European J of Heart Fail - 2022 - Beer - Early Risk Stratification in Patients With Cardiogenic Shock Irrespective of The

European Journal of Heart Failure (2022) 24, 657–667 RESEARCH ARTICLE
doi:10.1002/ejhf.2449
Early risk stratification in patients with

cardiogenic shock irrespective of the
underlying cause – the Cardiogenic
Shock Score
Benedikt N. Beer1,2, Jacob C. Jentzer3, Jessica Weimann1, Salim Dabboura1,2,
Isabell Yan1, Jonas Sundermeyer1, Paulus Kirchhof1,2,4, Stefan Blankenberg1,2,
Benedikt Schrage1,2†, and Dirk Westermann1,2*†
1 Department of Cardiology, University Heart and Vascular Center Hamburg, Hamburg, Germany; 2 German Centre for Cardiovascular Research (DZHK), Partner Site
Hamburg/Lübeck/Kiel, Hamburg, Germany; 3 Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA; and 4 Institute of Cardiovascular Sciences, University of
Birmingham, Birmingham, UK
Received 6 October 2021; revised 25 January 2022; accepted 31 January 2022 ; online publish-ahead-of-print 14 February 2022
Aims Early risk stratification is essential to guide treatment in cardiogenic shock (CS). Existing CS risk scores were derived
in selected cohorts, without accounting for the heterogeneity of CS. The aim of this study was to develop a universal
risk score (the Cardiogenic Shock Score, CSS) for all CS patients, irrespective of the underlying cause.
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Methods Within a registry of 1308 CS unselected patients admitted to a tertiary care hospital between 2009 and 2019, a
and results Cox regression model was fitted to derive the CSS, with 30-day mortality as main outcome. The CSS’s predictive
ability was compared to the IABP-SHOCK II score, the CardShock score and SCAI classification by C-indices and
validated in an external cohort of 934 CS patients. Based on the Cox regression, nine predictors were included in
the CSS: age, sex, acute myocardial infarction (AMI-CS), systolic blood pressure, heart rate, pH, lactate, glucose and
cardiac arrest. The CSS had the highest C-index in the overall cohort (0.740 vs. 0.677/0.683 for IABP-SHOCK II
score/CardShock score), in patients with AMI-CS (0.738 vs. 0.675/0.689 for IABP-SHOCK II score/CardShock score)
and in patients with non-AMI-CS (0.734 vs. 0.677/0.669 for IABP-SHOCK II score/CardShock score). In the external
validation cohort, the CSS had a C-index of 0.73, which was higher than all other tested scores.
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Conclusion The CSS provides improved information on the risk of death in unselected patients with CS compared to existing
scores, irrespective of its cause. Because it is based on point-of-care variables which can be obtained even in critical
situations, the CSS has the potential to guide treatment decisions in CS.
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..
*Corresponding author. University Heart and Vascular Center Hamburg, Department of Cardiology, Martinistr. 52, 20246 Hamburg, Germany. Email: d.westermann@uke.de
† Shared co-last authorship.
© 2022 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and
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658 B.N. Beer et al.
Graphical Abstract
Cardiogenic shock (CS) is a multi-cause, critical condition associated with high mortality. The novel Cardiogenic Shock Score (CSS) was developed
in 1308 all-cause CS patients and externally validated. CSS is superior in predicting 30-day mortality to established scores independent of CS
cause. Its point-of-care calculation facilitates urgent decision making and targeted treatment approaches. AMI, acute myocardial infarction; CPR,
cardiopulmonary resuscitation; HF, heart failure; SBP, systolic blood pressure; SCAI, Society for Cardiovascular Angiography and Interventions.
..........................................................................................................
Keywords Cardiogenic shock • Risk stratification • Score • Targeted treatment approach • Mechanical
circulatory support
Introduction trials enrolling unselected patients with shock due to AMI.2,6–11

................................
Furthermore, criticism regarding the use of MCS in CS is centred

