**9.1 Role of ECMO in cardiogenic shock due to acute myocardial infarction and nonacute myocardial infarction cardiogenic shock**

Acute myocardial infarction (AMI) remains the leading cause of CS. However, non-AMI-related CS is on the rise. Etiologies of cardiogenic shock are enumerated in **Table 3** [74]. The management and response to the intervention vary based on etiology. Despite optimal management, CS continues to be associated with significant morbidity and 30–60% mortality [75]. Various AMCS devices that are available for the management of these patients are IABP, Impella, Protec Duo cannula, CentriMag pump, TandemHeart, and VA-ECMO to provide left- and/or right-heart support [76]. Among all AMCS devices, IABP remains the most widely used, although the use of other more robust devices is increasing [76–78]. Among all the available devices, ECMO provides the highest level of cardiopulmonary support.


#### **Table 3.**

*Potential indications for acute mechanical circulatory support device in cardiogenic shock.*

In the subsequent sections, we will discuss the role of ECMO in CS due to AMI (AMICS) and in the subsequent section, we will discuss the role of ECMO in non-AMI CS including septic shock.

### **9.2 Role of ECMO in post-acute myocardial infarction cardiogenic shock**

Shock is a condition of cellular and tissue hypoxia due to decreased oxygen delivery, increased oxygen demand, or inefficient oxygen utilization, or a combination of these [79]. Acute shock is reversible for a short duration, but it quickly becomes irreversible, leading to multi-organ failure (MOF) and death [80]. Cardiogenic shock (CS) occurs due to cardiac pump failure and defined as a primary cardiac disorder that results in both clinical and biochemical evidences of tissue hypoperfusion including altered mental status, oliguria, and respiratory failure. Clinical criteria include systolic blood pressure (SBP) ≤90 mmHg for ≥30 minutes or need for support to maintain systolic blood pressure ≥90 mmHg and urine output less ≤ 30 mL/h or cool extremities. Hemodynamic criteria include a depressed cardiac index (≤2.2 L/min/m2

of body surface area) and an elevated pulmonary-capillary wedge pressure (PCWP) >15 mmHg [81, 82].

Acute myocardial infarction complicated by cardiogenic shock (AMICS) is a grievous condition associated with significant morbidity and mortality. In several observational studies in patients with AMI, conservative therapy has >80% mortality [83]. Despite primary percutaneous intervention (PCI) with coronary artery angioplasty has significantly improved the survival and has become standard of care for the management of AMI, no definitive management is available for the patients with AMICS [84]. In patients with AMI, 3–10% patients develop CS. Emergency revascularization does not significantly reduce 30-day mortality but significantly improves the sixmonth survival and long-term outcome in patients with AMICS [83]. In patients with AMICS, mortality rate is 30–50% with primary PCI and >80% in patients without primary PCI [85–87].

Acute myocardial infarction due to acute myocardial ischemia results in severe systolic and diastolic dysfunction of the heart with elevation in left ventricular end-diastolic pressure (LVEDP), PCWP, pulmonary edema, decrease in stroke volume, and low cardiac output [88]. Therefore, the aim of treating AMICS patients is to alleviate myocardial ischemia, reduce ventricular loading, support cardiac and respiratory function, and improve end-organ perfusion [89].

Given the high early mortality rate associated with AMICS despite revascularization therapies, physicians have sought out other therapies to improve results. Advancement in the technology has expanded the availability of acute mechanical circulatory support (AMCS) devices such as intra-aortic balloon pump (IABP), Impella, and ECMO. IABP was the earliest available AMCS device. Positive impact in improving coronary and systemic perfusion and reducing the myocardial oxygen demand in the setting of heart failure reported in various animal and human studies in the late 1990s and early 2000s led to widespread use of IABP in patients with AMI [90, 91]. The SHOCK (Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock) registry also showed >15% reduction in in-hospital mortality with use of IABP in patients with AMI who underwent thrombolysis (46.5% in thrombolysis and IABP vs. 62.9% in thrombolysis alone, *P* < 0.005). However, when the SHOCK Trial and Registry established the significant impact of early revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) on the survival in patients with AMI, use of IABP went into disrepute [83, 92]. Subsequent IABP-SHOCK II (Intra-aortic Balloon Support for Myocardial Infarction with Cardiogenic Shock) trial in 2012 that included 600 patients failed to demonstrate any benefit of IABP over medical therapy alone immediately prior to coronary revascularization in terms of reduced 30-day mortality, achieving hemodynamic stability, ICU stay, organ perfusion, dose of catecholamine, rate of stroke, bleeding, peripheral ischemic complications, recurrent AMI, and stent thrombosis [93]. Further 12-month and 6-year follow-ups of SHOCK-IABP II trial patients also did not show any mortality benefit [94, 95]. All of these led to downgradation of IABP use in patients with AMI-CS to class IIIB in the European Society of Cardiology and class IIb recommendation in the American College of Cardiology/ American Heart Association guidelines [96, 97]. Subsequently, use of other AMCS devices has increased for the management of AMICS. In last decade, Impella has become the most commonly used device after IABP in patients with AMICS with LV dysfunction for periprocedural management. However, in patients with biventricular

