Heart Rate Regularization in Atrial Fibrilation and Heart Failure

Heart Failure Clinical Trial

— PACE-FIB  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05029570
• Other study ID #: PACE-FIB
• Status: Recruiting
• Phase: N/A
• Start date: April 29, 2022
• Est. completion date: November 1, 2026

Study information

• Verified date: March 2023
• Source: Hospital Universitario 12 de Octubre
• Contact: Daniel Rodriguez Muñoz, MD, PhD
• Phone: +34 917792742
• Email: danielantonio.rodriguez[@]salud.madrid.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 334
• Est. completion date: November 1, 2026
• Est. primary completion date: November 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Atrial Fibrillation
• Heart Failure

Intervention

Device:
• Conduction System Pacing (pacemaker implantation)
Conduction System Pacing (pacemaker implantation) and Atrioventricular node ablation

Locations

Country	Name	City	State
Spain	Hospital Universitario 12 de Octubre	Madrid

Sponsors (2)

Lead Sponsor	Collaborator
Daniel Rodríguez Muñoz	Sociedad Castellana de Cardiologia

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Composite primary endpoint	All-cause mortality, heart failure hospitalisation and worsening heart failure	36 months
Secondary	All-cause mortality	Mortality due to any cause	36 months
Secondary	Cardiovascular mortality	Mortality due to cardiovascular causes	36 months
Secondary	Heart failure hospitalization	Hospitalization due to heart failure decompensation	36 months
Secondary	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
Secondary	Unplanned cardiovascular hospitalisation	Unplanned cardiovascular hospitalisation	36 months
Secondary	Left ventricular ejection fraction	assessed by the Simpson method	12 months
Secondary	Change in left ventricular dimension	end-diastolic and end-systolic volumes	12 months
Secondary	Change in degree of mitral regurgitation	Change in degree of mitral regurgitation	12 months
Secondary	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
Secondary	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
Secondary	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