Journal Pre-proof

Acute Myocardial Infarction Complicated by Cardiogenic Shock:

Analysis of the Position Statement from the European Society of
Cardiology- Acute Cardiovascular Care Association (ACCA) with
Perioperative Implications

Daniel S. Cormican MD , Abraham Sonny MD, FASE ,

Jerome Crowley MD , Richard Sheu MD, FASE , Terri Sun MD ,
Christina M. Gibson DO , Iván J. Núñez-Gil MD,PhD, FESC ,
Harish Ramakrishna MD, FACC, FESC, FASE

PII: S1053-0770(20)31176-9
DOI: https://doi.org/10.1053/j.jvca.2020.10.062
Reference: YJCAN 6318

To appear in: Journal of Cardiothoracic and Vascular Anesthesia

Please cite this article as: Daniel S. Cormican MD , Abraham Sonny MD, FASE ,
Jerome Crowley MD , Richard Sheu MD, FASE , Terri Sun MD , Christina M. Gibson DO ,
Iván J. Núñez-Gil MD,PhD, FESC , Harish Ramakrishna MD, FACC, FESC, FASE , Acute My-
ocardial Infarction Complicated by Cardiogenic Shock: Analysis of the Position Statement
from the European Society of Cardiology- Acute Cardiovascular Care Association (ACCA)
with Perioperative Implications, Journal of Cardiothoracic and Vascular Anesthesia (2020), doi:
https://doi.org/10.1053/j.jvca.2020.10.062

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 1

Category: [Expert Review]

Acute Myocardial Infarction Complicated by Cardiogenic Shock: Analysis of the Position

Statement from the European Society of Cardiology- Acute Cardiovascular Care Association

(ACCA) with Perioperative Implications

Daniel S. Cormican, MDa; Abraham Sonny, MD, FASEb; Jerome Crowley, MDb; Richard Sheu, MD,
e
FASEc; Terri Sun, MDc; Christina M. Gibson, DOd; Iván J. Núñez-Gil,MD,PhD, FESC , Harish

Ramakrishna, MD, FACC, FESC, FASEf

a
Department of Anesthesiology, Divisions of Cardiothoracic Anesthesiology and Critical Care Medicine,

Allegheny Health Network, Pittsburgh, Pennsylvania, USA; e-mail: Daniel.Cormican@AHN.org

b
Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston,

Massachusetts, USA; e-mail: ASONNY@mgh.harvard.edu and JCCROWLEY@mgh.harvard.edu

c
Department of Anesthesiology & Pain Medicine, University of Washington Medical Center, Seattle,

Washington, USA; e-mail: dr.rsheu@gmail.com and terri.sun@gmail.com

d
Department of Anesthesiology, Allegheny Health Network, Pittsburgh, Pennsylvania, USA; e-mail:

Christina.Gibson@AHN.org

e
Iván J. Núñez-Gil, Interventional Cardiology. Cardiovascular Institute. Hospital Clínico San

Carlos, Madrid. Spain

f
Division of Cardiovascular and Thoracic Anesthesiology, Department of Anesthesiology and

Perioperative Medicine, Mayo Clinic, Rochester, Minnesota, USA; e-mail:

Ramakrishna.Harish@mayo.edu

Corresponding Author: Harish Ramakrishna, MD, FACC, FESC, FASE; Division of Cardiovascular and

Thoracic Anesthesiology, Department of Anesthesia and Perioperative Medicine, Mayo Clinic, 200 First
 2

Street SW, Rochester, MN 55901. Telephone: 507-255-7481; Fax: 507-255-5167; E-mail:

Ramakrishna.harish@mayo.edu

The authors have no conflicts of interest to report.

This research did not receive any specific grant from funding agencies in the public, commercial, or not-

for-profit sectors.

Acknowledgments: Barbara Weisser, Mayo Clinic Academic Support Office, Scottsdale, Arizona, USA.

Text word count: 3,709

No. of Tables: 1

No. of Figures: 0

©2020 Mayo Foundation for Medical Education and Research

 3

Abstract

Effective management of cardiogenic shock (CS) is hampered by a lack of evidence-based information.

This is a high-mortality condition, without clear, evidence based guidelines for perioperative

management, specifically-a lack of target end points for treatment (e.g.: mean arterial pressure or

oxygenation), utility of regional care systems or the benefits of palliative care.

The Acute Cardiovascular Care Association (ACCA) of the European Society of Cardiology (ESC)

recently published a position statement that aims to offer contemporary guidance on the diagnosis and

treatment of acute myocardial infarction (AMI) complicated by CS. Herein, we review this complex

clinical topic and review the ACCA statement on AMI associated with CS with a focus on relevance to

perioperative management.

Introduction

Cardiogenic shock (CS) is a condition with complex pathophysiology due to low cardiac

output leading to end-organ hypoperfusion resulting in organ dysfunction; CS is a failure of

oxygen delivery to meet oxygen consumption.1, 2 CS is a feared complication of acute

myocardial infarction (AMI), as the mortality rate of patients with CS as a result of AMI is still

near 40-50% even with current treatment options including early revascularization.3

Management of CS is complex: the CS after AMI can manifest from various different etiologies

– including left ventricular (LV) failure, right ventricular (RV) failure or mechanical

complications such as free wall rupture and papillary muscle rupture, among others - each

specific cause of CS requires its own specific treatment.

