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OPINION An overview of international cardiogenic shock
guidelines and application in clinical practice
Sean van Diepen a,b,c and Holger Thiele d

Purpose of review
In this review, we compare central differences in cardiogenic shock recommendations in international
clinical practice guidelines, scientific statements, and the strength of the supporting evidence. Furthermore,
we discuss their associations with adherence to guidelines in registry studies.
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Recent findings
The evidence base underpinning American Heart Association/American College of Cardiology’s and
European Society of Cardiology’s recommendations for an early invasive approach is relatively strong, but
adherence to these recommendations is poor in registry and population-based studies. There is little
evidence supporting the use of temporary mechanical circulatory support or pulmonary arterial
catherization in cardiogenic shock, and international guidelines provide weak and conflicting
recommendations, yet studies show mechanical circulatory support use is rising exponentially while
pulmonary arterial catherization use remains low. Guidelines provide conflicting information on the optimal
first-line vasoactive agent and norepinephrine remains the most widely used agent.
There are some inconsistencies between individual guideline recommendations, but there are no consistent
associations between the strength of underlying evidence, weight of guideline recommendations, and
adherence to guidelines in clinical practice. Improved knowledge translation of recommendations with a
strong evidence base, together with research efforts to address priority cardiogenic shock research needs,
could serve-to-harmonize recommendations and improve patient outcomes.
cardiogenic shock, clinical practice guidelines, knowledge translation

INTRODUCTION practice standards reported in many clinical regis-

Cardiogenic shock is a cardiac disorder that results tries [3,4]. Thus, efforts to improve outcomes in this
in life-threatening clinical and laboratory hypoper- high-acuity and high-risk population should be
fusion of end-organ tissues [1 ]. In a contemporary focused on both knowledge translation to increase
multicenter registry, acute coronary syndromes the adoption of evidence-based best practices, and
(ACS, 81%), chronic heart failure (11%) and valvu- the evaluation of new therapeutic interventions
lar heart disease (6%) were the leading causes of through clinical trials. In this review, we compare
shock [2]. ST-segment elevation myocardial infarc- the differences in central cardiogenic shock thera-
tion (STEMI) is the best studied cause with an inci- peutic and monitoring guideline recommendations
dence of 6–10% and accounts for the majority of
ACS-associated cardiogenic shock [2,3]. Despite sig-
nificant temporal improvements in mortality fol- Department of Critical Care, bDivision of Cardiology, Department of
Medicine, cCanadian VIGOUR Center, University of Alberta, Edmonton,
lowing the publication of the SHOCK (Should We
Alberta, Canada and dHeart Center Leipzig at University of Leipzig and
Emergently Revascularize Occluded Coronaries for Leipzig Heart Institute, Leipzig, Germany
Cardiogenic Shock?) trial, outcomes remain rela- Correspondence to Sean van Diepen, MD, MSc, 2C2 Cardiology Walter
tively poor with short-term mortality rates of 40– MacKenzie Center, University of Alberta Hospital, 8440-11 St., Edmonton,
47% in clinical trials and 30–51% in registry studies AB, Canada T6G 2B7. Tel: +1 780 407 6948; fax: +1 780 407 7485;
& &
[3,4,5 ,6,7 ,8]. These temporal improvements, e-mail: sv9@ualberta.ca
however, may belie treatment disparities and/or Curr Opin Crit Care 2019, 25:365–370
the suboptimal application of evidence-based DOI:10.1097/MCC.0000000000000624

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Cardiogenic shock

dysfunction [1 ]. PAC can also be used to monitor
KEY POINTS responses to vasoactive therapies, mechanical circu-
 There is no clear association between the weight of latory support (MCS), or fluid shifts, and can also
guideline recommendations and adherence to provide prognostic information, such as cardiac
guidelines in clinical practice. power output [14]. The effect of routine PAC use
on clinical outcomes in the cardiogenic shock
 Understanding the barriers to adherence to guideline
population, however, remains unclear. Multiple
recommendations, and priority efforts to implement best
practices could improve survival in cardiogenic shock. randomized trials in noncardiogenic shock popula-
tions have demonstrated either no benefit or harm
 Further cardiogenic shock research could potentially with routine PAC use, while small observational
help harmonize clinical practice studies have suggested reduced mortality in patients
guidelines recommendations.
with cardiogenic shock [15–17]. This clinical uncer-
tainty likely reflects the discrepancy in guideline
recommendations; the AHA/ACC STEMI and heart
across major American and European STEMI, failure guidelines lean toward routine use, while the
heart failure guidelines and cardiogenic shock sci- ESC guidelines both provide a class IIb recommen-
entific statements, qualitatively discuss if (in)con- dation [9–12]. The AHA scientific statement sugges-
sistencies in recommendations may be associated tion of PAC ‘in cases of diagnostic or cardiogenic
with practice variation, and propose priority shock management uncertainty or in patients
research needs to improve cardiogenic shock out- with moderate to severe cardiogenic shock who
comes [1 ,9–13]. are unresponsive to initial therapy’ strikes a more
intermediate stance [1 ]. These conflicting recom-
mendations, coupled with lack of evidence, are
DIFFERENCES IN CLINICAL PRACTICE likely reflected by the less than 10% PAC utilization
GUIDELINE AND SCIENTIFIC STATEMENT rate reported in population-based studies, and
CARDIOGENIC SHOCK highlight the need for dedicated trials in this popu-
A summary of central monitoring and treatment
recommendations in the American Heart Associa-
tion (AHA)/American College of Cardiology (ACC) Vasoactive therapy
and European Society of Cardiology (ESC) STEMI The weight of existing clinical trial evidence sup-
and heart failure guidelines, the ESC revasculariza- ports the use of norepinephrine as a first-line vaso-
tion guidelines, and the AHA’s CS Scientific constrictive agent in patients with cardiogenic
Statement’s suggestions are summarized in Fig. 1.
&& &
shock if the blood pressure is low [18 ,19,20 ].
In this framework, Class I recommendations On the strength of these studies, a recent European
have evidence, or a general agreement, that an prospective cohort reported that the majority of
intervention is indicated. In Class II recommen- patients with cardiogenic shock are being treated
dations, there is conflicting evidence or opinion with norepinephrine (75%), while dopamine and
wherein Class IIa recommendations should be epinephrine are used in 26 and 21% (percentages
considered and IIb may be considered. Class III not-mutually exclusive), respectively [21]. Cur-
recommendations indicate that a treatment is not rently, none of the guidelines and statements have
recommended and may even cause harm. Recom- provided norepinephrine a class I recommenda-
mendations with level of evidence A are supported tion. The AHA/ACC heart failure guidelines list
by multiple randomized control trials (RCTs) or inotropes as a potential first-line vasoactive option
meta-analyses, level B are derived from single RCTs and, while both STEMI guidelines and the AHA
or large nonrandomized trials, whereas level scientific statement state that norepinephrine
C recommendations are based on expert opinion may be a safer alternative, the AHA/ACC STEMI
or small studies. guidelines and AHA scientific statement advocate
for an individualized approach based on cause and/
or hemodynamic phenotype [1 ,9–12]. The latter
Monitoring therapeutic recommendation may be grounded in
There are multiple potential advantages of routine the recognition of the breadth of cardiogenic shock
pulmonary arterial catheterization (PAC) in patients severity, causes, and hemodynamics observed clin-
with cardiogenic shock. It can serve as a tool to help ically that have yet to be evaluated within clinical
confirm the diagnosis, severity, hemodynamic phe-
trials [1 ,22]. This may explain the ongoing use of
notype, and the presence of right ventricular (RV) either dopamine or epinephrine in up to 50% of

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Overview of international cardiogenic shock guidelines van Diepen and Thiele

American Heart Associaon and/or American College of Cardiology European Society of Cardiology
2013 STEMI[9] 2013 Heart Failure[10] AHA Scienfic Statement[1] 2017 STEMI[11] 2016 Heart Failure[12] 2018 Revascularizaon[13]

Monitoring and Imaging

Echocardiogram 1C 1C Suggested IC IC None
(for all STEMI paents) (all paents) (without delaying angiography)
Pulmonary Arterial No Grade 1C Suggested IIb B IIb C None
Catheter “invasive monitoring to guide” (diagnosc or management
vasoacve therapy uncertainty)
Arterial Line None None Suggested IC IC None
Vasoacve Therapy
First line vasoacve No Grade Inotropes 1 C Individualized to phenotype and No Grade Inotropes IIb C No grade
Individualized therapy. eology “Dobutamine inial therapy” Norepinephrine IIb B “Inotropic support”
Dopamine may be “associated “Norepinephrine is associated with “Norepinephrine may be safer”
with excess hazard” fewer arrhythmias” than Dopamine
Fluid challenge None None Suggested No Grade IC None
“hypovolemia should be corrected” (if no signs of overload)
Venlatory support* None None Suggested IIa B NIMV IIa B NIMV No grade
I C IMV I C IMV “Venlatory support”
Early Invasive Approach IB None Suggested IA IC IB
PCI Revascularizaon of None None Suggested IRA only Complete index revascularizaon None III B
Mulvessel Disease (pending CULPRIT-SHOCK results) IIa C (Non-IRA revascularizaon)
Fibrinolysis IB None Suggested IIa C None None
(if not a candidate for PCI or (if early invasive approach cannot be (If PCI not available in ≤120 min)
CABG) completed in mely fashion)
CABG IB None Suggested IB None IB
(If anatomy not suitable for (individualized decisions for mul- (if anatomy not suitable for PCI) (if anatomy not amenable to
PCI) vessel or le main) PCI)
Mechanical Circulatory Support
IABP IIa B None Acute MR or VSD Suggested Roune III B III B III B
Acute MR or VSD IIa C
Temporary MCS IIb C IIa B Suggested IIb C IIb C IIb C
(paents selected by muldisciplinary
Systems of Care
Transfer to PCI hospital 1B None Dedicated Cardiogenic Shock Systems of 1C 1C 1B
Care Suggested (all STEMI paents) (dedicated terary (regional network for all
center) STEMI)

