Cardiogenic Shock Classification to Predict Mortality in the Cardiac Intensive Care Unit

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

VOL.

-, NO. -, 2019

ª 2019 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION PUBLISHED BY ELSEVIER

Cardiogenic Shock Classification to Predict Mortality in the Cardiac Intensive Care Unit Jacob C. Jentzer, MD,a,b Sean van Diepen, MD, MSC,c Gregory W. Barsness, MD,a Timothy D. Henry, MD,d Venu Menon, MD,e Charanjit S. Rihal, MD, MBA,a Srihari S. Naidu, MD,f David A. Baran, MDg

ABSTRACT BACKGROUND A new 5-stage cardiogenic shock (CS) classification scheme was recently proposed by the Society for Cardiovascular Angiography and Intervention (SCAI) for the purpose of risk stratification. OBJECTIVES This study sought to apply the SCAI shock classification in a cardiac intensive care unit (CICU) population. METHODS The study retrospectively analyzed Mayo Clinic CICU patients admitted between 2007 and 2015. SCAI CS stages A through E were classified retrospectively using CICU admission data based on the presence of hypotension or tachycardia, hypoperfusion, deterioration, and refractory shock. Hospital mortality in each SCAI shock stage was stratified by cardiac arrest (CA). RESULTS Among the 10,004 unique patients, 43.1% had acute coronary syndrome, 46.1% had heart failure, and 12.1% had CA. The proportion of patients in SCAI CS stages A through E was 46.0%, 30.0%, 15.7%, 7.3%, and 1.0% and unadjusted hospital mortality in these stages was 3.0%, 7.1%, 12.4%, 40.4%, and 67.0% (p < 0.001), respectively. After multivariable adjustment, each higher SCAI shock stage was associated with increased hospital mortality (adjusted odds ratio: 1.53 to 6.80; all p < 0.001) compared with SCAI shock stage A, as was CA (adjusted odds ratio: 3.99; 95% confidence interval: 3.27 to 4.86; p < 0.001). Results were consistent in the subset of patients with acute coronary syndrome or heart failure. CONCLUSIONS When assessed at the time of CICU admission, the SCAI CS classification, including presence or absence of CA, provided robust hospital mortality risk stratification. This classification system could be implemented as a clinical and research tool to identify, communicate, and predict the risk of death in patients with, and at risk for, CS. (J Am Coll Cardiol 2019;-:-–-) © 2019 by the American College of Cardiology Foundation.

C

ardiogenic shock (CS) continues to be associ-

revascularization for patients with acute myocardial

ated with high rates of morbidity and

infarction (MI), no other intervention has demon-

mortality, posing a therapeutic challenge

strated an improvement in short-term survival among

for clinicians (1–4). Although the mortality among pa-

patients with CS, and no established beneficial thera-

tients with

time,

pies exist for patients with non-MI etiologies of CS

short-term mortality rates remain 35% to 40% in

(1,5–9). A recent scientific statement from the Amer-

recent studies (1–9). Other

ican Heart Association highlighted several potential

CS

may

be

decreasing

over

than culprit vessel

From the aDepartment of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota; bDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota; cDepartment of Critical Care Medicine and Division of Cardiology, Department of Medicine, University of Alberta Hospital, Edmonton, Alberta, Canada; dCarl and Edyth Lindner Center for Research and Education, Christ Hospital Health Network, Cincinnati, Ohio; eDepartment of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio; fWestchester Heart and Vascular Institute, Westchester Medical Center and New York Medical College, Valhalla, New York; and the gSentara Heart Hospital, Advanced Heart Failure Center and Eastern Virginia Medical School, Norfolk, Virginia. Dr. Baran has served as a consultant for Abiomed, Abbott, Getinge, and LivaNova; and has served as a speaker for Novartis. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Manuscript received May 22, 2019; revised manuscript received July 5, 2019, accepted July 7, 2019.

ISSN 0735-1097/$36.00

https://doi.org/10.1016/j.jacc.2019.07.077

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Jentzer et al.

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ABBREVIATIONS

priorities for the future of CS research, to

AND ACRONYMS

address the limited therapeutic options and uncertainty about the efficacy of standard

ACS = acute coronary

Although diagnostic criteria for CS have

AKI = acute kidney injury APACHE = Acute Physiology and Chronic Health Evaluation

been clearly defined in the literature, a major

Presence of any of the following criteria:
Admission systolic BP <90 mm Hg
Minimum systolic BP <90 mm Hg during first 1h
Admission MAP <60 mm Hg
Minimum MAP <60 mm Hg during first 1 h
Admission HR >100 beats/min
Maximum HR >100 beats/min during first 1 h
Admission HR > admission systolic BP
Mean HR > mean systolic BP during first 1 h

Hypoperfusion

Presence of any of the following criteria:
Admission lactate >2 mmol/l
Urine output <720 ml during first 24 h
Creatinine increased by $0.3 mg/dl during first 24 h

Deterioration

Presence of any of the following criteria:
Maximum lactate > admission lactate
Number of vasoactives during first 24 h > number of vasoactives during first 1 h
Maximum VIS during first 24 h > VIS during first 1 h
Maximum NEE during first 24 h > NEE during first 1 h

gap in the field of CS research has been the characterize

CA = cardiac arrest CCI = Charlson Comorbidity Index

CICU = cardiac intensive care

severity across

research

protocols and individual centers (1). CS populations encompass a broad spectrum of hemodynamic

