Anders Englund

Radiofrequency ablation as initial therapy in paroxysmal atrial fibrillation.

BACKGROUND There are limited data comparing radiofrequency catheter ablation with antiarrhythmic drug therapy as first-line treatment in patients with paroxysmal atrial fibrillation. METHODS We randomly assigned 294 patients with paroxysmal atrial fibrillation and no history of antiarrhythmic drug use to an initial treatment strategy of either radiofrequency catheter ablation (146 patients) or therapy with class IC or class III antiarrhythmic agents (148 patients). Follow-up included 7-day Holter-monitor recording at 3, 6, 12, 18, and 24 months. Primary end points were the cumulative and per-visit burden of atrial fibrillation (i.e., percentage of time in atrial fibrillation on Holter-monitor recordings). Analyses were performed on an intention-to-treat basis. RESULTS There was no significant difference between the ablation and drug-therapy groups in the cumulative burden of atrial fibrillation (90th percentile of arrhythmia burden, 13% and 19%, respectively; P=0.10) or the burden at 3, 6, 12, or 18 months. At 24 months, the burden of atrial fibrillation was significantly lower in the ablation group than in the drug-therapy group (90th percentile, 9% vs. 18%; P=0.007), and more patients in the ablation group were free from any atrial fibrillation (85% vs. 71%, P=0.004) and from symptomatic atrial fibrillation (93% vs. 84%, P=0.01). One death in the ablation group was due to a procedure-related stroke; there were three cases of cardiac tamponade in the ablation group. In the drug-therapy group, 54 patients (36%) underwent supplementary ablation. CONCLUSIONS In comparing radiofrequency ablation with antiarrhythmic drug therapy as first-line treatment in patients with paroxysmal atrial fibrillation, we found no significant difference between the treatment groups in the cumulative burden of atrial fibrillation over a period of 2 years. (Funded by the Danish Heart Foundation and others; MANTRA-PAF ClinicalTrials.gov number, NCT00133211.).

Postoperative atrial fibrillation in patients undergoing aortocoronary bypass surgery carries an eightfold risk of future atrial fibrillation and a doubled cardiovascular mortality

OBJECTIVE This article presents a study of postoperative atrial fibrillation (AF) and its long-term effects on mortality and heart rhythm. METHODS The study cohort consisted of 571 patients with no history of AF who underwent primary aortocoronary bypass surgery from 1999 to 2000. Postoperative AF occurred in 165/571 patients (28.9%). After a median follow-up of 6 years, questionnaires were obtained from 91.6% of surviving patients and an electrocardiogram (ECG) from 88.6% of all patients. Data from hospitalisations due to arrhythmia or stroke during follow-up were analysed. The causes of death were obtained for deceased patients. RESULTS In postoperative AF patients, 25.4% had atrial fibrillation at follow-up compared with 3.6% of patients with no AF at surgery (p<0.001). An episode of postoperative AF was the strongest independent risk factor for development of late AF, with an adjusted risk ratio of 8.31 (95% confidence interval (CI) 4.20-16.43). Mortality was 29.7% (49 deaths/165 patients) in the AF group and 14.8% (60 deaths/406 patients) in the non-AF group (p<0.001). Death due to cerebral ischaemia was more common in the postoperative AF group (4.2% vs 0.2%, p<0.001), as was death due to myocardial infarction (6.7% vs 3.0%, p=0.041). Postoperative AF was an age-independent risk factor for late mortality, with an adjusted hazard ratio of 1.57 (95% CI 1.05-2.34). CONCLUSIONS Postoperative AF patients have an eightfold increased risk of developing AF in the future, and a doubled long-term cardiovascular mortality.

Comorbidity and Myocardial Dysfunction Are the Main Explanations for the Higher 1-Year Mortality in Acute Myocardial Infarction With Left Bundle-Branch Block

Background—The purpose of this study was to assess the independent contribution of left bundle-branch block (LBBB) on cause-specific 1-year mortality in a large cohort with acute myocardial infarction (MI). Methods and Results—We studied a prospective cohort of 88 026 cases of MI from the Register of Information and Knowledge about Swedish Heart Intensive care Admissions in 72 hospitals in 1995 to 2001. Long-term mortality was calculated by Cox regression analysis, adjusted for multiple covariates that affect mortality by calculation of a propensity score. LBBB was present in 9% (8041 of 88 026) of the MI admissions. Patients with LBBB were older and had a higher prevalence of comorbid conditions than patients with no LBBB. The unadjusted relative risk of death within 1 year was 2.16 (95% CI, 2.08 to 2.24; P<0.001) for LBBB (42%, 3350 of 8041) compared with those with no LBBB (22%, 17 044 of 79 011). After adjustment for a propensity score that takes into account differences in risk factors and acute intervention, LBBB was associated with a relative risk of death of 1.19 (95% CI, 1.14 to 1.24; P<0.001). In a subgroup of 11 812 patients for whom left ventricular ejection fraction was available and could be added to the analysis, the contributing relative risk of LBBB for death was only 1.08 (95% CI, 0.93 to 1.25; P=0.33). The most common cause of death in both groups was ischemic heart disease. Conclusions—MI patients with LBBB have more comorbid conditions and an increased unadjusted 1-year mortality. When adjusted for age, baseline characteristics, concomitant diseases, and left ventricular ejection fraction, LBBB does not appear to be an important independent predictor of 1-year mortality in MI.

Source of inflammatory markers in patients with atrial fibrillation

AIMS Elevated levels of C-reactive protein and other inflammatory markers have been reported in some patients with atrial fibrillation (AF). Whether this finding is related to AF per se or to other conditions remains unclear. In addition, the source of inflammatory markers is unknown. Therefore, in the present study, we sought to assess the extent and the source of inflammation in patients with AF and no other concomitant heart or inflammatory conditions. METHODS AND RESULTS The study group consisted of 29 patients referred for radiofrequency catheter ablation: 10 patients with paroxysmal AF, 8 patients with permanent AF, and 10 control patients with Wolf-Parkinson-White (WPW) syndrome and no evidence of AF (mean age 54 +/- 11 vs. 57 +/- 13 vs. 43 +/- 16). No patient had structural heart diseases or inflammatory conditions. High-sensitive C-reactive protein, interleukin-6 (IL-6), and interleukin-8 (IL-8) were assessed in blood samples from the femoral vein, right atrium, coronary sinus, and the left and right upper pulmonary veins. All samples were collected before ablation. Compared with controls and patients with paroxysmal AF, patients with permanent AF had higher plasma levels of IL-8 in the samples from the femoral vein, right atrium, and coronary sinus, but not in the samples from the pulmonary veins (median values in the femoral vein: 2.58 vs. 2.97 vs. 4.66 pg/mL, P = 0.003; right atrium: 2.30 vs. 3.06 vs. 3.93 pg/mL, P = 0.013; coronary sinus: 2.85 vs. 3.15 vs. 4.07, P = 0.016). A high-degree correlation existed between the IL-8 levels in these samples (correlation coefficient between 0.929 and 0.976, P < 0.05). No differences in the C-reactive protein and IL-6 levels were noted between the three groups of patients. CONCLUSION The normal levels of C-reactive protein and IL-6, along with the elevated levels of IL-8 in patients with permanent AF but not in those with paroxysmal AF, suggest a link between a low-grade inflammatory reaction and long-lasting AF. The elevated IL-8 levels in the peripheral blood, right atrium, and coronary sinus but not in the pulmonary veins suggest a possible source of inflammation in the systemic circulation.

Atorvastatin and persistent atrial fibrillation following cardioversion: a randomized placebo-controlled multicentre study

AIMS To evaluate the effect of atorvastatin in achieving stable sinus rhythm (SR) 30 days after electrical cardioversion (CV) in patients with persistent atrial fibrillation (AF). METHODS AND RESULTS The study included 234 patients. The patients were randomized to treatment with atorvastatin 80 mg daily (n = 118) or placebo (n = 116) in a prospective, double-blinded fashion. Treatment was initiated 14 days before CV and was continued 30 days after CV. The two groups were well-balanced with respect to baseline characteristics. Mean age was 65 +/- 10 years, 76% of the patients were male and 4% had ischaemic heart disease. Study medication was well-tolerated in all patients but one. Before primary endpoint 12 patients were excluded. In the atorvastatin group 99 patients (89%) converted to SR at electrical CV compared with 95 (86%) in the placebo group (P = 0.42). An intention-to-treat analysis with the available data, by randomization group, showed that 57 (51%) in the atorvastatin group and 47 (42%) in the placebo group were in SR 30 days after CV (OR 1.44, 95%CI 0.85-2.44, P = 0.18). CONCLUSION Atorvastatin was not statistically superior to placebo with regards to maintaining SR 30 days after CV in patients with persistent AF.

Patients with postoperative atrial fibrillation have a doubled cardiovascular mortality

Objectives. To investigate the impact of postoperative AF on late mortality and cause of death in CABG patients. Design. All CABG patients without preoperative AF surgically treated between January 1, 1997 and June 30, 2000 were included (N = 1419). Altogether, 419 patients (29.5%) developed postoperative AF. After a median follow-up of 8.0 years, survival data were obtained, causes of death were compared and Cox proportional hazard analysis was used to determine predictors of late mortality. Results. The total mortality was 140 deaths/419 patients (33.4%) in postoperative AF patients and 191 deaths/1 000 patients (19.1%) in patients without AF. Death due to cerebral ischemia (2.6% vs. 0.5%), myocardial infarction (7.4% vs. 3.0%), sudden death (2.6% vs. 0.9%), and heart failure (6.7% vs. 2.7%) was more common among postoperative AF patients. Postoperative AF was an age-independent risk indicator for late mortality with a hazard ratio (HR) of 1.56 (95% confidence interval 1.23–1.98). Conclusions. Postoperative AF is an age-independent risk factor for late mortality in CABG patients, explained by an increased risk of cardiovascular death.

Radiofrequency ablation as initial therapy in paroxysmal atrial fibrillation: results on health-related quality of life and symptom burden. The MANTRA-PAF trial

AIMS The Medical ANtiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation (MANTRA-PAF) trial assessed the long-term efficacy of an initial strategy of radiofrequency ablation (RFA) vs. antiarrhythmic drug therapy (AAD) as first-line treatment for patients with PAF. In this substudy, we evaluated the effect of these treatment modalities on the Health-Related Quality of Life (HRQoL) and symptom burden of patients at 12 and 24 months. METHODS AND RESULTS During the study period, 294 patients were enrolled in the MANTRA-PAF trial and randomized to receive AAD (N = 148) or RFA (N = 146). Two generic questionnaires were used to assess the HRQoL [Short Form-36 (SF-36) and EuroQol-five dimensions (EQ-5D)], and the Arrhythmia-Specific questionnaire in Tachycardia and Arrhythmia (ASTA) was used to evaluate the symptoms appearing during the trial. All comparisons were made on an intention-to-treat basis. Both randomization groups showed significant improvements in assessments with both SF-36 and EQ-5D, at 24 months. Patients randomized to RFA showed significantly greater improvement in four physically related scales of the SF-36. The three most frequently reported symptoms were breathlessness during activity, pronounced tiredness, and worry/anxiety. In both groups, there was a significant reduction in ASTA symptom index and in the severity of seven of the eight symptoms over time. CONCLUSION Both AAD and RFA as first-line treatment resulted in substantial improvement of HRQoL and symptom burden in patients with PAF. Patients randomized to RFA showed greater improvement in physical scales (SF-36) and the EQ-visual analogue scale. CLINICAL TRIAL REGISTRATION URL http://www.clinicaltrials.gov. Unique identifier: NCT00133211.

