Leadless Versus Conventional Pacemakers: Effects on Heart Function and Heart Failure (LEAP HF)

Leadless Pacing and Heart Failure: A Prospective, Randomized, Open-Label, Non-Inferiority Trial

People with a slow heart rhythm may need a permanent pacemaker. Conventional pacemakers use a device placed under the skin and wires that pass through veins into the heart. Leadless pacemakers are placed directly inside the heart without a chest pocket or these wires. Both approaches can provide pacing, but their effects on heart function and heart-failure-related problems need to be compared.

LEAP-HF will compare an indication-adapted leadless pacemaker strategy with a conventional transvenous pacemaker strategy in 760 adults for whom either approach is clinically appropriate. Participants must have a left ventricular ejection fraction above 40% and must not require a defibrillator, cardiac resynchronization therapy, or chronic atrial pacing. Participants will be assigned by chance, in equal proportions, to the two strategies. The device and pacing mode will be selected according to the participant's clinical indication within the assigned strategy.

The main question is whether the leadless strategy is not unacceptably worse than the conventional strategy for pacing-induced cardiac dysfunction during 12 months of follow-up. This outcome includes a qualifying deterioration in heart pumping function, pacemaker syndrome, heart failure requiring hospitalization, or an upgrade to cardiac resynchronization therapy. The prespecified non-inferiority margin is an absolute difference of 7 percentage points.

Assessments include heart ultrasound, pacemaker checks, an electrocardiogram, a blood test for NT-proBNP, symptom assessment, and questionnaires about health and quality of life. There will be a telephone contact at 6 weeks and in-person visits at 6 and 12 months after implantation. The study will also compare heart function, complications, further procedures, and deaths. Participants and treating teams will know which pacing system was implanted; selected clinical events will be reviewed by an independent committee unaware of the assigned treatment.

Study Overview

• Status: Not yet recruiting
• Conditions: Heart Failure; Bradycardia; Atrioventricular Block; Pacing Therapy; Pacing Induced Dyssynchrony; Leadless Pacemaker; Pacing Induced Cardiomyopathy
• Intervention / Treatment: Device: Leadless pacemaker implantation; Device: Conventional transvenous pacemaker implantation

Detailed Description

LEAP-HF is a prospective, randomized, controlled, open-label, strategy-based non-inferiority trial coordinated by University Hospital St. Pölten, Austria. Multicentre participation is planned, with a total of 3 to 5 Austrian centres. Recruitment is planned over 24 months, with 12 months of follow-up after each participant's implantation.

Participants will be randomized 1:1 through a centralized web-based system with concealed allocation and variable block sizes. Randomization is stratified by centre, baseline rhythm, and baseline left ventricular ejection fraction. Within the assigned strategy, device selection and programming follow an indication-based algorithm. The comparator is conventional right ventricular pacing; conduction system pacing is not a planned treatment in either randomized strategy.

Baseline assessments are performed within 14 days before implantation and before randomization. Procedural and device data are collected at implantation and discharge. A telephone contact is scheduled at 6 weeks. The in-person 6- and 12-month visits have a window of plus or minus 30 days and include clinical assessment, pacemaker interrogation, standardized echocardiography, a 12-lead electrocardiogram, NT-proBNP measurement, and KCCQ-12 and EQ-5D-5L questionnaires.

The primary analysis includes all randomized participants according to their assigned strategy, irrespective of implantation success, crossover, or protocol deviations. The primary treatment contrast is the absolute difference in 12-month cumulative incidence of pacing-induced cardiac dysfunction, leadless minus transvenous. Death before a qualifying event is a competing event. Non-inferiority is established if the upper bound of the two-sided 95% confidence interval is below 7 percentage points. Per-protocol and as-treated analyses are supportive.