CI = confidence interval

CS

derangement

ranging

from

isolated hypoperfusion that is easily reversed

unit

with initial therapies to refractory shock with

CS = cardiogenic shock

multiorgan

failure

and

hemodynamic

collapse (1). Patients with differing degrees of

ECMO = extracorporeal membrane oxygenation

shock severity may have varying respon-

HF = heart failure

siveness to therapeutic interventions and

MCS = mechanical circulatory

different clinical outcomes, yet they are

support

considered the same for the purposes of

MI = myocardial infarction

clinical trial and registry enrollment, leading

OR = odds ratio

to substantial heterogeneity in CS study

SCAI = Society for

populations. Multiple risk scores exist to

Cardiovascular Angiography

predict mortality in patients with CS, but

and Intervention

these apply primarily to CS complicating

VIS = vasoactive-inotropic

acute MI and the need for multiple input

Definition

Hypotension/ tachycardia

lack of a standard schema to uniformly

BP = blood pressure

score

T A B L E 1 Study Definitions of Hypotension, Tachycardia,

Hypoperfusion, Deterioration, and Refractory Shock Term

treatment modalities in CS (1).

syndrome

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Shock Classification Stratifies Mortality Risk

Refractory shock Presence of any of the following criteria:
Mean systolic BP during first 1 h <80 and on vasoactives
Mean systolic MAP during first 1 h <50 and on vasoactives
Number of vasoactives during first 1 h >2
Number of vasoactives during first 1 h >1 and IABP during first 24 h
Admission lactate $10 mmol/l

variables reduces their clinical applicability (10,11). Although these scores can provide mortality risk stratification, they fail to provide meaningful characterization of the severity of CS in a way that can be easily communicated between providers and inform treatment and transfer decisions. Prior studies have failed to determine the effects that overall

VIS is calculated as using vasoactive drug doses (in mg/kg/min), as follows: VIS ¼ dobutamine þ dopamine þ (10 * phenylephrine þ milrinone) þ (100 * [epinephrine þ norepinephrine]) þ (10,000 * units/kg/min vasopressin). NEE is calculated using the dose equivalency as follows: 0.1 mg/kg/min norepinephrine ¼ 0.1 mg/kg/min epinephrine ¼ 15 mg/kg/min dopamine ¼ 1 mg/kg/ min phenylephrine ¼ 0.04 U/min vasopressin. BP ¼ blood pressure; HR ¼ heart rate; IABP ¼ intra-aortic balloon pump; MAP ¼ mean arterial pressure; NEE ¼ norepinephrine-equivalent vasopressor dose; VIS ¼ vasoactive-inotropic score.

illness severity may have on the risk-benefit profile of available therapeutic interventions (7–11). To overcome these limitations, the Society for Cardiovascular Angiography and Intervention (SCAI) developed an expert consensus statement, endorsed by multiple relevant societies, proposing a novel CS

admission to predict mortality in unselected CICU patients.

METHODS

classification scheme, which categorizes patients with or at risk of CS into worsening stages of hemo-

STUDY

dynamic compromise for the purposes of facilitating

Board of the Mayo Clinic (IRB # 16-000722) approved

POPULATION. The

Institutional

Review

patient care and research (12). The SCAI CS classifi-

the study as posing minimal risk to patients, and it

cation consensus statement describes 5 stages of CS,

was performed under a waiver of informed consent.

each of which may have an “A” modifier signifying

We analyzed a database of consecutive unique adult

the occurrence of cardiac arrest (CA) (12). This clas-

patients $18 years of age admitted to the CICU at

sification schema was developed based on expert

Mayo Clinic Hospital St. Mary’s Campus between

consensus opinion and its ability to discriminate

January 1, 2007, and December 31, 2015 (13–15). The

among levels of mortality risk in critically ill patients

Mayo Clinic CICU is a closed, 16-bed unit serving

remains to be established. The goal of this study was

critically ill cardiac medical patients. Post-operative

to examine the construct validity of the SCAI CS

cardiac surgery patients and patients receiving

staging schema by demonstrating the ability of a

extracorporeal membrane oxygenation (ECMO) sup-

simple functional classification of SCAI shock stages

port are cared for in a separate cardiovascular surgical

at the time of cardiac intensive care unit (CICU)

intensive care unit. To minimize the risk of survival

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Shock Classification Stratifies Mortality Risk

C ENTR AL I LL U STRA T I O N Definitions of Society for Cardiovascular Angiography and Intervention Shock Stages A Through E, With Associated Cardiac Intensive Care Unit and Hospital Mortality in Each Society for Cardiovascular Angiography and Intervention Shock Stage

Study Definition

70 %

%

Hypoperfusion WITH deterioration AND refractory shock

60

Stage E (”Extremis“)

%

Hypoperfusion WITH deterioration NOT refractory shock

50

Stage D (”Deteriorating)”

%

Hypoperfusion WITHOUT deterioration

40

Stage C (”Classic”)

30 %

Hypotension/tachycardia WITHOUT hypoperfusion

%

Stage B (”Beginning”)

20

Neither hypotension/tachycardia nor hypoperfusion

0%

Stage A (”At risk”)

%

Observed Mortality in Overall Cohort

10

Cardiogenic Shock Stage

Cardiac Intensive Care Unit Mortality Hospital Mortality Jentzer, J.C. et al. J Am Coll Cardiol. 2019;-(-):-–-.

Cardiac intensive care unit and hospital mortality increased as a function of higher Society for Cardiovascular Angiography and Intervention shock stage.

and treatment biases associated with CICU read-

examination data were not available (13–15). All rele-

mission, only data from each patient’s first CICU

vant data were extracted electronically from the

admission were analyzed. According to Minnesota

medical record using the Multidisciplinary Epidemi-

state law statute 144.295, patients may decline

ology and Translational Research in Intensive Care

authorization for inclusion in observational research

Data Mart, a repository storing clinical data from all

studies; patients who declined Minnesota Research

intensive care unit admissions at the Mayo Clinic

Authorization were excluded from the study.

Rochester (16). The admission value of all vital signs, clinical measurements, and laboratory values was

DATA SOURCES. We recorded demographic, vital

defined as either the first value recorded after CICU

sign, laboratory, clinical, and outcome data, as well

admission or the value recorded closest to CICU

as procedures and therapies performed during the

admission. In addition, vital signs were recorded

CICU and hospital stay, as previously described;

every 15 min during the first hour after CICU admis-

radiographic, invasive hemodynamic, and physical

sion. Peak vasoactive medication (vasopressor and

T A B L E 2 Definition of CS Stages Used in this Study, Based on the SCAI Consensus Statement Classification

CS Stage

SCAI Definition

Stage A (“at risk”)

Patients without CS who are hemodynamically stable but have acute cardiovascular disease putting them at risk of developing CS

Stage B (“beginning”)

Patients without CS who display hemodynamic instability, including hypotension and/or tachycardia, but with normal perfusion

Stage C (“classic”)

Patients with CS, manifested by hypoperfusion (lactic acidosis, oliguria, cool/clammy periphery, or altered mentation) requiring intervention

Stage D (“deteriorating)”

Patients with CS whose hemodynamic instability and/or hypoperfusion fails to respond to initial interventions

Stage E (“extremis”)

Patients with CS and overt or impending circulatory collapse, including CA with ongoing resuscitation

Adapted with permission from Baran et al. (12). CA ¼ cardiac arrest; CS ¼ cardiogenic shock; SCAI ¼ Society for Cardiovascular Angiography and Intervention.

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Shock Classification Stratifies Mortality Risk

F I G U R E 1 Study Inclusion and Exclusion Criteria and Distribution of SCAI Shock Stages

All CICU admissions between January 1, 2007 and April 30, 2018 (n = 12,904)

Excluded 2,900 admissions: • 1,877 readmissions • 755 no research authorization • 268 admitted outside the study period Final study population (n = 10,004)

Stage A (n = 4,602)

Stage B (n = 2,998)

Stage C (n = 1,575)

Stage D (n = 732)

Stage E (n = 97)

The final study population included 10,004 unique patients. CICU ¼ cardiac intensive care unit; SCAI ¼ Society for Cardiovascular Angiography and Intervention.

inotrope) doses were used to calculate the vasoactive-

creatinine from baseline, increase in serum creatinine

inotropic score and norepinephrine-equivalent vaso-

to $4.0 mg/dl, or new dialysis initiation; patients with

pressor dose (17–19). Admission diagnoses included

a prior history of dialysis were excluded from this

all

analysis (14).

International

Classification

of

Diseases-9th

Revision diagnostic codes recorded on the day of CICU admission and the day before or after CICU

DEFINITION OF SHOCK STAGES. We defined hypo-

admission; these admission diagnoses were not

tension or tachycardia, hypoperfusion, deterioration,

mutually exclusive, and the primary admission diag-

and refractory shock using data from CICU admission

nosis could not be determined. Admission diagnoses

through the first 24 h in the CICU (Table 1). Hypo-

syndrome

tension and tachycardia were defined within the first

(ACS), heart failure (HF), supraventricular tachy-

1 h of CICU admission. The definition of hypo-

of

interest

included

acute

fibrillation,

perfusion included an elevated lactate level on

respiratory

admission or AKI developing within 24 h after

The Acute Physiology and Chronic Health Evalua-

vasoactive drug requirements after the first hour or a

tion (APACHE)-III score, APACHE-IV predicted hospital

rising lactate level after admission. We used prag-

mortality, and Sequential Organ Failure Assessment

matic and simplified definitions to divide patients

score were automatically calculated for all patients

into the 5 SCAI shock stages with increasing severity

using data from the first 24 h of CICU admission using

(A through E) using combinations of these variables

previously

(Central Illustration). Importantly, the SCAI shock

cardia,

atrial

ventricular

fibrillation,

coronary

tachycardia,

ventricular shock,

CA,

failure, and sepsis.

validated

admission. Deterioration was defined as increasing

electronic

algorithms,

with

missing variables imputed as normal as the default

classification system (Table 2) involves details such as

(13–15,20–22). The Charlson Comorbidity Index (CCI)

rapid escalation of inotropes or addition of temporary

and individual comorbidities were determined from

mechanical circulatory support (MCS) devices, which

the medical record using a previously validated elec-

were not available in the database (12) Late deterio-

tronic algorithm (23). Severe acute kidney injury (AKI)

ration was defined as increasing vasopressor re-

during the CICU stay was defined as doubling of serum

quirements after 24 h.

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Shock Classification Stratifies Mortality Risk

T A B L E 3 Baseline Characteristics, Comorbidities, Admission Diagnoses, and Therapies of Patients According to SCAI Shock Stage

With Data, %

Stage A (n ¼ 4,602)

Stage B (n ¼ 2,998)

Stage C (n ¼ 1,575)

Stage D (n ¼ 732)

Stage E (n ¼ 97)

p Value

Demographics Age, yrs

100.0

67.1  14.7

66.4  15.7

69.9  16.0

68.7  14.1

68.3  14.7

<0.001

Female

100.0

1,562 (33.9)

1,216 (40.6)

654 (41.5)

278 (38.0)

36 (37.1)

<0.001

White

100.0

4,289 (93.2)

2,779 (92.7)

1,430 (90.8)

659 (90.0)

79 (81.4)

<0.001 <0.001

Comorbidities Charlson Comorbidity Index

99.8

2.1  2.5

2.5  2.6

2.8  2.8

3.0  2.8

2.1  2.6

History of MI

99.8

914 (19.9)

581 (19.4)

311 (19.8)

