REVIEWS

Management of refractory cardiogenic

shock
Alex Reyentovich1, Maya H. Barghash1 and Judith S. Hochman2
Abstract | Cardiogenic shock is a life-threatening condition that occurs in response to reduced
cardiac output in the presence of adequate intravascular volume and results in tissue hypoxia.
Cardiogenic shock has several underlying aetiologies, with the most common being acute
myocardial infarction (AMI). Refractory cardiogenic shock presents as persistent tissue
hypoperfusion despite administration of adequate doses of two vasoactive medications and
treatment of the underlying aetiology. Investigators of the SHOCK trial reported a long-term
mortality benefit of emergency revascularization for shock complicating AMI. Since the
publication of the SHOCK trial and subsequent guideline recommendations, the increase in
community-based use of percutaneous coronary intervention for this condition has resulted
in a significant decline in mortality. Despite these successes in the past 15 years, mortality still
remains exceptionally high, particularly in patients with refractory cardiogenic shock. In this
Review, we discuss the aetiology and pathophysiology of cardiogenic shock and summarize the
data on the available therapeutics and their limitations. Although new mechanical circulatory
support devices have been shown to improve haemodynamic variables in patients with shock
complicating AMI, they did not improve clinical outcomes and are associated with high costs
and complications.

1
Division of Cardiology,
New York University–Langone
Medical Center, 530 First
Avenue, New York,
New York 10016, USA.
2
Department of Medicine,
Cardiovascular Clinical
Research Center, 530 First
Avenue, New York, New York
10016, USA.
Correspondence to A.R.
alex.reyentovich@nyumc.org
doi:10.1038/nrcardio.2016.96
Published online 30 June 2016
Cardiogenic shock describes a physiological state of
end-organ hypoperfusion characterized by reduced
cardiac output in the presence of adequate intravascu-
lar volume1. The overall incidence of cardiogenic shock
has not changed from 2001 to 2014, although in 2014 a
higher proportion of patients presented with cardiogenic
shock on admission (1.9% in 2001 versus 2.7% in 2014,
P = <0.01) and fewer developed cardiogenic shock dur-
ing hospitalization (4.8% in 2001 versus 2.1% in 2014,
P = 0.01)2. Cardiogenic shock has a wide spectrum of
presentation, ranging from preshock to refractory
cardio­genic shock, and patients with refractory cardio-
genic shock have the worst prognosis3,4. At present, there
is no agreed consensus on the criteria that define cardio­
genic shock, nor is there a well-established severity
scale. Clinical recognition of signs of preshock (that is,
hypoperfusion without hypotension) is critical for early
intervention. In the SHOCK trial registry 5, patients with
nonhypotensive cardiogenic shock had high systemic
vascular resistance and stable blood pressure levels, but
low cardiac indices, low ejection fraction, and elevated
pulmonary capillary wedge pressure (PCWP), similar to
those with classic cardiogenic shock. Inhospital mortal-
ity in patients with nonhypotensive cardiogenic shock
was lower than in those with hypotensive cardiogenic
shock5. The clinical criteria for cardiogenic shock used
in the trial included hypotension (defined as systolic
blood pressure (SBP) <90 mmHg for at least 30 min, or
mean arterial pressure 30 mmHg lower than baseline,
or the need for pharmacological or intra-aortic balloon
pump (IABP) support to maintain SBP >90 mm Hg) and
end-organ hypoperfusion (defined as cool extremities,
oliguria with urine output of <30 ml/h, altered mental
status, serum lactate >2.0 mmol/l, and clinical signs of
pulmonary congestion)6. Haemodynamic criteria, when
central monitoring was available, included cardiac index
≤2.2 l/min/m2 and adequate or elevated left ventricular
(LV) filling pressures (that is, PCWP >15 mmHg 1,2,7).
In the IABP-SHOCK II trial8, the investigators defined
persistent cardiogenic shock complicating myocardial
infarction (MI) as hypoperfusion with SBP <100 mmHg
(despite treatment with ≥7 mcg/kg/min of dopamine or
equivalent dose of noradrenaline), low cardiac index
(<2.2 l/min/m2 if measured off IABP, or <2.5 l/min/m2 if
measured on IABP), and PCWP >15 mmHg (despite
establishing a patent infarct-related artery). In a trial
utilizing mechanical circulatory support (MCS),
severe refractory cardiogenic shock was defined as SBP
<90 mmHg, cardiac index <2.0 l/min/m2, and evidence
of end-organ failure despite IABP or pressor support 9.

