Cardiogenic Shock 

Cardiogenic shock (see the image below) is a major, and frequently fatal, complication of a variety of acute and chronic disorders that impair the ability of the heart to maintain adequate tissue perfusion. Cardiac failure with cardiogenic shock continues to be a frustrating clinical problem; the management of this condition requires a rapid and well-organized approach.

Cardiogenic shock is a physiologic state in which inadequate tissue perfusion results from cardiac dysfunction, most commonly following acute myocardial infarction (MI). Although ST-elevation MI (STEMI, previously termed Q-wave MI) is encountered in most patients, cardiogenic shock may also develop in patients with non–ST-elevation acute coronary syndrome (NSTEMI, NSTACS, or unstable angina). The clinical definition of cardiogenic shock is decreased cardiac output and evidence of tissue hypoxia in the presence of adequate intravascular volume. Hemodynamic criteria for cardiogenic shock are sustained hypotension (systolic blood pressure < 90 mm Hg for at least 30 min) and a reduced cardiac index (< 2.2 L/min/m²) in the presence of elevated pulmonary capillary occlusion pressure (>15 mm Hg).

The diagnosis of cardiogenic shock can sometimes be made at the bedside by observing hypotension and clinical signs of poor tissue perfusion, which include oliguria, cyanosis, cool extremities, and altered mentation. These signs usually persist after attempts have been made to correct hypovolemia, arrhythmia, hypoxia, and acidosis.

Historical aspects

MI is the most common cause of cardiogenic shock in modern times. Morgagni first recognized MI in 1761, and it was subsequently described by Caleb Parry in 1788 and by Heberden in 1802. John Hunter, a surgeon at St. George's Hospital in London, England described his personal experience with MI in 1773. Adam Hammer, a physician in Mannheim, Germany, identified the role of coronary thrombosis in the causation of MI in 1878. The clinical features of acute MI and survival of patients after such an event were reported in 1912 in the Journal of the American Medical Association by James Herrick, a Chicago physician. In the late 20th century, clinicians recognized cardiogenic shock as a low cardiac output state secondary to extensive left ventricular infarction, development of a mechanical defect (eg, ventricular septal defect or papillary muscle rupture), and right ventricular (RV) infarction.

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.

Frequency

United States

The incidence rate of cardiogenic shock ranges from 5-10% in patients with acute MI. In the Worcester Heart Attack Study, a community-wide analysis, the reported incidence rate is 7.5%.^[1] The literature contains few data on cardiogenic shock in patients without ischemia.

International

Several multicenter thrombolytic trials in Europe report a prevalence rate of cardiogenic shock following MI of approximately 7%.

Mortality/Morbidity

The historic mortality rates from cardiogenic shock are 80-90%; more recent studies have reported somewhat lower in-hospital mortality rates, in the range of 56-67%. With the advent of thrombolytics, improved interventional procedures, and better medical therapies for heart failure, the mortality rates from cardiogenic shock are expected to decline.

The following predictors of mortality were identified from the GUSTO-I trial^[2] : increasing age; prior MI; altered sensorium; cold, clammy skin; and oliguria.

Mortality rates are similar in patients with cardiogenic shock secondary to STEMI and NSTACS.

Echocardiographic predictors such as left ventricular ejection fraction (EF) and mitral regurgitation are independent predictors. EF of less than 28% is associated with a survival rate of 24% at 1 year compared to a survival rate of 56% with a higher EF. Moderate or severe mitral regurgitation led to a 1-year survival rate of 31% compared to a survival rate of 58% in those with no regurgitation.

Sex

The overall incidence of cardiogenic shock is higher in men compared to women because of the increased prevalence of coronary artery disease in males. However, the percentage of female patients with MI who develop cardiogenic shock is higher compared to their male counterparts.