### *Overview of Venoarterial Extracorporeal Membrane Oxygenation (VA-ECMO) Support… DOI: http://dx.doi.org/10.5772/intechopen.105838*

failure, associated respiratory distress or acute respiratory distress syndrome (ARDS), and mechanical complications of AMI such as mitral regurgitation or ventricular septal defect, ECMO is preferred over other devices. In resource-limited countries where other AMCS devices are not available apart from IABP and ECMO, ECMO can be used for periprocedural management. Further, ECMO is the only AMCS device that provides complete cardiopulmonary support and improves end-organ perfusion. Studies have also supported the role of ECMO in the management of AMICS patients. A study by Sheu et al. including patients with AMICS who underwent primary PCI without the ECMO (115 patients) and primary PCI with ECMO (219 patients) found significantly reduced 30-day mortality (30.1% for ECMO group vs. 41.7% for non-ECMO group) with the use of ECMO [98]. Another study by Tsao et al. also evaluated the role of ECMO in patients with AMICS and managed with primary PCI. The first group managed with IABP (25 patients), and the second group managed with ECMO (33 patients). Baseline characteristics and disease severity including age, gender, coronary risk factors, TIMI risk scores for STEMI and NSTEMI, euro SCORE, APACHE score, and SYNTAX score (including the number of coronary vessels that were involved) were comparable in both the groups. Patients in the ECMO group had significantly increased survival compared to IABP group (44% in IABP group vs. 81.82% in ECMO group), and this trend continued through the 1-year follow-up (survival in IABP group 24% vs. survival in ECMO group 63.64%) [99]. A retrospective single-center study done by Esper et al. included 18 patients who received VA-ECMO for AMICS, after the revascularization therapy. ECMO run lasted for an average of 3.2 ± 2.5 days with a mean hospital stay of 23.4 days, and 67% of patients survived to discharge [100].

Another study by Negi et al. included 15 patients with AMI and refractory CS who were placed on VA-ECMO. One-third of these patients had OHCA and 60% had ST elevated AMI. In 60% of patients, IABP was inserted in addition to VA-ECMO. Median duration of VA-ECMO support was 45 hours, and 50% of patients were successfully weaned off VA-ECMO. The survival to discharge was 47%, and all survivors were alive 30 days after discharge. In total, 53% of patients experienced vascular complications [101]. Another observational study by Vallabhajosyula et al. utilizing the National Inpatient Sample database also reported 40.8% survival with use of VA-ECMO in patients with AMICS. The study analyzed 2962 patients over a period of 14 years. There was a notable trend toward improving survival over the course of time, and 12% of patients were bridged to a left ventricular assist device (LVAD) or heart transplantation [102]. A systematic review of nine studies of patients with acute myocardial infection-induced cardiac shock concluded that using venoarterial extracorporeal membrane oxygenation provides temporary support has more benefits compared to standards of care and can assure a higher survival rate [103].

Although various retrospective observational studies support the role of ECMO in the management of patients with AMICS, there have been no randomized controlled trials (RCTs) assessing the use of ECMO in AMICS. Currently, two European RCTs, EURO-SHOCK, and ECLS-SHOCK, are enrolling the patients. EURO-SHOCK will randomly assign 428 patients to ECMO or conventional therapy and evaluate 30-day mortality as the primary result; the study is anticipated to conclude in February 2024 [104]. ECLS SHOCK will also randomize 420 patients with AMICS undergoing revascularization to ECMO or medical treatment alone. The primary outcome is 30-day mortality, and the trial is anticipated to conclude in August 2023 [105].