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Key points
• Cardiogenic shock is characterized by acute hypoperfusion and end-organ
dysfunction owing to reduced cardiac output, and is commonly caused by acute
myocardial infarction (AMI) with left ventricular dysfunction
• Emergent revascularization is the only therapy that has been shown to reduce
mortality in patients with cardiogenic shock complicating AMI
• Refractory cardiogenic shock can be defined as ongoing evidence of tissue
hypoperfusion despite administration of adequate doses of two vasoactive
medications and treatment of the underlying aetiology
• Refractory cardiogenic shock carries a poor prognosis, with an inhospital mortality of
~50% despite pharmacological and mechanical circulatory support
• The use of mechanical circulatory support devices for cardiogenic shock is increasing,
but there is currently no evidence showing that they improve clinical outcomes
• Novel therapeutics and robust randomized trial data are needed to address the
persistently high mortality in patients with refractory cardiogenic shock
In this Review, we provide a brief overview of the
epidemiology, aetiology, and pathophysiology of cardio­
genic shock. Diagnostic strategies will also be high-
lighted, and the current therapeutic strategies used to
manage and treat patients with refractory cardiogenic
shock will be discussed. Although much is known about
this condition, mortality remains very high, emphasizing
the need for further research.
Aetiology
Cardiogenic shock can be caused by an acute cardiac con-
dition or a systemic illness that triggers a chronic cardiac
condition associated with minimal cardiac reserve. Acute
MI (AMI), unstable angina, postcardiotomy syndrome,
valvular heart disease, myocardial disease (such as myo-
carditis), LV outflow obstruction in hypertrophic cardio­
myopathy, stress-induced cardiomyopathy, pericardial
tamponade, congenital lesions, and mechanical injury to
the heart have all been implicated in the pathogenesis of
cardiogenic shock (BOX 1).
Acute coronary syndrome (ACS) with or without
ST-segment elevation is the most common cause of
cardio­genic shock, accounting for up to 80% of all cases10.
Among all cases of cardiogenic shock complicating AMI
in the SHOCK trial and registry5,6, 78.5% were attributable
to predominant LV failure. Among these patients, 58.8%
presented with anterior MI, whereas 34.4% presented
with MI in the inferior wall without anterior involvement.
Of the patients with primary inferior wall MI leading to
cardiogenic shock, 38.3% had a history of MI. Other non-
primary LV failure-related causes of cardio­genic shock
complicating AMI include isolated right ventricu­lar (RV)
shock and mechanical complications such as acute severe
mitral regurgitation (caused by papillary muscle rupture
or dysfunction), ventricular s­ eptal rupture, free wall rup-
ture, cardiac tamponade, a history of severe valvular heart
disease, excessive β­ ‑­blockade or Ca2+ channel-blockade,
or procedural complications5. The majority of patients
who develop cardio­genic shock as a result of MI do not
present with cardiogenic shock at the time of initial med­
ical contact or hospital­ization. In the SHOCK trial6, the
median time from symptom onset of MI to cardiogenic
shock owing to LV failure was 5.5 h. Several studies
have reported that cardiogenic shock occurs within 24 h
(early shock) after MI symptom onset in 50–75% of
patients (including those with mechanical complica-
tions), and within the following 3 days in the remainder
of patients5,9,11,12.
Cardiogenic shock can also occur secondary to myo-
carditis, an inflammatory condition of the heart muscle
that manifests commonly as a cardiac complication of
viral infection13. While most patients show only mild
symptoms, a small subset of patients develop a severe
form of myocarditis — known as fulminant myo­carditis
— that results in heart failure and cardiogenic shock
character­ized by severe haemodynamic compromise
requiring high-dose vasopressor and MCS. The factors
that determine whether a patient presents with fulminant
or nonfulminant myocarditis are not known, as the clin-
ical course of myocarditis has little correlation with the
degree of lymphocytic infiltration, necrosis, or fibrosis14.
Patients presenting with fulminant myocarditis are more
likely to have a fever or flu-like symptoms than those with
the nonfulminant form of the disease, and are more likely
to present with sudden onset of symptoms, in addition
to severe global LV dysfunction with normal LV dimen-
sions15. Both giant cell myocarditis and active lymphocytic
myocarditis can lead to cardiogenic shock13. Like ACS,
myocarditis is characterized by elevated troponin levels
and electrocardiographic changes such as ST‑segment
eleva­tion, T‑wave inversions, ST‑segment depressions,
and pathological Q waves. A diagnosis of acute myo­
carditis should be considered in young patients p ­ resenting
with ACS without traditional coronary risk factors14,16.
Postcardiotomy cardiogenic shock complicates 2–6%
of all cases of cardiothoracic surgery 17,18 and is character­
ized by development of low cardiac output and hypo­
perfusion in the early postoperative period19. Several
factors predispose patients to developing postcardiotomy
low output syndrome, including LV ejection fraction
<20%, reoperative or emergency surgery, age >70 years,
diabetes mellitus, triple-vessel or left main disease, and
recent MI20. Mortality for postcardiotomy cardiogenic
shock is 50–80%19. Several centres have used temporary
surgically implanted extracorporeal centrifugal pumps to
treat postcardiotomy shock21,22.
RV shock can occur after MI, postcardiotomy syn-
drome, heart transplantation, or LV assist device (LVAD)
placement, or can be a complication of chronic heart fail-
ure, pulmonary embolism, or myocarditis. Isolated RV
failure occurs in ~3% of patients presenting with cardio-
genic shock complicating AMI23, and these patients tend
to be younger, and are more likely to have an inferior
MI and a single-vessel right coronary artery occlusion
than patients with cardiogenic shock owing primarily
to LV failure. RV shock also tends to present sooner
after MI diagnosis in these patients24. Despite younger
age and inferior location of MI, patients with RV shock
have similarly high inhospital mortality to those with LV
shock (53.1% versus 60.8%; P = 0.296)23. Most patients
with acute ischaemic RV dysfunction display spontane-
ous haemodynamic improvement within 3–10 days, and
recovery of RV function within 3–12 months, regardless
of patency of the infarct-related artery 24–27.

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Refractory cardiogenic shock can be a manifestation
of any of the aforementioned acute aetiologies of cardio­
genic shock or a manifestation of acute decompen­
sation of chronic heart failure. The relative incidence of
refractory cardiogenic shock attributed to the various
­aetiologies has not yet been described.
Pathophysiology
Regardless of the initiating cause of cardiogenic shock,
the heart’s inability to deliver adequate cardiac output
leads to tissue hypoperfusion. Cardiac dysfunction
resulting from cardiogenic shock is usually caused by
a large MI, and the degree of myocardial necrosis is
an important predictor of risk of cardiogenic shock28.
Myocardial dysfunction leads to a reduction in stroke
volume and cardiac output, consequently increas-
ing ventricular diastolic pressure and wall stress, all
of which further reduce coronary perfusion pressure.
Furthermore, LV dysfunction and ischaemia increase
diastolic stiffness, which elevates left atrial pressure,
leading to pulmonary congestion, hypoxia, and worsen-
ing ischaemia. Myocardial perfusion is further reduced
by the presence of hypotension and tachycardia12,29.
Compensatory mechanisms are activated dur-
ing cardiogenic shock to increase sympathetic tone,
which increases heart rate and contractility, and to
stimulate the renin–angiotensin–aldosterone system,
which leads to fluid retention, increased preload, and
vaso­constriction to maintain systemic blood pressure.
An increase in systemic inflammatory response is often
a consequence of a large infarction and prolonged hypo­
perfusion. Activation of the inflammatory cascade leads
to release and activation of inducible nitric oxide syn-
thase, resulting in further vaso­dilatation and worsen­ing
hypotension and hypoperfusion4. Furthermore, activa-
tion of this cascade results in the paradoxically low sys-
temic vascular resistance observed in the SHOCK trial6
and might contribute to the development of refractory
cardiogenic shock (FIG. 1). The presence of concomi­
tant low systemic vascular resistance and systemic
inflammatory response syndrome with cardiogenic
shock is associated with the development of sepsis and
poor outcomes30–32.
Diagnosis
The classic clinical syndrome of cardiogenic shock
owing to LV failure is characterized by systemic hypo-
tension, SBP <90 mmHg or the need for high-dose ino-
tropic support to maintain SBP between 90–100 mmHg,
and symptoms or signs of organ hypoperfusion and
pulmonary congestion. Notably, up to 25% of patients
presenting with cardiogenic shock owing to LV failure
in the setting of AMI do not present with the classic
symptoms, instead displaying isolated hypoperfusion
in the absence of pulmonary congestion, despite high
PCWP12. On clinical examination, cardiogenic shock
normally presents as distant heart sounds, but might
also present with third or fourth heart sounds and
a systolic murmur, which should raise suspicion for a
mechanical complication such as mitral regurgita-
tion or ventricular septal rupture33. Meanwhile, shock
owing to RV infarction presents as hypotension with
an i­ nferior wall MI, elevated jugular venous pressure,
and no evidence of pulmonary congestion on exam or
chest radio­graphy. An electrocardiogram is helpful for
diagnosing this particular aetiology of shock33. Anterior
MI with LV pump failure as a cause of cardiogenic
shock is likely in patients with ST‑segment elevation
in the pre­cordial leads. In the case of a first inferior
ST‑segment elevation MI (STEMI) as the cause of
Box 1 | Causes of cardiogenic shock
Acute myocardial infarction
Left ventricular failure
• Large infarction
• Small/moderate infarction with
-- pre-existing dysfunction
-- extensive ischaemia
• Global ischaemia
Right ventricular failure
• Large infarction
• Small/moderate infarction with
-- pre-existing dysfunction
-- pulmonary hypertension
Mechanical complications
• Acute mitral regurgitation with
-- rupture of a papillary muscle
-- rupture of chordae tendinae
-- severe papillary muscle dysfunction
• Ventricular septal defect caused by rupture of the
interventricular septum
• Left ventricular free wall rupture
• Pericardial tamponade owing to rupture of the left
ventricular free wall or haemorrhagic pericardial
effusion
Concomitant conditions causing mixed aetiology
• Haemorrhage
• Infection
• Excess negative inotropic or vasodilator medications
• Sustained bradyarrhythmia or tachyarrhythmia
• Hyperglycaemia or ketoacidosis
Other conditions
End-stage cardiomyopathy
Myocarditis
Septic shock with severe myocardial depression
Left ventricular outflow tract obstruction
• Aortic stenosis
• Hypertrophic obstructive cardiomyopathy
Obstruction to left ventricular filling
• Mitral stenosis
• Left atrial myxoma
Acute mitral regurgitation (chordal rupture)
Acute aortic insufficiency
Myocardial contusion
Postcardiotomy shock
Global ischaemia
Stress-induced cardiomyopathy
Cardiac tamponade

