Håkan Walfridsson

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.).

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.

Incidence of Sudden Death After Radiofrequency Ablation of the Atrioventricular Junction for Atrial Fibrillation

This study assesses the incidence of sudden death and classifies the causes of death following radiofrequency ablation of the atrioventricular (AV) junction. We studied 220 patients with paroxysmal (n = 105) or chronic (n = 115) atrial fibrillation (AF) and a mean age of 64 +/- 12 years. These patients were followed 31 +/- 15 months after radiofrequency ablation of the AV junction and pacemaker implantation. In 86 patients, structural heart disease was identified before the procedure. All patients were traced via the Swedish National Civic Registry and Cause of Death Registry. The cause-of-death was classified according to data from death certificates, autopsy protocols, and medical records. Thirty-one patients (mean age 69 +/- 11 years, 16 men) died 15 +/- 15 months (range 0.2 to 60) after the procedure. There were 6 sudden unexplained deaths, 14 cardiovascular deaths, and 11 deaths from noncardiovascular causes. Eleven patients, all with structural heart disease, died suddenly out of hospital 16 +/- 16 months (range 0.2 to 42) after the procedure. In 6 of these there was no obvious cause of death. Three of these 6 patients underwent autopsy, which showed extensive coronary artery disease (n = 1), severe heart failure (n = 1) and cardiac hypertrophy and dilation (n = 1). The remaining 3 all had depressed left ventricular systolic function and a history of congestive heart failure. Five of the patients who died suddenly from cardiovascular causes had autopsies that revealed acute myocardial infarction (n = 4) and massive pulmonary embolism (n = 1).

Predictive importance of clinical findings and a predischarge exercise test in patients with suspected unstable coronary artery disease

The prognostic information of clinical variables and a predischarge exercise test was studied in 400 patients (282 men, 118 women) admitted to the coronary care unit with suspected unstable coronary artery disease, that is, recurring chest pain of new onset, increasing anginal pain in formerly stable angina pectoris or suspected nontransmural acute myocardial infarction. Forty-nine coronary events occurred in the 276 men who performed the exercise test during the following year, whereas only 5 coronary events occurred among the 118 women. The only variable of prognostic importance in women was nontransmural myocardial infarction. In men, the clinical variables increasing age, duration of angina, ST- or T-segment changes on the rest electrocardiogram and increasing angina or nontransmural myocardial infarction as inclusion criteria were associated with increased occurrence of coronary artery bypass surgery, transmural myocardial infarction or cardiac death. Findings of ST-segment depression, limiting chest pain or low rate-pressure product during the exercise test were of greater value than any clinical variable in prediction of coronary artery bypass surgery, transmural myocardial infarction or cardiac death. Within all clinical subgroups of men, the results of the exercise test had an additive predictive value for future coronary events. Combinations of clinical data and exercise test results enabled the best identification of patients with high or low risk for coronary events.

The Impact of Supraventricular Tachycardias on Driving Ability in Patients Referred for Radiofrequency Catheter Ablation

Aim: The aim of the present study was to evaluate the occurrence of arrhythmia‐related symptoms in patients with supraventricular tachycardia (SVT) referred for radiofrequency catheter ablation (RF ablation) with special focus on driving ability.

The Medical ANtiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation (MANTRA-PAF) Trial: clinical rationale, study design, and implementation

AIMS No large randomized multicentre trial has evaluated the efficacy of radiofrequency ablation (RFA) vs. anti-arrhythmic drug (AAD) therapy as a first-line treatment of paroxysmal atrial fibrillation (AF). METHODS AND RESULTS The Medical ANtiarrhythmic Treatment or Radiofrequency Ablation (MANTRA-PAF) trial is a randomized, controlled, parallel group, multicentre study designed to test whether catheter-based RFA is superior to optimized AAD therapy in suppressing relapse within 24 months of symptomatic and/or asymptomatic AF in patients with paroxysmal AF without prior AAD therapy. The primary endpoint is cumulative AF burden on repeated 7 days Holter monitoring. Secondary endpoints are: thromboembolic events, hospitalization due to arrhythmia, pro-arrhythmic events, procedure/treatment-related side effects, health economics, quality of life, and change in left ventricular function. Ten centres in Scandinavia and Germany are participating in the study. Enrolment was started in 2005 and as of November 2008, 260 patients have been enrolled into the study. It is expected that enrolment will end by March 2009, when 300 patients have been included. CONCLUSION The MANTRA-PAF trial will determine whether catheter-based RFA is superior to optimized AAD therapy as a first-line treatment in suppressing long-term relapse of symptomatic and/or asymptomatic AF.

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.

Wolff-Parkinson-White Syndrome and Atrioventricular Nodal Re-Entry Tachycardia in a Swedish Population: Consequences on Health-Related Quality of Life

Background: Living with paroxysmal supraventricular tachycardia affects a patients whole life situation, but few studies have addressed health‐related quality of life (HRQOL) aspects in these patients. The aim was therefore to describe HRQOL in patients with atrioventricular nodal re‐entry tachycardia (AVNRT) or Wolff‐Parkinson‐White (WPW) syndrome, referred for radiofrequency ablation (RF‐ablation), compared to age‐ and gender‐matched Swedish reference groups.

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).

Prophylactic cavotricuspid isthmus block during atrial fibrillation ablation in patients without atrial flutter: a randomised controlled trial

Objectives: This randomised trial evaluated if patients with atrial fibrillation (AF) and no history of atrial flutter (AFL) had any benefit of prophylactic cavotricuspid isthmus block (CTIB) in addition to circumferential pulmonary vein ablation (CPVA). Methods: 149 patients with AF (54% paroxysmal) were randomised to CPVA and CTIB (group CTIB+, n = 73) or CPVA alone (group CTIB−, n = 76). Patients were followed for 12 months with repetitive 7-day Holter monitoring after 3, 6 and 12 months. Results: Six patients (4%) had cardiac tamponade, and one patient had a stroke. No difference was found in the cumulative AFL-free rate between the two treatment groups (CTIB+: 88% vs CTIB−: 84%, hazard ratio (HR) 0.80, 95% CI (0.34 to 1.90), p = 0.61). There was no difference in the cumulative AF-free rate between the groups (CTIB+: 34% vs CTIB−: 32%, HR 0.93, 95% CI (0.63 to 1.38), p = 0.71). Overall, 33% of the patients were free of AF after a single procedure. Including reprocedures, a complete or partial beneficial effect was noted in 62% of the patients at 12 months. At 12-month follow-up, 24 (50%) patients with documented AF or AFL in the Holter recordings were asymptomatic. Conclusions: It was not possible to demonstrate any beneficial effect of CTIB in addition to CPVA with regard to AFL or AF recurrences during follow-up. Repetitive long-term Holter monitoring demonstrated a 33% rate of freedom from AF during a 1-year follow-up. Including additional CPVA procedures, a clinical effect was noted in 62% of the patients at 12 months. Patients with AF or AFL recurrences were often asymptomatic.