 4

Pathophysiology of Acute Myocardial Infarction

Acute myocardial infarction (AMI) can be classified into several forms: type 1 describes

coronary occlusion that results from disruption or erosion of atherothrombotic coronary artery

plaque, leading to intraluminal thrombosis, type 2 describes ischemia resulting from myriad of

causes, elementally attributable to mismatched myocardial oxygen demand and supply, without

acute plaque rupture or disruption. Type 3-5 MI are also described, but beyond the scope of this

review.4, 5 On a cellular level, ischemia triggers a cascade of events that may ultimately leads to

heart failure and CS, if this cascade is not interrupted: within 10-15 minutes of inciting ischemia,

events such as glycogen depletion, myofibril relaxation, myocytic sarcolemma depletion, and

mitochondrial abnormalities occur. Unimpeded, this process leads to cellular apoptosis and

culminates in subendocardial and subepicardial necrosis that occur within hours.6, 7

The pathophysiology of heart failure is complex, best explained by a pathological

paradigm comprised of 1) circulatory failure from inadequate cardiac output, and 2) maladaptive

and unchecked neurohormonal responses.8, 9 Inadequate cardiac output not only causes systemic

hypoperfusion, but also leads to increased left ventricular filling pressures. This can further

impair coronary perfusion and lead to pulmonary congestion, thereby exacerbating myocardial

ischemia and hypoxemia. Circulatory failure triggers systemic vasoconstriction as the body

attempts to maintain adequate end organ perfusion pressure through the activation of the

sympathetic nervous system and the renin-angiotensin-aldosterone system. Although initially

adaptive, this eventually leads to further impairment of cardiac function through increasing

afterload and myocardial oxygen consumption, and chronically causes both sodium and water

retention.10 Pathological activation of a plethora of inflammatory mediators has been implicated.

 5

This includes inducible nitric oxide synthase, which causes vasodilation and inhibits myocardial

contractility, as well as expression of inflammatory mediators such as CRP, TNF-alpha and

specific interleukins.11-15 Inflammatory mediators may contribute to the systemic inflammatory

response observed in almost 20% of patients who presented in one large clinical trial of CS.16

Progression from AMI to CS can develop quickly, with a median time of 5.6-6.2 hours

after AMI.17, 18 CS was defined as the inadequacy of blood delivery to meet resting tissue

metabolism due to impaired heart function by the ACCA/ESC position statement.9 This

definition is largely in line with those proposed by other organizations, albeit simplified.8, 19 It is

widely accepted that further stratification of CS can be based on tissue hypo perfusion severity

(at risk, beginning, classic, deteriorating, and extremis) or peripheral circulation and

intravascular volume status (cold-wet, cold-dry, warm-wet, and warm-dry).19, 20 The diagnosis

of infarct-related CS proposed by the ACCA/ESC position statement includes fulfillment of all

the following criteria: persistent hypotension, evidence of end-organ hypo perfusion, signs of

elevated left-ventricular filling pressure, and confirmed primary cardiac disorder from AMI

sequela. Objective parameters for hypotension (systolic blood pressure < 90 mmHg for more

than 30 minutes or vasopressor support needed to maintain systolic blood pressure > 90 mmHg)

were derived from two large-scale trials and widely accepted in the literature.21, 22 Symptoms of

end-organ hypoperfusion and elevated left-ventricular filling pressure listed include mental status

change, clammy extremities, orthopnea, etc. Semi-objective biochemical markers such as arterial

lactate levels and direct catheterization data may provide additional evidence for state of

physiologic shock.

There are several paths through which AMI can lead to CS, including left ventricular

systolic and diastolic dysfunction (74.5%), acute mitral regurgitation (8.3%), ventricular septal
 6

rupture (4.6%), isolated right ventricular failure (3.4%), and tamponade or cardiac rupture

(1.7%) and others (8%).23, 24 Right ventricular failure can be caused by ischemia or increased

right ventricular afterload from left ventricular failure leading to increased left-sided filling

pressures.25 Right heart failure, in a vicious cycle, exacerbates left heart failure through

reduction in preload and alteration of left ventricular geometry and contractility (interventricular

dependence).26 It is of utmost importance to distinguish CS from other forms of shock (i.e.

hypovolemic, distributive, and obstructive) as their respective management and treatment

strategies are drastically different.27 Misdiagnosis may lead to not only delayed treatment but

also adverse outcomes. Once the diagnosis of AMI is established, history, physical examination,

and echocardiography are the tools of choice to facilitate the diagnosis of CS.9 Other imaging

techniques such as chest X-ray or computed tomography may be of help. Coronary angiography

will be needed to make the definitive diagnosis of coronary artery occlusion.

ACCA/ESC Recommendations for Management of Cardiogenic Shock

After Acute Myocardial Infarction

General Recommendations for Left and/or Right Ventricular Failure

Revascularization Strategy

Over 20 years ago, the SHOCK trial established the superiority of initial

revascularization - as compared to fibrinolytic therapy - for acute myocardial infarction (MI)

complicated by cardiogenic shock (CS).22 They randomized 302 patients with acute MI

complicated by shock from left ventricular dysfunction into early invasive therapy versus initial

medical stabilization. Although 30-day mortality was similar, the 6-month mortality was lower

with early invasive therapy (50% vs 63%) which continued in long term follow up until 6
 7

years.22, 28 Hence, similar to the 2017 European Society of Cardiology (ESC) ST elevation MI

(STEMI) guidelines, the ACCA/ESC position statement recommends early invasive

revascularization therapy over fibrinolytics in patients with acute MI complicated by CS. There

are no randomized controlled trials (RCTs) comparing percutaneous coronary interventions

(PCI) and coronary artery bypass grafting as options for early invasive revascularization among

patients with CS. Although many observational studies report no difference between their

outcomes, selection bias and small sample sizes make results difficult to interpret.29 In

contemporary practice for AMI interventions, coronary artery bypass grafting accounts for only

4%; PCI is the predominantly favored modality. The ACCA/ESC position statement suggests

coronary artery bypass grafting in patients with unsuccessful PCI or when the coronary anatomy

is unsuitable for PCI.

The authors discuss PCI strategies based on the recently published CULPRIT-SHOCK

trial.30 This multicentric RCT, randomized 706 patients with multivessel coronary artery disease

presenting with acute MI and CS to either PCI of only the culprit lesion (with potential for future

staged revascularization of other lesions) or multivessel PCI. The 30-day risk of death and/or

renal replacement therapy was lower with initial PCI of only the culprit lesion (45.9% vs 55.4%).

Hence, the ACCA/ESC position statement recommends that initial PCI in patients with acute MI

complicated by CS should be limited to the culprit lesion.

Antithrombotic Therapy

The ACCA/ESC authors acknowledge the lack of evidence on optimal antithrombotic

therapy in patients with CS after AMI. Important considerations include uncertain

gastrointestinal absorption of orally administered antiplatelet agents in patients with CS.

Although intravenous antiplatelet agents (glycoprotein IIb/IIIa inhibitors abciximab, eptifibatide

 8

and tirofiban and the P2Y12 inhibitor cangrelor) or intravenous anticoagulants may obviate the

absorption concern, data on their efficacy is mostly limited to observational studies. The only

RCT published in this setting randomized 80 patients with AMI complicated by CS undergoing

primary PCI to either receive upfront abciximab infusion for 12 hours (starting pre-procedurally)

or to standard therapy.31 About 35% of patients in the standard therapy group also received

abciximab (compared to 100% in upfront abciximab group). Although no clinical benefit was

demonstrated in either arm, the small sample size makes results difficult to interpret. While we

await results from other ongoing RCTs, the ACCA/ESC statement defers to the 2017 ESC

STEMI guidelines on use of antithrombotic agents, and makes no special recommendations in

the setting of CS.

Sedation and Neurohormonal Blockade

The authors recommend following the 2017 ESC STEMI guidelines on anxiolysis (with

benzodiazepine) and analgesia (with a titrated intravenous opioid, like morphine). However, the

ACCA/ESC position statement caution against over sedation since it can worsen CS. The

benefits of early beta blockade after STEMI and of renin-angiotensin-aldosterone-system

inhibitors after MI with heart failure is well established.32, 33 However, their early initiation in

the context of ongoing cardiogenic shock may have detrimental hemodynamic effects. A

secondary analysis of the TRIUMPH trial reports higher 30-day mortality when beta blockers

and/or renin-angiotensin-aldosterone-system inhibitors were administered within 24 hours of

AMI with CS (27.3% vs 16.9%).34 Hence, the ACCA/ESC position statement recommends

avoiding beta blockers and renin-angiotensin-aldosterone-system inhibitors until shock is

resolved.

Targeted Temperature Management

 9

The benefit of therapeutic hypothermia after cardiopulmonary resuscitation is well

established. Three RCTs show that moderate hypothermia (32- 34 degrees C) for 12- 24 hours

improves neurological outcome after return of spontaneous circulation from a shockable or non-

shockable out-of-hospital cardiac arrest.35-37 However, all these trials completely or partly

exclude patients with CS after return of spontaneous circulation. Hence, the impact of

therapeutic hypothermia on patients with ongoing CS is not well understood. The recently

published SHOCK COOL trial randomized 40 patients presenting for PCI after AMI complicated

by CS to either receive hypothermia (33 degrees Celsius) for 24 hours or not.38 Although the

hypothermia group had a slower decline in arterial lactate, the cardiac power index was similar

between the groups at 24 hours. Notably, the study was not powered to evaluate mortality.

Nevertheless, due to overwhelming evidence on favorable neurological outcome, the

ACCA/ESC position statement recommends moderate hypothermia in CS after cardiopulmonary

resuscitation.