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cardiogenic shock, the electrocardiogram should show
marked ST‑segment elevation in the inferior leads with
anterior ST‑segment depressions reflecting posterior
infarction. RV infarction can complicate acute inferior
MI and can be denoted by precordial ST‑segment ele-
vation predomi­nantly in V1–V2, as well as ST‑segment
eleva­tion in the right-sided leads. In general, cardio-
genic shock owing to a first inferior MI should immedi­
ately prompt echocardio­graphic screening to detect
papillary muscle rupture with acute mitral regurgitation
or ­ventricular septal rupture34,35.
Echocardiography is essential for the evaluation of
RV and LV function, and assessment of mechanical
complications, including free wall rupture with cardiac
tamponade, acute mitral regurgitation, and ventricular
septal rupture. Left atrial pressure estimation and car-
diac output measured using echocardiography can aid in
the timely diagnosis of cardiogenic shock. A restrictive
filling pattern on echocardiography, defined as a mitral
inflow deceleration time of <140 ms, was seen in 60.9%
of patients in the SHOCK trial5, and was predictive of
both a lower ejection fraction and PCWP ≥20 mmHg.
No association was observed between a restrictive filling
pattern and mortality 34.
Myocardial injury
↓ Cardiac output
↓ Stroke volume
↑ NOS
↑ NO
↑ Peroxynitrite
Hypotension
Vasodilatation ↑ Inflammatory
↓ SVR cytokines
↓ Systemic ↓ Coronary
perfusion perfusion pressure
Systemic
inflammation
Worsening
myocardial
function
End-organ
dysfunction
Death
Figure 1 | The downward spiral of refractory cardiogenicNature shock.Reviews
The downward
| Cardiology
spiral of refractory cardiogenic shock results from severe cardiac dysfunction, most often
due to myocardial injury, leading to ongoing systemic and coronary hypoperfusion.
A commonly observed systemic inflammatory response might lead to vasodilatation
and further contribute to ongoing cardiac dysfunction and end-organ insult.
Cardiogenic shock will inevitably lead to death if the cycle of damage is not interrupted.
NO, nitric oxide; NOS, nitric oxide synthase; SVR, systemic vascular resistance.
Invasive haemodynamic assessment using pulmo-
nary artery catheterization is not recommended for
routine use, but is useful to confirm and characterize
suspected shock, and is often used to manage refrac-
tory cardiogenic shock. For patients with cardiogenic
shock owing predominantly to LV failure, right heart
catheterization can confirm low cardiac output (cardiac
index <2.2 l/min/m2) and high filling pressures (PCWP
≥15 mmHg)35,32. For other aetiologies of cardio­genic
shock complicating AMI, such as ventricular septal
­rupture, a step‑up in oxygen saturation can be seen
from the right atrium to ventricle. Furthermore, in acute
severe mitral regurgitation, pulmonary artery wedge
CV waves (large systolic waves seen in atrial tracing
indicating increased atrial filling) are often 10 mmHg
above mean PCWP, and in RV shock, disproportion-
ately high right-sided filling pressures and Kussmaul’s
sign (a paradox­ical rise in jugular venous pressure upon
inspiration) can be observed23. Emergency coronary
angiography in the setting of cardiogenic shock com-
plicating MI is used to determine the distribution and
extent of coronary artery obstruction and guide either
percutaneous or surgical revascularization36.
Prognosis
Various clinical and haemodynamic criteria can be used
to develop prognostic markers that provide a frame-
work to understand predictors of refractory cardiogenic
shock. The most common cause of death after cardio-
genic shock is pump failure, which often occurs within
days after the event 37. Two scoring systems based on
multivariate models for cardiogenic shock severity have
been devised based on data from the SHOCK trial38: the
stage 1 risk score based on clinical data, and the stage 2
risk score that incorporates haemodynamic data. In the
stage 1 model, eight clinical risk factors were identified
as predictors of inhospital mortality: advanced age, shock
on admission, clinical evidence of end-organ hypoper-
fusion, anoxic brain damage, decreasing SBP, previous
CABG surgery, noninferior MI, and creatinine levels
>1.9 mg/dl. Mortality associated with this disease stage
ranged from 22% to 88%, depending on score category 38.
For the stage 2 model, risk factors included advanced
age, end-organ hypoperfusion, anoxic brain damage,
decreasing stroke work, and LV ejection fraction <28%.
The effect of early revascularization did not vary by risk
category, suggesting that all patients will derive benefit
from early revascular­ization38. In the multicentre, ran-
domized TRIUMPH study 39, predictors of mortality
in patients with persistent vasodepressor-dependent
cardio­genic shock following AMI despite a patent infarct-­
related artery included treatment with a high number of
vasopressors, decreased SBP, and low creatinine clear-
ance40. The observational CardShock study 41, conducted
between 2010 and 2015 to identify prognostic factors for
both ACS and non-ACS aetiologies of cardiogenic shock,
determined that advanced age, a history of MI or CABG
surgery, altered mental status, low LV ejection frac-
tion, low estimated glomerular filtration rate, and high
blood lactate levels were independently associated with
increased inhospital mortality 41.

