Pacing Advancements With Cost and Experience VALuation for Unified Patient-Led Clinical Evidence - the PACEVALUE Study (PACEVALUE)

The PACEVALUE study is a large, international observational study aiming to improve the treatment of patients receiving cardiac implantable electronic devices (CIEDs) such as pacemakers, implantable cardioverter-defibrillators (ICDs), and cardiac resynchronization therapy (CRT) devices. While these devices are vital for managing heart rhythm disorders and heart failure, chronic right ventricular pacing can sometimes cause a condition called pacing-induced cardiomyopathy (PICM), where the left side of the heart weakens over time, leading to increased hospitalizations and higher mortality.

The main goal of the study is to develop and validate a risk prediction model using routine clinical and device data to identify patients at highest risk of PICM before device implantation. By stratifying patients according to this risk score, the study aims to guide personalized pacing strategies, including conduction system pacing (CSP) and CRT options, to improve outcomes and reduce complications.

The study will include approximately 4,500 patients across centers in Switzerland, Germany, Poland, Croatia, Bulgaria, Cyprus, and Australia, with planned inclusion of sites in the UK. Patients are included in two arms. In the prospective arm, consecutive patients are enrolled at the time of their device procedure. In the retrospective arm, centers include patients they have already treated, using data already recorded during clinical care. Both arms use the same case report form and the same endpoint definitions. Participants are followed annually for up to ten years, with data collection including heart function imaging, device data, clinical outcomes, patient-reported outcomes (PROMs/PREMs), and healthcare costs.

This observational study will also compare clinical practices and cost-effectiveness of different pacing strategies across diverse healthcare systems, aiming to inform evidence-based, patient-centered, and economically efficient device therapy decisions. The findings will lay the groundwork for future registry-based randomized controlled trials to further optimize pacing treatments.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure; Arrhythmias, Cardiac; Cardiomyopathy, Secondary; Conduction System Pacing; Pacing Induced Cardiomyopathy

• Study Type: Observational
• Enrollment (Estimated): 4500

Contacts and Locations

• Study Contact: Name: Nikola A. Kozhuharov, PD Dr. med.; Phone Number: +41 31 63 2 36 50; Email: nikola.kozhuharov@insel.ch

Study Locations

• Australia
  • Australian Capital Territory
    • Canberra, Australian Capital Territory, Australia
      • Recruiting
      • Canberra Health Services
• Bulgaria
  • Sofia, Bulgaria
    • Not yet recruiting
    • Acibadem City Clinic Tokuda Hospital
  • Sofia, Bulgaria
    • Not yet recruiting
    • University Hospital Tsaritsa Yoanna ISUL
• Croatia
  • Zagreb, Croatia
    • Not yet recruiting
    • Dubrava University Hospital
• Cyprus
  • Nicosia, Cyprus
    • Not yet recruiting
    • Nicosia General Hospital
• Germany
  • Bad Krozingen, Germany
    • Not yet recruiting
    • University Heart Center Freiburg-Bad Krozingen
• Poland
  • Rzeszów, Poland
    • Not yet recruiting
    • Clinical Provincial Hospital No. 2
  • Warsaw, Poland
    • Not yet recruiting
    • National Institute of Cardiology
  • Wroclaw, Poland
    • Not yet recruiting
    • 4th Military Clinical Hospital
  • Zabrze, Poland
    • Not yet recruiting
    • Medical University of Silesia
• Switzerland
  • Baden, Switzerland
    • Not yet recruiting
    • Kantonsspital Baden
  • Bern, Switzerland, 3010
    • Recruiting
    • Inselspital, University Hospital Bern
  • Geneva, Switzerland
    • Not yet recruiting
    • Hopitaux Universitaires de Geneve

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population includes adults undergoing a cardiac implantable electronic device (CIED) procedure for standard clinical indications, included in two arms. In the prospective arm, consecutive patients at a participating center are enrolled at the time of the procedure. In the retrospective arm, centers include all consecutive patients who underwent a CIED procedure from a center-specific start date up to the date of data extraction, using data already recorded during clinical care. Participants are drawn from centers in Switzerland, Germany, Poland, Croatia, Bulgaria, Cyprus, and Australia, with planned activation of sites in the UK. The population includes patients receiving pacemakers, ICDs, or CRT devices; patients with existing CRT at baseline serve as a comparator. Both arms use the same case report form and the same endpoint definitions. Enrollment reflects diverse healthcare settings and demographics.

