Gender and age differences in symptoms and health-related quality of life in patients with atrial fibrillation referred for catheter ablation.

BACKGROUND: Primary indication for catheter ablation of atrial fibrillation (AF) is to reduce symptoms and improve health-related quality of life (HRQoL). There are data showing differences between the genders and between younger and older patients. To evaluate this, we studied a large Scandinavian cohort of patients referred for catheter ablation of AF. METHODS: Consecutive patients filled out the ASTA questionnaire, assessing symptoms, HRQoL, and perception of arrhythmia, prior to ablation. Patients were recruited from four Swedish and one Danish tertiary center. RESULTS: A total of 2493 patients (72% men) filled out the ASTA questionnaire. Women experienced eight of the nine ASTA scale symptoms more often than men. Patients <65 years reported four symptoms more often, only tiredness was more frequent in those ≥65 years (P = .007). Women and patients <65 years experienced more often palpitations and regarding close to fainting and this was more common among women, no age differences were seen. Women and men scored differently in 10 of the 13 HRQoL items. Only negative impact on sexual life was more common in men (P < .001). Older patients reported more negative influence in four of the HRQoL items and the younger in one; ability to concentrate. CONCLUSIONS: Women experienced a more pronounced symptom burden and were more negatively affected in all HRQoL concerns, except for the negative impact on sexual life, where men reported more influence of AF. Differences between age groups were less pronounced. Disease-specific patient-reported outcomes measures (PROMs) add important information where gender differences should be considered in the care.

Transvenous interventional implantation of CRT-D in a critically ill Mustard patient waiting for heart transplant.

Cardiac resynchronization therapy may stabilize patients with severe heart failure awaiting heart transplant. Transvenous interventional implantation aided by intracardiac echocardiography is feasible in patients with adult congenital heart disease.

A decade of catheter ablation of cardiac arrhythmias in Sweden: ablation practices and outcomes.

AIMS: Catheter ablation is considered the treatment of choice for many tachyarrhythmias, but convincing 'real-world' data on efficacy and safety are lacking. Using Swedish national registry data, the ablation spectrum, procedural characteristics, as well as ablation efficacy and reported adverse events are reported. METHODS AND RESULTS: Consecutive patients (≥18 years of age) undergoing catheter ablation in Sweden between 01 January 2006 and 31 December 2015 were included in the study. Follow-up (repeat ablation and vital status) was collected through 31 December 2016. A total of 26 642 patients (57 ± 15 years, 62% men), undergoing a total of 34 428 ablation procedures were included in the study. In total, 4034 accessory pathway/Wolff-Parkinson-White syndrome (12%), 7358 AV-nodal re-entrant tachycardia (21%), 1813 atrial tachycardia (5.2%), 5481 typical atrial flutter (16%), 11 916 atrial fibrillation (AF, 35%), 2415 AV-nodal (7.0%), 581 premature ventricular contraction (PVC, 1.7%), and 964 ventricular tachycardia (VT) ablations (2.8%) were performed. Median follow-up time was 4.7 years (interquartile range 2.7-7.0). The spectrum of treated arrhythmias changed over time, with a gradual increase in AF, VT, and PVC ablation (P < 0.001). Decreasing procedural times and utilization of fluoroscopy with time, were seen for all arrhythmia types. The rates of repeat ablation differed between ablation types, with the highest repeat ablation seen in AF (41% within 3 years). The rate of reported adverse events was low (n = 595, 1.7%). Death in the immediate period following ablation was rare (n = 116, 0.34%). CONCLUSION: Catheter ablations have shifted towards more complex procedures over the past decade. Fluoroscopy time has markedly decreased and the efficacy of catheter ablation seems to improve for AF.

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.

Higher burden of supraventricular ectopic complexes early after catheter ablation for atrial fibrillation is associated with increased risk of recurrent atrial fibrillation.