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The prognostic and management implications
of RV involvement in cardiogenic shock in condi-
tions other than RV MI have not been established.
Haemodynamic variables that were used to predict
RV failure after dur­able LVAD implantation (cen-
tral venous pressure (CVP) >10 mmHg, CVP/PCWP
>0.63, pulmonary artery pulsatility index <2.0, and RV
stroke work index <450 mmHg/ml/m2) were evaluated
in a patient cohort with cardiogenic shock and AMI
using data from the SHOCK trial and registry 5,6,42. RV
dysfunction was found to be present in 37% and 36%
of patients in the trial and the registry, respectively 42.
Future studies are needed to establish the utility of
these variables as ­indicators of RV function in clinical
management decisions.
In addition to clinical and haemodynamic ­factors,
echocardiographic criteria, including severity of mitral
regurgitation and reduction of LV ejection fraction
are also independently associated with survival in
patients with cardiogenic shock. Importantly, a sur-
vival benefit from early revascularization was noted
across the spectrum of LV ejection fractions and mitral
regurgitation severity 43.
Of all causes of cardiogenic shock in patients
with MI in the SHOCK registry 5, ventricular septal
rupture was associated with the highest inhospital
mortal­ity (87%)44. In an observational study involving
117 patients with refractory cardiogenic shock, 68% of
all cases of shock were attributable to ischaemic cardio­
myopathy, predomin­antly AMI. The remaining cases
were attribut­able to nonischaemic aetiologies includ-
ing myocarditis, valvular disease, orthotopic heart
transplant rejection, peripartum cardiomyopathy,
­sarcoidosis, and Takotsubo syndrome9.
Mortality from cardiogenic shock complicating AMI
has fallen over the past decades with increasing use of
reperfusion therapy, particularly percutaneous coronary
intervention (PCI). In the US Worcester Mass Heart
Attack Study 45, 76% of patients who developed cardio-
genic shock died in the hospital between 1975 and 1990
(compared with 16.5% who did not develop cardio­
genic  shock), consistent with 81% mortality for
­cardiogenic shock described by Killip and Kimball in
1967 (REF. 46). Between 2003 and 2005, 45.4% of patients
with AMI who developed cardiogenic shock died dur-
ing hospitalization, compared with 7.3% of those who
did not develop cardiogenic shock45. Not surprisingly,
­inhospital mortality of cardiogenic shock was higher
among elderly patients, with 35.7% mortality in patients
aged 65–74 and 64.7% in patients aged >85 years45.
Management of cardiogenic shock
The initial goal in the management of cardiogenic shock
is to identify and address all reversible causes. While
ACS accounts for the majority of cases of cardiogenic
shock, alternative aetiologies must be rapidly identified
if coronary thrombosis is not present. An emphasis has
been placed on a ‘golden hour’ when managing many
clinical conditions, including trauma, STEMI, and acute
stroke. The golden hour refers to a time period in which
medical management that addresses reversible causes
results in increased likelihood of survival. A critical
timeframe of treatment must also be defined for patients
with cardiogenic shock, after which the consequences of
prolonged end-organ insult will inevitably lead to death.
This timeframe will be particularly relevant for patients
with refractory cardiogenic shock, who have ongoing
hypoperfusion despite addressing all reversible causes
of shock. The remainder of this Review will focus on the
management of patients with AMI who develop cardio-
genic shock owing to LV failure, although certain prin-
ciples and therapies (such as inotropes and mechanical
circulatory support) can be applied to a broader range
of patients with cardiogenic shock.
Emergency revascularization
Emergency cardiac catheterization and revasculariza-
tion are guideline-recommended (class I, level of evi-
dence B) for patients with ACS36,47,48. In the SHOCK
trial6, 302 patients with STEMI and cardiogenic shock
owing to LV dysfunction were randomized within 36 h
of MI onset to either emergency revascularization
or to i­nitial medical stabilization for ≥54 h, followed
by cardiac catheterization and revascularization as
clinically indicated. The majority of patients in both
treatment groups were treated with IABP and ino-
tropes or vasopressors. The average cardiac index was
1.8 l/min/m2 and nearly one-third of patients suffered
cardiac arrest before random­ization. Angiography in
patients with cardio­genic shock owing to AMI often
revealed multivessel disease, with left main disease
in 23% of patients and triple-­vessel disease in 64%3,49.
While the primary end point of all-cause mortality at
30 days was not different between an invasive strat-
egy of emergent revascularization and a conservative
strategy of initial medical stabil­ization (46.7% versus
56.0%; P = 0.11), at the 6‑month follow‑up, mortality
was significantly lower with revascular­ization (50.3%
versus 63.1%; P = 0.027). This mortality benefit rep-
resented a large treatment effect, with the number
needed to treat of eight to save one life6, and persisted
up to 11 years (average 6 years follow‑up; 32.8% ver-
sus 19.6%; P = 0.03)50. Among patients random­ized
to emergency revascularization in the SHOCK trial6,
those treated with CABG surgery (~40%) had a higher
prevalence of diabetes and more extensive coronary
disease (three-vessel and left main coronary artery dis-
ease) than those treated with PCI. However, survival
rates at 30 days and 1 year were similar between these
revascular­ization modalities. Emergency CABG surgery
should be considered in patients with multivessel coro-
nary disease, and should be performed instead of PCI in
patients with mech­anical complications of AMI, such as
ventricular septal rupture or papillary muscle rupture8.
Since the publication of the SHOCK trial and
updated guideline recommendations for early
revascular­ization in cardiogenic shock complicating
MI, the use of revascular­ization for the management
of cardiogenic shock has increased47. This observed
increase is primarily attributable to an increased rate
of PCI, as the total number of CABG surgeries per-
formed did not increase. Despite the marked decrease

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Percent migration Total annual hospital impact
10% $254,010,000
25% $635,025,000
50% $1,270,050,000
100% $2,540,100,000
$3,000,000,000
Projected incremental hospital cost
$2,500,000,000
w/IABP to pVAD migration
$2,000,000,000
$1,500,000,000
$1,000,000,000
$500,000,000
$–
10% 25% 50% 100%
migration migration migration migration
Figure 2 | An analysis of potential incremental
Nature cost of
Reviews | Cardiology
shifting from using intra-aortic balloon pumps (IABP)
to percutaneous left ventricular assist devices (pVAD).
The data show an incremental increase in cost of
$33,957,839 for the hospital system in the USA associated
with use of pVAD in patients with cardiogenic shock
undergoing percutaneous coronary intervention, without
an associated improvement in mortality, reduced hospital
length of stay, or hospital readmission. Reprinted from
Shah, A. et al. Clinical and economic effectiveness of
percutaneous ventricular assist devices for high-risk
patients undergoing percutaneous coronary intervention.
J. Invasive Cardiol. 27, 148–154 (2015), with permission
from HMP Communications.
in overall mortality over time attributable to increased
use of PCI, as noted above, mortality in patients with
cardiogenic shock managed with PCI has not fallen over
time. In 2013, the large CathPCI Registry 47 reported
a significant rise in inhospital mortality in patients
treated with PCI from 27.6% in 2005–2006 to 30.6%
in 2011–2013. Refractory cardio­genic shock might
possibly be the result of incomplete revascularization.
CABG surgery has remained i­ nfrequently used despite
the high preva­lence of multi­vessel disease in patients
who develop cardiogenic shock and the potential of
CABG surgery to provide complete revascularization47.
A multicentre, prospective, observational study con-
ducted from 1998 to 2010 demonstrated that patients
receiving culprit-only PCI when presenting with cardio-
genic shock had signifi­cantly worse 6‑month survival
than patients receiving multivessel PCI (43.9% versus
20.4%, P = 0.008)51. The benefit of culprit versus multi­
vessel PCI for the treatment of cardiogenic shock com-
plicating MI is the s­ ubject of an ongoing r­ andomized
clinical trial52.
Pharmacological circulatory support
Sympathomimetic inotropic and vasopressor agents
are the first-line drugs for patients who develop cardio-
genic shock. Although the data comparing the efficacy
of these agents are limited, findings from the SOAP II
randomized trial53 suggest that noradrenaline is prefer­
able to dopamine for initial management. In total,
1,679 patients with circulatory shock of varying aetiolo-
gies (280 patients had cardiogenic shock) were assigned
to initial therapy with either dopamine or noradrena-
line. Within the subgroup of patients with cardiogenic
shock, the rate of death at 28 days was higher with dopa-
mine than with noradrenaline, although this finding
must be viewed in the context of an overall nonsignifi-
cant difference in mortality and lack of heterogeneity of
treatment effect. An overall higher rate of arrhythmias
— predomi­nantly atrial fibrillation — in patients treated
with dopamine was also observed in the cardiogenic
shock subgroup53. In general, efforts should be made
to minimize the number of drugs used, as well as their
dose and dur­ation, owing to the risk of arrhythmia and
vasopressor-­mediated end-organ insult. A vasopressor
(typically noradrenaline) is usually initiated in patients
with severe hypotension (SBP <80 mm Hg or mean
arterial pressure <60 mm Hg). The use of dobutamine
alone is limited to patients with a low cardiac index,
high PCWP, and a relatively stable SBP (80–90 mmHg).
Patients in a low output state who do not have hypo-
tension can be treated with vaso­dilators, including
intravenous nitroglycerin or nitroprusside, initiated
in low doses. In general, a third agent probably has no
additional benefit if there is evidence of hypoperfusion
despite therapeutic doses of two vasoactive agents.
Percutaneous and surgical MCS devices
MCS devices can maintain organ perfusion, reduce
cardiac filling pressures, reduce LV volume and wall
stress, decrease myocardial oxygen consumption, and
augment coronary perfusion54. The first clinically used
MCS device, the IABP, was developed in the 1960s
when mortality from cardiogenic shock complicating
MI was exceptionally high46 (~80%), before the advent
of life-saving reperfusion. On the basis of observa-
tional evidence showing that IABP improves haemo­
dynamics and systemic perfusion55, IABP became the
stan­dard of care in most tertiary centres in the USA
despite a lack of randomized trial evidence demon-
strating its effect on mortality. Newer percutaneous
and surgically implanted devices have since been
developed to provide greater haemodynamic support
to address the cohort of patients with persistently high
mortality owing to refractory cardiogenic shock. Again,
although no clinical trial evidence exists showing the
benefit of these devices in reducing mortality, their use
is increasing on the basis of superior haemodynamic
support 56. This increase in the use of novel percutane-
ous support devices, despite lack of demonstrable clin-
ical benefit, has a potentially large effect on health-care
expenditure (FIG. 2).
Temporary MCS devices are suitable for candidates
with refractory cardiogenic shock despite optimization
of volume status, preload, afterload, and the use of ino-
tropic or vasopressor support. The use of temporary
MCS devices in this patient cohort is also based on
the likelihood of recovery of organ function, and after

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consideration of more advanced heart failure therapies54.
The decision as to which device to use is predicated on
understanding the potential haemodynamic benefits
of each device, as well as knowledge of their various
complications and limitations (TABLE 1). Uncommon
conditions, such as acute fulminant myocarditis or
peripartum cardiomyopathy, are associated with a high
likelihood of recovery of myocardial function and are
often well-suited for temporary MCS. Patients can be
gradually weaned from MCS as ventricular function
recovers, without the need for long-term mechanical
support or heart transplantation. For the larger cohort
of patients with cardiogenic shock post‑MI with irre-
versible myocardial necrosis or acute decompensation
of chronic systolic heart failure, the candidacy of these
patients for long-term mechanical support or heart
transplantation should be assessed when considering
whether a t­ emporary MCS device is suitable.
Intra-aortic balloon pump. From its development in
the late 1960s, the IABP became the standard of care in
patients with cardiogenic shock. In the SHOCK trial6,
85% of patients with cardiogenic shock were treated
with an IABP. The IABP can decrease myocardial
oxygen consumption, increase coronary artery perfu-
sion, enhance cardiac output by augmenting diastolic
arterial pressure and coronary blood flow during the
balloon inflation phase, and increase LV stroke vol-
ume by lower­ing LV afterload57,58. Although preclinical
reports have suggested that early (prerevascularization)
implementation of mechanical support can reduce
infarct size, no confirmatory data in patients have been
reported59. Although the IABP is widely available, the
IABP Shock Trial60 demonstrated that IABP treatment
conferred negli­gible haemodynamic benefit compared
with medical therapy alone60. Optimal haemodynamic
benefit of an IABP depends on its position in the aorta,
the blood displacement volume, the balloon diameter
in relation to aortic diameter, timing of balloon infla-
tion in diastole and deflation in systole, intrinsic heart
rate, systemic vascular resistance, and blood pressure54.
For the device to be effective, there must be a minimum
level of LV function and electrical stability 37.
In 2009, a meta-analysis of several randomized
­trials and cohort studies reported minimal evidence-­
based support for widespread use of IABP therapy in
patients with AMI complicated by cardiogenic shock61.
Although no benefit was observed in the meta-­analysis
of randomized trials, the meta-analysis of cohort studies
demonstrated that the use of IABP with thrombolysis
was associated with an 18% reduction in mortality 61.
The subsequent randomized IABP-SHOCK II trial8
evaluated the efficacy of IABP support in 600 patients
with cardio­g enic shock complicating AMI, all of
whom received early revascularization (predomi-
nantly PCI). No differences in mortality or complica-
tion rate were detected between patients treated with
IABP and those not treated with IABP8. At present,
an IABP for cardio­genic shock complicating MI is
given a class IIa, level of evidence B recommendation
in the 2013 AHA/ACC STEMI practice guidelines, a
class IIb recommendation in the ESC STEMI practice
guidelines36,62–65, and a class III r­ ecommendation in the
ESC non-STEMI guidelines48.

Table 1 | Temporary mechanical circulatory support devices

Device IABP Impella 2.5 Impella CP Impella 5 VA ECMO TandemHeart CentriMag Impella RP
features PTVA System
Pump Pneumatic Axial flow Axial flow Axial flow Centrifugal Centrifugal Centrifugal Axial flow
mechanism
Cannula 8 Fr 13 Fr 14 Fr 23 Fr • 18‑21 Fr • 21 Fr inflow • 32 Fr venous 9 Fr
inflow • 15–17 Fr • 22 Fr arterial
• 15–22 Fr outflow
outflow
Insertion Percutaneous; Percutaneous; Percutaneous; Surgical Percutaneous Percutaneous; Surgical; RVAD: Percutaneous;
descending femoral femoral cutdown: and surgical; inflow via inflow via RA or femoral
aorta via artery artery femoral inflow via femoral vein; RV, outflow via vein across
femoral retrograde retrograde artery femoral vein, outflow via PA; LVAD: inflow pulmonic
artery across aortic across aortic retrograde outflow via femoral artery via LA and LV, valve
valve valve across femoral artery outflow via aorta
aortic valve
Haemodynamic 0–1 l/min 2.5 l/min 3–4 l/min 5 l/min >4.5 l/min 4 l/min 5–10 l/min >2.5 l/min RV
support Biventricular Biventricular
Limb ischaemia + ++ ++ ++ +++ +++ - +

Haemolysis + ++ ++ ++ ++ ++ - ++
Afterload Reduced Neutral Neutral Neutral Increased Increased Neutral Neutral
PCWP Slightly Slightly Slightly Slightly Variable Reduced Reduced Neutral
reduced reduced reduced reduced or slightly
increased
Fr, French; IABP, intra-aortic balloon pump; LA, left atrium; LV, left ventricle; LVAD, left ventricular assist device; PA, pulmonary artery; PCWP, pulmonary capillary
wedge pressure; PTVA, percutaneous transseptal ventricular assist; RA, right atrium; RCT, randomized controlled trial; RV, right ventricle; RVAD, right ventricular
assist device; VA ECMO, veno-arterial extracorporeal membrane oxygenation.

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Rapid reversal of systemic hypoperfusion with IABP in infarct size after reperfusion with Impella 2.5 sup-
is associated with improved prognosis
100 port 68, no randomized clinical trial data demonstrating
Log-rank P <0.001, Wilcoxon P <0.001 the benefits of its use in the management of cardiogenic
90
NCRH (n = 117) shock are available. In a randomized trial comparing
80
CRH (n = 68) Impella 2.5 with IABP placement in patients with
cardiogenic shock, haemodynamics variables were
All-cause mortality (%)

70
60
50
40
30
20
10
0 time points <24 h), with no increase in the requirement
0 2 4 6 8 10 12
Time since randomization (months)
Figure 3 | Rapid reversal of systemic hypoperfusion with an intra-aortic balloon
pump (IABP) is associated with improved prognosis. Complete Nature Reviews
reversal Cardiology
of |systemic
hypoperfusion 30 min after placement of an IABP is independently associated with
markedly lower 1‑year mortality in the SHOCK trial, as compared with patients without
complete reversal. CRH, complete reversal systemic hypoperfusion; NCRH,
non-complete reversal systemic hypoperfusion. Reprinted from Ramanathan, K. et al.
Rapid complete reversal of systemic hypoperfusion after intra-aortic balloon pump
counterpulsation and survival in cardiogenic shock complicating acute myocardial
infarction. Am. Heart J. 162, 268–275 (2011) with permission from Elsevier.
Interestingly, although minimal data are available
demonstrating the efficacy of IABP therapy in patients
with cardiogenic shock, lack of response to IABP
counter­pulsation in patients with cardiogenic shock
owing to predominant LV failure post‑MI seems to be
a powerful prognostic marker. Incomplete reversal of
systemic hypoperfusion, defined as inability to reverse
extremity hypoperfusion, or lack of improvement in
mentation after 30 min of 1:1 augmentation with IABP,
were independently associated with higher inhospital
and 1‑year mortality in the SHOCK trial66 (FIG. 3).
New MCS devices. New temporary MCS devices have
been developed for patients with potentially reversible
multiorgan failure who demonstrate ongoing hypo­
perfusion and shock despite pharmacological therapy
and IABP. Peripherally inserted devices include axial flow
pumps and left atrial to left femoral artery bypass pumps,
which are typically implanted in a cardiac catheterization
setting. Veno-arterial extra­corporeal ­membrane oxygen-
ation (VA ECMO) can either be implanted peripherally
or centrally (via surgery). Surgically placed temporary
extracorporeal centrifugal pumps can ­provide full left,
right, or biventricular support.
The Impella 2.5 (Abiomed, USA) is a temporary
percutaneous LVAD with a nonpulsatile axial flow
pump that propels blood from the left ventricle into
the ascending aorta through the catheter. The Impella
2.5 is inserted percutaneously via the femoral artery.
The device requires adequate RV function or con-
comitant RV support to maintain LV preload and is
contra­indicated in patients with a mechanical aortic
valve or LV thrombus54,67. Although preclinical studies
with a­ nimal models of MI have reported a reduction
significantly improved with Impella support, but no
difference in 30‑day mortality was detected (45% in
the IABP group versus 43% in the Impella 2.5 group);
of note, this study was not powered to detect differences
between mortality 69. In addition, no difference in major
bleeding was observed, but patients who were treated
with an Impella 2.5 had significantly more haemolysis
in the first 24 h (P <0.05 between treatment groups at
for packed red blood cells and fresh-frozen plasma.
One patient in the Impella 2.5 group had acute limb
­ischaemia that required surgery 69.
The TandemHeart PTVA System (CardiacAssist,
Inc., USA) is a percutaneous ventricular assist device
that can be used for short-term circulatory support.
The device can be inserted in the cardiac catheterization
laboratory using a transseptal puncture, with a venous
inflow ­cannula inserted into the left atrium, or it can
be implanted surgically 54. Oxygenated blood is drawn
from the left atrium and returned extracorporeally via
a centrifugal pump to the femoral artery, bypassing
the left ventricle. LV unloading occurs by redirecting
blood from the left atrium to the ileofemoral arterial
system. The system is capable of delivering flow of up
to 5.0 l/min, depending on the size of the femoral artery
cannula. Two small randomized clinical trials comparing
IABP to the TandemHeart device in patients with cardio-
genic shock showed favourable haemodynamic variables
with TandemHeart support 70,71. However, complications
were more common with use of TandemHeart, includ-
ing severe bleeding (RR 2.35, 95% CI 1.40–3.93) and a
trend towards more limb ischaemia (RR 2.59, 95% CI
0.75–8.97)72. No differences in mortality were detected
between the two treatment groups in a meta-analysis,
but the studies analysed were not powered to detect
mortality differences73 (FIG. 4).
The Impella 2.5 and TandemHeart percutaneous
devices are both resource-intensive and associated with
complications. Although randomized clinical trials have
shown improved haemodynamics with use of these
devices compared with IABP, meta-analyses published
in the past two years reported no demonstrable bene-
fits on outcomes or costs with use of these devices72,74.
The 2013 ACC/AHA guidelines for the management of
STEMI recommends that alternative LVADs might be
considered in patients with refractory cardiogenic shock
(class IIb, level of evidence C), although the guidelines
do not specify which devices36. The consensus statement
on the use of percutaneous MCS in cardiovascular care
published in 2015 provides a guideline for MCS use and
offers an expansive summary of the potential haemo-
dynamic benefits of these therapies54. Importantly, the
authors of this statement acknowledge the need for
regis­tries and randomized clinical trial data to justify the
increase in the use of these devices in clinical practice54.