Cardiogenic shock (CS) is a life-threatening condition with high on poor patient selection coupled with a high risk of complica-
mortality despite contemporary treatment, resulting in prolonged tions with these devices.12–15 Although implanting MCS devices
suffering in affected patients and substantial healthcare costs.1,2 early in CS may yield greater efficacy, this also risks treating
Early revascularisation of the culprit artery can improve survival patients who might not need this invasive therapy and expose
when CS is caused by acute myocardial infarction (AMI).3–5 To them to complications. Implanting MCS devices late in CS inher-
improve survival, several methods providing mechanical circula- its the risk of providing support once CS has reached a stage
tory support (MCS) as a ‘bridge to recovery’ have been intro- where cardiac output is no longer the primary determinant of
duced in clinical practice. Neither of the MCS therapies tested favourable outcome.16,17 Thus, early risk stratification of patients
so far improves survival compared to usual care in controlled in CS is of high interest, as it might provide guidance for the use
Early risk stratification in patients with cardiogenic shock 659
of MCS and other treatments individualized to patient risk in the systolic blood pressure, heart rate, pH, lactate, sodium, glucose and
........................................................................................................................................................................
future.18 duration of cardiopulmonary resuscitation (CPR). Invasively measured
Standard severity of illness risk scores perform poorly for haemodynamic parameters like used in other scores were not avail-
predicting mortality in CS patients.19,20 Several CS-specific risk able.30 Missing data were imputed using chained equations (using the
R package mice, 50 imputed datasets). Afterwards, a multivariable Cox
tools have been established recently, including scores derived from
regression model was fitted to identify predictors of 30-day mortality.
the IABP-SHOCK II trial and the CardShock study.18 Utilizing
The proportional hazards assumption was assessed graphically, only
data from the IABP-SHOCK II trial (including only patients with small deviations from the assumption were observed; thus, the model
AMI), a 30-day mortality prediction score was established.21 On was adequately tested.31,32 This final model was then transformed into
the other hand, the CardShock study was not restricted to AMI the novel CSS, with points assigned according to the beta coefficient
only, although >80% of included patients had AMI.22 Importantly, of each variable significantly associated with the endpoint in the final
both scores include variables which are not always available at first model (pooled by Rubin’s rule).33,34
contact with the patient or may not be applicable to all CS patients
(e.g. coronary flow after revascularisation for the IABP-SHOCK II
score), which further limits their applicability in clinical practice. Internal validation of the novel
Therefore, the aim of this study was to derive and validate a Cardiogenic Shock Score
novel CS score (the Cardiogenic Shock Score, CSS), specifically In the derivation cohort, C-indices for the novel CSS were calculated
built to assess risk in all CS patients irrespective of the underlying in all imputed datasets with 300 bootstrap samples and pooling in
cause and based only on point-of-care variables, which are readily the end (e.g. the final C-index of a score would be the pooled
available in the emergency setting (similar to the MEESSI-AHF score mean of all calculated C-indices of that score). This was done in the
in a different acute heart failure setting not restricted to CS).23 This overall derivation cohort as well as in the derivation cohort stratified
novel score will then be compared to the above described estab- by presence/absence of AMI. For the strata we excluded the AMI
predictor from the model.
lished CS scores as well as the rather novel Society for Cardiovas-
cular Angiography and Interventions (SCAI) classification.24–28
Comparison to established cardiogenic
Methods shock scores in the derivation cohort
The novel CSS was then compared to the IABP-SHOCK II as well as the
Study design CardShock scores and the SCAI classification in the derivation cohort.
We derived the novel CSS in an all-comers CS cohort from the Uni- These scores were selected as comparators for three main reasons:
versity Heart and Vascular Center Hamburg using only point-of-care (i) quality and awareness of each of the underlying trials, (ii) different
variables which are readily available in the emergency setting. The settings and population characteristics between these trials, and (iii)
CSS was internally validated via bootstrapping and compared to the possibility to apply these scores to our database with respect to the
established CS scores (IABP-SHOCK II score, CardShock score, SCAI available parameters. Nevertheless, not all variables were available in
stages). The novel CSS and established CS scores were then externally our database, necessitating pragmatic interpretation of some of the
validated in a cohort of consecutive CS patients from the Mayo Clinic original scores’ parameters. For IABP-SHOCK II, we chose to integrate
Cardiac Intensive Care Unit. the lactate level regardless of its origin (original: arterial blood only);
This study was performed in accordance with the Declaration of post-interventional TIMI flow grade was not available. For CardShock,
Helsinki and was approved by the local ethics committee at each we included the patient’s vigilance at the time of the index event
institution. as a surrogate parameter for the original’s confusion at detection
All analyses were performed using R version 4.0.3 (derivation of shock.
cohort) and JMP 14.1 Pro (external validation cohort). For these scores, we then also calculated the C-indices as described
above.
Derivation of the novel Cardiogenic External validation cohort

Shock Score To perform external validation of the CSS, we examined its associa-
For the development of the novel CSS, consecutive CS patients tion with 30-day mortality in a previously described cohort of con-
≥18 years old treated at the University Heart and Vascular Center secutive unique CS patients from the Mayo Clinic cardiac intensive
Hamburg between 2009 and 2019 were analysed to derive the score. care unit.35 Briefly, included patients were admitted from 2007 to
Details on this cohort have been reported previously.29 Briefly, to 2015 and had an ICD-9/10 admission diagnosis of CS with evidence
identify patients for this cohort, the hospital claims database was of haemodynamic instability on admission. The CSS, CardShock and
scanned for the International Classification of Diseases-Tenth Revision IABP-SHOCK II scores were calculated using available data, although
(ICD-10) code of CS (R57.0). Every patient was manually reviewed to TIMI flow grade was not available. Data were not available regard-
validate that CS was the primary diagnosis. Baseline and follow-up data ing the duration of cardiac arrest, so the presence and rhythm of
were available during the hospital stay and patients were censored after cardiac arrest were substituted for the CSS: patients with ventricu-
discharge from hospital or after 30 days for the mortality endpoint. lar fibrillation on cardiac arrest received 2 points, and patients with
To derive and internally validate the novel CSS, only available non-ventricular fibrillation cardiac arrest received 3 points. To simulate
point-of-care parameters which are readily available in the emergency the real-world performance of the CSS, missing data were imputed as
setting were considered as candidate variables: age, sex, cause of CS, normal (rather than multiple imputation), as is standard for severity of
Table 1 Baseline characteristics
All (n = 1308) Non-AMI-CS (n = 672) AMI-CS (n = 636)

