Cardiac AmyloidosisPACE-ATTRNCT07413081
Increased Pacemaker Lower Rate in ATTR Cardiac Amyloidosis
A study testing Increasing the pacemaker lower rate and Standard setting in people with Cardiac Amyloidosis and Pacemaker, run by Region Skane at 9 sites in 2 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cardiac Amyloidosis, Pacemaker
- What is being tested?
- Increasing the pacemaker lower rate and Standard setting
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 9 sitesin 2 countries
- Study dates
- 1 Feb 2026to 31 Dec 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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)
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
9 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
9 sites in 2 countries
Sweden7 sites
Sahlgrenska University Hospital
Gothenburg
Entela Bollano, MD, PhD, +46313421000, entela.bollano@vgregion.se
Entela Bollano
Linköping University Hospital
Linköping
Henriette Henriette van der Wal, MD, PhD, +4610-103 00 00, Henriette.van.der.Wal@regionostergotland.se
Skane University Hospital
Lund
Arash Mokhtari, MD, PhD, +4646171000, arash.mokhtari.0561@med.lu.se
arash.mokhtari.0561@med.lu.se
Skellefteå Hospital
Skellefteå
Kurt Boman, MD, PhD, +4690-785 00 00, kurt.boman@regionvasterbotten.se
Kurt Boman
Karolinska University Hospital
Stockholm
Per Eldhagen, MD, PhD, +468-123 700 00, per.eldhagen@regionstockholm.se
Per Eldhagen
Norrland University Hospital
Umeå
Björn Pilebro, MD, PhD, +4690-785 00 00, Bjorn.Pilebro@regionvasterbotten.se
Björn Pilebro
Academic University Hospital
Uppsala
Tymon Pol, MD, PhD, +4618-611 00 00, tymon.pol@medsci.uu.se
Tymon Pol
Denmark2 sites
Aarhus University Hospital
Aarhus
Steen Hvitfeldt Poulsen, MD, PhD, +45 7846 1698, steen.hvitfeldt@rm.dk
Steen Hvitfeldt Poulsen
Rigshospitalet
Copenhagen
Mads Ersbøll, MD, PhD, +4535 45 35 45, mads.kristian.ersboell.02@regionh.dk
Mads Ersbøll
About this study
Official title: Increased Pacemaker Lower Rate in ATTR Cardiac Amyloidosis: a Randomized, Crossover Clinical Trial (PACE-ATTR)
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.
Read the detailed 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.
- Conditions
- Cardiac Amyloidosis, Pacemaker
- Being tested
- Increasing the pacemaker lower rate, Standard setting
- Medical subject headings
- Amyloid Neuropathies, Familial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Increasing the pacemaker lower rateDevice
Increasing the pacemaker lower rate from 60 to 80 bpm
Standard settingDevice
Lower rate setting of 60 bpm
| Study group | Role | What they receive |
|---|---|---|
| 80 bpm | Active comparator | Not described Receives: Device: Increasing the pacemaker lower rate |
| 60 bpm | Other | Not described Receives: Device: Standard setting |
What is being measured
The primary outcome is the main question the study is designed to answer.
Minnesota Living with Heart Failure Questionnaire (MLHFQ)
The MLHFQ is a validated patient-reported outcome assessing heart failure-related quality of life. It consists of 21 items scored 0-5, yielding a total score range of 0-105. Higher scores indicate worse quality of life. MLHFQ is collected at Visits 1-4.
Measured: End of each treatment period (Visit 2 at approximately 3 months and Visit 4 at approximately 7 months)
Secondary outcomes (8)
Distance walked during the 6-Minute Walk Test (6MWT)
The 6-Minute Walk Test measures the distance walked in meters during six minutes on a flat, hard surface. The distance walked ranges from 0 meters upward, with higher distances indicating better functional capacity. The 6MWT is performed at Visits 1-4.
Measured: End of each treatment period (Visit 2 at approximately 3 months and Visit 4 at approximately 7 months)
Levels of N-terminal pro-B-type Natriuretic Peptide (NT-proBNP)
NT-proBNP is a circulating biomarker of myocardial wall stress and heart failure severity. It is measured in pg/mL. Higher concentrations indicate worse cardiac function. NT-proBNP is assessed at Visits 1-4.
Measured: End of each treatment period (Visit 2 at approximately 3 months and Visit 4 at approximately 7 months)
New York Heart Association (NYHA) Functional Class
NYHA functional class is a measure of heart failure severity ranging from Class I to Class IV, with higher class indicating worse functional status. NYHA class is assessed at Visits 1-4.
Measured: End of each treatment period (Visit 2 at approximately 3 months and Visit 4 at approximately 7 months)
National Amyloidosis Centre (NAC) Stage
National Amyloidosis Centre (NAC) stage is a prognostic staging system for transthyretin cardiac amyloidosis based on cardiac biomarkers. It is categorized as Stage I, II, or III, with higher stage indicating more advanced disease. NAC stage is assessed at Visits 1-4.
Measured: End of each treatment period (Visit 2 at approximately 3 months and Visit 4 at approximately 7 months)
Number of participants with hospitalization or urgent outpatient visit for atrial fibrillation
This outcome captures atrial fibrillation-related hospitalizations or urgent outpatient visits occurring during each treatment period.
