Cardiogenic shock (CS) is a common cause of mortality, and management remains challenging
despite advances in therapeutic options. CS is caused by severe impairment of myocardial
performance that results in diminished cardiac output, end‐organ hypoperfusion, and
hypoxia.1 Clinically this presents as hypotension refractory to volume resuscitation
with features of end‐organ hypoperfusion requiring pharmacological or mechanical intervention.1
Acute myocardial infarction (MI) accounts for 81% of patient in CS.2
Contemporary trials and guidelines (Table 1)3, 4, 5, 6, 7 outline clinical criteria
for defining CS and are limited by lack of uniformity. The SHOCK (Should We Emergently
Revascularize Occluded Coronaries for Cardiogenic Shock) and intra‐aortic balloon
pump (IABP)‐SHOCK II trials used systolic blood pressure (SBP) measurements of <90 mm Hg
for ≥30 minutes or use of pharmacological and/or mechanical support to maintain an
SBP ≥90 mm Hg.1, 3, 4 Evidence of end‐organ hypoperfusion varied between the trials
but typically included urine output of <30 mL/h, cool extremities, altered mental
status, and/or serum lactate >2.0 mmol/L.1, 3, 4 The SHOCK Trial included cardiac
index (CI) of ≤2.2 L/min per m2 and a pulmonary capillary wedge pressure (PCWP) of
≥15 mm Hg.3 An SBP <90 mm Hg that is refractory to fluid resuscitation with clinical
and laboratory evidence of end‐organ dysfunction, in the setting of suspected cardiac
dysfunction, is essential to the definition of CS. However, CS is a continuum that
extends from pre‐shock to refractory shock states, which influence the timely considerations
of various interventions.8 Acknowledging this continuum in future trials would likely
facilitate the unification of clinical and hemodynamic criteria in defining CS.
Table 1
Clinical Features of CS as Defined in Contemporary Trials and Guidelines
Clinical Trial/Guideline
CS Criteria
SHOCK Trial (1999)3
SBP <90 mm Hg for >30 min or vasopressor support to maintain SBP >90 mm Hg
Evidence of end‐organ damage (UO <30 mL/h or cool extremities)
Hemodynamic criteria: CI <2.2 and PCWP >15 mm Hg
IABP‐SOAP II (2012)4
MAP <70 mm Hg or SBP <100 mm Hg despite adequate fluid resuscitation (at least 1 L
of crystalloids or 500 mL of colloids)
Evidence of end‐organ damage (AMS, mottled skin, UO <0.5 mL/kg for 1 h, or serum lactate
>2 mmol/L)
EHS‐PCI (2012)5
SBP <90 mm Hg for 30 min or inotropes use to maintain SBP >90 mm Hg
Evidence of end‐organ damage and increased filling pressures
ESC‐HF Guidelines (2016)6
SBP <90 mm Hg with appropriate fluid resuscitation with clinical and laboratory evidence
of end‐organ damage
Clinical: cold extremities, oliguria, AMS, narrow pulse pressure. Laboratory: metabolic
acidosis, elevated serum lactate, elevated serum creatinine
KAMIR‐NIH (2018)7
SBP <90 mm Hg for >30 min or supportive intervention to maintain SBP >90 mm Hg
Evidence of end‐organ damage (AMS, UO <30 mL/h, or cool extremities)
AMS indicates altered mental status; CI, cardiac index; EHS PCI, Euro Heart Survey
Percutaneous Coronary Intervention Registry; ESC HF, European Society of Cardiology
Heart Failure; IABP‐SOAP II, intra‐aortic balloon pump in cardiogenic shock II; KAMIR‐NIH,
Korean Acute Myocardial Infarction Registry‐National Institutes of Health; MAP, mean
arterial pressure; PCWP, pulmonary capillary wedge pressure; SBP, systolic blood pressure;
SHOCK, Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock;
UO, urine output.
