Cardiac Magnetic Resonance GUIDEd Management of Mild-moderate Left Ventricular Systolic Dysfunction. (CMR_GUIDE)

Cardiac Magnetic Resonance GUIDEd Management of Mild-moderate Left Ventricular Systolic Dysfunction

Contemporary heart failure (HF) guidelines recommend insertion of a primary prevention implantable defibrillator (ICD) in patients with left ventricular ejection fraction less than 35% (LVEF < 35%) on maximally tolerated medical therapy. Nevertheless, there are a substantial number of HF patients who have LVEF>35% and hence do not qualify for ICD, who succumb to sudden cardiac death (SCD). At present our tools to reliably risk stratify these patients with mild-moderate systolic dysfunction (LVEF 36-50%) are poor. It is likely that these patients have ventricular scar and/or replacement fibrosis as a substrate for their malignant arrhythmia. Cardiovascular magnetic resonance imaging (CMR) can reliably identify and quantify both ventricular scar (seen in Ischaemic cardiomyopathy, ICM) and replacement myocardial fibrosis (seen in Non-Ischemic Cardiomyopathy, NICM).

Methods/Design: A multi-centre randomised controlled trial in which 428 patients with mild-moderate left-ventricular systolic dysfunction (either ICM or NICM) and ventricular scar/fibrosis on cardiovascular magnetic resonance are randomized to either ICD or implantable loop recorder (ILR) insertion and are followed up until the last patient recruited has been in the study for 3 years.

Potentially eligible patients will have a screening CMR and will be enrolled into the device arm of study based on the presence of any ventricular scar/fibrosis (CMR +). Patients who do not have ventricular scar/fibrosis will be followed up in an observational registry, and will not be randomised.

In both the device and registry arms, we aim to enrol 700 patients in Australia and 355 in Europe.

The primary hypothesis is that among patients with mild-moderate left ventricular systolic dysfunction, a routine CMR guided management strategy of ICD insertion is superior to a conservative strategy of standard care.

Study Overview

• Status: Active, not recruiting
• Conditions: Heart Failure; Left Ventricular Systolic Dysfunction
• Intervention / Treatment: Device: ICD; Device: ILR

• Study Type: Interventional
• Enrollment (Actual): 449
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Joseph B Selvanayagam, MBBS; Phone Number: +61 8 8404 2195; Email: joseph.selvanayagam@flinders.edu.au

Study Locations

• Australia
  • New South Wales
    • New Lambton, New South Wales, Australia, 2305
      • John Hunter Hospital
  • Queensland
    • Brisbane, Queensland, Australia, 4102
      • Princess Alexandra Hospital
    • Herston, Queensland, Australia, 4029
      • Royal Brisbane & Women's Hospital
  • South Australia
    • Bedford Park, South Australia, Australia, 5042
      • Flinders Medical Centre
    • Elizabeth Vale, South Australia, Australia, 5112
      • Lyell McEwin Hospital
  • Tasmania
    • Hobart, Tasmania, Australia, 7000
      • Royal Hobart Hospital
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
      • St Vincent's Hospital
    • Melbourne, Victoria, Australia, 3004
      • The Alfred
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Sir Charles Gairdner Hospital
    • Perth, Western Australia, Australia, 6000
      • Royal Perth Hospital
• Germany
  • Coburg, Germany, 96450
    • Coburg Hospital
  • Villingen-Schwenningen, Germany, 78052
    • Schwarzwald-Baar Klinikum
  • Wurzburg, Germany, 97080
    • University Hospital Würzburg
• United Kingdom
  • Belfast, United Kingdom, BT12 6NT
    • Belfast Health and Social Care Trust
  • Bristol, United Kingdom, BS2 8HW
    • The Bristol Heart Institute
  • Clydebank, United Kingdom, G814DY
    • Golden Jubilee National Hospital
  • Leicester, United Kingdom, LE39QP
    • Glenfield General Hospital
  • Manchester, United Kingdom, M23 9LT
    • University Hospital of South Manchester NHS Foundation Trust