After primary non-inferiority is established, key secondary outcomes are tested in a fixed sequence: change in left ventricular ejection fraction, 12-month NT-proBNP adjusted for baseline, and the composite of all-cause death, any heart-failure hospitalization, or urgent pacemaker-related reintervention. The first two tests assess non-inferiority, with margins of -3.5 percentage points and a ratio of adjusted geometric means of 1.5, respectively; the third assesses superiority. Tests after an unsuccessful step are exploratory rather than confirmatory. The statistical analysis plan will be finalized before recruitment, including handling of death and missing assessments and verification of the sample-size assumptions.

Qualifying clinical events are counted through the nominal 12-month anniversary of implantation. Echocardiographic measurements obtained within the scheduled visit window are assigned to the nominal visit. A qualifying event at 6 months remains part of the 12-month composite even if the condition subsequently improves. Safety events are collected from randomization through the final protocol contact.

Echocardiographic examinations are evaluated independently using standardized procedures. Treatment allocation, nominal visit, previous measurements, and clinical outcomes are not disclosed to readers. Complete masking cannot be guaranteed because implanted hardware, or its absence, may be recognizable. Heart-failure hospitalizations and cardiac resynchronization therapy upgrades are adjudicated by an independent committee blinded to treatment allocation using prespecified criteria and redacted source documents.

An embedded prospective screening registry is planned, subject to applicable consent and regulatory requirements, to characterize screened candidates and external validity. Nonrandomized registry participants are not included in the randomized trial's planned enrollment of 760. Study data are captured in REDCap with role-based access and audit trails. Results will be disseminated regardless of their direction.

• Study Type: Interventional
• Enrollment (Estimated): 760
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Matthias Schöner, MD; Phone Number: 12541 +43 2742 9004; Email: matthias.schoener@stpoelten.lknoe.at

Study Locations

• Austria
  • Lower Austria
    • Sankt Pölten, Lower Austria, Austria, 3100
      • University Hospital St. Pölten, Department of Internal Medicine 3 - Cardiology
      • Contact: Matthias Schöner, MD; Phone Number: 12541 +43 2742 9004; Email: matthias.schoener@stpoelten.lknoe.at

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18 years or older.
• Guideline-based indication for permanent ventricular pacing for which both leadless and transvenous strategies are clinically appropriate, such as permanent atrial fibrillation with slow ventricular response, high-degree atrioventricular block, or pacing after atrioventricular junction ablation.
• Baseline left ventricular ejection fraction above 40%, assessed within 14 days before implantation and before randomization. Absence of a guideline-based indication for cardiac resynchronization therapy or an implantable cardioverter-defibrillator must be confirmed separately.
• No guideline-based requirement for chronic atrial pacing, such as symptomatic sinus node dysfunction requiring an atrial lead.
• No baseline indication for cardiac resynchronization therapy or implantable cardioverter-defibrillator therapy.
• Technical and clinical feasibility of both leadless and transvenous implantation approaches.
• Written informed consent and willingness and ability to comply with follow-up for at least 12 months.

Exclusion Criteria:

