Insight From Dissection of the Methodology and Findings of the CAPLA Study
- Adequate sample size and follow-up duration are crucial while evaluating the efficacy of an ablation strategy.
- A consensual approach including definition of boundaries of the left atrial posterior wall (LAPW) to be targeted for electrical isolation, box lesion versus focal ablations throughout the LAPW until complete electrical isolation is achieved, and ablation parameters such as power use, lesion duration, and strategy to prevent thermal injury to esophagus, is needed to fairly appraise the benefits of the LAPW isolation procedure.
In the recently held annual scientific meeting of the European Society of Cardiology (ESC), Dr. Peter Kistler from University of Melbourne presented the findings from the CAPLA (Catheter Ablation for Persistent Atrial Fibrillation: A Multicenter Randomized Trial of Pulmonary Vein Isolation Versus PVI with Posterior Left Atrial Wall Isolation) study.
This international trial was designed to assess the additional benefits of electrical isolation of left atrial posterior wall (PWI) in terms of off-drug arrhythmia-free survival in persistent atrial fibrillation (AF) patients undergoing their first catheter ablation procedure. Patients were randomized 1:1 to pulmonary vein isolation (PVI) alone or PVI + PWI; PVI involved wide antral circumferential isolation of PVs, while PWI included floor and roof lines connecting the PV-encircling lesions and additional mapping and targeting of the earliest electrograms within the box.1 Patients were included only if the duration of persistent AF was ≤3 years. All participants were followed up for 1 year for heart rhythm monitoring. Sample size of 169 per arm was calculated assuming a benefit of 15% from adding PWI. The authors reported no advantages of additional PWI compared to PVI-alone in the study participants.
The findings from this study are not only contradictory to prior data from multiple randomized trials (RCT) demonstrating the incremental benefit of PWI, but also appear to be based on some flaws in the study design and subsequent misinterpretations of the outcome.2
The authors calculated the sample size based on the success rate of PVI reported in the STAR AF II trial.3 However, the 60% success rate in the STAR AF II trial (that was used for the calculation) was with or without antiarrhythmic drugs (AAD) and the outcome was assessed at 18 months whereas the primary endpoint in the CAPLA study was off-drug freedom from survival at 12 months of follow-up. Secondly, the authors assumed that ablation of the posterior wall would result in an additional 15% benefit, which was much higher than the ≤10% effect size that was presumed by other RCTs investigating PVI versus PWI.4,5 A properly calculated sample size could have resulted in a different outcome.
Additionally, the primary outcome was assessed at 1 year. A longer follow-up duration would have given a better evaluation of the added benefits of PWI (or disadvantage of PVI alone) at long-term. Moreover, with the possibility that many of the study participants were in early persistent AF that would arguably respond as well to PVI as the paroxysmal AF cases, it is highly likely that no added advantage of PWI was noted at 1 year follow-up. Furthermore, pooled estimate from previous studies has shown 63% reconnection rate when left atrial posterior wall isolation (LAPWI) was performed using box lesion with power output from 20-35 watts, similar to the current study.6 Given the high failure rate of this ablation technique, it is difficult to prove the efficacy of the procedure. It is noteworthy to mention here that the PRECEPT study reported the single-procedure clinical success rate at 15 months in persistent AF to be 80.4% with subsequent improvement in quality of life and reduction in healthcare utilization, which was most likely due to improved ablation technique.7,8
Lastly, the ablation strategy to isolate the posterior wall was seemingly inadequate. The authors created the box lesion by placing the roof and the floor line that connected the superior and inferior ends of bilateral PV-encircling lesions. However, the true LAPW spans further down from the inferior borders of the inferior PVs to the superior margin of the vestibule, the region surrounding the mitral valve orifice.9,10 In our experience, triggers from PW originate from the whole area, including the lower part and point-by-point ablation of the area between the PVs extended to the 'true' posterior wall down to the level of coronary sinus, making it necessary to achieve superior ablation success when combined with PVI.
To conclude, although the CAPLA study was well conducted, it failed to deliver the outcome in favor of the study's hypothesis, most likely because of deficits in the study design and ablation strategy. While designing future RCTs to evaluate relative benefit of ablation strategies, investigators should follow standardized approaches and definitions for a fair comparison.
- Chieng D, Sugumar H, Ling LH, et al. Catheter ablation for persistent atrial fibrillation: a multicenter randomized trial of pulmonary vein isolation (PVI) versus PVI with posterior left atrial wall isolation (PWI) - The CAPLA study. Am Heart J 2022;243:210-20.
- Kanitsoraphan C, Rattanawong P, Techorueangwiwat C, et al. The efficacy of posterior wall isolation in atrial fibrillation ablation: a systematic review and meta-analysis of randomized controlled trials. J Arrhythm 2022;38:275-86.
- Verma A, Jiang CY, Betts TR, et al. Approaches to catheter ablation for persistent atrial fibrillation. N Engl J Med 2015;372:1812-22.
- Kim JS, Shin SY, Na JO, et al. Does isolation of the left atrial posterior wall improve clinical outcomes after radiofrequency catheter ablation for persistent atrial fibrillation?: a prospective randomized clinical trial. Int J Cardiol 2015;181:277-83.
- Pak HN, Park J, Park JW, et al. Electrical posterior box isolation in persistent atrial fibrillation changed to paroxysmal atrial fibrillation: a multicenter, prospective, randomized study. Circ Arrhythm Electrophysiol 2020;13:e008531.
- Thiyagarajah A, Kadhim K, Lau DH, et al. Feasibility, safety, and efficacy of posterior wall isolation during atrial fibrillation ablation: a systematic review and meta-analysis. Circ Arrhythm Electrophysiol 2019;12:e007005.
- Mansour M, Calkins H, Osorio J, et al. Persistent atrial fibrillation ablation with contact force-sensing catheter: the prospective multicenter PRECEPT trial. JACC Clin Electrophysiol 2020;6:958-69.
- Natale A, Calkins H, Osorio J, et al. Positive clinical benefit on patient care, quality of life, and symptoms after contact force-guided radiofrequency ablation in persistent atrial fibrillation: analyses from the PRECEPT prospective multicenter study. Circ Arrhythm Electrophysiol 2021;14:e008867.
- Aryana A. Rationale and outcomes of cryoballoon ablation of the left atrial posterior wall in conjunction with pulmonary vein isolation. J Innov Card Rhythm Manag 2021;12:4633-46.
- Elbatran AI, Anderson RH, Mori S, Saba MM. The rationale for isolation of the left atrial pulmonary venous component to control atrial fibrillation: a review article. Heart Rhythm 2019;16:1392-98.
Keywords: ESC Congress, ESC22, Pulmonary Veins, Atrial Fibrillation, Anti-Arrhythmia Agents, Quality of Life, Follow-Up Studies, Coronary Sinus, Mitral Valve, Sample Size, Catheter Ablation, Patient Acceptance of Health Care
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