Assessment of ECMO in Acute Myocardial Infarction Cardiogenic Shock (ANCHOR)

Assessment of ECMO in Acute Myocardial Infarction With Non-reversible Cardiogenic Shock to Halt Organ Failure and Reduce Mortality (ANCHOR)

Data from case series and large retrospective trials suggest that the early treatment of cardiogenic shock AMI patients with the association of VA-ECMO and IABP may significantly decrease mortality, which is still unacceptably high nowadays (40-50% at 30 days). An important benefit for the patients randomized to the ECMO arm is expected and the risk-to-benefit ratio is expected to be in favor of the experimental treatment arm.

Scientific background - Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is used more and more frequently in patients with acute myocardial infarction (AMI) and refractory cardiogenic shock despite the absence of high level scientific evidence to recommend the use of temporary circulatory support devices (TCS) in this setting.TCS support may also benefit to cardiogenic shock patients not initially refractory to conventional medical management since their mortality exceeds 40% and most of deaths are due to the development of refractory cardiogenic shock and multiple organ failure. The ANCHOR trial is therefore designed to test the hypothesis that VA-ECMO support associated with IABP results in improved outcomes in comparison with optimal medical treatment alone in patients with AMI and cardiogenic shock. An ethical rescue option to VA-ECMO will however be provided to control patients with cardiogenic shock refractory to conventional medical treatment since recent data suggested survival up-to 50% with ECMO support in this setting. Main objective - To determine if early VA-ECMO combined with IABP support and optimal medical treatment would improve the outcomes of patients with acute myocardial infarction complicated by cardiogenic shock as compared with optimal medical treatment alone. Scope of the study - Patients satisfying all of the Inclusion and Exclusion Criteria will be classified as 'Eligible'. Consent to research will be obtained from a close relative or surrogate for all eligible patients prior to randomization. Should such a person be absent, eligible patients will be randomized according to the specifications of emergency consent and the patient will be asked to give his/her consent for the continuation of the trial when his/her condition will allow. Randomization will be possible in centers with robust experience in the management of AMI and cardiogenic shock but no on-site ECMO capability providing that an ECMO retrieval team from the nearest ECMO center can establish ECMO no later than 2 hours after randomization. Before randomization, physicians at the non-ECMO center will check that the ECMO team is immediately available and that an ICU/CCU bed is available at the ECMO center. Thereafter, if the patient is randomized to the ECMO arm, the mobile ECMO retrieval team will travel to the center, initiate VA-ECMO and will rapidly transfer the patient on VA-ECMO to the ECMO center. Description of experimental ECMO + IABP Arm Protocolized conventional management of cardiogenic shock VA-ECMO will be started as soon as possible For patients randomized at non-ECMO centers, a mobile ECMO team will initiate ECMO at the non-ECMO center and transport the patient to the ECMO center immediately IABP inserted in the contralateral femoral artery (unless technically not possible) ECMO management according to protocol ECMO weaning according to protocol Description of conventional treatment Arm Protocolized conventional management of cardiogenic shock IABP not recommended. No other TCS device (e.g., ECMO, Impella, Thoratec PHP, TandemHeart) permitted Rescue VA-ECMO only if one of 1 or 2 or 3 applies: 1. Refractory cardiogenic shock defined as Cardiac index <1.2 l/min/m² or VTI <6 cm AND Assessment and correction of hypovolemia AND (dobutamine ≥15 microg/kg/min + norepinephrine ≥1.5 microg/kg/min) OR epinephrine ≥ 0.75 microg/kg/min Serum lactate >5 mmol/L or serum lactate increased >50% in the last 6 hours 2. Uncontrolled lethal arrhythmia despite K >4.5 mmol/l AND Mg >1.0 mmol/l AND Intubation and mechanical ventilation with deep sedation AND IV Loading of amiodarone AND IV xylocaine 3. Refractory cardiac arrest Mandatory validation of rescue VA-ECMO by an independent adjudicator.

A multicenter, prospective, randomized, comparative open trial will be conducted on two parallel groups of patients with AMI complicated by cardiogenic shock.

VA-ECMO will be instituted percutaneously under echo guidance via the femoral route as soon as possible. An IABP will be systematically inserted in the contralateral femoral artery (unless technically not possible).

