). J Am Coll Cardiol. 1992; 29: 74A Google Scholar , 7 Bailin S.J. Adler S.W. Giudici M.C. Hill M.R.S. Solinger B. Bachmann’s bundle pacing for the atrial fibrillation: initial trends in a multi-center randomized prospective study (abstr). PACE. 1992; 22: 727 Google Scholar , 8 Padeletti L. Porciani C. Antonio M. Colella A. Ticci P. Vena S. Costoli A. Ciapetti C. Pieragnoli P. Gensini G.F. Interatrial septum pacing A new approach to prevent recurrent atrial fibrillation. J Intervent Cardiac Electrophysiol. 1992; 3: 35-43 Crossref Scopus (113) Google Scholar However, the electrophysiologic characteristics during atrial septal pacing in patients with and without AF have not adequately been investigated. Some investigators have shown that the electrophysiologic abnormalities of the atrial muscle in patients with paroxysmal AF could be detected by P-wave signal-averaged electrocardiography (P-SAE). 9 Fukunami M. Yamada T. Ohmori M. Kumagai K. Umemoto K. Sakai A. Kondoh N. Minamino T. Hoki N. Detection of patients at risk for paroxysmal atrial fibrillation during sinus rhythm by P wave-triggered signal-averaged electrocardiogram. Circulation. 1992; 83: 162-169 Crossref Scopus (288) Google Scholar , 10 Stafford P.J. Turner I. Vincent R. Quantitative analysis of signal-averaged P waves in idiopathic paroxysmal atrial fibrillation. Am J Cardiol. 1992; 68: 751-755 Abstract Full Text PDF Scopus (111) Google Scholar , 11 Yamada T. Fukunami M. Ohmori M. Kumagai K. Sakai A. Kondoh N. Minamino T. Hoki N. Characteristics of frequency content of atrial signal-averaged electrocardiograms during sinus rhythm in patients with paroxysmal atrial fibrillation. J Am Coll Cardiol. 1992; 19: 559-563 Abstract Full Text PDF PubMed Scopus (57) Google Scholar , 12 Guidera S.A. Steinberg J.S. The signal-averaged P wave duration A rapid and noninvasive marker of risk of atrial fibrillation. J Am Coll Cardiol. 1992; 21: 1645-1651 Abstract Full Text PDF Scopus (200) Google Scholar Recently, it has also been reported that the risk of AF recurrence could be assessed by P-wave duration dispersion (P-dispersion) and atrial late potentials on the P-SAE. 13 Yamada T. Fukunami M. Shimonagata T. Kumagai K. Sanada S. Ogita H. Asano Y. Hori M. Hoki N. Dispersion of signal-averaged P wave duration on precordial body surface in patients with paroxysmal atrial fibrillation. Eur Heart J. 1992; 20: 211-220 Crossref Scopus (79) Google Scholar , 14 Abe Y. Fukunami M. Yamada T. Shimonagata T. Kumagai K. Kim J. Sanada S. Hori M. Hoki N. Prediction of transition to chronic atrial fibrillation in patients with paroxysmal atrial fibrillation by signal-averaged electrocardiography A prospective study. Circulation. 1992; 96: 2612-2616 Crossref Scopus (104) Google Scholar The aim of this study was to clarify the electrophysiologic mechanism for preventing AF recurrence by atrial septal pacing from the viewpoint of P-dispersion and atrial late potentials.