When Propensity Score Does Not Always Match?

When Propensity Score Does Not Always Match? | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL Journal of Cardiovascular Electrophysiology This is a preprint and has not been peer reviewed. Data may be preliminary. 6 May 2025 V1 Latest version Share on When Propensity Score Does Not Always Match? Authors : Antoine Da Costa 0000-0003-3302-9988 [email protected] , Cedric Yvorel , and Karim Benali Authors Info & Affiliations https://doi.org/10.22541/au.174650241.18523779/v1 318 views 209 downloads Contents Abstract Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract The sub-study of EU-PORIA registry by Hirokami J et al. discussed on efficacy and safety of pulsed-field ablation (PFA) using the pentaspline multi-electrode catheter in symptomatic persistent atrial fibrillation (PeAF). This study focused on the interest of additional linear ablation or extra-pulmonary substrate approaches in symptomatic PeAF with PFA. They compared the strategy of pulmonary (PVI) only or PVI + α based on the controversial literature. The authors concluded that based on the propensity matched score study, PVI plus extra PV ablation using pentaspline PFA catheter would be associated with a higher incidence of atrial tachycardia recurrences suggesting that for Pe AF, PVI alone may be more effective with PFA. In our letter response we discussed the methodology used mainly the initial Pe AFib classification used in the propensity score as well as many other confounding factors. Letter to the Editor “When Propensity Score Does Not Always Match?” by Antoine Da Costa et al. based on “Hirokami J, Chun KRJ, Bordignon S et al. Pulsed field ablation for persistent atrial fibrillation in EU-PORIA registry. J Cardiovasc Electrophysiol 2025; 1-11.” Antoine Da Costa, MD, PhD, Cedric Yvorel, MD; Karim Benali, MD. From the Division of Cardiology, Jean Monnet University (ADC, CY, KB), Saint-Etienne, France. Address for Correspondence: Professor Antoine Da Costa, Service de Cardiologie, Hôpital Nord, Centre Hospitalier Universitaire de Saint-Etienne, F-42055 Saint-Etienne Cedex 2. Tel.: +33 (0)4 77 82 82 42; fax: +33 (0)4 77 82 81 64; email: [email protected] Dear Editor, We read with great interest the sub-study of EU-PORIA registry by Hirokami J et al. on efficacy and safety of pulsed-field ablation (PFA) using the pentaspline multi-electrode catheter in symptomatic persistent atrial fibrillation (PeAF) (1). This study focused on the interest of additional linear ablation or extra-pulmonary substrate approaches in symptomatic PeAF with PFA (1). They compared the strategy of pulmonary (PVI) only or PVI + α based on the controversial literature mainly both STAR-AF II and EARNST-PVI studies (2, 3). The authors concluded that based on the propensity matched score study, PVI plus extra PV ablation using pentaspline PFA catheter would be associated with a higher incidence of atrial tachycardia recurrences and suggest that for Pe AF, PVI alone may be more effective with PFA (1). We appreciated the authors’ efforts and the quality of their work, but we have some concerns about the initial AFib classification and the methodology used mainly the propensity score methodology. PeAF represents a marker of more severe atrial electrical and anatomical remodeling that means more atrial fibrosis, atrial dilatation and abundant non-pulmonary vein triggers compared to paroxysmal AF (4). Recently, several prospective randomized studies have validated the superiority of linear or additional lesions in Pe AFib in order to improve the free arrythmia long-term survival but it was with the thermal energy (5-10). The PFA appears to be very challenging even in Pe AFib due to safety and durability of PVI but also the accessibility to safe linear lesions (11). The considerable difference in mechanisms responsible for lesion creation with pulsed field ablation (high-voltage electric fields leading to irreversible tissue injury by electroporation), and the more limited effects of the technique on the autonomic nervous system, may differentially affect the recurrences and but also transmural lesions. Thus, Hirokami J et al. study launches a new debate on the use of PFA in PeAF (1). On the other side, many limitations of their study deserve commentaries. AFib is subclassified into paroxysmal AF (PAF) and PeAFib, but both are often difficult to differentiate and are recognized as non-mutually exclusive categories (12). Based on their retrospective observational study design, the PeAF selection remains unclear (1). The PeAF definition was not mentioned in the study design and despite the seven European high-volume participation in this trial, the rigorous AFib classification is not a guarantee such as it was not pre-specified in the original protocol (1, 13). Indeed, in the original protocol an electronic database was designed to retrospectively collect patient data and the entire population included 1233 patients. The population was classified as paroxysmal, persistent, and long-standing persistent AF in 60%, 37%, and 3% respectively (1, 13). This item