Cardiogenic shock is on a continuum with congestive heart failure and decompensated heart failure. Congestive heart failure patients are hypervolemic but perfusing and qualify as the wet and warm profile of the Forrester Classification. Decompensated heart failure starts the decline into organ dysfunction or the cold and wet profile. They usually only meet the hemodynamic or imaging criteria and will begin having renal or liver injury due to the congestion more than decreased perfusion. When organ dysfunction occurs due to decreased oxygen delivery and lactic acid formation begins, it becomes cardiogenic shock.
Figure 1: Heart failure continuum
Figure 2: Forrester's heart failure profiles
The pathophysiology of cardiogenic shock is complex and involves both the systolic and diastolic components of the cardiac cycle. Additionally, it creates a feedback loop that will continue to spiral downward to death.
The easiest explanation for the initiation of this cycle is starting with acute myocardial infarction (AMI). When there is ischemia it damages the myocardium. In systole, it leads to a depression of the myocytes and decreased contractility which decreases stroke volume. In diastole, it leads to a decrease in relaxation which decreases the filling volume and worsens stroke volume. It also increases ventricular pressure which leads to pulmonary edema and venous congestion. Both decreased contractility (inotropy) and decreased relaxation (lusitropy) were talked about in a previous lecture on the 5 -tropies of the heart.
Hemodynamics of Cardiogenic Shock:
Breaking down cardiac output, the end result of cardiogenic shock will be an elevated preload, decreased contractility, and an elevated afterload.
Figure 3: Breakdown of cardiac output in cardiogenic shock
On the pressure-volume loop, decreased inotropy with lead to a right shift in the end-systolic pressure-volume relationship (ESPVR) and the decreased lusitropy will lead to a rise in the end-diastolic pressure-volume relationship (EDPVR). The decrease in stroke volume and relaxation leads to higher end-diastolic left ventricular volume and the loop will shift to the right and get smaller and smaller.
Figure 4: Normal left ventricular pressure-volume (PV) loop
Figure 5: Normal PV loop vs cardiogenic shock PV loop
Systemic compensatory response:
With this drop in relaxation and contractility, there is a large drop in stroke volume and cardiac output as shown above. The body will then attempt to compensate for this decrease in stroke volume.
1. Tachycardia:
Sympathetic release:
The decreased blood pressure due to the drop in stroke volume activates the sympathetic system and releases epinephrine and norepinephrine, leading to peripheral vasoconstriction, tachycardia, and increased contractility of the heart. The increase of beta 1 increases heart rate and further increases the oxygen demand of the heart.
2. Vasoconstriction:
Sympathetic release:
The sympathetic system also leads to peripheral vasoconstriction and an increase in contractility of the heart. The increase in alpha 1 causes vasoconstriction, increasing the afterload, making more pressure on the myocytes to overcome and increasing oxygen consumption/demand.
Renin-Angiotensin-Aldosterone-System (RAAS)
The decreased stroke volume causes decreased flow to the kidneys and activates the RAAS. This increases angiotensin II which will vasoconstrict and worsen afterload as above.
3. Fluid retention:
Renin-Angiotensin-Aldosterone-System (RAAS)
The decrease in stroke volume causes a decrease in flow to the kidneys and activates RAAS. This will increase aldosterone which will lead to an increase in fluid retention. Fluid retention will lead to increased preload, overstretch, and movement to the descending limb of the Starling curve.
Overall consequences:
Fluid backup:
The decrease in forward flow leads to a backup of fluid proximal to the ischemic area. This will lead to stretching and dilation of the ventricles and atria of the heart which worsens the function and puts pressure on the walls which leads to capillary ischemia.
Decreased oxygen delivery:
The decrease in stroke volume is typically more than the compensatory tachycardia can overcome, leading to a drop in cardiac output and a decrease in oxygen delivery to the heart and other organs.
Decreased coronary perfusion:
Hypotension leads to a decrease in coronary perfusion which also causes and drop in oxygen delivery to the myocardium.
Cardiogenic Shock Death Spiral:
The reason for the high mortality of cardiogenic shock is that it creates a feedback loop. The ischemia leads to low flow and hypotension which leads to more ischemia which leads to more low flow and hypotension.
Figure 6: Cardiogenic Shock Spiral of Death
Other ischemic consequences:
1. Inflammation:
When there is a large enough area of ischemia, either as the initial insult or secondary to the shock itself, there is a large release of cytokines. The major cytokines are IL-1, IL-6, and TNF-alpha which cause vasodilation and can also worsen cardiac function.
This vasodilation is in direct opposition to vasoconstriction occurring as a body compensation. This vasodilation will often lead to these patients being incorrectly diagnosed as having septic shock. Cardiogenic shock patients can have low cardiac output and low systemic vascular resistance temporarily in the acute phase. This usually lasts 12-24 hours and often requires vasopressor support until it resolves.
2. Hibernation:
When ischemia occurs, there will be permanent damage to the myocardium that will lead to necrosis, but the heart is able to save some of the muscle by having it go into a sort of hibernation. This way the myocardium will use very little oxygen and not sustain damage. This hibernating myocardium will look dysfunctional with imaging but can return to normal function once the ischemia has resolved. This is a significant reason why being quick and aggressive on treatment can make such a difference.
Breaking the cycle:
In order to reduce the mortality rate in cardiogenic shock, the spiral must be broken. This can be done with medical management or mechanical circulatory support (MCS). Part 3 will discuss these options and their risks and benefits, and part 4 will put all of this together and show why a cardiogenic shock team and treatment algorithm are so important.
REFERENCES:
Jones TL, Nakamura K, McCabe JM. Cardiogenic shock: evolving definitions and future directions in management. Open Heart. 2019;6(1):e000960.
Moghaddam N, van Diepen S, So D, Lawler PR, Fordyce CB. Cardiogenic shock teams and centres: a contemporary review of multidisciplinary care for cardiogenic shock. ESC Heart Fail. 2021;8(2):988-98.
Thiele H, Ohman EM, Desch S, Eitel I, de Waha S. Management of cardiogenic shock. Eur Heart J. 2015;36(20):1223-30.
Vahdatpour C, Collins D, Goldberg S. Cardiogenic Shock. J Am Heart Assoc. 2019;8(8):e011991.
Combes A, Price S, Slutsky AS, Brodie D. Temporary circulatory support for cardiogenic shock. The Lancet. 2020;396(10245):199-212.
Levy B, Clere-Jehl R, Legras A, Morichau-Beauchant T, Leone M, Frederique G, et al. Epinephrine Versus Norepinephrine for Cardiogenic Shock After Acute Myocardial Infarction. J Am Coll Cardiol. 2018;72(2):173-82.
Basir MB, Schreiber TL, Grines CL, Dixon SR, Moses JW, Maini BS, et al. Effect of Early Initiation of Mechanical Circulatory Support on Survival in Cardiogenic Shock. Am J Cardiol. 2017;119(6):845-51.
Esposito ML, Kapur NK. Acute mechanical circulatory support for cardiogenic shock: the "door to support" time. F1000Res. 2017;6:737.
Fincke R, Hochman JS, Lowe AM, Menon V, Slater JN, Webb JG, et al. Cardiac power is the strongest hemodynamic correlate of mortality in cardiogenic shock: a report from the SHOCK trial registry. J Am Coll Cardiol. 2004;44(2):340-8.
Basir MB, Kapur NK, Patel K, Salam MA, Schreiber T, Kaki A, et al. Improved Outcomes Associated with the use of Shock Protocols: Updates from the National Cardiogenic Shock Initiative. Catheter Cardiovasc Interv. 2019;93(7):1173-83.