Cardiac resynchronization therapy with or without atrioventricular node ablation in atrial fibrillation: the CAAN-AF trial

Prashanthan Sanders; Jonathan P Ariyaratnam; Martin K Stiles; Alexis Puvrez; Stephen J Nicholls; Walter P Abhayaratna; Mark J Perrin; Jeff Alison; Rajeev K Pathak; Anand Ganesan; Vincent Paul; Stuart P Thomas; Gijo Thomas; Melissa E Middeldorp; Elnaz Shahmohamadi; Adrian D Elliott; Robert Park; Haris Haqqani; Dean Boddington; Peter M Kistler; Paul Martin; Raymond W Sy; Stephan Willems; Paul Stobie; Matthew Webber; Gerald Kaye; Paul MacIntyre; Bobby John; Daniel Steven; Azlan Hussin; Suresh Singarayar; David Whalley; David O'Donnell; Nigel Lever; Rajiv Mahajan; Daniel Ninio; John Amerena; Adrian Esterman; Derek P Chew; Matthew Worthley; Andrew Tonkin; Carmine G De Pasquale; Jonathan M Kalman

doi:10.1093/eurheartj/ehag206

Cardiac resynchronization therapy with or without atrioventricular node ablation in atrial fibrillation: the CAAN-AF trial

Eur Heart J. 2026 Apr 16:ehag206. doi: 10.1093/eurheartj/ehag206. Online ahead of print.

Authors

Prashanthan Sanders^{1

2}, Jonathan P Ariyaratnam^{1

2}, Martin K Stiles³, Alexis Puvrez¹, Stephen J Nicholls⁴, Walter P Abhayaratna⁵, Mark J Perrin⁶, Jeff Alison³, Rajeev K Pathak⁷, Anand Ganesan⁸, Vincent Paul⁹, Stuart P Thomas¹⁰, Gijo Thomas¹, Melissa E Middeldorp^{1

2}, Elnaz Shahmohamadi¹, Adrian D Elliott^{1

2}, Robert Park¹¹, Haris Haqqani¹², Dean Boddington¹³, Peter M Kistler¹⁴, Paul Martin¹⁵, Raymond W Sy¹⁶, Stephan Willems¹⁷, Paul Stobie¹⁸, Matthew Webber¹⁹, Gerald Kaye²⁰, Paul MacIntyre²¹, Bobby John²², Daniel Steven²³, Azlan Hussin²⁴, Suresh Singarayar²⁵, David Whalley²⁶, David O'Donnell²⁷, Nigel Lever²⁸, Rajiv Mahajan^{1

