Pathophysiology

Disorders that can result in the acute deterioration of cardiac function and can lead to cardiogenic
shock include MI or myocardial ischemia, acute myocarditis, sustained arrhythmia, acute
valvular catastrophe, and decompensation of end-stage cardiomyopathy from multiple etiologies.
Autopsy studies show that cardiogenic shock is generally associated with the loss of more than
40% of the left ventricular myocardial muscle. The pathophysiology of cardiogenic shock, which
is well understood in the setting of coronary artery disease, is described below.
Myocardial pathology
Cardiogenic shock is characterized by both systolic and diastolic dysfunction. Patients who
develop cardiogenic shock from acute MI consistently have evidence of progressive myocardial
necrosis with infarct extension. Decreased coronary perfusion pressure and increased myocardial
oxygen demand play a role in the vicious cycle that leads to cardiogenic shock. These patients
often have multivessel coronary artery disease with limited coronary blood flow reserve.
Ischemia remote from the infarcted zone is an important contributor to shock. Myocardial
diastolic function is also impaired because ischemia causes decreased myocardial compliance,
thereby increasing left ventricular filling pressure, which may lead to pulmonary edema and
hypoxemia.
Cellular pathology
Tissue hypoperfusion, with consequent cellular hypoxia, causes anaerobic glycolysis, the
accumulation of lactic acid, and intracellular acidosis. Also, myocyte membrane transport pumps
fail, which decreases transmembrane potential and causes intracellular accumulation of sodium
and calcium, resulting in myocyte swelling. If ischemia is severe and prolonged, myocardial
cellular injury becomes irreversible and leads to myonecrosis, which includes mitochondrial
swelling, the accumulation of denatured proteins and chromatin, and lysosomal breakdown.
These pathophysiologic events induce fracture of the mitochondria, nuclear envelopes, and
plasma membranes. Additionally, apoptosis (programmed cell death) may occur in peri-infarcted
areas and may contribute to myocyte loss. Activation of inflammatory cascades, oxidative stress,
and stretching of the myocytes produces mediators that overpower inhibitors of apoptosis, thus
activating the apoptosis.
Reversible myocardial dysfunction
Understanding that large areas of dysfunctional but viable myocardium can contribute to the
development of cardiogenic shock in patients with MI is important. This potentially reversible
dysfunction is often described as myocardial stunning or hibernating myocardium.
Myocardial stunning represents postischemic dysfunction that persists despite restoration of
normal blood flow. By definition, myocardial dysfunction from stunning eventually resolves
completely. The mechanism of myocardial stunning involves a combination of oxidative stress,
abnormalities of calcium homeostasis, and circulating myocardial depressant substances.

Hibernating myocardium is a state of persistently impaired myocardial function at rest, which

occurs because of the severely reduced coronary blood flow. Hibernation appears to be an
adaptive response to hypoperfusion that may minimize the potential for further ischemia or
necrosis. Revascularization of the hibernating (and/or stunned) myocardium generally leads to
improved myocardial function.
Consideration for the presence of myocardial stunning and hibernation is vital in patients with
cardiogenic shock because of the therapeutic implications of these conditions. Hibernating
myocardium improves with revascularization, whereas the stunned myocardium retains inotropic
reserve and can respond to inotropic stimulation. Although hibernation is considered a different
physiologic process than that of myocardial stunning, the conditions are difficult to distinguish in
the clinical setting and they often coexist.
Cardiovascular mechanics of cardiogenic shock
The main mechanical defect in cardiogenic shock is that the left ventricular end-systolic
pressure-volume curve shifts to the right because of a marked reduction in contractility. As a
result, at a similar or even lower systolic pressure, the ventricle is able to eject less blood volume
per beat. Therefore, the end-systolic volume is usually greatly increased in persons with
cardiogenic shock. The stroke volume is decreased. To compensate for the diminished stroke
volume, the curvilinear diastolic pressure-volume curve also shifts to the right, with a decrease in
diastolic compliance. This leads to increased diastolic filling that is associated with an increase in
end-diastolic pressure. The attempt to enhance cardiac output by this mechanism comes at the
cost of having a higher left ventricular diastolic filling pressure, which ultimately increases
myocardial oxygen demand and causes pulmonary edema.
As a result of decreased contractility, the patient develops elevated left ventricular and RV filling
pressures and low cardiac output. Mixed venous oxygen saturation falls because of the increased
tissue oxygen extraction, which is due to the low cardiac output. This, combined with the
intrapulmonary shunting that is often present, contributes to substantial arterial oxygen
desaturation.
Systemic effects
When a critical mass of left ventricular myocardium becomes ischemic and fails to pump
effectively, stroke volume and cardiac output are curtailed. Myocardial ischemia is further
exacerbated by compromised myocardial perfusion due to hypotension and tachycardia. The
pump failure increases ventricular diastolic pressures concomitantly, causing additional wall
stress, hence elevating myocardial oxygen requirements. Systemic perfusion is compromised by
decreased cardiac output, with tissue hypoperfusion intensifying anaerobic metabolism and
instigating the formation of lactic acid, which further deteriorates the systolic performance of the
myocardium.
Depressed myocardial function also leads to the activation of several physiologic compensatory
mechanisms. These include sympathetic stimulation, which increases the heart rate and cardiac
contractility and causes renal fluid retention, hence augmenting the left ventricular preload. The