• Current guideline-based indication for cardiac resynchronization therapy or an implantable cardioverter-defibrillator, or a requirement for chronic atrial pacing.
• Recent myocardial infarction or active myocarditis within 3 months, or another planned cardiac intervention likely to affect left ventricular ejection fraction within 12 months, such as severe valve disease requiring intervention.
• Severe right ventricular dysfunction, for example tricuspid annular plane systolic excursion below 12 mm or right ventricular systolic tissue Doppler velocity below 8 cm/s, where advanced right ventricular failure could confound the pacing strategy comparison.
• Active systemic infection or endocarditis.
• Severe renal dysfunction, defined as estimated glomerular filtration rate below 20 mL/min/1.73 m2, or dialysis dependence.
• Anatomical or clinical contraindication to leadless implantation, such as a mechanical tricuspid valve prosthesis or known intracardiac thrombus, or contraindication to transvenous implantation.
• Severe uncontrolled coagulopathy or a bleeding disorder precluding safe implantation.
• Pregnancy.
• Inability to provide informed consent or adhere to follow-up.
• Life expectancy below 12 months due to cardiac or noncardiac comorbidity.
• Strong patient preference for a specific pacing strategy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Leadless pacing strategy; Participants receive an indication-adapted leadless pacing strategy. Permanent atrial fibrillation with bradycardia or after atrioventricular junction ablation is treated with leadless VVI/VVIR pacing. In sinus rhythm without a requirement for chronic atrial pacing, an approved atrioventricular-synchronous ventricular pacing algorithm or dual-chamber leadless pacing is used when clinically appropriate. Device selection and programming follow the prespecified study algorithm.	Device: Leadless pacemaker implantation; Implantation and indication-adapted programming of a leadless pacemaker system. The current protocol lists Medtronic Micra VR2, Medtronic Micra AV2, Abbott AVEIR VR, and Abbott AVEIR AR/VR dual-chamber systems. The selected system must be appropriate for the clinical indication and permitted by the applicable approvals and study protocol. Follow-up includes standardized device interrogation and assessment of ventricular pacing burden.
Active Comparator: Conventional transvenous pacing strategy; Participants receive conventional transvenous right ventricular pacing. Permanent atrial fibrillation is treated with VVI/VVIR pacing. In sinus rhythm, DDD/DDDR pacing is used when atrioventricular-synchronous pacing is clinically indicated. VVI/VVIR is permitted only when clinically appropriate under the prespecified indication criteria; absence of an atrial pacing requirement alone is insufficient justification. Conduction system pacing is not a planned treatment. Right ventricular lead position and programming are documented.	Device: Conventional transvenous pacemaker implantation; Implantation and indication-adapted programming of a conventional transvenous single- or dual-chamber pacemaker with right ventricular pacing. The current protocol lists systems from Abbott, Biotronik, Boston Scientific, Medtronic, and MicroPort/Sorin. Device type and pacing mode are selected according to the prespecified clinical algorithm. Lead position, electrical parameters, programming, and right ventricular pacing burden are documented. Conduction system pacing is not part of the assigned strategy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative incidence of pacing-induced cardiac dysfunction	Participant-level composite of: (1) LVEF decline of at least 10 percentage points to below 50%, RV pacing burden at least 40%, and no alternative cause; (2) new or worsened symptoms compatible with loss of AV synchrony, reduced AV synchrony, and RV pacing burden at least 40% at the last available interrogation; (3) hospitalization primarily for acute decompensated heart failure requiring IV diuretics and/or vasodilators, with RV pacing burden at least 40%; or (4) CRT upgrade for symptomatic heart failure, LVEF below 50%, and RV pacing burden at least 40%. HF admissions and CRT upgrades use the prespecified interrogation rule and blinded adjudication. Each participant is counted once. Death before PICD is a competing event, not a component. An event at 6 months remains an event at 12 months. LVEF=left ventricular ejection fraction; RV=right ventricular; AV=atrioventricular; CRT=cardiac resynchronization therapy; HF=heart failure; PICD=pacing-induced cardiac dysfunction.	Up to 12 months after implantation for clinical events; echocardiographic assessments at 6 and 12 months after implantation (each +/-30 days).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in left ventricular ejection fraction from baseline to 12 months	Change in left ventricular ejection fraction (LVEF), expressed in percentage points, assessed by standardized independent echocardiographic evaluation. The treatment contrast is leadless minus transvenous. Non-inferiority requires the lower bound of the two-sided 95% confidence interval to exceed -3.5 percentage points. This is the first key secondary test and is confirmatory only after primary non-inferiority has been established. Handling of death and missing assessments will be prespecified in the statistical analysis plan.	Baseline (within 14 days before implantation and before randomization) and 12 months after implantation (+/-30 days).