Standard management of cardiogenic shock due to myocardial infarction according to the current ESC guidelines. It is not recommended to use IABP support and no other TCS device (e.g., ECMO, Impella, Thoratec PHP, TandemHeart) will be permitted in the control group.

The ECMO device will be the CardioHelp (MAQUET, GETINGE, Orléans, France) using the veno-arterial setting and percutaneous femoro-femoral cannulation with MAQUET GETINGE HLS cannulae. Intraortic balloon pump will be MEGA 50 cc or 40cc, (MAQUET, GETINGE, Orléans, France).

Major Adverse Cardiovascular Events are defined as death, stroke (any new neurological symptoms in association with signs of ischemia or hemorrhage in a cranial CT or MRI), recurrent myocardial infarction, need for repeat revascularization (PCI and/or CABG), renal replacement therapy, re-hospitalization for heart failure, escalation to permanent left ventricular assist device (LVAD) or total artificial heart, cardiac transplant.

Any new neurological symptoms in association with signs of ischemia or hemorrhage in a cranial CT or MRI

Major bleeding (TIMI definition): Any intracranial bleeding (excluding microhemorrhages <10 mm evident only on gradient-echo MRI) OR Clinically overt signs of hemorrhage associated with a drop in hemoglobin of ≥5 g/dL or a ≥15% absolute decrease in hematocrit OR Fatal bleeding (bleeding that directly results in death within 7 d)

Number of days alive without organ failure(s) defined with the SOFA score, catecholamine support, mechanical ventilation and renal replacement therapy

ECMO-related complications (infection at VA-ECMO cannulation sites requiring antibiotics, hemorrhage, limb ischemia requiring surgery, cannula or circuit thrombosis, overt pulmonary edema, thrombocytopenia, gaseous emboli and hemolysis).

Treatment failure defined as death (all-cause) in the ECMO group and death (all-cause) OR rescue ECMO in the control group.

MACE, Major Adverse Cardiovascular Events are defined as death, stroke (any new neurological symptoms in association with signs of ischemia or hemorrhage in a cranial CT or MRI), recurrent myocardial infarction, need for repeat revascularization (PCI and/or CABG), renal replacement therapy, re-hospitalization for heart failure, escalation to permanent left ventricular assist device (LVAD) or total artificial heart, cardiac transplant.

Stroke (any new neurological symptoms in association with signs of ischemia or hemorrhage in a cranial CT or MRI),

Major bleeding (TIMI definition): Any intracranial bleeding (excluding microhemorrhages <10 mm evident only on gradient-echo MRI) OR Clinically overt signs of hemorrhage associated with a drop in hemoglobin of ≥5 g/dL or a ≥15% absolute decrease in hematocrit OR Fatal bleeding (bleeding that directly results in death within 7 d)

Inclusion Criteria: Cardiogenic shock complicating acute myocardial infarction (STEMI or NSTEMI) Revascularization by PCI for acute myocardial infarction has been performed or is planned in the following 60 minutes Systolic blood pressure <90 mmHg for >30 min or catecholamine support required to maintain systolic blood pressure >90 mmHg Signs of pulmonary congestion Signs of impaired organ perfusion with at least one of the following: Altered mental status OR cold, clammy skin and extremities OR oliguria with urine output <30 ml/h OR serum lactate >2.0 mmol/l Exclusion Criteria: Age <18 years Pregnancy Onset of shock >24 Hours Shock of other cause (hypovolemic, anaphylactic or vagal shock) Shock due to massive pulmonary embolism Resuscitation >30 minutes No intrinsic heart activity Patient moribund on the day of randomization or SAPS II >90 Surgical revascularization for AMI (CABG) planned or already performed prior to randomization Cerebral deficit with fixed dilated pupils or Irreversible neurological pathology Mechanical infarction complication (massive mitral regurgitation, pericardium drainage required, septal ventricular defect) Severe peripheral artery disease or previous aortic or ilio-femoral surgery precluding ECMO and IABP insertion Aortic regurgitation > II Other severe concomitant disease with limited life expectancy < 1 year Proven heparin-induced thrombocytopenia ECMO device not immediately available

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