raised heart rate and contractility increases myocardial oxygen demand, further worsening
myocardial ischemia. Fluid retention and impaired left ventricular diastolic filling triggered by
tachycardia and ischemia contribute to pulmonary venous congestion and hypoxemia.
Sympathetically mediated vasoconstriction to maintain systemic blood pressure amplifies
myocardial afterload, which additionally impairs cardiac performance. Finally, excessive
myocardial oxygen demand with simultaneous inadequate myocardial perfusion worsens
myocardial ischemia, initiating a vicious cycle that ultimately ends in death, if uninterrupted.
Usually, both systolic myocardial dysfunction and diastolic myocardial dysfunction are present
in patients with cardiogenic shock. Metabolic derangements that impair myocardial contractility
further compromise systolic ventricular function. Myocardial ischemia decreases myocardial
compliance, thereby elevating left ventricular filling pressure at a given end-diastolic volume
(diastolic dysfunction), which leads to pulmonary congestion and congestive heart failure. For
more information, see Medscape's Heart Failure Resource Center.
Shock state
Shock state, irrespective of the etiology, is described as a syndrome initiated by acute systemic
hypoperfusion that leads to tissue hypoxia and vital organ dysfunction. All forms of shock are
characterized by inadequate perfusion to meet the metabolic demands of the tissues. A
maldistribution of blood flow to end organs begets cellular hypoxia and end organ damage, the
well-described multisystem organ dysfunction syndrome. The organs of vital importance are the
brain, heart, and kidneys.
A decline in higher cortical function may indicate diminished perfusion of the brain, which leads
to an altered mental status ranging from confusion and agitation to flaccid coma. The heart plays
a central role in propagating shock. Depressed coronary perfusion leads to worsening cardiac
dysfunction and a cycle of self-perpetuating progression of global hypoperfusion. Renal
compensation for reduced perfusion results in diminished glomerular filtration, causing oliguria
and subsequent renal failure.

Physical
Cardiogenic shock is diagnosed after documentation of myocardial dysfunction and exclusion of
alternative causes of hypotension, such as hypovolemia, hemorrhage, sepsis, pulmonary
embolism, pericardial tamponade, aortic dissection, or preexisting valvular disease. Shock is
present if evidence of multisystem organ hypoperfusion is detected upon physical examination.

Patients in shock usually appear ashen or cyanotic and have cool skin and mottled
extremities.

Peripheral pulses are rapid and faint and may be irregular if arrhythmias are present.

Jugular venous distention and crackles in the lungs are usually (but not always) present.
Peripheral edema also may be present.

Heart sounds are usually distant, and both third and fourth heart sounds may be present.

The pulse pressure may be low, and patients are usually tachycardic.

Patients show signs of hypoperfusion, such as altered mental status and decreased urine
output.

A systolic murmur is generally heard in patients with acute mitral regurgitation or

ventricular septal rupture.

The associated parasternal thrill indicates the presence of a ventricular septal defect,
whereas the murmur of mitral regurgitation may be limited to early systole.

The systolic murmur, which becomes louder upon Valsalva and prompt standing,
suggests hypertrophic obstructive cardiomyopathy (idiopathic hypertropic subaortic
stenosis).