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VA ECMO or percutaneous cardiopulmonary bypass might not be adequate to reduce ventricular wall stress.
provides full haemodynamic support and might be Theoretically, this high oxygen demand has negative
helpful in biventricular failure, although the use of this consequences on myocardial protection, unless the LV
device is limited to centres with expertise in the perfu- is vented (centrally) or unloaded by concomitant IABP
sion technique. A main advantage of modern VA ECMO or percutaneous LVAD; however, no evidence showing
is its rapid implementation peripherally at the bedside that this practice can improve clinical outcomes exists75.
(outside of the catheterization laboratory or operating The most common complication reported in patients
room) and its capacity to provide therapeutic hypother- from the Extracorporeal Life Support Registry 76 is can-
mia in patients who had a cardiac arrest 54. VA ECMO nula bleeding from the peripherally placed VA ECMO
provides systemic circulatory support with flow velo­city (20.5%) or surgical bleeding in centrally placed VA
that can exceed 6 l/min, depending on cannula size54. ECMO (25.5%). Limb ischaemia is reported in up to
Owing to high myocardial oxygen demand (secondary 20% of patients in some centres, but is only partially
to high filling pressures and volume), VA ECMO alone addressed with the use of distal perfusion catheters77.
Surgically implanted extracorporeal centrifugal
pumps offer temporary support either as a LVAD, RV
LVAD IABP Cardiac index P(heterogeneity) = 0.22 assist device (RVAD), or a biventricular assist device,
mean ± SD mean ± SD mean difference I2 = 34.0%
and can be performed with or without cardiopulmonary
Thiele et al.71 2.3 ± 0.6 1.8 ± 0.4 0.55 (0.23 to 0.87) bypass. A RVAD uses the right atrium as the inflow and
Burkhoff et al.70 2.2 ± 0.6 2.1 ± 0.2 0.16 (–0.14 to 0.46) the main pulmonary artery as outflow, while a LVAD can
Seyfarth et al. 69
2.2 ± 0.6 1.8 ± 0.7 0.36 (–0.16 to 0.88) use multiple sites for inflow cannulation, including the
Pooled 0.35 (0.09 to 0.61) left atrium or the left ventricle via LV apical cannulation
or by advancing the left atrial cannula across the mitral
–2 –1 0 1 2
Favours IABP Favours LVAD valve into the ventricle78. The outflow cannula for the
LVAD is in the ascending aorta. Although these pumps
LVAD IABP Mean arterial pressure P(heterogeneity) = 0.10 are designed for short-term support, several techniques
mean ± SD mean ± SD mean difference I2 = 55.9%
allow for mobilization and prolonged use79. Data from
Thiele et al.71 76 ± 10 70 ± 16 5.5 (–2.9 to 13.9) centres with experience in using surgically implanted
Burkhoff et al.70 91 ± 16 72 ± 12 18.6 (9.4 to 27.9) extracorporeal pumps for management of refractory
Seyfarth et al.69 87 ± 18 71 ± 22 16.0 (0.5 to 31.5) cardio­genic shock (n = 143 patients) showed major
Pooled 12.8 (3.6 to 22.0) bleeding events in 33% of patients and cerebrovascular
accidents in 14%80.
–50 –25 0 25 50
Favours IABP Favours LVAD Although currently no randomized trial data support
the routine use of these more invasive and expensive
LVAD IABP Pulmonary wedge pressure P(heterogeneity) = 0.01
mean ± SD mean ± SD mean difference I2 = 76.6%
therapeutics, VA ECMO and extracorporeal ventricular
assist devices have become widely embraced at several
Thiele et al.71 16 ± 5 22 ± 7 –5.6 (–9.2 to –2.1)
tertiary-care centres. The outcomes data available in the
Burkhoff et al.70 16 ± 4 25 ± 3 –8.4 (–11.0 to –5.8) literature are mostly derived from small single-­centre
Seyfarth et al.69 19 ± 5 20 ± 6 –1.0 (–5.2 to 3.2) studies80,81. One such study investigated the use of extra-
Pooled –5.3 (–9.4 to –1.2) corporeal ventricular assist devices or VA ECMO in
–20 –10 0 10 20 90 patients with refractory cardiogenic shock attribut-
Favours LVAD Favours IABP able to AMI, chronic heart failure, or myocarditis, and
demonstrated a rate of survival to hospital discharge of
LVAD IABP 30-day mortality P(heterogeneity) = 0.83
n/N n/N relative risk I2 = 0% 49%82. How broadly applicable these results are remains
Thiele et al.71 9/21 9/20
unknown, particularly for less-experienced centres.
0.95 (0.48 to 1.90)
Burkhoff et al.70 9/19 5/14 1.33 (0.57 to 3.10) Management of RV shock
Seyfarth et al.69 6/13 6/13 1.00 (0.44 to 2.29) Optimal management of RV shock is aimed at supporting
Pooled 24/53 20/47 1.06 (0.68 to 1.66) the right ventricle and reversing any ischaemia. Medical
0.1 1 10 therapy for RV shock consists of maintaining RV preload
Favours LVAD Favours IABP with adequate volume resuscitation, restoring physio­
Figure 4 | Meta-analysis of randomized trials comparingNature the effect of | Cardiology
Reviews logical rhythm, reducing RV afterload, and enhancing
percutaneous left ventricular assist devices (LVAD) versus the intra-aortic RV contractility with inotropic support33. Treatment with
balloon pump (IABP) on 30‑day mortality and haemodynamics. Despite clear nitrates and morphine should be avoided as they reduce
improvements in haemodynamics with percutaneous LVAD compared with IABP, 30‑day RV preload. Excess fluid administration is also detrimen-
mortality appeared to be similar. However, these trials were not powered to test for tal, as it can lead to marked RV dilatation with septal shift
mortality differences. Random effect models were used for meta-analysis. For the top
into the left ventricle, which diminishes LV filling 33.
three panels, weighted mean differences with 95% confidence intervals are presented on
the right of the figure. For the bottom panel, relative risks with 95% confidence intervals In those patients with refractory RV shock despite
are presented on the right of the figure. Modified from Cheng, M. et al. Percutaneous left medical management and revascularization, treatment
ventricular assist devices versus intra-aortic balloon pump counterpulsation for options include atrial septostomy, temporary MCS, VA
treatment of cardiogenic shock: a meta-analysis of controlled trials. Eur. Heart J. 2009; ECMO, and heart transplantation. Percutaneous RVADs
30 (17): 2102–2108, with permission from Oxford University Press. can also improve haemodynamics during recovery from