Aims: Early identification of patients who could benefit from early re-intervention after catheter ablation is highly warranted. Our aim was to investigate the association between post-procedural burden of supraventricular ectopic complexes (SVEC) and the risk of long-term atrial fibrillation (AF) recurrence. Methods and results: A total of 125 patients undergoing catheter ablation for AF were included. Patients underwent 7-day Holter recordings immediately post-procedural. The number of SVEC in post-procedural Holter recordings was categorized into quartiles: 0-72, 73-212, 213-782 and ≥ 783 SVEC/day. Long-term AF recurrence was defined as a combined endpoint of AF ≥ 1 min during follow-up Holter recordings, cardioversion or hospitalization for AF after a 3-month blanking period and within 24 months of follow-up. High post-procedural supraventricular ectopy burden was associated with an increased risk of long-term AF recurrence in a dose-dependent manner (≥ 783 SVEC: HR 4.6 [1.9-11.5], P < 0.001) irrespective of AF recurrence during the blanking period or other risk factors. In patients with early AF recurrence < 90 days after catheter ablation ectopy burden was also highly predictive of long-term AF recurrence (SVEC ≥ 213: HR 3.0 [1.3-6.7], P = 0.007). Correspondingly, patients with early AF recurrence but low ectopy burden remained at low risk of long-term AF recurrence after the blanking period. Conclusion: Our results indicate that post-procedural ectopy burden is highly associated with long-term AF recurrence and could be a potent risk marker for selection of patients for early re-ablation. Development of future ablation risk stratification and strategies should include focus on post-procedural ectopy burden.

Long-term outcomes of the current remote magnetic catheter navigation technique for ablation of atrial fibrillation.

OBJECTIVES: Comparisons between remote magnetic (RMN) and manual catheter navigation for atrial fibrillation (AF) ablation have earlier been reported with controversial results. However, these reports were based on earlier generations of the RMN system. DESIGN: To evaluate the outcomes of the most current RMN system for AF ablation in a larger patient population with longer follow-up time, 112 patients with AF (78 paroxysmal, 34 persistent) who underwent AF ablation utilizing RMN (RMN group) were compared to 102 AF ablation patients (72 paroxysmal, 30 persistent) utilizing manual technique (Manual group). RESULTS: The RMN group was associated with significantly shorter fluoroscopy time (10.4 ± 6.4 vs. 16.3 ± 10.9 min, p < .001) but used more RF energy (64.1 ± 19.4KJ vs. 54.3 ± 24.1 KJ, p < .05), while total procedure time showed no significant difference (201 ± 35 vs. 196 ± 44 min, NS). After 39 ± 9/44 ± 10 months of follow-up, AF-free rates at 1year, 2 years and 3.5 years post ablation were 63%, 46% and 42% in the RMN group vs. 60%, 32% and 30% (survival analysis p < .05) in the Manual group, whereas clinically effective rates were 82%, 73% and 70% for the former vs. 70%, 56% and 49% for the latter (survival analysis p < .005). CONCLUSION: Differing from previous reports, our data from a larger patient population and longer follow-up time demonstrates that compared to manual technique, the most current RMN technique is associated with better procedural and clinical outcomes for AF ablation.

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.

Left atrial appendage occlusion versus standard medical care in patients with atrial fibrillation and intracerebral haemorrhage: a propensity score-matched follow-up study.

AIMS: The aim of this study was to investigate the prognosis in patients with atrial fibrillation (AF) and intracerebral haemorrhage (ICH) having a left atrial appendage occlusion (LAAO) versus patients receiving standard medical therapy. METHODS AND RESULTS: A total of 151 patients from the Nordic countries with AF and previous ICH who underwent LAAO using the AMPLATZER Cardiac Plug or the AMPLATZER AMULET were compared to a propensity score-matched group of 151 patients receiving standard medical therapy. The two groups were matched so that their risks for stroke and bleeding were similar (CHA2DS2-VASc and HAS-BLED scores). The standard care patients were identified from the Danish Stroke Registry among 787 patients with AF and ICH. The primary endpoint was a composite of all-cause mortality, ischaemic stroke and major bleeding. Patients with AF and a prior ICH treated with LAAO had a lower risk of the composite outcome as compared to patients treated with standard medical care (events/1,000 years [95% confidence interval]: 53.3 [44.3-64.1] vs. 366.7 [298.2-450.9]; hazard ratio 0.16 [0.07-0.37]). CONCLUSIONS: LAAO is suggested to be of major clinical benefit in AF patients having sustained an ICH. These results have to be confirmed in a randomised clinical trial.