Causes
Based on the etiology and pathophysiology, cardiogenic shock can be divided into systolic
dysfunction, diastolic dysfunction, valvular dysfunction, cardiac arrhythmias, coronary artery
disease, and mechanical complications.
Systolic dysfunction
The primary abnormality in systolic dysfunction is abated myocardial contractility. Acute MI or
ischemia is the most common cause; cardiogenic shock is more likely to be associated with
anterior MI. The other causes of systolic dysfunction leading to cardiogenic shock are severe
myocarditis, end-stage cardiomyopathy (including valvular causes), myocardial contusion, and
prolonged cardiopulmonary bypass.
Diastolic dysfunction
Increased left ventricular diastolic chamber stiffness contributes to cardiogenic shock during
cardiac ischemia, but also in the late stages of hypovolemic shock and septic shock. Increased
diastolic dysfunction is particularly detrimental when systolic contractility is also depressed. The
causes of cardiogenic shock due primarily to diastolic dysfunction are listed in Diastolic
dysfunction.
Valvular dysfunction
Valvular dysfunction may immediately lead to cardiogenic shock or may aggravate other
etiologies of shock. Acute mitral regurgitation secondary to papillary muscle rupture or
dysfunction is caused by ischemic injury. Rarely, acute obstruction of the mitral valve by left
atrial thrombus may result in cardiogenic shock by means of severely decreased cardiac output.

Aortic and mitral regurgitation reduce forward flow, raise end-diastolic pressure, and aggravate
shock associated with other etiologies.
Cardiac arrhythmias
Ventricular tachyarrhythmias are often associated with cardiogenic shock. Furthermore,
bradyarrhythmias may cause or aggravate shock due to another etiology. Sinus tachycardia and
atrial tachyarrhythmias contribute to hypoperfusion and aggravate shock.
Coronary artery disease
Cardiogenic shock is generally associated with the loss of more than 40% of the left ventricular
myocardium, although in patients with previously compromised left ventricular function, even a
small infarction may precipitate shock. Cardiogenic shock is more likely to develop in people
who are elderly or diabetic or in those who have had a previous inferior infarction.
Mechanical complications
Complication of acute MI, such as acute mitral regurgitation, large RV infarction, and rupture of
the interventricular septum or left ventricular free wall, are other causes of cardiogenic shock.
Specific causes of cardiogenic shock include the following:
Left ventricular failure

Systolic dysfunction (decreased contractility)

o Ischemia/MI
o Global hypoxemia
o Valvular disease (see Valvular or structural abnormality)
o Myocardial depressant drugs (eg, beta-blockers, calcium channel blockers,
antiarrhythmics)
o Myocardial contusion
o Respiratory acidosis
o Metabolic derangements (eg, acidosis, hypophosphatemia, hypocalcemia)

Diastolic dysfunction/increased myocardial diastolic stiffness

o Ischemia

o Ventricular hypertrophy
o Restrictive cardiomyopathy
o Consequence of prolonged hypovolemic or septic shock
o Ventricular interdependence
o External compression by pericardial tamponade

Greatly increased afterload

o Aortic stenosis
o Hypertrophic cardiomyopathy
o Dynamic aortic outflow tract obstruction
o Coarctation of the aorta
o Malignant hypertension

Valvular or structural abnormality

o Mitral stenosis
o Endocarditis
o Mitral aortic regurgitation
o Obstruction due to atrial myxoma or thrombus
o Papillary muscle dysfunction or rupture
o Ruptured septum or free wall arrhythmias

Decreased contractility
o RV infarction
o Ischemia
o Hypoxia

o Acidosis
Right ventricular failure

Greatly increased afterload

o Pulmonary embolism
o Pulmonary vascular disease (eg, pulmonary arterial hypertension, veno-occlusive
disease)
o Hypoxic pulmonary vasoconstriction
o Peak end-expiratory pressure
o High alveolar pressure
o Acute respiratory distress syndrome
o Pulmonary fibrosis
o Sleep disordered breathing
o Chronic obstructive pulmonary disease

Arrhythmias
o Atrial and ventricular arrhythmias (tachycardia-mediated cardiomyopathy)
o Conduction abnormalities (eg, atrioventricular blocks, sinus bradycardia)