Increased Pacemaker Lower Rate in ATTR Cardiac Amyloidosis (PACE-ATTR)

Region Skane

Status

Not yet enrolling

Conditions

Cardiac Amyloidosis

Pacemaker

Treatments

Device: Increasing the pacemaker lower rate

Device: Standard setting

Study type

Interventional

Funder types

Other

Identifiers

NCT07413081

2025-07764-01

Details and patient eligibility

About

In cardiac amyloidosis, the heart muscle becomes thick and stiff, making it difficult to pump enough blood with each beat. The heart also often cannot increase its stroke volume, making patients with cardiac amyloidosis more dependent on having an adequate heart rate. Many develop conduction problems and need a pacemaker. In a related condition, heart failure with preserved ejection fraction, setting a higher pacemaker rate improved patients' quality of life. It is not known if the same benefits apply to amyloidosis. This study will test whether raising the pacemaker rate improves well-being and daily function in affected patients.

Full description

Transthyretin amyloid cardiomyopathy (ATTR-CM) is an increasingly recognized cause of restrictive cardiomyopathy, characterized by reduced ventricular compliance, low stroke volume, and marked dependence on heart rate for maintenance of cardiac output. Conduction disease is common in ATTR-CM, and a substantial proportion of patients require permanent pacemaker implantation.

Although disease-modifying therapy can slow disease progression, evidence guiding optimization of pacemaker therapy in ATTR-CM is lacking. In heart failure with preserved ejection fraction, a condition also characterized by reduced ventricular compliance, increased pacemaker lower rate settings have been shown to improve functional capacity and quality of life. However, patients with cardiac amyloidosis were excluded from these studies. Consequently, current practice in ATTR-CM relies largely on extrapolation and expert opinion.

In this randomized multicenter 2×2 crossover trial, we aim to determine whether a higher pacemaker lower rate (80 bpm) improves health-related quality of life (QoL) and functional capacity in patients with ATTR-CM compared with the standard setting of 60 bpm.

Enrollment

34 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

ATTR-CM defined as one of the following:
a.Positive cardiac biopsy for ATTR amyloidosis
b.Positive extra-cardiac biopsy for ATTR amyloidosis AND cardiac involvement demonstrated by CMR or echocardiography
c.Grade 2-3 uptake on DPD-scintigraphy AND negative serum free light chain and negative urine and serum immunofixation AND cardiac involvement demonstrated by CMR or echocardiography
Ongoing treatment with a transthyretin stabilizer or silencer OR considered not to be a candidate for these therapies with no planned initiation during the study period.
NYHA functional class II-III
Pre-existing pacemaker and either:
a.Atrial pacing with minimal RV pacing (<2%), or
b.His bundle or left bundle branch area pacing, or
c.Biventricular pacing, or
d.Ongoing RV pacing with a high degree of RV pace (>80%)
NT-proBNP >600 ng/L
Age ≥18 years
Ability and willingness to provide written informed consent
Pacing >80% with a programmed lower rate of 60 (AAI/CSP/CRT/RV-pace)

Exclusion criteria

Inability to perform the 6-minute walk test.
Planned coronary revascularization, ablation of atrial flutter/fibrillation, or any severe (obstructive or regurgitant) valvular heart disease expected to require intervention during the trial in the investigator's opinion.
MI, unstable angina, coronary revascularization (percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG)), ablation of atrial flutter/fibrillation, cardioversion, valve repair/replacement, hospitalization for decompensated heart failure or cardiac resynchronisation therapy within 12 weeks prior to enrollment.
Planned upgrade to CRT or conduction system pacing in patients with RV pacing.
More than moderate valvular stenosis or regurgitation
Inability of the patient, in the opinion of the investigator, to understand and/or comply with procedures and/or follow-up OR any conditions that, in the opinion of the investigator, may render the patient unable to complete the study
Presence of any other disease than heart failure with a life expectancy of < 1year in the investigators opinion
Enrollment in other interventional device or drug trials during the study period, with the exception of open label extension studies
Listed for cardiac transplantation
Initiation of SGLT2-inhibitor or mineralocorticoid receptor antagonist within 4 weeks prior to enrollment
Initiation or change in loop diuretic therapy within 4 weeks prior to enrollment