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

Not Applicable

Active, not recruiting

• Conditions: Heart Failure; Left Ventricular Systolic Dysfunction
• Interventions: Device: ICD; Device: ILR

• Registration Number: NCT01918215
• Lead Sponsor: Flinders University

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-04-19
• Study First Submitted QC: 2013-08-05
• Study First Posted: 2013-08-07
• Study Start: 2015-07
• Status Verified: 2023-03
• Last Update Submitted: 2023-03-03
• Last Update Posted: 2023-03-07
• Primary Completion: 2025-08
• Study Completion: 2025-08

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 449

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Device Implantation	ILR	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 Implantation	ICD	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

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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
Health economic evaluation of cost	At study completion, average of 4 years	Australia only
Quality of life assessed by Minnesota Living with Heart Failure Questionnaire	3, 6,12, 24, 36, 48 months
Heart failure related hospitalizations	Through to study completion, an average of 4 years
Quality of life assessed by EuroQol-5D-5L questionnaire	3, 6,12, 24, 36, 48 months

Trial Locations

Locations (18)

The Bristol Heart Institute; 🇬🇧 Bristol, United Kingdom

The Alfred; 🇦🇺 Melbourne, Victoria, Australia

St Vincent's Hospital; 🇦🇺 Fitzroy, Victoria, Australia

John Hunter Hospital; 🇦🇺 New Lambton, New South Wales, Australia

Princess Alexandra Hospital; 🇦🇺 Brisbane, Queensland, Australia

Lyell McEwin Hospital; 🇦🇺 Elizabeth Vale, South Australia, Australia

Flinders Medical Centre; 🇦🇺 Bedford Park, South Australia, Australia

Coburg Hospital; 🇩🇪 Coburg, Germany

Sir Charles Gairdner Hospital; 🇦🇺 Nedlands, Western Australia, Australia

Royal Perth Hospital; 🇦🇺 Perth, Western Australia, Australia

University Hospital Wurzburg; 🇩🇪 Wurzburg, Germany

Schwarzwald-Baar Klinikum; 🇩🇪 Villingen-Schwenningen, Germany

Golden Jubilee National Hospital; 🇬🇧 Clydebank, United Kingdom

Glenfield General Hospital; 🇬🇧 Leicester, United Kingdom

University Hospital of South Manchester NHS Foundation Trust; 🇬🇧 Manchester, United Kingdom

Royal Brisbane & Women's Hospital; 🇦🇺 Herston, Queensland, Australia

Royal Hobart Hospital; 🇦🇺 Hobart, Tasmania, Australia

Belfast Health and Social Care Trust; 🇬🇧 Belfast, United Kingdom