Hemodynamic Management

The ACCA/ESC treatment algorithm for CS recommends a fluid challenge in absence of

signs of fluid overload or pulmonary edema, but recommends diuresis in the setting of

pulmonary edema. These are both class I recommendations in the 2016 ESC heart failure

guidelines.33 In patients in CS with volume overload found to be refractory to diuretics,

continuous veno-venous ultrafiltration may be used to facilitate volume removal. Although

routine use of pulmonary artery catheter has not demonstrated benefit in clinical trials, the

ACCA/ESC position statement supports the 2016 ESC heart failure guidelines which give a

Class IIb recommendation (level of evidence C) for pulmonary artery catheterization in the

presence of refractory symptoms despite initial pharmacological treatment. 33

 10

Although extrapolated from non-CS population, a mean arterial pressure goal of 65 mm

Hg is accepted as a reasonable target. The authors do note that targeting a higher blood pressure

might be associated with side effects, and hence recommend using vasoactive medications for at

the lowest possible dose for the shortest possible duration. The literature on optimal first-line

vasoactive medication in CS is sparse. The SOAP II trial, which compared dopamine with

norepinephrine as the pressor of choice in septic shock, had a pre-specified subgroup for CS

consisting of 280 patients.39 Although dopamine was associated with a higher risk of

arrhythmias in this subgroup, validity of these findings has been questioned due to criticisms on

methodology and sample size. OptimaCC, a recent small double blinded RCT compared

norepinephrine with epinephrine among patients who developed CS after AMI.40 The study was

terminated early after enrolling 57 patients due a higher rate of refractory shock in the

epinephrine group (37% vs 7%). Hence the ACCA/ESC position statement recommends

norepinephrine as the first line vasopressor in patients with hypotension and insufficient tissue

perfusion. There is limited data comparing other inotropes, and the ACCA/ESC position

statement makes no recommendation in this regard. Reference is made to the 2016 ESC heart

failure guidelines, which classifies treatment with either dobutamine or levosimendan as a class

IIb recommendation (level of evidence C).33 Of note, although levosimendan is used in many

countries, its use is not yet approved by the United States Food and Drug Administration.

Mechanical Circulatory Support of the Left Ventricle

During hemodynamic management with volume resuscitation and vasoactive or inotropic

agents, the authors recommend assessment of left ventricular filling pressure to rule out

hypovolemia as the cause of shock. Additionally, the authors discuss the evidence for use of
 11

temporary MCS devices in the setting of CS due to left ventricular failure. The IABP-SHOCK II

trial randomized 600 patients with CS after MI to either receive intra-aortic balloon pump or

not.21 There was no difference in 30-day mortality or any pre-specified secondary endpoints.

Follow up data showed no difference between treatment groups at 1 and 6 years as well.41, 42

Therefore, the ACCA/ESC position statement does not recommend the routine use of intra-aortic

balloon pump (IABP) in patients with MI complicated by CS, except in the presence of

mechanical complications.

Data on percutaneous MCS devices in setting of left ventricular failure after acute MI is

limited to small RCTs. A recent meta-analysis including 148 patients pooled data from 4 such

RCTs, comparing the IABP (as a control) with several MCS devices: 2 with TandemHeart

[LivaNova, London, England], 1 with Impella 2.5 [Abiomed, Danvers, MA, USA] and 1 with

Impella CP [Abiomed, Danvers, MA, USA].43 Although patients treated with MCS had a higher

mean arterial pressure, lower lactate and higher bleeding complications, there was no difference

in 30-day mortality. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) provides

support to both cardiovascular and respiratory systems. In general, rates of ECMO use have

increased in the last decade, although several drawbacks of VA-ECMO need to be kept in mind

including large cannula sizes, limb and bleeding complications, and inadequate left ventricular

unloading. To date, there are no adequate clinical trials assessing effectiveness of VA-ECMO in

CS after myocardial infarction.

The ACCA/ESC position statement does not recommend MCS as the first line treatment

in CS. They recommend that ECMO and percutaneous MCS only be used in refractory CS, and

be tailored to institutional experience. Furthermore, the authors suggest that a rising lactate

despite increasing catecholamine requirements might be a helpful indicator for MCS need.
 12

Results from ongoing RCTs evaluating effectiveness of newer percutaneous MCS devices and

ECMO may offer further clarification and guidance on these important therapies.

Specific Recommendations for Cardiogenic Shock due to Right Ventricular Dysfunction

Acute right ventricular (RV) dysfunction is the cause of CS from AMI approximately 7%

of the time. Due to its relative rarity compared to acute left ventricular dysfunction, a high

clinical suspicion must be maintained in the appropriate setting. Classically, the patient with

acute RV failure will present with hypotension and evidence of venous congestion ( elevated

jugular venous pressure, peripheral edema and hepatic congestion to name some key features).

