Management of Cardiogenic Shock Unrelated To Acute Myocardial Infarction

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Management of Cardiogenic Shock Unrelated to Acute Myocardial Infarction
Christopher F. Barnett, MD, MPH, Samuel B. Brusca, MD, Thomas C. Hanff, MD

MSCE, Vanessa Blumer, MD, Adnan Kaliff, MD, Manreet Kanwar, MD
PII: S0828-282X(23)00069-7
DOI: https://doi.org/10.1016/j.cjca.2023.01.023
Reference: CJCA 4569
To appear in: Canadian Journal of Cardiology
Received Date: 19 November 2022

Revised Date: 18 January 2023
Accepted Date: 19 January 2023
Please cite this article as: Barnett CF, Brusca SB, Hanff TC, Blumer V, Kaliff A, Kanwar M, Management
of Cardiogenic Shock Unrelated to Acute Myocardial Infarction, Canadian Journal of Cardiology (2023),
doi: https://doi.org/10.1016/j.cjca.2023.01.023.
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1 Management of Cardiogenic Shock Unrelated to Acute Myocardial Infarction
2
3 Short Title: Non-AMI Cardiogenic Shock
4
5 Journal: Canadian Journal of Cardiology
6
7 Christopher F Barnett MD, MPH 1, Samuel B Brusca MD1, Thomas C Hanff MD
8 MSCE 2, Vanessa Blumer MD3, Adnan Kaliff MD4, Manreet Kanwar MD4
9
1
10 Division of Cardiology, University of California, San Francisco, San Francisco, CA
2
11 Division of Cardiovascular Medicine, Department of Internal Medicine, University
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12 of Utah School of Medicine, Salt Lake City, UT
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13 Department of Cardiovascular Medicine, Heart and Vascular Institute, Kaufman
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14 Center for Heart Failure, Cleveland Clinic, Cleveland, OH
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4
15 Cardiovascular Institute at Allegheny Health Network, Pittsburgh, PA
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17 Corresponding Author
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19 Manreet Kanwar
AGH McGinnis Cardiovascular Institute
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21 Allegheny General Hospital
320 E North Ave, 1st floor
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23 Pittsburgh, PA 15212
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24 Email: manreet.kanwar@ahn.org
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26
27 Word count: 7082
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29 Disclosures:
30 Barnett, Brusca, Blumer and Kaliff: None
31 Kanwar: Advisory Board for Abiomed
32
33 Funding sources:
34 None
35
36
Non- AMI Cardiogenic Shock Page 2
37 Abstract
38 Cardiogenic shock is an extreme manifestation of acute decompensated heart
39 failure. Cardiogenic shock is often caused by and has traditionally been studied in
40 the setting of acute myocardial infarction (AMI CS); however, there is increasing
41 incidence and recognition of cardiogenic shock not associated with acute
42 myocardial infarction (non-AMI CS) as a distinct entity. Despite decades of study
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43 and technological advancements, cardiogenic shock mortality remains as high as
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44 50%, regardless of etiology. New approaches to shock phenotyping and
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45 classification have emerged, with a focus on appropriately matching patient
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46 physiology to a growing list of available interventions. Further study is needed to

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47 determine whether these efforts will lead to more nuanced utilization of

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48 mechanical circulatory support and improved patient outcomes, especially in non-

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49 AMI CS. In the meantime, models of care incorporating multidisciplinary decision
50 making such as shock teams may improve patient selection and outcomes.
51
52 Introduction
53 Cardiogenic shock (CS) is an extreme manifestation of acute
54 decompensated heart failure (ADHF), with an in-hospital mortality rate of 30%-
55 50%.1 The two most common etiologies of CS are acute myocardial infarction
56 (AMI CS) and progression of heart failure, not secondary to AMI (non-AMI CS).
57 The latter can be the result of de-novo ADHF or as a sequalae of chronic, end-
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58 stage disease. Although the pathophysiology and management of AMI CS have
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59 been the focus of intense investigation, non-AMI CS is less well studied and likely
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60 represents a distinct disease entity.
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61 With this in mind, there is growing interest in characterizing AMI and non-
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62 AMI CS as distinct CS phenotypes, including their differing presentations,

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63 responses to therapy, and clinical outcomes.2, 3 At a fundamental level, the

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64 clinical deterioration of patients with AMI-CS begins with hypotension, which
65 leads to hypoperfusion and congestion. In contrast, patients with non-AMI CS
66 commonly present with ADHF and congestion, leading to hypoperfusion and
67 hypotension.4 Epidemiologically, patients with non-AMI CS experience lower in-
68 hospital mortality and receive more heart replacement therapies (HRT), including
69 durable left ventricular assist devices (LVAD) and heart transplantation.5 Finally, it
70 is increasingly recognized that the traditional definitions and hemodynamic

71 profiles of CS, both of which have been derived largely from clinical trials in AMI
72 CS, may not apply to non-AMI CS. Although further study is required, it seems
73 likely that risk stratification and management of CS will benefit from further
74 individualization based on the underlying physiology.6
75 In this review, we describe the pathophysiology, epidemiology, and
76 management of non-AMI CS. We also characterize contemporary models of CS
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77 management, including multidisciplinary team approaches, as well as medical and
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78 device-based management. re
79
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80 Pathophysiology of non-AMI cardiogenic shock

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81 The differential diagnosis in non-AMI CS is broad and includes progression

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82 of chronic cardiomyopathy, malignant arrhythmias, valvular heart disease,

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83 inflammatory myocarditis, and pericardial diseases.7 These conditions share the
84 commonality that they are not associated with a proximal acute coronary
85 syndrome; however, they are otherwise vastly different conditions with unique
86 pathophysiologies. Recognition of the precipitating factors involved in CS is of the
87 utmost importance, as rapid intervention (e.g. appropriate structural
88 interventions for acute decompensated valve disorders) may stem irrecoverable
89 hemodynamic collapse.
90 All CS conditions share a common final pathway: the “ischemic spiral.”
91 Pathologically reduced stroke volume (SV) and cardiac output (CO) incite a
92 cascade of downstream sequalae, leading to hypotension, maladaptive
93 vasoconstriction, elevated cardiac chamber filling pressures, cardiac ischemia,
94 end-organ congestion and hypoperfusion, and ultimately multi-organ failure and
95 death.7, 8 These elements synergize in a negative feedback loop, worsening
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96 cardiac ischemia (even in the absence of coronary obstruction) and cardiac
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97 contractility, further reducing CO and propagating end organ failure (Figure 1).
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98 There is also a growing acknowledgement of a role for inflammation in CS, with
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99 endothelial damage leading to Nitric Oxide and cytokine release. 9, 10 The release
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100 of these factors contributes to the ischemic cascade by inducing hypotension and
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101 reducing inotropy. Further, they can complicate the hemodynamic picture of CS,
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102 by inducing a “mixed shock phenotype.” Though the inflammatory component of
103 CS has primarily been studied in and is likely most prominent in AMI-CS, it may
104 also play a role in other CS varieties and is associated with worse outcomes in a
105 broad range of CS patients. 11
106
107 Phenotyping Cardiogenic Shock
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109 The simplest framework for phenotyping CS is an extension of that used to
110 classify patients with ADHF, incorporating a 2x2 table that categorizes patients
111 based on the presence of congestion and the status of patients’ systemic vascular
112 resistance (Figure 2).7 Similar to the classic table used in ADHF, patients
113 characterized as “cold and wet” and “cold and dry,” are both hypoperfused but
114 differ based on the presence or absence of volume overload. However, all
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115 patients in the CS table have “shock,” and thus are lacking in perfusion. Therefore,
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116 patients in the “warm and wet” box are representative of a mixed shock
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117 phenotype as opposed to a volume overloaded patient without end organ
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118 hypoperfusion.
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119 Another useful framework for phenotyping CS has to do with the acuity of
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120 the cardiac insult. Like in AMI CS, patients who develop de-novo pump failure in
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121 the setting of acute conditions such as myocarditis or abrupt severe aortic
122 regurgitation have not developed compensatory LV hypertrophy nor the ability to
123 accommodate increased ventricular volume. LV compliance is reduced and the
124 ventricular end-diastolic pressure-volume relationship increased, yet the ventricle
125 has not remodeled so as to maintain SV. This scenario can be visualized using
126 pressure-volume loops, which demonstrate a short and narrow loop, which is
127 shifted up and to the right and is characterized hemodynamically by decreased

128 stroke work and cardiac power output.12, 13 Alternatively, non-AMI CS in the
129 setting of progressive dilated cardiomyopathy or chronic regurgitant valvular
130 lesions operates at a higher point on the end-diastolic pressure-volume curve and
131 the ventricle often maintains SV (Figure 3). This has implications for management
132 (e.g. afterload responsiveness or utility of intra-aortic balloon pump) as well as for
133 the predictive power of prognostic markers, as stroke work and cardiac power
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134 output may be of less relevance.14, 15 A deeper understanding of pressure-volume
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135 loops may aid in understanding the pathophysiologic differences between acute
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136 and chronic HF and how these differences manifest during CS. 13, 14
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137 Finally, though these traditional methods of phenotyping are clinically

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138 useful, there has been increased interest in further stratifying patients that would
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139 otherwise be lumped together. Using machine learning, three distinct profiles
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140 have been identified, including non-congested CS, cardiorenal CS, and
141 cardiometabolic CS.16 Non-congested CS patients are typically younger with fewer
142 comorbidities and have less pronounced hemodynamic derangements and end
143 organ dysfunction. Cardiorenal CS patients are typically older with significant
144 medical comorbidities such as diabetes. Though they too have less pronounced
145 hemodynamic derangements, primarily left sided congestion and out of
146 proportion renal dysfunction is present. Finally, cardiometabolic CS is

147 characterized by more pronounced hypotension and tachycardia, more right
148 sided congestion, and higher lactate levels. Importantly, these phenotypes have
149 prognostic implications, with mortality highest in the cardiometabolic group and
150 lowest in the non-congested group across multiple registries.16, 17 The biologic
151 underpinnings of these phenotypes as well as why patients develop one
152 phenotype as opposed to the others remains to be determined.
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154 Clinical Presentation re
155 As mentioned above, CS typically presents with elevated cardiac filling
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156 pressures along with hypotension, tissue hypoperfusion, or a combination of

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157 hypotension and hypoperfusion. Hypoperfusion is correlated with reduced CO,

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158 but at the tissue level its presence is inferred indirectly from elevated peripheral
159 blood lactate or end-organ dysfunction such as acute kidney injury, acute liver
160 injury, altered mental status, or gut ischemia. Hypotension refers to a systolic
161 blood pressure < 90 mmHg or mean arterial blood pressure < 60 mmHg. The
162 Society for Cardiovascular Angiography and Interventions (SCAI) CS classification
163 identifies the presence of hypoperfusion as the principal feature defining SCAI
164 stages C-E, and the presence of isolated hypotension is the defining characteristic
165 of “pre-shock” SCAI stage B (Figure 4).18 Notably, an amended and more clinically
166 applicable SCAI staging system has been proposed by the Cardiogenic Shock
167 Working Group.19 They propose including normotensive CS in Stage B (e.g. lactic
168 acidosis without hypotension) and include criteria for the number of employed
169 medications or devices to achieve clinical stability.
170 Increasing SCAI CS stages are associated with increased short- and long-
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171 term mortality .20-22 However, the incremental, independent prognostic value of
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172 hypotension and hypoperfusion at presentation may differ between AMI CS and
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non-AMI CS. For example, Jentzer and colleagues analyzed 10,000 CS patients
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174 admitted to the cardiac intensive care unit (CICU) in a single hospital system.23
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175 Patients were characterized as having hypotension, hypoperfusion (defined

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176 broadly to include acute kidney injury, oliguria, or lactate > 2mmol/L), or both. In
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177 contrast to AMI, in the non-AMI CS population, isolated hypoperfusion did not
178 exhibit higher mortality compared to either isolated hypotension (P=0.15) or
179 combined hypoperfusion and hypotension (P=0.33). Thus, the presence of
180 isolated hypoperfusion may be more prognostically meaningful in AMI CS than
181 non-AMI CS. Alternatively, because hypoperfusion was inferred indirectly from
182 end-organ dysfunction such as acute kidney injury, these findings could also
183 represent misclassification of the cardiorenal syndrome as CS, which may be more
184 prevalent (and potentially less morbid) in the non-AMI CS population.

185 The acute on chronic presentation of non-AMI CS frequently occurs in the
186 background of chronic multisystem changes to peripheral vascular function,
187 altered lymphatic system compliance, greater exposure to neurohormonal
188 antagonists, more prevalent end-organ dysfunction, and an indolent systemic
189 inflammatory response.24 These chronic changes may modify the response to an
190 acute or subacute decline in CO in both adaptive and maladaptive ways. For
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191 example, chronic elevation of pulmonary hydrostatic pressure increases lymph
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192 flow to 30 times the normal rate, which may explain lesser pulmonary edema in
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193 non-AMI CS relative to AMI CS at comparable filling pressures.25, 26 Chronic
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194 changes to vascular endothelial responsiveness and systemic inflammation may

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195 also attenuate the clinical impact of hemodynamic changes in non-AMI CS, who
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196 tend to have comparable CO, filling pressures, blood pressure, and heart rate at
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197 presentation as AMI CS but nearly half the up-front in-hospital mortality risk (25%
198 vs 41% in the Cardiogenic Shock Working Group cohort).27
199 Diagnosis
200 Timely intervention and de-escalation of hemodynamically tailored
201 therapies is critical in non-AMI CS, leading to the adage “right time, right patient,
202 and right therapy.” Compared to AMI CS, in which an acute up-front event marks
203 the onset of hemodynamic compromise and shock pathophysiology, non-AMI CS
204 has a more variable trajectory that can be challenging to diagnose without a high-
205 degree of suspicion. Moreover, unlike AMI CS, where the affected coronary
206 distribution dictates ventricular involvement in a reliable fashion, non-AMI CS
207 more frequently presents with biventricular involvement or concurrent pre-
208 capillary pulmonary hypertension whose management strategies differ and
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209 whose clinical identification may be more challenging.
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Invasive hemodynamic assessment plays a crucial role early in the diagnosis
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211 of non-AMI CS. In particular, when there is a clinical suspicion of CS based on low-
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212 output symptoms, physical exam, hypotension, or end-organ hypoperfusion, early

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213 hemodynamic profiling may help confirm CS, grade its severity, and phenotype
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214 left versus right versus biventricular dysfunction. Of note, no randomized
215 controlled trial has evaluated the use of PAC in CS. Several non-invasive
216 echocardiographic measurements and other invasive diagnostic tests may also
217 help diagnose, phenotype, and risk-stratify non-AMI CS. Echocardiography plays a
218 critical role, ensuring the full structure and function of the cardiac chambers and
219 valves is understood as it relates to CS, and whether alternative etiologies for CS
220 may exist such as cardiac tamponade, restrictive cardiomyopathy, infiltrative
221 cardiomyopathy, or obstruction. 28 Echocardiography-based measurements of

222 stroke volume such as left or right ventricular outflow tract velocity time integral
223 may also correlate with or replace invasive hemodynamics in some situations29
224 though often these are limited by inter-user variability and less frequent
225 measurements. There is an important diagnostic role for coronary angiography in
226 non-AMI CS, given that patients with known or unknown ischemic
227 cardiomyopathy may still present with CS outside of the acute MI setting. Most
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228 adult patients with a decline in left ventricular function and unknown coronary
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229 patency warrant ischemic evaluation, particularly those with regional variation in
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230 ventricular function or elevated risk for coronary artery disease. Finally, select
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231 patients with non-AMI CS should undergo endomyocardial biopsy to diagnose

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232 disease processes such as giant-cell myocarditis or infiltrative diseases.30

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233 Contemporary Cardiogenic Shock Models of Care
234 CS models of care are emerging with the aim of standardizing disparities in
235 evidence-based care and reducing in-hospital mortality related to CS. An ideal
236 model of care for CS would integrate shock teams, transfer protocols (including
237 hub-and-spoke models), and multidisciplinary cardiac intensive care unit (CICU)
238 teams (Figure 5). While the current landscape of CS care is notably varied with
239 diverse practice patterns and access to care, the implementation of shock teams,
240 hub-and-spoke transfer models, and multidisciplinary CICUs have all shown
241 promising results at improving early recognition of shock, access to high-level
242 care, and short-term survival. 1, 7
243
244 Multi-disciplinary Shock teams
245 Shock teams have been established as a means to streamline care delivery
246 and optimize outcomes.31 Most commonly, shock teams are comprised of a
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247 critical care cardiologist or intensivist, heart failure cardiologist, cardiothoracic
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248 surgeon, and an interventional cardiologist. Once a patient is deemed to have CS,
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249 the main goal of the shock team is to expedite multidisciplinary decision-making
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250 surrounding patient management, and particularly, the utility/appropriateness of

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251 any invasive interventions. 32 In this regard, it is commonplace for shock teams to
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252 partake in decisions involving timely diagnosis of CS, decision to transfer,

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253 interpretation of invasive hemodynamics, revascularization strategies, as well as
254 implementation and escalation of mechanical circularity support (MCS).
255 Outcomes associated with shock teams have been varied, with an overall greater
256 benefit when interventions are geared towards AMI CS. 32
257
258 Transfer Models

259 Most CS literature blends the implementation of shock teams with a hub-
260 and-spoke transfer model. This model attempts to effectively centralize the
261 management of complex CS patients at the centers with highest capabilities. In
262 the hub-and-spoke model, “hub” hospitals tend to be high-volume tertiary
263 cardiovascular centers, while “spoke” hospitals are referral or community
264 hospitals with less on-site capabilities. 7 Cardiovascular care capability tiers akin to
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265 those used for trauma centers have been proposed to further standardize inter-
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266 hospital communication and transfer (Table 1).33
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267 While there may be subtle differences in the elements that define
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268 individual hub-and-spoke models, prior experiences have highlighted several key
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269 components: 1) a well-defined protocol that allows the early recognition and
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270 quick transfer of CS patients, 2) a physician should be empowered to activate a

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271 transfer with a single phone call, and 3) the spoke centers should be within a
272 reasonable distance from the hub center.1, 7
273
274 Multidisciplinary CICU care
275 CS is now among the leading indication for admission to contemporary
276 CICUs.34 CS patients present with high illness severity and acuity and are at great
277 risk for multisystem organ failure. Care decisions are often nuanced and require
278 an understanding of invasive hemodynamics, pharmacologic therapy, circulatory
279 support devices, and eligibility for downstream resources – including, but not
280 limited to palliative inotropes, ventricular assist devices, and cardiac
281 transplantation. Frequently, expertise in both cardiac critical care and advanced
282 heart failure and transplant cardiology must be leveraged for these patients to
283 achieve positive outcomes. Although controversy remains regarding the ideal
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284 training background for cardiologists staffing contemporary CICUs,35, 36 it is likely
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285 more important that CS care be provided within well developed ICU care
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286 pathways, utilizing comprehensive, collaborative, and multidisciplinary team
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287 based decision making. Notably, multiple studies have demonstrated that high-
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288 intensity CICU physician staffing in a closed CICU or with mandatory intensivist
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289 consultation is associated with improved outcomes, including one study reporting
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290 39% lower ICU mortality and as well as reduced length of stay and reduced in
291 hospital mortality.33 Thus, inclusion of an intensivist in the CS patient care team,
292 either a critical care cardiologist, or an intensivist with other non-cardiology
293 training, is likely important to optimize patient outcomes.
294
295 Palliative care

296 Lastly, while it is important to promptly identify and treat patients with CS,
297 it is equally important to recognize when escalation measures might be futile and
298 psychosocial and spiritual support more appropriate. Although the optimal
299 mechanism for palliative care delivery in the CS is unknown7, it is important to
300 recognize that as an integral part of an effective interdisciplinary approach,
301 palliative care consultation can improve the quality of life for patients and their
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302 families, facilitating goals of care conversations and decision making.37
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303 Management of cardiogenic shock
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304 Early recognition

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305 Failure to recognize CS early and rapidly initiate treatment may contribute
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306 to the persistent high mortality seen in contemporary trials. One hypothesis is
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307 that early reversal of hemodynamic perturbations such as of low CO and
308 increased cardiac filling pressures can prevent the development of end organ
309 hypoperfusion, congestion, and inflammation that leads to multi system organ
310 dysfunction.38 Indeed a quality metric of “door to support time” analogous to the
311 “door-to-balloon time” utilized in the management of STEMI has been proposed
312 but to date there no (Figure 5).39

313 Further, the benefit of shock team activation, including early involvement of
314 intensivists, is likely driven in part by early recognition that enables early
315 intervention. It is possible that early intervention may be an important
316 mechanism by which shock teams improve patient outcomes31. . 32, 40
317 Prognosis and risk assessment
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318 Determining risk and patient prognosis at the time of CS presentation and
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319 the ability to adjust this understanding during treatment is necessary to select
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320 appropriate intervention and care de-escalation. Classical approaches to defining
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321 and staging CS include the Killip classification and the SHOCK trial definition.41
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322 These classification systems incorporateonly a few limited data points and
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323 identify patients in whom shock has already advanced to the point of severe
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324 illness. However, they fail to capture and characterize patients along the entire
325 continuum of shock. Risk scoring systems developed in general ICU populations,
326 such as APACHE and SAPS, have successfully been applied to CS patients,
327 however, these tools require numerous data points, serially enteredover time
328 and are not calibrated in CS populations. Limitations in CS risk assessment tools
329 may have contributed to the failure of CS intervention trials due to suboptimal
330 patient selection. In an effort to improve shock risk classification, the SCAI shock
331 stage classification was developed by expert consensus in 2019 and updated in
332 2022. Five stages of CS are defined from stage A, (At risk), a patient not in shock
333 but at risk of developing shock, to stage E, (Extremis), a patient experiencing
334 cardiac arrest and being supported by multiple interventions (Figure 4).22
335 Numerous validation studies have been performed demonstrating the predictive
336 value of the SCAI shock stages across all clinical subgroups. A variety of
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337 approaches and criteria to assigning the SCAI shock stages have also been
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338 described, including physician assigned stages versus combinations of clinical
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339 variables.22 Validation studies have uniformly demonstrated that higher SCAI
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340 shock stages are associated with high higher short- and long-term mortality
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341 regardless of etiology. 22 Further study is required; however, the SCAI

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342 classification is a promising tool for patient risk stratification and optimal patient
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343 selection for clinical trials.
344
345 Targets of treatment
346 The primary goals of CS treatment are 1) Restoring and maintaining
347 adequate CO to achieve end organ perfusion, 2)Normalization of cardiac filling
348 pressures, and 3) Normalization of total body volume. In the presence of a low
349 output state, priority should be given to restoring adequate CO to perfuse end
350 organs, stop end organ injury and prevent the progression from hemodynamic CS
351 to hemometabolic CS. Additionally, fluid removal and decongestion may not be
352 possible until adequate renal blood flow is restored. The degree of effectiveness
353 of vasoactive drugs is difficult to predict and adverse effects are common. Thus,
354 CS patients require frequent clinical, laboratory, and hemodynamic reassessment
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355 when drips are being titrated.
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The optimal strategy for hemodynamic assessment and targets for therapy
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357 in CS remain uncertain.42 Although clinical trials have not demonstrated benefit
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358 from routine use of PAC in heart failure, more recent observational studies have
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359 suggested improved outcomes in CS patients managed with a PAC.43 These data
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360 suggest that tailoring interventions to hemodynamic targets obtained from the
361 PAC may be beneficial. Regardless of PAC utilization, the overall approach should
362 focus on restoration and maintenance of adequate end organ perfusion. Serial
363 assessment of clinical and laboratory markers such a serum lactate, central
364 venous oxygen saturation, urine output, renal function, electrolytes and liver
365 function tests and mental status are all useful to determine if end organ perfusion
366 is adequate. In patients with hypotension, treatment with vasopressors may be
367 required and titration to a traditional target of SBP > 90 mm Hg or MAP > 65 mm
368 Hg is often selected. Recognizing that the optimal MAP may vary from patient to
369 patient, we recommend careful adjustment of this goal lower or higher to
370 maintain end organ perfusion.
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372 Medical management
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373 In CS patients who present with low CO in the setting of normotension or
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hypertension, afterload reduction alone may be sufficient to increase stroke
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375 volume and restore end organ perfusion. Sodium nitroprusside is an arterial
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376 vasodilator that is commonly employed in this setting. Close attention must be
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377 paid to the dose and duration of this therapy, as cyanide toxicity can develop
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378 after prolonged use and develops morefrequently with renal dysfunction. Serum
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379 thiocyanate levels should be measured and drug dosing adjusted to avoid toxicity.
380 Due to the narrow therapeutic index and pharmacy and nursing complexities of
381 using this drug, some institutions favor the use of intravenous nitroglycerin.
382 Because nitroglycerine is primarily a venodilator, it has the added hemodynamic
383 benefit of reducing ventricular pre-load.

384 Inotropic agents (also referred to as inodilators because of arterial
385 vasodilator effects) are commonly necessary to increase CO. Dobutamine is a
386 beta-1 and beta-2 agonist that increases myocardial contractility. Milrinone is
387 phosphodiesterase 3 inhibitor that increases cardiac inotropy indirectly, by
388 inhibiting the breakdown of cyclic AMP, without activating the beta receptors.
389 Dobutamine has a short onset of action and half-life, with effects of dose changes
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390 readily apparent in about 30 minutes. In contrast maximal effects following
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391 milrinone titration may take up to 4 hours Because milrinone activity is not
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392 dependent on the beta receptor, fewer arrhythmia, better efficacy in beta blocker
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393 treated patients, and less increase in myocardial oxygen demand has been
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394 hypothesized. Milrinone is also thought to cause vasodilation and hypotension,

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395 especially in patients with significant renal impairment. Despite these proposed
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396 differences, the recent, single-center DOREMI trial found no differences in CS
397 patients treated with dobutamine versus milrinone.44 In patients with
398 predominant hypotension, epinephrine which activates both the alpha and beta
399 receptors (thus increasing blood pressure and inotropy) may be useful. Another
400 strategy is treatment with norepinephrine which also activates both the alpha and
401 beta receptor alone or in combination dobutamine or milrinone. In a subset

402 analysis of the SOAP trial, dopamine was associated with worse outcomes in CS
403 and use of dopamine is now discouraged.45
404 Intravenous diuretics that inhibit sodium reabsorption in the loop of Henle
405 are the first line agents to induce fluid removal and normalize cardiac filling
406 pressures and total body volume overload. The patient response to loop diuretics
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407 therapy does not depend on the choice of drug bolus versus continuous infusion
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408 strategies.46 More important than diuretic administration method is frequent
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reassessment of patient response, ensuring that fluid removal targets are met.
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410 Rapid intensification with high doses of loop diuretics and the addition of thiazide
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411 diuretics may be required to achieve adequate diuresis. Use of adjunctive agents
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412 such as tolvapatan in patients with hyponatremia or acetazolamide in patients

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with elevated bicarbonate may also be considered.47 For patients in whom fluid
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413
414 removal targets cannot be achieved despite maximal diuretic therapy, mechanical
415 fluid removal with ultrafiltration or hemodialysis should be considered.48
416 Re-initiation of guideline directed medical therapy (GDMT) should be
417 considered as soon as possible in the treatment of CS. In selected patients with
418 adequate renal function, captopril, which is also short acting, may be initiated and
419 later converted to an angiotensin receptor blocker to facilitate transition to

420 sacubitril/valsartan . Because beta blockers can precipitate CS, it is prudent to
421 withholdbeta blocker treatment until euvolemia has been achieved and inotropes
422 have been discontinued for at least 48 hours, an approach that is known to be
423 safe following AMI.49 Patients should be monitored closely for recurrence of CS
424 after inotropes are discontinued and during titration of GDMT.50
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425
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426 Mechanical circulatory support
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Patients with non-AMICS in the setting of progressive heart failure tolerate
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428 relative hypotension better than patients with AMI-CS.4 Therefore, decisions
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429 regarding the need for or escalation of temporary mechanical circulatory support
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430 (tMCS) largely depend on the degree of congestion and hypoperfusion. Early
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431 invasive hemodynamic profiling aids in shock phenotyping and enables improved
432 recognition of shock severity. An initial trial of diuresis, vasodilator and/or
433 inotropic therapy in patients demonstrating evidence of hypoperfusion and low
434 cardiac index <2.2L/min/m2 is common in non-AMICS, however, in patients with
435 persistent hypotension and/or worsening end-organ function as evidenced by
436 increasing lactate levels, worsening renal or liver function, escalation to tMCS
437 should be considered.

438 Appropriate patient selection in non-AMICS typically requires an extensive
439 assessment of clinical, hemodynamic, laboratory and imaging data. Currently
440 there are no adequate risk prediction models in the non-AMICS population to
441 inform tMCS decisions, as most of the prior validation studies have been
442 performed in patients with AMI CS.51 Furthermore, patients that have been
443 deemed candidates or at least potential candidates for HRT are also typically
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444 considered appropriate candidates for tMCS. With this in mind, there remains
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445 wide variation in the overall use of tMCS devices among patients with non-AMI
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446 CS.52 Clinicians currently select devices likely to provide a significant
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447 hemodynamic response in patients with more severe presentations of shock,

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448 however, the specific thresholds for doing so in the heart failure population are
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449 highly variable. (Table 2)

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450
451 Intra-aortic balloon pump
452 Intra-aortic balloon pumps (IABP) are balloon mounted catheters that use
453 helium to inflate a balloon positioned in the descending aorta during diastole,
454 augmenting central aortic diastolic pressure and improving coronary perfusion.
455 Physiologically, the IABP provides only a minimal increase in CO in patients with
456 AMI CS (Table 2). Further, the use of IABP in AMI CS has failed to show a
457 reduction in mortality in randomized control trials.53 However, in patients with
458 non-AMI CS, IABP use has been associated with improved outcomes as a bridge to
459 heart transplantation or durable left ventricular assist device.54 The use of IABP in
460 the United States and Europe declined over the past decade, largely due to the
461 absence of improved clinical outcomes in randomized controlled trials.55
462 However, despite these trends, data from recent contemporary registries have
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463 identified the IABP as the most commonly utilized tMCS platform in patients with
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464 non-AMI CS.2 The use of percutaneous axillary cannulation for IABP placement
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465 has also increased during this time period, allowing for patients with CS awaiting
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466 heart transplant to rehabilitate. Further studies are needed to understand the
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467 role of the IABP in the non-AMI CS population.56

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468
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469 Impella
470 Transvalvular continuous micro-axial flow pumps known as Impella devices
471 (Abiomed, Inc) have been used with increasing frequency in CS patients.57 These
472 pumps can be placed percutaneously (2.5, CP) or by surgical cutdown (5.0, 5.5)
473 using the femoral or axillary artery (Table 2). The devices are positioned such that
474 the pump inlet sits within the left ventricle while the catheter crosses the aortic
475 valve in retrograde fashion. The outlet resides in the ascending aorta and
476 augments systemic perfusion while simultaneously unloading the left ventricle. By
477 aspirating blood from the LV and ejecting it into the aorta, the Impella device
478 unloads the ventricle, reduces ventricular end-diastolic pressure, increases blood
479 pressure, and decreases myocardial oxygen consumption. The evidence for
480 efficacy of these devices has been limited to small randomized controlled trials,
481 primarily in patients with AMI CS. Cumulatively, the data suggest that Impellas
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482 improve hemodynamics without overall improvements in survival.58 Importantly,
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483 there have been no head-head comparisons of IABP versus Impella in patients
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484 with non-AMI CS. Hemodynamic phenotyping helps guide device selection in
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485 patients with non-AMI CS, such that recognizing the degree of LV or RV
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486 involvement, severity of shock and/or the presence of concomitant vascular

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487 disease may dictate which device is utilized.

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488
489 Veno-arterial Extracorporeal Membrane Oxygenation (VA-ECMO)
490 The percutaneous venoarterial configuration of ECMO can provide both
491 rapid oxygenation and hemodynamic support. VA-ECMO withdraws
492 deoxygenated venous blood and returns oxygenated blood to the systemic
493 arterial circulation. The most common percutaneous configuration includes a
494 withdrawal cannula placed in the femoral vein and advanced to the superior vena
495 cava-right atrial junction. Subsequently a return cannula is placed into the femoral
496 artery to provide retrograde perfusion of the systemic circulation.
497 VA-ECMO provides robust biventricular support in patients with severe
498 refractory CS. It can provide between 4 L/min and 6 L/min of flow, but notably
499 increases systemic afterload and thereby will increase LV end-diastolic pressure
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500 (Table 2). The impact of increased afterload on the LV may further depress native
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501 cardiac output and potentiate a persistent congested state necessitating the
502
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addition of an LV venting strategy. This is usually employed by placing an IABP or
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503 Impella device to facilitate unloading while on VA-ECMO.59
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504 To date, the data for use of VA-ECMO in patients with CS is limited. ECMO
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505 as a bridge to HRT has been evaluated in a few registries and single center
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506 studies. Its use has been associated with increased mortality when compared to
507 IABP or other temporary MCS strategies.60
508 TandemHeart
509 The TandemHeart system (LivaNova, Inc) functions as an extracorporeal
510 continuous centrifugal flow pump that unloads the left ventricle by draining blood
511 from the left atrium via trans-septal approach and subsequently pumping it
512 directly into the femoral artery analogous to a VA-ECMO circuit. Placement of the
513 device requires interventional cardiology operators skilled in transseptal puncture
514 and large-bore access to insert the system under fluoroscopic and/or
515 echocardiographic guidance. Hemodynamically it increases cardiac output and
516 mean arterial pressure, decreases left ventricular filling pressures by venting the
517 left atrium and can provide up to 5.0 L/min of flow (Table 2). It has been studied
518 in two very small randomized trials where it demonstrated improvement in
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519 hemodynamic and metabolic parameters (higher cardiac power index and lower
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520 pulmonary capillary wedge pressure) but more complications (ie, severe bleeding
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521 and limb ischemia) when compared to the IABP, with no improvement in overall
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522 survival.61 It is often used in the setting of non-AMI CS when there are active
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523 contraindications to use of other more readily available devices such as in the
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524 presence of LV thrombus or significant aortic regurgitation.

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525
526 Organization and delivery of critical care to cardiogenic shock patients
527 Multidisciplinary care of patients with MCS among CICU physicians,
528 including heart failure cardiologists, critical care, interventional cardiologists and
529 cardiac surgeons is critical. Multidisciplinary team care is known to improve
530 outcomes and reduce complications of ICU care and recommendations for the
531 organization and management of the multidisciplinary team have been

532 reported62, 63. Key determinants of morbidity and mortality in the ICU include
533 early recognition and management of limb ischemia and bleeding associated with
534 MCS. With the increasing use of large bore access to facilitate placement of
535 temporary MCS devices, knowledge of safe vascular access techniques such as
536 ultrasound and fluoroscopic guidance, micropuncture needle access, initial and
537 completion femoral access angiography, placement of distal perfusion catheters,
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538 pre-closure technique of arteriotomy and venotomy access sites, and the
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539 institution of continuous neurovascular evaluation in the CICU can help mitigate
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540 complications.64 Monitoring of anticoagulation status via aPTT, ACT and/or anti-Xa
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541 levels helps prevent pump thrombosis for patients on Impella or VA-ECMO. This
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542 risk must be weighed against the concomitant risk of bleeding associated with
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543 large bore MCS strategies. Standardized protocols to minimize complications in

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544 the CICU should be instituted to maintain safety while patients are being
545 managed with tMC.6 Infectious complications from MCS are typically related to
546 the location of access and duration of support rather than device specific causes.
547 Initiation of antibiotic therapy should be assessed clinically and the data to guide
548 prophylactic initiation of antibiotics is limited to subsets of patients at increased
549 risk, such as open chest central VA-ECMO patients.65 An important consideration
550 for patients undergoing tMCS in no-AMI CS is access site location. Increased
551 utilization of axillary site cannulation, either via percutaneous or surgical cutdown
552 has facilitated the potential for early mobilization of patients in the ICU. Often
553 patients in CS are restricted to bedrest, which can further exacerbate baseline
554 deconditioning and weakness associated with critical illness. ICU patients that
555 receive early rehabilitation have demonstrated decreased rates of delirium,66
556 shorter duration of mechanical ventilation, improved rates of returning to
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557 baseline functional status and decreased ICU length of stay.67 Use of axillary artery
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558 cannulation has allowed for earlier patient mobility and the potential for
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559 rehabilitation for patients that may require prolonged duration of hemodynamic
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560 support. 68
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562 De-escalation of temporary mechanical circulatory support

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563 Daily evaluation to determine readiness to wean from tMCS is necessary for
564 patients in non-AMI CS. Assessment of readiness for de-escalation of tMCS occurs
565 when hemodynamic stability, normalization of end-organ function, correction of
566 acidemia, improvement in pulmonary edema, and net negative fluid balance have
567 been achieved. Reduction in vasopressor and inotropic support to minimal
568 requirements can also help facilitate weaning of tMCS. Multiple weaning
569 algorithms have been proposed although there are currently no agreed upon
570 strategies for patients with non-AMI CS.69 Assessment using clinical examination,
571 invasive hemodynamics, echocardiographic parameters, and laboratory tests can
572 guide weaning decisions (Table 3). These criteria should be assessed prior to
573 weaning and during repeat serial assessments as tMCS is weaned. It is important
574 to employ consistent terminology tailored to individual devices when preparing
575 for device de-escalation and explantation. These include assessment for
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576 ‘readiness-to-wean’, weaning trials and ‘readiness-to-explant’. Equally
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577 importantly, the ‘what if’ strategies should be pre-determined prior to device
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578 weaning and explantation based on the long-term planning for the patient, in the
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579 event the patient deteriorates. Involving palliative care and supportive services
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580 early on is critical to optimal patient management in such circumstances. Future

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581 research is needed to better understand optimal timing and implementation of

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582 standardized protocols to achieve successful tMCS weaning and explant.
583
584 MCS Knowledge Gaps
585 Currently, much of the evidence derived for management of patients in CS
586 have been extrapolated from studies in patients with AMI CS. There remains a
587 paucity of randomized trials to address use of tMCS in patients with non-AMI CS
588 specifically, and especially in patients with CS due to progressive heart failure. Our
589 current understanding of device utilization and outcomes is assessed from real-
590 word registry data and there is an increased need for dedicated trials in this
591 space.2
592
593 Management of non-cardiac organ dysfunction
594
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595 Heightened interest in the field of critical care cardiology comes in part
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596 from increased recognition that CS is frequently complicated by concurrent non-
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597 cardiac multi-organ failure, and that these non-cardiac issues are significant
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598 drivers of patient morbidity and mortality.70-73 Several position papers have
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599 outlined potential management recommendations for non-cardiac organ failure in

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600 CS, including sedation management, respiratory failure, renal failure, and
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601 infections; however, these are largely adapted from the general critical care
602 medicine literature and their application to CS based on expert opinion. 1, 62, 74
603 Though a comprehensive review of non-cardiac management of multi-organ
604 failure in CS is beyond the scope of this review, it is important to recognize several
605 pearls.
606 Pain, agitation, and delirium are commonplace in ICUs and likely amongst
607 CS patients. 62, 75 The general critical care medicine literature supports a
608 standardized approach to pain and agitation management, utilizing bundled care
609 (such as the ABCEDF bundle) as well as assessment tools that can be utilized both
610 by verbal and nonverbal patients.75 It must be remembered that hypnotic
611 sedatives such as benzodiazepines and propofol do not provide analgesia, and as
612 such they must be co-administered with analgesics such as opiates, especially in
613 intubated patients. There are also notable hemodynamic implications for some of
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614 the commonly used sedative agents. In addition to the hypotension that nearly all
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615 sedatives induce, both propofol and dexmedetomidine cause significant negative
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616 inotropy and dexmedetomidine causes significant bradycardia.62, 76 Though these
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617 effects are theoretically worth avoiding in CS, numerous trials have demonstrated
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618 the relative safety of these agents even amongst patients with significant cardiac
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619 dysfunction in the post cardiotomy setting.77, 78 Regardless of the sedation

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620 regimen used, sedation should be limited as possible to aide in early extubation,
621 mobilization, and avoidance of delirium.
622 Respiratory failure and mechanical ventilation are commonplace in the
623 CICU with the former having been recently described as the top reason for CICU
624 admission.34, 79 Despite this high burden of disease, the complication rate of
625 mechanical ventilation in CICUs is unknown and the ideal ventilatory strategy in
626 CS specifically has not been established. With this in mind, CS patients are likely at
627 risk of lung injury akin to other critically ill patients and it may be preferable to
628 adhere to traditional protective ventilatory strategies, including application of
629 sufficient positive end-expiratory pressure, limiting excessive tidal volumes (goal
630 8cc/kg in non-acute respiratory distress syndrome patients), and avoidance of
631 excess transpulmonary pressure (plateau pressure < 30 cm H20).80 However,
632 these goals must be balanced with the competing priorities of avoiding patient-
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633 ventilator dyssynchrony and excess sedation, and thus it may be more
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634 appropriate to allow ventilatory leniency in CS patients who demonstrate normal
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635 lung compliance.62, 81 Finally, there are pathophysiologic effects of positive
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636 pressure ventilation (e.g. decreased venous return, increased RV afterload, and
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637 decreased LV afterload) that may have clinical implications in CS patients. At this
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638 point however, they remain pathophysiologic guiding principles without backing
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639 in observational or randomized trials.
640 Like respiratory failure, acute kidney injury (AKI) is common in CS and is
641 associated with worse clinical outcomes.82 Also similar, there are no clear CS
642 specific guidelines for management of AKI, and much is adapted from general
643 critical care literature. Notably, ICU trials have demonstrated no benefit to early
644 initiation or higher doses of renal replacement therapy (RRT) as compared to
645 delayed and lower dose therapy. Indeed, many patients in the delayed RRT arm
646 never ended up requiring RRT at all.83, 84 Though these trials have included a high
647 proportion of patients on vasoactive medications and having received iodinated
648 contrast dye, the proportion of primary cardiac patients is small. Further, these
649 results are not clearly applicable to CS, where volume removal may be key to
650 improved cardiac function and resolution of shock. In this setting, earlier RRT in
651 diuretic refractory patients may be appropriate, and randomized trials in this
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652 population are needed. This notion is supported by a body of literature
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653 demonstrating improved outcomes with early RRT initiation post cardiothoracic
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654 surgery patients.85
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655 Heart replacement therapy

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656 Heart transplantation and LVAD remain the gold standard therapy for
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657 patients with non-AMI CS who fail to recover sufficient cardiac function or
658 vasomotor tone to be removed from tMCS and inotropes. In conjunction with a
659 rising incidence of non-AMI CS over the last decade,86 the proportion of
660 transplant and LVAD recipients with a history of non-ischemic cardiomyopathy
661 has been increasing, as has the proportion of patients undergoing these therapies
662 who are in advanced shock.87, 88
663 Certain features may suggest transplant versus LVAD as the preferred
664 strategy, and vice versa. Typically, transplant is the preferred therapy for most
665 patients given longer anticipated survival.89, 90 However, LVAD durability and
666 survival free of pump thrombosis have improved considerably in recent years
667 since the commercial release of the HeartMate 3 LVAD,91 and the median survival
668 post-LVAD may continue to improve as existing patients push this boundary
669 further out. That said, advanced age, prohibitive allosensitization, irreversible
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670 severe pulmonary hypertension, or an excess burden of comorbidities may limit
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671 post-transplant survival and restrict access to this option. Conversely, the
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672 presence of severe right-ventricular dysfunction or need for kidney replacement
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673 therapy may impede outcomes after LVAD and favor heart (or multiorgan)
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674 transplant.
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675 When LVAD is used in non-AMI CS, it may be considered as a bridge to
676 transplantation, a bridge to decision about transplantation, or a destination
677 therapy when transplant is not an option. In addition, LVAD may be used as a
678 bridge to recovery when temporary support options are incompatible with a
679 sufficient duration of support. After implant, optimized LVAD mechanical
680 unloading coupled with a standardized pharmacologic regimen of neurohormonal
681 blockade improves the probability of recovery, as seen in RESTAGE-HF where 40%
682 of a select group of patients underwent LVAD explant with sustained remission
683 from HF at 12 months.92 Moreover, young patients with non-AMI CS and a short
684 duration of HF < 2 years may particularly benefit from a recovery strategy,93 so
685 there may be cases where an LVAD-first strategy is preferred in order to delay or
686 obviate the need for eventual transplant
687 Conclusion
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688 Despite decades of research and numerous technological advancements,
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689 outcomes for patients with non-AMI CS remain poor. New approaches to
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phenotyping and classifying CS may facilitate better matching of patients with
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691 currently available and the developement of future therapies. Additionally,
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692 randomized clinical trials are needed to determine how to use available
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693 treatments for non-AMI CS, as the large majority of trials have only included
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694 patients with AMI. A growing body of evidence supports management of CS
695 patients using collaborative, team-based approaches to care, such as with
696 cardiogenic shock teams. This is likely especially true in non-AMI CS, where
697 patients tend to have a pre-existing relationship with heart failure cardiologists
698 and may eventually require heart replacement therapies.
699
700 Table 1 . Characteristics of cardiac intensive care units according to level.
Level 1 • Leadership by a critical care cardiologist, high intensity
staffing
• Management of all cardiac conditions
• STEMI coverage 24/7, cardiac surgery available
• Capability for PAC
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• Capability for advanced MCS including VA-ECMO and durable
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• Capable of providing all ICU therapies such as mechanical
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ventilation, renal replacement therapy, and therapeutic

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Level 2 • Management of most cardiovascular conditions

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• Capability to manage STEMI
• Capability for IABP
• Transfers to level 1 center if patient needs exceed capabilities
Level 3 • Initial diagnosis and management of common cardiac
conditions
• Basic cardiac imaging

• Transfers to level 2 or 3 centers when patient needs exceed
capabilities
701 Abbreviations: STEMI, ST elevation myocardial infarction; PAC, pulmonary artery catheter; MCS, mechanical
702 circulatory support; VA-ECMO, venoarterial extracorporeal membrane oxygenation; LVAD, left ventricular assist
703 device; IABP, intra-aortic balloon pump.
704 Adapted from Rab, T., et al. (2018). "Cardiac Shock Care Centers: JACC Review Topic of the Week." J Am Coll
705 Cardiol 72(16): 1972-1980.
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706
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707 Table 2. Temporary Mechanical Circulatory Support Devices
Device IABP
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Impella (2.5, CP, TandemHeart/ VA-ECMO
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RP, 5.0, 5.5) Protek Duo
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Flow 0.5-1L/min 1.5-5L/min 4-6L/min 4-6L/min
Mechanism Pneumatic Micro-axial flow Centrifugal Flow Centrifugal

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Cannula Size 7-8Fr 12-23 Fr 15 - 19 Fr outflow 15 - 19 Fr inflow

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21-29 Fr inflow 21 - 29 Fr outflow
Insertion Percutaneous Percutaneous or Percutaneous Percutaneous or

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Surgical Surgical
Femoral or Femoral or
axillary axillary
Duration of use 7-10 days 7-21 days 14-21 days 21-28 days
(device
dependent)
Ventricle Support LV LV and/or RV LV or RV LV and RV
Pros Easy insertion Multiple Highest cardiac Biventricular

platforms to output generation support
Minimal choose
vascular Highest cardiac
complications output
Cons Minimal Hemolysis Vascular Vascular

improvement compromise compromise
in cardiac Vascular
output in compromise Device migration
acute MI shock
Need for
transseptal
puncture for LV
support
Contraindications Severe aortic Severe aortic Severe aortic Severe aortic

regurgitation regurgitation regurgitation regurgitation
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Aortic Left ventricular Severe PVD Severe PVD
dissection thrombus
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AAA Mechanical
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aortic valve
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Severe PVD Severe PVD
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708 Abbreviations: IABP, intra-aortic balloon pump; VA-ECMO, venoarterial extracorporeal membrane
709 oxygenation; LV, left ventricle; RV, right ventricle; AAA, abdominal aortic aneurysm; PVD, peripheral
710 vascular disease.
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711 Table 3: Suggested goals for weaning support in patients with non-acute
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myocardial infarction cardiogenic shock.

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712
Hemodynamic Metabolic Imaging variables
variables parameters
Central venous pressure Lactic acid < 2 mg/dL Left ventricular ejection fraction
(CVP) <12, Pulmonary (LVEF) > 25%*
artery pulsatility index
(PAPI) > 2
Pulmonary artery wedge Liver enzymes, Left ventricular outflow tract
pressure (PAWP) < 18 normalizing and/or velocity time integral (LVOT VTI) >
mmHg downtrending 15 cm
Cardiac index > 2.2 Renal function - Resolution/improvement of
improving valvular dysfunction
1 vasopressor or 1 Resolution of cardiac ischemia
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713 Abbreviations: CVP, central venous pressure; PAPI, pulmonary arterty pulsatility index; LVEF, left
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714 ventricular ejection fraction; PAWP, pulmonary artery wedge pressure; LVOT VTI, Left ventricular
715 outflow tract velocity time integral.

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716 *In patients with an LVEF <25% at baseline, goal should be to at least improve LVEF to baseline
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717 functioning
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719 Figure legends
720 Figure 1: Pathophysiology of non-myocardial infarction cardiogenic shock. Non-
721 myocardial infarction cardiogenic shock (non-AMI CS) can be precipitated by
722 multiple potential triggers; however, the end result is a common final pathway.
723 Reduced cardiac output, vasoconstriction and volume overload precipitate
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724 inflammation and end organ ischemia, including cardiac ischemia (without
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725 coronary obstruction), which further reduces cardiac output. This represents a
726
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progressive spiral that if not interrupted leads to patient death.
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727 Figure 2: Phenotyping cardiogenic shock. In an approach to phenotyping

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728 cardiogenic shock similar to that utilized to describe classic acute decompensated
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729 heart failure, this 2x2 table incorporates volume status (congestion) and the
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730 status of patients’ systemic vascular resistance. However, unlike the traditional
731 table, patients in all four quadrants are hypoperfused.
732 Figure 3: Pressure-volume loops in acute vs chronic non-myocardial infarction
733 cardiogenic shock. In progressive heart failure leading to cardiogenic shock (red
734 line), the left ventricle has typically remodeled, and stroke volume is relatively
735 preserved compared to normal (blue line), despite operating at higher volumes
736 and pressures. In acute or de-novo cardiogenic shock (yellow line), left ventricular
737 pressures rise quickly without adaptive ventricular dilation, leading to a severely
738 reduced stroke volume akin to that in acute myocardial infarction.
739 Figure 4: Society for Cardiovascular Angiography and Intervention classification

740 of cardiogenic shock. A) The Society for Cardiovascular Angiography and
741 Intervention (SCAI) shock classification provides a framework to approach
742 patients with cardiogenic shock (CS) and predicts CS outcomes. B) With the
743 exception of catastrophic events such as cardiac arrest, all patients will CS at least
744 transiently have stage C shock, with stage D reserved for those who fail to
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745 respond to therapy (medical or device). Adapted with permission from: Naidu, S. S.,
746 et al. (2022). "SCAI SHOCK Stage Classification Expert Consensus Update: A Review and Incorporation of
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747 Validation Studies: This statement was endorsed by the American College of Cardiology (ACC), American
748 College of Emergency Physicians (ACEP), American Heart Association (AHA), European Society of
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749 Cardiology (ESC) Association for Acute Cardiovascular Care (ACVC), International Society for Heart and
750 Lung Transplantation (ISHLT), Society of Critical Care Medicine (SCCM), and Society of Thoracic Surgeons
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751 (STS) in December 2021." J Am Coll Cardiol 79(9): 933-946.
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752
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753 Figure 5. Models of cardiogenic shock care. A multidisciplinary team approach to

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754 cardiogenic shock care is recommended. This includes transfer of patients to

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755 hospitals with a full range of mechanical circulatory support and heart
756 replacement capabilities, multidisciplinary evaluation and management by
757 cardiogenic shock teams, as well as collaboration with palliative care services. The
758 goal of multidisciplinary care is to facilitate early recognition of cardiogenic shock,
759 provide rapid risk assessment, and implement therapies to restore perfusion and
760 interrupt the ischemic spiral.

