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

Overview

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%).

Interventions

• Device Pulmonary Vein Isolation
  PVI
• Procedure Atrioventricular Node Ablation
  AVJ
• Drug Pharmacological Rate Control
  Rate

Primary outcome measures

• Composite of cardiovascular mortality, stroke, and total number of heart failure events [Time frame: 5 years]

Secondary outcome measures (12)

• Composite of ejection fraction, distance on the 6-minute walk test, and QOL score [Time frame: 1 year]
• Time to death from any cause [Time frame: 5 years]
• Time to death from cardiovascular cause [Time frame: 5 years]
• Number of Participants with unplanned emergency department visit or all-cause hospitalisation [Time frame: 5 years]
• Number of Participants with unplanned emergency department visit or hospitalisation for heart failure [Time frame: 5 years]
• Number of Participants with unplanned emergency department visit or hospitalisation for atrial fibrillation or arrhythmia [Time frame: 5 years]
• Number of Participants with heart failure event [Time frame: 5 years]
• Change in Quality of Life from baseline [Time frame: 5 years]
• Number of Participants with ischemic stroke or systemic arterial emboli [Time frame: 5 years]
• Number of Participants with new onset cognitive dysfunction [Time frame: 5 years]
• Change in left ventricular function (ejection fraction) [Time frame: 5 years]
• Time to first appropriate and inappropriate ICD intervention (ATP or ICD shock) [Time frame: 5 years]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07238452 · H24-02147

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