29}, Daniel Ninio², John Amerena⁶, Adrian Esterman³⁰, Derek P Chew^{4

8}, Matthew Worthley^{1

2}, Andrew Tonkin³¹, Carmine G De Pasquale⁸, Jonathan M Kalman³²

Affiliations

¹ Centre for Heart Rhythm Disorders, Adelaide University, Adelaide, South Australia, Australia.
² Department of Cardiology, Central Adelaide Local Health Network, Adelaide, South Australia, Australia.
³ Waikato Clinical School, University of Auckland, Hamilton, New Zealand.
⁴ Victorian Heart Institute, Monash University, Melbourne, Victoria, Australia.
⁵ Department of Medicine, Canberra Hospital and the Australian National University, Canberra, Australian Capital Territory, Australia.
⁶ Department of Cardiology, University Hospital, Geelong, Victoria, Australia.
⁷ Canberra Heart Rhythm, Canberra, Australian Capital Territory, Australia.
⁸ Department of Cardiology, Flinders University and Flinders Medical Centre, Adelaide, South Australia, Australia.
⁹ Department of Cardiology, Fiona Stanley Hospital, Perth, Western Australia, Australia.
¹⁰ Department of Cardiology, Westmead Hospital, Sydney, New South Wales, Australia.
¹¹ Department of Cardiology, Gold Coast Hospital, Gold Coast, Queensland, Australia.
¹² Department of Cardiology, Prince Charles Hospital, Brisbane, Queensland, Australia.
¹³ Department of Cardiology, Tauranga Hospital, Tauranga, New Zealand.
¹⁴ Department of Cardiology, Alfred Hospital, Melbourne, Victoria, Australia.
¹⁵ Department of Cardiology, Royal Brisbane Hospital, Brisbane, Queensland, Australia.
¹⁶ Department of Cardiology, Royal Prince Alfred Hospital & Concord Repatriation General Hospital, Sydney, New South Wales, Australia.
¹⁷ Department of Cardiology, Asklepios Clinic St.Georg, Hamburg, Germany.
¹⁸ Department of Cardiology, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia.
¹⁹ Department of Cardiology, Capital & Coast Wellington Hospital, Wellington, New Zealand.
²⁰ Department of Cardiology, Princess Alexandria Hospital, Brisbane, Queensland, Australia.
²¹ Department of Cardiology, Royal Hobart Hospital, Hobart, Tasmania, Australia.
²² Department of Cardiology, Townsville Hospital, Townsville, Queensland, Australia.
²³ Department of Electrophysiology, University Hospital Cologne, Cologne, Germany.
²⁴ Department of Cardiology, National Heart Institute, Kuala Lumpur, Malaysia.
²⁵ Department of Cardiology, Prince of Wales Hospital, Sydney, New South Wales, Australia.
²⁶ RDepartment of Cardiology, oyal North Shore Hospital, Sydney, New South Wales, Australia.
²⁷ Department of Cardiology, Austin Health, Melbourne, Victoria, Australia.
²⁸ Department of Cardiology, Auckland City Hospital, Auckland, New Zealand.
²⁹ Department of Cardiology, Lyell McEwin Hospital, Adelaide, South Australia, Australia.
³⁰ College of Health, Adelaide University, Adelaide, South Australia, Australia.
³¹ Department of Epidemiology and Preventative Medicine, Monash University, Melbourne, Victoria, Australia.
³² Department of Cardiology, Melbourne Health and University of Melbourne, Melbourne, Victoria, Australia.

PMID: 41985940
DOI: 10.1093/eurheartj/ehag206

Abstract

Background and aims: Patients with heart failure with reduced ejection fraction (HFrEF) derive less benefit from cardiac resynchronization therapy (CRT) if they have coexisting atrial fibrillation (AF). Observational data suggest that atrioventricular node ablation (AVNA) may enhance CRT efficacy in this population. This trial aimed to evaluate the effect of AVNA compared with medical rate control therapy (MRCT) on CRT outcomes in patients with HFrEF and permanent AF.

Methods: The CAAN-AF trial was an international, prospective, multicentre, randomized controlled trial evaluating the impact of AVNA in patients with HFrEF, permanent AF, and CRT-defibrillators (CRT-D). Participants were randomly assigned (1:1) to AVNA or MRCT targeting a resting heart rate <90 bpm. All participants received device optimization. The primary endpoint was a composite of all-cause mortality and nonfatal heart failure events. Secondary endpoints included cardiovascular mortality, unplanned hospitalizations, ventricular arrhythmias requiring device therapy, 6-min walk distance (6MWD), and quality of life.

Results: With early termination of the trial due to futility, a total of 143 patients were randomized (67 to AVNA, 76 to MRCT). Baseline characteristics were similar across groups. No significant difference was found in the primary endpoint [47 vs. 46 events; incident rate ratio (IRR), 1.16; 95% confidence interval (CI), 0.60-2.24]. Secondary outcomes, including cardiovascular mortality (odds ratio, 1.93; 95% CI 0.60-6.20), unplanned hospitalizations (IRR, 1.01; 95% CI 0.71-1.74), ventricular arrhythmias requiring device therapy (IRR, 0.68; 95% CI 0.17-2.63), 6MWD, and SF-36 scores, also showed no significant differences.

Conclusions: This randomized trial of patients with permanent AF and CRT-D found no evidence of a reduction in all-cause mortality and nonfatal heart failure events with AVNA compared with MRCT.

Trial registration: NCT01522898.

Keywords: AV node ablation; Cardiac resynchronization; Heart failure; Rate control.

Associated data

ClinicalTrials.gov/NCT01522898

Grants and funding

1080920/National Health and Medical Research