Epidemiology
CS complicates 5% to 10% of cases of acute MI and is the leading cause of death after
MI.1, 9 ST‐segment–elevation myocardial infarction (STEMI) is associated with a 2‐fold
increased risk for development of CS compared with non–ST‐segment–elevation myocardial
infarction (NSTEMI). Patients with NSTEMI‐associated CS are less likely to undergo
early cardiac catheterization, delaying PCI and/or coronary artery bypass graft and
increasing the risk of mortality compared with patients with STEMI‐associated CS.10
Higher incidences of CS are observed in women, Asian/Pacific Islanders, and patients
aged >75 years.9 The incidence of CS has increased in recent years, while the reason
for increasing incidence is unclear, improved diagnosis and better access to care
are both likely contributory.9 While the in‐hospital mortality has improved,1 the
6‐ to 12‐month mortality in cardiogenic shock has remained unchanged at ≈50% over
the past 2 decades.3, 4, 11
Survivors of MI‐associated CS have an 18.6% risk of 30‐day readmission after discharge,
with a median time of 10 days. The risk of readmission is slightly lower among patients
with STEMI versus NSTEMI. The most common causes of readmission are congestive heart
failure and new myocardial infarction. Female sex, low socioeconomic status, mechanical
circulatory support (MCS) device placement, atrial fibrillation, and ventricular tachycardia
are predictors of readmission.12
Pathophysiology
The primary insult is a reduction in myocardial contractility resulting in diminished
cardiac output, hypotension, systemic vasoconstriction, and cardiac ischemia.1 The
hallmark is peripheral vasoconstriction and vital end‐organ damage, which stems from
ineffective stroke volume and insufficient circulatory compensation.1, 13 Compensatory
peripheral vasoconstriction may initially improve coronary and peripheral perfusion,
however it contributes to increased cardiac afterload that overburdens damaged myocardium.1,
13 This results in diminished oxygenated blood flow to peripheral tissue and, ultimately,
the heart.
Systemic inflammation causes pathological vasodilation, releasing nitric oxide synthase
and peroxynitrite, which have cardiotoxic inotropic effects.1, 13 Interleukins and
tumor necrosis factor alpha (TNF‐α) are additional systemic inflammatory mediators
that result in vasodilation and contribute to mortality in patients with CS.1, 14
Under normal physiological stresses, the right ventricular stroke volume and the left
ventricular stroke volume are equal. Right ventricular failure (RVF) occurs when the
ventricular diastolic and/or systolic pressures are insufficiently compensated by
normal myocardial adaptive processes to provide appropriate stroke volumes.15 Inadequate
forward blood flow in a compromised right ventricle (RV) accounts for end‐organ perfusion
deficits in conjunction with increased venous pressures.15 The RV is less adaptive
to pressure afterload and more tolerant of volume overload than the left ventricle
(LV) and this explains the inability of the right ventricle to tolerate severely elevated
pulmonary artery pressures.15 As RVF results in RV dilation, the interventricular
septum is displaced into the left ventricular space, compromising LV diastolic filling
and further exacerbating systemic hypoperfusion.15, 16
Clinical Presentation and Physical Examination
In the setting of CS, classic ACS symptoms and signs are combined with altered mental
status, hypotension, arrhythmia, diminished pulses, dyspnea, peripheral edema, jugular
venous distention, and orthopnea (Figure 1). These features reflect an infarction
involving >40% of the left ventricle,17 and can occur in the setting of an acute infarct
superimposed on an old MI or a new massive MI.
Figure 1
Physical findings suggestive of the ventricle primarily involved in cardiogenic shock.
Often pro‐inflammatory states induced by shock physiology causes a blunted performance
of the less affected side. Both sides often contribute to the clinical presentation
and physical exam findings.
Patients with CS most commonly present with cool extremities and signs of pulmonary
congestion. This presentation is termed “cold and wet” and reflects a reduced cardiac
index (CI), increased systemic vascular resistance, and increased PCWP. Patients may
also present euvolemic or “dry and cold”, which indicates a reduced CI, increased
systemic vascular resistance, and normal PCWP. Euvolemic presentations were more likely
to have previous MI or chronic kidney disease in comparison with those with classic
“cold and wet” features.18
An under‐recognized presentation of CS is the “wet and warm” subtype. This represents
a systemic inflammatory response syndrome reaction in conjunction with an MI and is
associated with a higher incidence of sepsis and mortality.13, 19, 20, 21 These patients
have a reduced CI, low‐to‐normal systemic vascular resistance, and an elevated PCWP.
Systemic inflammatory response syndrome should be suspected by the presence of fever,
an elevated white cell count, and low systemic vascular resistance. Nineteen percent
of patients had suspected sepsis in the SHOCK trial, with higher risk in younger patients
and those with low systemic vascular resistance.21 ACS‐associated CS patients with
culture‐positive sepsis have 2 times the risk of mortality.21 Systemic inflammatory
response syndrome is prevalent on admission in 25% of patients with STEMI. Tachycardia,
tachypnea, and leukocytosis are independent risk factors for mortality.20
Differential Diagnosis
Alternative diagnoses include other shock etiologies such as hypovolemic, distributive,
and obstructive. Other types of shock may contribute to CS as either the main insult
or in combination. Thorough medication reconciliation should be performed to discontinue
agents that exacerbate hemodynamic dysfunction.
Initial Investigations
Cardiac catheterization is both the definitive diagnostic investigation and guides
therapeutic intervention in CS complicating acute MI. Cardiac catheterization is typically
preceded by several initial investigations and non‐interventional management strategies.
