Clinical trial NCT05029570: Heart Rate Regularization in Atrial Fibrilation and Heart Failure
Official title: Conduction System PACing and Atrioventricular Node Ablation in Patients With hEart Failure, Left Ventricular Ejection Fraction >40% and Permanent Atrial FIBrilation: the PACE-FIB Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Heart Failure
Atrial Fibrillation
Keywords: atrial fibrillation;
heart failure;
conduction system pacing;
heart rate regularization
Lead sponsor: Hospital Universitario 12 de Octubre
Sponsor class: OTHER
Collaborators: name: Sociedad Castellana de Cardiologia
First posted: 2021-08-31
Enrollment: 334
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Medical Device: Conduction System Pacing (pacemaker implantation)
Primary purpose: TREATMENT

Brief summary: The PACE-FIB trial is a multicentre, randomised, open-label clinical trial. Patients older than 18 years, with permanent AF, LVEF\>40%, average resting heart rate ≤ 110 beats per minute (bpm), at least one hospitalisation due to HF in the previous year and basal NT-proBNP level\>900 pg/ml will be randomised to either CSP and subsequent AV node ablation (intervention group) vs. pharmacologic rate control optimised according to clinical practice guidelines. The impact of both strategies on a composite primary endpoint of all-cause mortality, HF hospitalisation and worsening HF will be evaluated during a 36-month follow-up.

Detailed description: Permanent atrial fibrillation (AF) causes beat-to-beat heart rate irregularity, which has shown to decrease cardiac output. Observational data suggest that heart rate regularization through atrioventricular (AV) node ablation and pacemaker implantation improves outcomes in heart failure (HF) patients. However, no trials have been conducted to assess its potential benefit in HF and left ventricular ejection fraction (LVEF)\>40%, a population in whom treatment strategies effectively improving outcomes are scarce.

The goal of this trial is to assess the benefit of heart rate regularization through AV node ablation and conduction system pacing (CSP) in patients with permanent AF and HF with preserved or mildly reduced systolic function. The investigators hypothesize that heart rate regularization added to physiological pacing - preventing the deleterious effect of right apical pacing - reduces mortality, HF hospitalisations or worsening HF in these patients.

Eligibility criteria: Inclusion Criteria:

* Permanent atrial fibrillation
* At least one episode of hospitalisation due to heart failure in the previous 12 months.
* Left ventricular ejection fraction \> 40%
* Average resting heart rate ≤ 110 beats per minute
* NT-proBNP ≥ 900 pg/ml in the 30 days prior to enrollment
* Age ≥ 18 years
* Capacity to understand the nature of the study, legal ability and willingness to give informed consent.

Exclusion Criteria:

* Severe frailty (Clinical Frailty Scale ≥ 7) or comorbidity reducing life expectancy to \< 12 months.
* Acute heart failure at the time of enrollment or systolic blood pressure \< 80 mmHg in the absence of inotropic agents.
* Severe chronic kidney disease (estimated Glomerular Filtration Rate ≤ 20 ml/1,73 m2
* Severe mitral or aortic valvular heart disease
* Anaemia (Haemoglobin \< 10 g/dl)
* Morbid obesity (BMI ≥ 35)
* Severe Chronic Obstructive Pulmonary Disease (Gold ≥ 3)
* Presence of a different indication for pacing of implantable cardioverter-defibrillator (ICD)
* Obstructive hypertrophic cardiomyopathy
* Infiltrative cardiomyopathy (amyloidosis, sarcoidosis, Fabry disease, others)
* Simultaneous participation in a different trial

Primary outcomes:
measure: Composite primary endpoint
timeFrame: 36 months
Secondary outcomes:
measure: All-cause mortality
timeFrame: 36 months
measure: Cardiovascular mortality
timeFrame: 36 months
measure: Heart failure hospitalization
timeFrame: 36 months
measure: Worsening heart failure
timeFrame: 36 months
measure: Unplanned cardiovascular hospitalisation
timeFrame: 36 months
measure: Left ventricular ejection fraction
timeFrame: 12 months
measure: Change in left ventricular dimension
timeFrame: 12 months
measure: Change in degree of mitral regurgitation
timeFrame: 12 months
measure: Change in functional status
timeFrame: 36 months
measure: Major adverse events during or in the first 30-days following pacemaker implantation
timeFrame: 30 days
measure: Major adverse events during or in the first 30-days following atrioventricular node ablation
timeFrame: 30 days
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
Study officials:
affiliation: Hospital Universitario 12 de Octubre
name: Fernando Arribas Ynsaurriaga, MD, PhD
role: STUDY_CHAIR
References: