Arne Johannessen

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.).

The incidence and prognostic significance of new-onset atrial fibrillation in patients with acute myocardial infarction and left ventricular systolic dysfunction: A CARISMA substudy

BACKGROUND The incidence and risk associated with new-onset atrial fibrillation (AF) occurring after discharge in patients with acute myocardial infarction (MI) remains unknown. OBJECTIVE This study sought to describe the incidence and clinical risk associated with postdischarge new-onset AF in post-MI patients with left ventricular systolic dysfunction. METHODS The population included 271 post-MI patients with left ventricular ejection fraction ≤ 40% and no history of previous AF from the Cardiac Arrhythmias and Risk Stratification after Acute Myocardial Infarction (CARISMA) study. All patients were implanted with an implantable cardiac monitor and followed up every 3 months for 2 years. Major cardiovascular events were defined as reinfarction, stroke, hospitalization for heart failure, or death. RESULTS The risk of new-onset AF is highest during the first 2 months after the acute MI (16% event rate) and decreases until month 12 post-MI, after which the risk for new-onset AF is stable. The risk of major cardiovascular events was increased in patients with AF events ≥ 30 seconds (hazard ratio [95% CI] = 2.73 [1.35 to 5.50], P = .005), but not in patients with AF events lasting <30 seconds (hazard ratio [95% CI] = 1.17 [0.35 to 3.92], P = .80). More than 90% of all recorded AF events were asymptomatic. CONCLUSION Using an implantable cardiac monitor, the incidence of new-onset AF was found to be 4-fold higher than earlier reported. In the study population, in which treatment with beta-blockers was optimized, the vast majority of AF events were asymptomatic, emphasizing the importance of using continuous monitoring for studies concerning AF in heart failure patients. A duration of 30 seconds or more identified clinically important AF episodes documented by an implantable cardiac monitor.

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.

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).

Long-term efficacy of catheter ablation as first-line therapy for paroxysmal atrial fibrillation: 5-year outcome in a randomised clinical trial

Objective The Medical ANtiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation (MANTRA-PAF) trial compared radiofrequency catheter ablation (RFA) with antiarrhythmic drug therapy (AAD) as first-line treatment for paroxysmal atrial fibrillation (AF). Endpoint of ablation was elimination of electrical activity inside pulmonary veins. We present the results of the 5-year follow-up. Methods This pre-specified 5-year follow-up included assessment of any AF and symptomatic AF burden by one 7-day Holter recording and quality of life (QoL) assessment, using SF-36 questionnaire physical and mental component scores. Analysis was intention-to-treat. Imputation was used to compensate for missing Holter data. Results 245 of 294 patients (83%) randomised to RFA (n=125) or AAD (n=120) attended the 5-year follow-up, 227 with Holter recording. Use of class I or III AAD was more frequent in AAD group (N=61 vs 13, p<0.001). More patients in the RFA group were free from AF (126/146 (86%) vs 105/148 (71%), p=0.001, relative risk (RR) 0.82; 95% CI 0.73 to 0.93) and symptomatic AF (137/146 (94%) vs 126/148 (85%), p=0.015, χ2 test, RR 0.91; 95% CI 0.84 to 0.98) in 7-day Holter recording. AF burden was significantly lower in the RFA group (any AF: p=0.003; symptomatic AF: p=0.02). QoL scores did not differ between randomisation groups. QoL scores remained improved from baseline (both components p<0.001), and did not differ from 2-year scores. Conclusions At 5 years, the occurrence and burden of any AF and symptomatic AF were significantly lower in the RFA group than in the AAD group. Improved QoL scores observed after 2 years persisted after 5 years without between-group differences. Trial registration number NCT00133211; Results.