NT-proBNP at 12 months adjusted for baseline NT-proBNP	N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 12 months, analysed on the logarithmic scale with adjustment for baseline NT-proBNP. The treatment contrast is the ratio of adjusted geometric means, leadless divided by transvenous. Non-inferiority requires the upper bound of the two-sided 95% confidence interval to be below 1.5. This is the second key secondary test and is confirmatory only if all preceding tests succeed. Handling of death and missing assessments will be prespecified in the statistical analysis plan.	Baseline (within 14 days before implantation and before randomization) and 12 months after implantation (+/-30 days)
Participants with all-cause death, any heart-failure hospitalization, or urgent pacemaker-related reintervention	Number and percentage of participants with at least one of the following: death from any cause, any heart-failure hospitalization, or urgent pacemaker-related reintervention. Each participant is counted once for the composite. Unlike the primary composite, heart-failure hospitalization in this outcome is not restricted by a right ventricular pacing burden threshold. This is the third key secondary test, assessed for superiority at a two-sided significance level of 0.05 only if all preceding tests succeed; otherwise, the comparison is exploratory.	From implantation up to 12 months after implantation.
Change in left ventricular ejection fraction from baseline to 6 months	Change in left ventricular ejection fraction, expressed in percentage points, measured by standardized independent echocardiographic evaluation. This analysis is supportive and is not part of the fixed confirmatory testing sequence.	Baseline (within 14 days before implantation and before randomization) and 6 months after implantation (+/-30 days).
Change in NT-proBNP from baseline to 6 months	Change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration from baseline to 6 months, expressed in pg/mL. This is a supportive biomarker outcome and is not part of the fixed confirmatory testing sequence.	Baseline (within 14 days before implantation and before randomization) and 6 months after implantation (+/-30 days).
New York Heart Association functional class	Distribution of participants across New York Heart Association (NYHA) functional classes I to IV at each assessment. Class I indicates no limitation of physical activity; class IV indicates symptoms at rest and inability to undertake physical activity without discomfort. Higher classes indicate greater functional limitation. Results are reported separately at 6 and 12 months.	At 6 and 12 months after implantation (each +/-30 days).
All-cause mortality	Number and percentage of participants who die from any cause during follow-up. Mortality is reported separately from the primary pacing-induced cardiac dysfunction outcome.	From implantation up to 12 months after implantation.
Participants with pacing-induced cardiomyopathy	Number and percentage of participants with an absolute decline in left ventricular ejection fraction of at least 10 percentage points from baseline to below 50%, documented right ventricular pacing burden of at least 40%, and no alternative explanation such as myocardial infarction, myocarditis, or severe valve deterioration. Echocardiographic assessment is performed independently. A qualifying event detected at 6 months remains an event even if ventricular function subsequently improves.	Up to 12 months after implantation, including the 12-month echocardiographic assessment window (+/-30 days); additional assessment at 6 months (+/-30 days).
Participants with heart-failure hospitalization meeting the primary endpoint criteria	Number and percentage of participants hospitalized with a primary diagnosis of acute decompensated heart failure requiring intravenous diuretics and/or vasodilators, with right ventricular pacing burden of at least 40% established according to the prespecified interrogation rule. Events are confirmed by the blinded clinical events committee.	From implantation up to 12 months after implantation.
Participants with cardiac resynchronization therapy upgrade meeting the primary endpoint criteria	Number and percentage of participants receiving a cardiac resynchronization therapy system for symptomatic heart failure with left ventricular ejection fraction below 50% and right ventricular pacing burden of at least 40%, established according to the prespecified interrogation rule. Events are confirmed by the blinded clinical events committee. Clinical treatment decisions remain independent of study endpoint classification.	From implantation up to 12 months after implantation.
Participants with any heart-failure hospitalization	Number and percentage of participants with at least one heart-failure hospitalization, irrespective of whether the right ventricular pacing burden criterion of the primary endpoint is met. Events are assessed according to the prespecified adjudication criteria.	From implantation up to 12 months after implantation.
Participants with urgent pacemaker-related reintervention	Number and percentage of participants undergoing at least one urgent pacemaker-related reintervention, as defined in the prespecified endpoint manual. This is an individual component of the key secondary clinical composite.	From implantation up to 12 months after implantation.
