Despite significant improvements in catheter ablation. Original Article

Transcription

1 Original Article Electrical Reconnection After Pulmonary Vein Isolation Is Contingent on Contact Force During Initial Treatment Results From the EFFICAS I Study Petr Neuzil, MD, PhD; Vivek Y. Reddy, MD; Josef Kautzner, MD, PhD; Jan Petru, MD; Dan Wichterle, MD, PhD; Dipen Shah, MD; Hendrik Lambert, PhD; Aude Yulzari, MSc; Erik Wissner, MD; Karl-Heinz Kuck, MD, PhD, FHRS Downloaded from by guest on June 15, 2018 Background Pulmonary vein isolation is the most prevalent approach for catheter ablation of paroxysmal atrial fibrillation. Long-term success of the procedure is diminished by arrhythmia recurrences occurring predominantly because of reconnections in previously isolated pulmonary veins. The aim of the EFFICAS I multicenter study was to demonstrate the correlation between contact force (CF) parameters during initial procedure and the incidence of isolation gaps (gap) at 3-month follow-up. Method and Results A radiofrequency ablation catheter with integrated CF sensor (TactiCath, Endosense, Geneva, Switzerland) was used to perform pulmonary vein isolation in 46 patients with paroxysmal atrial fibrillation. During the ablation procedure, the operator was blinded to CF information. At follow-up, an interventional diagnostic procedure was performed to assess gap location as correlated to index procedure ablation parameters. At follow-up, 65% (26/40) of patients showed 1 gaps. Ablations with minimum Force Time Integral (FTI) <400 gs showed increased likelihood for reconnection (P<0.001). Reconnection correlated strongly with minimum CF (P<0.0001) and minimum FTI (P=0.0007) at the site of gap. Gap occurrence showed a strong trend with lower average CF and average FTI. CF and FTI are generally higher on the right side, although the left anterior segment presents a unique challenge to achieve stable position with good CF. Conclusions Minimum CF and minimum FTI values are strong predictors of gap formation. Optimal CF parameter recommendations are a target CF of 20 g and a minimum FTI of 400 gs for each new lesion. (Circ Arrhythm Electrophysiol. 2013;6: ) Key Words: atrial fibrillation catheter ablation contact force gaps Despite significant improvements in catheter ablation strategies to treat atrial fibrillation in recent years, refractory recurrence of arrhythmia remains a continuing concern. Recurrence rates of atrial fibrillation after a radiofrequency (RF) ablation are still relatively high (from 20% to 55%). 1 5 For patients treated with circumferential isolation of the pulmonary veins (PVs), it is well understood that failure to create durable lesions may result in gaps in the isolation line allowing PV potentials to reconnect with the left atrium. The specific relationship between gap formation and subsequent recurrence of clinical arrhythmia is less clear, 6 although the likelihood of recurrence increases in the presence of gaps. Clinical Perspective on p 333 Isolation gaps in the ipsilateral line may result either from areas omitted from initial treatment or from lesions that are not sufficiently transmural to prevent conduction. Modern visualization techniques, including 3-dimensional imagery, intracardiac echo, and fluoroscopy, have been used to ensure that the catheter tip is well positioned to create contiguous lesions, thus minimizing the risk of untreated areas. New technologies using real-time monitoring of tip-to-tissue contact force (CF) are also useful to confirm that appropriate pressure is applied by the ablating electrode to effectively facilitate RF energy transfer and the ensuing thermal injury. CF has been identified as a potential determinant of lesion quality during RF ablation Previous studies have characterized the optimal CF parameters needed to achieve transmurality, whereas other trials have shown a clear correlation with long-term freedom from recurrence. 12 To date, no clinical study has prospectively examined the recurrent conductivity of specific lesion sites as a function of initial treatment parameters. Received September 13, 2012; accepted February 24, From the Department of Cardiology, Na Homolce Hospital, Prague, Czech Republic (P.N., J.P.); Cardiac Arrhythmia Service, Mount Sinai School of Medicine, New York, NY (V.Y.R.); Department of Cardiology, Institute for Clinical & Experimental Medicine (IKEM), Prague, Czech Republic (J.K., D.W.); Hopital Universitaire Geneve, Geneve, Switzerland (D.S.); Endosense SA, Geneva, Switzerland (H.L., A.Y.); and Abt Kardiologie, Asklepios Klinik St. Georg, Hamburg, Germany (E.W., K.-H.K.). The online-only Data Supplement is available at Correspondence to Petr Neuzil, MD, PhD, Department of Cardiology, Na Homolce Hospital, Roentgenova 2, Prague 5, Czech Republic. Petr.Neuzil@homolka.cz 2013 American Heart Association, Inc. Circ Arrhythm Electrophysiol is available at DOI: /CIRCEP

2 328 Circ Arrhythm Electrophysiol April 2013 An irrigated RF ablation catheter able to measure real time CF between the catheter tip and the beating heart wall (TactiCath, Endosense, Geneva, Switzerland) was used during the Toccata clinical trial, to show that the number of ablations made with low CF was a predictor of clinical outcome at 12 months. These low-cf applications may be related to incomplete, impermanent, or superficial lesions resulting in isolation gaps. The left atrial substrate is not uniform with differences in wall thickness, positional stability, and access contributing to lesion effectiveness. This variation may result in more or shorter ablations in specific segments, particularly when catheter position is difficult to maintain. The CF parameter may be a useful tool to describe these challenges relative to the anatomy. The EFFICAS I study was undertaken to investigate the exact relationship between CF parameters measured during ablation and the incidence of isolation gaps in the PV line measured invasively during a 3-month follow-up electrophysiological study. It was hypothesized that lesions produced with inadequate CF would result in a measurable increase in the rate of reconnection, thus giving rise to more arrhythmia recurrence. In addition, a comparison of CF parameters during lesion delivery across segments might expose risks of reconnection as a function of anatomy. Finally, it was expected that a detailed examination of CF parameters used in an actual clinical setting would yield information about minimal CF criterion for success. Methods Study Protocol EFFICAS I was a multicenter study conducted at 3 European centers. The protocol was approved by the institutional review board (Ethics Committee) at each center and consisted of 2 procedures: an index ablation procedure for pulmonary vein isolation (PVI), at which the operator was blinded to CF data, and a follow-up procedure at 3 months to invasively assess isolation gap occurrence in the PVI lines. The study end point was to correlate the occurrence of either an isolation gap (gap) or successful isolation at 3 months with the CF parameters applied at each location on the PVI line during initial ablation. Study participation ended with a follow-up examination at 3 months, an interval traditionally construed to coincide with the end of blanking. An isolation gap was defined by the detection of a PV potential using a circular mapping catheter and pacing, if needed, to conclusively differentiate these potentials from far-field signals. Complications related to the procedures were recorded to comply with local regulatory requirements for safety and vigilance. Patient Population Forty-six consecutive patients with predominantly paroxysmal atrial fibrillation following ACC/AHA/ESC (American College of Cardiology/American Heart Association/European Society of Cardiology) guidelines 4 who signed informed consent before the procedure were enrolled. Patient characteristics are given in Table 1, and cardiovascular history are available in the online-only Data Supplement for the enrolled patient population and for the subgroup of 40 patients who participated in the 3-month follow-up procedure. Patient characteristics are similar in both the enrolled population and subgroup. Contact Force Sensing Catheter and Display The TactiCath catheter with CF capabilities was used for index procedures in the study. It includes a deflectable 3.5 mm electrode, 6 hole irrigation (between 17 and 30 cc/min), and was used with an approved pump and RF generator. This technology uses the diffraction of light to gauge real-time tip deflection with a sensitivity of 1 g of force in any direction. Three individual sensors (Fiber Bragg Grating type) aligned circumferentially around the tip electrode allow for the calculation of CF as a vector, thus providing information on the total force (vector sum) as well as the direction (orientation) of applied force. CF data are sampled every 100 ms and are simultaneously recorded in a digital log file for later retrieval and analysis. Sensor operation is unaffected by ablation energy. A comprehensive real-time display of CF in numeric and graphical formats is normally available to the user. In this study, the operator was blinded to the screen with CF information to prevent bias and adaptation. In effect, the operator manipulated the catheter as he would any similar device without the benefit of CF information. To characterize the effect of CF applied over time, the system automatically detects the beginning and end of RF current delivery and calculates the Force Time Integral (FTI) defined as the total CF integrated over the time of RF delivery. 11 Index Ablation Procedure PVI was achieved with a wide antrum ablation line around the PVs guided by a 3-dimensional mapping system (EnSite, SJM, St. Paul, MN). The specifics of line creation was left to the operators standard practice, as were settings for RF power and choice of long or steerable sheath. The site of RF application was recorded relative to 8 predefined circumferential positions around each ipsilateral pair of PVs 14 : numbered 1 to 8 around the left PV (LPV) and 9 to 16 around the right PV (RPV; Figure 1A). The 8 positions were later consolidated into 4 larger segments to facilitate comparison with 3-month data, to maintain an acceptable level of localization accuracy and to provide a more anatomic representation (Figure 1B). Specifically, multiple anterior positions were grouped together and referred to as the anterior segment for LPV and RPV, as were posterior positions. The following parameters were recorded for each ablation: position, segment, RF power, CF, FTI, duration of ablation, and sheath type. The PVI was achieved with either point (focal) or dragging lesions depending on each operator s technique. Each lesion was limited to a maximum of 60 seconds in a single position to allow for clear identification of the energy delivered to each of the positions. At the end of LPV and RPV isolation, a circumferential diagnostic catheter was used to confirm PVI by entrance block. For the sake of consistency, the waiting period and attempts to provoke dormant conduction were minimized. Follow-up Procedure at 3 Months The invasive follow-up procedure was performed following similar preparatory steps as during the index procedure. 15 A diagnostic catheter was used to evaluate the status of isolation or reconnection per vein. To define successful treatment of a patient, all 8 segments needed to be gap free. Gap sites were determined for each segment and vein. The location of each gap was defined as site of PV potential Table 1. Patient Characteristics for the 46 Patients Who Were Enrolled 46 Patients Index Range/Percentage 40 Patients Follow-up Range/Percentage Age, y 60± ± Sex (males) % % Paroxysmal atrial fibrillation % % Persistent atrial fibrillation out-of-protocol 1 2.2% 1 2.5%

3 Neuzil et al Contact Force Predicts Gaps in PVI 329 on the diagnostic catheter, and in the case of retreatment, confirmed by a change in PV activation. Correlation of CF Parameters to Outcome Results related to the index procedure are presented for the 8 positions around each pair of PVs. Results related to the follow-up procedure are presented for the 4 segments. Ablation parameters, CF, and FTI from all index procedure ablations were correlated to the isolation status of each segment at follow-up (gap or successful isolation). CF parameters and incidence of gaps were tabulated for each segment. Aggregate isolation success across all patients was used to deduce criterion for optimal CF parameters. Statistical Analysis CF, FTI, number of ablations. and power are reported as median and mean±sd. Mann Whitney s nonparametric test was performed. The results reached a level of significance when P<0.05. To compare success ratios, odds ratios and Fisher s test were calculated to account for size effects between ablation parameters and the outcome. All statistical calculations were done using Excel 2007 or Prism 5 (2008). Results Index Ablation Procedure Ten operators treated 46 patients at index procedure at 3 sites. All 92 pairs of PVs (100%) were successfully isolated. Figure 1. Data collection around pulmonary veins. A, Data collection at 8 numbered positions: 1, 9: superior; 2, 16: anterior superior; 3, 15: anterior middle; 4, 14: anterior inferior; 5, 13: inferior; 6, 12: posterior inferior; 7, 11: posterior middle; 8, 10: posterior superior. B, Positions 2,3,4 and 14,15,16 were grouped, respectively, into left and right anterior segments and positions 6,7,8 and 10,11,12 were grouped, respectively, into left and right posterior segments. Reflecting the variety of approaches used, delivered RF power ranged from 10 to 40 Watts, total number of ablations was from 37 to 131, and total RF time ranged from 1200 to 4260 seconds per patient. CF and FTI distribution for all ablations at index procedure (n=3152) are displayed in Figure 2A and 2B. Mean CF was 19.4±16.2 g, and median was 14.9 g. The average FTI per ablation was 730±773 gs, and the median FTI was 479 gs. A deflectable sheath was used for 22 patients (Agilis, SJM, St. Paul, MN), and a nondeflectable sheath (SL1, SJM, St. Paul, MN) was used for 26 patients. The CF was similar in both groups (medians of 14.9 g versus 14.9 g; P=0.82), with an average CF of 19.5±16.8 g versus 19.3±15.8 g. The average waiting period after PV isolation to assess acute reconnection was 2±2 minutes. CF was generally higher at all positions in the RPV than in the LPV (Figure 2C) with the exception of the posterior superior position. Lowest CFs were observed in the LPV, from 15.2±14.4 g at the anterior superior (ridge) and down to 10.7±8.8 g in the anterior inferior. The anterior inferior in the RPV was remarkable for having the highest average CF of all positions at 29.5±21.8 g. FTI values were also generally higher on the right side with clearly lower FTIs in the left anterior positions (Figure 2D).

