ODSSEY-SCD_Identification Of Markers to preDict the rISk of Sudden Cardiac Death in Moderated LVEF in ischEmic cardiomyopathY

Objectives Identify risk markers for sudden cardiac death in patients with ischemic heart disease and moderately impaired left ventricular ejection fraction (between 35 and 50%) in order to develop a risk score predictive of the risk of sudden death in this population.

Type of study: Interventional, exploratory, multicenter, prospective.

Number of centers: 17

Study description Inclusion in French high-volume centers of post-myocardial infarction patients with LVEF between 35% and 50%. Patients will be included at least 40 days after myocardial infarction, if their LVEF is between 35% and 50%.

All patients will undergo cardiac MRI. The score published by De Chillou et al. will be calculated. In a second phase, after further examinations (see below), patients will be followed for 60 months to assess the risk of SCD and malignant ventricular arrhythmia. Follow-up will be clinical and by implanting an implantable loop recorder (ILR) with remote monitoring (RM).

Several examinations will be carried out: transthoracic echocardiography, ECG, blood sampling [with the creation of a biological collection to explore myocardial fibrosis and inflammatory biomarkers (e.g. PIIINP, PICP, ICTP, Galectin 3, sST2), genetic evaluation], Holter ECG.

Primary endpoint

• Occurrence of sudden cardiac death or cardiovascular death or malignant ventricular arrhythmias (life-threatening ventricular arrhythmias: ventricular tachycardia (>30s) or ventricular fibrillation) at 60 months follow-up (dependent variable)
• Various markers recovered during the various initial examinations and during follow-up (clinical and remote monitoring) to predict the risk of SCD or malignant ventricular arrhythmia (independent variable)

Number of subjects: 400 patients

Inclusion criteria

• Patients over 18 years of age
• Hospitalized for acute STEMI within 6 months (Type 1 myocardial infarction according to ESC recommendations, Thygesen EHJ 2018).
• Left ventricular ejection fraction between 35% and 50% at least 40 days after acute myocardial infarction (see above).
• Under optimal tolerated medical treatment.
• Covered by a social security scheme.
• Legally competent to give voluntary informed consent to participate in the study.
• Patient who will not participate in further studies involving an investigational drug or device until the end of the trial (i.e. 60 months). Participation in registries is authorized

Non-inclusion criteria

• Presence of a secondary prevention indication for implantation of an implantable automatic defibrillator (ICD)
• Presence of a pacemaker
• Administration of ventricular antiarrhythmic drugs other than beta-blockers (i.e. amiodarone, sotalol, flecainide)
• Patients with systemic diseases (cancer, liver failure or end-stage renal disease)
• Patients with assessed life expectancy < 1 year.
• Age > 80
• Adult patient under legal protection (guardianship, curatorship or other legal protection measure)
• The subject is pregnant or nursing or positive beta HCG for women of childbearing age
• Patient participating in another clinical research protocol involving an investigational drug or device within the last 30 days (participation in a registry is permitted at the same time).

Brief description of the device The patients included in the follow-up will benefit from an ILR (Boston Scientific, LUX-DxTM ICM) associated with RM, which enables permanent cardiac rhythm monitoring, including recording of ventricular arrhythmias.

Study procedure Patients who have had a STEMI at least 40 days previously, with an LVEF between 35 and 50%, will undergo myocardial MRI, electrocardiogram (ECG), trans-thoracic echocardiography (TTE), biological sampling with creation of a serum bank, genetic sampling, ECG Holter and implantation of an implantable holter (LUX-DxTM ICM, Boston Scientific). These various examinations will provide information for the creation of a risk score to predict the risk of sudden death.

These patients will benefit from annual clinical cardiological follow-up with conventional cardiological assessment [clinical examination, blood pressure, ECG, ETT, biological workup (CBC, Plqt, NA, K, urea, creatininemia, CKD-EPI, NT-ProBNP, EAL, fasting glycemia, TSH, beta-HCG)] and implantable holter telecardiological follow-up.

The use of ventricular anti-arrhythmics (i.e. amiodarone, sotalol, flecainide) is prohibited throughout the patient's follow-up, with the exception of beta-blockers.

In addition, algorithms for the management of different arrhythmias are proposed:

• Non-sustained ventricular tachycardia (NSVT): defined as < 30 seconds. At the discretion of the clinician in charge of the patient: beta-blocker augmentation and/or electrophysiological exploration and right ventricular pacing leading to implantation of an ICD according to ESC 2022 recommendations (IIa) and the PRESERVE-EF study.
• Sustained ventricular tachycardia: Implantation of a ICD for primary prevention according to ESC 2022 recommendations (Class IIa, Level B). Possibility of ventricular tachycardia ablation (ESC 2022: Class IIa, level C).
• Ventricular fibrillation: Implantation of a ICD for primary prevention according to ESC 2022 recommendations (Class I, level C). Possibility of ventricular tachycardia ablation.
• Death: retrieval of LUX-DxTM ICM for interrogation and retrieval of data from RM
• Atrial fibrillation: usual management for anticoagulation (ESC guidelines 2024). If atrial fibrillation is not tolerated, an ablation procedure should be preferred. The use of atrial anti-arrhythmics (i.e. amiodarone, sotalol, flecainide) is prohibited throughout the patient's follow-up, with the exception of beta-blockers.

If a ICD is implanted, a monitor zone should be programmed to monitor the occurrence of monomorphic slow VT that does not require anti-tachycardia pacing (ATP). Therapy zones (ATP / shock) will of course be programmed at the clinician's discretion, in line with current recommendations.

Inclusion criteria

• Patients over 18 years of age
• Hospitalized for acute STEMI within 6 months (Type 1 myocardial infarction according to ESC recommendations, Thygesen EHJ 2018).
• Left ventricular ejection fraction between 35% and 50% at least 40 days after acute myocardial infarction (see above).
• Under optimal tolerated medical treatment.
• Covered by a social security scheme.
• Legally competent to give voluntary informed consent to participate in the study.
• Patient who will not participate in further studies involving an investigational drug or device until the end of the trial (i.e. 60 months). Participation in registries is authorized

Exclusion criteria

• Presence of a secondary prevention indication for implantation of an implantable automatic defibrillator (ICD)
• Presence of a pacemaker
• Administration of ventricular antiarrhythmic drugs other than beta-blockers (i.e. amiodarone, sotalol, flecainide)
• Patients with systemic diseases (cancer, liver failure or end-stage renal disease)
• Patients with assessed life expectancy < 1 year.
• Age > 80
• Adult patient under legal protection (guardianship, curatorship or other legal protection measure)
• The subject is pregnant or nursing or positive beta HCG for women of childbearing age
• Patient participating in another clinical research protocol involving an investigational drug or device within the last 30 days (participation in a registry is permitted at the same time).