Respiratory Sinus Arrhythmia (RSA) Pacing Post-CABG Surgery in Patients With HFrEF (RSA-PACE)

Ceryx Medical Ltd

Status: Enrolling

Conditions: Heart Failure With Reduced Ejection Fraction

Treatments: Device: Atrial pacing with respiratory sinus arrhythmia (RSA) variability; Device: Monotonic right atrial overdrive pacing

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT06359938

Cer22/01

Details and patient eligibility

About

The goal of this clinical trial is to test a new type of pacemaker in heart failure patients following a heart bypass operation. The new pacemaker restores respiratory sinus arrhythmia which is a natural pattern where the heart rate increases when the participants breathe in and slows down when participants breathe out.

The main questions the trial aims to answer are:

• Is the new type of pacemaker safe?
• Does the new type of pacemaker improve how patients' hearts work (also known as cardiac output)?

Participants will have a range of tests before their operation and during their recovery in hospital while participants have the new type of pacemaker in place, and will be monitored very closely. Participants will also receive a phone call 1 month after their surgery. Researchers will compare the new type of heart pacing against standard treatment to see if it is as safe, and if it is any better for patients.

Full description

This is a first-in-human (FIH) clinical investigation of a modification of an existing medical device. It will be a comparative, multicentre, randomised controlled trial (RCT) design. RSA modulated atrial pacing will be compared against monotonic atrial pacing in patients with HFrEF who have had CABG surgery.

The purpose of this clinical investigation is to explore the risk/benefit profile of the use of RSA pacing in patients with HFrEF following CABG. Based on the prior animal models the investigators hypothesise an improvement in cardiac function over several days of RSA pacing, with no increase in risk compared to typical pacemaker use.

Primary hypothesis - Atrial pacing with additional RSA variability (for up to 10 days) is feasible and safe in patients with heart failure and reduced ejection fraction. The primary outcome is measuring arrhythmia episodes.

Secondary hypothesis - Atrial pacing with additional RSA variability improves cardiac function in patients with heart failure and reduced ejection fraction following CABG surgery. The secondary outcomes is measuring cardiac function, cardiac output, apnoea episodes.

Respiratory sinus arrhythmia is part of normal physiology and RSA pacing is looking to restore this. In heart failure, RSA is severely reduced. Therefore the investigators have identified that, post-CABG surgery patients with heart failure and reduced ejection fraction are the ideal candidates for this study. Following surgery it is standard of care for a surgeon to leave temporary pacing wires attached to the heart as a precaution and it is not uncommon to leave them in for 10 days or longer. Hence, these temporary wires can be used to deliver RSA pacing. Adjusting pacing rates is common in both implanted or temporary pacemakers.

Potential patients awaiting CABG surgery with heart failure with reduced ejection fraction will be identified using two routes - inpatients and outpatients.

The investigators would randomly allocate patients to either the RSA external pacemaker box or the normal external pacemaker for a maximum of 10 days. Patients will be connected to nasal prongs to monitor their respiration and in the RSA group, this signal will be fed to the external pacemaker to deliver RSA pacing.

Enrollment: 54 estimated patients

Sex: All

Ages: 22+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adult patients (≥ 22 years) selected for isolated, on-pump coronary artery bypass graft (CABG)
• Established diagnosis of heart failure with reduced ejection fraction (HFrEF).
• Elective or urgent admission routes
• Echocardiography assessment of left ventricular ejection fraction (EF) of 20%-40% (within 1 month of planned surgery)
• Sinus rhythm
• Any number of coronary vessels replaced. Must include left anterior descending artery.
• Able to provide written informed consent

Exclusion criteria

• Requirement for concurrent valve replacement surgery.
• Off-pump CABG.
• Emergency CABG
• History of paroxysmal or permanent atrial fibrillation or flutter
• History of atrioventricular-node dependent tachycardia
• Patients lacking capacity to consent
• Patient testing positive for Covid-19 within 14 days of intended CABG (PCR or lateral flow test)
• Intrinsic resting heart rate > 100bpm
• Pregnancy
• Implanted pacemaker or defibrillator
• Failure to obtain Uscom signals

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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54 participants in 2 patient groups

Atrial pacing with respiratory sinus arrhythmia (RSA) variability

Experimental group

Description:

The experimental arm is atrial pacing with additional respiratory sinus arrhythmia (RSA) modulation following coronary artery bypass graft (CABG) surgery. Pacing impulses will be grouped together during inspiration, such that heart rate (HR) will increase by approximately 6 bpm above median during inspiration, and decrease by around 6 bpm below median during expiration. Five pacing rates will be used to accommodate a range of patients' intrinsic HR. Pacing will be initiated after randomisation, after the patient is removed from ventilator support (Pacing Day 1, PD1). This is usually the day after surgery. Pacing will continue until the patient is ready for discharge or there is a clinical decision to stop pacing and remove the leads (whichever is soonest). Pacing is delivered by a PACE204 pacemaker (Osypka Medical AG) modulated to respiratory phase by a Ceryx device (intervention)

Treatment:

Device: Atrial pacing with respiratory sinus arrhythmia (RSA) variability

Monotonic atrial pacing

Active Comparator group

Description:

The control arm is standard monotonic right atrial pacing at the relevant median rate following coronary artery bypass graft (CABG) surgery. Pacing will be initiated after randomisation, after the patient is removed from ventilator support (Pacing Day 1, PD1). This is usually the day after surgery. Pacing will continue until the patient is ready for discharge or there is a clinical decision to stop pacing and remove the leads (whichever is soonest). Pacing is delivered by a PACE204 pacemaker (Osypka Medical AG) delivering standard monotonic right atrial pacing.

Treatment:

Device: Monotonic right atrial overdrive pacing