761
762
763 1. Chioncel O, Parissis J, Mebazaa A, et al. Epidemiology, pathophysiology and

764 contemporary management of cardiogenic shock - a position statement from the Heart
765 Failure Association of the European Society of Cardiology. Eur J Heart Fail.
766 2020;22:1315-1341.
767 2. Hernandez-Montfort J, Sinha SS, Thayer KL, et al. Clinical Outcomes Associated With
768 Acute Mechanical Circulatory Support Utilization in Heart Failure Related Cardiogenic
769 Shock. Circ Heart Fail. 2021;14:e007924.
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770 3. Bhatt AS, Berg DD, Bohula EA, et al. De Novo vs Acute-on-Chronic Presentations of
771 Heart Failure-Related Cardiogenic Shock: Insights from the Critical Care Cardiology
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772 Trials Network Registry. J Card Fail. 2021;27:1073-1081.
773 4. Abraham J, Blumer V, Burkhoff D, et al. Heart Failure-Related Cardiogenic Shock:
774
775 -p
Pathophysiology, Evaluation and Management Considerations: Review of Heart Failure-
Related Cardiogenic Shock. J Card Fail. 2021;27:1126-1140.
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776 5. Sinha SS, Rosner CM, Tehrani BN, et al. Cardiogenic Shock From Heart Failure Versus
777 Acute Myocardial Infarction: Clinical Characteristics, Hospital Course, and 1-Year
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778 Outcomes. Circ Heart Fail. 2022;15:e009279.

779 6. Tehrani BN, Truesdell AG, Psotka MA, et al. A Standardized and Comprehensive
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780 Approach to the Management of Cardiogenic Shock. JACC Heart Fail. 2020;8:879-891.
781 7. van Diepen S, Katz JN, Albert NM, et al. Contemporary Management of Cardiogenic
782 Shock: A Scientific Statement From the American Heart Association. Circulation.
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783 2017;136:e232-e268.
784 8. Vahdatpour C, Collins D, Goldberg S. Cardiogenic Shock. J Am Heart Assoc.
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785 2019;8:e011991.
786 9. Prondzinsky R, Unverzagt S, Lemm H, et al. Interleukin-6, -7, -8 and -10 predict outcome
787 in acute myocardial infarction complicated by cardiogenic shock. Clin Res Cardiol.
788 2012;101:375-384.
789 10. Hochman JS. Cardiogenic shock complicating acute myocardial infarction: expanding the
790 paradigm. Circulation. 2003;107:2998-3002.
791 11. Jentzer JC, Lawler PR, van Diepen S, et al. Systemic Inflammatory Response Syndrome
792 Is Associated With Increased Mortality Across the Spectrum of Shock Severity in Cardiac
793 Intensive Care Patients. Circ Cardiovasc Qual Outcomes. 2020;13:e006956.
794 12. Bastos MB, Burkhoff D, Maly J, et al. Invasive left ventricle pressure-volume analysis:
795 overview and practical clinical implications. Eur Heart J. 2020;41:1286-1297.
796 13. Brener MI, Rosenblum HR, Burkhoff D. Pathophysiology and Advanced Hemodynamic
797 Assessment of Cardiogenic Shock. Methodist Debakey Cardiovasc J. 2020;16:7-15.
798 14. Belkin MN, Shah J, Neyestanak ME, Burkhoff D, Grinstein J. Should We Be Using Aortic
799 Pulsatility Index Over Cardiac Power Output in Heart Failure Cardiogenic Shock? Circ
800 Heart Fail. 2022;15:e009601.
801 15. Belkin MN, Alenghat FJ, Besser SA, et al. Aortic pulsatility index predicts clinical
802 outcomes in heart failure: a sub-analysis of the ESCAPE trial. ESC Heart Fail.
803 2021;8:1522-1530.
804 16. Zweck E, Thayer KL, Helgestad OKL, et al. Phenotyping Cardiogenic Shock. J Am Heart
805 Assoc. 2021;10:e020085.
806 17. Jentzer JC, Soussi S, Lawler PR, Kennedy JN, Kashani KB. Validation of cardiogenic
807 shock phenotypes in a mixed cardiac intensive care unit population. Catheter Cardiovasc
808 Interv. 2022;99:1006-1014.
809 18. Baran DA, Grines CL, Bailey S, et al. SCAI clinical expert consensus statement on the
810 classification of cardiogenic shock: This document was endorsed by the American College
811 of Cardiology (ACC), the American Heart Association (AHA), the Society of Critical Care
812 Medicine (SCCM), and the Society of Thoracic Surgeons (STS) in April 2019. Catheter
813 Cardiovasc Interv. 2019;94:29-37.
814 19. Kapur NK, Kanwar M, Sinha SS, et al. Criteria for Defining Stages of Cardiogenic Shock
of
815 Severity. J Am Coll Cardiol. 2022;80:185-198.
816 20. Jentzer JC, van Diepen S, Barsness GW, et al. Cardiogenic Shock Classification to Predict
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817 Mortality in the Cardiac Intensive Care Unit. J Am Coll Cardiol. 2019;74:2117-2128.
818 21. Jentzer JC, Baran DA, van Diepen S, et al. Admission Society for Cardiovascular
819
820 -p
Angiography and Intervention shock stage stratifies post-discharge mortality risk in cardiac
intensive care unit patients. Am Heart J. 2020;219:37-46.
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821 22. Naidu SS, Baran DA, Jentzer JC, et al. SCAI SHOCK Stage Classification Expert
822 Consensus Update: A Review and Incorporation of Validation Studies: This statement was
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823 endorsed by the American College of Cardiology (ACC), American College of Emergency
824 Physicians (ACEP), American Heart Association (AHA), European Society of Cardiology
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825 (ESC) Association for Acute Cardiovascular Care (ACVC), International Society for Heart
826 and Lung Transplantation (ISHLT), Society of Critical Care Medicine (SCCM), and
827 Society of Thoracic Surgeons (STS) in December 2021. J Am Coll Cardiol. 2022;79:933-
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828 946.
829 23. Jentzer JC, Burstein B, Van Diepen S, et al. Defining Shock and Preshock for Mortality
Jo
830 Risk Stratification in Cardiac Intensive Care Unit Patients. Circ Heart Fail.
831 2021;14:e007678.
832 24. Mann DL. Innate immunity and the failing heart: the cytokine hypothesis revisited. Circ
833 Res. 2015;116:1254-1268.
834 25. Uhley HN, Leeds SE, Sampson JJ, Friedman M. Role of pulmonary lymphatics in chronic
835 pulmonary edema. Circ Res. 1962;11:966-970.
836 26. Fudim M, Salah HM, Sathananthan J, et al. Lymphatic Dysregulation in Patients
837 With Heart Failure: JACC Review Topic of the Week. J Am Coll Cardiol. 2021;78:66-76.
838 27. Thayer KL, Zweck E, Ayouty M, et al. Invasive Hemodynamic Assessment and
839 Classification of In-Hospital Mortality Risk Among Patients With Cardiogenic Shock. Circ
840 Heart Fail. 2020;13:e007099.
841 28. Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA Guideline for the
842 Management of Heart Failure: Executive Summary: A Report of the American College of
843 Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.
844 Circulation. 2022;145:e876-e894.
845 29. Blanco P. Rationale for using the velocity-time integral and the minute distance for
846 assessing the stroke volume and cardiac output in point-of-care settings. Ultrasound J.
847 2020;12:21.
848 30. Cooper LT, Baughman KL, Feldman AM, et al. The role of endomyocardial biopsy in the
849 management of cardiovascular disease: a scientific statement from the American Heart
850 Association, the American College of Cardiology, and the European Society of Cardiology.
851 Endorsed by the Heart Failure Society of America and the Heart Failure Association of the
852 European Society of Cardiology. J Am Coll Cardiol. 2007;50:1914-1931.
853 31. Taleb I, Koliopoulou AG, Tandar A, et al. Shock Team Approach in Refractory
854 Cardiogenic Shock Requiring Short-Term Mechanical Circulatory Support: A Proof of
855 Concept. Circulation. 2019;140:98-100.
856 32. Moghaddam N, van Diepen S, So D, Lawler PR, Fordyce CB. Cardiogenic shock teams
857 and centres: a contemporary review of multidisciplinary care for cardiogenic shock. ESC
858 Heart Fail. 2021;8:988-998.
of
859 33. Morrow DA, Fang JC, Fintel DJ, et al. Evolution of critical care cardiology: transformation
860 of the cardiovascular intensive care unit and the emerging need for new medical staffing
ro
861 and training models: a scientific statement from the American Heart Association.
862 Circulation. 2012;126:1408-1428.
863
864
34.
-p
Bohula EA, Katz JN, van Diepen S, et al. Demographics, Care Patterns, and Outcomes of
Patients Admitted to Cardiac Intensive Care Units: The Critical Care Cardiology Trials
re
865 Network Prospective North American Multicenter Registry of Cardiac Critical Illness.
866 JAMA Cardiol. 2019;4:928-935.
lP
867 35. Sims DB, Kim Y, Kalininskiy A, et al. Full-Time Cardiac Intensive Care Unit Staffing by
868 Heart Failure Specialists and its Association with Mortality Rates. J Card Fail.
na
869 2022;28:394-402.
870 36. Carnicelli AP, Blumer V, Genovese L, et al. The Road Not Yet Traveled: Distinction in
871 Critical Care Cardiology through the Advanced Heart Failure and Transplant Cardiology
ur
872 Training Pathway. J Card Fail. 2022;28:339-342.