The role of local voltage potentials in outflow tract ectopy

AIMS Discrete, fragmented, local voltage potentials (LVPs) have been observed in electrograms recorded at the ablation site in patients undergoing radiofrequency ablation for arrhythmias originating in both the right and left ventricular outflow tract; however, the incidence and the significance of the LVP with respect to arrhythmogenesis is uncertain. METHODS AND RESULTS We studied 25 patients with outflow tract arrhythmias referred for radiofrequency catheter ablation and recorded high-amplified intracardiac electrograms close to the site of origin of the arrhythmia. Ten patients undergoing ablation for supraventricular arrhythmias served as controls. During sinus rhythm, LVPs were recorded in 24 of the 25 patients, 10-85 ms (41 +/- 19 ms) after the onset of the QRS complex, duration 33 +/- 11 ms, voltage 2.0 +/- 1.5 mV. The same potential was recorded 10-52 ms (mean 37 +/- 11 ms) prior to the V potential in the ventricular premature beats. In 10 patients, ventricular parasystole was suggested by varying coupling intervals >100 ms, and fusion beats allowing for the estimation of the least common denominator of R-R intervals. In 23 of the 25 patients, the 12-lead electrocardiogram (ECG) and intracardiac contact mapping located the arrhythmias to an area of 3-4 cm(2) in the septal region of the right ventricular outflow tract; in two patients, the site of origin was in the left coronary cusp. Radiofrequency ablation carried out in 24 of the 25 patients was successful in 21 patients, and after successful ablation, the LVP could still be recorded in all these 21 patients. The LVP was not present in 10 controls. CONCLUSION Local potentials are recorded close to the site of origin of ventricular ectopy in >90% of patients with idiopathic outflow tract ectopy and imply successful ablation. The potentials may reflect an area of depressed conductivity known to be a prerequisite for experimental ventricular ectopy including parasystole.

Antiarrhythmic medication is superior to catheter ablation in suppressing supraventricular ectopic complexes in patients with atrial fibrillation

BACKGROUND Supraventricular ectopic complexes (SVEC) originating in the pulmonary veins are known triggers of atrial fibrillation (AF) which led to the development of pulmonary vein isolation for AF. However, the long-term prevalence of SVEC after catheter ablation (CA) as compared to antiarrhythmic medication (AAD) is unknown. Our aims were to compare the prevalence of SVEC after AAD and CA and to estimate the association between baseline SVEC burden and AF burden during 24months of follow-up. METHODS Patients with paroxysmal AF (N=260) enrolled in the MANTRA PAF trial were treated with AAD (N=132) or CA (N=128). At baseline and 3, 6, 12, 18 and 24months follow-up patients underwent 7-day Holter monitoring to assess SVEC and AF burden. We compared SVEC burden between treatments with Wilcoxon sum rank test. RESULTS Patients treated with AAD had significantly lower daily SVEC burden during follow-up as compared to CA (AAD: 19 [6-58] versus CA: 39 [14-125], p=0.003). SVEC burden increased post-procedurally followed by a decrease after CA whereas after AAD SVEC burden decreased and stabilized after 3months of follow-up. Patients with low SVEC burden had low AF burden after both treatments albeit this was more pronounced after CA at 24months of follow-up. CONCLUSION AAD was superior to CA in suppressing SVEC burden after treatment of paroxysmal AF. After CA SVEC burden increased immediately post-procedural followed by a decrease whereas after AAD an early decrease was observed. Lower SVEC burden was highly associated with lower AF burden during follow-up especially after CA.

The impact of supraventricular ectopic complexes in different age groups and risk of recurrent atrial fibrillation after antiarrhythmic medication or catheter ablation

INTRODUCTION Supraventricular ectopic complexes (SVEC) are known risk factors of recurrent atrial fibrillation (AF). However, the impact of SVEC in different age groups is unknown. We aimed to investigate the risk of AF recurrence with higher SVEC burden in patients ±57years, respectively, after treatment with antiarrhythmic medication (AAD) or catheter ablation (CA). METHODS In total, 260 patients with LVEF >40% and age ≤70 years were randomized to AAD (N=132) or CA (N=128) as first-line treatment for paroxysmal AF. All patients underwent 7-day Holter monitoring at baseline, and after 3, 6, 12, 18 and 24months and were categorized according to median age ±57years. We used multivariate Cox regression analyses and we defined high SVEC burden at 3months of follow-up as the upper 75th percentile >195SVEC/day. AF recurrence was defined as AF ≥1min, AF-related cardioversion or hospitalization. RESULTS Age >57years were significantly associated with higher AF recurrence rate after CA (58% vs 36%, p=0.02). After CA, we observed a higher SVEC burden during follow-up in patients >57years which was not observed in the younger age group treated with CA (p=0.006). High SVEC burden at 3months after CA was associated with AF recurrence in older patients but not in younger patients (>57years: HR 3.4 [1.4-7.9], p=0.005). We did not find any age-related differences after AAD. CONCLUSION We found that younger and older patients respond differently to CA and that SVEC burden was only associated with AF recurrence in older patients.