The ACCA/ESC position statement highlights the importance of EKG, echocardiography and

right heart catheterization in diagnosis of right ventricular failure. Any patient presenting in

shock from a presumed MI should have right-sided EKG leads (V3R and V4R has high

specificity) placed to better identify RV involvement. Echocardiography is also immensely

helpful in identifying RV failure. Characteristics such as RV dilation, RV free wall hypokinesis,

or severe tricuspid regurgitation may be suggestive of RV dysfunction as the etiology of shock.

Invasive hemodynamics with pulmonary artery catheterization also plays an important role in the

diagnosis and risk stratification of acute RV failure.25

The ACCA/ESC position statement for management of acute RV dysfunction follows a

linear algorithm, similar to the aforementioned management of left ventricular dysfunction.

Nonetheless, there are some important items to underscore in regards to CS due to RV failure.

In the absence of volume overload, CS due to RV failure may benefit from judicious use of fluid

challenges to treat hypotension and restore adequate systemic perfusion. Emergent

 13

revascularization of the culprit artery (right coronary artery) usually leads to rapid hemodynamic

improvement. Pulmonary artery catheterization may be specifically useful here in order to

identify progression of RV dysfunction as well as to evaluate the response to therapies.

Restoration of atrial-ventricular synchrony is often necessary in RV failure, and early

cardioversion or dual-chamber pacing may be indicated in order to improve cardiac performance.

For patients in respiratory distress and hypoxia, mechanical ventilation should be initiated

in order to reduce stress on the myocardium and provide adequate oxygenation. Patients with

acute RV failure may particularly benefit from correction of hypoxia and hypercapnia, as this

will reduce pulmonary vascular resistance and therefore reduce RV afterload. In placing patients

on mechanical ventilation, it must be noted that positive pressure ventilation may reduce RV

preload and therefore RV cardiac output, which may be very poorly tolerated in the setting of

RV dysfunction.

If evidence of impaired end-organ perfusion persists despite maximal medical therapy,

the ACCA/ESC treatment algorithm recommends considering short-term MCS. There is no

evidence to support placement of an intra-aortic balloon pump for acute right ventricular

dysfunction.21 Isolated right ventricular support (as would be provided by the Impella RP

[Abiomed, Danvers, MA, USA] and Protek Duo [LivaNova, London, England]) is an attractive

option. Veno-arterial ECMO is another option for mechanical support for acute RV failure.25

The ACCA/ESC position statement makes no specific recommendations on the type of support

due to lack of adequate clinical trials. Patients who persist with RV dysfunction despite

revascularization and optimization of hemodynamics using maximal medical management and

temporary mechanical support have limited options. There is currently no approved durable right
 14

ventricular support device although there are reports of using approved durable left-ventricular

assist devices to support the RV on an emergent/compassionate use basis, with limited success.44

Recommendations for Cardiogenic Shock due to Mechanical Complications

Mechanical complications of myocardial infarction are associated with a high morbidity

and mortality. The ACCA/ESC position statement recommends early and aggressive

management depending on the type of complication. Similar to other cases of cardiogenic shock

related to myocardial infarction, emergent angiography leading to revascularization, and urgent

echocardiography to identify the cause of shock are mainstays of therapy. However, the

ACCA/ESC treatment algorithm also provides the option for conservative management in the

context of medical futility, as decided by the treating cardiac teams. Due to the high mortality of

mechanical complications from an acute myocardial infarction and acknowledging that they may

represent a late finding in which revascularization may not rapidly reverse the existing

pathology, patients with significant comorbidities that portend a poor prognosis may be best

served with conservative, less-invasive management.

The ACCA/ESC treatment algorithm supports the class I recommendation from 2017

ESC STEMI guidelines that simultaneous revascularization should be considered, if a patient is

undergoing treatment for a mechanical complication, with either PCI (for percutaneous

correction) or coronary artery bypass grafting (if surgical repair is pursued).

Free wall rupture carries a high mortality (75%) despite advances in management.45

Diagnosis is usually made using echocardiography when there is clinical suspicion of impending

tamponade based on hemodynamics. Management can include either percutaneous drainage or

 15

surgical repair. ACCA/ESC position statement recommends considering a percutaneous drainage

to restore hemodynamic stability initially, and if bleeding persists, then surgical repair should be

considered.

Ventricular septal defects (VSD) arise from rupture of ischemic septum leading to acute

RV failure initially, and eventually progressing to bi-ventricular failure if the VSD is not

intervened upon. Conservative management of an infarct VSD has a very high mortality and in

patients for whom aggressive management is appropriate early surgical intervention should be

pursued. Waiting for myocardial scarring and fibrosis in order to improve surgical targets for

repair is not appropriate due to the high mortality associated with delaying surgery; patients who

have a successful early operation have better survival.46 In patients in whom the VSD is

amendable to percutaneous closure, endovascular options may be appropriate, however mortality

remains high for patients in CS.47

Acute mitral regurgitation is common following a severe myocardial infarction. A rare

but potentially catastrophic cause of mitral regurgitation is from papillary muscle rupture leading

to acute severe mitral regurgitation. Diagnosis is commonly made using echocardiography;

transesophageal echocardiography may be needed to delineate valve pathology. Patients with

acute severe mitral regurgitation typically present with severe cardiogenic shock and severe

pulmonary edema necessitating mechanical ventilation. Current recommendations are for urgent

surgical management in appropriate candidates.48

Based on the theoretical benefits of an intra-aortic balloon pump (reducing afterload and

improving coronary perfusion), the ACCA/ESC position statement supports the 2017 ESC