160 (21.9)

14 (14.4)

0.79

History of HF

99.8

746 (16.2)

638 (21.3)

339 (21.6)

212 (29.0)

18 (18.6)

<0.001

History of diabetes mellitus

99.8

1,222 (26.6)

851 (28.5)

483 (30.8)

257 (35.2)

24 (24.7)

<0.001

History of CKD

99.8

770 (16.8)

604 (20.2)

418 (26.6)

221 (30.2)

18 (20.4)

<0.001

Prior dialysis

100.0

131 (2.8)

130 (4.3)

192 (12.2)

107 (14.6)

11 (11.3)

<0.001

Admission ICD-9 diagnoses* ACS

99.0

2,111 (46.4)

1,172 (39.4)

634 (40.7)

300 (41.3)

50 (52.6)

<0.001

HF

99.0

1,675 (36.8)

1,562 (52.5)

758 (48.7)

513 (70.7)

56 (59.0)

<0.001

Cardiac arrest

99.0

330 (7.3)

311 (10.5)

219 (14.1)

280 (38.6)

53 (55.8)

<0.001

Shock

99.0

217 (4.8)

449 (15.1)

166 (10.7)

429 (59.1)

88 (92.6)

<0.001

Respiratory failure

99.0

506 (11.1)

660 (22.2)

389 (25.0)

460 (63.4)

64 (67.4)

<0.001

Sepsis

99.0

102 (2.2)

205 (6.9)

100 (6.4)

163 (22.4)

35 (36.8)

<0.001

AF/SVT

99.0

1,165 (25.6)

1,150 (38.7)

571 (36.7)

304 (41.9)

30 (31.6)

<0.001

VT/VF

99.0

665 (14.6)

516 (17.4)

247 (15.9)

158 (21.8)

22 (23.2)

<0.001

Therapies and procedures Vasoactives first 1 h

100.0

126 (2.7)

339 (11.3)

90 (5.7)

249 (34.0)

81 (83.5)

<0.001

Number of vasoactives first 1 h

100.0

0.0  0.2

0.1  0.4

0.1  0.3

0.4  0.6

1.4  1.0

<0.001

VIS first 1 h

99.1

0.2  1.6

1.3  10.5

1.4  12.1

5.4  15.3

30.1  46.7

<0.001

NEE first 1 h

100.0

0.00  0.01

0.01  0.10

0.01  0.12

0.05  0.15

0.29  0.47

<0.001

Invasive ventilator first 24 h

100.0

257 (5.6)

419 (14.0)

232 (14.7)

417 (57.0)

73 (75.3)

<0.001

Dialysis

100.0

119 (2.6)

138 (4.6)

72 (4.6)

137 (18.7)

21 (21.6)

<0.001

CRRT

100.0

9 (0.2)

30 (1.0)

23 (1.5)

94 (12.8)

11 (11.3)

<0.001

IABP during hospitalization

100.0

266 (5.8)

330 (11.0)

69 (4.4)

162 (22.1)

38 (39.2)

<0.001

Impella

100.0

5 (0.1)

7 (0.2)

4 (0.2)

3 (0.4)

2 (2.1)

0.004

ECMO

100.0

15 (0.3)

28 (0.9)

8 (0.5)

16 (2.2)

5 (5.2)

0.02

PAC

100.0

239 (5.2)

245 (8.2)

49 (3.1)

163 (22.3)

25 (25.8)

<0.001

Coronary angiogram

100.0

2,694 (58.5)

1,471 (49.1)

720 (45.7)

349 (47.7)

50 (51.6)

<0.001

PCI

100.0

1,834 (39.8)

932 (31.1)

430 (27.3)

205 (28.0)

26 (26.8)

<0.001

RBC transfusion

100.0

308 (6.7)

403 (13.4)

197 (12.5)

228 (31.2)

37 (28.1)

<0.001

Values are mean  SD or n (%), unless otherwise indicated. The p value is for the trend across SCAI shock stages A to E. *Admission diagnoses are not mutually exclusive and sum to >100%. ACS ¼ acute coronary syndrome; AF ¼ atrial fibrillation; CICU ¼ cardiac intensive care unit; CKD ¼ chronic kidney disease; CRRT ¼ continuous renal-replacement therapy; ECMO ¼ extracorporeal membrane oxygenation; HF ¼ heart failure; ICD-9 ¼ International Classification of Diseases-9th Revision; MI ¼ myocardial infarction; PAC ¼ pulmonary artery catheter; PCI ¼ percutaneous coronary intervention; RBC ¼ red blood cell; SVT ¼ supraventricular tachycardia; VF ¼ ventricular fibrillation; VT ¼ ventricular tachycardia; other abbreviations as in Tables 1 and 2.

STATISTICAL ANALYSIS. The primary endpoint was

medications, intra-aortic balloon pump, coronary

all-cause hospital mortality; secondary endpoints

angiography, percutaneous coronary intervention,

included CICU mortality. Hospital disposition and all-

and

cause mortality were determined using electronic re-

assessed using the area under the receiver-operating

view of medical records. Categorical variables are re-

characteristic curve (C-statistic) value. Two-tailed

mechanical

ventilation.

Discrimination

was

ported as number and percentage and the Pearson chi-

p values <0.05 were considered statistically signifi-

square test was used to compare groups. Continuous

cant. Statistical analyses were performed using JMP

variables are reported as mean  SD. Trends across the

Pro version 14.1.0 (SAS Institute, Cary, North Carolina).

SCAI shock stages were determined using linear regression. Logistic regression was used to determine

RESULTS

the association between the SCAI shock stages and hospital mortality before and after adjusting for age,

STUDY POPULATION. We screened 12,904 adult ad-

sex, CCI, APACHE-IV predicted hospital mortality,

missions to the CICU during the study period and

admission diagnosis of CA, and the use of vasoactive

excluded 2,900 patients (1,877 readmissions, 755

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Shock Classification Stratifies Mortality Risk

T A B L E 4 Severity of Illness Scores, Vital Signs, and Laboratory Data of Patients According to SCAI Shock Stage

With Data, %

Stage A (n ¼ 4,602)

Stage B (n ¼ 2,998)

Stage C (n ¼ 1,575)

Stage D (n ¼ 732)

Stage E (n ¼ 97)

APACHE-III score

100.0

51.3  18.2

60.8  20.4

APACHE-IV predicted hospital mortality, %

100.0

9.9  11.6

15.8  16.7

69.5  24.4

97.4  31.5

118.5  38.8

<0.001

22.0  20.7

48.4  28.1

64.8  27.8

<0.001

Day 1 SOFA score

99.9

2.3  2.0

3.4  2.7

Severe AKI

89.2

257 (6.1)

333 (12.4)

4.4  2.9

9.1  3.9

11.4  3.9

<0.001

233 (17.8)

269 (44.2)

40 (49.4)

<0.001

100.0

188 (4.1)

190 (6.3)

108 (6.9)

205 (28.0)

17 (17.5)

<0.001

Systolic blood pressure, mm Hg

99.4

130.8  22.9

Diastolic blood pressure, mm Hg

96.2

72.1  14.5

114.4  26.1

123.0  27.7

113.8  27.9

99.8  25.3

<0.001

67.1  18.6

68.8  17.8

65.7  19.5

57.6  19.4

Mean arterial pressure, mm Hg

96.2

<0.001

87.2  15.1

79.6  19.6

83.1  18.9

79.9  20.9

70.1  20.9

Heart rate, beats/min

<0.001

99.4

72.4  13.9

93.1  26.8

84.8  25.5

89.4  24.7

95.5  27.9

<0.001

Shock index*

99.4

0.57  0.15

0.84  0.29

0.72  0.28

0.83  0.29

1.04  0.38

<0.001

Respiratory rate, breaths/min

95.9

17.3  5.2

19.1  6.0

19.3  5.9

20.2  5.9

21.8  6.5

<0.001

Pulse oximetry, %

99.4

96.6  4.2

95.6  5.6

95.2  7.3

93.2  9.0

86.5  16.8

<0.001

Glasgow Coma Scale

97.3

14.5  2.0

13.9  2.9

13.6  3.3

9.8  5.1

8.3  5.1

<0.001

Urine output first 24 h, l

97.0

2.16  1.10

2.26  1.42

1.02  1.12

1.25  1.33

1.41  2.41

<0.001 <0.001

p Value

Severity of illness

Late deterioration Admission vital sign data

Admission laboratory data Creatinine, mg/dl

96.3

1.2  0.8

1.3  1.0

1.7  1.7

1.9  1.4

1.9  1.2

BUN, mg/dl

96.0

23.5  16.4

27.0  18.9

30.0  20.4

36.0  23.1

34.6  20.5

<0.001

ALT, U/ml

46.5

51.9  139.5

76.2  222.2

127.3  529.8

270.8  675.0

644.5  1211.5

<0.001 <0.001

Peak troponin T, mg/dl

63.3

1.8  3.3

1.7  3.2

1.8  3.4

3.3  6.9

4.0  6.5

Hemoglobin, g/l

96.4

12.5  2.0

11.9  2.2

11.9  2.3

11.8  2.5

11.6  2.5

<0.001

Arterial pH

32.3

7.39  0.08

7.36  0.10

7.36  0.10

7.30  0.11

7.20  0.15

<0.001

Bicarbonate, mEq/l

96.9

24.6  3.7

23.9  4.4

23.4  4.6

21.2  5.3

16.7  6.5

<0.001

Anion gap, mEq/l

89.3

11.0  2.9

11.5  3.2

12.6  3.8

14.4  4.3

20.6  8.7

<0.001

Lactate, mmol/l

21.3

1.2  0.4

1.3  0.4

3.0  2.3

3.6  2.3

10.6  5.1

<0.001

Values are mean  SD or n (%), unless otherwise indicated. The p value is for the trend across SCAI shock stages A to E. *Shock index is defined as the ratio of heart rate to systolic blood pressure. AKI ¼ acute kidney injury; ALT ¼ alanine aminotransferase; APACHE, Acute Physiology and Chronic Health Evaluation; BUN ¼ blood urea nitrogen; SCAI ¼ Society for Cardiovascular Angiography and Intervention; SOFA ¼ Sequential Organ Failure Assessment.

patients without Minnesota Research Authorization,

Hypotension or tachycardia during the first hour in

and 268 patients whose admission did not occur

the CICU was present in 4,367 (43.7%) patients,

entirely within the study period), as demonstrated in

including 2,545 (25.4%) who met criteria for hypo-

Figure 1 (13–15). The final study population of 10,004

tension and 2,956 (29.5%) who met criteria for

unique patients had a mean age of 67.4  15.2 years,

tachycardia; 1,134 (11.3%) patients met criteria for

including 3,746 (37.4%) women. The mean CCI was

both hypotension and tachycardia. Hypoperfusion

2.4  2.6 and the mean APACHE-IV predicted hospital

was present in 2,404 (24.0%) patients, including an

mortality was 16.9  20.0% overall. Admission di-

admission lactate level >2 mmol/l in 888 (41.6%) of

agnoses (not mutually exclusive) included ACS in

2,135 patients with available data. Deterioration

4,267 (43.1%) patients, HF in 4,564 (46.1%) patients,

within 24 h of admission occurred in 2,075 (20.7%)

and CA in 1,193 (12.1%) patients; 2,704 (27.3%) pa-

patients, and refractory shock was identified in 153

tients had neither ACS nor HF as an admis-

(1.5%) patients. Late deterioration after 24 h occurred

sion diagnosis.

in 708 (7.1%) patients.

A total of 2,468 (24.7%) patients received vasoac-

The proportion of patients with SCAI shock stages

tive drugs during the CICU stay, including vasopres-

A through E were 46.0%, 30.0%, 15.7%, 7.3%, and

sors in 2,090 (20.9%) and inotropes in 928 (9.3%).

1.0%, respectively (Figure 1). Baseline demographics,

Among patients receiving vasoactive drugs, 1,182

comorbidities, admission diagnoses, and critical care

(47.9%) received >1 vasoactive drug. An intra-aortic

therapies varied significantly across the SCAI shock

balloon pump was placed during the CICU stay in

stages (Table 3). The prevalence of CA increased

865 (8.6%) patients and Impella (Abiomed, Danvers,

across the SCAI shock stages, from 7.3% in stage A to

Massachusetts) or ECMO support was used during the

55.8% in stage E. As the SCAI shock stage increased,

hospitalization in 21 (0.2%) and 72 (0.7%) patients,

there were more extensive vital sign and laboratory

respectively.

abnormalities, higher severity of illness scores, and

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F I G U R E 2 Hospital Mortality as a Function of SCAI Shock Stage Among Patients With and Without an Admission Diagnosis of CA

80%

Observed Hospital Mortality (%)

70% 60% 50% 40% 30% 20% 10% 0% Stage A

Stage B Stage C Stage D SCAI Shock Stage

No Admission Diagnosis of CA

Stage E

Admission Diagnosis of CA

Hospital mortality was higher among patients with an admission diagnosis of cardiac arrest (CA) in each Society for Cardiovascular Angiography and Intervention (SCAI) shock stage (all p < 0.001).

more frequent AKI (Table 4). The use and dosage of

shock stages B through E were 2.44, 4.56, 21.80, and

vasoactive medications and supportive therapies

65.22, respectively. The unadjusted OR value for

including mechanical ventilation, MCS, and dialysis

hospital mortality was 12.17 (95% confidence interval

increased across the SCAI shock stages (Table 4). The

[CI]: 10.34 to 14.31; p < 0.001) in patients meeting

prevalence of late deterioration increased as a func-

criteria for SCAI shock stage D or E, compared with

tion of SCAI shock stage, being highest in SCAI shock

SCAI shock stages A through C. The SCAI shock clas-

stage D (Table 4).

sification itself had an area under the receiveroperating characteristic curve value of 0.765 for

CICU AND HOSPITAL MORTALITY. There was a step-

hospital mortality overall, 0.775 among patients with

wise increase in unadjusted CICU and hospital mor-

ACS, and 0.732 among patients with HF.

tality with each higher SCAI shock stage in the overall

After multivariable adjustment, each higher SCAI

population, with hospital mortality rising from 3.0%

shock stage was associated with increased hospital

in SCAI shock stage A to 67.0% in SCAI shock stage E

mortality compared with SCAI shock stage A (all

(p < 0.001) (Central Illustration). Unadjusted hospital

p < 0.001), as was CA (adjusted OR: 3.99; 95% CI: 3.27

mortality was higher among patients with CA at each

to 4.86, 95% CI; p < 0.001); the final multivariable

SCAI shock stage (Figure 2) (all p < 0.001). The same

model area under the receiver-operating character-

stepwise increase in hospital mortality was seen in

istic curve value was 0.883 in the overall population.

patients with ACS and HF and in patients without a

Compared with SCAI shock stage A, the adjusted OR

diagnosis of either ACS or HF (Figure 3). Patients with

values for hospital mortality in SCAI shock stages B

late deterioration had higher mortality overall (31.4%

through E were 1.53, 2.62, 3.07, and 6.80, respectively

vs. 7.4%; p < 0.001), and in each SCAI shock stage

(Figure 5). Each higher SCAI shock stage was associ-

except stage E (Figure 4).

ated

with

higher

adjusted

hospital

mortality

Compared with SCAI shock stage A, the unadjusted

compared with SCAI shock stage A among patients

odds ratio (OR) values for hospital mortality in SCAI

with ACS (all p < 0.001), HF (all p < 0.001), and

7

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Shock Classification Stratifies Mortality Risk

F I G U R E 3 Hospital Mortality as a Function of SCAI Shock Stage

80% 70% Observed Hospital Mortality

8

60% 50% 40% 30% 20% 10% 0% ACS (n = 4,267) Stage A

HF (n = 4,564)

Stage B

Stage C

Neither ACS nor HF (n = 2,704) Stage D

Stage E

Hospital mortality as a function of Society for Cardiovascular Angiography and Intervention (SCAI) shock stage among patients with acute coronary syndrome (ACS) (left), heart failure (HF) (middle), or neither ACS nor HF (right). Hospital mortality increased as a function of higher SCAI shock stage in patients with ACS or HF.

neither ACS nor HF (all p < 0.001). Likewise, CA was

diagnosis of CA increased the risk of hospital mor-

associated with higher adjusted hospital mortality in

tality among patients with each SCAI shock stage,

each of these subgroups (all p < 0.001).

supporting its inclusion as an effect modifier in the SCAI shock classification schema. These data support

DISCUSSION

the validity of the recent SCAI classification of CS stages for mortality risk stratification as a framework

Using a large cohort of unselected CICU patients, we

for future CS clinical practice and research. Our ex-

validated the association between

recently

amination of a mixed CICU cohort allowed us to

described SCAI shock classification and hospital

demonstrate the predictive ability of this classifica-

mortality. We stratified patients into 5 SCAI shock

tion system in patients with diagnoses of ACS and HF,

stages at the time of CICU admission, reflecting a

which are the dominant causes of CS, as well as in

continuum of increasing shock severity using a

patients without these diagnoses. The strong associ-

simplified definition based on hypotension or tachy-

ation between SCAI shock stages and mortality in a

cardia, hypoperfusion, deterioration, and refractory

heterogeneous CICU population, even after adjust-

shock, which can be easily applied in clinical practice.

ment for known predictors of mortality, emphasizes

the

This functional SCAI shock stages classification

the robustness of this classification system and its

effectively stratified mortality risk and performed

potential to be applied in other critically ill patient

similarly in patients with admission diagnoses of ACS

cohorts.

and HF, even when adjusting for the higher illness

The SCAI shock classification was developed using

severity and greater use of hemodynamic support at

expert consensus for the purpose of describing CS

higher shock stages. Patients with refractory shock

severity to clarify communication of patient status

(SCAI shock stage E) had >20-fold higher crude hos-

between providers in different care settings to facili-

pital mortality than hemodynamically stable patients

tate patient triage and selection for advanced thera-

without shock (SCAI shock stage A). An admission

pies (12). In addition, the SCAI classification of CS

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Shock Classification Stratifies Mortality Risk

stages was designed to facilitate clinical research by simplifying the heterogeneity inherent to CS pop-

F I G U R E 4 Hospital Mortality and SCAI Shock Stage in Patients With and Without Late

Deterioration, Defined as Rising Vasopressor Requirements After 24 h

ulations and help determine whether treatment interactions exist as a function of CS severity. A similar

80%

classification problem was addressed by the development of the INTERMACS (Interagency Registry for

70%

which subdivided patients with advanced HF into clinically relevant groups to determine their need for durable MCS (24). In essence, most patients with CS would typically be classified as INTERMACS profile 1 (“crash and burn”) or 2 (“sliding on inotropes”), and the SCAI classification provides further granularity by dividing these patients into stages C, D and E (12,24). In addition, the INTERMACS profiles are intended for application at the single time point of implantation of a durable MCS device and do not have a construct to

Observed Hospital Mortality

Mechanically Assisted Circulatory Support) profiles,

60% 50% 40% 30% 20%

assess deterioration of status. Nearly one-half of this CICU population was clas-

10%

sified as SCAI shock stage A (“at risk”) and the 3% observed hospital mortality in this group suggests

0%

that patients without hypotension, tachycardia, or

Stage A

hypoperfusion at the time of CICU admission have a favorable prognosis. Crude hospital mortality more

Stage B Stage C Stage D SCAI Shock Stage

Stage E

Late Deterioration (n = 708)

than doubled among patients with evidence of he-

No Late Deterioration (n = 9,296)

modynamic instability (SCAI shock stage B [“beginning”]), and nearly doubled again among patients with hypoperfusion (SCAI shock stage C [“classic

Hospital mortality was higher among patients with late deterioration in each Society for

shock”]). Crude hospital mortality rose to 40% among

Cardiovascular Angiography and Intervention (SCAI) shock stage, except stage E

patients with deterioration (SCAI shock stage D

(all other p < 0.001).

[“deteriorating”]), similar to that observed in recent randomized

controlled

trials

and

observational

studies of CS (2–4,6–9). This suggests that patients with CS who respond to initial stabilization measures

SCAI statement authors clearly emphasize the added

(SCAI shock stage C) have a relatively favorable

hazard posed by the presence of CA occurring in pa-

prognosis, while the majority of patients included in

tients with or at risk of CS (12). In this cohort, the

published studies of CS likely meet criteria for SCAI

prevalence

shock stage D. The marked step-up in short-term

increasing shock stage, highlighting the correlation

mortality risk among patients with SCAI shock stage

between CA and severe shock in CICU patients. In our

D and E (“extremis”) suggests a potential role for

analysis, we clearly demonstrate the added mortality

advanced hemodynamic support options including

hazard posed by CA at all levels of shock severity,

MCS in patients demonstrating evidence of deterio-

validating CA as a prognostically important modifier

ration. More than two-thirds of patients classified as

in the SCAI shock classification. Shock severity

SCAI shock stage E died in the hospital, emphasizing

demonstrated a stepwise association with mortality

the need to identify improved therapies for these

in patients with CA, emphasizing the synergistic

highest-risk patients. The prevalence of hemody-

mortality effects of concomitant CS and CA in CICU

namic deterioration after 24 h increased with higher

patients, as previously demonstrated in patients with

SCAI shock stages and was associated with higher

acute MI (25). The relative effect of CA on mortality

hospital mortality.

appeared to be greater among patients with mild or

of

CA

increased

substantially

with

CA is common in CS populations and has been

no shock (SCAI shock stages A through C). Although it

associated with an increased risk of death, yet the

remains clear that the presence of CA among CS pa-

influence of this major risk modifier on therapeutic

tients is associated with worse outcomes, it is un-

responses has not been well studied (7,9,25,26). The

likely that all such events carry the same hazard and

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Shock Classification Stratifies Mortality Risk

F I G U R E 5 Adjusted OR Plot for Hospital Mortality

Stage A (Referent)

Stage B SCAI Shock Stage

10

Stage C

Stage D

Stage E

0

1

2

3 4 5 6 7 8 9 10 Adjusted OR for Hospital Mortality

11

12

Adjusted odds ratios (ORs) and 95% confidence intervals for hospital mortality with each Society for Cardiovascular Angiography and Intervention (SCAI) shock stage derived from multivariable logistic regression, using stage A as referent. Higher SCAI shock stages had incrementally higher adjusted odds for hospital mortality.

future studies should address whether brief CA epi-

or clinical deterioration, to highlight their escalating

sodes have any prognostic importance and whether

mortality risk in real time and facilitate early

the presence of brain injury from CA modifies the

transfer or involvement of palliative care services if

response to CS therapies (26).

indicated (1).

Van Diepen et al. (1) have proposed a “hub-and-

We propose that the relative efficacy of various

spoke” care model involving transfer to tertiary cen-

therapeutic interventions at each CS stage should be

ters for patients with CS, as has been instituted for

further explored, as CS severity might determine the

other high-acuity medical conditions such as trauma.

need for and clinical response to specific therapies.

Uncertainty remains regarding when transfer to a

For example, temporary MCS devices can effectively

higher level of care is warranted, and ideally this

increase cardiac output in CS, yet none of these

should be determined early in the course if a patient

temporary MCS devices has resulted in a proven

is not responding as expected to initial therapy.

improvement in survival in published randomized

Based on the high risk of mortality after the onset of

clinical trials of CS patients (1,8,9,27). Notwith-

hemodynamic deterioration (SCAI shock stage D), we

standing their established hemodynamic benefits, the

propose that patients with hypoperfusion (SCAI shock

invasive nature and acquisition costs of temporary

stage C) who do not rapidly stabilize (i.e., progression

MCS devices emphasize the need to evaluate when

to SCAI shock stage D) should be considered for

and in whom these devices may be most effective for

transfer to a higher level of care before development

improving patient-centered outcomes (1,8,27). We

of overt deterioration. The simple functional defini-

suspect that each temporary MCS device will have a

tions used in this study could be leveraged by an

different risk-benefit profile at a given CS stage, but

electronic medical record system to identify patients

this hypothesis will need to be tested in future

with new onset or increasing severity of shock

studies.

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STUDY LIMITATIONS. Despite its large sample size

CONCLUSIONS

and granular data, this study has a number of limitations that are inherent to all retrospective cohort

In a large, heterogeneous CICU cohort, we demon-

studies, including the need for prospective validation

strated the feasibility of classifying patients into 5

and the potential for unmeasured confounders and

shock stages (SCAI shock stages A to E) reflecting

missing data to have influenced the results. Owing to

progressively increasing levels of illness severity.

lack of available invasive hemodynamic data, we

This pragmatic SCAI shock stages classification pro-

cannot be sure to what extent the shock states in this

vided robust mortality risk stratification in the overall

cohort were cardiogenic in nature. The inclusion of a

cohort including patients with ACS and HF, in a

mixed CICU population implies that some patients

manner that was amplified by the presence of CA.

meeting criteria for shock had noncardiogenic or

Despite its limitations, the functional adaptation of

mixed shock states, similar to a recent multicenter

the SCAI shock classification described herein had

CICU registry (4). To focus on the presence of shock

very good discrimination for mortality, emphasizing

on admission, we defined the shock stages using

its validity and practical utility with the potential for

variables from within 1 to 24 h of CICU admission,

improved risk stratification when rigorously applied.

recognizing that many patients develop CS after

The simple, intuitive SCAI shock stage definitions we

hospital admission; owing to data availability, our

report herein could be easily applied in clinical

limited definition of late deterioration only included

practice by providers with different levels of exper-

vasopressor dosage and not worsening SCAI shock

tise. We suggest that future CS clinical trials consider

stage (3). We were unable to include prognostically

stratifying patients according to SCAI shock stage and

relevant physical examination findings such as cool

the presence of CA, to ensure consistent outcomes

or clammy extremities or altered mental status in our

reporting and to assess whether the effects of the

definition of hypoperfusion; the inclusion of oliguria

tested intervention vary by CS stage.

and rising creatinine in the definition of hypoperfusion is less relevant among patients with end-

ADDRESS FOR CORRESPONDENCE: Dr. Jacob C.

stage renal disease (28). In addition, the definition

Jentzer, Department of Cardiovascular Medicine and

for SCAI shock stage C includes the requirement for

Division of Pulmonary and Critical Care Medicine,

an intervention to treat hypoperfusion, a criterion we

Department of Internal Medicine, The Mayo Clinic, 200

did not include in our definition of stage C for ease of

First Street SW, Rochester, Minnesota 55905. E-mail:

application (12). The infrequent use of advanced

[email protected]. Twitter: @davebaran.

temporary MCS devices (e.g., Impella or ECMO) in this cohort could have influenced the observed mortality, particularly

among

patients

with

higher

shock

PERSPECTIVES

severity; nonetheless, the overall utilization of MCS devices in this population is consistent with national utilization among patients with CS (29). By using International Classification of Diseases-Ninth Revision codes to define admission diagnoses, we were unable to define the primary admission diagnoses and could not distinguish in-hospital CA from outof-hospital

CA.

Data

regarding

timing,

arrest

rhythm, and neurologic status of patients with CA were not available. We grouped patients based on the presence of ACS without distinguishing between ACS subtypes, limiting our ability to draw conclusions about CS caused by acute MI. Data regarding resuscitation status and limitations of therapies were not available.

COMPETENCY IN PATIENT CARE AND PROCEDURAL SKILLS: A CS classification system developed by the SCAI can effectively stratify patients in a CICU, including those with an ACS or HF, for risk of mortality. Patients with SCAI cardiogenic shock stages D and E are at higher risk and may benefit from early transfer to specialized centers offering advanced modalities for circulatory support. TRANSLATIONAL OUTLOOK: Prospective studies using a systematic approach to shock assessment and management are needed to determine if the efficacy of various advanced modalities is related to disease severity.

11

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KEY WORDS cardiac intensive care unit, cardiogenic shock, critical care, mortality, shock