Cryoballoon vs. radiofrequency contact force ablation for paroxysmal atrial fibrillation: a propensity score analysis Circumferential pulmonary vein isolation with the cryoballoon technique results from a prospective 3-center study. Ablation of atrial fibrillation with cryoballoon or duty-cycled radiofrequency pulmonary vein ablation catheter: a randomized controlled study comparing the clinical outcome and safety; the AF-COR study. Pulmonary venous isolation by antral ablation with a large cryoballoon for treatment of paroxysmal and persistent atrial fibrillation: medium-term outcomes and non-randomised comparison with pulmonary venous isolation by radiofrequency ablation Rationale and Design of FIRE AND ICE: A multicenter randomized trial comparing efficacy and safety of pulmonary vein isolation using a cryoballoon versus radiofrequency ablation with 3D-reconstruction. Cryoballoon or Radiofrequency Ablation for Paroxysmal Atrial Fibrillation. Comparison of cryoballoon and radiofrequency ablation of pulmonary veins in 40 patients with paroxysmal atrial fibrillation: a case-control study. Contact-force guided radiofrequency vs. second-generation balloon cryotherapy for pulmonary vein isolation in patients with paroxysmal atrial fibrillation-a prospective evaluation. Pericardial effusion in atrial fibrillation ablation: a comparison between cryoballoon and radiofrequency pulmonary vein isolation. Mesh ablator vs. cryoballoon pulmonary vein ablation of symptomatic paroxysmal atrial fibrillation: results of the MACPAF study. Cryoballoon ablation of pulmonary veins for paroxysmal atrial fibrillation: first results of the North American Arctic Front (STOP AF) pivotal trial. Cryoballoon versus radiofrequency for pulmonary vein re-isolation after a failed initial ablation procedure in patients with paroxysmal atrial fibrillation. Cryoballoon vs. open irrigated radiofrequency ablation for paroxysmal atrial fibrillation: long-term FreezeAF outcomes Cryoballoon Versus Open Irrigated Radiofrequency Ablation in Patients With Paroxysmal Atrial Fibrillation Long-term comparison of cryoballoon and radiofrequency ablation of paroxysmal atrial fibrillation: a propensity score matched analysis. MEDAFI-Trial (Micro-embolization during ablation of atrial fibrillation): comparison of pulmonary vein isolation using cryoballoon technique vs. radiofrequency energy. Cryoballoon versus radiofrequency catheter ablation for paroxysmal atrial fibrillation. Circumferential pulmonary vein isolation as index procedure for persistent atrial fibrillation: a comparison between radiofrequency catheter ablation and second-generation cryoballoon ablation. Point-by-Point Radiofrequency Ablation Versus the Cryoballoon or a Novel Combined Approach: A Randomized Trial Comparing 3 Methods of Pulmonary Vein Isolation for Paroxysmal Atrial Fibrillation (The Cryo Versus RF Trial). Radiofrequency catheter ablation versus balloon cryoablation of atrial fibrillation: markers of myocardial damage, inflammation, and thrombogenesis Segmental pulmonary vein antrum isolation using the "large-size" lasso catheter in patients with atrial fibrillation. Approaches to catheter ablation for persistent atrial fibrillation. German ablation registry: Cryoballoon vs. radiofrequency ablation in paroxysmal atrial fibrillation--One-year outcome data. Early Recurrence After Pulmonary Vein Isolation of Paroxysmal Atrial Fibrillation With Different Ablation Technologies - Prospective Comparison of Radiofrequency vs. Second-Generation Cryoballoon Ablation. Randomized, Controlled Trial of the Safety and Effectiveness of a Contact Force–Sensing Irrigated Catheter for Ablation of Paroxysmal Atrial Fibrillation: Results of the TactiCath Contact Force Ablation Catheter Study for Atrial Fibrillation (TOCCASTAR) Study Randomised clinical trial of cryoballoon versus irrigated radio frequency catheter ablation for atrial fibrillation—the effect of double short versus standard exposure cryoablation duration during pulmonary vein isolation (CIRCA-DOSE): methods and rationale Results from a multicentre comparison of cryoballoon vs. radiofrequency ablation for paroxysmal atrial fibrillation: is cryoablation more reproducible?
Background Radiofrequency and cryoballoon pulmonary vein isolation are common approaches for paroxysmal atrial fibrillation treatment , showing similar results in recent multicenter studies , including heterogeneous tools and protocol s. The aim of this study is to compare prospect ively in a single , high-volume center the outcome of paroxysmal atrial fibrillation ablation performed specifically by second-generation cryoballoon or contact force radiofrequency ablation . Methods Consecutive patients scheduled for paroxysmal atrial fibrillation transcatheter ablation have been included and prospect ively followed up . Aim ing to reduce potential bias deriving from baseline characteristics , a propensity score matching analysis has been performed to analyze safety and efficacy outcomes . Results Out of consecutive patients undergoing atrial fibrillation transcatheter ablation between January 2015 and December 2016 , 46 patients approached by cryoablation  were matched 1 : 1 by propensity score to a similar population treated by last-generation radiofrequency ablation .  Freedom from atrial fibrillation after 12 months ( 76 vs. 78 % , P = 0.804 ) and incidence of complications ( 4 vs. 6 % , P = 0.168 ) did not differ between the two groups . Radiological exposure was higher for the cryoballoon group ( 11 vs. 4 min , P < 0.001 ) , whereas procedural duration did not differ ( P = 0.174 ) . Aim ing to assess the potential impact of a learning curve in patients undergoing cryoablation , the first-third of patients ( n = 15 ) were compared with the remaining , reporting longer radiological exposure ( P < 0.001 ) , but similar safety and efficacy . Conclusion In this propensity score analysis , last-generation cryoballoon and radiofrequency catheters for atrial fibrillation ablation present similar efficacy and safety .  