873 37. Patarroyo Aponte MM, Manrique C, Kar B. Systems of Care in Cardiogenic Shock.
Jo
874 Methodist Debakey Cardiovasc J. 2020;16:50-56.

875 38. Lawler PR, Mehra MR. Advancing from a "hemodynamic model" to a "mechanistic
876 disease-modifying model" of cardiogenic shock. J Heart Lung Transplant. 2018;37:1285-
877 1288.
878 39. Esposito ML, Kapur NK. Acute mechanical circulatory support for cardiogenic shock: the
879 "door to support" time. F1000Res. 2017;6:737.
880 40. Papolos AI, Kenigsberg BB, Berg DD, et al. Management and Outcomes of Cardiogenic
881 Shock in Cardiac ICUs With Versus Without Shock Teams. J Am Coll Cardiol.
882 2021;78:1309-1317.
883 41. Baran DA, Long A, Jentzer JC. The Stages of CS: Clinical and Translational Update. Curr
884 Heart Fail Rep. 2020;17:333-340.
885 42. Mathew R, Fernando SM, Hu K, et al. Optimal Perfusion Targets in Cardiogenic Shock.
886 JACC: Advances. 2022;1:1-14.
887 43. Ranka S, Mastoris I, Kapur NK, et al. Right Heart Catheterization in Cardiogenic Shock Is
888 Associated With Improved Outcomes: Insights From the Nationwide Readmissions
889 Database. J Am Heart Assoc. 2021;10:e019843.
890 44. Mathew R, Di Santo P, Jung RG, et al. Milrinone as Compared with Dobutamine in the
891 Treatment of Cardiogenic Shock. N Engl J Med. 2021;385:516-525.
892 45. De Backer D, Biston P, Devriendt J, et al. Comparison of dopamine and norepinephrine in
893 the treatment of shock. N Engl J Med. 2010;362:779-789.
894 46. Felker GM, Lee KL, Bull DA, et al. Diuretic strategies in patients with acute
895 decompensated heart failure. N Engl J Med. 2011;364:797-805.
896 47. Cox ZL, Hung R, Lenihan DJ, Testani JM. Diuretic Strategies for Loop Diuretic Resistance
897 in Acute Heart Failure: The 3T Trial. JACC Heart Fail. 2020;8:157-168.
898 48. Verbrugge FH. Editor's Choice-Diuretic resistance in acute heart failure. Eur Heart J Acute
899 Cardiovasc Care. 2018;7:379-389.
900 49. Bahit MC, Kochar A, Granger CB. Post-Myocardial Infarction Heart Failure. JACC Heart
901 Fail. 2018;6:179-186.
902 50. Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA Guideline for the
903 Management of Heart Failure: A Report of the American College of Cardiology/American
of
904 Heart Association Joint Committee on Clinical Practice Guidelines. Circulation.
905 2022;145:e895-e1032.
ro
906 51. Kalra S, Ranard LS, Memon S, et al. Risk Prediction in Cardiogenic Shock: Current State
907 of Knowledge, Challenges and Opportunities. J Card Fail. 2021;27:1099-1110.
908
909
52.
-p
Berg DD, Barnett CF, Kenigsberg BB, et al. Clinical Practice Patterns in Temporary
Mechanical Circulatory Support for Shock in the Critical Care Cardiology Trials Network
re
910 (CCCTN) Registry. Circ Heart Fail. 2019;12:e006635.
911 53. Thiele H, Zeymer U, Thelemann N, et al. Intraaortic Balloon Pump in Cardiogenic Shock
lP
912 Complicating Acute Myocardial Infarction: Long-Term 6-Year Outcome of the

913 Randomized IABP-SHOCK II Trial. Circulation. 2019;139:395-403.
na
914 54. Huckaby LV, Seese LM, Mathier MA, Hickey GW, Kilic A. Intra-Aortic Balloon Pump
915 Bridging to Heart Transplantation: Impact of the 2018 Allocation Change. Circ Heart Fail.
916 2020;13:e006971.
ur
917 55. Strom JB, Zhao Y, Shen C, et al. National trends, predictors of use, and in-hospital
918 outcomes in mechanical circulatory support for cardiogenic shock. EuroIntervention.
Jo
919 2018;13:e2152-e2159.
920 56. Morici N, Oliva F, Ajello S, et al. Management of cardiogenic shock in acute
921 decompensated chronic heart failure: The ALTSHOCK phase II clinical trial. Am Heart J.
922 2018;204:196-201.
923 57. Stretch R, Sauer CM, Yuh DD, Bonde P. National trends in the utilization of short-term
924 mechanical circulatory support: incidence, outcomes, and cost analysis. J Am Coll Cardiol.
925 2014;64:1407-1415.
926 58. Ouweneel DM, Eriksen E, Sjauw KD, et al. Percutaneous Mechanical Circulatory Support
927 Versus Intra-Aortic Balloon Pump in Cardiogenic Shock After Acute Myocardial
928 Infarction. J Am Coll Cardiol. 2017;69:278-287.
929 59. Guglin M, Zucker MJ, Bazan VM, et al. Venoarterial ECMO for Adults: JACC Scientific
930 Expert Panel. J Am Coll Cardiol. 2019;73:698-716.
931 60. Hernandez-Montfort JA, Xie R, Ton VK, et al. Longitudinal impact of temporary
932 mechanical circulatory support on durable ventricular assist device outcomes: An IMACS
933 registry propensity matched analysis. J Heart Lung Transplant. 2020;39:145-156.
934 61. Burkhoff D, Cohen H, Brunckhorst C, O'Neill WW. A randomized multicenter clinical
935 study to evaluate the safety and efficacy of the TandemHeart percutaneous ventricular
936 assist device versus conventional therapy with intraaortic balloon pumping for treatment
937 of cardiogenic shock. Am Heart J. 2006;152:469.e461-468.
938 62. Fordyce CB, Katz JN, Alviar CL, et al. Prevention of Complications in the Cardiac
939 Intensive Care Unit: A Scientific Statement From the American Heart Association.
940 Circulation. 2020;142:e379-e406.
941 63. Kim MM, Barnato AE, Angus DC, Fleisher LA, Kahn JM. The effect of multidisciplinary
942 care teams on intensive care unit mortality. Arch Intern Med. 2010;170:369-376.
943 64. Sandoval Y, Burke MN, Lobo AS, et al. Contemporary Arterial Access in the Cardiac
944 Catheterization Laboratory. JACC Cardiovasc Interv. 2017;10:2233-2241.
945 65. O'Horo JC, Cawcutt KA, De Moraes AG, Sampathkumar P, Schears GJ. The Evidence
946 Base for Prophylactic Antibiotics in Patients Receiving Extracorporeal Membrane
947 Oxygenation. Asaio j. 2016;62:6-10.
948 66. Burtin C, Clerckx B, Robbeets C, et al. Early exercise in critically ill patients enhances
949 short-term functional recovery. Crit Care Med. 2009;37:2499-2505.
of
950 67. Schweickert WD, Pohlman MC, Pohlman AS, et al. Early physical and occupational
951 therapy in mechanically ventilated, critically ill patients: a randomised controlled trial.
ro
952 Lancet. 2009;373:1874-1882.
953 68. Bhimaraj A, Agrawal T, Duran A, et al. Percutaneous Left Axillary Artery Placement of
954
955 -p
Intra-Aortic Balloon Pump in Advanced Heart Failure Patients. JACC Heart Fail.
2020;8:313-323.
re
956 69. Randhawa VK, Al-Fares A, Tong MZY, et al. A Pragmatic Approach to
957 Weaning Temporary Mechanical Circulatory Support: A State-of-the-Art Review. JACC
lP
958 Heart Fail. 2021;9:664-673.

959 70. Sinha SS, Sjoding MW, Sukul D, et al. Changes in Primary Noncardiac Diagnoses Over
na
960 Time Among Elderly Cardiac Intensive Care Unit Patients in the United States. Circ
961 Cardiovasc Qual Outcomes. 2017;10:e003616.
962 71. Holland EM, Moss TJ. Acute Noncardiovascular Illness in the Cardiac Intensive Care Unit.
ur
963 J Am Coll Cardiol. 2017;69:1999-2007.

