MAgnetic Resonance Imaging-guided implanTation of Cardioverter DEFibrillators (SMART-DEF)

Multicenter randomiSed Trial on MAgnetic Resonance Imaging-guided implanTation of Cardioverter DEFibrillators

Implantable cardioverter-defibrillators (ICD) are currently recommended for the primary prevention of sudden cardiac death (SCD) in patients with a remote (>6 weeks) myocardial infarction (MI) and a low (≤35%) left ventricular ejection fraction (LVEF).

Ventricular tachycardia (VT) and/or ventricular fibrillation (VF), which are responsible for most SCDs, result from the presence of surviving myocytes embedded within fibrotic MI-scar. The presence of these surviving myocytes, as well as their specific arrhythmic characteristics, is not captured by LVEF. Hence, the use of LVEF as a unique risk-stratifier of SCD results in a low proportion (17 to 31%) of appropriate ICD device therapy at 2 years. Consequently, most patients with a prophylactic ICD do not present VT/VF requiring ICD therapy prior to their first-ICD battery depletion. Thus, many patients are exposed to ICD complications, such as inappropriate shocks, without deriving any health benefit. Therefore, the current implantation strategy of prophylactic ICDs, based on LVEF only, needs to be improved in post-MI patients.

Study Overview

• Status: Not yet recruiting
• Conditions: Myocardial Infarction; Ventricular Fibrillation; Ventricular Tachycardia; Sudden Cardiac Death
• Intervention / Treatment: Device: MRI screening; Device: Implantable Loop Recorder; Device: Implantable Cardioverter Defibrillator

• Study Type: Interventional
• Enrollment (Estimated): 1812
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Christian de CHILLOU, MD, PhD; Email: c.dechillou@chru-nancy.fr
• Study Contact Backup: Name: Guilaume DROUOT, PhD; Email: g.drouot@chru-nancy.fr

Study Locations

• France
  • Vandœuvre-lès-Nancy, France, 54511
    • CHRU Nancy
    • Contact: Christian de CHILLOU, MD, PhD; Email: c.dechillou@chru-nancy.fr
    • Contact: Guillaume DROUOT, PhD; Email: g.drouot@chru-nancy.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age > 18 years;
• Patients with a LVEF≤35% assessed at least after a 40 to 90 days period (depending on the presence of coronary revascularization) following an index myocardial infarction;
• Left ventricular systolic impairment as defined by LVEF≤35% by any current standard technique (echocardiogram, multiple gated acquisition scan, or MRI) within 2 months;
• Able and willing to comply with all pre-, post- and follow-up testing, and requirements;
• Use of maximum tolerated doses of ACE inhibitors (or Angiotensin II Receptor Blockers if intolerant of ACE) and Beta Blockers and MRA as per ESC guidelines;
• Person affiliated to or beneficiary of a social security plan
• Person informed about study organization and having signed the informed consent

Exclusion Criteria:

• History of cardiac arrest or sustained VT or VF unless within 48 hours of an acute myocardial infarction;
• Standard contraindications for cardiac LGE-MRI;
• Hypersensitivity to gadolinium-based contrast agent;
• Currently implanted permanent pacemaker and/or ICD;
• Patient refusal of ICD/ILR implantation;
• Currently implanted permanent pacemaker and/or ICD;
• Clinical indication for or Cardiac Resynchronization Therapy (CRT);
• Severe renal insufficiency defined by a glomerular filtration rate (GFR) < 30 mL/min/1.73m²;
• Recent PTCA (within 30 days) or CABG (within 90 days);
• Baseline NYHA functional class IV;
• Contraindication for ICD implantation according to current guidelines;
• Woman of childbearing age without effective contraception;
• Person referred in articles L.1121-5, L. 1121-7 and L.1121-8 of the French Public Health Code.

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
Experimental: Implantable Loop Recorder; Patients identified at very low-risk of VT/VF randomized to be implanted with an ILR (experimental strategy). Following randomization, these patients will be followed using remote ILR monitoring.	Device: MRI screening; Cardiac Magnetic Resonance imaging for the quantification of the infarct intramural scar; Device: Implantable Loop Recorder; Inplantation of the Implantable Loop Recorder (ILR) for the patients assigned to the experimental group
Other: Implantable Cardioverter Defibrillator; Patients identified at very low-risk of VT/VF randomized to be implanted with an ICD (reference strategy), which corresponds to the currently recommended treatment in post-MI patients with a LVEF ≤35% (European Society of Cardiology guidelines 2015) (Zeppenfeld et al., 2022).	Device: MRI screening; Cardiac Magnetic Resonance imaging for the quantification of the infarct intramural scar; Device: Implantable Cardioverter Defibrillator; Inplantation of the Implantable Cardioverter Defibrillator (ICD) for the patients assigned to the control group, according to the current guidelines

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of Sudden Cardiac Death (SCD) during the follow-up period	Occurrence of SCD during the follow-up period, as defined by the World Health Organization in 10-ICD: death occurring within 24 hours from onset of symptoms.	72 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total number of deaths during the follow-up period		72 months
Total number of deaths from cardiovascular cause during the follow-up period		72 months
Total number of SCD due to ventricular arrhythmia during the follow-up period		72 months
Total number (per patient) of sustained VT episodes treated by the ICD or recorded by the ILR during the follow-up period		72 months
Total number (per patient) of VF episodes treated by the ICD or recorded by the ILR during the follow-up period		72 months
Total number of hospitalizations due to cardiovascular causes during the follow-up period		72 months
Duration of hospitalizations due to cardiovascular causes during the follow-up period		72 months
Total number of hospitalizations from any cause during the follow-up period		72 months
Duration of hospitalizations from any cause during the follow-up period		72 months
Quality of life assessed by the scoring obtained from EuroQol questionnaires (EQ-5D-5L) during the follow-up period		72 months
Measurements of the estimated costs	Measurements of the estimated costs for the National Health Insurance System (NHIS) in the different arms of the trial	72 months
Dice scores of the segmentation of the left ventricle and scar obtained from new MR sequences	Dice scores of the segmentation of the left ventricle and scar obtained from new MR sequences, LGE segmentation by cardiologists/radiologists as the ground truth	36 months
Contour distance metrics of the segmentation of the left ventricle and scar obtained from new MR sequences	Contour distance metrics of the segmentation of the left ventricle and scar obtained from new MR sequences, LGE segmentation by cardiologists/radiologists as the ground truth	36 months
Dice scores of the accuracy of fully automated segmentation of the left ventricle and scar	Dice scores of the accuracy of fully automated segmentation of the left ventricle and scar, using manually corrected segmentation by cardiologists/radiologists as the ground truth	36 months
Contour distance metrics of the accuracy of fully automated segmentation of the left ventricle and scar	Contour distance metrics of the accuracy of fully automated segmentation of the left ventricle and scar, using manually corrected segmentation by cardiologists/radiologists as the ground truth	36 months

Collaborators and Investigators

• Sponsor: Central Hospital, Nancy, France

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): April 1, 2030
• Study Completion (Estimated): April 1, 2030

Study Registration Dates

• First Submitted: January 16, 2024
• First Submitted That Met QC Criteria: February 19, 2024
• First Posted (Estimated): February 21, 2024

Study Record Updates

• Last Update Posted (Estimated): February 21, 2024
• Last Update Submitted That Met QC Criteria: February 19, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Myocardial Infarction
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Death, Sudden; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Heart Arrest; Myocardial Infarction; Infarction; Death; Ventricular Fibrillation; Tachycardia; Tachycardia, Ventricular; Death, Sudden, Cardiac
• Other Study ID Numbers: 2023-A01353-42

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No