AMEND-CRT: Mechanical Dyssynchrony as Selection Criterion for CRT (AMEND-CRT)

Assessment of MEchaNical Dyssynchrony as Selection Criterion for Cardiac Resynchronization Therapy

Previous experience with cardiac resynchronization therapy (CRT) candidates suggests that selection of these patients can be improved. Current clinical guideline approaches are mainly too unspecific and lead to a high non-responder rate of 30-40%, which causes a burden on health care systems and puts patients at risk of an unnecessary treatment who might benefit more from a conservative approach. Previous work indicated that using the assessment of mechanical dyssynchrony on echocardiography can lower the non-responder rate at least by 50% without compromising sensitivity for detecting amendable patients. The current prospective, randomized, multi-center trial was therefore designed to prove that the characterization of the mechanical properties of the left ventricle can improve patient selection for CRT. Patients will be randomized into one of two study arms: a control study arm with treatment recommendation based on clinical guidelines criteria, or an experimental study arm with treatment recommendation based on the presence of mechanical dyssynchrony. All patients will receive a CRT implantation. In the control study arm, bi-ventricular pacing will be turned on. In the experimental study arm, bi-ventricular pacing will be turned on or off, depending on the presence or absence of mechanical dyssynchrony, respectively. The primary endpoint will be non-inferiority in outcome of a treatment recommendation based on mechanical dyssynchrony, achieved with a lower number of CRT devices implanted, effectively leading to a lower number needed to treat. Outcome measures are the average relative change in continuously measured LVESV per arm and the percentage 'worsened' according to the Packer Clinical Composite Score per arm after 1 year follow-up.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure; Cardiomyopathy, Dilated; Left Ventricular Dyssynchrony; Cardiac Remodeling, Ventricular
• Intervention / Treatment: Device: Cardiac resynchronization therapy ON; Device: Cardiac resynchronization therapy OFF

• Study Type: Interventional
• Enrollment (Estimated): 700
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jens-Uwe Voigt, MD, PhD; Phone Number: +32 16 34 90 16; Email: jens-uwe.voigt@uzleuven.be
• Study Contact Backup: Name: Alexis Puvrez, MD; Phone Number: +32 16 34 58 43; Email: alexis.puvrez@kuleuven.be