However, CS is a clinical diagnosis and no investigation should delay emergent cardiac
catheterization.
ECG
The ECG should be ordered within 10 minutes of presentation.22, 23 ECG findings in
ACS are divided into 3 groups: ST‐segment elevation, ST‐segment depression, and non–ST‐segment
deviation.24 Early ECG changes of early coronary occlusion and transmural infarction
includes hyperacute T waves, which tend to be short‐lived and progress rapidly to
ST‐segment elevation.25 The presence of ST‐segment elevation in ≥2 contiguous leads
is an indication for urgent reperfusion.23 Transient ST‐segment elevation, ST‐segment
depression, and/or T‐wave inversions should raise clinical suspicion of ACS. These
patients should be treated with aggressive medical therapy and be evaluated immediately
for early coronary angiography.23 New guidelines suggest that left bundle branch block
(LBBB) is no longer an indication for urgent catheterization.26 In the appropriate
clinical context and in the presence of suggestive diagnostic evidence, urgent catheterization
should still be considered. Pathologic Q waves are a reflection of total size of MI,
rather than transmural extent, and their presence predicts a lower ejection fraction
(EF) and a larger MI.27 In the absence of previously described changes and high clinical
suspicion of ACS, true posterior wall myocardial infarction is suggested by the following:
ST‐segment depressions in the septal and anterior precordial leads (V1–V4), an R:S
wave ratio >1 in V1‐V2, ST‐segment elevations in the posterior leads of a poster ECG
(V7–V9).28 If there is co‐existing inferior wall myocardial infarction, there will
be ST‐segment elevations in the inferior leads (II, III, and aVF). A normal ECG is
not necessarily reassuring as posterior and lateral walls are not fully represented
on ECG and thus may not exclude ischemia.23 STEs confer a higher mortality risk in
ACS complicated by CS. It has been suggested that patients have a similar 90‐day prognosis
if effective revascularization takes place, regardless of ST segment patterns.24 Other
findings on (Figure 2) that are suggestive of ACS include sustained ventricular tachycardia,
ventricular fibrillation, atrial fibrillation, new bundle branch block, or worsening
of a symptomatic high‐degree atrioventricular block.29
Figure 2
ECG and coronary angiogram of a 53‐year‐old male who presented following sudden onset
of diaphoresis, nausea, and syncope. The patient was profoundly hypotensive on arrival
and an ECG revealed complete atrioventricular dissociation with junctional bradycardia.
Coronary angiography demonstrated (A) a high‐grade proximal LAD stenosis with Thrombolysis
in Myocardial Infarction 2 flow and (B) a total thrombotic proximal right coronary
artery (RCA) occlusion. An Impella 2.5 was inserted for left ventricular support and
PCI to the LAD was performed with a drug eluting stent. He recovered, the Impella
was discontinued, and he was discharged. LAD indicates left anterior descending; PCI,
percutaneous intervention.
Routine Initial Investigations
Complete blood counts and metabolic panels should be obtained every 12 to 24 hours
as they offer valuable information about oxygenation, electrolyte status, and end‐organ
damage.
Type 1 MI is caused by an acute atherothrombosis as result of plaque rupture or erosion.30
Frequent monitoring of troponins may reflect extent of injury that is time‐dependent
from the initial insult. In the setting of CS, as in STEMI, it is not recommended
to wait for the presence of elevated cardiac enzymes before emergent catheterization.
Troponins are typically trended every 6 hours starting from initial clinical suspicion.
N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) will be elevated during an acute
decompensation of heart failure. In CS resulting from ACS, raised levels of natriuretic
peptides are associated with increased mortality.31, 32
CS causes reduced oxygenation to peripheral tissues that results in lower pO2 levels
and elevated pCO2 levels. Higher levels of lactic acid can be associated with increased
mortality.33, 34 Blood gas and lactic acid should be trended (eg, every 1–6 hours
initially) to assess response to initial resuscitation.
Echocardiography may be beneficial, especially if there is clinical concern for an
MI‐related mechanical complication precipitating CS; however, it should not delay
cardiac catheterization. Ultimately, patients presenting with acute RVF or LVF of
suspected ischemic etiology should undergo immediate cardiac catheterization for the
assessment of coronary anatomy, intracardiac pressures, valvular dysfunction, and
structural impairments that often complicate ACS and contribute to CS.