STEMI guidelines stating a class IIa recommendation for insertion of intra-aortic balloon pump

in the setting of an infarct VSD or papillary muscle rupture. However, intra-aortic balloon pump
 16

has not been rigorously studied in these patients, and hence should not delay surgical or

percutaneous corrective interventions. Due to the severity of CS that often accompanies

mechanical complications of an acute MI these patients are often considered for temporary MCS.

While no randomized trial has proven a benefit to temporary MCS, it is reasonable to consider in

patients who are refractory to medical management. Due to the nature of the injury, the most

commonly used device in this setting is veno-arterial ECMO, as this avoids directly

instrumenting the heart. It is also important to note that these patients often develop biventricular

failure and require significant oxygenation support due to pulmonary edema.

Table 1 summarizes the class I recommendations made by the ACCA/ESC document.9

CONCLUSION

The ACCA/ESC position statement on management of AMI complicated by CS is a

focused yet thorough guide to diagnosis and treatment of a harrowing clinical condition. It

builds on the foundation of guidance put forth in the 2017 American Heart Association (AHA)

Scientific Statement on Contemporary Management of Cardiogenic Shock. The European

document references important new literature that was not available for consideration in the

AHA document, and addresses specific clinical considerations (e.g.: mechanical complications

of AMI, RV failure) germane to those caring for these complex patients.8, 9 As noted within the

ACCA/ESC statement, continued study of this patient population will bring more clarity to

optimal management of those with CS after AMI.

Disclosures-None
 17

References

1. Kim JH, Sunkara A, Varnado S. Management of Cardiogenic Shock in a Cardiac

Intensive Care Unit. Methodist Debakey Cardiovasc J. 2020;16(1):36-42.

2. Lim HS. Cardiogenic Shock: Failure of Oxygen Delivery and Oxygen Utilization. Clin

Cardiol. 2016;39(8):477-483.

3. Miller L. Cardiogenic Shock in Acute Myocardial Infarction: The Era of Mechanical

Support. J Am Coll Cardiol. 2016;67(16):1881-1884.

4. Thygesen K, Alpert JS, Jaffe AS, et al. Fourth Universal Definition of Myocardial

Infarction (2018). Circulation. 2018;138(20):e618-e651.

5. Bentzon JF, Otsuka F, Virmani R, et al. Mechanisms of plaque formation and rupture.

Circ Res. 2014;114(12):1852-1866.

6. Jennings RB, Ganote CE. Structural changes in myocardium during acute ischemia. Circ

Res. 1974;35 Suppl 3:156-172.

7. Ooi DS, Isotalo PA, Veinot JP. Correlation of antemortem serum creatine kinase, creatine

kinase-MB, troponin I, and troponin T with cardiac pathology. Clin Chem. 2000;46(3):338-344.

8. van Diepen S, Katz JN, Albert NM, et al. Contemporary Management of Cardiogenic

Shock: A Scientific Statement From the American Heart Association. Circulation.

2017;136(16):e232-e268.

9. Zeymer U, Bueno H, Granger CB, et al. Acute Cardiovascular Care Association position

statement for the diagnosis and treatment of patients with acute myocardial infarction

complicated by cardiogenic shock: A document of the Acute Cardiovascular Care Association of

the European Society of Cardiology. Eur Heart J Acute Cardiovasc Care. 2020;9(2):183-197.
 18

10. Shah AH, Puri R, Kalra A. Management of cardiogenic shock complicating acute

myocardial infarction: A review. Clin Cardiol. 2019;42(4):484-493.

11. Barth E, Radermacher P, Thiemermann C, et al. Role of inducible nitric oxide synthase in

the reduced responsiveness of the myocardium to catecholamines in a hyperdynamic, murine

model of septic shock. Crit Care Med. 2006;34(2):307-313.

12. Cotter G, Kaluski E, Milo O, et al. LINCS: L-NAME (a NO synthase inhibitor) in the

treatment of refractory cardiogenic shock: a prospective randomized study. Eur Heart J.

2003;24(14):1287-1295.

13. Searles CD. The nitric oxide pathway and oxidative stress in heart failure. Congest Heart

Fail. 2002;8(3):142-147, 155.

14. Granger CB, Mahaffey KW, Weaver WD, et al. Pexelizumab, an anti-C5 complement

antibody, as adjunctive therapy to primary percutaneous coronary intervention in acute

myocardial infarction: the COMplement inhibition in Myocardial infarction treated with

Angioplasty (COMMA) trial. Circulation. 2003;108(10):1184-1190.

15. Prondzinsky R, Unverzagt S, Lemm H, et al. Interleukin-6, -7, -8 and -10 predict

outcome in acute myocardial infarction complicated by cardiogenic shock. Clin Res Cardiol.

