Using rituximab to improve heart function after a heart attack

Inclusion Criteria:

* Age ≥ 18 years with no upper limit (women must be either postmenopausal defined as being amenorrhoeic for greater than 2 years with an appropriate clinical profile, e.g. age appropriate (\>55 years old), history of vasomotor symptoms) or having documented hysterectomy and/or bilateral oophorectomy) ;
* Clinical evidence at presentation of anterior ST-elevation myocardial infarction (STEMI) ) involving the proximal or mid left anterior descending (LAD) defined as symptoms suggestive of acute myocardial ischemia, an electrocardiogram showing ST-segment elevation ≥2 mm in ≥2 contiguous leads in V1 to V4 or a large inferior MI (right coronary artery (RCA), or left circumflex (LCx) coronary artery) with evidence of low-ejection fraction (LVEF\<45%);
* Complete occlusion (i.e. TIMI flow 0-1) of proximal or mid left anterior descending (LAD) right coronary artery (RCA), or left circumflex (LCx) coronary artery on urgent angiography interpreted as the infarct-related artery (IRA);
* Onset of worse symptoms within 48 hours before primary PCI;
* Patients with neutrophils \>1.5 x 109/L at the moment of admission
* Patients with platelet counts \>75 x 109 /L at the moment of admission
* Plan to provide primary percutaneous angioplasty (PPCI) for the patient within 2 hours of ECG diagnosis; confirmed before enrollment;
* Ability to start infusion of rituximab within 3 hours of PPCI ; confirmed before enrollment;
* Written informed consent.

Exclusion Criteria:

Exclusion Criteria :

* History of previous MI without documented preserved left ventricular ejection fraction (LVEF \>50%) prior to the current admission will be an exclusion criterion;
* Presentation with cardiac arrest;
* Cardiogenic shock (defined as systolic blood pressure \<90 mmHg for \>30minutes, or necessitating vasopressors to achieve a blood pressure ≥90 mmHg);
* Cardiac electrical instability (defined as complete heart block needing temporary pacing or any tachyarrhythmia needing cardioversion);
* Patients with Killip class III heart failure;
* History of severe chronic renal failure (define as stage 4 (GFR = 15-29 mL/min) or worse);
* History of hepatitis B, HIV or tuberculosis;
* Patient positive for point of care bedside test of Ag HBs;
* Severe, progressive infections documented;
* Active COVID-19 infection or COVID-19 infection within 3 months;
* Patient with documented severe immune deficiency;
* Presence, or history in ≤ five years, of an ongoing cancer, (except in situ cancer of the cervix or basal cell carcinoma);
* QTcF\> 450 msecs in males, \> 470msecs in females;
* Any oral or intravenous immunosuppressive treatment, immune modulatory monoclonal antibodies or immunodepleting therapy at any time (inhalers and topical creams with corticosteroids are permitted);
* Previous history of major organ transplant including renal transplant;
* Known hypersensitivity to the active substance of rituximab or to proteins of murine origin, or to any of the other excipients;
* Any contraindications to any of the rituximab premedication drugs;
* Contraindications to injectable Polaramine:

Risk of closed-angle glaucoma, Risk of urinary retention linked to urethro-prostatic disorders;

* Expected need for vaccination with a live attenuated vaccine during the study, including incomplete vaccination courses (in case, life, attenuated vaccine must be administered at least 30 days before inclusion in study);
* Absence of a complete COVID-19 vaccination scheme (including recovery from documented COVID infection) as approved at the time of enrollment in the country where the patient is recruited;
* Any obvious contraindications for MRI or conditions which will impede image acquisition for example:

Severe claustrophobia

Non-MRI compatible permanent pacemaker

Patients who have a metallic foreign body (metal silver) in their eye, or who have an aneurysm clip in their brain

Patients who have had metallic devices placed in their back

Known hypersensitivity to imaging products (gadoteric acid, meglumin or any drug containing gadolinium)

* Known hepatic failure;
* Previous history of progressive multifocal leukoencephalopathy;
* Inclusion in other interventional drug study within the previous 3 months;
* Inability to comply with study procedures;
* Patients under guardianship or curatorship.