Stabilization and Resuscitation Strategy
Intravenous Fluids
Fluid resuscitation strategy is a clinical challenge in the early management of CS
as it is often difficult to assess and can vary over time. In right‐sided heart failure,
right atrial pressures and pulmonary artery wedge pressures are poor predictors of
fluid response.15, 35 Echocardiography can assess right‐sided heart volume status
and rule out pericardial fluid collection.15 The definitive method of volume status
assessment and adequacy of resuscitation is right heart catheterization, which should
be performed in conjunction with coronary angiography. If hypovolemia is present,
conservative boluses of crystalloids (250–500 mL) are reasonable while the patient
is being stabilized for cardiac catheterization.
Oxygenation and Ventilation
Continuous pulse oximetry should be used to monitor for respiratory compromise. Oxygen
goals vary depending on patient comorbidities, but in the acute care setting blood
oxygen saturations of >90% are acceptable.
When non‐invasive forms of oxygenation and ventilation are inadequate, invasive ventilation
is required. Low tidal volumes (5–7 mL/kg of ideal body weight) used in the management
of acute respiratory distress syndrome are considered lung protective and decrease
the incidence of RVF from 60% to 25% in this cohort of patients.36 Low tidal volumes
optimize blood flow between the pulmonary and parenchymal vasculature. The decreased
resistance in the pulmonary circuit lowers stress on the RV, compared with higher
tidal volumes. Therefore, a low tidal volume strategy is recommended when mechanically
ventilating patients in CS.
Vasopressor Support
Vasopressors (Table 2) should be titrated to a mean arterial pressure with a typical
goal of >65 mm Hg. Vasopressin has less pulmonary vasoconstriction than norepinephrine;
and may be more beneficial as a first‐line vasopressor in patients with CS with acute
RVF.37 Pulmonary vasoactivity can be modified by inodilators, phosphodiesterase III
inhibitors, or nitric oxide (Table 3). When using these agents invasive blood pressure
monitoring is required as they can rapidly induce hypotension.
Table 2
Summary of Systemic Vasopressors
Agents
Mechanism
Effect
Indications
Considerations
Phenylephrine
A1 agonist
Vasoconstriction
Various forms of shock
Caution in cardiac dysfunction as it increases afterload
Norepinephrine
A<B agonist
Inotropy, chronotropy, dromotropy, and vasoconstriction
Most common first line agent in shock
Most benefits demonstrated in septic shock
Epinephrine
A≪B agonist
Inotropy, chronotropy, dromotropy, and vasoconstriction
Commonly used as second line agent or first line in anaphylactic shock
Surviving Sepsis Guidelines has most data for epinephrine as second line agent
Dopamine
Dose dependent A, B, and D agonism
Inotropy, dromotropy, chronotropy, and vasoconstriction (at highest doses)
Second line agent in most forms of shock
SOAP II trial demonstrated more incidence of tachy‐arrythmias and increased mortality
in CS patients when dopamine was used as first line
Vasopressin
V1 agonist
Vasoconstriction
Second line agent in most forms of shock
On or Off dosing, can cause hyponatremia
Dobutamine
B agonist
Inotropy and mild vasodilation
Commonly used in cardiogenic shock
May contribute to hypotension
Levosimendan
Myofilament Ca2+ sensitizer and K+ channel modifier
Ionotropy and inodilator
Used in acutely decompensated chronic heart failure
Minimal effect on myocardial oxygen consumption
CS indicates cardiogenic shock; SOAP, Sepsis Occurrence in Acutely Ill Patients.
Table 3
Summary of Vasoactive Agents Within the Pulmonary Circuit
Agent
Mechanism
Route
Side Effects
Nitric Oxide
↑ cGMP
Inhaled
Blurred vision, confusion, sweating, malaise, headache, bleeding
Milrinone
Phosphodiesterase 3 inhibitor
Intravenous
Bleeding, hypotension, chest pain, tremors, bronchospasm, hypokalemia
Prostacyclin
↑ cAMP, ↑ K, ↓ ET‐1, and ↑ K+
Inhaled or Intravenous
Bleeding, arrhythmias, diarrhea, edema, fevers, chills
Dobutamine
B agonist
Intravenous
Hypotension, tachyarrhythmia, headache, thrombocytopenia
Continuous Renal Replacement Therapy
Acute kidney injury occurs in 13% to 28% in patients with CS, and 20% will require
continuous renal replacement therapy.1, 38, 39 Continuous renal replacement therapy
should be considered with stage 2 kidney injury as defined by elevated serum creatinine
(≥2× baseline) and urine output <0.5 mL/kg per hour for ≥12 hours; or when life‐threatening
changes in fluid, electrolyte, and acid‐base balance precipitates the need for dialysis.40
Hemodynamic Monitoring
Goals of hemodynamic monitoring should be focused on hemodynamic modification to produce
stable vital signs and adequate tissue perfusion. Continuous blood pressure monitoring
with an arterial line, telemetry, continuous pulse oximetry, temperature, respiratory
rate, and urinary output are rudimentary parameters to monitor.