4 330 Circ Arrhythm Electrophysiol April 2013 Figure 2. Distributions of force parameters at index procedure. Forty-six patients received 3152 ablations. A, Histogram of contact forces. B, Histogram of Force Time Integral. C, Distribution of average contact forces per position. D, Distribution of average Force Time Integrals per position. The power on the posterior wall was significantly lower than in other locations (average 24.1±4.8 W versus 26.8±6.3 W, median 25.0 W versus 25.0 W; P<0.0001). Follow-up Procedure Six patients withdrew from the study leaving 40 who underwent the 3-month follow-up procedure (87%). Of these, 26 patients (65%) had 1 gaps. Six of the patients had gaps only in the LPV, and 7 patients had gaps only in the RPV. Thirteen patients had gaps in both LPV and RPV. Specifically, of 80 ipsilateral PV pairs, 39 (49%) were reconnected at 3 months. Of the 318 segments originally treated, there were 52 segments with gaps (16%), whereas isolation was confirmed in 266 segments (84%). The power for gap and no gap segments was not different (26.1 versus 25.0 W; P=0.26). Twenty patients with follow-up procedures (50%) were treated with a deflectable sheath. Sheath type had no impact on gap ratio at 3 months. Gaps occurred in all 4 segments around each pair of veins. A majority of gaps appeared on the physically larger posterior and anterior segments, especially the right posterior (12 gaps, 23%) and left anterior (13 gaps, 25%). gaps but not strongly significant. There was significant differences in the number of ablations in segments without and with gaps. The greatest significance was noted when comparing minimum CF in segments with no gap versus gap (8.1 g versus 3.6 g; P<0.0001; Figure 3A) and minimum FTI (232 gs versus 118 gs; P=0.0007; Figure 3B). In terms of success ratio, segments with a minimum FTI >400 gs had a 95% chance of remaining isolated compared with those with a minimum FTI < 400 gs, which had a 79% chance of remaining isolated (P<0.001; Figure 4A). The likelihood of successful treatment for the full patient results from the aggregate isolation rates of each segment. For successful treatment of a patient, all 8 segments need to be gap free. If the number of segments with minimum FTI <400 gs in the same patient increases, then the probability of successful treatment of the patient (extrapolated from isolation of all PVI rates) results from the multiplication of probabilities for each segment and decreases rapidly. If all 8 segments had a minimum FTI <400 gs, the likelihood of successful treatment of the patient would drop to 15%. Discriminative CF Parameters For the 40 patients who completed follow-up, Table 2 summarizes the ablation parameters for the segments that remained isolated at 3 months compared with those that had gaps. Average CF and FTI were higher in segments without Serious Adverse Events There were no serious adverse events within 30 days after index procedure. One patient (2.5%) developed a pericardial effusion after the follow-up procedure with Thermocool Celsius catheter (Biosense Webster, Diamond Bar, CA).