Cryoablation requires longer fluoroscopy exposure compared with radiofrequency , although this is reduced by increased experience OBJECTIVES The purpose of this study was to investigate the efficacy safety of the novel cryoballoon device ( A rct ic Front , Cryocath , Quebec , Canada ) . BACKGROUND Antral pulmonary vein ( PV ) ablation with radiofrequency energy is widely used as a strategy for catheter ablation of paroxysmal atrial fibrillation ( PAF ) . A novel double lumen cryoballoon catheter was design ed for circumferential pulmonary vein isolation ( PVI ) with the cryoablation technique . METHODS We consecutively enrolled 346 patients with symptomatic , drug refractory paroxysmal ( n = 293 ) or persistent ( n = 53 ) atrial fibrillation ( AF ) . In all patients , PVI of all targeted PVs was the therapeutic aim . The primary end points of this nonr and omized study were : 1 ) acute isolation rate of targeted PV ; and 2 ) first electrocardiogram-documented recurrence of AF . The secondary end point was occurrence of PV stenosis or atrio-esophageal fistula . RESULTS The 1,360 of 1,403 PVs ( 97 % ) were targeted with balloons or balloons in combination with the use of Freezor Max ( Cryocath ) . We found that ablation with the cryoballoon result ed in maintenance of sinus rhythm in 74 % of patients with PAF and 42 % of patients with persistent AF . No PV narrowing occurred . The most frequent complication was right phrenic nerve palsy observed during cryoballoon ablation at the right superior PV . CONCLUSIONS Pulmonary vein isolation with a new cryoballoon technique is feasible . Sinus rhythm can be maintained in the majority of patients with PAF by circumferential PVI using a cryoballoon ablation system . Cryoablation was less effective in patients with persistent AF than in patients with PAF AIMS The urge to facilitate the atrial fibrillation ( AF ) ablation procedure has led to the development of new ablation catheters specifically design ed as ' one-shot tools ' for pulmonary vein isolation ( PVI ) . The purpose of this study was to compare the efficacy , safety , and procedure times for two such catheters using different energy sources . METHODS AND RESULTS One hundred and ten patients , referred for ablation of paroxysmal or persistent AF , were r and omized to treatment with either the cryoballoon or the circular multipolar duty-cycled radiofrequency-based pulmonary vein ablation catheter ( PVAC ) .  Complete PVI was achieved in 98 vs. 93 % patients in the cryoballoon and PVAC group , respectively , with complication rates of 8 vs. 2 % ( P = 0.2 ) . Complete freedom from AF , without antiarrhythmic drugs , after one single ablation procedure was seen in 46 % in the cryoballoon vs. 34 % after 12 months ( P = 0.2 ) . Procedure times were comparable , but fluoroscopy time was shorter for the cryoballoon ( 32 ± 16 min ) than for the PVAC procedures ( 47 ± 17 min ) ( P < 0.001 ) . A significant improvement of quality of life ( QoL ) and arrhythmia-related symptoms was seen in both groups after ablation . CONCLUSION Both catheters proved comparably effective and safe in achieving acute PVI , apart from the shorter fluoroscopy times achieved with the cryoballoon . At follow-up , there was no statistically significant difference between the groups regarding freedom from AF and clinical success . The QoL increased to the same levels as for the general Swedish population in both groups Background To prevent  atrial fibrillation ( AF ) recurrence after catheter ablation , pulmonary venous isolation ( PVI ) at an antral level is more effective than segmental ostial ablation . Cryoablation around the pulmonary venous ( PV ) ostia for AF therapy is potentially safer compared to radiofrequency ablation ( RFA ) . The aim of this study was to investigate the efficacy of a strategy using a large cryoablation balloon to perform antral cryoablation with ‘ touch-up ’ ostial cryoablation for PVI in patients with paroxysmal and persistent AF . Methods Paroxysmal and persistent AF patients undergoing their first left atrial ablation were recruited . After cryoballoon therapy , each PV was assessed for isolation and if necessary , treated with focal ostial cryoablation until PVI was achieved . Follow-up with Holter monitoring was performed . Clinical outcomes of the cryoablation protocol were compared , with consecutive patients undergoing PVI by RFA . Results 124 consecutive patients underwent cryoablation . 77 % of paroxysmal and 48 % of persistent AF subjects were free from AF at 12 months after a single procedure . Over the same time period , 53 consecutive paroxysmal AF subjects underwent PVI with RFA and at 12 months , 72 % were free from AF at 12 months ( p = NS ) . There were too few persistent AF subjects ( n=8 ) undergoing solely PVI by RFA as a comparison group . Procedural and fluoroscopic times during cryoablation were significantly shorter than RFA . Conclusions PV isolation can be achieved in less than 2 h by a simple cryoablation protocol with excellent results after a single intervention , particularly for paroxysmal AF BACKGROUND Atrial fibrillation ( AF ) is the most common sustained cardiac arrhythmia imposing substantial morbidity and mortality . Catheter-based pulmonary vein isolation ( PVI ) using radiofrequency current ( RFC ) has become a st and ard treatment for drug-resistant and symptomatic paroxysmal AF ( PAF ) . In recent years , the cryoballoon-based technique is increasingly used as a promising alternative with a short learning curve . METHODS The FIRE AND ICE trial is a prospect i ve , r and omized , controlled , open , blinded outcome assessment , noninferiority trial comparing cryoballoon- , and RFC-based PVI .  Patients with drug-resistant PAF will be r and omized in a 1:1 matrix in multiple European centers . The primary hypothesis is that cryoballoon ablation is not inferior to RFC ablation using 3-dimensional mapping with respect to clinical efficacy . The primary endpoint is defined as the time to first documented clinical failure , including : ( 1 ) recurrence of AF ; ( 2 ) atrial flutter or atrial tachycardia ; ( 3 ) prescription of class I or III antiarrhythmic drugs ; or ( 4 ) re-ablation , whichever comes first , following a blanking period of 3 months after the index ablation procedure . The primary safety endpoint is a composite of death , stroke/transient ischemic attack , cardiac arrhythmias ( apart from AF recurrence ) causally related to the therapeutic intervention , and procedure-related serious adverse events . CONCLUSION The FIRE AND ICE trial compares 2 different technologies to perform catheter ablation of PAF with respect to efficacy and safety . It aims at providing objective data to guide selection and usage of ablation catheters in the treatment of AF BACKGROUND Current guidelines recommend pulmonary-vein isolation by means of catheter ablation as treatment for drug-refractory paroxysmal atrial fibrillation .  