FIGURE 1. Differences in selected cardiogenic shock international guideline recommendations and scientific statement
suggestions. AHA, American Heart Association; CABG, coronary artery bypass grafting; IABP, intra-aortic balloon pump; IRA,
infarct-related artery; IMV, invasive mechanical ventilation; MCS, mechanical circulatory support; MR, mitral regurgitation;
NIMV, noninvasive mechanical ventilation; PCI, percutaneous coronary intervention; STEMI, ST-segment elevation myocardial
infarction; VSD, ventricular septal defect. aPlease refer to each document for clinical criteria for intubation, invasive, and/or
noninvasive mechanical ventilation.

patients with cardiogenic shock and explain the mortality or renal replacement therapy with culprit-
&& &
lack of a strong endorsement of one agent in prac- lesion only revascularization [24 ,25 ]. This was
tice guidelines. Testing norepinephrine across the mainly driven by a significant reduction in 30-day
range of underlying etiologies, cardiogenic shock mortality. In addition, the guidelines provide guid-
severity, and in patients with RV dysfunction ance for emergency CABG in patients with anatomy
remain unanswered scientific questions in that is either not suitable for PCI or with multivessel
this field. disease, and allowances for selective fibrinolysis in
patients if timely PCI is not feasible. Alarmingly,
revascularization rates in both the United States and
Revascularization Europe remain suboptimal. In the French FAST-MI
The SHOCK trial demonstrated a significant reduc- program, only 57% of patients with STEMI compli-
tion in 6-month and long-term mortality among cated by cardiogenic shock underwent reperfusion
patients with a myocardial infarction (MI) compli- therapy in 2010, including 51% primary PCI, 3%
cated by cardiogenic shock undergoing an early CABG, and 6% prehospital fibrinolysis [4]. Similarly,
invasive approach [5 ]. In addition, there were no an American Nationwide Inpatient Sample reported
differences in outcomes between patients revascu- that in 2010 only 54% underwent PCI, 3% CABG,
larized with percutaneous coronary intervention and 4% fibrinolysis [3]. In the GRACE registry,
(PCI) or coronary artery bypass grafting (CABG), only 57% of patients with cardiogenic shock under-
although the revascularization strategy was not ran- went angiography, among whom 70% underwent
domized [23]. On the basis of this trial, current PCI and 16% underwent CABG [26]. Although the
international guidelines are consistent in their reasons underpinning the low utilization of revas-
strong recommendations for an early invasive cularization in STEMI patients complicated by car-
approach in MI complicated by cardiogenic shock. diogenic shock require further research, the low
All guidelines advocate a preference for PCI and the rates in both the United States and Europe despite
recent CULPRIT-SHOCK trial demonstrated a lower high-quality evidence and strong guideline recom-
30-day and 1-year combined endpoint consisting of mendations represent the biggest potential area

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Cardiogenic shock

wherein stronger adherence to guidelines could implantation in patients with MI complicated by

improve clinical outcomes. shock, the use of IABP has dropped significantly
[7 ,35,36]. Currently, ESC guidelines discourage
the use of routine IABP; the lone exception is the
Systems of care AHA/ACC STEMI guidelines which were published
To facilitate an early invasive approach, guidelines on-line the same year as the IABP SHOCK-II trial [9].
recommend the transfer of patients with cardio- The guidelines and scientific statement continue to
genic shock to a PCI-capable center. Based largely recommend IABP use in patients with mechanical
on studies showing improved outcomes in other complications of STEMI, given this high-risk group
complex and time-sensitive conditions that poten- was excluded from the IABP SHOCK-II trial, and
tially require multidisciplinary care, and modest based on theoretical assumptions. However, the
associations between higher cardiogenic shock hos- evidence behind this recommendation is only based
pital volume and increased adherence to guidelines on expert consensus and represents a level of
with reduced in-hospital mortality, there is a grow- evidence C.
ing call for formally established systems of cardio-
genic shock care that mirror those of other
conditions such as trauma, STEMI, and out-of-hos- ADOPTING EVIDENCE INTO PRACTICE
pital cardiac arrest [1 ,27–31]. Thus far, studies In this qualitative assessment of clinical practice
have only demonstrated the feasibility of this guidelines, we observed some inconsistencies in
approach and this represents an important research the strength or level of evidence underpinning indi-
need [32]. vidual guideline common monitoring or treatment
recommendations across six international societal
guidelines. We hypothesize these differences may,
Mechanical circulatory support in part, be due to differences in the year of publica-
Arguably the most interesting disconnect between tion relative to seminal trials, differential interpre-
evidence and cardiogenic shock practice is the tation of lower quality evidence, and/or underlying
growing utilization of temporary MCS despite lack pathologies. In addition, there does not appear to be
of clear survival benefit and absence of strong a consistent association between the strength or
recommendations in practice guidelines. Cur- level of evidence and adherence to guidelines in
rently, there is no strong evidence from random- clinical practice. Somewhat paradoxically, the appli-
ized controlled trials showing that temporary MCS cation of Class I recommendations with a strong
devices improve mortality. Hence, the American evidence-base, such as an early invasive approach in
STEMI and European STEMI, heart failure, and suspected ACS, remains suboptimal while use of
revascularization guidelines provide a class IIb IABPs remains common despite the publications
recommendation, whereas the American heart fail- of IABP-SHOCK II trial and new class III recommen-
ure guidelines provide a class IIa recommendation dations in ESC guidelines. Although we acknowl-
[9– 13]. The AHA scientific statement suggests edge the well recognized delays between evidence
temporary over durable MCS to facilitate stabiliza- publications, guideline adoption, and change in
tion, a therapeutic procedure, allow full candidacy clinical practice, the relatively poor cardiogenic
evaluation, or when surgical risk is prohibitive, shock outcomes coupled with the lack of adherence
and that candidates should be selected by a to guidelines represent an important knowledge
multidisciplinary team [1 ]. Despite these weak translation initiative that can potentially improve
endorsements, multiple studies have documented survival.
an exponential increase in the use of temporary
MCS, including veno-arterial extracorporeal
membrane oxygenation and Impella (Danvers, PRIORITY RESEARCH NEEDS
Massachusetts, USA) [6,33 –35]. We surmise that Our observation that only two of the cardiogenic
a strong belief in the efficacy of MCS among shock monitoring or treatment recommendations
clinicians may be driving this change in practice outlined in Fig. 1 received a consensus Class I rec-
in the absence of a strong evidence base, and eval- ommendation based on either level A or B of evi-
uating the efficacy, safety and patient selection dence (early invasive approach in suspected ACS,
may be the most pressing research priority in and CABG in patients with anatomy not suitable for
this field. PCI) may reflect both the relative paucity of research
Following the publication of the intra-aortic and the challenges of performing controlled trials in
balloon pump in cardiogenic shock II (IABP-SHOCK this population. Notwithstanding, these factors
II) trial, which showed no benefit with routine IABP coupled with the relatively poor outcomes in the

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Overview of international cardiogenic shock guidelines van Diepen and Thiele

Table 1. Proposed research needs in cardiogenic shock

Cardiogenic shock
treatment or monitoring Research need

Monitoring Testing outcomes of PAC use in patients with CS

Treatment Anti-inflammatory treatment targets in CS
Testing norepinephrine and the role of inotropes across a range of underlying pathologies, CS
severity, and in patients with RV dysfunction
Optimal hemodynamic/blood pressure targets
Interventional/Revascularization CABG or primary culprit only PCI revascularization in patients with CS and multivessel disease
Optimal anticoagulation strategies
Radial versus femoral access
MCS Testing if MCS devices save lives in CS
Head-to-head testing of MCS devices
Defining patients who may benefit from MCS
Role of ECMO in refractory cardiac arrest
Systems of care Testing if coordinated systems of care including dedicated CS centers improve survival
Knowledge translation Understanding barriers to adoption and the implementation of best practices

CABG, coronary artery bypass grafting; CS, cardiogenic shock; ECMO, extracorporeal membrane oxygenation; MCS, mechanical circulatory support; PAC,
pulmonary arterial catheterization; PCI, percutaneous coronary intervention; RV, right ventricular.

cardiogenic shock population help to highlight the Conflicts of interest

pressing need for more RCTs in this acute patient There are no conflicts of interest.
population. In Table 1, we propose some priority
research needs.
CONCLUSION Papers of particular interest, published within the annual period of review, have
been highlighted as:
Cardiogenic shock is an acute and potentially time- & of special interest
&& of outstanding interest
sensitive condition associated with high morbidity
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