Image Supported Lead Placement in CRT (ADVISE)

Advanced Image Supported Lead Placement in Cardiac Resynchronization Therapy

Cardiac resynchronization therapy (CRT) is an established pacemaker therapy for patients with symptomatic chronic heart failure, but is hampered by a non-response rate of 30-40%. Optimising left ventricular (LV) lead placement is the cornerstone of improving treatment. The optimal location for the lead is remote from scar but within segments demonstrating late electromechanical activation. The present study aims to investigate the efficacy and clinical effect of the use of real-time guided lead placement using cardiac MRI and fluoroscopy in a blinded, multicenter, randomized controlled trial.

Study Overview

• Status: Active, not recruiting
• Conditions: Heart Failure
• Intervention / Treatment: Device: CARTBox

• Study Type: Interventional
• Enrollment (Estimated): 130
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands
    • Amsterdam UMC
  • Groningen, Netherlands
    • UMC Groningen
  • Maastricht, Netherlands
    • Maastricht UMC+
  • Nieuwegein, Netherlands
    • St. Antonius Nieuwegein
  • Utrecht, Netherlands
    • UMC Utrecht
  • Zwolle, Netherlands
    • Isala Zwolle
  • Zuid-Holland
    • Rotterdam, Zuid-Holland, Netherlands, 3015 GD
      • Erasmus MC

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Heart failure with LV ejection fraction ≤ 35%;
• New York Heart Association class II, III, or IV (ambulatory);
• Optimal medical treatment that is tolerable;
• Left bundle branch block (LBBB) and QRS ≥ 130 ms, OR non-LBBB and QRS ≥ 150 ms.

Exclusion Criteria:

• Pregnancy or lactation;
• Subjects with impaired renal function (severe renal insufficiency, GFR < 30 ml/min/1.73m2);
• Atrial fibrillation or atrial fibrillation during MRI
• Documented allergic reaction to gadolinium;
• Impossibility to undergo an MRI scan;
• Participation in another clinical study that prohibits any procedures other than standard.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention group; Live visualised, fluoroscopy-fused, image-guided, left ventricular lead placement on the basis of avoiding scar and targeting late mechanically activated segments.	Device: CARTBox; CARTBox performs analysis of cardiac MRI scans. The result is a treatment file that displays optimal targets for left ventricular lead implantation in CRT. This file will be used as an overlay with live fluoroscopy during the implantation procedure in the intervention group.
No Intervention: Control group; Empirical standard-of-care left ventricular lead placement, in line with current CRT implantation guidelines with electrical guiding on the basis of Q-LV sense.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differences in % of patients with succesfull LV lead location	Lead location, defined as being within, adjacent, or remote from the pre-defined target.	Direct post-CRT

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in reverse remodelling and volumetric response	Measured as the relative decrease in LV end-systolic volume, indexed to body surface area (LVESVi). Response defined as LVESVi-reduction ≥ 15%.	6 months
Change in EQ-5D-5L	A quality of life questionnaire	6, 12 and 24 months
Change in Kansas City Cardiomyopathy Questionnaire	A quality of life questionnaire	6, 12 and 24 months
Change in CRT response score	A hierarchical clinical endpoints, combining relative LVESVi-decrease, change in New York Heart Association class, and death at 12 month follow-up.	12 months
Health Technology Assessment	The value of image-guided lead placement will be investigated in terms of healthcare expenditure revolving heart failure care. This assesment will be based on a previously conducted preliminary economic analysis.	24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in total implantation procedure time.	Compared between both groups. Measured in minutes.	Direct post-CRT
Difference in total fluoroscopy time during procedure.	Compared between both groups. Measured in minutes.	Direct post-CRT
Difference in total contrast dose used during procedure.	Compared between both groups. Measured in dose area product.	Direct post-CRT
Difference in change in QRS duration	Compared between groups and according to LV lead location. Measured in ms.	Direct post-CRT and 6 months
Difference in change in QRSarea	Compared between groups and according to LV lead location. Measured in μVs.	Direct post-CRT and 6 months
Difference in Q-LV sense	Compared between groups and according to LV lead location. Measured in ms.	Direct post-CRT
Difference in pacing threshold	Compared between groups and according to LV lead location. Measured in mV.	Direct post-CRT
Difference in % of patients with disappearance of apical rocking	Compared between groups and according to LV lead location. Option to assess other indices of mechanical recoordination.	Direct post-CRT and 6 months

Collaborators and Investigators

• Sponsor: UMC Utrecht
• Collaborators: ZonMw: The Netherlands Organisation for Health Research and Development; Health Holland; CART-Tech B.V.
• Investigators: Principal Investigator: Mathias Meine, MD, PhD, UMC Utrecht

Publications and helpful links

General Publications

• Wouters PC, van Slochteren FJ, Tuinenburg AE, Doevendans PA, Cramer MM, Delnoy PHM, van Dijk VF, Meine M. On-screen image-guided lead placement in cardiac resynchronization therapy: Feasibility and outcome in a multicenter setting. Heart Rhythm O2. 2022 Oct 18;4(1):9-17. doi: 10.1016/j.hroo.2022.10.002. eCollection 2023 Jan.
• Wouters PC, van Lieshout C, van Dijk VF, Delnoy PH, Doevendans PA, Cramer MJ, Frederix GW, van Slochteren FJ, Meine M. Advanced image-supported lead placement in cardiac resynchronisation therapy: protocol for the multicentre, randomised controlled ADVISE trial and early economic evaluation. BMJ Open. 2021 Oct 25;11(10):e054115. doi: 10.1136/bmjopen-2021-054115.
• Gerrits W, Wouters PC, Chiu CSL, Guglielmo M, Cramer MJ, van der Harst P, Vernooy K, van Stipdonk AMW, van Halm VP, van Dijk VF, Ghani A, Maass AH, Yap SC, van Slochteren FJ, Meine M. Optimizing CRT Lead Placement Accuracy With CMR-Guided On-Screen Targeting: A Randomized Controlled Trial (ADVISE-CRT III). JACC Clin Electrophysiol. 2025 Mar 3:S2405-500X(25)00081-7. doi: 10.1016/j.jacep.2025.01.022. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): February 8, 2021
• Primary Completion (Actual): October 1, 2023
• Study Completion (Estimated): October 1, 2025

Study Registration Dates

• First Submitted: August 27, 2021
• First Submitted That Met QC Criteria: September 13, 2021
• First Posted (Actual): September 22, 2021

Study Record Updates

• Last Update Posted (Actual): April 1, 2025
• Last Update Submitted That Met QC Criteria: March 26, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: MRI; Cardiac Resynchronization Therapy; Image-guided therapy; Lead placement
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure
• Other Study ID Numbers: NL73416.041.20; 404460098327 (Other Grant/Funding Number: ZonMW); LSHM191o3-Ho7o (Other Grant/Funding Number: Health-Holland)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Within legal and ethical limits, deidentified individual clinical trial participant-level data (IPD), generated by our research, can be made available. Upon publication, data will be made available upon reasonable request and in agreement with a collaboration agreement. A data sharing and management plan is provided.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No