Heart Failure With Reduced Ejection FractionPhase 3OPTIMal AF-HFNCT07238452
Optimal PharmacoTherapy and Invasive Management of Atrial Fibrillation in Patients With Heart Failure
A Phase 3 study testing Pulmonary Vein Isolation in people with Heart Failure With Reduced Ejection Fraction and Atrial Fibrillation (AF), run by University of British Columbia.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Heart Failure With Reduced Ejection Fraction, Atrial Fibrillation (AF)
- What is being tested?
- Pulmonary Vein Isolation
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,050 participants
- Where
- No sites listed yet
- Study dates
- 1 Nov 2026to 1 Jan 2033
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age of 18 years or older on the date of Informed Consent,
- Atrial fibrillation (paroxysmal, persistent or long-standing persistent)
- Left Ventricular Ejection Fraction of 40% or less, measured within 6 months of enrollment,
- Receiving (current/planned uptitration) guideline directed medical therapy for heart failure,
- Receiving stroke prevention therapy, initiated according to guidelines for treatment of AF
Who cannot join
- Anticipated life expectancy less than one year from the consent date,
- Continuous atrial fibrillation of > 2 years in duration at time of enrollment
- Note: AF duration does not refer to time from index AF diagnosis but the duration of the current AF episode,
- Previous left atrial ablation or left atrial surgery,
- Left atrial dimension greater than 6 cm,
- The presence of a percutaneous left atrial appendage closure device,
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- Uncontrolled hypo- or hyperthyroidism,
- Subject known to be pregnant or breast-feeding,
- Contraindication to oral anticoagulation therapy,
- Left atrial myxoma,
- Type I myocardial infarction or percutaneous coronary intervention within 1-month of consent,
- Requirement for dialysis due to terminal renal failure,
- 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,
- Participation in another investigational drug or device study
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
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 is 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 designed to restore and maintain sinus rhythm (e.g., catheter-based pulmonary vein isolation). Studies have suggested that catheter ablation procedures may provide sustained improvements in quality of life, decreased hospitalisation and, potentially, improved survival for patients with co-existing AF and HF, when compared to pharmacotherapy. However, significant limitations in these small trials have limited their impact on clinical practice. We propose a randomised controlled trial to definitively answer the question regarding the optimal treatment of AF in patients with heart failure with reduced ejection fraction (HFrEF), specifically aiming to determine if catheter ablation can reduce death, stroke, and heart failure events.
- Being tested
- Pulmonary Vein Isolation, Pharmacological Rate Control
- Keywords
- Atrial fibrillation, heart failure, cardiomyopathy, catheter ablation, pulsed field ablation, conduction system pacing, cardiac resyncronization therapy
- Medical subject headings
- Atrial Fibrillation, Heart Failure, Cardiomyopathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pulmonary Vein IsolationDevice
PVI
Pharmacological Rate ControlDrug
Rate
| Study group | Role | What they receive |
|---|---|---|
| Standard Therapy | Active comparator | Patients randomised to standard therapy will receive evidence-based beta-blockers (extended-release metoprolol succinate, bisoprolol, carvedilol), titrated to achieve a resting heart rate of <100 bpm during AF, in accordance with contemporary heart failure and atrial fibrillation guidelines. Further pharmacological management of AF will be left to the discretion of the treating teams, in accordance with contemporary guidelines. Programming of the pacemaker-defibrillator will be standardised based on contemporary best practices. Of note, for those where rhythm control is chosen, in the standard therapy group it would be conducted through cardioversion and/or medical treatment in accordance with contemporary guidelines. Receives: Drug: Pharmacological Rate Control |
| Catheter Ablation with The Goal of Sinus Rhythm Restoration (Pulmonary Vein Isolation) | Active comparator | Patients randomised to invasive rhythm control will undergo a percutaneous catheter ablation procedure using standardised techniques to achieve pulmonary vein isolation. The procedure will be performed with a pulsed-field energy ablation catheter. Circumferential lesions around the veins will be considered complete when spontaneous, associated PV potentials are no longer recorded by the multielectrode catheter (entrance block) and when exit block (dissociated spontaneous PV ectopy, and/or local PV capture without conduction from the pulmonary vein into the left atrium) has been demonstrated. Receives: Device: Pulmonary Vein Isolation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Composite of time to first cardiovascular mortality, stroke, or heart failure event
Measured: 5 years
Secondary outcomes (14)
Composite of all-cause mortality and urgent cardiovascular hospitalisations
Measured: 5 years
Time to death from any cause
Measured: 5 years
Time to death from cardiovascular cause
Measured: 5 years
Time to first, and number of unplanned emergency department visit or all-cause hospitalisation
Measured: 5 years
Time to first, and number of unplanned emergency department visit or hospitalisation for heart failure
Measured: 5 years
Time to first, and number of unplanned emergency department visit or hospitalisation for atrial fibrillation or arrhythmia
Measured: 5 years
Number of Participants with heart failure event
Measured: 5 years
Change in Quality of Life from baseline
Measured: 5 years
Number of Participants with ischemic stroke or systemic arterial emboli
Measured: 5 years
Number of Participants with new onset cognitive dysfunction
Measured: 5 years
Change in left ventricular function (ejection fraction), NT-proBNP, NYHA functional Class
Measured: 5 years
Change in distance on 6-minute walk test
Measured: 5 years
Time to first appropriate and inappropriate ICD intervention (ATP or ICD shock)
Measured: 5 years
Atrial fibrillation recurrence and atrial fibrillation burden
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2025
- Study start1 Nov 2026 (estimated)
- Primary completion1 Dec 2032 (estimated)
- Study completion1 Jan 2033 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart Failure With Reduced Ejection FractionStudies of the same condition, open and under way.
- More trials run by University of British ColumbiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 1,050 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of British Columbia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jason Andrade, University of British Columbia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07238452
- Sponsor's protocol ID
- H24-02147
- Acronym
- OPTIMal AF-HF
- Status last verified
- Oct 2026
- First submitted
- 27 May 2025
- Last updated
- 14 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Undecided: The decision to share IPD will be decided at a later dat by the academic steering committee.