5 Neuzil et al Contact Force Predicts Gaps in PVI 331 Table 2. Ablation Parameters for the Segments That Remained Isolated at 3 Months Compared With Those That Had Gaps for the 40 Patients Who Completed Follow-up Parameters Medians for Isolated Segments Medians for Gap Segments P Value CF, g P=0.022 FTI, gs P=0.090 Total number of ablations 6 9 P< Minimum CF, g P< Minimum FTI, gs P= N=2519 ablations (40 patients who completed follow-up). CF indicates contact force; and FTI, Force Time Integral. Discussion Acute isolation of PVs in patients with atrial fibrillation is usually achievable (100% in this study), but recurrence resulting from PV reconnection is common. 4,5 Most clinicians would agree that freedom from early recurrence is a good measure of treatment success. This study did not measure long-term clinical recurrence, yet it is likely that the number of veins that remain isolated at the end of a 3-month blanking period is a predictor of long-term success. The opportunity to assess PV reconnection normally occurs only at the time of retreatment, thus giving an incomplete picture of the actual reconnections that occur in the full patient population after PVI. In this study, the 3-month follow-up study revealed that as many as 65% of patients had PV reconnections. The invasive diagnostic technique used in this protocol definitively identified the location of gaps as compared with other clinical measures, therefore gaps were found more frequently than usually reported clinical recurrence rates. 4,5 CF Parameters In the TOCCATA study, an average CF >20 g was associated with higher long-term treatment success, although this was obtained by only half of operators. 12 In EFFICAS I, the average CF for all index procedures was nearly 20 g, perhaps suggesting a high level of experience at participating sites despite being blinded to CF. Also in TOCCATA, ablations with CF <10 g were associated with unstable catheter contact and reduced patient outcome at 12 months. Similarly, EFFICAS I showed a tendency for better isolation results at segments with higher average CF and FTI. However, the strongest indicators for isolation versus gap occurrence at 3 months are minimum CF and minimum FTI per segment. In segments with a minimum FTI <400 gs, the probability for isolation reaches only 79%, but increases to 95% when the Minimum FTI is >400 gs. One may observe that ablations in any given segment are only as effective as the worst ablation performed in that segment, quantified by the minimum FTI. Consecutive segments with low-minimum FTI may considerably decrease the likelihood for successful outcome (Figure 4). There may be several reasons why the worst ablation, defined as ablation with minimum FTI at a given site, is a strong predictor for electric reconnection of a PV. One is that the tissue surface is altered because of initial RF current, making subsequent ablations more difficult to penetrate deep in the tissue. 16 A more plausible explanation is that creation of a nontransmural lesion results in edema. It has been reported that heart wall thickness can double after 1 minute of ablation because of tissue edema formation. 16 Hence, a nontransmural first lesion may increase wall thickness, reducing the effect of tissue heating and making it difficult to achieve full transmurality with subsequent ablations. Therefore, the goal of any RF ablation should be to achieve transmurality with the first attempt. Another important lesson from the study is that the average number of ablations per segment is inversely correlated to isolation. This suggests that successful and transmural first lesions do not require subsequent corrections, but once a bad ablation is made (FTI <400 gs), it becomes very difficult to correct for it afterward and the risk of gap increases. This might further support the idea of edema formation as a complication for subsequent ablations at the same site. Figure 3. Force parameters discriminators for segments with isolation vs gaps. A, Minimum contact force per segment is shown for successful ablations (left) and for gaps (right) in box plot graph with 5% to 95% limits. B, The minimum Force Time Integral (FTI) per segments is shown for successful ablations (left) and for gaps (right). Statistically significant difference between each group s median is observed and specified above graphs.