Study Locations

• Belgium
  • Antwerp, Belgium, 2020
    • Recruiting
    • ZNA Middelheim
    • Contact: Edgard Prihadi, MD
  • Antwerp, Belgium, 2000
    • Recruiting
    • University hospital Antwerp
    • Contact: Johanna Seghers
    • Contact: Nathalie Brosens
    • Principal Investigator: Johan Saenen, MD, PhD
  • Brugge, Belgium, 8000
    • Recruiting
    • AZ Sint-Jan Brugge
    • Contact: Noa Kozmine, MSc
    • Principal Investigator: Sander Trenson, MD, PhD
  • Ghent, Belgium, 9000
    • Recruiting
    • Ghent University Hospital
    • Contact: Pieter Vervaet
    • Principal Investigator: Frank Timmermans, MD, PhD
  • Ghent, Belgium, 9000
    • Recruiting
    • AZ Maria Middelares
    • Contact: Anne-Marie Willems
    • Principal Investigator: Nico Van De Veire, MD, PhD
  • Leuven, Belgium, 3000
    • Recruiting
    • UZ Leuven
    • Principal Investigator: Jens-Uwe Voigt, MD, PhD
    • Contact: Alexis Puvrez, MD; Email: alexis.puvrez@kuleuven.be
  • Ostend, Belgium, 8400
    • Recruiting
    • AZ Damiaan
    • Contact: Tineke Vandeputte
    • Principal Investigator: Stefan Ketels, MD
  • Roeselare, Belgium, 8800
    • Recruiting
    • AZ Delta
    • Contact: Tessy Van Tomme
    • Principal Investigator: Karl Dujardin, MD
• Brazil
  • São Paulo, Brazil, 04012-909
    • Recruiting
    • Dante Pazzanese Institute of Cardiology
    • Contact: Renato Hortegal, MD, PhD
• France
  • Brest, France, 29200
    • Recruiting
    • CHRU Brest
  • Lille, France, 59800 Lille
    • Recruiting
    • Groupements des hôpitaux de l'institut catholique de Lille
    • Contact: Dorothée Brzyski
    • Principal Investigator: Sylvestre Marechaux, Md, PhD
  • Rennes, France, 35000
    • Recruiting
    • CHU Rennes - Pontchaillou Hospital
    • Contact: Eleonore Serrano
    • Principal Investigator: Erwan Donal, MD, PhD
• Germany
  • Köln, Germany, 50733
    • Recruiting
    • St. Vinzenz-Hospital
    • Contact: Judith Simons
    • Contact: Doris Balling
    • Principal Investigator: Stefan Winter, MD
  • Rostock, Germany, 18057
    • Recruiting
    • Universitatsmedizin Rostock
    • Contact: Kerry Theelke, MSc
  • Würzburg, Germany, 97080
    • Recruiting
    • Universitatsklinikum Wurzburg
    • Contact: Caroline Morbach, MD, PhD
• Hungary
  • Budapest, Hungary, 1122
    • Recruiting
    • Semmelweis University Heart Center
    • Principal Investigator: Bela Merkely, MD, PhD
    • Contact: Astrid Apor, MD, PhD
• Latvia
  • Riga, Latvia, LV-1002
    • Recruiting
    • Paul Stradins Clinical University hospital
    • Contact: Kaspars Kupics, MD
• Poland
  • Poznań, Poland, 61-701
    • Recruiting
    • Poznan University of Medical Sciences
    • Contact: Aleksancra Cieplucha, MD
  • Warsaw, Poland, 04-628
    • Recruiting
    • Klinika Wad Wrodzonych Serca
    • Contact: Karolina Plaskota, MD
    • Principal Investigator: Miroslaw Kowalski, MD, PhD
  • Zabrze, Poland, 41-800
    • Recruiting
    • Silesian Center for Heart Diseases
    • Contact: Tomasz Kukulski, MD, PhD
• Portugal
  • Porto, Portugal, 4200-319
    • Recruiting
    • CHU de São João
    • Contact: Pedro Diogo, MD
• Romania
  • Cluj-Napoca, Romania, 400001
    • Recruiting
    • Heart Institute Nicolae Stancioiu
    • Contact: Razvan Mada, MD
    • Principal Investigator: Ruxandra Beyer, MD, PhD
• Spain
  • Barcelona, Spain, 08036
    • Recruiting
    • Hospital Clínico de Barcelona
    • Contact: Marta Sitges, MD, PhD
• Switzerland
  • Zürich, Switzerland, 8091
    • Recruiting
    • Universitätsspital Zürich
    • Contact: Anne-Sophie Karnbrock

Participation Criteria

Eligibility Criteria

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

Description

(- - - - - - - - - Inclusion Criteria - - - - - - - - -)

The proposed inclusion criteria represent the minimum recommendations for CRT implantation in heart failure patients according to the ESC 2021 guidelines. In addition:

• Patient has a LVEF ≤ 35%
• Patient has a LVEDD ≥ 2.7cm/m² or LVEDD ≥ 50mm (m) and ≥45mm (f)
• Patient has been in a stable medical condition for ≥ 1 month prior inclusion
• Patient underwent complete revascularization in case of ischemia
• Patients is able to understand and willing to provide a written informed consent
• Patient is 18 years or older

(- - - - - - - - - Exclusion Criteria - - - - - - - - -)

Patients with the following conditions will be excluded:

• unreliable left ventricular volume measurements
• severe MR or more than moderate other valvular disease
• pulmonary hypertension, other than secondary to left heart disease
• patient on hemodialysis
• life expectancy < 1 year
• pregnant or breastfeeding

Patients with prior right ventricular pacing between 20% to 80% will be excluded.