Mixed venous oxygen saturation (SvO2) is measured from a sample of blood drawn from
the central venous system, ideally from the distal port of a pulmonary artery catheter.
A low SvO2 may indicate reduced CO, anemia, hypoxemia, or increased oxygen consumption.41
A reduced SvO2 saturation is typically present in CS; however, this is also often
the case in hypovolemic and obstructive shock. SvO2 measurement can help assess response
to therapy when measured frequently. During the early stages of hemodynamic monitoring,
SvO2 measurements should be drawn every 4 hours after central line placement.
Common structural complications of MI should be suspected by appearance of a new systolic
murmur on clinical examination. Echocardiography can confirm early mechanical complications
such as papillary muscle rupture, ventricular septal defect, and free wall rupture,
which present most frequently within 24 hours of hospitalization.42, 43 Right ventricular
free wall hypertrophy indicates long term right‐sided pressure elevation, while right
ventricular dilation offers prognostic values.15, 44 During the treatment phase, echocardiography
and catheterization are used together to assess the hemodynamic response to intervention.
A pulmonary artery catheter (PAC) is typically placed during cardiac catheterization
and can assist with identification of patients requiring mechanical circulatory support.
It often remains in place thereafter for continuous hemodynamic monitoring—including
precise measurements of fluid states, central venous oxygen saturation, response to
therapy, and indicates the effectiveness of ventricular support. PACs offer therapeutic
advantages via continuous monitoring of cardiac output during inotrope and pulmonary
artery vasodilator titration.15, 45 This intervention is helpful because patient response
to mechanical circulatory support is dependent on several factors including volume
status, intrinsic RV contractility, properties of the systemic and pulmonary vasculature,
and the presence of valvular lesions.46 PACs can also aid the diagnosis of mechanical
circulatory support device complications such as pump thrombosis.46 Pump thrombosis
should be suspected in patients who exhibit clinical features of recurrent cardiogenic
shock accompanied by sudden elevation of pulmonary artery or PCWP.
Despite its more precise measurements, PAC use does not confer a mortality benefit
or reduce the length of intensive care unit or hospital stays. In fact its use in
the critically ill has been associated with increased mortality.47 Complications of
PACs include pulmonary infarcts, cardiac arrhythmias such as heart block, infection,
and balloon rupture. An LBBB, commonly seen in ACS, is a contraindication to a PAC
without backup ventricular pacing because of the risk of precipitating a right bundle
branch block (RBBB). In critically ill patients, a PAC is not always time effective
and clinical decisions are frequently made in the absence of this investigation.
MCS Devices
While inotropic agents are used widely, mortality is higher with an increased number
of prescribed inotropes/vasopressors.48, 49 Furthermore, catecholamine therapy is
associated with significant limitations including arrhythmias, increased myocardial
oxygen consumption, and inadequate circulatory support.50 MCS devices (Table 4)11,
51, 52, 53 offer significant advantages over vasopressor therapy including substantial
cardiovascular support without increased risk of myocardial ischemia and possible
decreased myocardial oxygen demand.54 Most importantly, there are registry data indicating
that early MCS device use is associated with improved survival rates.49 Thus, early
use of support devices is an important therapeutic intervention. Options for acute
percutaneous MCS include the intra‐aortic balloon pump (IABP), axial flow pumps (Impella
LP 2.5, Impella CP), left atrial‐to‐femoral arterial ventricular assist devices (Tandem
Heart) and venous‐arterial extracorporeal membrane oxygenation (ECMO).
Table 4
Mechanical Circulatory Support Device Evidence
Trial/Registry
Findings
IABP Shock II (2012)4
Randomized Control Trial
n=600
IABP vs OMT
No mortality benefit at 30 d, 6 mo, and 12 mo
Limitations: no emphasis on early MCS insertion, operator‐dependent revascularization
strategy, multiple crossovers to IABP group may represent sicker patients
Shock Trial Registry analysis (2004)51
Prospective Analysis
n=541
Identified CPO as strongest independent hemodynamic correlate of mortality in CS
Protect II Trial (2012)52
Randomized Clinical Trial
n=448
IABP vs Impella
Impella provided greater CPO
No MAEs difference at 30 d
However, Impella associated with decreased MAEs at 90 d
IMPRESS in Severe Shock (2017)
Randomized Clinical Trial
n=48
IABP vs Impella
No mortality difference at 30 days
Catheter‐based Ventricular Assist Device Registry analysis (2017)49
Prospective Analysis
n=287
Early MCS implantation before starting inotrope/vasopressor support and before PCI
independently associated with improved survival rates
Detroit Cardiogenic Shock Initiative (2018—ongoing)53
Randomized Control Trial
n=500 (target enrollment)
Reporting 76% survival rates
Improvement on stagnant ≈50% mortality rates over the past 2 decades
CPO indicates cardiac power output; CS, cariogenic shock; IABP, intra‐aortic balloon
pump; MAE, major adverse events; MCS, mechanical circulatory support; OMT, optimal
medical therapy; PCI, percutaneous coronary intervention; IMPRESS, IMPella versus
IABP Reduces mortality in STEMI patients treated with primary PCI in Severe cardiogenic
Shock.
The left ventricular pressure‐volume loop (PVL) illustrates the 4 phases of the cardiac
cycle—(1) isovolumetric contraction, (2) ejection, (3) isovolumetric relaxation and
(4) filling. In the absence of pathology the loop is trapezoidal with a rounded top,
but the position and morphology of the loop depend on ventricular preload and afterload.
Preload is the cardiac “wall stress”; it is the end‐diastolic volume that results
in the greatest average sarcomere stretch in the myocardium. Afterload is the pressure
that the left ventricle contracts against and is determined by the hemodynamic characteristics
of the vascular system. The PVL and normal LV mechanics provide a basis for understanding
ventricular mechanical support devices (Figure 3). They also offer insight into myocardial
oxygen consumption, which is related to the ventricular pressure‐volume area.46
Figure 3
MCS devices effect on pressure‐volume loops. (1) The normal left ventricular pressure‐volume
loop, (2) with effect of IABP and (3) with effect of Impella.55
IABP indicates intra‐aortic balloon pump, PV, pressure volume.
There are 3 circuit configurations for MCS devices—pumping from the (1) RA/central
vein to a systemic artery, (2) LA to a systemic artery or (3) LV to a systemic artery.
Peak flow rates of available devices range from 2.5 to 7 L/min.46
The IABP was introduced almost 5 decades ago and remains the most common support device
used in CS. IABP is believed to decrease myocardial oxygen consumption, increase coronary
artery perfusion, decrease afterload and modestly increase cardiac output (0.8–1 L/min).16
It is inserted via an 8Fr sheath in either the femoral or axillary artery.56
The IABP Shock II Trial included 600 patients with CS from acute MI receiving early
revascularization and randomized them to IABP support or optimal medical therapy.
The study showed no mortality benefit at 30 days.4 Follow‐up at 6 and 12 months showed
no reduction in all‐cause mortality or improvement in quality of life assessments.57
These findings may be because of the fact that the IABP plays no role in myocardium
salvage.57, 58 This study has a number of limitations. IABP insertion occurred within
24 hours, both before and after PCI. This does not align with contemporary thinking
that emphasizes early MCS. However, pre‐ or post‐PCI IABP insertion showed no mortality
difference. Additionally, the pursuit of culprit versus multivessel PCI was determined
by the operator. Furthermore, 30 crossovers occurred (26 of these non‐protocol) to
the IABP group and these may represent sicker patients.
There are a number of LV‐to‐aorta devices, however those most commonly used in the
setting of CS are the Impella devices. The Impella devices are axial flow pumps that
are advanced from the common femoral artery and passed retrograde across the aortic
valve into the LV and eject blood into the ascending aorta. The Impella 2.5 and Impella
CP devices are percutaneously inserted and can maintain a cardiac output of 2.5 to
4 L/min. Impella RP is a right‐sided device introduced via an 11Fr catheter that pumps
blood from the inferior vena cava to the pulmonary artery and delivers a flow rate
>4 L/min. The Impella 5.0 is a larger device that can achieve a cardiac output of
5 L/min, however, it requires a 22‐Fr sheath, necessitating a surgical cutdown of
the femoral artery. Continuous pumping of blood from the LV, independent of the cardiac
cycle, results in the loss of the normal isovolumic periods, transforming the PVL
from its trapezoidal morphology to a triangular shape. In contrast to the IABP, the
Impella acts independent of heart function and rhythm and as the pump flow rate increases
it progressively unloads the LV (resulting in a leftward PVL shift), peak LV pressure
decreases and there are decreases in pressure‐volume area and myocardial oxygen consumption.
Also, aortic pressure increases with escalating flow rate causing a widening dissociation
between aortic pressure and peak LV pressure (“LV‐Ao uncoupling”). This unloading
also results in decreased LA and wedge pressures.46 Impella use is contraindicated
in moderate‐to‐severe aortic valve disease, mechanical aortic valve and severe peripheral
arterial disease.54
Analysis of the Shock Trial Registry showed that cardiac power output (CPO) is the
strongest independent hemodynamic correlate of mortality in CS.51 CPO couples both
pressure (mean arterial pressure) and flow (cardiac output) variables to derive a
numerical value of cardiac pumping (CPO=mean arterial pressure×cardiac output/451).
