Myocardial Work and Metabolism in CRT (WORK-CRT)

Investigating Inhomogeneities of Regional Myocardial WORKload and Metabolism in a Cardiac Resynchronisation Therapy Patient Population

Several attempts have been made to refine selection criteria for cardiac resynchronisation therapy (CRT) in heart failure patients with reduced ejection fraction (HFrEF). Previously proposed parameters probably do not sufficiently reflect the underlying mechanical dyssynchrony of the left ventricle (LV). Earlier work of our research group suggests that better candidate selection can rely on the direct observation or measurement of this LV mechanical dyssynchrony by means of non-invasive imaging. In this study apical rocking and other non-invasive measures of LV mechanical dyssynchrony will be applied to evaluate regional myocardial workload and metabolism, and determine their predictive value in CRT response.

Study Overview

• Status: Active, not recruiting
• Conditions: Heart Failure; Cardiomyopathy; Left Ventricular Dyssynchrony; Left Bundle Branch Block
• Intervention / Treatment: Other: Magnetic Resonance Imaging; Device: Cardiac resynchronisation therapy; Other: Echocardiography; Other: Positron Emission Tomography

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • Universitaire Ziekenhuizen Leuven
• Norway
  • Oslo, Norway, 0372
    • Oslo University Hospital

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

Subject is eligible for CRT implantation according to current European Society of Cardiology guidelines of 2013.

• The patient should receive guideline-directed optimal medical therapy for heart failure and left ventricular (LV) function must be severely depressed (LV ejection fraction ≤35%).
• The patients should be in NYHA functional class II, III or ambulatory IV.
• The patient should present a left bundle branch block (LBBB) with QRS duration of >120ms or a non-LBBB with QRS >150ms.
• Also patients with conventional pacemaker in NYHA functional class III and ambulatory IV if high percentage of ventricular pacing, are eligible for CRT implantation.
• Subject is in stable sinus rhythm at the time of CRT implant and during the last 2 weeks prior to inclusion.
• Subject is 18 years or older and able and willing to consent.

Exclusion Criteria:

• Impossible to obtain LV volumes by echocardiography.
• Right bundle branch block.
• Permanent atrial fibrillation, flutter or tachycardia (>100 bpm).
• Recent myocardial infarction, within 40 days prior to enrolment.
• Subject underwent coronary artery bypass graft (CABG) or valve surgery, within 90 days.
• Post heart transplantation, or is actively listed on the transplantation list, or has reasonable probability (per investigator's discretion) of undergoing transplantation in the next year.
• Implanted with a LV assist device (LVAD), or has reasonable probability (per investigator's discretion) of receiving a LVAD in the next year.
• Severe aortic stenosis (with a valve area of <1.0 cm2 or significant valve disease expected to be operated on within study period).
• Complex and uncorrected congenital heart disease.
• Breastfeeding women, women of child bearing potential.
• Enrolled in one or more concurrent studies that would confound the results of this study.

Study Plan

How is the study designed?

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Cardiac resynchronisation therapy implantation; Patients with current guideline-based indication for CRT implantation.	Other: Magnetic Resonance Imaging; Device: Cardiac resynchronisation therapy; Other: Echocardiography; Other: Positron Emission Tomography

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiac resynchronisation therapy (CRT) response assessed by echocardiography	Reduction in LVESV ≥15% from baseline	Change of left ventricular end-systolic volume (LVESV) between baseline and 6 months after CRT implantation
CRT response assessed by echocardiography	Reduction in LVESV ≥15% from baseline	Change of LVESV between baseline and 12 months after CRT implantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reverse left ventricular remodelling measured as changes in left ventricular volume by echocardiography	Measured as changes in left ventricular volume by echocardiography	Change of remodelling between baseline, 6 and 12 months after CRT implantation
Reverse left ventricular remodelling measured as changes in left ventricular ejection fraction by echocardiography	Measured as changes in left ventricular ejection fraction by echocardiography	Change of remodelling between baseline, 6 and 12 months after CRT implantation
New York Heart Association (NYHA) class changes	A decrease of ≥1 NYHA class	Change of NYHA class between baseline, 6 and 12 months after CRT implantation
Functional capacity changes assessed by 6-minute walking test	Assessed by 6-minute walking test	Change of functional capacity between baseline and 6 months after CRT implantation
Functional capacity changes assessed by peak oxygen uptake ergospirometry (VO2max)	Assessed by peak oxygen uptake ergospirometry (VO2max)	Change of functional capacity between baseline and 6 months after CRT implantation
Quality of Life changes		Change of QoL between baseline, 6 and 12 months after CRT implantation
Heart failure related hospital admissions		Assessment of the number of hospital admissions at 6 and 12 months after CRT implantation
Death	Death by heart failure, sudden cardiac death and all-cause death	Assessment of possible death at 6 and 12 months after CRT implantation

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven
• Collaborators: Oslo University Hospital
• Investigators: Principal Investigator: Jens-Uwe Voigt, MD, PhD, Universitaire Ziekenhuizen KU Leuven; Principal Investigator: Otto A Smiseth, MD, PhD, Oslo University Hospital

Publications and helpful links

General Publications

• Degtiarova G, Claus P, Duchenne J, Cvijic M, Schramm G, Nuyts J, Voigt JU, Gheysens O. Low septal to lateral wall 18F-FDG ratio is highly associated with mechanical dyssynchrony in non-ischemic CRT candidates. EJNMMI Res. 2019 Dec 9;9(1):105. doi: 10.1186/s13550-019-0575-9.

Study record dates

Study Major Dates

• Study Start: September 1, 2015
• Primary Completion (Actual): December 1, 2018
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: August 12, 2015
• First Submitted That Met QC Criteria: August 28, 2015
• First Posted (Estimate): September 2, 2015

Study Record Updates

• Last Update Posted (Actual): January 9, 2020
• Last Update Submitted That Met QC Criteria: January 7, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Heart Failure; Echocardiography; Cardiac Resynchronisation Therapy; Apical rocking; Septal flash; Left ventricular dyssynchrony
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Heart Block; Heart Failure; Bundle-Branch Block; Cardiomyopathies
• Other Study ID Numbers: S538235_v1.2