BACKGROUND: Compared with antiarrhythmic drugs, pulmonary vein isolation (PVI) reduces atrial fibrillation (AF) recurrences and AF burden. All but one previous study was unblinded, raising the possibility of a placebo effect of catheter ablation. OBJECTIVE: This study aimed to compare PVI using pulsed field (PF) energy to a sham procedure in patients with symptomatic AF. METHODS: PFA-SHAM is a single-blind, randomized trial of symptomatic patients with paroxysmal or persistent AF, and an Atrial Fibrillation Effect On Quality-of-Life (AFEQT) questionnaire score ≤50. At enrollment, all patients receive an implantable cardiac monitor, and an electrophysiology study is scheduled 30 days later. After excluding supraventricular tachycardia as a cause of AF, patients are randomized to either sham or PVI using the pentaspline PF ablation catheter. The 2 co-primary outcomes are (1) freedom from recurrent AF, atrial tachycardia, or atrial flutter lasting >30 seconds, assessed as time to first recurrence (post 2-month blanking); and (2) change in quality of life according to the AFEQT score at 6-month post-ablation, compared between groups. Cross-over is permitted for patients with significant symptom worsening according to pre-specified rules. Key secondary outcomes include AF burden at 6 months, and differences in the Hospital Anxiety and Depression Scale, compared between groups. RESULTS: Enrollment in the study was initiated in September 2023. As of January 2025, 50 patients have been enrolled. Results are expected by the end of 2025. CONCLUSION: This study compares PVI using PF energy to a sham procedure. The study will assess the effect of PVI on AF recurrences and quality of life. TRIAL REGISTRATION NUMBER: NCT02426944.

Cardiocenter 3rd Faculty of Medicine Charles University Prague and University Hospital Kralovske Vinohrady Prague Czech Republic

Cardiocenter Department of Cardiology Na Homolce Hospital Prague Czech Republic

Department of Anesthesiology Charles University Prague and University Hospital Kralovske Vinohrady Prague Czech Republic

Department of Statistical Analyses Prague University of Economics and Business Prague Czech Republic

Helmsley Electrophysiology Center Mount Sinai Fuster Heart Hospital Icahn School of Medicine at Mount Sinai New York New York

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Packer D.L., Mark D.B., Robb R.A., et al. Effect of catheter ablation vs antiarrhythmic drug therapy on mortality, stroke, bleeding, and cardiac arrest among patients with atrial fibrillation: the CABANA randomized clinical trial. JAMA. 2019;321:1261–1274. PubMed PMC

Wilber D.J., Pappone C., Neuzil P., et al. Comparison of antiarrhythmic drug therapy and radiofrequency catheter ablation in patients with paroxysmal atrial fibrillation: a randomized controlled trial. JAMA. 2010;303:333–340. PubMed

Piccini J.P., Lopes R.D., Kong M.H., Hasselblad V., Jackson K., Al-Khatib S.M. Pulmonary vein isolation for the maintenance of sinus rhythm in patients with atrial fibrillation: a meta-analysis of randomized, controlled trials. Circ Arrhythm Electrophysiol. 2009;2:626–633. PubMed

Wazni O.M., Marrouche N.F., Martin D.O., et al. Radiofrequency ablation vs antiarrhythmic drugs as first-line treatment of symptomatic atrial fibrillation: a randomized trial. JAMA. 2005;293:2634–2640. PubMed

Andrade J.G., Wells G.A., Deyell M.W., et al. Cryoablation or drug therapy for initial treatment of atrial fibrillation. N Engl J Med. 2021;384:305–315. PubMed

Turagam M.K., Garg J., Whang W., et al. Catheter ablation of atrial fibrillation in patients with heart failure: a meta-analysis of randomized controlled trials. Ann Intern Med. 2019;170:41–50. PubMed

Olshansky B. Placebo and nocebo in cardiovascular health: implications for healthcare, research, and the doctor-patient relationship. J Am Coll Cardiol. 2007;49:415–421. PubMed

Bakris G.L., Townsend R.R., Liu M., et al. Impact of renal denervation on 24-hour ambulatory blood pressure: results from SYMPLICITY HTN-3. J Am Coll Cardiol. 2014;64:1071–1078. PubMed