Right ventricular pacing capture threshold	Right ventricular pacing capture threshold measured during device interrogation, expressed in volts. The pulse duration at which the threshold is measured is documented. Values are reported separately at 6 and 12 months.	At 6 and 12 months after implantation (each +/-30 days).
Right ventricular sensing amplitude	Intrinsic right ventricular sensing amplitude measured during device interrogation, expressed in millivolts. Values are reported separately at 6 and 12 months.	At 6 and 12 months after implantation (each +/-30 days).
Right ventricular pacing impedance	Right ventricular pacing impedance measured during device interrogation, expressed in ohms. Values are reported separately at 6 and 12 months.	At 6 and 12 months after implantation (each +/-30 days).
Estimated remaining pacemaker battery longevity	Device-reported estimate of remaining battery longevity, expressed in years, obtained during interrogation. This is an estimated remaining lifespan rather than observed time to battery depletion. Values are reported separately at 6 and 12 months and, where applicable, separately for individual implanted leadless units.	At 6 and 12 months after implantation (each +/-30 days).
Right ventricular pacing burden	Percentage of ventricular beats paced, obtained from pacemaker interrogation. The device interrogation interval is documented. Values are reported separately at 6 and 12 months.	At 6 and 12 months after implantation (each +/-30 days).
Duration of the index pacemaker implantation procedure	Duration of the index pacemaker implantation procedure, expressed in minutes and recorded according to the study procedural data collection rules.	Day 0 (during the index pacemaker implantation procedure).
Fluoroscopy time during the index implantation	Total fluoroscopy time during the index pacemaker implantation procedure, expressed in minutes.	Day 0 (during the index pacemaker implantation procedure).
Fluoroscopy dose-area product during the index implantation	Total fluoroscopy dose-area product during the index pacemaker implantation procedure, expressed in Gy cm2 after harmonization of the source equipment units.	Day 0 (during the index pacemaker implantation procedure).
Contrast medium volume during the index implantation	Total volume of contrast medium administered during the index pacemaker implantation procedure, expressed in mL.	Day 0 (during the index pacemaker implantation procedure).
Participants with major procedure- or device-related complications	Number and percentage of participants with at least one major procedure- or device-related complication, including cardiac perforation or tamponade, vascular access complications, pneumothorax, pocket haematoma, or lead dislodgement or failure. Classification follows the prespecified safety definitions. Cumulative results through 6 and 12 months are reported separately.	From implantation up to 12 months after implantation, with cumulative assessments at 6 and 12 months.
Participants with device-system infection	Number and percentage of participants with an infection involving the implanted pacemaker system during follow-up, classified according to the prespecified safety definitions.	From implantation up to 12 months after implantation.
Participants with device-system revision or reintervention	Number and percentage of participants with at least one device-system revision or reintervention, including lead revision, device retrieval, device upgrade, or another surgical or catheter-based intervention related to device or procedural complications. This outcome includes urgent and nonurgent interventions. Routine noninvasive programming adjustments alone are not counted as reoperations.	From implantation up to 12 months after implantation.
Length of the index hospital stay	Duration of the hospital admission during which the index pacemaker implantation is performed, expressed in days from admission to discharge.	From admission to discharge from the index hospitalization, an estimated average of 3 days.

Collaborators and Investigators

• Sponsor: Karl Landsteiner University of Health Sciences
• Investigators: Study Chair: Julia Mascherbauer, MD, University Hospital St. Polten

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2027
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: October 13, 2026
• First Submitted That Met QC Criteria: November 4, 2026
• First Posted (Actual): November 10, 2026

Study Record Updates

• Last Update Posted (Actual): November 10, 2026
• Last Update Submitted That Met QC Criteria: November 4, 2026
• Last Verified: October 1, 2026

More Information

Terms related to this study

• Keywords: Right ventricular pacing; Non-inferiority trial; Pacemaker syndrome; Leadless cardiac pacing; Transvenous cardiac pacing; Pacing-induced cardiomyopathy; Atrioventricular synchrony
• Additional Relevant MeSH Terms: Cardiac Conduction System Disease; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Heart Block; Pathological Conditions, Signs and Symptoms; Heart Failure; Atrioventricular Block; Bradycardia
• Other Study ID Numbers: LEAP HF Trial; GS3-EK-3/286-2026 (Other Identifier: Ethics Committee of Lower Austria)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No