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Pathophysiology

The most common insult for cardiogenic shock is left ventricular pump failure in the setting of acute myocardial infarction. It usually takes a considerable area of infarcted myocardium (around 40%) to lead to cardiogenic shock, nevertheless, a smaller infarct may also originate this condition in a patient with a previously compromised ventricle function. However, there may also be other etiologies, other parts of the circulatory system may contribute, either alone or in combination, with inadequate compensation, or additional defects for this shock of cardiac origin, such as:

• Systolic Left Ventricular Dysfunction - acute myocardial infarction, CHF, Cardiomyopathy, Coronary artery bypass grafting, Myocarditis, Myocardial contusion and Hypophosphatemia
• Diastolic Left Ventricular Dysfunction - Ischemia
• Obstruction of Left Ventricular Outflow, with Increased Afterload - Aortic stenosis, Hypertrophic Cardiomyopathy, Coarctation of the Aorta and Malignant Hypertension
• Reversal of flow into the left ventricle - Acute aortic insufficiency and endocarditis
• Inadequate left ventricular filling due to mechanical causes - Tamponade and pulmonary embolism
• Inadequate left ventricular filling due to inadequate filling time - Tachycardia and tachycardia-mediated cardiomyopathy
• Conduction abnormalities - Atrioventricular block and sinus bradycardia
• Mechanical defect - VSD and left ventricle free wall rupture
• Right ventricular failure - Pulmonary embolism and hypoxic pulmonary vasoconstriction

Luckily many of these abnormalities are fully or partially reversible. This justifies the fact that most of the survivors have good chances of having a good outcome and living with considerable quality of life, assuming that they follow their physician's orders.

The Pathophysiologic "Spiral" of Cardiogenic shock

The pathologic process begins with myocardial ischemia leading to an abnormal function of the cardiac muscle. This abnormality worsens the initial ischemia, which then deteriorates even further the ventricular function, creating the so called "downward spiral". When ischemia reaches a point that the left ventricular myocardium fails to pump properly, parameters like stroke volume and cardiac output will therefore decrease. The pressure gradient produced between the pressure within the coronary arteries and the left ventricle, along with the duration of the diastole, dictate myocardial perfusion. This will be compromised by the hypotension and the tachycardia, worsening the myocardial ischemia and the perfusion of other vital organs. The fact that the heart is the only organ that benefits from a low blood pressure, as afterload decreases, makes these hemodynamical changes both beneficial and detrimental. The pump failure will then decrease the ability to push the blood out of the ventricle, thereby increasing the ventricular diastolic pressures. This will not only reduce the coronary perfusion pressure, as it will also increase the ventricle wall stress, so that the myocardial oxygen requirements will also raise, consequently propagating the ischemia.

Other important reference to make in the setting of cardiac pump failure and hypoperfusion of the peripheral tissues is that this last one, leads to the release of catecholamines. Catecholamines such as norepinephrine, will increase the heart's contractility and peripheral blood flow, by causing constriction of arterioles, together with angiotensin II, to maintain perfusion, however, this will also increase the heart's oxygen demand and have proarrhythmic and myocardiotoxic consequences. The increased SVR coupled with the low cardiac output will lead to an even more pronounced reduction of tissue perfusion.

The ischemia generated by all these processes increases the diastolic stiffness of the ventricle wall and this, along with the left ventricular dysfunction, will increase the left atrial pressure. The increased left atrial pressure will propagate through the pulmonary veins, generating pulmonary congestion, which by decreasing oxygen exchanges, leads to hypoxia. The hypoxia will further worsen the ischemia of the myocardium and the pulmonary congestion will propagate its effect through the pulmonary arteries to the right ventricle, hence jeopardizing its performance. Once myocardial function is affected, the body will put in motion compensatory mechanisms to try to increase the cardiac output. These include:

• Tachycardia and increased contractility through sympathetic stimulation
• Activation of the renin/angiotensin/aldosterone system, leading to fluid retention and consequently increased preload

However, these compensatory mechanisms eventually become maladaptive seeing that:

• Tachycardia and increased contractility will increase cardiac muscle oxygen demand, thereby exacerbating the initial ischemia;
• Vasoconstriction, as a response to impaired cardiac output, in order to try to maintain coronary artery perfusion and systemic blood pressure (SVR) increases myocardial afterload, leading to an impairment in myocardial performance and an increase in its oxygen demand, worsening ischemia;
• The activation of the neurohormonal cascade will promote retention of water and sodium, in order to compensate for the hypotension and improve perfusion, yet this will also exacerbate pulmonary edema.

The prolonged systemic hypoperfusion and hypoxia will cause a shift in cellular metabolism, prioritizing glycolysis, leading to a state of lactic acidosis, which jeopardizes contractility and systolic performance, thereby affecting the previously described system. All these factors affecting oxygen demand and cardiac performance create a vicious cycle that if not interrupted, may eventually lead to death. The therapeutic approach to cardiogenic shock focuses in disrupting this cycle.

Besides the area of original infarct, remote territories may also exhibit some kind of myocardial damage, called myocardial stunning, in response to an ischemic insult which further reduces myocardial performance. Myocardial stunning is the name given the myocardium which remains dysfunctional even though the restoration to normal perfusion. The pathophysiology of myocardial stunning is multifactorial and involves calcium overload in the sarcolemma and diastolic dysfunction, as well as the release of myocardial depressant substances. This calcium overload is responsible for the activation of proteases called calpains. These and other proteases will be responsible for the degradation of myofilaments, which will decrease the response to calcium, thereby explaining the temporary myocardial dysfunction after reperfusion. Areas of stunned myocardium may remain stunned after revascularization due to the need to resynthetize new myofilaments. However, these regions retain contractile reserve and usually respond to inotropic stimulation. In contrast to stunned myocardium, hibernating myocardium does respond earlier to revascularization since myocardial cells remain viable and when reperfused, calcium levels normalize.

Right Ventricle Myocardial Infarction

Accounts for about 5% of the cases but represents as high mortality rate as left ventricular shock. The right ventricular regions more commonly affected by infarction are the inferior and inferior-posterior walls. The coronary arteries frequently occluded in this setting are the right coronary artery, or the left circumflex coronary artery, in a left dominant system. Patients with right coronary artery occlusion, in a right dominant system, are at higher risk of developing papillary muscle rupture and therefore undergoing valvular heart disease, such as mitral regurgitation.

Right ventricle failure may affect left ventricular performance by several means:

• Decrease in right ventricular output leading to a decrease in left ventricular filling thereby affecting overall cardiac output;
• Increased right ventricular telediastolic pressure, leading to a shifting of the interventricular septum into the left ventricle, therefore jeopardizing left ventricular filling and systolic function.

Cardiogenic shock and Inflammatory Mediators

The Pathophysiologic "Spiral" of Cardiogenic shock

Among patients with acute MI, there is often a downward spiral of hypoperfusion leading to further ischemia which leads to a further reduction in cardiac output and further hypoperfusion. The lactic acidosis that develops as a result of poor systemic perfusion can further reduce cardiac contractility. Reduced cardiac output leads to activation of the sympathetic nervous system, and the ensuing tachycardia that develops further exacerbates the myocardial ischemia. The increased left ventricular end diastolic pressures is associated with a rise in wall stress which results in further myocardial ischemia. Hypotension reduces epicardial perfusion pressure which in turn further increases myocardial ischemia.

Patients with cardiogenic shock in the setting of STEMI more often have multivessel disease, and myocardial ischemia may be present in multiple territories. It is for this reason that multivessel angioplasty may be of benefit in the patient with cardiogenic shock.

The multifactorial nature of cardiogenic shock can also be operative in the patient with critical aortic stenosis who has "spiraled": There is impairment of left ventricular outflow, with a drop in cardiac output there is greater subendocardial ischemia and poorer flow in the coronary arteries, this leads to further left ventricular systolic dysfunction, given the subendocardial ischemia, the left ventricle develops diastolic dysfunction and becomes harder to fill. Inadvertent administration of vasodilators and venodilators may further reduce cardiac output and accelerate or trigger such a spiral.

Pathophysiologic Mechanisms to Compensate for Cardiogenic shock

Cardiac output is the product of stroke volume and heart rate. In order to compensate for a reduction in stroke volume, there is a rise in the heart rate in patients with cardiogenic shock. As a result of the reduction in cardiac output, peripheral tissues extract more oxygen from the limited blood that does flow to them, and this leaves the blood deoxygenated when it returns to the right heart resulting in a fall in the mixed venous oxygen saturation.

Pathophysiology of Multiorgan Failure

The poor perfusion of organs results in hypoxia and metabolic acidosis. Inadequate perfusion to meet the metabolic demands of the brain, kidneys and heart leads to multiorgan failure.

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Differential Diagnosis

Classification of shock based on hemodynamic parameters. (CO, cardiac output; CVP; central venous pressure; PAD, pulmonary artery diastolic pressure; PAS, pulmonary artery systolic pressure; RVD, right ventricular diastolic pressure; RVS, right ventricular systolic pressure; SVO2, systemic venous oxygen saturation; SVR, systemic vascular resistance.)

Type of Shock	Etiology	CO	SVR	PCWP	CVP	SVO2	RVS	RVD	PAS	PAD
Cardiogenic	Acute Ventricular Septal Defect	↓↓	↑	N — ↑	↑↑	↑ — ↑↑	N — ↑	↑	N — ↑	N — ↑
	Acute Mitral Regurgitation	↓↓	↑	↑↑	↑ — ↑↑	↓	↑	N — ↑	↑	↑
	Myocardial Dysfunction	↓↓	↑	↑↑	↑↑	↓	N — ↑	N — ↑	N — ↑	↑
	Right Ventricular Infarction	↓↓	↑	N — ↓	↑↑	↓	↓ — ↑	↑	↓ — ↑	↓ — ↑
Obstructive	Pulmonary Embolism	↓↓	↑	N — ↓	↑↑	↓	↓ — ↑	↑	↓ — ↑	↓ — ↑
	Cardiac Tamponade	↓ — ↓↓	↑	↑↑	↑↑	↓	N — ↑	↑	N — ↑	N — ↑
Distributive	Septic Shock	N — ↑↑	↓ — ↓↓	N — ↓	N — ↓	↑ — ↑↑	N — ↓	N — ↓	↓	↓
	Anaphylactic Shock	N — ↑↑	↓ — ↓↓	N — ↓	N — ↓	↑ — ↑↑	N — ↓	N — ↓	↓	↓
Hypovolemic	Volume Depletion	↓↓	↑	↓↓	↓↓	↓	N — ↓	N — ↓	↓	↓