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

Study Overview
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Brief Summary
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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.

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

Conditions
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Heart Failure, Left Ventricular Systolic Dysfunction

Intervention / Treatment
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* Device: ICD
* Device: ILR


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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Device Implantation<br>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<br> <br> Device: ILR<br> <br> |
| No Intervention: Observational Registry<br>A prospective observational registry of patients with LVEF 36-50% and no LGE on CMR | |

What is the study measuring?
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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 |