clarifies on the number of patients with PeFA definitely included in their sub-study and but not how the 101 out of 448 Pe AFib pts were initially allocated for additional PVI + α treatment (1, 13). This point may have been a selection bias. Accordingly, despite the propensity score methodology used, Pe AFib categorization based on the operators’ choice may have largely influenced the study results (1, 13). Even though, the propensity scores provide a more balanced comparison between the treatment and control groups by equating covariates, or background characteristics, across groups, the initial groups comparison remains fundamental (14, 15). Researchers needs to create a fair comparison with similar distributions of key variables, leading to accurately estimating the treatment effect (14, 15). For Pe AF definition, we have several remarks on the classification used by the authors which could affect the validity of the comparison. Indeed, even if the variables used in the propensity score are equally distributed, the variables used do not guarantee an exact comparison of patients PeAF population. As recognized by the authors in the limitation section, PeAF represents an evolutive atrial disease with many factors impacting the ablation prognosis such as mainly the correlation between diagnosis‑to‑ablation time and the atrial remodeling substrate or left atrial size (16). Such substrate modifications may have been prone to influence the occurrence or recurrences of atrial tachyarrhythmias (1, 12, 16). The authors stated in the statistical analysis that for considering the freedom predictors of recurrence they used a priori variables validated in the literature (1). Accordingly, some variables missing in the initial classification may have largely influenced the comparison on PFA Farapulse strategy used. One another major factor that may have influenced significantly the results study is based on the catheter technology used in each group (1). The 35 mm pentaspline PFA catheter was more frequently utilized in the PVI + α group (26% vs. 51%, p < 0.001) (1). Such variable was not adjusted in the propensity score and may have an influence on the results. Preliminary data show longer procedure times and fluoroscopy times using the 35 mm device as well as a higher rate of PV reconnections especially at the septal PVs (17). Most importantly, a trend towards worse clinical outcomes using the larger 35 mm pentaspline PFA catheter is discussed in the literature (1, 17). The authors’ analysis if I understood well is in favor of an initial misclassification of PeAF patients regarding that patients who underwent PVI alone were more likely to use smaller 31 mm catheters (74% vs. 49%, p < 0.001). That means an unintentional bias based on the operator 35 mm catheter choice in more severe patients (1). Furthermore, depending on left atrial anatomy, theoretically, using a larger 35 mm catheter could result in a narrower distance between unintentionally created PVI lesions on the LAPW. Therefore, patients who underwent PVI with a 31 mm catheter may be less prone to recurrence of AT (1). Lastly, having a moderate to large sample size is preferable, as it facilitates finding good matches (14, 15. Even if the initial retrospective cohort was large in the EU-PORIA registry, the power study appears low with 75 patients in each group regarding the end-point study (1). Additional data on the power study measurement would be welcome. The authors are certainly right when discussing some challenging questions with additional lesions with PFA in Pe AFib population, but the real question is whether their study proves their assumptions based on the methodology used in the EU-PORIA registry…. for our point of view the propensity score methodology used is not always appropriate and certainly requires more precise definitions concerning Pe AF evolution (1). If propensity scores provide a more balanced comparison between the treatment and control groups by equating covariates, or background characteristics, across groups, the estimating treatment effect remains dependent of exact group comparison. . References 1. Hirokami J, Chun KRJ, Bordignon S et al. Pulsed field ablation for persistent atrial fibrillation in EU-PORIA registry. J Cardiovasc Electrophysiol 2025; 1-11. 2. A. Verma, C. Jiang, T. R. Betts, et al., “Approaches to Catheter Ablation for Persistent Atrial Fibrillation,” New England Journal of Medicine 372, no. 19 (2015): 1812–1822, https://doi.org/10.1056/ nejmoa1408288. 3. M. Masuda, K. Inoue, N. Tanaka, et al., “Long‐Term Impact of Additional Ablation After Pulmonary Vein Isolation: Results From Earnest‐PVI Trial,” Journal of the American Heart Association 12, no. 17 (2023): 1–12, https://doi.org/10.1161/JAHA.123.029651. 4. Ganesan AN, Chew DP, Hartshorne T, Selvanayagam JB, Aylward PE, Sanders P, et al. The impact of atrial fibrillation type on the risk of thromboembolism, mortality, and bleeding: a systematic review and meta-analysis. Eur Heart J 2016; 37:1591–602. 