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NCT Number: NCT07238452

Optimising Pacing Therapy, Integrated Medical Therapy, and Catheter AbLation for Atrial Fibrillation in Heart Failure Trial

Atrial Fibrillation (AF) and Heart Failure (HF) are colliding global cardiovascular epidemics, individually impairing quality of life and cardiac performance, as well as increasing the risk of hospitalisation and mortality. When AF and HF co-exist, disease progression accelerates and the adverse outcomes are magnified, leading to incrementally higher morbidity, mortality, and healthcare expenditure. The management of AF has been dichotomised into the restoration and maintenance of sinus rhythm ("Rhythm control") or acceptance of AF with control of the ventricular response ("Rate control"). Previous studies suggested that pharmacologic rhythm control and pharmacologic rate control confer similar survival and morbidity outcomes in patients with significant left ventricular dysfunction. Recognising the limitations of pharmacotherapy, more recent studies have examined the utility of catheter ablation procedures, either designed to restore and maintain sinus rhythm (e.g., catheter-based pulmonary vein isolation) or control the ventricular response (e.g., pacemaker implantation in combination with catheter ablation of the atrioventricular junction). Compared to pharmacotherapy, these studies have suggested that catheter ablation may provide sustained improvements in quality of life, decreased hospitalisation and, potentially, improved survival for patients with co-existing AF and HF. However, these studies were performed prior to the modern era of quadruple LV enhancing therapy (beta-blocker, an angiotensin receptor-neprilysin inhibitor, mineralocorticoid receptor antagonist, and an SGLT2 inhibitor). The true impact of catheter-based interventions, and thus the optimal management of AF for patients with co-existing HF is not known. The investigators propose a randomised controlled trial to definitively answer the question regarding the optimal invasive treatment of AF in patients with heart failure with reduced ejection fraction (HFrEF - LVEF ≤ 40%).

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Key information

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age of 18 years or older on the date of Informed Consent,
  • Atrial fibrillation,
  • Left ventricular ejection fraction of 40% or less, measured within 6 months of enrollment,
  • Receiving stable foundational HF quadruple therapy at maximally tolerated dose,
  • BNP ≥ 100 pg/mL (NT-proBNP ≥ 400 pg/ml), measured within 1 month of randomisation.

Exclusion criteria

  • Anticipated life expectancy less than one year from the consent date,
  • Continuous atrial fibrillation of >1 year in duration,
  • Left atrial anteroposterior diameter > 6 cm, volume > 100 mL, or volume index > 60 mL/m2,
  • Previous left atrial ablation or left atrial surgery,
  • The presence of a percutaneous left atrial appendage closure device,
  • Uncontrolled hypo- or hyperthyroidism,
  • Subject known to be pregnant or breast-feeding,
  • Contraindication to oral anticoagulation therapy,
  • Left atrial myxoma,
  • Myocardial infarction or percutaneous coronary intervention within 3-months of consent,
  • History of, or anticipated to undergo heart transplant, ventricular assist device insertion, or mitral or tricuspid valve repair or replacement within 3-months of the consent date.

Treatment and study plan

Pulmonary vein isolation

Device

PVI

Atrioventricular Node Ablation

Procedure

AVJ

Pharmacological Rate Control

Drug

Rate

Primary outcomes

  1. Composite of cardiovascular mortality, stroke, and total number of heart failure events

    Time frame: 5 years

Secondary outcomes

  1. Composite of ejection fraction, distance on the 6-minute walk test, and QOL score

    Time frame: 1 year

  2. Time to death from any cause

    Time frame: 5 years

  3. Time to death from cardiovascular cause

    Time frame: 5 years

  4. Number of Participants with unplanned emergency department visit or all-cause hospitalisation

    Time frame: 5 years

  5. Number of Participants with unplanned emergency department visit or hospitalisation for heart failure

    Time frame: 5 years

  6. Number of Participants with unplanned emergency department visit or hospitalisation for atrial fibrillation or arrhythmia

    Time frame: 5 years

  7. Number of Participants with heart failure event

    Time frame: 5 years

  8. Change in Quality of Life from baseline

    Time frame: 5 years

  9. Number of Participants with ischemic stroke or systemic arterial emboli

    Time frame: 5 years

  10. Number of Participants with new onset cognitive dysfunction

    Time frame: 5 years

  11. Change in left ventricular function (ejection fraction)

    Time frame: 5 years

  12. Time to first appropriate and inappropriate ICD intervention (ATP or ICD shock)

    Time frame: 5 years

Study contacts

Contact information is provided by the study sponsor or research team.

Jason Andrade

CONTACT

[email protected]

6048755069

Sponsors and collaborators

Lead sponsor

University of British Columbia

Other

Registry information

Acronym: OPTIMAL AF-HF

Important dates

Study start
2025
Primary completion
2032
Study completion
2033
First posted
Nov 20, 2025
Registry last updated
Nov 28, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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