Impella has demonstrated greater intraprocedural hemodynamic stability (smaller decrease
in mean arterial pressure and CPO).52 Thus, given the importance of CPO in CS and
the improved hemodynamics offered by Impella, it appears to be the most optimal therapy.
The Protect II Trial showed that, in patients with complex triple‐vessel or left main
stem disease and severely reduced LV function undergoing non‐emergent PCI, Impella
provided superior hemodynamic support compared with IABP as measured by CPO. Notably,
the incidence of major adverse events at 30 days was not statistically different between
these 2 groups. However, at 90 days, Impella was associated with decreased major adverse
events.52 It should be noted that Protect II did not, however, include patients with
CS.
Other advantages of Impella over IABP includes that it acts independent of heart function,
simultaneously unloads the left ventricle and supports arterial pressure, permits
prolonged balloon inflations, multiple passes with atherectomy devices, and supports
circulation during complex coronary interventional procedures.
Although there is some evidence that Impella use results in reduced peri‐ and post‐procedural
major adverse events in high‐risk PCI,59, 60 the theoretical benefit of Impella over
IABP is not borne out in larger trials of mechanical circulatory support in CS that
are focused on major outcomes.
The IMPRESS in Severe Shock (IMPella versus IABP Reduces mortality in STEMI patients
treated with primary PCI in Severe cardiogenic Shock) trial was a randomized comparison
of Impella CP versus IABP in patients suffering acute MI with CS. The primary end
point was 30‐day mortality and the study found no significant difference in 30‐day
mortality (≈50% for both groups).11 A limitation of the study was the small sample
size (n=48). Notably, it supported prior findings of increased bleeding risk with
Impella.61 Overall, the study suggests that the clinical benefits of Impella may be
more similar to IABP than expected.
The SHOCK,3 IABP‐SHOCK II,4 and IMPRESS in Severe Shock11 trials all showed ≈50% mortality
over 6 to 12 months, illustrating the constant mortality outcomes in CS over the past
2 decades despite the widespread use of MCS devices. Recent analysis of the cVAD (Catheter‐based
Ventricular Assist Device) Registry indicates that early MCS implantation in CS, before
starting inotrope/vasopressor support and before PCI, is independently associated
with improved survival rates in patients with CS because of acute MI.49 With this
in mind, the Detroit Cardiogenic Shock Initiative proposed the use of standardized
protocols with emphasis on early Impella insertion before PCI. The Detroit Cardiogenic
Shock Initiative Pilot Study reported 76% survival to discharge with this approach
and is expanding into a National Cardiogenic Shock Initiative.53
The Tandem Heart is an LA‐to‐arterial MCS device. A cannula is passed into the femoral
vein and an atrial septal puncture is performed to access oxygenated LA blood, which
is aspirated and pumped into one or both femoral arteries.54 Since blood is withdrawn
directly from the LA this unloads the LV, resulting in decreased PCWP and LVEDP.46
It improves peripheral tissue perfusion in spite of the mild increase in afterload
caused by the pumping of blood back into the femoral arteries.54 Use of Tandem Heart
is limited by its requirement of a specialized skillset that includes transseptal
puncture and time from door‐to‐LV unloading.
Venous arterial‐ECMO involves drainage of venous blood, passing it through an oxygenator
and returning the oxygenated blood to systemic circulation using a centrifugal pump.
It can be performed centrally by cannulation of the right atrium and aorta or peripherally
with cannulation of the femoral artery and vein. Peripheral ECMO can reduce LV preload;
however, this can cause increased ventricular wall tension due to retrograde flow
from femoral artery cannulation and therefore requires closer monitoring than central
ECMO.54 ECMO has a complex and variable hemodynamic response, which may be partially
explained by the variability of secondary effects of ECMO on total peripheral resistance
and left ventricular contractility.46 ECMO has been used in ≈13 000 patients and its
rate of survival‐to‐discharge is 39% when used in cardiac support.62 The absence of
large randomized controlled trials of ECMO in patients with CS consigns its use to
refractory cases as a bridging therapy to LVAD or emergent heart transplantation.54
Coronary Angiography
The most important investigation in patients diagnosed with CS is coronary angiography
(Figure 2). It enables physicians to identify the precise location of the lesion that
precipitated CS. On coronary angiography ≈15% patients are found to have significant
left main lesions and >50% have triple‐vessel disease. Mortality is associated with
the culprit vessel—left main coronary artery (78.6%), saphenous vein graft (69.7%),
circumflex coronary artery (42.4%), left anterior descending coronary artery (42.3%)
and right coronary artery (37.4%). Additionally, mortality is inversely related to
the Thrombolysis in Myocardial Infarction flow grade.63 After evaluation of coronary
anatomy patients typically undergo primary percutaneous coronary intervention (PCI).