Radiofrequency ablation is the most common method , and cryoballoon ablation is the second most frequently used technology . METHODS We conducted a multicenter , r and omized trial to determine whether cryoballoon ablation was noninferior to radiofrequency ablation in symptomatic patients with drug-refractory paroxysmal atrial fibrillation . The primary efficacy end point in a time-to-event analysis was the first documented clinical failure ( recurrence of atrial fibrillation , occurrence of atrial flutter or atrial tachycardia , use of antiarrhythmic drugs , or repeat ablation ) following a 90-day period after the index ablation . The noninferiority margin was prespecified as a hazard ratio of 1.43 . The primary safety end point was a composite of death , cerebrovascular events , or serious treatment-related adverse events . RESULTS A total of 762 patients underwent r and omization ( 378 assigned to cryoballoon ablation and 384 assigned to radiofrequency ablation ) . The mean duration of follow-up was 1.5 years . The primary efficacy end point occurred in 138 patients in the cryoballoon group and in 143 in the radiofrequency group ( 1-year Kaplan-Meier event rate estimates , 34.6 % and 35.9 % , respectively ; hazard ratio , 0.96 ; 95 % confidence interval [ CI ] , 0.76 to 1.22 ; P<0.001 for noninferiority ) . The primary safety end point occurred in 40 patients in the cryoballoon group and in 51 patients in the radiofrequency group ( 1-year Kaplan-Meier event rate estimates , 10.2 % and 12.8 % , respectively ; hazard ratio , 0.78 ; 95 % CI , 0.52 to 1.18 ; P=0.24 ) . CONCLUSIONS In this r and omized trial , cryoballoon ablation was noninferior to radiofrequency ablation with respect to efficacy for the treatment of patients with drug-refractory paroxysmal atrial fibrillation , and there was no significant difference between the two methods with regard to overall safety . ( Funded by Medtronic ; FIRE AND ICE Clinical Trials.gov number , NCT01490814 . ) INTRODUCTION Ablation of pulmonary veins ( PV ) is an established therapeutic option for patients with symptomatic drug-refractory paroxysmal atrial fibrillation ( AF ) .  Radiofrequency ( RF ) is currently the most widespread energy source for PV ablation . Cryothermal energy applied with a cryoballoon technique as an alternative has recently evolved . METHODS AND RESULTS In a case-control setting , we compared 20 patients with paroxysmal AF who underwent their first PV ablation with the cryoballoon technique to 20 matched patients with conventional RF ablation .  In the case of persistent electrical potentials after cryoballoon ablation , it was combined with ablation with a conventional cryocatheter . All patients performed daily event recording for 3 months after ablation procedure . Ablation parameters and success rate after 3 and 6 months were compared . In the cryoballoon group , the overall success rate was 55 % ( 50 % in the cryoballoon only group [ 14 patients ] and 66 % in the combination group [ 6 patients ] ) , as opposed to the RF group with 45 % . AF episode burden was lower after cryoballoon ablation . There was no significant difference between cryoballoon and RF ablation regarding procedure parameters . In the cryoballoon group , 3 phrenic nerve palsies occurred using the 23 mm balloon that resolved spontaneously . CONCLUSION PV ablation with the cryoballoon technique is feasible and seems to have a similar success rate in comparison to RF ablation . Procedure- and fluoroscopy duration are not longer than in conventional RF ablation AIMS In the setting of paroxysmal atrial fibrillation ( AF ) , there are no available data comparing the mid-term outcome of patients undergoing pulmonary vein isolation ( PVI ) catheter ablation using contact-force (CF)-guided radiofrequency ( RF ) vs. second-generation balloon cryotherapy . METHODS AND RESULTS Prospect i ve single-centre evaluation , carried out from March 2011 to February 2013 , comparing CF radiofrequency ( Thermocool ( ® ) SmartTouch ™ , Biosense Webster , Inc. ) ( CF group ) with cryoballoon ablation ( A rct ic Front Advance ™ 28 mm cryoballoon , Medtronic , Inc. ) ( CB group ) , in regards to procedural safety and efficacy , as well as recurrence at 12 months . Overall , 150 consecutive patients were enrolled ( 75 in each group ) . The characteristics of patients of both the groups were similar ( 61.2 ± 9.9 years , women 25.3 % , mean AF duration 4.1 ± 4.0 years , mean CHA2DS2-VASc score 1.4 ± 1.3 , mean HAS-BLED 1.4 ± 0.6 ) . Duration of the procedure was significantly lower in the CF group ( 110.7 ± 32.5 vs. 134.5 ± 48.3 min , P = 0.001 ) , with a lower duration of fluoroscopy ( 21.5 ± 8.5 vs. 25.3 ± 9.9 min , P = 0.017 ) and X-ray exposure ( 4748 ± 2411 cGy cm² vs. 7734 ± 5361 cGy cm² , P = 0.001 ) . In contrast , no significant difference was found regarding significant procedural complication ( 2.7 vs. 1.3 % in CF and CB groups , respectively ; P = 0.56 ) , and PVI was eventually achieved in all cases . At 12 months , AF recurrence occurred in 11 patients ( 14.7 % ) in the CB group and in 9 patients ( 12.0 % ) in the CF group ( HR = 1.20 95 % CI 0.50 - 2.90 ; log rank P = 0.682 ) . CONCLUSIONS Our preliminary findings suggest that CF-guided radiofrequency and cryotherapy present very similar performances in the setting of paroxysmal AF catheter ablation AIMS  Atrial fibrillation ( AF ) ablation  is increasingly being performed in electrophysiology laboratories . Pericardial effusion ( PE ) is certainly one of the most frequently observed complications during AF ablation . The aim of our study was to investigate the incidence and outcome of PE following cryothermal energy balloon ablation ( CBA ) in comparison with conventional circumferential pulmonary vein isolation with a focal radiofrequency ( RF ) catheter . METHODS AND RESULTS A total of 133 consecutive patients ( 105 males ) with paroxysmal AF were included in this study . Forty-six patients ( 36 males ) underwent CBA  ( A rct ic Front , Medtronic , USA ) and 87 ( 69 males ) point-by-point RF ablation guided by electroanatomical mapping ( Carto , Biosense Webster , Diamond Bar , CA , USA ) . Ablation was performed under general anaesthesia with both techniques . All patients underwent a 2D transthoracic echocardiogram within 24 h before and after the procedure as routinely performed in our centre . Pericardial effusion was detected in 19 ( 14.2 % ) of 133 patients . Sixteen patients presented mild effusion , one moderate effusion , and two pericardial tamponades . There was no significant difference in the incidence of PE between the cryoballoon and the RF group ( 11 vs. 16 % ) . A longer procedural time , coronary artery disease , and arterial hypertension were found to be independent predictors of PE during AF ablation . CONCLUSION Pericardial effusion occurred in a similar proportion following CBA and RF ablation for AF .  