2012;101(5):375-384.

16. Kohsaka S, Menon V, Lowe AM, et al. Systemic inflammatory response syndrome after

acute myocardial infarction complicated by cardiogenic shock. Arch Intern Med.

2005;165(14):1643-1650.

17. Hochman JS, Boland J, Sleeper LA, et al. Current spectrum of cardiogenic shock and

effect of early revascularization on mortality. Results of an International Registry. SHOCK

Registry Investigators. Circulation. 1995;91(3):873-881.

 19

18. Hochman JS, Buller CE, Sleeper LA, et al. Cardiogenic shock complicating acute

myocardial infarction--etiologies, management and outcome: a report from the SHOCK Trial

Registry. SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK? J

Am Coll Cardiol. 2000;36(3 Suppl A):1063-1070.

19. Chioncel O, Parissis J, Mebazaa A, et al. Epidemiology, pathophysiology and

contemporary management of cardiogenic shock - a position statement from the Heart Failure

Association of the European Society of Cardiology. Eur J Heart Fail. 2020.

20. Baran DA, Grines CL, Bailey S, et al. SCAI clinical expert consensus statement on the

classification of cardiogenic shock: This document was endorsed by the American College of

Cardiology (ACC), the American Heart Association (AHA), the Society of Critical Care

Medicine (SCCM), and the Society of Thoracic Surgeons (STS) in April 2019. Catheter

Cardiovasc Interv. 2019;94(1):29-37.

21. Thiele H, Zeymer U, Neumann FJ, et al. Intraaortic balloon support for myocardial

infarction with cardiogenic shock. N Engl J Med. 2012;367(14):1287-1296.

22. Hochman JS, Sleeper LA, Webb JG, et al. Early revascularization in acute myocardial

infarction complicated by cardiogenic shock. SHOCK Investigators. Should We Emergently

Revascularize Occluded Coronaries for Cardiogenic Shock. N Engl J Med. 1999;341(9):625-

634.

23. Reynolds HR, Anand SK, Fox JM, et al. Restrictive physiology in cardiogenic shock:

observations from echocardiography. Am Heart J. 2006;151(4):890 e899-815.

24. Khalid L, Dhakam SH. A review of cardiogenic shock in acute myocardial infarction.

Curr Cardiol Rev. 2008;4(1):34-40.

 20

25. Kapur NK, Esposito ML, Bader Y, et al. Mechanical Circulatory Support Devices for

Acute Right Ventricular Failure. Circulation. 2017;136(3):314-326.

26. Jacobs AK, Leopold JA, Bates E, et al. Cardiogenic shock caused by right ventricular

infarction: a report from the SHOCK registry. J Am Coll Cardiol. 2003;41(8):1273-1279.

27. Standl T, Annecke T, Cascorbi I, et al. The Nomenclature, Definition and Distinction of

Types of Shock. Dtsch Arztebl Int. 2018;115(45):757-768.

28. Hochman JS, Sleeper LA, Webb JG, et al. Early revascularization and long-term survival

in cardiogenic shock complicating acute myocardial infarction. JAMA. 2006;295(21):2511-

2515.

29. Mehta RH, Lopes RD, Ballotta A, et al. Percutaneous coronary intervention or coronary

artery bypass surgery for cardiogenic shock and multivessel coronary artery disease? Am Heart

J. 2010;159(1):141-147.

30. Thiele H, Akin I, Sandri M, et al. PCI Strategies in Patients with Acute Myocardial

Infarction and Cardiogenic Shock. N Engl J Med. 2017;377(25):2419-2432.

31. Tousek P, Rokyta R, Tesarova J, et al. Routine upfront abciximab versus standard

periprocedural therapy in patients undergoing primary percutaneous coronary intervention for

cardiogenic shock: The PRAGUE-7 Study. An open randomized multicentre study. Acute Card

Care. 2011;13(3):116-122.

32. Ibanez B, James S, Agewall S, et al. 2017 ESC Guidelines for the management of acute

myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the

management of acute myocardial infarction in patients presenting with ST-segment elevation of

the European Society of Cardiology (ESC). Eur Heart J. 2018;39(2):119-177.

 21

33. Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines for the diagnosis and

treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of

acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the

special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail.

2016;18(8):891-975.

34. van Diepen S, Reynolds HR, Stebbins A, et al. Incidence and outcomes associated with

early heart failure pharmacotherapy in patients with ongoing cardiogenic shock. Crit Care Med.

2014;42(2):281-288.

35. Bernard SA, Gray TW, Buist MD, et al. Treatment of comatose survivors of out-of-

hospital cardiac arrest with induced hypothermia. N Engl J Med. 2002;346(8):557-563.

36. Hypothermia after Cardiac Arrest Study G. Mild therapeutic hypothermia to improve the

neurologic outcome after cardiac arrest. N Engl J Med. 2002;346(8):549-556.