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acute RV failure83,84. The Impella RP System (Abiomed,
USA) is a RVAD that provides peripherally placed
mechanical circulatory support for up to 14  days
in patients with refractory RV shock. The pump is
inserted via the femoral vein, into the right atrium, and
through to the pulmonary artery, and can provide flow
of up to 5 l/min at a maximal speed of 32,000 rpm85.
The TandemHeart right ventricular support device
(CardiacAssist, Inc., USA) is a centrifugal flow pump
that can be implanted percutaneously via a bifemoral or
right internal jugular approach, surgically by direct can-
nulation of the right atrium and pulmonary artery, or by
peripheral cannulation of the femoral vein and direct can-
nulation of the pulmonary artery. The use of this device
has been associated with an acute reduction in right heart
filling pressures and improved cardiac index over a 48‑h
period in a wide array of clinical conditions leading to
RV failure68. Finally, as with acute mechanical LV support
devices, no available randomized trial data demonstrate
improved clinical outcomes in patients with RV shock
with these aforementioned devices for RV support.
Long-term MCS
A clear end point must be established before instituting
temporary support, because approximately one-third
of patients who survive temporary support will do so
by receiving a cardiac transplant or surgical ventricular
assist device. The ability to progress to long-term MCS
or cardiac transplant if cardiac function does not recover
is predicated on recovery of end-organ function. Patients
undergoing long-term LVAD implantation in the set-
ting of AMI have similar outcomes to the other patients
receiving LVAD, despite being more ill before implanta-
tion86. Furthermore, retrospective data suggest that no
differences exist in long-term LVAD outcome between
early and late ventricular assist device i­mplantation
after MI87.
The landmark, randomized REMATCH trial88 was
designed to evaluate the suitability of the HeartMate
XVE (vented electric) LVAD (Thoratec Corporation,
USA) for long-term use in patients who were ineligi-
ble for cardiac transplantation. The LVAD conferred
a clinically meaningful survival benefit and improved
quality-of‑life measures. A subsequent randomized
trial published in 2009 compared the pulsatile-flow
HeartMate XVE with the continuous-flow Heartmate II
(Thoratec Corporation, USA)89. Both devices signifi­
cantly improved quality of life and functional cap­
acity, but the continuous-flow LVAD further improved
probability of stroke-free survival compared with the
pulsatile device. Although these two randomized trials
predominantly included patients with chronic systolic
heart failure, some patients probably also met criteria
for cardiogenic shock88,89. The Seventh INTERMACS
registry 90 annual report indicated that the proportion
of patients considered to fit the profile of cardiogenic
shock at the time of implant with a long-term LVAD or
a total artificial heart was approximately 15%. Patients
with cardiogenic shock at the time of implant have worse
postimplant survival than more stable patients, as well as
increased postoperative length of stay 91.
Conclusion
While the overall outcomes for patients with cardiogenic
shock have improved over the past several decades,
patients with refractory cardiogenic shock continue to
pose a clinical challenge. Although mechanical support
therapies are available, no randomized trial evidence
exists to support their widespread use, and outcomes
continue to be poor even with the most invasive
and resource-intensive therapeutics. Observational and
randomized data have shown improvement in haemo­
dynamic support with the use of temporary MCS, but no
improvement in mortality rates has been reported, even
when studies are pooled in a meta-analysis. Registries
should be developed to improve the understanding of
practice patterns across the spectrum of hospitals (from
community to quaternary) and to serve as a platform for
pragmatic trials to answer unresolved questions. In light
of the persistently high mortality associated with refrac-
tory cardiogenic shock, the lack of incremental improve-
ment in mortality despite use of PCI, and the high cost of
current treatment patterns, there is a critical need to find
a treatment strategy besides reperfusion or revascular­
ization that can improve outcomes for patients with
cardiogenic shock.

1. Hasdai, D. Cardiogenic shock: diagnosis and
treatment (Humana Press, 2002).
2. De Luca, L. et al. Temporal trends in the epidemiology,
management, and outcome of patients with
cardiogenic shock complicating acute coronary
syndromes. Eur. J. Heart Fail. 17, 1124–1132 (2015).
3. Dzavik, V. et al. Effects of nitric oxide synthase
inhibition on hemodynamics and outcome of patients
with persistent cardiogenic shock complicating acute
myocardial infarction: a phase II dose-ranging study.
Eur. Heart J. 28, 1109–1116 (2007).
4. Kohsaka, S. et al. Systemic inflammatory response
syndrome after acute myocardial infarction
complicated by cardiogenic shock. Arch. Intern. Med.
165, 1643–1650 (2005).
5. Hochman, J. S. et al. Cardiogenic shock complicating
acute myocardial infarction — etiologies,
management, and outcome: a report from the SHOCK
trial registry. J. Am. Coll. Cardiol. 36, 1063–1070
(2000).
6. Hochman, J. S. et al. Early revascularization in acute
myocardial infarction complicated by cardiogenic
shock. N. Engl. J. Med. 341, 625–634 (1999).
7. Holmes, D. R. et al. GUSTO‑I Investigators.
Contemporary reperfusion therapy for cardiogenic
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Author contributions
All authors researched data for the article, made substantial
contribution to discussion of the content, and wrote,
reviewed, and edited the manuscript before submission.
Competing interests statement
The authors declare no competing interests.

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