Description

Inclusion Criteria:

• Age ≥18 years at the time of the CIED procedure
• Undergoing, or having undergone, a CIED procedure (permanent pacemaker, ICD, or CRT)
• A lawful basis for inclusion: signed informed consent prior to enrollment in the prospective arm, or a lawful basis for the further use of health-related personal data in the retrospective arm
• Prospective arm only: willing and able to participate in long-term follow-up
• Prospective arm only: sufficient language comprehension (or support) to provide informed consent and complete PROMs/PREMs

Exclusion Criteria:

• Prospective arm only: severe cognitive impairment without a legal representative
• A documented objection to the use of health-related data for research

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants developing PICM, defined as an absolute decline in left ventricular ejection fraction (LVEF) of ≥10 percentage points to <50% during follow-up after a CIED procedure	up to 10 years after the CIED procedure

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of participants who died from any cause on follow-up	up to 10 years after the CIED procedure
Number of participants hospitalized for heart failure on follow-up	up to 10 years after the CIED procedure
Number of participants hospitalized for other cardiovascular events (excluding heart failure) on follow-up	up to 10 years after the CIED procedure
Number of participants hospitalized for non-cardiovascular reasons on follow-up	up to 10 years after the CIED procedure
Number of participants undergoing upgrade to CRT on follow-up	up to 10 years after the CIED procedure
Number of participants with device-related complications on follow-up	up to 10 years after the CIED procedure
Change in EQ-5D-5L Index Score from Baseline (range 0-1; higher scores indicate better quality of life)	at Baseline, 8 weeks, and annually to year 10
Change in patient satisfaction score with remote monitoring from Baseline (range 0-10; higher scores indicate higher satisfaction)	Baseline, 8 weeks, and annually to year 10
Total healthcare costs per patient for CSP versus right ventricular pacing, applying the PICM risk prediction score	up to 10 years after the CIED procedure
Incremental cost-effectiveness ratio (ICER) of CSP versus right ventricular pacing per quality-adjusted life year (QALY) gained, applying the PICM risk prediction score	up to 10 years after the CIED procedure
Inter-center and inter-country variation in CIED practice, including percentage of patients receiving CSP	up to 10 years after the CIED procedure
Average percentage of ventricular pacing on follow-up	up to 10 years after the CIED procedure
Number of participants with device-detected subclinical atrial fibrillation on follow-up	up to 10 years after the CIED procedure
Number of participants experiencing stroke, stratified by modified Rankin Score on follow-up	up to 10 years after the CIED procedure
Number of participants with moderate or severe tricuspid valve regurgitation on echocardiography on follow-up	up to 10 years after the CIED procedure

Collaborators and Investigators

• Sponsor: Insel Gruppe AG, University Hospital Bern
• Investigators: Principal Investigator: Nikola A. Kozhuharov, PD Dr. med., Inselspital, University Hospital Bern, Clinic of Cardiology

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2031

Study Registration Dates

• First Submitted: November 28, 2025
• First Submitted That Met QC Criteria: November 28, 2025
• First Posted (Actual): December 10, 2025

Study Record Updates

• Last Update Posted (Actual): September 11, 2026
• Last Update Submitted That Met QC Criteria: September 8, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Pathological Conditions, Signs and Symptoms; Heart Failure; Cardiomyopathies; Arrhythmias, Cardiac
• Other Study ID Numbers: 2025-02109; 2025 (U.S. NIH Grant/Contract: Faculty of Social Sciences Scientific Grant at the University of Gdańsk)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared. The prediction model is published in full, including every coefficient, the baseline risk at each prediction horizon, the shrinkage applied and the functional forms, in sufficient detail for a predicted risk to be computed without contacting the investigators. Analyses are conducted within the collaboration under the applicable agreements and reported according to TRIPOD+AI.

Drug and device information, study documents

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