Pericardial effusion was mostly mild and asymptomatic , with benign clinical outcome not requiring additional hospitalization days AIMS Catheter ablation of the pulmonary veins ( PVs ) is a promising therapeutic approach for symptomatic atrial fibrillation ( AF ) . The prospect i ve r and omized single-centre study ' Mesh Ablator versus Cryoballoon Pulmonary Vein Ablation of Symptomatic Paroxysmal Atrial Fibrillation ' ( MACPAF ; clinical trials.gov NCT01061931 ) compared the efficacy and safety of two balloon-based PV ablation systems . METHODS AND RESULTS Thirty-two patients underwent PV ablation for symptomatic paroxysmal AF using the A rct ic Front ® or the HD Mesh Ablator ® catheter  according to study protocol . The primary endpoint was complete PV isolation ( PVI ) at the end of the ablation procedure , determined by exit block after achieving entrance block . Long-term follow-up data are not included in this publication . Patients ' mean age was 61.7 ± 8.9 years , 43.2 % were female , and median CHA₂DS₂-VASc score was 2.0 . In the intention-to-treat analysis , the rate of the primary endpoint was 56.5 % in patients r and omized to the A rct ic Front ® and 9.5 % in patients r and omized to the HD Mesh Ablator ® catheter ( P = 0.001 ) . In the per- protocol analysis , complete PVI was achieved in 13 ( 76.5 % ) of 17 A rct ic Front ® patients but in none of the 15 HD Mesh Ablator ® patients ( P < 0.0001 ) . There were one major and two minor complications in each study arm but no clinical ly evident stroke . Post-procedural AF recurrence was detected within hospital stay in two ( 11.8 % ) A rct ic Front ® patients and in seven ( 46.7 % ) HD Mesh Ablator ® patients ( P = 0.049 ) . CONCLUSION The MACPAF study revealed a superiority of the A rct ic Front ® catheter concerning complete PVI . Owing to the insufficient efficacy of the HD Mesh Ablator ® catheter , the safety board decided to stop MACPAF prematurely OBJECTIVES This study sought to assess the safety and effectiveness of a novel cryoballoon ablation technology design ed to achieve single-delivery pulmonary vein ( PV ) isolation . BACKGROUND St and ard radiofrequency ablation is effective in eliminating atrial fibrillation ( AF ) but requires multiple lesion delivery at the risk of significant complications . METHODS Patients with documented symptomatic paroxysmal AF and previously failed therapy with ≥ 1 membrane active antiarrhythmic drug underwent 2:1 r and omization to either cryoballoon ablation ( n = 163 ) or drug therapy ( n = 82 ) . A 90-day blanking period allowed for optimization of antiarrhythmic drug therapy and reablation if necessary . Effectiveness of the cryoablation procedure versus drug therapy was determined at 12 months . RESULTS Patients had highly symptomatic AF ( 78 % paroxysmal , 22 % early persistent ) and experienced failure of at least one antiarrhythmic drug . Cryoablation produced acute isolation of three or more PVs in 98.2 % and all four PVs in 97.6 % of patients . PVs isolation was achieved with the balloon catheter alone in 83 % . At 12 months , treatment success was 69.9 % ( 114 of 163 ) of cryoblation patients compared with 7.3 % of antiarrhythmic drug patients ( absolute difference , 62.6 % [ p < 0.001 ] ) . Sixty-five ( 79 % ) drug-treated patients crossed over to cryoablation during 12 months of study follow-up due to recurrent , symptomatic AF , constituting drug treatment failure . There were 7 of the result ing 228 cryoablated patients ( 3.1 % ) with a > 75 % reduction in PV area during 12 months of follow-up . Twenty-nine of 259 procedures ( 11.2 % ) were associated with phrenic nerve palsy as determined by radiographic screening ; 25 of these had resolved by 12 months . Cryoablation patients had significantly improved symptoms at 12 months . CONCLUSIONS The STOP AF trial demonstrated that cryoballoon ablation is a safe and effective alternative to antiarrhythmic medication for the treatment of patients with symptomatic paroxysmal AF , for whom at least one antiarrhythmic drug has failed , with risks within accepted st and ards for ablation therapy . ( A Clinical Study of the A rct ic Front Cryoablation Balloon for the Treatment of Paroxysmal Atrial Fibrillation [ Stop AF ] ; NCT00523978 ) AIM Catheter ablation of paroxysmal atrial fibrillation ( PAF ) is associated with an important risk of early and late recurrence , necessitating repeat ablation procedures . The aim of this prospect i ve r and omized patient-blind study was to compare the efficacy and safety of cryoballoon ( Cryo ) versus radiofrequency ( RF ) ablation of PAF after failed initial RF ablation procedure . METHODS Patients with a history of symptomatic PAF after a previous failed first RF ablation procedure were eligible for this study . Patients were r and omized to Cryo or RF redo ablation . The primary endpoint of the study was recurrence of atrial tachyarrhythmia , including AF and left atrial flutter/tachycardia , after a second ablation procedure at 1 year of follow-up . All patients were implanted with a cardiac monitor ( Reveal XT , Medtronic ) to continuously track the cardiac rhythm . Patients with an AF burden ( AF% ) ≤ 0.5 % were considered AF-free ( Responders ) , while those with an AF% > 0.5 % were classified as patients with AF recurrences ( non-Responders ) . RESULTS Eighty patients with AF recurrences after a first RF pulmonary vein isolation ( PVI ) were r and omized to Cryo ( N = 40 ) or to RF ( N = 40 ) . Electrical potentials were recorded in 77 mapped PVs ( 1.9 ± 0.8 per patient ) in Cryo Group and 72 PVs ( 1.7 ± 0.8 per patient ) in RF Group ( P = 0.62 ) , all of which were targeted . In Cryo group , 68 ( 88 % ) of the 77 PVs were re-isolated using only Cryo technique ; the remaining 9 PVs were re-isolated using RF . In RF group , all 72 PVs were successfully re-isolated ( P = 0.003 vs Cryo ) . By intention-to-treat , 23 ( 58 % ) RF patients were AF-free vs 17 ( 43 % ) Cryo patients on no antiarrhythmic drugs at 1 year ( P = 0.06 ) . Three patients had temporary phrenic nerve paralysis in the Cryo group ; the RF group had no complications . Of the 29 patients who had only Cryo PVI without any RF ablation , 11 ( 38 % ) were AF-free vs 20 ( 59 % ) of the 34 patients who had RF only ( P = 0.021 ) . CONCLUSION When patients require a redo pulmonary vein isolation ablation procedure for recurrent PAF , RF appears to be the preferred energy source relative to Cryo Background Effective treatment of paroxysmal atrial fibrillation ( AF ) is essential for reducing the risk of stroke and heart failure .  