Syed M., Osman M., Alhamoud H., et al. The state of renal sympathetic denervation for the management of patients with hypertension: a systematic review and meta-analysis. Catheter Cardiovasc Interv. 2021;97:E438–E445. PubMed PMC

Maron D.J., Hochman J.S., Reynolds H.R., et al. Initial invasive or conservative strategy for stable coronary disease. N Engl J Med. 2020;382:1395–1407. PubMed PMC

Al-Lamee R., Thompson D., Dehbi H.M., et al. Percutaneous coronary intervention in stable angina (ORBITA): a double-blind, randomised controlled trial. Lancet. 2018;391:31–40. PubMed

Reddy V.Y., Dukkipati S.R., Neuzil P., et al. Pulsed field ablation of paroxysmal atrial fibrillation: 1-year outcomes of IMPULSE, PEFCAT, and PEFCAT II. JACC Clin Electrophysiol. 2021;7:614–627. PubMed

Dulai R., Sulke N., Freemantle N., et al. Pulmonary vein isolation vs sham intervention in symptomatic atrial fibrillation: the SHAM-PVI randomized clinical trial. JAMA. 2024;332:1165–1173. PubMed PMC

Spertus J., Dorian P., Bubien R., et al. Development and validation of the Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT) Questionnaire in patients with atrial fibrillation. Circ Arrhythm Electrophysiol. 2011;4:15–25. PubMed

Freeman J.V., Simon D.N., Go A.S., et al. Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) investigators and patients. Association between atrial fibrillation symptoms, quality of life, and patient outcomes: results from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) Circ Cardiovasc Qual Outcomes. 2015;8:393–402. PubMed

Holmes D.N., Piccini J.P., Allen L.A., et al. Defining clinically important difference in the atrial fibrillation effect on quality-of-life score. Circ Cardiovasc Qual Outcomes. 2019;12 PubMed

Blomström-Lundqvist C., Gizurarson S., Schwieler J., et al. Effect of catheter ablation vs antiarrhythmic medication on quality of life in patients with atrial fibrillation: the CAPTAF randomized clinical trial. JAMA. 2019;321:1059–1068. PubMed PMC

Bjelland I., Dahl A.A., Haug T.T., Neckelmann D. The validity of the Hospital Anxiety and Depression Scale. An updated literature review. J Psychosom Res. 2002;52:69–77. PubMed

Bang H., Ni L., Davis C.E. Assessment of blinding in clinical trials. Control Clin Trials. 2004;25:143–156. PubMed

Spiegelhalter D.J., Abrams K.R., Myles J.P. John Wiley & Sons; Chichester, United Kingdom: 2024. Bayesian Approaches to Clinical Trials and Health-Care Evaluation.

Zhou T., Ji Y. On Bayesian sequential clinical trial designs. N Engl J Stat Data Sci. 2024;2:136–151.

Mandrola J., Althouse A.D., Foy A., Bhatt D.L. Adaptive trials in cardiology: some considerations and examples. Can J Cardiol. 2021;37:1428–1437. PubMed

Reddy V.Y., Gerstenfeld E.P., Natale A., et al. Pulsed field or conventional thermal ablation for paroxysmal atrial fibrillation. N Engl J Med. 2023;389:1660–1671. PubMed

Giovagnoli A. The Bayesian design of adaptive clinical trials. Int J Environ Res Public Health. 2021;18:530. PubMed PMC

Chevret S. Bayesian adaptive clinical trials: a dream for statisticians only? Stat Med. 2012;31:1002–1013. PubMed

Gelman A., Carlin J.B., Stern H.S., Dunson D.B., Vehtari A., Rubin D.B. 3rd ed. Chapman & Hall/CRC; New York, NY: 2013. (Bayesian Data Analysis).

Broglio K.R., Connor J.T., Berry S.M. Not too big, not too small: a goldilocks approach to sample size selection. J Biopharm Stat. 2014;24:685–705. PubMed

Al-Kaisey A.M., Parameswaran R., Bryant C., et al. Atrial fibrillation catheter ablation vs medical therapy and psychological distress: a randomized clinical trial. JAMA. 2023;330:925–933. PubMed PMC

Gönen M., Johnson W.O., Lu Y., Westfall P.H. The Bayesian two-sample t test. Am Stat. 2005;59:252–257.

Zobrazit více v PubMed

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