6 332 Circ Arrhythm Electrophysiol April 2013 Figure 4. Minimum Force Time Integral success ratio. In 40 patients, 318 segments were ablated. Success or isolation ratio is shown in black per segments ablated with minimum Force Time Integral (FTI) < or >400 gs, respectively. Level of statistical difference and odds ratio are displayed above graph. Number of segments is indicated for each group below the graph. Anatomic Variation Gaps were found in all segments but as expected, they were most prevalent in the ridge between the LPV and the appendage, and in the RPV posterior and superior segments. The relatively low-fti value on all left anterior positions indicates that operators had difficulty sustaining both CF and duration. The difficulty associated with catheter stability at this segment is well understood and may be responsible for the increased number of ablations (14.9±6.6) compared with other segments. 17 Given these limitations, it is advisable that the operator evaluates the quality and stability of the catheter contact before each application of RF energy. A practical observation among a variety of operators confirms that starting an ablation before ensuring catheter stability is commonplace, resulting in high numbers of short and abrupt ablations. This is consistent with the EFFICAS I data, showing a high rate of low FTI (FTI <400 gs in over 40% of lesions; Figure 2B) many of which arose in the left anterior segment. To ensure transmurality, each ablation should be delivered with adequate CF and FTI levels. A persistently successful PVI is critically dependent on the weakest ablation of each segment. The probability of successful treatment for each patient is the product of all probabilities for each segment and becomes very low in case of multiple bad ablations. In summary, EFFICAS I has shown that ablations performed with low-minimum CF and minimum FTI predict delayed gap formation, and that segments with gaps received more ablations than those with no gap. Based on these findings, and combined with the TOCCATA study results, we make the following current recommendations: (1) position the catheter carefully before ablation, preferably with a CF of 20 g but not <10 g; (2) ensure positional stability by monitoring CF before applying RF; (3) sustain RF delivery until a minimum FTI of 400 gs is achieved before moving the catheter to a new location. These findings will be tested prospectively in a subsequent study. The EFFICAS II trial will unblind operators to CF at the initial procedure in an otherwise identical protocol. Study Limitations 1. Treatment methodology specified by the protocol (fixed 60 s duration per ablation, point-by-point or limiting dragging allowed) describes one of several ablation strategies in current clinical practice. 2. The goal of the study had an electrophysiology end point at 3 months. Translation into clinical results on longer term recurrence may be inferred. Conclusion Invasive electrophysiological assessment of conduction gaps at PVI ablation sites at 3-month follow-up has shown that the minimum CF and minimum FTI values obtained at the index procedure ablations correlate strongly with subsequent gap formation. The 3-month ablation outcome at any segment is only as effective as the minimum FTI of any ablation delivered in that segment, particularly when the ablation is <400 gs. CF stability is required before ablation to minimize the risk of unstable contact and ineffective lesions, particularly in the left anterior segment. To achieve durable successful PVI, a target CF of 20 g is recommended, with an absolute minimum CF of 10 g and an absolute minimum FTI of 400 gs per individual ablation lesion. Acknowledgments Data were analyzed by Olivier Frémont from the engineering department of the Ecole Polytechnique Fédérale, Lausanne (EPFL), Switzerland. Sources of Funding This study was supported by a research grant from Endosense SA. Disclosures Authors hereafter mentioned are consultants for the following companies: J. Kautzner for Medtronic, Biosense Webster, Boston Scientific, Hansen Medical, Siemens, and St. Jude Medical; K.-H. Kuck for Stereotaxis and Biotronik; P. Neuzil for Ev3, Endosense, and CryoCath Technologies; V.Y. Reddy is a consultant for Ev3 and Voyage Medical, and is also advisor for CardioFocus and Endosense. K.