Patients with prior right ventricular pacing ≤ 20% or no pacemaker / ICD will be excluded if they have any of the following criteria:

• PR duration > 250ms
• second / third degree atrioventricular block
• intrinsic QRS duration < 130ms
• atrial fibrillation with resting HR < 50/min or > 80/min

Patients with prior right ventricular pacing ≥ 80% will be excluded if they have any of the following criteria:

• sensed AV delay > 250ms
• paced AV delay > 280ms

Patients with a prior pacemaker / ICD scheduled for LBBaP will be excluded regardless of pacing percentage

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
Active Comparator: Treatment recommendation based on guidelines; Treatment of the patient assigned to this arm will be based on the current guidelines for CRT implantation, as issued by the European Society of Cardiology. All patients will receive CRT implantation, with bi-ventricular pacing ON.	Device: Cardiac resynchronization therapy ON; Implantation of a CRT device. Bi-ventricular pacing will be turned ON.
Experimental: Treatment recommendation based on mechanical dyssynchrony; Treatment of the patients assigned to this arm will be based on the presence of mechanical dyssynchrony. All patients will receive CRT implantation. Bi-ventricular pacing will be either turned ON or OFF, based on respectively the presence or absence of mechanical dyssynchrony.	Device: Cardiac resynchronization therapy ON; Implantation of a CRT device. Bi-ventricular pacing will be turned ON.; Device: Cardiac resynchronization therapy OFF; Implantation of a CRT device. Bi-ventricular pacing will be turned OFF.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Volume response and Packer Clinical Composite Score	Non-inferiority in outcome of a treatment recommendation based on mechanical dyssynchrony, achieved with a lower number of CRT devices implanted, effectively leading to a lower number needed to treat. Outcome measures are the average relative change in left ventricular end-systolic volume and the proportion of patients 'worsened' according to the Packer Clinical Composite Score after 12 months follow-up.	12 months follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect on left ventricular function in both arms	≥ 10% difference in relative change in left ventricular ejection fraction and/or; ≥1.5% difference in absolute change in global longitudinal strain and/or; improvement in myocardial work from baseline to month 12	12 months follow-up
Difference in quality of life as measured by the Minnesota Living with Heart Failure questionnaire score and EuroQol 5D index score in both arms	≥ 5 points difference in change on the Minnesota Living with Heart Failure questionnaire score and/or; ≥0.08 points difference in change on the EuroQol 5D index score from baseline to month 12	12 months follow-up
Difference in 6 minute walk test distance in both arms	≥ 45 meters difference in change from baseline to month 12	12 months follow-up
Difference in predictive value for volume response	≥15% relative reduction in left ventricular end-systolic volume from baseline to month 12 will be considered as a response	12 months follow-up
Difference in predictive value for long-term patient outcome in both arms	Cox's proportional hazards model: At 1 year for 'worsened' PCCS; At 3 and 5 years for cardiovascular mortality and heart failure hospitalization	1 year, 3 years and 5 years follow-up
Difference in long-term patient outcome in both arms	Kaplan Meier survival analysis for heart failure hospitalization; Kaplan Meier survival analysis for cardiovascular mortality; Kaplan Meier survival analysis for combined heart failure hospitalization and cardiovascular mortality; Kaplan Meier survival analysis for all-cause mortality	3 years and 5 years follow-up

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven
• Investigators: Principal Investigator: Jens-Uwe Voigt, MD, PhD, Universitaire Ziekenhuizen KU Leuven

Study record dates

Study Major Dates

• Study Start (Actual): December 10, 2020
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: January 8, 2020
• First Submitted That Met QC Criteria: January 8, 2020
• First Posted (Actual): January 13, 2020

Study Record Updates

• Last Update Posted (Actual): December 6, 2023
• Last Update Submitted That Met QC Criteria: November 29, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Heart failure; Echocardiography; Cardiac resynchronization therapy; Mechanical dyssynchrony; Apical rocking; Septal flash; Left ventricle
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Genetic Diseases, Inborn; Pathological Conditions, Anatomical; Cardiomegaly; Laminopathies; Heart Failure; Cardiomyopathies; Cardiomyopathy, Dilated; Ventricular Remodeling
• Other Study ID Numbers: S64188_v4.0

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Available upon reasonable request after acceptance of publications.

Drug and device information, study documents

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