964 72. Miller PE, Van Diepen S, Metkus TS, et al. Association between Respiratory Failure and
Jo
965 Clinical Outcomes in Patients with Acute Heart Failure: Analysis of 5 Pooled Clinical
966 Trials. J Card Fail. 2021;27:602-606.
967 73. Miller PE, Thomas A, Breen TJ, et al. Prevalence of Noncardiac Multimorbidity in Patients
968 Admitted to Two Cardiac Intensive Care Units and Their Association with Mortality. Am
969 J Med. 2021;134:653-661.e655.
970 74. van Diepen S, Katz JN, Albert NM, et al. Contemporary Management of Cardiogenic
971 Shock: A Scientific Statement From the American Heart Association. Circulation.
972 2017;136:e232-e268.
973 75. Devlin JW, Skrobik Y, Gélinas C, et al. Clinical Practice Guidelines for the Prevention and
974 Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in
975 Adult Patients in the ICU. Crit Care Med. 2018;46:e825-e873.
976 76. Zakaria S, Kwong HJ, Sevransky JE, Williams MS, Chandra-Strobos N. Editor's Choice-
977 The cardiovascular implications of sedatives in the cardiac intensive care unit. Eur Heart
978 J Acute Cardiovasc Care. 2018;7:671-683.
979 77. Liu X, Xie G, Zhang K, et al. Dexmedetomidine vs propofol sedation reduces delirium in
980 patients after cardiac surgery: A meta-analysis with trial sequential analysis of randomized
981 controlled trials. J Crit Care. 2017;38:190-196.
982 78. Liu H, Ji F, Peng K, Applegate RL, 2nd, Fleming N. Sedation After Cardiac Surgery: Is
983 One Drug Better Than Another? Anesth Analg. 2017;124:1061-1070.
984 79. Metkus TS, Miller PE, Alviar CL, et al. Advanced Respiratory Support in the
985 Contemporary Cardiac ICU. Crit Care Explor. 2020;2:e0182.
986 80. Goligher EC, Dres M, Patel BK, et al. Lung- and Diaphragm-Protective Ventilation. Am J
987 Respir Crit Care Med. 2020;202:950-961.
988 81. Alviar CL, Miller PE, McAreavey D, et al. Positive Pressure Ventilation in the Cardiac
989 Intensive Care Unit. J Am Coll Cardiol. 2018;72:1532-1553.
990 82. Jentzer JC, Bihorac A, Brusca SB, et al. Contemporary Management of Severe Acute
991 Kidney Injury and Refractory Cardiorenal Syndrome: JACC Council Perspectives. J Am
992 Coll Cardiol. 2020;76:1084-1101.
993 83. Gaudry S, Hajage D, Benichou N, et al. Delayed versus early initiation of renal replacement
994 therapy for severe acute kidney injury: a systematic review and individual patient data
995 meta-analysis of randomised clinical trials. Lancet. 2020;395:1506-1515.
of
996 84. Bagshaw SM, Wald R, Adhikari NKJ, et al. Timing of Initiation of Renal-Replacement
997 Therapy in Acute Kidney Injury. N Engl J Med. 2020;383:240-251.
ro
998 85. Zou H, Hong Q, Xu G. Early versus late initiation of renal replacement therapy impacts
999 mortality in patients with acute kidney injury post cardiac surgery: a meta-analysis. Crit
1000
1001 86.
Care. 2017;21:150.
-p
Osman M, Syed M, Patibandla S, et al. Fifteen-Year Trends in Incidence of Cardiogenic
re
1002 Shock Hospitalization and In-Hospital Mortality in the United States. J Am Heart Assoc.
1003 2021;10:e021061.
lP
1004 87. Colvin M, Smith JM, Ahn Y, et al. OPTN/SRTR 2020 Annual Data Report: Heart. Am J
1005 Transplant. 2022;22 Suppl 2:350-437.
na
1006 88. Shah P, Yuzefpolskaya M, Hickey GW, et al. Twelfth Interagency Registry for
1007 Mechanically Assisted Circulatory Support Report: Readmissions After Left Ventricular
1008 Assist Device. Ann Thorac Surg. 2022;113:722-737.
ur
1009 89. Lala A, Rowland JC, Ferket BS, et al. Strategies of Wait-listing for Heart Transplant vs
1010 Durable Mechanical Circulatory Support Alone for Patients With Advanced Heart Failure.
Jo
1011 JAMA Cardiol. 2020;5:652-659.

1012 90. Brescia AA, Watt TMF, Pagani FD, et al. Assessment of Mortality Among Durable Left
1013 Ventricular Assist Device Recipients Ineligible for Clinical Trials. JAMA Netw Open.
1014 2021;4:e2032865.
1015 91. Mehra MR, Uriel N, Naka Y, et al. A Fully Magnetically Levitated Left Ventricular Assist
1016 Device - Final Report. N Engl J Med. 2019;380:1618-1627.
1017 92. Birks EJ, Drakos SG, Patel SR, et al. Prospective Multicenter Study of Myocardial
1018 Recovery Using Left Ventricular Assist Devices (RESTAGE-HF [Remission from Stage
1019 D Heart Failure]): Medium-Term and Primary End Point Results. Circulation.
1020 2020;142:2016-2028.
1021 93. Wever-Pinzon O, Drakos SG, McKellar SH, et al. Cardiac Recovery During Long-Term
1022 Left Ventricular Assist Device Support. J Am Coll Cardiol. 2016;68:1540-1553.
1023
Cardiogenic Shock Pathophysiology: The Ischemic Spiral
Figure 1
Precipitating Cause of Cardiogenic Shock
Chronic cardiomyopathy progression
Arrhythmia
Valvular heart disease
Pericardial disease
Myocarditis
f
roo
-p
Reduced cardiac output
re
Hypotension
Vasoconstriction
lP
na
ur
Jo
Congestion
End organ hypoperfusion and ischemia
Systemic inflammation
Myocardial ischemia
Death
Figure 2
Congestion
Volume overloaded Euvolemic/Volume down
(Wet) (Dry)
Systemic Vascular Resistance (SVR)
Elevated SVR
(Cold)
Classic Cardiogenic Euvolemic
f
oo
Shock Cardiogenic Shock
r
-p
re
lP
na
Low/Normal SVR
ur
Jo
(Warm)
Mixed Shock Distributive Shock

Figure 3
Normal
Chronic HF
Left Ventricular Pressure
Acute HF
f
oo r
-p
re
lP
na
ur
Jo
Left Ventricular Volume
Figure 4
B
A
Jo
ur
na
lP
re
-p
r oo
f
Figure 5
Cardiogenic Shock Models of Care
Transfer Protocol Multidisciplinary CICU Care
f
oo
Shock Team Palliative Care
r
-p
re
lP
na
Medical
Management
ur
Goals of
Early Recognition Risk Assessment
Jo
Treatment
Device
Management
Contemporary Management
Management of Cardiogenic Shock Not due to Acute Myocardial Infarction
Non-AMI CS AMI CS
f
r oo
-p
Acute on chronic Importance of: Acute only
re
-Bi-V failure more common -LV >> RV
lP
-Early diagnosis
-Ventricles remodeled, dilated -Ventricles not remodeled
na
-Hemodynamics
-Diverse etiologies -Only ACS
ur
-SCAI shock stages
-Role for inflammation? -Inflammation pivotal
Jo
-Multi-D decisions
-Lower mortality in registries -Non-cardiac organ -Higher mortality in registries
failure
-Few tMCS randomized trials -Many tMCS randomized trials
-Palliative care
-More likely to receive HRT -Less likely to receive HRT
Abbreviations: Bi-V, biventricular; tMCS, temporary mechanical circulatory support; HRT, heart replacement therapy; LV, left
ventricle; RV, right ventricle; ACS, acute coronary syndrome.

Management of Cardiogenic Shock Unrelated To Acute Myocardial Infarction

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Management of Cardiogenic Shock Unrelated to Acute Myocardial Infarction

Christopher F. Barnett, MD, MPH, Samuel B. Brusca, MD, Thomas C. Hanff, MD

To appear in: Canadian Journal of Cardiology

Received Date: 19 November 2022

© 2023 Published by Elsevier Inc. on behalf of the Canadian Cardiovascular Society.

38 Cardiogenic shock is an extreme manifestation of acute decompensated heart

41 incidence and recognition of cardiogenic shock not associated with acute

42 myocardial infarction (non-AMI CS) as a distinct entity. Despite decades of study

46 physiology to a growing list of available interventions. Further study is needed to

47 determine whether these efforts will lead to more nuanced utilization of

48 mechanical circulatory support and improved patient outcomes, especially in non-

49 AMI CS. In the meantime, models of care incorporating multidisciplinary decision

53 Cardiogenic shock (CS) is an extreme manifestation of acute

54 decompensated heart failure (ADHF), with an in-hospital mortality rate of 30%-

62 AMI CS as distinct CS phenotypes, including their differing presentations,

63 responses to therapy, and clinical outcomes.2, 3 At a fundamental level, the

64 clinical deterioration of patients with AMI-CS begins with hypotension, which

65 leads to hypoperfusion and congestion. In contrast, patients with non-AMI CS

66 commonly present with ADHF and congestion, leading to hypoperfusion and

67 hypotension.4 Epidemiologically, patients with non-AMI CS experience lower in-

70 is increasingly recognized that the traditional definitions and hemodynamic

74 individualization based on the underlying physiology.6

75 In this review, we describe the pathophysiology, epidemiology, and

76 management of non-AMI CS. We also characterize contemporary models of CS

80 Pathophysiology of non-AMI cardiogenic shock

81 The differential diagnosis in non-AMI CS is broad and includes progression

82 of chronic cardiomyopathy, malignant arrhythmias, valvular heart disease,

83 inflammatory myocarditis, and pericardial diseases.7 These conditions share the

86 pathophysiologies. Recognition of the precipitating factors involved in CS is of the

87 utmost importance, as rapid intervention (e.g. appropriate structural

88 interventions for acute decompensated valve disorders) may stem irrecoverable

90 All CS conditions share a common final pathway: the “ischemic spiral.”

92 cascade of downstream sequalae, leading to hypotension, maladaptive

93 vasoconstriction, elevated cardiac chamber filling pressures, cardiac ischemia,

94 end-organ congestion and hypoperfusion, and ultimately multi-organ failure and

95 death.7, 8 These elements synergize in a negative feedback loop, worsening

102 by inducing a “mixed shock phenotype.” Though the inflammatory component of

105 broad range of CS patients. 11

107 Phenotyping Cardiogenic Shock

109 The simplest framework for phenotyping CS is an extension of that used to

123 accommodate increased ventricular volume. LV compliance is reduced and the

124 ventricular end-diastolic pressure-volume relationship increased, yet the ventricle

127 shifted up and to the right and is characterized hemodynamically by decreased

129 setting of progressive dilated cardiomyopathy or chronic regurgitant valvular

137 Finally, though these traditional methods of phenotyping are clinically

145 hemodynamic derangements, primarily left sided congestion and out of

146 proportion renal dysfunction is present. Finally, cardiometabolic CS is

147 characterized by more pronounced hypotension and tachycardia, more right

151 underpinnings of these phenotypes as well as why patients develop one

152 phenotype as opposed to the others remains to be determined.

156 pressures along with hypotension, tissue hypoperfusion, or a combination of

157 hypotension and hypoperfusion. Hypoperfusion is correlated with reduced CO,

162 Society for Cardiovascular Angiography and Interventions (SCAI) CS classification

169 medications or devices to achieve clinical stability.

175 Patients were characterized as having hypotension, hypoperfusion (defined

178 exhibit higher mortality compared to either isolated hypotension (P=0.15) or

179 combined hypoperfusion and hypotension (P=0.33). Thus, the presence of

180 isolated hypoperfusion may be more prognostically meaningful in AMI CS than

184 prevalent (and potentially less morbid) in the non-AMI CS population.

185 The acute on chronic presentation of non-AMI CS frequently occurs in the

186 background of chronic multisystem changes to peripheral vascular function,

187 altered lymphatic system compliance, greater exposure to neurohormonal