-H. Kuck and D.C. Shah are advisors and stakeholders of Endosense. E. Wissner received speaker honoraria from Biosense Webster, Biotronik, CardioFocus, and Medtronic. H. Lambert and A. Yulzari are Endosense employees. References 1. Wilber DJ, Pappone C, Neuzil P, De Paola A, Marchlinski F, Natale A, Macle L, Daoud EG, Calkins H, Hall B, Reddy V, Augello G, Reynolds MR, Vinekar C, Liu CY, Berry SM, Berry DA; ThermoCool AF Trial Investigators. Comparison of antiarrhythmic drug therapy and radiofrequency catheter ablation in patients with paroxysmal atrial fibrillation: a randomized controlled trial. JAMA. 2010;303: Ouyang F, Tilz R, Chun J, Schmidt B, Wissner E, Zerm T, Neven K, Köktürk B, Konstantinidou M, Metzner A, Fuernkranz A, Kuck KH. Long-term results of catheter ablation in paroxysmal atrial fibrillation: lessons from a 5-year follow-up. Circulation. 2010;122: Hussein AA, Saliba WI, Martin DO, Bhargava M, Sherman M, Magnelli- Reyes C, Chamsi-Pasha M, John S, Williams-Adrews M, Baranowski B, Dresing T, Callahan T, Kanj M, Tchou P, Lindsay BD, Natale A, Wazni O. Natural history and long-term outcomes of ablated atrial fibrillation. Circ Arrhythm Electrophysiol. 2011;4: Natale A, Raviele A, Arentz T, Calkins H, Chen SA, Haïssaguerre M, Hindricks G, Ho Y, Kuck KH, Marchlinski F, Napolitano C, Packer D, Pappone C, Prystowsky EN, Schilling R, Shah D, Themistoclakis S, Verma A. Venice Chart international consensus document on atrial fibrillation ablation. J Cardiovasc Electrophysiol. 2007;18:

7 Neuzil et al Contact Force Predicts Gaps in PVI Calkins H, Kuck KH, Cappato R, Brugada J, Camm AJ, Chen SA, Crijns HJ, Damiano RJ Jr, Davies DW, DiMarco J, Edgerton J, Ellenbogen K, Ezekowitz MD, Haines DE, Haissaguerre M, Hindricks G, Iesaka Y, Jackman W, Jalife J, Jais P, Kalman J, Keane D, Kim YH, Kirchhof P, Klein G, Kottkamp H, Kumagai K, Lindsay BD, Mansour M, Marchlinski FE, McCarthy PM, Mont JL, Morady F, Nademanee K, Nakagawa H, Natale A, Nattel S, Packer DL, Pappone C, Prystowsky E, Raviele A, Reddy V, Ruskin JN, Shemin RJ, Tsao HM, Wilber D HRS/EHRA/ ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation. Europace. 2012;14: Pratola C, Baldo E, Notarstefano P, Toselli T, Ferrari R. Radiofrequency ablation of atrial fibrillation: is the persistence of all intraprocedural targets necessary for long-term maintenance of sinus rhythm? Circulation. 2008;117: Yokoyama K, Nakagawa H, Shah DC, Lambert H, Leo G, Aeby N, Ikeda A, Pitha JV, Sharma T, Lazzara R, Jackman WM. Novel contact force sensor incorporated in irrigated radiofrequency ablation catheter predicts lesion size and incidence of steam pop and thrombus. Circ Arrhythm Electrophysiol. 2008;1: Santangeli P, Di Biase L, Burkhardt DJ, Horton R, Sanchez J, Bai R, Pump A, Perez M, Wang PJ, Natale A, Al-Ahmad A. Catheter ablation of atrial fibrillation: state-of-the-art techniques and future perspectives. J Cardiovasc Med (Hagerstown). 2012;13: Thiagalingam A, D Avila A, Foley L, Guerrero JL, Lambert H, Leo G, Ruskin JN, Reddy VY. Importance of catheter contact force during irrigated radiofrequency ablation: evaluation in a porcine ex vivo model using a force-sensing catheter. J Cardiovasc Electrophysiol. 2010;21: Okumura Y, Johnson SB, Bunch TJ, Henz BD, O Brien CJ, Packer DL. A systematical analysis of in vivo contact forces on virtual catheter tip/tissue surface contact during cardiac mapping and intervention. J Cardiovasc Electrophysiol. 2008;19: Shah DC, Lambert H, Nakagawa H, Langenkamp A, Aeby N, Leo G. Area under the real-time contact force curve (force-time integral) predicts radiofrequency lesion size in an in vitro contractile model. J Cardiovasc Electrophysiol. 2010;21: Reddy VY, Shah D, Kautzner J, Schmidt B, Saoudi N, Herrera C, Jaïs P, Hindricks G, Peichl P, Yulzari A, Lambert H, Neuzil P, Natale A, Kuck KH. The relationship between contact force and clinical outcome during radiofrequency catheter ablation of atrial fibrillation in the TOCCATA study. Heart Rhythm. 2012;9: Kuck KH, Reddy VY, Schmidt B, Natale A, Neuzil P, Saoudi N, Kautzner J, Herrera C, Hindricks G, Jaïs P, Nakagawa H, Lambert H, Shah DC. A novel radiofrequency ablation catheter using contact force sensing: Toccata study. Heart Rhythm. 