The cost-effectiveness of radiofrequency catheter ablation as first-line treatment for paroxysmal atrial fibrillation: results from a MANTRA-PAF substudy

AIM The aim of this prospective substudy was to estimate the cost-effectiveness of treating paroxysmal atrial fibrillation (AF) with radiofrequency catheter ablation (RFA) compared with antiarrhythmic drugs (AADs) as first-line treatment. METHODS AND RESULTS A decision-analytic Markov model, based on MANTRA-PAF (Medical Antiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation) study data, was developed to study long-term effects and costs of RFA compared with AADs as first-line treatment. Positive clinical effects were found in the overall population, a gain of an average 0.06 quality-adjusted life years (QALYs) to an incremental cost of €3033, resulting in an incremental cost-effectiveness ratio of €50 570/QALY. However, the result of the subgroup analyses showed that RFA was less costly and more effective in younger patients. This implied an incremental cost-effectiveness ratio of €3434/QALY in ≤50-year-old patients respectively €108 937/QALY in >50-year-old patients. CONCLUSION Radiofrequency catheter ablation as first-line treatment is a cost-effective strategy for younger patients with paroxysmal AF. However, the cost-effectiveness of using RFA as first-line therapy in older patients is uncertain, and in most of these AADs should be attempted before RFA (MANTRA-PAF ClinicalTrials.gov number; NCT00133211).

Radiofrequency catheter ablation maintains its efficacy better than antiarrhythmic medication in patients with paroxysmal atrial fibrillation: On-treatment analysis of the randomized controlled MANTRA-PAF trial.

BACKGROUND The Medical ANtiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation (MANTRA-PAF) is a randomized trial comparing radiofrequency catheter ablation (RFA) to antiarrhythmic drugs (AADs) as first-line treatment of paroxysmal atrial fibrillation (PAF). In order to eliminate the clouding effect of crossover we performed an on-treatment analysis of the data. METHODS AND RESULTS Patients (n=294) were divided into three groups: those receiving only the assigned therapy (RFA and AAD groups) and those receiving both therapies (crossover group). The primary end points were AF burden in 7-day Holter recordings at 3, 6, 12, 18, and 24 months and cumulative AF burden in all recordings. At 24 months, AF burden was significantly lower in the RFA (n=110) than in the AAD (n=92) and the crossover (n=84) groups (90th percentile 1% vs. 10% vs. 16%, P=0.007), and more patients were free from any AF (89% vs. 73% vs. 74%, P=0.006). In the RFA, AAD and the crossover groups 63%, 59% and 21% (P<0.001) of the patients had no AF episodes in any Holter recording, respectively. Quality of life improved significantly in all groups. There were no differences in serious adverse events between the RFA, AAD and crossover groups (19% vs. 8% vs. 23%) (P=0.10). CONCLUSIONS In the treatment of antiarrhythmic therapy naïve patients with PAF long-term efficacy of RFA was superior to AAD therapy. Thus, it is reasonable to offer RFA as first-line treatment for highly symptomatic patients who accept the risks of the procedure and are aware of frequent need for reablation(s).

Disopyramide stress test: a sensitive and specific tool for predicting impending high degree atrioventricular block in patients with bifascicular block.

OBJECTIVE--To study the value of intravenous disopyramide as part of an invasive electrophysiological study in predicting impending high degree atrioventricular block in patients with bifascicular block. DESIGN--An invasive electrophysiological study was performed in the basal state and after the infusion of disopyramide (2 mg/kg body weight). The progression to high degree atrioventricular block was assessed by bradycardia-detecting pacemakers or repeated 12-lead electrocardiogram recordings, or both. PATIENTS--73 patients with bifascicular block were included, of whom 25 had a history of unexplained syncope. The remaining 48 patients had no arrhythmia related symptoms and were included as controls. All patients had an ejection fraction of > 35%. RESULTS--After a mean follow up of 23 months, seven patients in the syncope group and three in the non-syncope group had a documented high degree atrioventricular block or pacemaker-detected bradycardia of < or = 30 beats/min for > or = 6 s. The sensitivity of the disopyramide test was 71% and the specificity 98%. The corresponding figures for an abnormal electrophysiological study in the basal state were 14% and 91%, respectively. CONCLUSIONS--The sensitivity of an invasive electrophysiological study in patients with bifascicular block and syncope can be markedly increased by the use of intravenous disopyramide. A positive test is a highly specific finding and warrants pacemaker implantation.