Cryoballoon ( CB ) ablation has been developed as an alternative to the use of radiofrequency ( RF ) energy for electrical isolation of the pulmonary veins . Herein , we provide long-term data regarding the efficacy of CB ablation in comparison to RF . Methods FreezeAF was a r and omised non-inferiority study comparing CB ablation with RF ablation for the treatment of patients with drug-refractory paroxysmal AF . Procedural success for the long-term follow-up ( 30 months ) was defined as freedom from AF with an absence of persistent complications . Results Of the 315 patients that were r and omised and received catheter ablation , 292 ( 92.7 % ) completed the 30-month follow-up ( 147 in the RF group and 145 in the CB group ) . The baseline characteristics of the RF and CB groups were similar . Single-procedure success was achieved by 40 % of patients in the RF group and 42 % of the CB group ( p < 0.001 for non-inferiority ) . When including re-do procedures in the analysis , the multiple procedure success rate was 72 % in the RF group and 76 % in the CB group . Conclusion The data provide long-term evidence that CB ablation is non-inferior to RF ablation , with high proportions of patients reporting freedom from AF 30 months after the index procedure . Trial registration Clinical Trials.gov Identifier : NCT00774566 ; first registered October 16 , 2008 ; first patient included October 20 , 2008 Background — There is a lack of data on the comparative efficacy and procedural safety of open irrigated radiofrequency ( RF ) and cryoballoon catheter ( CB ) ablation for pulmonary vein isolation in patients with paroxysmal atrial fibrillation . Methods and Results — In a prospect i ve , noninferiority study , 315 patients were r and omly assigned to RF ( n=159 ) or CB ( n=156 ) ablation . The primary end point was freedom from atrial arrhythmia with absence of persistent complications . Patients were largely comparable between groups with more vascular disease in the RF group ( 8.2 % versus 2.6 % for CB ; P=0.028 ) . The primary end point at 12 months was achieved by 70.7 % with RF and 73.6 % with CB ( multiple procedure success ) , including 31 redo procedures in each group ( 19.5 % of RF versus 19.9 % of CB ; P=0.933 ) . For the intention-to-treat population , noninferiority of CB was revealed for the predefined inferiority margin ( risk difference , 0.029 ; 95 % confidence interval , −0.074 to 0.132 ; P<0.001 ) . Rates at 6 months were 63.1 % and 64.1 % for the RF and CB groups ( single procedure success ) , and noninferiority was confirmed ( risk difference , 0.010 ; 95 % confidence interval , −0.097 to 0.116 ; P=0.002 ) . Periprocedural complications for the index procedure were more frequent in the CB group ( 5.0 % RF , 12.2 % CB ; P=0.022 ) with a significant difference in phrenic nerve palsies ( 0 % RF , 5.8 % CB ; P=0.002 ) . Conclusion — This large , prospect i ve , r and omized , controlled study demonstrates noninferiority of CB ablation versus RF ablation for treating patients with paroxysmal atrial fibrillation . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00774566 BACKGROUND Although radiofrequency ( RF ) and cryoballoon ( CB ) based technologies for pulmonary vein isolation ( PVI ) have both individually been demonstrated to be effective and safe for the treatment of paroxysmal AF , head-to-head comparisons are lacking . The purpose of this study was to compare the outcome of cryoballoon versus radiofrequency ablation in patients with paroxysmal atrial fibrillation undergoing pulmonary vein isolation . METHODS Out of a prospect i ve registry of 327 patients undergoing PVI , 208 patients ( age 58±11 years , ejection fraction 59±6 % , left atrial size 39±6 mm ) with paroxysmal AF were identified . The presented data set was obtained by 1:1 propensity score matching and contained 142 patients undergoing CB-PVI or RF-PVI in conjunction with a 3D mapping system , respectively . We compared single procedure efficacy of the two methods using a Cox proportional hazards model . RESULTS After a mean follow-up of 28 months and a single procedure , AF recurred in 37 of 71 ( 52 % ) in the CB-PVI group and in 31 of 71 patients ( 44 % ) in the RF-PVI group ( HR [ 95 % CI]=1.19 [ 0.74 , 1.92 ] , p=0.48 ) . Recurrence of AF for PVI using solely the CB was observed in 23 of 51 ( 45 % ) patients and in 23 of 51 ( 45 % ) patients in the corresponding RF-PVI group ( HR [ 95 % CI]=0.93 [ 0.52 , 1.66 ] , p=0.81 ) . Complication rate was not different between the groups . CONCLUSION A propensity score matched comparison between CB-PVI and RF-PVI using a 3D-mapping system for AF ablation showed similar long-term success rates AIMS Cerebral embolism is a possible serious complication during catheter ablation of atrial fibrillation ( AF ) .  The purpose of this prospect i ve pilot study was to analyse the incidence and possible impact of cryo ablation on cerebral lesions and possible differences to radiofrequency ( RF ) ablation during pulmonary vein isolation ( PVI ) . METHODS AND RESULTS Pulmonary vein isolation was performed in 89 patients , either with the cryoballoon technique ( n = 45 ) or with RF ablation ( n = 44 ) .  Phenprocoumon was stopped 3 days before intervention and replaced by subcutaneous low-molecular-weight heparin . During the catheter procedure , an infusion of unfractionated heparin was maintained to achieve an activated clotting time ( ACT ) of > 300 s. Cerebral magnetic resonance imaging scans were performed 1 day before and after PVI , and at 3-month follow-up . Chronic lesions were observed in 11 patients ( 12.3 % ) before PVI without statistically significant difference between the two groups . None of the patients had neurological symptoms during or following the procedure . Seven patients ( 7.9 % ) developed acute lesions 1 day after PVI , without statistically significant difference between the group treated by cryoenergy ( 8.9 % ) and RF ablation ( 6.8 % ) . Patients with acute lesions were significantly older compared with those without acute cerebral lesions . No additional cerebral lesions during follow-up were observed . CONCLUSION A considerable portion of patients with AF but without any neurological symptoms had chronic cerebral lesions before PVI . Additional acute lesions could be added after the procedure . Both ablation techniques showed additional cerebral acute lesions with no neurological symptoms after PVI BACKGROUND Catheter ablation is an established treatment for atrial fibrillation ( AF ) .  