2012;9: Wang XH, Shi HF, Sun YM, Gu JN, Zhou L, Liu X. Circumferential pulmonary vein isolation: the role of key target sites. Europace. 2008;10: Ahmed H, Neuzil P, Skoda J, D Avila A, Donaldson DM, Laragy MC, Reddy VY. The permanency of pulmonary vein isolation using a balloon cryoablation catheter. J Cardiovasc Electrophysiol. 2010;21: Ren JF, Callans DJ, Schwartzman D, Michele JJ, Marchlinski FE. Changes in local wall thickness correlate with pathologic lesion size following radiofrequency catheter ablation: an intracardiac echocardiographic imaging study. Echocardiography. 2001;18: Kistler PM, Ho SY, Rajappan K, Morper M, Harris S, Abrams D, Sporton SC, Schilling RJ. Electrophysiologic and anatomic characterization of sites resistant to electrical isolation during circumferential pulmonary vein ablation for atrial fibrillation: a prospective study. J Cardiovasc Electrophysiol. 2007;18: CLINICAL PERSPECTIVE EFFICAS I is a prospective multicenter study, providing new insights into potential causes of poor long-term results of radiofrequency catheter ablation for paroxysmal atrial fibrillation and relationship to contact force sensing. We compare pulmonary vein (PV) reconnection sites in patients undergoing ablation and evaluate the factors likely to account for nondurable lesion delivery. The isolation rate around 8 PV segments (eg, anterior aspect of left ipsilateral PV, superior aspect of right ipsilateral PV) at a 3-month remapping electrophysiology study is used as a predictor of long-term success. The PV segments with reconnection at 3 months are associated with reduced contact force parameters, below specific thresholds of minimum contact force (10 g) and Force Time Integral, or Force Time Integral (400 gs). PV segments isolated at 3 months had minimum contact force (P<0.0001) and minimum Force Time Integral (P=0.0007) above the respective thresholds and received fewer lesions than segments with reconduction. In addition, the study shows that ablations with lowest Force Time Integral (<400 gs) are responsible for quality of the entire circumferential lesion line around each PV, and thus also contributors toward unsuccessful outcome. To reduce the edema that is formed quickly after any ablation, we believe it is important that in daily clinical practice, each ablation should be delivered with care and should result in a transmural lesion at once. These new parameters will help improve PV isolation ablation and may make it more efficient for the operator and more effective for the patient.

8 Electrical Reconnection After Pulmonary Vein Isolation Is Contingent on Contact Force During Initial Treatment: Results From the EFFICAS I Study Petr Neuzil, Vivek Y. Reddy, Josef Kautzner, Jan Petru, Dan Wichterle, Dipen Shah, Hendrik Lambert, Aude Yulzari, Erik Wissner and Karl-Heinz Kuck Circ Arrhythm Electrophysiol. 2013;6: ; originally published online March 20, 2013; doi: /CIRCEP Circulation: Arrhythmia and Electrophysiology is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX Copyright 2013 American Heart Association, Inc. All rights reserved. Print ISSN: Online ISSN: The online version of this article, along with updated information and services, is located on the World Wide Web at: Data Supplement (unedited) at: Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in Circulation: Arrhythmia and Electrophysiology can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. Once the online version of the published article for which permission is being requested is located, click Request Permissions in the middle column of the Web page under Services. Further information about this process is available in the Permissions and Rights Question and Answer document. Reprints: Information about reprints can be found online at: Subscriptions: Information about subscribing to Circulation: Arrhythmia and Electrophysiology is online at:

9 SUPPLEMENTAL MATERIAL

10 Table: Cardiovascular History 46 patients Percentage / 40 patients Percentage / index Range follow-up Range Previous AAD * % % No other disease % % Other cardiac disease % % Hypertension % % Diabetes 4 8.7% 3 7.5% Transient ischemic attack 3 6.5% 3 7.5% Valvular regurgitation 3 6.5% 3 7.5% Obesity 3 6.5% 3 7.5% NYHA Classification n/a NYHA 4 8.7% 3 7.5% NYHA Class I or II % % Left Atrium diameter (mm) 42+/ / * Anti-arrhythmic drug New-York Heart Association