Heart Rate Regularization in Atrial Fibrilation and Heart Failure (PACE-FIB)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure; Atrial Fibrillation
• Intervention / Treatment: Device: Conduction System Pacing (pacemaker implantation)

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.

• Study Type: Interventional
• Enrollment (Estimated): 334
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Daniel Rodríguez Muñoz, MD, PhD; Phone Number: +34 917792742; Email: danielantonio.rodriguez@salud.madrid.org
• Study Contact Backup: Name: Ana Isabel Castillo Varón, PhD; Phone Number: +34 917792742; Email: aicastillo.imas12@h12o.es

Study Locations

• Spain
  • Madrid
    • Madrid, Madrid, Spain, 28041
      • Recruiting
      • Hospital Universitario 12 de Octubre
      • Contact: Daniel Rodríguez Muñoz, MD, PhD; Phone Number: +34 917792742; Email: danielantonio.rodriguez@salud.madrid.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Conduction System Pacing and AV node ablation; Atrioventricular node ablation and subsequent conduction system pacing	Device: Conduction System Pacing (pacemaker implantation); Conduction System Pacing (pacemaker implantation) and Atrioventricular node ablation; Other Names: Atrioventricular node ablation
No Intervention: Medical treatment for rate control of AF; Pharmacological rate control based on clinical practice guidelines

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite primary endpoint	All-cause mortality, heart failure hospitalisation and worsening heart failure	36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality	Mortality due to any cause	36 months
Cardiovascular mortality	Mortality due to cardiovascular causes	36 months
Heart failure hospitalization	Hospitalization due to heart failure decompensation	36 months
Worsening heart failure	An episode of heart failure diagnosed based on symptoms, signs, imaging and analytical criteria that requires unplanned medical attention and intravenous diuretic therapy	36 months
Unplanned cardiovascular hospitalisation	Unplanned cardiovascular hospitalisation	36 months
Left ventricular ejection fraction	assessed by the Simpson method	12 months
Change in left ventricular dimension	end-diastolic and end-systolic volumes	12 months
Change in degree of mitral regurgitation	Change in degree of mitral regurgitation	12 months
Change in functional status	Assessed by New York Heart Association (NYHA) on a I to IV scale (I being better functional status and IV worst possible functional status)	36 months
Major adverse events during or in the first 30-days following pacemaker implantation	Percentage of patients suffering one of the following: death, cardiac tamponade, perforation requiring cardiac surgery, pneumothorax, haemothorax, device infection, endocarditis, lead displacement requiring re-intervention	30 days
Major adverse events during or in the first 30-days following atrioventricular node ablation	Percentage of patients suffering one of the following: death, cardiac tamponade, perforation requiring cardiac surgery, puncture site vascular complications requiring vascular surgery	30 days

Collaborators and Investigators

• Sponsor: Daniel Rodríguez Muñoz
• Collaborators: Sociedad Castellana de Cardiologia
• Investigators: Study Chair: Fernando Arribas Ynsaurriaga, MD, PhD, Hospital Universitario 12 de Octubre

Study record dates

Study Major Dates

• Study Start (Actual): April 29, 2022
• Primary Completion (Estimated): July 31, 2030
• Study Completion (Estimated): September 1, 2030

Study Registration Dates

• First Submitted: August 26, 2021
• First Submitted That Met QC Criteria: August 26, 2021
• First Posted (Actual): August 31, 2021

Study Record Updates

• Last Update Posted (Estimated): September 9, 2025
• Last Update Submitted That Met QC Criteria: September 2, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: atrial fibrillation;; heart failure;; conduction system pacing;; heart rate regularization
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Pathological Conditions, Signs and Symptoms; Heart Failure; Atrial Fibrillation
• Other Study ID Numbers: PACE-FIB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No