Cryoballoon ablation ( CBA ) has emerged as an alternative to radiofrequency ablation ( RFA ) . However , there are few data comparing these modalities for treatment of paroxysmal AF ( pAF ) in the U.S. POPULATION The purpose of this study was to compare procedural times , safety , and efficacy of CBA against RFA . METHODS A single-center prospect i ve cohort study evaluated patients who underwent catheter ablation for pAF using CBA or RFA between January 1 , 2010 and October 31 , 2013 . Patients with prior ablation and those without rhythm follow-up for at least 3 months were excluded . The primary end point was freedom from AF , atrial flutter , and atrial tachycardia ( FFAF ) > 30 seconds after a 3-month blanking period without requirement for antiarrhythmic drugs . We also compared rates of successful pulmonary vein isolation ( PVI ) , fluoroscopy and procedure times , and major complication rates . RESULTS A total of 201 patients were included ( CBA = 101 , RFA = 100 ) . The rate of successful PVI was 99.3 % in CBA versus 97.4 % in RFA ( P = 0.08 ) . Procedure times were shorter with CBA ( 192.9 ± 44.0 minutes vs 283.7 ± 78.0 minutes , P < 0.001 ) as well as total fluoroscopy times ( 46.0 ± 22.4 minutes vs 73.0 ± 30.1 minutes , P < 0.001 ) . Overall complication rates were equivalent ; however , fewer cardiac perforations occurred with CBA ( 0 % vs 4 % , P = 0.042 ) . The 1-year FFAF rates were 60.3 % for CBA and 61.1 % for RFA ( log rank P = 0.93 ) . CONCLUSION CBA was associated with equivalent 1-year FFAF rate as RFA for pAF . Procedure and fluoroscopy times were shorter for CBA and fewer cardiac perforations occurred AIMS To assess the 1 year efficacy of pulmonary vein isolation ( PVI ) as index procedure for persistent atrial fibrillation ( PersAF ) comparing conventional radiofrequency irrigated-tip catheter ablation ( RFCA ) using contact-force technology and ablation using the second-generation cryoballoon ( CB-AdvA ) . METHODS AND RESULTS One hundred consecutive patients ( 74 male , 74 % ; mean age 62.4 ± 9.6 years ) with drug-refractory PersAF undergoing PVI using RFCA and CB-AdvA were enrolled . Follow-up was based on outpatient clinic visits including Holter-electrocardiograms . Recurrence of atrial tachyarrhythmias ( ATas ) was defined as a symptomatic or documented episode > 30 s. Among 100 patients , 50 underwent RFCA whereas 50 CB-AdvA.  Mean procedure and fluoroscopy times were 90.5 ± 41.7 vs. 140.2 ± 46.9 min and 14.5 ± 6.6 vs. 19.8 ± 6.8 min in the CB-Adv and in the RFCA group , respectively ( P < 0.01 ) . At 1 year follow-up , after a 3 months blanking period ( BP ) , freedom from ATas off-drugs after a single procedure was 60 % ( 28/50 patients ) in the CB-Adv and 56 % ( 27/50 patients ) in the RFCA group ( P = 0.71 ) . Multivariate analysis demonstrated that PersAF duration ( P = 0.01 ) and relapses during BP ( P = 0.02 ) were independent predictors of ATa recurrences following the index procedure . CONCLUSION Freedom from ATas following PersAF ablation with RFCA and CB-Adv is comparable at 1 year follow-up after a single procedure . Ablation with the CB-Adv is associated with shorter procedure time and radiation exposure as compared with RFCA . Atrial tachyarrhythmias occurrence during BP and longer time of PersAF seem to be significant predictors of arrhythmia recurrences after the index procedure INTRODUCTION Catheter ablation of paroxysmal AF using the Cryoballoon ( CRYO ) has yielded similar success rates to conventional wide encirclement using radiofrequency catheter ablation ( RFCA ) , but r and omized data are lacking . Pilot data suggested a high success rate with a combined approach ( COMBINED ) using wide encirclement with RFCA followed by 2 CRYO applications to each vein . We compared these 3 strategies in a r and omized controlled trial . METHODS AND RESULTS Patients undergoing first time paroxysmal AF ablation were r and omized to RFCA , CRYO , or COMBINED . Patients were followed up at 3 , 6 , and 12 months with 7 days of ambulatory ECG monitoring . Success was defined as freedom from arrhythmia without antiarrhythmic drugs after a single procedure . A total of 237 patients were r and omized . Success at 1 year was achieved in 47 % in the RFCA group , 67 % in the CRYO group , and 76 % in the COMBINED group ( P < 0.001 for RFCA vs. CRYO , P<0.001 for RFCA vs. COMBINED , and P = 0.220 for CRYO vs. COMBINED ) . Procedure time was 211 ( IQR 174 - 256 ) minutes for RFCA compared to 167 ( 136 - 202 ) minutes for CRYO and 278 ( 243 - 327 ) minutes for COMBINED ( P < 0.001 for RFCA vs. COMBINED , RFCA vs. CRYO , and CRYO vs. COMBINED groups ) . CONCLUSIONS Pulmonary vein isolation for paroxysmal AF is faster with CRYO and results in a higher single procedure success rate than conventional point by point RFCA . The COMBINED approach was not superior to CRYO alone Summary Background Evidence from animal and human studies suggests that cryoablation might be associated with a lesser inflammatory response and activation of coagulation compared with radiofrequency ablation . The study was aim ed at comparing the effect of cryoballoon and radiofrequency catheter ablation of paroxysmal atrial fibrillation on markers of myocardial damage , inflammation , and activation of coagulation . Methods Forty-one patients received either cryoballoon  ( n = 23 ) or radiofrequency ( n = 18 ) ablation of atrial fibrillation .  We measured troponin I , high-sensitivity CRP , and interleukin 6 at baseline from the cubital vein , and from the right and left atrium before and after ablation , and from the cubital vein the following day . Prothrombin fragments 1 + 2 , soluble P‑selectin , and D‑dimer were measured before and after ablation from both atria . Results We observed higher troponin I release in the cryoballoon than in the radiofrequency group ( 7.01 mcg/l ( interquartile range [ IQR ] : 5.30–9.09 ) vs 2.32 mcg/l ( IQR : 1.45–2.98 ) , p < 0.001 ) . The levels of inflammatory markers ( high-sensitivity CRP and interleukin 6 ) in the two groups were comparable , as were the levels of markers of coagulation activation . Procedure duration , fluoroscopy times , and mid-term success ( 23 months , IQR 7–32 ) of the two groups were also comparable . Conclusions Cryoballoon ablation of atrial fibrillation causes more significant myocardial damage , that is , more extensive ablation lesions , compared with radiofrequency catheter ablation . However , no major differences between these two ablation techniques with regard to the inflammatory response and activation of the coagulation system were observed BACKGROUND The limited efficacy and complications of segmental ostial pulmonary vein isolation ( PVI ) for treating atrial fibrillation ( AF ) have been discussed so , in the present study the feasibility and efficiency of performing segmental pulmonary vein ( PV ) antrum isolation to treat AF were assessed . METHODS AND RESULTS A total of 187 patients with drug-refractory AF ( paroxysmal 120 , persistent 67 ) underwent segmental PVI guided by circumferential 20-electrode catheters ( Lasso ) . Radiofrequency ( RF ) current was delivered either at the ostium using a regular Lasso ( 15 - 20 mm in diameter , 70 patients : Group 1 ) or at the antrum using a larger Lasso ( 25 - 30 mm in diameter , 117 patients : Group 2 ) . A significantly wider region had to be ablated , with a longer RF application time , to isolate all 4 PVs in Group 2 patients than in Group 1 patients . Although the rate of recurrence of AF after the initial session was equal in both groups , a significantly greater number of patients were free from AF after a mean of 1.4 procedures in Group 2 than in Group 1 ( 93 % vs 76 % for paroxysmal AF , 78 % vs 48 % for persistent AF ) . CONCLUSIONS Segmental antral PVI using large-sized Lasso catheters was found to be more effective and safer than ostial PVI for the treatment of AF BACKGROUND Catheter ablation is less successful for persistent atrial fibrillation than for paroxysmal atrial fibrillation . Guidelines suggest that adjuvant substrate modification in addition to pulmonary-vein isolation is required in persistent atrial fibrillation . METHODS We r and omly assigned 589 patients with persistent atrial fibrillation in a 1:4:4 ratio to ablation with pulmonary-vein isolation alone ( 67 patients  ) , pulmonary-vein isolation plus ablation of electrograms showing complex fractionated activity ( 263 patients  ) , or pulmonary-vein isolation plus additional linear ablation across the left atrial roof and mitral valve isthmus ( 259 patients ) . The duration of follow-up was 18 months . The primary end point was freedom from any documented recurrence of atrial fibrillation lasting longer than 30 seconds after a single ablation procedure . RESULTS Procedure time was significantly shorter for pulmonary-vein isolation alone than for the other two procedures ( P<0.001 ) . After 18 months , 59 % of patients assigned to pulmonary-vein isolation alone were free from recurrent atrial fibrillation , as compared with 49 % of patients assigned to pulmonary-vein isolation plus complex electrogram ablation and 46 % of patients assigned to pulmonary-vein isolation plus linear ablation ( P=0.15 ) . There were also no significant differences among the three groups for the secondary end points , including freedom from atrial fibrillation after two ablation procedures and freedom from any atrial arrhythmia . Complications included tamponade ( three patients ) , stroke or transient ischemic attack ( three patients ) , and atrioesophageal fistula ( one patient ) . CONCLUSIONS Among patients with persistent atrial fibrillation , we found no reduction in the rate of recurrent atrial fibrillation when either linear ablation or ablation of complex fractionated electrograms was performed in addition to pulmonary-vein isolation . ( Funded by St. Jude Medical ; Clinical Trials.gov number , NCT01203748 . ) BACKGROUND Although radiofrequency ( RF ) ablation has long been the st and ard of care for atrial fibrillation ( AF ) ablation , cryoballoon technology has emerged as a feasible approach with promising results . Prospect i ve multicenter registry data referring to both ablation technologies in AF ablation are lacking so far . OBJECTIVE The purpose of this study was to report data from the German ablation registry with respect to efficacy and safety in pulmonary vein ablation with different energy sources for paroxysmal AF after 1-year follow-up . METHODS A total of 2306 patients with symptomatic paroxysmal AF from the German ablation registry were included in this analysis . The cohort was divided into two groups according to the ablation energy source used : cryoballoon and RF ablation .  MACCE was defined as a combination of death , myocardial infa rct ion , or stroke . RESULTS AF recurrence rate after a single ablation procedure at 1 year follow-up was not significantly different between the two groups ( 45.8 % after cryoablation and 45.4 % after RF ablation , P = .87 ) . Also , the rate of patients without AF recurrence and free of antiarrhythmic drug at 12-month follow-up was similar ( cryoablation 44.2 % and RF 41.4 % , P = .25 ) . MACCE occurred with an incidence of 0.7 % within 500 days after cryoablation and 1.4 % after RF ablation ( P = .30 ) . Persistent phrenic nerve palsy was more common after cryoablation compared to RF ablation ( 1.1 % vs. 0.3 % , P < .05 ) . CONCLUSION AF recurrence rate at 1-year follow-up was similar in RF ablation compared to cryoablation , whereas the spectrum and relevance of complications were significantly different between the two ablation methods . This finding might influence the choice of ablation method offered to the individual paroxysmal AF patient BACKGROUND Inflammation plays a prominent role in the etiology of the early recurrence of  atrial fibrillation ( ERAF ) . We prospect ively compared the proportion of ERAF and time-course patterns of biomarkers between radiofrequency ( RF ) and cryoballoon ( CB ) ablation . METHODS AND RESULTS We enrolled 82 consecutive paroxysmal AF patients undergoing pulmonary vein ( PV ) isolation , performed with either a 28-mm 2nd-generation CB and 3-min freeze technique or point-by-point RF ablation .  