5. M. Valderrábano, L. E. Peterson, V. Swarup, et al., “Effect of Catheter Ablation With Vein of Marshall Ethanol Infusion vs. Catheter Ablation Alone on Persistent Atrial Fibrillation: The VENUS Randomized Clinical Trial,” JAMA: The Journal of the American Medical Association 324 (2020): 1620–1628. 6. C. Sang, Q. Liu, Y. Lai, et al., “Pulmonary Vein Isolation With Optimized Linear Ablation vs Pulmonary Vein Isolation Alone for Persistent AF: The PROMPT‐AF Randomized Clinical Trial,” Journal of the American Medical Association 333 (2025): 381–389. 7. Li F, Sun JY, Wu LD et al. The Long-Term Outcomes of Ablation With Vein of Marshall Ethanol Infusion vs. Ablation Alone in Patients With Atrial Fibrillation: A Meta-Analysis. Front Cardiovasc Med 2022 Apr 29; 9:871654. 8. A. Verma, C. Jiang, T. R. Betts, et al., STAR AF II Investigators, “Approaches to Catheter Ablation for Persistent Atrial Fibrillation,” New England Journal of Medicine 372, no. 19 (2015): 1812–1822. 9. Deisenhofer I, Albenque JP, Busch S, and TAILORED-AF Investigators. Artificial intelligence for individualized treatment of persistent atrial fibrillation: a randomized controlled trial. Nat Med. 2025 Feb 14. doi: 10.1038/s41591-025-03517-w. 10. Huo Y, Gaspar T, Schönbauer R, Wojcik M, Fiedler L, Roithinger FX, et al. Low-voltage myocardium-guided ablation trial of persistent atrial fibrillation. NEJM Evid 2022;1: EVIDoa2200141. https://doi.org/10.1056/EVIDoa2200141. 11. B. Davong, R. Adeliño, H. Delasnerie, et al., “Pulsed‐Field Ablation on Mitral Isthmus in Persistent Atrial Fibrillation,” JACC: Clinical Electrophysiology 9, no. 7 (2023): 1070–1081, https://doi.org/10.1016/j. jacep.2023.03.021. 12. Benali K, Macle L, Haissaguere M, Nattel S, Deyell M, Da Costa A and Andrade JG. Impact of catheter ablation of atrial fibrillation on disease progression. JACC Clin Electrophysiol 2025 Feb;11(2):421-435. doi: 10.1016/j.jacep.2024.10.017. 13. B. Schmidt, S. Bordignon, K. Neven, et al., “European Real‐World Outcomes With Pulsed Field Ablation in Patients With Symptomatic Atrial Fibrillation: Lessons From the Multi‐Centre Eu‐Poria Registry,” Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology: Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology 25, no. 7 (2023): 1–11, https://doi.org/10.1093/europace/euad185. 14. Ralph B. D’Agostino. Propensity Scores in Cardiovascular Research. Circulation. 2007;115:2340-2343. 15. Saswata Deb, MD,a,b Peter C. Austin, PhD,b,c,d Jack V. Tu, MD, PhD,a,b,c Dennis T. Ko, MD, MSc,a,b,c C. David Mazer, MD,e Alex Kiss, PhD,d and Stephen E. Fremes, MD, MSca. Methods in Cardiovascular Research A Review of Propensity-Score Methods and Their Use in Cardiovascular Research. Canadian Journal of Cardiology. 2016 ; 32 : 259-265. 16. De Greef Y, Bogaerts K, Sofianos D, Buysschaert I. Impact of diagnosis-to-ablation time on af recurrence. JACC Clin Electrophysiol. 2023;9(11):2263–72. https://doi.org/10.1016/j.jacep. 2023.07.008. 17. D Schaack, S Tohoku, S Bordignon, L Urbanek, J Hirokami, R Ebrahimi, K Plank, S Chen, K R J Chun, B Schmidt. 31 vs 35 mm: a randomized comparison of the pentaspline pulsed field ablation catheter sizes. EP Europace, Volume 26, Issue Supplement_1, May 2024, euae102.723, https://doi.org/10.1093/europace/euae102.723. Abstract The sub-study of EU-PORIA registry by Hirokami J et al. discussed on efficacy and safety of pulsed-field ablation (PFA) using the pentaspline multi-electrode catheter in symptomatic persistent atrial fibrillation (PeAF). This study focused on the interest of additional linear ablation or extra-pulmonary substrate approaches in symptomatic PeAF with PFA. They compared the strategy of pulmonary (PVI) only or PVI + α based on the controversial literature. The authors concluded that based on the propensity matched score study, PVI plus extra PV ablation using pentaspline PFA catheter would be associated with a higher incidence of atrial tachycardia recurrences suggesting that for Pe AF, PVI alone may be more effective with PFA. In our letter response we discussed the methodology used mainly the initial Pe AFib classification used in the propensity score as well as many other confounding factors . Information & Authors Information Version history V1 Version 1 06 May 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Collection Journal of Cardiovascular Electrophysiology Keywords basic: atrial fibrillation/atrial arrhythmias clinical: catheter ablation – atrial fibrillation clinical: catheter ablation – atrial tachycardia clinical: catheter ablation – non-rf energy sources clinical: epidemiology/clinical trials Authors Affiliations Antoine Da Costa 0000-0003-3302-9988 [email protected] Universite Jean Monnet Saint-Etienne View all articles by this author Cedric Yvorel Universite Jean Monnet Saint-Etienne View all articles by this author Karim Benali Universite Jean Monnet Saint-Etienne View all articles by this author Metrics & Citations Metrics Article Usage 318 views 209 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Antoine Da Costa, Cedric Yvorel, Karim Benali. When Propensity Score Does Not Always Match?. Authorea . 06 May 2025. 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