Atrial average conduction velocity in patients with and without paroxysmal atrial fibrillation.

OBJECTIVES: To evaluate intra-atrial conduction delay in patients with atrial fibrillation (AF) via calculation of conduction velocities (CVs) of the right and left atria. METHODS: Electroanatomic mapping was performed during sinus rhythm, in the right atrium (RA) in eight patients with paroxysmal AF, in 12 controls with atrioventricular nodal re-entrant tachycardia (AVNRT) and in the left atrium (LA) in additional 16 AF patients. Three-dimensional maps of activation sequences of the RA and LA were obtained. Local CVs were specifically calculated in the direction of wave-front propagation on the activation maps by using 3-dimensional coordinates and local activation times of triads of sites. Average CVs of each atrium and each of 8 predefined RA and LA regions were calculated. RESULTS: During sinus rhythm, the average CVs of the RA were significantly slower (P<0·05) in the AF group (0·60 ± 0·12 m s-1 ) than in the controls (0·83 ± 0·13 m s-1 ). The average CVs of the RA basal, septal and annulus regions were significantly slower than the corresponding regions in controls (P<0·05). In patients with AF, the average CV of the LA was 0·51 ± 0·11 m s-1 , which is significantly slower than that of the RA and than that of LA as previously reported (P<0·05). CONCLUSION: Compared to patients with AVNRT, patients with AF are associated with conduction delay in both atria with the delay being more marked in the LA than in the RA, which suggests the involvement of conduction disturbances in the genesis and/or perpetuation of AF.

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).

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).

Maximum electrogram-guided ablation of cavotricuspid isthmus-dependent atrial flutter.

AIMS: To verify and re-emphasise the efficacy of the max electrogram-guided approach for ablation of cavotricuspid isthmus (CTI)-dependent atrial flutter (AFL). METHODS: Consecutive patients were alternatively assigned to receive either conventional linear radio-frequency (RF) ablation between the tricuspid annulus and inferior vena cava (the linear approach) or RF ablation at sites with the highest electrograms (the max electrogram-guided approach). Sustained, bi-directional CTI block was the endpoint. Procedure parameters and follow-up data were obtained. RESULTS: In total, 80 patients were included, 40 each for the linear approach and the max electrogram-guided approach. To achieve sustained bi-directional CTI block, the linear approach needed 841 ± 594 sec or 14.0 ± 9.9 RF applications, with total fluoroscopy time of 18.6 ± 9.4 min and total procedure time of 152 ± 58 min, as compared to the max electrogram-guided approach which needed 350 ± 319 sec (p < 0.0001) or 5.8 ± 5.3 RF applications (p < 0.0001), with total fluoroscopy time of 14.8 ± 6.0 min (p < 0.05) and total procedure time of 111 ± 36 min (p < 0.0005). The CTI block was obtained with 3 or less RF applications in 18 patients in the max electrogram-guided group (45%), but only in 2 patients in the linear ablation group (5%). During follow-up of 28 ± 14 months, recurrence cases were 2 in the linear and 1 in the max electrogram-guided group (NS). CONCLUSION: During ablation of AFL, directly targeting muscle bundles in the CTI as guided by the highest electrograms is more efficient than making a linear lesion across the entire CTI, since using the former approach needed less RF application, shorter fluoroscopy and procedure times than using the latter. The max electrogram-guided approach may be recommended for routine clinical use to replace the conventional linear ablation approach.

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.).

Ventricular repolarization sequences on the epicardium and endocardium. Monophasic action potential mapping in healthy pigs.

UNLABELLED: To investigate repolarization sequence, monophasic action potentials were recorded from a mean of 153 ± 54 left and right ventricular epicardial and endocardial sites in 10 pigs using the CARTO mapping system (Biosense Webster, Waterloo, Belgium). The activation time and end-of-repolarization (EOR) time were measured and 3-dimensional maps of activation and repolarization sequences constructed. RESULTS: In 8 of 9 pigs, both the activation and EOR times appeared first in the septum and last in the latero-basal areas on the endocardium, not on the epicardium. The EOR followed the activation sequence, both on the epicardium (in 8/9 pigs) and endocardium (in 8/8 pigs). The maximal EOR differences were 84 ± 20 ms, whereas the local EOR differences between paired sites against each other on the left ventricular epicardium and endocardium were 11 ± 9 ms in the apex and 12 ± 12 ms in the anterior wall. CONCLUSION: The EOR follows the activation sequence both on the epicardium and endocardium. The apico-basal gradients are predominant repolarization gradients, as compared with the epicardial-endocardial gradients.

Regional heterogeneity of right atrial repolarization. Monophasic action potential mapping in swine.

OBJECTIVES: To establish a set of reference values for regional dispersion of repolarization of the right atrium in the in situ heart of pigs and to see if the global dispersion of repolarization could be estimated from regional mapping. DESIGN: Monophasic action potential (MAP) were sequentially recorded from 28 ? 3 sites in seven different regional areas of the right atrium: lateral, anterior and posterior wall, septum, sinoatrial node (SAN), appendage, and near the tricuspid annulus (TA) in 10 healthy pigs using the CARTO mapping system. RESULTS: The activation time (AT), MAP duration (MAPd) and end of repolarization time (EOR) of the whole right atrium were 68 ± 7, 239 ± 20 and 270 ± 23 ms, respectively. There were no significant differences on MAPd and EOR among the seven regional areas, nor between each of the regional and global values. The global dispersions of the MAPd and EOR were 75 ± 19 and 103 ± 13 ms, which were significantly greater than those obtained from any of the seven regional areas and those between two remote regions, SAN vs. TA and SAN vs. appendage regions. CONCLUSIONS: The data of regional and global dispersion of repolarization in healthy pigs can serve as reference values for evaluation of increased dispersion of repolarization. The global dispersions of MAPd and EOR in the right atrium were poorly estimated from regional mapping, suggesting the importance of global mapping in evaluating the dispersion of atrial repolarization.

Preferential conduction patterns along the coronary sinus during atrial fibrillation in humans and their modification by pulmonary vein isolation.

INTRODUCTION: Correlation function analysis applied to endocardial electrograms has earlier been used for analysis of agreement between signals and direction of activation during atrial fibrillation (AF). This study was aimed at evaluating whether preferential activation patterns along the coronary sinus (CS) exist in patients with AF. METHODS: Twenty-seven patients (57 ± 10 years old) admitted for electrophysiological (EP) study (10 patients) and/or AF ablation (17 patients) were studied, 8 with permanent and 19 with persistent AF. Unipolar signals were recorded during 60 seconds from a 10-pole CS catheter during AF at baseline (BL) and after isolation of left and right pulmonary veins and after additional lines in the left atrium (LA) (End). Correlation function analysis was applied to signals from each pair of adjacent electrodes, and graphs of cumulated time delay were made to enable interpretation of direction of activation. RESULTS: Correlation between paired signals was highest in the distal and middle parts of CS and lowest in the proximal CS. In 21 patients, correlation values greater than 0.8 between closely spaced electrodes suggested uniform propagation of the fibrillatory waves. In 18 of 21 patients, preferential conduction pattern along CS was seen. Of those, 15 patients had left-to-right conduction, and 3 had right-to-left conduction. During ablation, atrial fibrillation cycle length increased from 184 ± 32 milliseconds at BL to 193 ± 39 milliseconds after pulmonary vein isolation and 215 ± 39 milliseconds at the end of ablation (P = .03, BL vs End). Because of ablation, preferential conduction along CS changed in 4 patients from left to right at BL to simultaneous CS activation or right to left. In 1 of 3 patients with simultaneous activation at BL, the direction changed to right to left. No direction change was observed in any of the 3 patients with right-to-left activation at BL. CONCLUSIONS: Atrial activation during AF exhibits a high degree of organization in distal and middle CS. Preferential conduction patterns observed in most patients may indicate either relatively dominant stable reentry circuits in the LA or activation spread from a focal source. The changes in preferential conduction during ablation of AF may reflect modification of AF substrate and indicate persistent right atrial sources not affected by ablation in the LA only.

Effects of AZD0837, a novel direct thrombin inhibitor, on the electrophysiological properties of the human heart: a randomized, double-blind, parallel-group, placebo-controlled study.

BACKGROUND: AZD0837 is an investigational oral anticoagulant that is bioconverted to its active form, AR-H067637, a selective direct thrombin inhibitor. OBJECTIVES: The objectives of the present study were to investigate if there are any clinically relevant adverse effects of intravenous AZD0837 on cardiac conduction, refractoriness and repolarization, and to study its safety and tolerability. METHODS: In this randomized, double-blind, parallel-group, placebo-controlled study (study code D1250C00026), invasive electrophysiological measurements were performed twice in 30 subjects with a history of, or ongoing, atrial flutter, starting 30 minutes after successful ablation of atrial flutter and then 60 minutes after start of an intravenous infusion of AZD0837. Pre-study warfarin therapy was not an exclusion criterion. The stimulation protocol was performed mainly at 500 and 400 ms drive cycle length. A 12-lead ECG was also recorded before and during AZD0837 infusion. Plasma concentrations of AZD0837 and its metabolites were obtained at predefined timepoints. RESULTS: Measurements were made at baseline and during stable plasma concentrations of the prodrug AZD0837 (mean +/- standard deviation 7.96 +/- 2.38 micromol/L, approximate target of 10 micromol/L), the intermediate metabolite AR-H69927 (1.26 +/- 0.39 micromol/L, target 1-2 micromol/L) and the active direct thrombin inhibitor AR-H067637 (0.35 +/- 0.14 micromol/L, target 0.5-1.0 micromol/L). There were no clinically relevant effects on cardiac conduction (QRS duration, PR interval, His bundle electrogram, Wenckebach point), refractoriness (atrial, atrioventricular and ventricular effective refractory periods) or repolarization (QT, QT interval corrected for heart rate using Fridericia's formula, QRS onset to the top of the T wave [QT(top)], QRS onset to the end of the T wave [QT(end)] or QT(top) - QT(end)). CONCLUSIONS: AZD0837 was well tolerated, and had no clinically relevant effects on cardiac electrophysiology of the target population, either in subjects previously treated with warfarin or in those without previous treatment.

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.

Interatrial right-to-left conduction in patients with paroxysmal atrial fibrillation.

PURPOSE: We wanted to illustrate the right-to-left impulse propagation routes during sinus in patients with paroxysmal atrial fibrillation (PAF), as alterations in conduction patterns have been linked to the pathogenesis of PAF, and as no large patient materials have been published. METHODS: Patients underwent 3-D electroanatomical contact mapping prior to catheter ablation. The site of the earliest left atrial (LA) activation was determined. RESULTS: Three different interatrial routes were identified, either as solitary pathways (36/50 patients, 72%) or in their combinations (14/50). Bachmann's bundle (BB) was involved in the majority of the cases with solitary routes (25/36). More seldom, impulse propagation occurred near the oval fossa (FO) (7/36) or the coronary sinus ostium (4/36). In patients with combined routes, both the BB (10/14) and FO routes (11/14) were included in most cases. CONCLUSIONS: In PAF patients, LA can be activated during sinus rhythm through three distinct connections, either encompassing a single route or via any combination of these connections. In one third, the earliest LA activation occurs outside BB. The knowledge of the propagation patterns may give insight into the pathophysiology of PAF and into refining ablation therapy.