37. Lascarrou JB, Merdji H, Le Gouge A, et al. Targeted Temperature Management for

Cardiac Arrest with Nonshockable Rhythm. N Engl J Med. 2019;381(24):2327-2337.

38. Fuernau G, Beck J, Desch S, et al. Mild Hypothermia in Cardiogenic Shock

Complicating Myocardial Infarction. Circulation. 2019;139(4):448-457.

39. De Backer D, Biston P, Devriendt J, et al. Comparison of dopamine and norepinephrine

in the treatment of shock. N Engl J Med. 2010;362(9):779-789.

40. Levy B, Clere-Jehl R, Legras A, et al. Epinephrine Versus Norepinephrine for

Cardiogenic Shock After Acute Myocardial Infarction. J Am Coll Cardiol. 2018;72(2):173-182.

41. Thiele H, Zeymer U, Neumann FJ, et al. Intra-aortic balloon counterpulsation in acute

myocardial infarction complicated by cardiogenic shock (IABP-SHOCK II): final 12 month

results of a randomised, open-label trial. Lancet. 2013;382(9905):1638-1645.

 22

42. Thiele H, Zeymer U, Thelemann N, et al. Intraaortic Balloon Pump in Cardiogenic Shock

Complicating Acute Myocardial Infarction: Long-Term 6-Year Outcome of the Randomized

IABP-SHOCK II Trial. Circulation. 2018.

43. Thiele H, Jobs A, Ouweneel DM, et al. Percutaneous short-term active mechanical

support devices in cardiogenic shock: a systematic review and collaborative meta-analysis of

randomized trials. Eur Heart J. 2017;38(47):3523-3531.

44. Vullaganti S, Tibrewala A, Rich JD, et al. The use of a durable right ventricular assist

device for isolated right ventricular failure due to combined pre- and postcapillary pulmonary

hypertension. Pulm Circ. 2019;9(2):2045894019831222.

45. Figueras J, Alcalde O, Barrabes JA, et al. Changes in hospital mortality rates in 425

patients with acute ST-elevation myocardial infarction and cardiac rupture over a 30-year period.

Circulation. 2008;118(25):2783-2789.

46. Arnaoutakis GJ, Zhao Y, George TJ, et al. Surgical repair of ventricular septal defect

after myocardial infarction: outcomes from the Society of Thoracic Surgeons National Database.

Ann Thorac Surg. 2012;94(2):436-443; discussion 443-434.

47. Schlotter F, de Waha S, Eitel I, et al. Interventional post-myocardial infarction ventricular

septal defect closure: a systematic review of current evidence. EuroIntervention. 2016;12(1):94-

102.

48. Russo A, Suri RM, Grigioni F, et al. Clinical outcome after surgical correction of mitral

regurgitation due to papillary muscle rupture. Circulation. 2008;118(15):1528-1534.

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Table 1. ACCA/ESC Management of AMI Complicated by CS: Class I Recommendations by Mechanism

for Shock

CS after Diagnosed STEMI or NSTEMI, due to LV Failure: (approximately 80% of CS)

1. Emergency angiography
2. Immediate echocardiography
3. Emergency PCI (or emergency CABG if PCI cannot be done)
4. Administer fluid challenge in patients without evidence of volume overload
5. Administer diuretics if evidence of pulmonary edema
6. Place invasive arterial blood pressure monitoring
7. Provide oxygen and/or ventilator support as needed, guided by blood gas analysis

CS after Diagnosed STEMI or NSTEMI, due to RV Failure: (approximately 7% of CS)

1. Emergency angiography
2. Immediate echocardiography
3. Emergency PCI (or emergency CABG if PCI cannot be done)
4. Administer fluid challenge in patients without evidence of volume overload
5. Place invasive arterial blood pressure monitoring
6. Provide oxygen and/or ventilator support as needed, guided by blood gas analysis

CS after Diagnosed STEMI or NSTEMI, due to mechanical complication of MI: (approximately

13% of CS)
1. Emergency angiography
2. Immediate echocardiography
a. If VSD:
i. Proceed to surgical or percutaneous interventional closure
ii. Perform concurrent CABG (if surgical closure) or PCI (if interventional closure)
b. If acute severe MR:
i. Proceed to surgical MV repair or replacement
ii. Perform concurrent CABG
c. If free wall rupture:
i. Proceed to surgical repair or pericardiocentesis
ii. Perform concurrent CABG (if surgical repair) or PCI (if pericardiocentesis)
3. Administer fluid challenge in patients without evidence of volume overload
4. Place invasive arterial blood pressure monitoring
5. Provide oxygen and/or ventilator support as needed, guided by blood gas analysis

ACCA: Acute Cardiovascular Care Association; ESC: European Society of Cardiology; AMI: acute
myocardial infarction; CS: cardiogenic shock; STEMI: ST elevation myocardial infarction; NSTEMI: non-ST
elevation myocardial infarction; LV: left ventricle; PCI: percutaneous coronary intervention; CABG:
coronary artery bypass grafting; RV: right ventricle; VSD: ventricular septal defect; MR: mitral
regurgitation; MV: mitral valve