In rare instances, and dependent on institutional resources, patients may proceed
to coronary artery bypass graft surgery, hybrid coronary artery bypass graft/PCI or
emergent cardiac transplantation.
PCI Strategy
Coronary reperfusion is an essential therapeutic intervention for patients with ACS
complicated by CS. The SHOCK trial provided strong evidence supporting the use of
PCI in cardiogenic shock. There were 302 patients diagnosed with acute MI complicated
by CS who were randomized to emergency revascularization or medical stabilization.
Overall mortality at 30 days was similar between the revascularization and medical
therapy groups. However, at 6 months mortality rates were significantly lower in the
revascularization cohort (50.3%) in comparison with the medical therapy group (63.1%).3
The marked mortality benefit in successful versus unsuccessful PCI was also clearly
demonstrated, 35% versus 80% respectfully.3 Subgroup analysis of the SHOCK trial demonstrated
a non‐significant trend towards increased 30‐day mortality in elderly patients receiving
early revascularization versus initial medical stabilization.3 However, an early revascularization
approach has subsequently been associated with lower short‐ (54.5% versus 72.1%) and
medium‐term (60.4% versus 80.1%) mortality when compared with initial medical stabilization
in this patient population.64 Of note, the SHOCK trial is now dated as only one‐third
of the revascularization cohort received intracoronary stents.
Complete revascularization, addressing both culprit and hemodynamically significant
non‐culprit lesions, has historically been the preferred strategy in patients with
acute MI and CS and was recommended in recent guidelines;1 however, this paradigm
has recently been challenged. The CULPRIT‐SHOCK (Culprit Lesion Only PCI versus Multivessel
PCI in Cardiogenic Shock) Trial randomized 706 patients with STEMI/NSTEMI and an identifiable
culprit lesion to multivessel or culprit lesion‐only PCI. The composite primary end
point was death or renal failure requiring dialysis at 30 days. The trial demonstrated
a 9.5% absolute risk reduction of the composite primary end point in the culprit lesion‐only
group (7.3% of which was attributable to an absolute risk reduction in all‐cause mortality).
Of note, the culprit‐lesion only cohort had the option for staged revascularization
of non‐culprit lesions and almost 20% of patients underwent further staged or urgent
PCI. Additionally, 75 patients crossed over from culprit lesion‐only to multivessel
PCI raising the possibility of including more complex and comorbid patients in the
multivessel PCI group, thus overestimating the benefit of culprit lesion‐only PCI.
Also, greater dye loads in multivessel PCI may partially account for observed differences
observed.65 Another limitation of the study was that low rates of MCS device use in
the multivessel PCI group. One‐year follow‐up showed no mortality difference between
the culprit lesion‐only and multivessel PCI groups (50% versus 56.9%, respectively).
The CULPRIT‐SHOCK Trial contradicts widespread current practice and prior studies
in non‐shock patients (DANAMI‐3‐PRIMULTI,66 PRAMI,67 CvLPRIT68) that suggested that
there may be a benefit from complete revascularization.
Data from the KAMIR‐NIH (Korea Acute Myocardial Infarction‐National Institutes of
Health) Registry are at odds with the findings from the CULPRIT‐SHOCK Trial. In this
national multicenter prospective registry 659 patients with STEMI and CS who underwent
PCI were studied. The risk of all‐cause death at 1 year was significantly lower in
the multivessel PCI group versus the culprit lesion‐only group (21.3% versus 31.7%;
P=0.001). Furthermore, multivessel PCI was associated with reduced rates in the composite
outcome of all‐cause death, MI, and repeat revascularization (28.4% versus 42.6%;
P<0.001).7 Larger trials that stratify patients according to door‐to‐LV unloading
time in tandem with randomization to culprit‐lesion versus multivessel PCI are needed
to resolve the discrepancy between the CULPRIT‐SHOCK and KAMIR‐NIH Registry findings.
Given the excellent long‐term patency rates of left internal mammary grafts coupled
with the advances in minimally invasive techniques and stent technology, hybrid coronary
revascularization procedures are a promising treatment modality for CS patients with
multivessel disease. Hybrid coronary revascularization refers to combined surgical
bypass with PCI during the same procedure or within 60 days.69
Despite significant advances in infarct management, persistently high mortality rates
have been observed in CS over the past 2 decades. However, available and emerging
evidence indicates promising avenues for contemporary management. A new approach that
emphasizes rapid LV unloading and prompt coronary revascularization may reduce mortality
of this devastating complication of AMI.
Disclosures
None.