Heart Rate Regularization in Atrial Fibrilation and Heart Failure

Daniel Rodríguez Muñoz334 enrolled

Overview

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.

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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

334

Conditions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Composite primary endpoint

All-cause mortality, heart failure hospitalisation and worsening heart failure

Time frame: 36 months

Secondary Outcomes

All-cause mortality

Mortality due to any cause

Time frame: 36 months

Cardiovascular mortality

Mortality due to cardiovascular causes

Time frame: 36 months

Heart failure hospitalization

Hospitalization due to heart failure decompensation

Time frame: 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

Time frame: 36 months

Unplanned cardiovascular hospitalisation

Time frame: 36 months

Left ventricular ejection fraction

assessed by the Simpson method

Time frame: 12 months

Change in left ventricular dimension

end-diastolic and end-systolic volumes

Time frame: 12 months

Change in degree of mitral regurgitation

Time frame: 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)

Time frame: 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

Time frame: 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

Time frame: 30 days

Heart Rate Regularization in Atrial Fibrilation and Heart Failure

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts