894254 ACC European Heart Journal: Acute Cardiovascular CareZeymer et al.

Position Statement
European Heart Journal: Acute Cardiovascular Care

Acute Cardiovascular Care 1­–15

© The European Society of Cardiology 2020
Article reuse guidelines:
Association position statement sagepub.com/journals-permissions
https://doi.org/10.1177/2048872619894254
DOI: 10.1177/2048872619894254
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of patients with acute myocardial

infarction complicated by cardiogenic
shock: A document of the Acute
Cardiovascular Care Association of
the European Society of Cardiology

Uwe Zeymer1,2, Hector Bueno3, Christopher B Granger4,

Judith Hochman5, Kurt Huber6,7, Maddalena Lettino8,
Susanna Price9, Francois Schiele10, Marco Tubaro11,
Pascal Vranckx12,13, Doron Zahger14 and Holger Thiele15,16
Reviewer coordinator: Sigrun Halvorsen; Document Reviewers: Christian Hassager,
Gilles Montalescot, Karl Werdan, Sean van Diepen, Alessandro Sionis

Abstract
Most of the guideline-recommended treatment strategies for patients with acute coronary syndromes have been tested
in large randomised clinical trials. Still, a major challenge is represented by patients with acute myocardial infarction
admitted with impending or established cardiogenic shock. Despite early revascularization the mortality of cardiogenic
shock remains high and roughly half of patients do not survive until hospital discharge or 30-day follow-up. However,
there is only limited evidence-based scientific knowledge in the cardiogenic shock setting. Therefore, recommendations
and actual treatments are often based on retrospective or prospective registry data and extrapolations from randomised
clinical trials in acute myocardial infarction patients without cardiogenic shock. This position statement will summarise
the current consensus of the diagnosis and treatment of patients with acute myocardial infarction complicated by
cardiogenic shock based on current evidence and will provide advice for clinical practice.

Keywords
Acute myocardial infarction; Cardiogenic shock; Revascularuzation therapies; mechanical circulatory support

1 14
 linikum Ludwigshafen, Germany
K S oroka University Medical Center, University of the Negev, Israel
2 15
Institut für Herzinfarktforschung, Germany Heart Center Leipzig, University of Leipzig, Germany
3 16
Centro Nacional de Investigaciones Cardiovasculares (CNIC), Spain Leipzig Heart Institute, Germany
4
Duke Medical Center, USA
5
New York University School of Medicine, USA Corresponding authors:
6
Wilhelminenhospital, Austria Uwe Zeymer, Klinikum Ludwigshafen, Institut für Herzinfarktforschung,
7
Sigmund Freud University, Austria Ludwigshafen, Bremser Str. 79, 67063 Ludwigshafen, Germany.
8
Humanitas Research Hospital, Italy Email: Uwe.Zeymer@t-online.de
9
Royal Brompton Hospital, UK
10
University Hospital Jean Minjoz, France Holger Thiele, Heart Center Leipzig, University of Leipzig, Strümpellstr.
11
San Filippo Neri Hospital, Italy 39, 04289 Leipzig, Germany.
12
Hartcentrum Hasselt, Belgium Email: holger.thiele@medizin.uni-leipzig.de
13
Department of Medicine and Life Sciences, University of Hasselt, Belgium
2 European Heart Journal: Acute Cardiovascular Care 00(0)

Introduction Hg and/or the need for catecholamines, pulmonary conges-

Despite major advances in the care of patients with acute
myocardial infarction (AMI) including early revasculariza-
tion, the mortality of cardiogenic shock (CS) remains high
and roughly half of patients do not survive until hospital
discharge or 30-day follow-up. In contrast to a large num-
ber of trials in patients with AMI without CS there is only
limited evidence-based scientific knowledge in the CS set-
ting. Therefore, recommendations and actual treatments are
often based on retrospective or prospective registry data
and extrapolations from randomised clinical trials in AMI
patients without CS. This Acute Cardiovascular Care
Association (ACCA) position statement will summarise the
current consensus of the diagnosis and treatment of patients
with AMI complicated by CS based on current evidence
and will provide advice for clinical practice.
Definition of CS
CS is a clinical condition defined as the inability of the heart,
generally as a result of impairment of its pumping function,
to deliver an adequate amount of blood to the tissues to meet
resting metabolic demands.1,2 The clinical definition of per-
sistent CS includes poor cardiac output and evidence of tis-
sue (end-organ) hypoxia in the presence of adequate
intravascular volume (e.g. indicating that the patient is not
hypovolaemic). The criteria for infarct-related CS most often
used are given in Table 1 and include hypotension <90 mm
tion and signs of end organ failure.
Just recently a new definition of cardiogenic shock,
including five categories of (a) at risk, (b) beginning or pre-
shock, (c) classical, (d) doom, and (e) extremis CS, has been
proposed.3 Pre-shock is defined as clinical evidence of rela-
tive hypotension or tachycardia without hypoperfusion.3
Such patients should be monitored closely and treated early
to avoid development of classical CS. Extremis CS includes
cases in which considerations about the futility of treatment
should be carried out and possibly palliative care initiated.
Epidemiology and prognosis of CS
The incidence of CS is approximately 5–10% in ST-segment
elevation myocardial infarction (STEMI) and 2–4% in non-
ST-segment elevation myocardial infarction (NSTEMI),
while the mortality of CS in these two conditions is simi-
lar.4,5 Based on these data, approximately 70,000–80,000
CS patients are admitted in Europe and 30,000–40,000 in
the USA per year.6 Data from large national registries sug-
gest a substantial decline in mortality over the years in
association with the widespread use of an early invasive
strategy and revascularization therapy.7–9 However, there
seems to be a plateau of in-hospital survival with CS which
does exceed 55–60% in randomised clinical trials and reg-
istries. Similarly, six-year mortality was 67.2% in the inva-
sive group of the SHOCK trial10 published in 2006 and
66.7% in the IABP-SHOCK II trial as reported recently.11

Table 1.  Most widely accepted definition of infarct-related cardiogenic shock. Patients should meet all of the following criteria
((a), (b), (c) and (d)).

Hypotension >30 min (a) Evidence (clinical symptoms and/or signs) of: Cause of shock is cardiogenic (d)

Tissue hypo-perfusion with Elevated left ventricular filling

at least one of the following
criteria (b):
Systolic blood pressure 1. Altered mental status
<90 mm Hg for >30 min 2. Cold, clammy skin and
or need of vasopressors to extremities
maintain pressure >90 mm 3. Oliguria with urine output
Hg during systole <30 ml/h
4. Arterial lactate >2.0
mmol/l
pressures (c)
Pulmonary congestion
confirmed by:
Clinical examination (new
orthopnoea) or chest
radiography
Pulmonary capillary wedge
pressure derived from:
•• Pulmonary artery
catheterization or
•• By Doppler
echocardiography (mitral
E wave deceleration time
≤130 ms)
Left ventricular end diastolic
pressure (LVEDP) at
catheterization >20 mm Hg
 
Left ventricular pump failure with
a left ventricular ejection fraction
<40% measured by:
•• Left ventriculography or
•• Echocardiography
Shock secondary to mechanical
causes:
•• Acute severe mitral regurgitation
and/or mitral apparatus rupture.
•• Severe underlying valvular heart
disease (e.g. aortic stenosis, mitral
stenosis, or aortic insufficiency)
•• Rupture of the ventricular
septum or free wall.
Shock secondary to predominant
right ventricular (RV) failure or
severe RV dysfunction of any cause
Shock due to brady-arrhythmia or
tachy-arrhythmia
Zeymer et al. 3

Figure 1.  Pathophysiology of infarct-related cardiogenic shock and possible treatment options.
CABG: coronary artery bypass grafting; ECMO: extracorporeal membrane oxygenation; eNOS: endothelial nitric oxide synthase; IABP: intraaortic
balloon pump; iNOS: inducible nitric oxide synthase; LVAD: lef ventricular assist device; LVEDP: left ventricular end-diastolic pressure; NO: nitric
oxide; PCI: percutaneous coronary intervention; SIRS: systemic inflammatory response syndrome; SVR: systemic vascular resistance; TNF-α: tumour
necrosis factor-α.

Pathophysiology of CS activation of the renin-angiotensin-aldosterone system to

The pathophysiology and possible treatment options to
interrupt the downward vicious cycle of CS due to predom-
inant left ventricular (LV) failure are shown in Figure 1. CS
is a clinical condition defined as the impairment of the
pumping function of the heart, resulting in its inability to
deliver adequate cardiac output.6,12,13 LV pump failure
caused by acute ischaemia is the principal mechanism in
most forms of CS but other parts of the circulatory system
contribute to shock with inadequate compensation or addi-
tional defects. The pathophysiological definition of persis-
tent CS includes severe myocardial ischaemia leading to
increased LV filling pressures first, and then to a reduction
in cardiac output, systemic hypotension and systemic tissue
hypoperfusion. All organs may be affected by the decrease
in cardiac output. Cardiac function is further impaired due
to the additional decrease in coronary perfusion, worsening
myocardial ischaemia, progressive cell death in the infarct
border zone and further impairment in LV diastolic and sys-
tolic function of the viable myocardium, which further
increases filling pressures and compromises cardiac output,
closing a vicious cycle (Figure 1). The rise in LV filling
pressures increases pulmonary capillary hydrostatic pres-
sure and leads to pulmonary congestion and oedema.
Hypoxaemia and the increase in lung compliance increase
respiratory work and oxygen consumption. Renal hypoper-
fusion reduces glomerular flow rate and triggers the
promote sodium and water retention. The vasoconstriction
of the splanchnic bed caused by sympathetic activation
mobilises blood to the central circulation but may trigger
barrier disruption in the microcirculation of the mesentery,
with translocation of bacteria or bacterial toxins and possi-
ble subsequent septic reaction. Altered mental status, as a
consequence of cerebral hypoperfusion, is common at pres-
entation in CS and is associated with worse prognosis.
In addition to the circulatory failure and maladaptive
neurohormonal responses, a physiological state compatible
with acute severe inflammatory response syndrome has
been described in a substantial proportion of patients with
CS, characterised by the activation of various inflammatory
cascades (free radical generation, complement formation,
cytokine release) and cellular components (leukocytes,
platelets, monocytes and endothelial cells).
Differential diagnosis of CS
The differential diagnosis of CS can be divided in two
parts: the differential diagnosis between pure CS and other
contributing causes of shock also referred to as mixed
shock, and the differential diagnosis among the different
causes of CS (Supplemental Material Table 1).
The differential diagnosis between CS and other causes
of shock (i.e. hypovolaemic, extracardiac obstructive,
4 European Heart Journal: Acute Cardiovascular Care 00(0)

Table 2.  The most important differential diagnosis of acute myocardial infarct-related cardiogenic shock and diagnostic tools.

Diagnosis Incidence Diagnostic tool

Aortic dissection Rare CT, MRI, TEE
Pulmonary embolism Common CT, TTE
Tension pneumothorax Rare Chest X-ray, CT
Myocarditis Intermediate Coronary angiography, cardiac MRI
Takotsubo syndrome Intermediate Coronary angiography, TTE
Valvular Intermediate TTE
Cardiomyopathy (ischaemic or non-ischaemic) Common TTE, history
Cardiac tamponade Rare TTE

CT: computed tomography; MRI: magnetic resonance imaging; TEE: trans-oesophageal echocardiography; TTE: transthoracic echocardiography.

Table 3.  Parameters and categories of the IABP-SHOCK
II risk score for early risk prediction in patients with infarct-
related cardiogenic shock undergoing percutaneous coronary
intervention (PCI).
Parameter Points
Age >73 years 1 with at least two catheterization laboratories with PCI
History of stroke 2
Glucose >191 mg/dl (>10.6 mmol/l) 1
Creatinine >1.5 mg/dl (>132.6 umol/l) 1
Arterial lactate >5 mmol/l 2
TIMI flow <3 after PCI 2
Risk categories  
Low 0-2
Intermediate 3-4
High 5-9
TIMI: Thrombolysis In Myocardial Infarction.
distributive) is based mainly on history, physical examination,
electrocardiogram (ECG), echocardiography and laboratory
data. Echocardiography should be performed promptly in all
patients with CS in the setting of AMI for rapid differential
diagnosis and rule-out of mechanical complications. LV dys-
function is a marker of CS, large RV with small LV may be a
marker of pulmonary embolism, pericardial fluid a marker of
cardiac tamponade, and small heart cavities with normal func-
tion a possible marker of hypovolaemic shock. Other imaging
techniques (like computed tomography (CT) scans) or haemo-
dynamic investigations using a pulmonary artery catheter
(PAC) can be of help, depending on the clinical situation. The
causes and diagnostic tools for the most important causes of
CS are listed in Table 2.
Logistic of care for CS
Given the important role of an early invasive strategy, all
patients with infarct-related CS should be directly admit-
ted by the emergency system to a percutaneous coronary
­intervention (PCI) hospital or if admitted to a non-PCI
hospital immediately transferred to a hospital with
24-hour/seven-day PCI capability.14,15 Since a number of
patients will need more advanced care with immediate
coronary artery bypass graft (CABG) surgery or mechan-
ical circulatory support (MCS) devices, which are not
available in most hospitals, it seems prudent to establish
regional CS centres. These centres should be equipped
service, on-site surgery and be experienced in the use of
at least two MCS devices.16 Patients not suitable for PCI,
with unsuccessful PCI or not improving after successful
PCI should be immediately transferred to such a CS
centre.
Initial risk assessment
Several published risk scores are available for early risk
stratification of patients with CS (Supplemental Material
Table 2). These scores are limited by insufficient valida-
tion and also practical applicability. So far, the only CS
score with both internal and external validation is derived
from the IABP-SHOCK II trial (Table 3).17 Based on six
variables, with a maximum of nine points this IABP-
SHOCK II score divides patients into three risk categories.
Patients in the low, intermediate and high risk categories
have 30-day mortality risk of 20–30%, 40–60% and 70–
90%, ­respectively.17 Therefore, this score may be a suita-
ble tool to select patients for more advanced treatments
such as MCS devices. However, the impact on individual
patient outcome of applying such a risk score has yet to be
demonstrated and all scores currently available were only
used for risk stratification.
An important feature in the initial risk assessment is the
occurrence of cardiac arrest, particularly with ongoing severe
anoxic brain injury in the days after cardiac arrest, that may
modify if and when to pursue aggressive interventions.
Monitoring
Every critically ill cardiac patient such as a CS patient
should be monitored in order to forewarn of impending car-
diovascular crisis, differentiate causes of haemodynamic
Zeymer et al. 5

Table 4.  Recommended critical care unit monitoring in patients with cardiogenic shock.

Monitoring parameter Frequency Comment/rationale

Non-invasive monitoring
ECG telemetry, pulse-oximetry,
respiratory rate
Passive leg raising
Invasive monitoring
Arterial blood pressure
monitoring
Central venous pressure (CVP)
Central venous oxygen
saturation
Urine output
Pulmonary artery catheter or
non-invasive cardiac output
monitor
Laboratory investigations
Complete blood counts
Serum electrolytes
Serum creatinine
Liver function tests
Lactate
Coagulation laboratories
Continuous High risk and incidence of arrhythmias, ventilator failure and/or
pulmonary oedema
Every 4 h An increase of blood pressure of >10 mm Hg indicates fluid
requirement
Continuous Consider continuing until full hemodynamic stabilization has been
achieved for 12–24 h
Continuous A central line is required for delivery of vasoactive medications.
Single point in time CVP measurements may be unreliable measures
of fluid status, but longitudinal CVP trends may provide information
on trends in fluid status
Every 4 h Trends in Scv02 in patients with a central line can be used to
monitor trends in cardiac output
Every hour Urine output along with serum creatinine monitoring are markers
of renal perfusion and acute kidney injury
Selected use Consider using early in the treatment course in patients not
responsive to initial therapy, or in cases of diagnostic or therapeutic
uncertainty
Every 12–24 h Consider more frequently in patients with or at high risk for
bleeding.
Every 6–12 h Frequency should be tailored to risks or presence of renal failure
and electrolyte disorders
Every 12–24 h Urine output along with serum creatinine monitoring are markers
of renal perfusion and acute kidney injury
Daily Monitoring for congestive hepatopathy and/or hypoperfusion
Every 1–4 h Lactate clearance is a marker of resolving end organ hypoperfusion
and lack of clearance is associated with a higher risk of mortality.
Every 4–6 h for those Altered drug elimination, high frequency use of antithrombotics,
on anti-coagulants until and use of mechanical support devices often necessitates
therapeutically stable, antithrombotic monitoring
every 24 h if not on anti-
coagulants

ECG: electrocardiogram.

instability and ongoing shock, enable monitoring of the Treatment

response to any therapeutic intervention, and determine if
the need for MCS may be indicated.1,18 The exact level
and type of monitoring will depend upon the local facili-
ties, and the clinical context of the patient. If intubated
and ventilated, additional monitoring should be per-
formed in accordance with published anaesthetic moni-
toring guidelines.18 Where the patient is being managed
with advanced MCS, additional monitoring will be nec-
essary including perfusionists if available. Calculation of
cardiac power, with monitoring of cardiac output by
Swan-Ganz catheter m ­ easurements, can assist in prog-
nostication especially in unclear haemodynamic situa-
tions, differential diagnosis of the cause of shock or even
mixed shock forms and in all patients with worsening
haemodynamics or increasing requirement for vasopres-
sors or inotropes.19 Table 4 ­summarises the recommenda-
tions for monitoring in patients with CS.
Revascularization therapy
Due to its limited efficacy especially in CS, fibrinolytic ther-
apy is reserved for STEMI patients when PCI is u­ navailable
according to current European Society of Cardiology (ESC)
guidelines with a class IIa C ­recommendation.14 The first
large randomised trial in patients with CS has been the
SHOCK trial, which established the clinical benefit of
an early invasive strategy with subsequent revascularization
in patients with CS (Figure 1 and Figure 2(a) and (b)). In
the SHOCK trial an initial invasive strategy with revasculari­
zation either by PCI or CABG led to a significant mortality
reduction at six months, and in long-term follow-up.10,20,21
To save one life, <8 patients need to be treated by early revas-
cularization in comparison to initial medical stabilization.
An important component in the positive effect of revas-
cularization is the time to reperfusion, therefore all efforts
6 European Heart Journal: Acute Cardiovascular Care 00(0)

Figure 2.  (continued)

Zeymer et al. 7

Figure 2.  Treatment algorithm for patients with cardiogenic shock (CS) complicating myocardial infarction. The class of
recommendation and level of evidence according to the most recent European Society of Cardiology (ESC) guidelines is provided if
available. (a) Treatment algorithm in predominant left ventricular failure. (b) Treatment algorithm in predominant right ventricular
failure. (c) Treatment algorithm in mechanical complications. CABG: coronary artery bypass graft; ECMO: extracorporeal membrane
oxygenation; IABP: intraaortic balloon pump; IRA: infarct related artery; MCS: mechanical circulatory support; NSTEMI: non-ST-
segment elevation myocardial infarction; PCI: percutaneous coronary intervention; STEMI: ST-segment elevation myocardial infarction.

should be made to reduce ischaemic time in CS.22 Numerous
registries have confirmed the survival advantage of early
revascularization leading to a subsequent reduction of CS
mortality in the young and also the elderly.
In observational reports comparing PCI versus CABG,
the type of revascularization did not appear to influence the
outcome of CS patients.23,24 Currently PCI is the most
widely available and most often performed revasculariza-
tion therapy in CS, while CABG is rarely performed with
only 4% of patients undergoing immediate CABG in the
IABP-SHOCK II-trial and registry which might represent
current clinical practice.25 Given the very high mortality of
patients with unsuccessful PCI, CABG should be consid-
ered in such cases, as well as in cases in which coronary
anatomy is unsuitable for PCI.
More than 70% of CS patients present with multivessel
coronary artery disease and/or left main disease, which is
associated with a higher mortality compared to patients
with single vessel disease. The Culprit Lesion Only PCI
versus Multivessel PCI in Cardiogenic Shock (CULPRIT-
SHOCK) trial,26 so far the largest randomised trial in CS,
showed a significant clinical benefit of a culprit-lesion-only
strategy (with possible stage revascularization of additional
lesions) with a reduction in the primary endpoint of 30-day
mortality or renal replacement therapy, which was mainly
driven by an absolute 8.2% reduction in 30-day mortality.26
The 30-day results of CULPRIT-SHOCK were recently
supported by a consistent reduction in the composite end-
point at one-year follow-up for the culprit-lesion-only PCI
with possible staged revascularization strategy.27 The
results were consistent across all predefined subgroups.
Therefore, according to the best current evidence, in the
vast majority of CS patients in clinical practice PCI should
be limited to the culprit lesion with possible staged revas-
cularization of other lesions. Some specific angiographic
scenarios, such as subtotal non-culprit lesions with reduced
Thrombolysis In Myocardial Infarction (TIMI) flow, or
multiple possible culprit lesions may benefit from
8 European Heart Journal: Acute Cardiovascular Care 00(0)

Figure 3.  Treatment algorithm for the use of revascularization therapies depending on coronary anatomy. CABG: coronary artery
bypass graft; IRA: infarct related artery; NSTEMI: non-ST-segment elevation myocardial infarction; PCI: percutaneous coronary
intervention; STEMI: ST-segment elevation myocardial infarction.

immediate multivessel PCI. However, this should be con-
sidered on an individual basis.
Figure 3 presents the recommended revascularization
strategies according to the extent of coronary disease of the
individual patient. In patients with a coronary anatomy
more suitable for CABG than for PCI an immediate evalu-
ation should be performed in the heart team which should
take into account age, comorbidities, previous resuscita-
tion, neurological status and also the time delay to perform
immediate CABG.
Antithrombotic therapy
No specific randomised trials on the optimal antithrombotic
treatment of patients with CS are available, with the excep-
tion of the relatively small PRAGUE-7 study (n=80 patients),
in which upstream therapy with the glycoprotein IIb/IIIa
inhibitor abciximab did not show any clinical benefit.28
In CS the use of agents administered orally (e.g. clopi-
dogrel, prasugrel, ticagrelor) in the acute phase may be lim-
ited or even impossible. Orodispersible tablets of ticagrelor
might be preferred in such situations. However, even if
crushed drug administration via a gastric tube is performed,
gastrointestinal absorption of these drugs may be delayed
and does not guarantee optimal platelet inhibition during
PCI.29 Accordingly, the use of intravenous antiplatelet
agents such as acetylsalicylic acid,30 glycoprotein receptor
blockers31 or cangrelor,32 and intravenous anticoagulants
like unfractionated heparin, low molecular heparin or biva-
lirudin are desirable to achieve an effective antithrombotic
strategy in the setting of PCI. An ongoing trial is currently
testing the intravenous P2Y12 inhibitor cangrelor in this
setting (Dual Antiplatelet Therapy for Shock patients with
Acute Myocardial Infarction (DAPT-SHOCK-AMI) trial;
ClinicalTrials.gov: NCT03551964). At present the ESC
STEMI guidelines should be followed with respect to
antithrombotic therapy in CS.14
Supportive medical therapies
Although the treatment of CS should be focused on treatment
of the underlying cardiac cause, pharmacotherapy considera-
tions are important in the initial treatment of the acute phase
for haemodynamic stabilization. Sedation and pain manage-
ment should be done according to the ESC STEMI guidelines
with a tranquiliser (a benzodiazepine) and a titrated intrave-
nous opiode (morphine).14 Analgesia and sedation tailored to
the patient’s haemodynamic status are of foremost impor-
tance. Caution should be applied to avoid oversedation which
can act both as a trigger and perpetuator of CS.
Beta-blockers should be avoided until the shock status
resolves. Likewise, inhibitors of the renin-angiotensin sys-
tem should be withheld in the acute phase. Once shock
resolves, especially if LV ejection fraction is low, these
treatments as well as an aldosterone receptor antagonist
should be gradually initiated. Although hypovolaemia is
uncommon in the CS setting, assessment of LV filling pres-
sures should be performed to exclude the possibility that
hypotension is due to inadequate LV filling pressures. This
is particularly important in shock with right ventricular
Zeymer et al. 9

Table 5.  Mechanism of action and haemodynamic effects of commonly vasoactive medications in cardiogenic shock (adapted from
van Diepen et al. Circulation 2017).1

Medication Usual infusion dose Receptor binding Haemodynamic effects

α1 β1 β2 DA
Vasoconstrictor/inotropes
Dopamine 0.5–2 mcg/kg/min - + - +++ ↑ CO
  5–10 mcg/kg/min + +++ + ++ ↑↑CO, ↑SVR
  10–20 mcg/kg/min +++ ++ - ++ ↑↑SVR, ↑CO
Norepinephrine 0.05–0.4 mcg/kg/min ++++ ++ + - ↑↑SVR, ↑CO
Epinephrine 0.01–0.5 mcg/kg/min ++++ ++++ +++ - ↑↑CO, ↑↑SVR
Phenylephrine 0.1–10 mcg/kg/min +++ - - - ↑↑SVR
Vasopressin 0.02–0.04 units/min Stimulates V1 receptors in vascular smooth muscle ↑↑SVR, ↔PVR
Inotropes
Dobutamine 2.5–20 mcg/kg/min + ++++ ++ - ↑↑CO, ↓SVR, ↓PVR, MAP↓
Isoproterenol 2.0–20 mcg/min - ++++ +++ - ↑↑CO, ↓SVR, ↓PVR MAP↓
Milrinone 0.125–0.75 mcg/kg/min PD-3 Inhibitor ↑CO, ↓SVR, ↓PVR MAP↓
Enoximone 2–10 mcg/kg/min PD-3 Inhibitor ↑CO, ↓SVR, ↓PVR MAP↓
Levosimendan 0.05–0.2 mcg/kg/min Myofilament Ca++ sensitiser, PD-3 inhibitor ↑CO, ↓SVR, ↓PVR MAP↓

Ca++: calcium; CO: cardiac output; DA: dopamine; MAP: mean arterial pressure; PD-3: phosphodiesterase-3; PVR: pulmonary vascular resistance;
SVR: systemic vascular resistance.

(RV) infarction, when a more aggressive fluid resuscitation
may be needed.
The target mean blood pressure in CS is not well defined,
but evidence in septic shock suggests that 65 mm Hg seems
to be sufficient, while targeting higher blood pressure levels
might be associated with more side effects.33 In order to
increase cardiac output and maintain a sufficient blood pres-
sure inotropic drugs and/or vasopressors (Table 5) are admin-
istered in >90% of patients in CS. These drugs increase
myocardial oxygen consumption and vasoconstriction,
which may impair microcirculation and increase afterload.
Therefore, any catecholamine should be administered at the
lowest possible dose and for the shortest possible duration.
A number of trials have compared some of these drugs,
particularly dopamine with norepinephrine, but the largest trial
was performed in patients with predominant septic shock. In
this situation dopamine was not associated with an increase in
mortality in the overall shock population.34 However, there
was a higher incidence of arrhythmic events compared to nor-
epinephrine administration. Based on the recent OptimaCC
trial suggesting less side-effects and less refractory CS with
norepinephrine compared with epinephrine,35 norepinephrine
may be the vasoconstrictor of choice when blood pressure is
low and tissue perfusion is insufficient (level of evidence IIb B
in ESC guidelines,2,14 Figure 2(a)–(c)).
The most recent ESC guidelines for the diagnosis and
treatment of acute and chronic heart failure were published
in 2016.2 In these guidelines, treatment with inotropic drugs
(e.g. dobutamine) in patients with hypotension (systolic
blood pressure <85 mm Hg) and/or hypoperfusion is classi-
fied as a class IIb recommendation, with a level of evidence
C.2 Treatment with levosimendan or a phosphodiesterase
inhibitor is classified as class IIb recommendation, also with
class C level of evidence. This reflects the uncertainty in this
field due to the lack of evidence-based medicine and the
need for large randomised trials in CS.
Mechanical ventilation
Oxygenation and airway protection are critical in the
therapy of patients with acute heart failure syndromes
­
and/or CS; intubation and mechanical ventilation are com-
monly required. Positive pressure ventilation can improve
­oxygenation, have positive effects on elevated pulmonary
capillary wedge pressure (PCWP) and/or left ventricular
dysfunction, and reduces the work of breathing. On the
contrary, it may also compromise venous return, preload
and, thus, cardiac output particularly in RV dysfunction
(Figure 1). Studies in patients with acute cardiogenic pul-
monary oedema have shown noninvasive ventilation to
improve haemodynamics and reduce the intubation rate.36
However, mortality remained unaffected.
In patients with CS not responding to initial more
conservative measures including noninvasive ventilation,
­
endotracheal intubation and invasive mechanical ­ventilation
represent an important therapeutic option. The primary indi-
cation for this option is respiratory failure leading to hypoxae-
mia (e.g. SpO2<90%, PaO2<6–7 kPa), h­ypercapnia
(respiratory rate >30–35/min), and acidosis (increased car-
bon dioxide pressure in the arterial blood PaCO2>9–10 KPa,
or pH<7.3 demonstrating that the patient cannot maintain a
normal pH by spontaneous breathing).37 Invasive mechanical
ventilation can decrease the negative sequalae of difficult
breathing at a time of severely impaired cardiac function
10 European Heart Journal: Acute Cardiovascular Care 00(0)

Figure 4.  Possible treatment algorithm for mechanical circulatory support selection based on clinical parameters of cardiogenic
shock severity and also factors which might oppose the use of mechanical circulatory support.
Based on predominant right ventricular (RV) or left ventricular (LV) dysfunction and also the requirement for oxygenation, different mechanical
circulatory support devices may be considered. Accordingly, schematic drawings of current percutaneous mechanical support devices are provided
and these devices should be considered with preference of some devices over others based on the underlying cause of cardiogenic shock. This
algorithm is based on theoretical assumptions but not based on current evidence. ECLS: extracorporeal life support; ECMO: extracorporeal
membrane oxygenation; MCS: mechanical circulatory support; PA: pulmonary artery.

(Figure 1). Physical exhaustion/patient discomfort, dimin-
ished consciousness and the inability to maintain or protect
the airway are other reasons to consider intubation and venti-
lation. Noninvasive methods of positive-pressure ventilation
(NIPPVs) in patients with acute cardiogenic pulmonary
oedema can avert tracheal intubation.36 A NIPPV induces a
more rapid improvement in respiratory distress and metabolic
disturbance than does standard oxygen therapy. However, no
mortality benefit was detected over oxygen for either continu-
ous or bilevel noninvasive ventilation.37 NIPPVs in coopera-
tive, fully conscious (not fatigued) patients with pulmonary
oedema, with the aim to improve breathlessness and reduce
hypercapnia and acidosis, has recently been categorised as
Class IIa, level of evidence B, in the ESC heart failure guide-
lines.2 A NIPPV is considered contraindicated in case of elec-
trical instability and vomiting.37
MCS devices
Intraaortic balloon counterpulsation
Intraaortic balloon pumping (IABP) is a relatively old tech-
nology after approximately five decades of use. By diastolic
inflation and rapid systolic deflation in the aorta it improves
peak diastolic pressure and lowers the end-systolic pressure.
However, haemodynamic effects on cardiac output or mean
arterial blood pressure are negligible.38 Currently, IABP is
still the most widely used MCS device for haemodynamic
support. Based on a small pilot trial in 40 patients with CS
the large randomised multicentre IABP-SHOCK II trial ran-
domised 600 patients with CS complicating AMI and early
revascularization to IABP or conventional treatment.25,39
There was no difference in the primary study endpoint of
30-day mortality between the two treatment groups and
these results were confirmed by a lack of beneficial effects
for any of the secondary study endpoints and mortality after
one year.25,39 Just recently the six-year data confirmed no
benefit of IABP on long-term outcome.11 Therefore, the rou-
tine use of IABP cannot be recommended based on the cur-
rent evidence and should be limited to patients with
mechanical complications (Figure 2(a)–(c)).
Percutaneous active MCS devices
Active percutaneous MCS devices have been used in
patients not responding to standard treatment including
Zeymer et al. 11
catecholamines, fluids and IABP, and also as first-line
treatment. However, the current experience and evidence of
benefit is limited. The current devices, mode of action and
evidence regarding percutaneous MCS devices in CS have
been summarised previously.40
Current devices include the TandemHeart (Cardiac
Assist, Inc., Pittsburgh, USA) which removes arterialised
blood from the left atrium and returns it to the lower
abdominal aorta or iliac arteries via a femoral artery can-
nula with retrograde perfusion of the abdominal and tho-
racic aorta. Another percutaneous device, the Impella 2.5,
CP or 5.0 (Abiomed Europe, Aachen, Germany), is placed
across the aortic valve using femoral access either percuta-
neously or by surgical cut-down. This device with the 2.5
litre version has been tested in a small randomised clinical
trial in 26 CS patients in comparison to IABP showing
improved cardiac index with the use of the Impella device.41
However, in another small trial no mortality benefit has
been reported for Impella CP use compared to IABP in CS
patients requiring ventilation.42 Newer left ventricular MCS
devices include the HeartMate PHP (Abbott, Lake Bluff,
Illinois, USA) deployed across the aortic valve and deliver-
ing blood from the left ventricle to the aorta, similarly to the
Impella family. Another investigational device is the para-
corporeal pulsatile iVAC 2L (PulseCath BV, Arnhem, The
Netherlands). For the iVAC and HeartMate PHP, results
from randomised trials are currently not available.
A meta-analysis reported the results of the four ran-
domised trials including only 148 patients comparing per-
cutaneous MCS versus IABP. MCS use did not show any
difference in 30-day mortality.43 Patients treated with active
MCS demonstrated improved haemodynamics as shown by
higher mean arterial pressure and lower lactate levels, but
had more bleeding and a trend towards more femoral access
complications.43 Based on these results percutaneous MCS
cannot be recommended as first-line treatment in CS. A
treatment algorithm including the potential role of these
devices is shown in Figure 2(a)–(c) and also in Figure 4.
Currently, there is an ongoing combined Danish and
German randomised trial with the Impella CP in compari-
son to standard treatment with or without IABP
(ClinicalTrials.gov: NCT03551964).
Extracorporeal membrane oxygenation
(ECMO)
After the introduction of the first cardiopulmonary bypass
system with oxygenation in 1953, further developments led
to percutaneous devices. ECMO systems consist mainly of
a blood pump and an oxygenator. There are different types
of ECMO according to the circuit of blood created. In
venous-arterial (VA) ECMO, the most commonly used in
CS, after pump priming blood is withdrawn from the right
atrium and pumped through a heat exchanger, a membrane
oxygenator, and ultimately returned into the femoral artery.
This allows a significant increase in oxygenated blood flow
to the periphery. However, there are several drawbacks of
these devices such as large cannulae sizes with possible
subsequent lower limb ischaemic complications, frequent
requirement of perfusionists, lack of direct LV unloading,
increase in afterload, and a limited time that the support can
be continued. The value of newer, smaller and portable
devices needs to be tested in future randomised trials. As
long as there are no adequate clinical trials assessing mean-
ingful clinical endpoints, the use of percutaneous MCS
devices including ECMO treatment should be restricted to
cases of refractory CS (definition provided by Baran et al.)3
and relying on individual experience in dedicated centres
for highly selected patients. In addition to an increase in the
need for catecholamines, increasing lactate levels might be
helpful to identify patients in whom MCS might be
indicated.
Currently two trials (EURO-SHOCK and ECLS-Shock)
adequately powered to assess the impact of VA-ECMO on
mortality in CS have started patient recruitment or are in
planning phases (ClinicalTrials.gov: NCT03813134 and
NCT02544594).
A possible treatment algorithm for the use of different
MCS devices in different situations and based on clinical
parameters is given in Figure 4.
Specific patient groups
Cardiopulmonary resuscitation
In the IABP-SHOCK II and the CULPRIT-SHOCK trial
more than 40% and 50% of patients,25,26 respectively, were
resuscitated before randomization with subsequent targeted
temperature control showing the relevance of this condition
in CS. Central in the care of post-resuscitation CS patients is
to ensure the optimal cardiocerebral outcome after return of
spontaneous circulation (ROSC). Immediately following
cerebral anoxia, structural and homeostatic changes induce
a myriad of processes ultimately leading to potentially irre-
versible brain damage. Even after ROSC, cerebral damage
may continue related to reperfusion injury, often referred to
as secondary brain injury. Many of these destructive pro-
cesses are temperature-dependent, hence the concept of pre-
venting a poor neurological outcome by temperature control
after ROSC. Two trials from 2002 and one recent trial from
2019 suggested that hypothermia improves neurological
outcome after return of ROSC in patients with a sockable
(i.e. ventricular fibrillation or ventricular tachycardia) and
non-shockable cardiac arrest.44–46 The three studies induced
mild to moderate hypothermia (32–34°C) in comatose
patients via external cooling, for up to 12 or 24 h. However,
hypothermia can trigger several physiological responses
that, at least theoretically, might negatively affect patients in
CS, including haemodynamic derangements, bleeding risk
and infection. The optimal timing of initiation of
12 European Heart Journal: Acute Cardiovascular Care 00(0)
Table 6.  Haemodynamic formulas to assess right ventricular (RV) function (adapted from Kapur et al. Circulation 2017).56
Name
Left and right cardiac filling pressures
Pulmonary artery pulsatility index (PAPI)
Pulmonary vascular resistance (PVR)
Transpulmonary gradient (TPG)
Diastolic pulmonary gradient (DPG)
RV stroke work (RVSW)
RV stroke work index (RVSWI)
PA compliance
PA elastance
CO: cardiac output; LVAD: left ventricular assist device; MI: myocardial infarction; mPAP: mean pulmonary artery pressure; PA: pulmonary artery;
PADP: pulmonary artery diastolic pressure; PASP: pulmonary artery systolic pressure; PCWP: pulmonary capillary wedge pressure; RAP: right atrial
pressure; RVF: right ventricular failure; SV: stroke volume.
hypothermia, its duration and speed of rewarming also
remain uncertain. In addition, the optimal temperature dur-
ing hypothermia is still unclear; widespread uncertainty also
remains about how to predict neurological outcome, as tra-
ditional algorithms predate the introduction of therapeutic
hypothermia. Hypothermia alters the pharmacokinetics and
pharmacodynamics of drugs, due to alterations in absorp-
tion and metabolization. This might also affect the efficacy
and safety of often-used antithrombotic agents in CS. The
recent randomised SHOCK-COOL trial in non-resuscitated
CS patients showed no benefit of hypothermia versus stand-
ard treatment on the surrogate endpoint cardiac power index
and may even have induced harm as indicated by impaired
lactate clearance.47 In summary, because of the favourable
effects on neurological outcome – despite some haemody-
namic disadvantages – the current evidence seems more in
favour of moderate therapeutic hypothermia (33°C) in CS
after resuscitation.
Mechanical complications
Rupture of the free wall, the interventricular septum or a
papillary muscle is an uncommon but extremely serious
complication of AMI, usually leading to profound haemo-
dynamic consequences. Prompt recognition and aggressive
management of these complications may offer a chance of
survival.
Cardiac rupture, whether of the free wall or the inter-
ventricular septum, is the second most common cause of
mortality among hospitalised patients with STEMI.48 Due
to the widespread use of primary PCI the incidence is
declining. Mortality in patients with cardiac rupture
decreased progressively over this time period from 94% to
75%, despite the increasing age of this cohort.49 This
decrease was mainly attributed to earlier diagnosis and
better management.
Formula Predictor of RVF
RAP/PCWP >0.63 (RVF after LVAD)
>0.86 (RVF in acute MI)
(PASP−PADP)/RAP <1.85 (RVF after LVAD)
<1.0 (RVF in acute MI)
mPAP−PCWP/CO >3.6 (RVF after LVAD)
mPAP−PCWP Not determined
PADP−PCWP Not determined
(mPAP−RAP)×SV×0.0136 <15 (RVF after LVAD)
<10 (RVF after acute MI)
(mPAP−RAP)/SV index <0.3–0.6 (RVF after LVAD)
SV/(PASP−PADP) <2.5 (RVF in chronic heart failure)
PASP/SV Not determined
The diagnosis of free wall rupture is based on clinical
and echocardiographic signs of pericardial tamponade.50 It
is important to distinguish acute rupture with tamponade
from free wall rupture that is rapidly sealed by the pericar-
dium and often presents as subacute rupture. This requires
a high clinical index of suspicion and confirmation since
diagnosis is difficult. The ECG typically shows pericardial
effusion with evidence of chamber compression. Emergent
pericardiocentesis should follow. If the fluid turns out to be
bloody, the diagnosis could be free wall rupture or haemor-
rhagic pericarditis, which can be extremely difficult to dif-
ferentiate. If the patient stabilises and bleeding stops, a
conservative approach might be justified, whereas further
bleeding should lead to prompt surgery.
Rupture of the interventricular septum has also become a
rare complication in the era of reperfusion.51 Acute septal
rupture causes left to right shunt with RV and later LV vol-
ume overload. With time, both ventricles usually fail.
Physical examination often reveals a loud systolic murmur
along the left parasternal area which radiates widely, includ-
ing to the right parasternal area. The diagnosis is based upon
echocardiographic demonstration of left to right shunting
across the ventricular septum. The prognosis of conserva-
tively managed ventricular septal rupture is extremely poor
and mortality exceeds 80%.52 Early surgical correction of
the defect seems to offer the best chance of survival and
patients who survive surgery have a relatively favourable
prognosis.53 Surgery should not be delayed to allow fibrosis
of the septum as most patients will not survive the delay due
to progressive heart failure and/or multiorgan failure and
infection. Recently, percutaneous closure has emerged as a
promising alternative to surgery.54
Mitral regurgitation is a common complication of AMI
and is usually the result of valve tethering due to ventricular
dysfunction. A rare but catastrophic form of acute mitral
regurgitation post-AMI involves rupture of a papillary
Zeymer et al. 13
muscle or chordae tendineae. The true prevalence of this
complication in the era of reperfusion is difficult to ascertain
but is probably less than 1% of cases. Unlike chronic mitral
regurgitation, left atrial compliance is often low in these
patients, leading to rapid equilibration of ventricular and
atrial pressures during systole; this, along with depressed
cardiac output, may lead to a very soft or absent murmur, the
detection of which is often made even more difficult by pul-
monary oedema and mechanical ventilation. The diagnosis is
best made echocardiographically; trans-oesophageal echo-
cardiography is often very helpful when imaging quality is
suboptimal in these acutely ill and often mechanically venti-
lated patients and may also be helpful to delineate details of
the valve pathology. Surgery currently offers a reasonable
chance of survival in these extremely sick patients.55
Based on theoretical assumptions, however, without any
evidence, current ESC guidelines recommend the use of
IABP in patients with ventricular septal defect or acute
mitral regurgitation (Figure 2(c)).14
RV failure
The deleterious effect of acute RV dysfunction in patients
suffering from AMI with RV involvement are well known.56,57
RV involvement may be asymptomatic or present as refrac-
tory CS. The typical triad is hypotension, distended jugular
veins and clear lungs. The three main elements forming the
basis of the diagnosis are ECG, echocardiography and right
heart catheterization using PACs. ST elevation in right
precordial leads (V3R and V4R) has high specificity for the
diagnosis of RV involvement, and these should be done in all
patients with STEMI, particularly if they are hypotensive.
Echocardiography plays a major role in the diagnosis of RV
involvement. RV dilation, particularly in the presence of RV
regional wall abnormalities, is highly suggestive.
Echocardiographic indices used to evaluate RV function
include: fractional shortening, tricuspid annular plane sys-
tolic excursion (TAPSE), pulsed Doppler tissue imaging and
the Tei index. Other important echocardiographic indices for
the investigation include RV distension, RV ejection fraction,
right atrial size, pulmonary or tricuspid regurgitation, estima-
tions of pulmonary pressures, evaluation of the LV, interven-
tricular septum and pericardium. Right heart catheterization
yields useful information on right atrial, pulmonary artery
(PA) and PCWPs, mixed venous oxygenation, cardiac output
and allows calculation of cardiac index, systemic vascular
resistance (SVR), pulmonary vascular resistance (PVR), pul-
monary artery pulsatility index (PAPI), and cardiac power
index. There is a multitude of different haemodynamic vari-
ables that have proven to be associated with impaired out-
come in acute RV dysfunction (see Table 6). Right heart
catheterization also makes it possible to evaluate the response
to filling tests and treatment.
The specific therapeutic management of RV-associated
CS is based on the aetiological treatment of RV dysfunction,
that is, coronary reperfusion, usually with primary PCI of an
occluded proximal right coronary artery, including acute
marginal branches if needed. Effective reperfusion usually
leads to rapid haemodynamic improvement. Restoring sinus
rhythm in patients with complete atrio-­ventricular block or
atrial fibrillation is also essential as the loss of atrial kicks
may cause a severe drop in cardiac output in patients with
acute severe RV involvement. If not restored after reperfu-
sion, synchronised dual chamber pacing or cardioversion
may be needed. The general principles of RV dysfunction
management have been reviewed ­elsewhere.57 These include
(a) optimal volume management with or without vasopres-
sor therapy; (b) optimization of heart rate; (c) enhanced RV
inotropy and improved ­cardiac output, usually with dobu-
tamine; (d) reduction of RV afterload and pulmonary resist-
ance. Lastly, the use of MCS devices with dedicated RV
support or VA-ECMO may be considered in certain patients
with refractory CS.56
Future perspective
While the widespread use of early revascularization ther-
apy with PCI or CABG encouraged by the results of the
first large CS trial has dramatically reduced mortality in
CS, there is a lack of evidence for most of the medical and
other supportive therapies. This calls for international col-
laboration, as successfully demonstrated in the CULPRIT-
SHOCK trial to further refine therapy in CS. Areas of
interest include the use of MCS devices, dosing of existing
inotropes and vasopressors and possibly the introduction of
new agents, definition of target blood pressure and optimi-
zation of fluid management, antithrombotic therapies and
ventilation.
Acknowledgements
Reviewer coordinator: Sigrun Halvorsen, Department of
Cardiology, Oslo University Hospital Ulleval, and University of
Oslo, Oslo, Norway. Reviewers: Christian Hassager, Department
of Cardiology, Rigshospitalet and Department of Clinical
Medicine, University of Copenhagen, Copenhagen, Denmark;
Gilles Montalescot, Sorbonne Université, ACTION Study Group,
Institut de Cardiologie, Pitié-Salpêtrière Hospital (AP-HP), Paris,
France; Karl Werdan, Department of Medicine III, University
Hospital Halle (Saale), Germany; Sean van Diepen, Department
of Critical Care Medicine and Division of Cardiology, Department
of Medicine, University of Albert; Alessandro Sionis, Cardiology
Department, Hospital de la Santa Creu i Sant Pau, Universitat
Autònoma de Barcelona.
Conflict of interest
The authors declare that there is no conflict of interest.
Funding
The authors received no financial support for the research,
­authorship and/or publication of this article.
14 European Heart Journal: Acute Cardiovascular Care 00(0)
Supplemental material
Supplemental material for this article is available online.
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