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 equal or greater than 18 years
• Patients with coronary artery disease (CAD) or dilated cardiomyopathy (DCM) of the idiopathic, chronic post myocarditis or familial type.
• Left ventricular systolic impairment as defined by left ventricular ejection fraction 36-50% by any current standard technique (echocardiogram, multiple gated acquisition scan (MUGA), angiography or CMR taken in the last six months. If a LGE CMR has been taken within 2 months this scan can be used for inclusion
• Able and willing to comply with all pre-, post- and follow-up testing, and requirements
• On maximum tolerated doses of ACE inhibitors (or Angiotensin and Receptor Blockers if intolerant of ACE) and Beta Blockers

Exclusion Criteria:

1. History of cardiac arrest or spontaneous or inducible sustained ventricular tachycardia or ventricular fibrillation unless within 48 hours of an acute MI
2. Cardiomyopathy related to sarcoidosis
3. Standard Cardiac Magnetic Resonance imaging contraindications (e.g. severe claustrophobia)
4. Currently implanted permanent pacemaker and/or pacemaker/ICD lead
5. Clinical indication for ICD or Pacemaker or cardiac resynchronisation therapy.
6. CMR LVEF ≤35% or>50%
7. Severe renal insufficiency (eGFR< 30mls/min/1.73m2)
8. Recent Myocardial Infarction (MI) (<40 days) or cardiac revascularization (<90 days)
9. New York Heart Association HF functional class IV at baseline
10. Conditions associated with life expectancy <1 year
11. Pregnancy or in females of child-bearing potential, the non-use of accepted forms of contraception

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Device Implantation; A prospective, blocked, randomised, placebo-controlled trial of primary prophylaxis ICD therapy or implantable loop recorder (ILR) insertion in patients with LVEF 36-50% and Late Gadolinium Enhancement(LGE)on CMR	Device: ICD; Device: ILR
No Intervention: Observational Registry; A prospective observational registry of patients with LVEF 36-50% and no LGE on CMR

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite of Sudden Cardiac Death or haemodynamically significant ventricular arrhythmia	Defined as: ventricular arrhythmia producing syncope (loss of consciousness) or associated with hypotension (SBP<90mmHg) except directly associated with device implant procedure.	Through to study completion, an average of 4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sudden Cardiac Death		Through to study completion, an average of 4 years
Haemodynamically significant ventricular arrhythmia		Through to study completion, an average of 4 years
All-cause mortality		Through to study completion, an average of 4 years
Change in New York Heart Association Functional class		3, 6,12, 24, 36, 48 months
Heart failure related hospitalizations		Through to study completion, an average of 4 years
Health economic evaluation of cost	Australia only	At study completion, average of 4 years
Quality of life assessed by Minnesota Living with Heart Failure Questionnaire		3, 6,12, 24, 36, 48 months
Quality of life assessed by EuroQol-5D-5L questionnaire		3, 6,12, 24, 36, 48 months

Collaborators and Investigators

• Sponsor: Flinders University
• Collaborators: South Australian Health and Medical Research Institute
• Investigators: Principal Investigator: Joseph B Selvanayagam, MBBS, Flinders Medical Centre

Publications and helpful links

General Publications

• Selvanayagam JB, Hartshorne T, Billot L, Grover S, Hillis GS, Jung W, Krum H, Prasad S, McGavigan AD. Cardiovascular magnetic resonance-GUIDEd management of mild to moderate left ventricular systolic dysfunction (CMR GUIDE): Study protocol for a randomized controlled trial. Ann Noninvasive Electrocardiol. 2017 Jul;22(4):e12420. doi: 10.1111/anec.12420. Epub 2017 Jan 24.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2015
• Primary Completion (Anticipated): August 1, 2025
• Study Completion (Anticipated): August 1, 2025

Study Registration Dates

• First Submitted: April 19, 2013
• First Submitted That Met QC Criteria: August 5, 2013
• First Posted (Estimate): August 7, 2013

Study Record Updates

• Last Update Posted (Estimate): March 7, 2023
• Last Update Submitted That Met QC Criteria: March 3, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Murmurs; Ventricular Dysfunction; Systolic Murmurs; Ventricular Dysfunction, Left
• Other Study ID Numbers: CMRG-HF-1