Sham-Controlled Trials and the Future of Electrophysiology: Reflections on SHAM-PFA

Mohammed Mhanna; John Mandrola; Brian Olshansky

doi:10.1016/j.hroo.2025.09.017

September 1, 2025Heart Rhythm O2Open Access

Sham-Controlled Trials and the Future of Electrophysiology: Reflections on SHAM-PFA

View Full Paper

Ask AI

Bookmark

Share

Why the study?

Does pulsed field ablation improve symptomatic and arrhythmia-related outcomes compared to a sham procedure in patients with atrial fibrillation?

Structured PICO

Does pulsed field ablation improve symptomatic and arrhythmia-related outcomes compared to a sham procedure in patients with atrial fibrillation?

P

Population

Patients with atrial fibrillation (AF), including those with comorbidities such as obesity, metabolic syndrome, and sleep apnea

I

Intervention

Pulsed field ablation (PFA) and catheter ablation (CA) with pulmonary vein isolation (PVI)

C

Comparator

Sham procedure

O

Outcome

Symptomatic and arrhythmia-related benefits (binary primary endpoints, quality of life, and arrhythmia recurrence/burden)

Limitations

Inadvertent unblinding risk due to the ubiquity of personal electrocardiographic devices for patient self-monitoring
Limited generalizability because consenting to an invasive sham procedure with a 6-month blinded phase requires a highly motivated, health-literate population
Comorbidities such as obesity, metabolic syndrome, and sleep apnea may dilute or misclassify treatment effects without careful stratification or adjustment
Crossovers from sham to active therapy reduce statistical power and diminish between-group differences
Allowing antiarrhythmic drugs and cardioversion during the blanking period complicates attribution of success to ablation alone
Design choices in SHAM-PFA such as binary primary endpoints, pragmatic rhythm management allowances, and optimistic power assumptions

Implication

This editorial highlights the critical importance and methodological challenges of sham-controlled trials, specifically the SHAM-PFA study, in distinguishing the true physiological benefits of pulsed field ablation for atrial fibrillation from powerful placebo and expectation effects.

Abstract

No abstract yet. The journal hasn't published one we can show.

Discussion

No takes yet. Share an insight, caveat, or question.

Cite This Study

Mhanna et al. (2025) studied this question.

synapsesocial.com/papers/6a70a571660549caf2c5449a https://doi.org/10.1016/j.hroo.2025.09.017

View Full Paper

Ask AI

Bookmark

Share

Sham-Controlled Trials and the Future of Electrophysiology: Reflections on SHAM-PFA

Structured PICO

Limitations

Implication

Abstract

Discussion

Cite This Study

Sham-Controlled Trials and the Future of Electrophysiology: Reflections on SHAM-PFA

Structured PICO

Limitations

Implication

Abstract

Discussion

Cite This Study

Keep reading

Keep reading