Measured: During each treatment period (approximately 3 months per period)
Atrial fibrillation burden assessed by implanted pacemaker
Atrial fibrillation (AF) burden is defined as the percentage of time spent in atrial fibrillation, as recorded by the implanted pacemaker's arrhythmia detection algorithms. Higher values indicate greater arrhythmia burden.
Measured: During each treatment period (approximately 3 months per period)
Physical activity level assessed by implanted pacemaker
Physical activity is assessed using the implanted pacemaker's built-in activity sensor. Higher values indicate greater physical activity.
Measured: During each treatment period (approximately 3 months per period)
Levels of High-Sensitivity Cardiac Troponin (hs-cTn)
High-sensitivity cardiac troponin (hs-cTn) is a biomarker of myocardial injury. It is measured in ng/L in plasma. Higher concentrations indicate greater myocardial injury. hs-cTn is assessed at Visits 1-4.
Measured: End of each treatment period (Visit 2 at approximately 3 months and Visit 4 at approximately 7 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2026
- Study start1 Feb 2026 (estimated)
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cardiac AmyloidosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 34 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Region Skane
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07413081
- Sponsor's protocol ID
- 2025-07764-01
- Other IDs
- 2025
- Acronym
- PACE-ATTR
- Status last verified
- Jan 2026
- First submitted
- 20 Jan 2026
- Last updated
- 17 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Increased Pacemaker Lower Rate in ATTR Cardiac Amyloidosis: a Randomized, Crossover Clinical Trial (PACE-ATTR)
- ClinicalTrials.gov ID
- NCT07413081
- Acronym / sponsor ID
- PACE-ATTR / 2025-07764-01
- Conditions
- Cardiac Amyloidosis, Pacemaker
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 34 participants (estimated)
- Lead sponsor
- Region SkaneUniversity, hospital or other
- Study start
- 1 Feb 2026 (estimated)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 17 Feb 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 80 bpm | Active comparator | Device: Increasing the pacemaker lower rate |
| 60 bpm | Other | Device: Standard setting |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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.
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Increasing the pacemaker lower rateIncreasing the pacemaker lower rate from 60 to 80 bpm | Device | 80 bpm |
| Standard settingLower rate setting of 60 bpm | Device | 60 bpm |
Primary outcome
Minnesota Living with Heart Failure Questionnaire (MLHFQ)
Time frame: End of each treatment period (Visit 2 at approximately 3 months and Visit 4 at approximately 7 months)
The MLHFQ is a validated patient-reported outcome assessing heart failure-related quality of life. It consists of 21 items scored 0-5, yielding a total score range of 0-105. Higher scores indicate worse quality of life. MLHFQ is collected at Visits 1-4.
8 secondary outcomes
Distance walked during the 6-Minute Walk Test (6MWT)
Time frame: End of each treatment period (Visit 2 at approximately 3 months and Visit 4 at approximately 7 months)
Levels of N-terminal pro-B-type Natriuretic Peptide (NT-proBNP)
Time frame: End of each treatment period (Visit 2 at approximately 3 months and Visit 4 at approximately 7 months)
New York Heart Association (NYHA) Functional Class
Time frame: End of each treatment period (Visit 2 at approximately 3 months and Visit 4 at approximately 7 months)
National Amyloidosis Centre (NAC) Stage
Time frame: End of each treatment period (Visit 2 at approximately 3 months and Visit 4 at approximately 7 months)
Number of participants with hospitalization or urgent outpatient visit for atrial fibrillation
Time frame: During each treatment period (approximately 3 months per period)
Atrial fibrillation burden assessed by implanted pacemaker
Time frame: During each treatment period (approximately 3 months per period)
Physical activity level assessed by implanted pacemaker
Time frame: During each treatment period (approximately 3 months per period)
Levels of High-Sensitivity Cardiac Troponin (hs-cTn)
Time frame: End of each treatment period (Visit 2 at approximately 3 months and Visit 4 at approximately 7 months)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2026.
Related trials for Cardiac Amyloidosis
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Not yet recruitingObservational study
PET/CT Imaging in Carriers of TTR Mutations
ATTR, ATTR Gene Mutation
Not yet recruitingPhase 3
Linvoseltamab Versus Daratumumab, Bortezomib, Cyclophosphamide, and Dexamethasone (Dara-Vcd) in Adult Participants With Newly Diagnosed Systemic Light Chain Amyloidosis
Newly Diagnosed Amyloidosis, Amyloidosis Stage I-IIIA
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CCM OPEN HF Registry
Heart Failure
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Single-arm, Multi-center Study Evaluating the Acceptance and Feasibility of a Digital Remote Monitoring Tool Configured for Patients With ATTR-CM: ACO-Monitor
Transthyretin Amyloid Cardiomyopathy (ATTR-CM)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
9 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Increasing the pacemaker lower rate and Standard setting in people with Cardiac Amyloidosis and Pacemaker, run by Region Skane at 9 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 17 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Sweden, Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Arash Mokhtari, MD, PhD (+4646171000, arash.mokhtari.0561@med.lu.se), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Minnesota Living with Heart Failure Questionnaire (MLHFQ) (time frame: End of each treatment period (Visit 2 at approximately 3 months and Visit 4 at approximately 7 months)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Feb 2026.