Each group had 41 patients . In the RF group , all PVs were successfully isolated with 28.9 ± 6.5 min of RF delivery . In the CB group , a mean of 5.3 ± 1.4 applications/patient was delivered . The proportion of ERAF was similar between the groups . The time-course patterns significantly differed between the groups for high-sensitivity C-reactive protein ( hs-CRP ) value ( P=0.006 ) and myocardial injury markers ( P<0.0001 ) . Greater myocardial injury was observed in the CB than in the RF group ( P<0.0001 ) , whereas the peak hs-CRP value was comparable between the groups . The 2-day post-procedure hs-CRP value was the sole factor correlating with ERAF as identified by the multivariable analysis ( hazard ratio 1.697 ; 95 % confidence interval , 1.005 - 2.865 ; P=0.048 ) in the RF , but not the CB group . CONCLUSIONS The proportion of ERAF was comparable after RF and 2nd-generation CB ablation . Despite CB ablation exhibiting greater myocardial injury than RF ablation , the inflammatory responses were comparable between the groups . The inflammatory response extent predicted ERAF post-RF ablation but not post-CB ablation Background — Contact force ( CF ) is a major determinant of lesion size and transmurality and has the potential to improve efficacy of atrial fibrillation ablation . This study sought to evaluate the safety and effectiveness of a novel irrigated radiofrequency ablation catheter that measures real-time CF in the treatment of patients with paroxysmal atrial fibrillation . Methods and Results — A total of 300 patients with symptomatic , drug-refractory , paroxysmal atrial fibrillation were enrolled in a prospect i ve , multicenter , r and omized , controlled trial and r and omized to radiofrequency ablation with either a novel CF-sensing catheter or a non-CF catheter ( control ) . The primary effectiveness end point consisted of acute electrical isolation of all pulmonary veins and freedom from recurrent symptomatic atrial arrhythmia off all antiarrhythmic drugs at 12 months . The primary safety end point included device-related serious adverse events . End points were powered to show noninferiority . All pulmonary veins were isolated in both groups . Effectiveness was achieved in 67.8 % and 69.4 % of subjects in the CF and control arms , respectively ( absolute difference , −1.6 % ; lower limit of 1-sided 95 % confidence interval , −10.7 % ; P=0.0073 for noninferiority ) . When the CF arm was stratified into optimal CF ( ≥90 % ablations with ≥10 g ) and nonoptimal CF groups , effectiveness was achieved in 75.9 % versus 58.1 % , respectively ( P=0.018 ) . The primary safety end point occurred in 1.97 % and 1.40 % of CF patients and control subjects , respectively ( absolute difference , 0.57 % ; upper limit of 1-sided 95 % confidence interval , 3.61 % ; P=0.0004 for noninferiority ) . Conclusions — The CF ablation catheter met the primary safety and effectiveness end points . Additionally , optimal CF was associated with improved effectiveness . Clinical Trial Registration — http://www . clinical trials.gov . Unique identifier : NCT01278953 Introduction Pulmonary vein isolation ( PVI ) is an effective therapy for paroxysmal atrial fibrillation ( AF ) , but it has limitations . The two most significant recent advances have centred on the integration of real-time quantitative assessment of catheter contact force into focal radio frequency ( RF ) ablation catheters and the development of dedicated ablation tools capable of achieving PVI with a single ablation lesion ( A rct ic Front cryoballoon , Medtronic , Minneapolis , MN , USA ) . Although each of these holds promise for improving the clinical success of catheter ablation of AF , there has not been a rigorous comparison of these advanced ablation technologies . Moreover , the optimal duration of cryoablation ( freezing time ) has not been determined . Methods and analysis Patients undergoing an initial PVI procedure for paroxysmal AF will be recruited . Patients will be r and omised 1:1:1 between contact-force irrigated RF ablation , short duration cryoballoon ablation ( 2 min applications ) and st and ard duration cryoballoon ablation ( 4 min applications ) . The primary outcome is time to first documented AF recurrence on implantable loop recorder . With a sample size of 111 per group and a two-sided 0.025 significance level ( to account for the two main comparisons ) , the study will have 80 % power ( using a log-rank test ) to detect a difference of 20 % between contact force RF catheter ablation and either of the two cryoballoon ablation groups . Factoring in a 4 % loss to follow-up , 116 patients per group should be r and omised and followed for a year ( total study population of 348 ) . Ethics and dissemination The study was approved by the University of British Columbia Office of Research ( Services ) Ethics Clinical Research Ethics Board . Results of the study will be su bmi tted for publication in a peer- review ed journal . Trial registration number NCT01913522 ; Pre- Aim Cryoballoon ablation ( Cryoballoon ) has emerged as a new alternative for the treatment of  symptomatic drug-refractory atrial fibrillation ( AF ) . Whether the results of Cryoballoon are more reproducible than those of radiofrequency ( RF ) ablation remains to be proved . Methods and results A total of 860 consecutive patients undergoing a first ablation procedure for paroxysmal AF ( 467 treated with RF and 393 treated with Cryoballoon ) were selected from a prospect i ve multicentre survey of AF ablation ( FrenchAF ) .  Radiofrequency and Cryoballoon were compared regarding mid-term efficacy and safety . During a median follow-up of 14 months ( interquartile range 8–23 ) , patients treated with Cryoballoon displayed similar rates of freedom from atrial arrhythmia relapse in centres performing this technique ( 68–80 % at 18 months ) . However , in centres performing RF , a greater heterogeneity in procedural results was observed ( 46–79 % were free from atrial arrhythmia relapse at 18 months ) . On multivariate analysis , Cryoballoon ( HR = 0.47 , 95 % CI 0.35–0.65 , P < 0.001 ) and annual AF ablation caseload ( HR = 0.87 per every 100 AF ablation procedures per year ; 95 % CI 0.80–0.96 , P = 0.003 ) were independent predictors of procedural success . However , on sensitivity analysis , according to the ablation method , annual AF ablation caseload predicted only sinus rhythm maintenance in the subgroup of patients treated with RF . Analysis of interoperator results with Cryoballoon and RF confirmed lower reproducibility of RF , but suggested that besides caseload , other operator-related factors may play a role . Conclusion Cryoballoon seems to be less operator-dependent and more reproducible than RF in the setting of paroxysmal AF ablation
Conclusion In patients with paroxysmal atrial fibrillation  , cryoballoon and radiofrequency ablation produce similar results in terms of freedom from recurrent atrial fibrillation or atrial tachyarrhythmias but with a different safety profile , being cryoballoon ablation less associated with cardiac complications but more likely to cause phrenic nerve palsy
Aims To perform an up date d meta- analysis to assess efficacy , safety and technical performance of pulmonary vein isolation using cryoballoon or radiofrequency catheter ablation in patients with paroxysmal or persistent atrial fibrillation .