A randomized sham-controlled study of pulmonary vein isolation in symptomatic atrial fibrillation (The SHAM-PVI study): Study design and rationale

Rajdip Dulai, Stephen S Furniss, Neil Sulke, Nick Freemantle, Pier D Lambiase, David Farwell, Neil T Srinivasan, Stuart Tan, Nikhil Patel, Adam Graham, Rick A Veasey, Rajdip Dulai, Stephen S Furniss, Neil Sulke, Nick Freemantle, Pier D Lambiase, David Farwell, Neil T Srinivasan, Stuart Tan, Nikhil Patel, Adam Graham, Rick A Veasey

Abstract

Introduction: Pulmonary vein (PV) isolation has been shown to reduce atrial fibrillation (AF) burden and symptoms in patients. However, to date previous studies have been unblinded raising the possibility of a placebo effect to account for differences in outcomes.

Hypothesis & methods: The objective of this study is to compare PV isolation to a sham procedure in patients with symptomatic AF. The SHAM-PVI study is a double blind randomized controlled clinical trial. 140 patients with symptomatic paroxysmal or persistent AF will be randomized to either PV isolation (with cryoballoon ablation) or a sham procedure (with phrenic nerve pacing). All patients will receive an implantable loop recorder. The primary outcome is total AF burden at 6 months postrandomisation (excluding the 3 month blanking period). Key secondary outcomes include (1) time to symptomatic and asymptomatic atrial tachyarrhythmia (2) total atrial tachyarrhythmia episodes and (3) patient reported outcome measures.

Results: Enrollment was initiated in January 2020. Through April 2023 119 patients have been recruited. Results are expected to be disseminated in 2024.

Conclusion: This study compares PV isolation using cryoablation to a sham procedure. The study will estimate the effect of PV isolation on AF burden.

Keywords: ablation; atrial fibrillation; catheter ablation; cryoablation; placebo; pulmonary vein isolation; sham.

Conflict of interest statement

N. S. is a trustee of Eastbourne Cardiology Research Charity Fund. PDL receives research grants from Medtronic, Abbott, and Boston Scientific. N. F. receives consulting fees from ALK, Sanofi Aventis, Gedeon Richter, Abbott, Galderma, AstraZeneka, Ipsen, Vertex, Thea, Novo Nordisk, Aimmune and sits on a DSMB for Orion. NTS receives research grants from Abbott. R. A. V. receives research grants from Medtronic. The remaining authors declare no conflict of interest.

© 2023 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.

Figures

Figure 1
Figure 1
The SHAM PVI study timeline. One hundred fourty patients will be enrolled and randomized in a 1:1 ratio to receive cryoablation or a sham procedure. All patients will receive an ILR. Outcomes will be assessed at 3 and 6 months post‐randomisation with the first 3 months constituting the blanking period. DCCV, Direct current cardioversion; ILR, implantable loop recorder.

References

    1. Krijthe BP, Kunst A, Benjamin EJ, et al. Projections on the number of individuals with atrial fibrillation in the european union, from 2000 to 2060. Eur Heart J. 2013;34(35):2746‐2751.
    1. Mark DB, Anstrom KJ, Sheng S, et al. Effect of catheter ablation vs medical therapy on quality of life among patients with atrial fibrillation: the CABANA randomized clinical trial. JAMA. 2019;321:1275‐1285.
    1. Packer DL, Mark DB, Robb RA, et al. Effect of catheter ablation vs antiarrhythmic drug therapy on mortality, stroke, bleeding, and cardiac arrest among patients with atrial fibrillation. JAMA. 2019;321(13):1261‐1274.
    1. Al‐Lamee R, Thompson D, Dehbi HM, et al. Percutaneous coronary intervention in stable angina (ORBITA): a double‐blind, randomised controlled trial. Lancet. 2018;391:31‐40.
    1. Bhatt DL, Kandzari DE, O'Neill WW, et al. A controlled trial of renal denervation for resistant hypertension. N Engl J Med. 2014;370(15):1393‐1401.
    1. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation. JACC. 2014;64(21):e1‐e76.
    1. Mittal S, Rogers J, Sarkar S, et al. Real‐world performance of an enhanced atrial fibrillation detection algorithm in an insertable cardiac monitor. Heart Rhythm. 2016;13(8):1624‐1630.
    1. Sanders P, Pürerfellner H, Pokushalov E, et al. Performance of a new atrial fibrillation detection algorithm in a miniaturized insertable cardiac monitor: results from the reveal LINQ usability study. Heart Rhythm. 2016;13(7):1425‐1430.
    1. Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J. 2016;37:2893‐2962.
    1. Marrouche NF, Brachmann J, Andresen D, et al. Catheter ablation for atrial fibrillation with heart failure. N Engl J Med. 2018;378(5):417‐427.
    1. Ozeke O, Cay S, Ozcan F, Topaloglu S, Aras D. The placebo effect in atrial fibrillation ablation: placebo or pseudo‐placebo effect? Pacing Clin Electrophysiol. 2018;41:872‐873.
    1. Ozeke O, Cay S, Ozcan F, Baser K, Topaloglu S, Aras D. Similarities between the renal artery and pulmonary vein denervation trials: do we have to use sham procedures for atrial fibrillation catheter ablation trials? Int J Cardiol. 2016;211:55‐57.
    1. Al‐Khatib SM, Benjamin EJ, Buxton AE, et al. Research needs and priorities for catheter ablation of atrial fibrillation: a report from a national heart, lung, and blood institute virtual workshop. Circulation. 2020;141:482‐492.
    1. Veasey R. Catheter ablation in symptomatic atrial fibrillation—full text view— [Internet]. Accessed June 2, 2023.
    1. Wachter R. Pulmonary vein isolation versus sham‐pulmonary vein isolation for symptomatic relief in patients with atrial fibrillation—a randomised trial—PVI‐SHAM‐AF [Internet]. . Report No.: NCT05119231. Accessed May 31, 2023.
    1. Freedman MD, Somberg JC. Pharmacology and pharmacokinetics of amiodarone. The Journal of Clinical Pharmacology. 1991;31(11):1061‐1069.
    1. 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(11):1059‐1068.
    1. Cosedis Nielsen J, Johannessen A, Raatikainen P, et al. Radiofrequency ablation as initial therapy in paroxysmal atrial fibrillation. N Engl J Med. 2012;367(17):1587‐1595.
    1. Verma A, Jiang C, Betts TR, et al. Approaches to catheter ablation for persistent atrial fibrillation. N Engl J Med. 2015;372(19):1812‐1822.

Source: PubMed

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

3
Sottoscrivi