...........................................................................................................................................
Age (years) 69.0 (58.0– 78.0) 68.0 (55.0–78.0) 70.0 (60.0–79.0)
Male sex, n (%) 930 (71.2) 455 (67.8) 475 (74.7)
BMI (kg/m2 ) 24.7 (24.2–28.7) 24.9 (23.5–29.1) 24.7 (24.2–28.1)
Cardiovascular risk factors and medical history
Arterial hypertension, n (%) 620 (51.6) 286 (46.1) 334 (57.4)
Diabetes mellitus, n (%) 337 (28.0) 146 (23.5) 191 (32.6)
CKD, n (%) 237 (19.6) 139 (22.4) 98 (16.6)
Prior CABG, n (%) 128 (10.5) 81 (13.0) 47 (7.9)
Ischaemic HF, n (%) 283 (23.3) 162 (26.1) 121 (20.4)
Dilated HF, n (%) 96 (7.9) 84 (13.5) 12 (2.0)
Other HF, n (%) 73 (6.0) 54 (8.7) 19 (3.2)
Index event
Acute myocardial infarction, n (%) 636 (49.1) 0 (0) 636 (100)
CPR
No CPR, n (%) 548 (48.6) 257 (44.9) 291 (52.5)
CPR <30 min, n (%) 230 (20.4) 138 (24.1) 92 (16.6)
CPR ≥30 min, n (%) 145 (12.9) 68 (11.9) 77 (13.9)
Refractory cardiac arrest, n (%) 204 (18.1) 110 (19.2) 94 (17.0)
Haemodynamics
Systolic blood pressure (mmHg) 100.0 (83.0–123.0) 99.0 (80.0–120.0) 105.0 (86.0–127.6)
Heart rate (bpm) 89.0 (70.0–110.0) 89.0 (69.0–115.0) 89.0 (72.0–106.0)
Transcutaneous oxygen saturation (%) 96.0 (92.0–99.0) 97.0 (92.0–99.0) 96.0 (92.0–99.0)
Laboratory
pH 7.3 (7.1–7.4) 7.3 (7.1–7.4) 7.3 (7.1–7.4)
Lactate (mmol/l) 4.0 (2.0–9.0) 5.0 (2.0–9.0) 4.0 (2.0–9.0)
Sodium (mmol/l) 139.0 (135.0–142.0) 139.0 (135.0–142.0) 139.0 (135.2–142.0)
Glucose (mg/dl) 177.0 (130.0–259.0) 164.5 (121.0–240.2) 195.0 (141.0–274.8)
Estimated GFR (ml/min) 41.7 (27.0–58.4) 37.3 (23.3–53.8) 46.5 (31.6–62.4)
Troponin T (pg/ml) 246.0 (59.2–1490.0) 109.5 (44.0–415.2) 798.0 (113.0–2998.2)
AST (U/L) 138.5 (54.0–446.0) 119.0 (47.0–393.7) 163.5 (60.0–461.1)
SCAI classification
B 34 (2.7) 13 (2.0) 21 (3.4)
C 560 (43.9) 278 (42.6) 282 (45.3)
D 396 (31.1) 217 (33.2) 179 (28.8)
E 285 (22.4) 145 (22.2) 140 (22.5)
Continuous variables are presented as median (25th–75th percentile), and binary variables as absolute and relative frequencies.
AMI, acute myocardial infarction; AST, aspartate aminotransferase; BMI, body mass index; CABG, coronary artery bypass grafting; CKD, chronic kidney disease; CPR,
cardiopulmonary resuscitation; CS, cardiogenic shock; GFR, glomerular filtration rate; HF, heart failure; SCAI, Society for Cardiovascular Angiography and Interventions.
illness risk scores including SOFA, APACHE-III and APACHE-IV which presence/absence of AMI are reported in Table 1. A total of 751
.............................................
were also calculated.19 Hereafter, C-indices were calculated for the (57.4%) patients died within 30 days after admission.
novel CSS and compared to the other scores, and the C-index was Out of the preselected variables, all but sodium (p = 0.66)
calculated for the novel CSS in patients with and without an admis- proved to be significantly associated with 30-day mortality and
sion diagnosis of AMI. Calibration was determined by plotting the
were therefore chosen for the final model as reported in Table 2.
observed mortality rates of the derivation cohort and the external
The median value of the CSS was 6 (interquartile range 4–9).
validation cohort against the predicted mortality based on the newly
derived CSS. Age, lactate and CPR had the strongest impact on this score,
while cause of CS, sex and glucose contributed less. AMI as
cause of CS decreased risk according to CSS, whereas increas-
Results ing duration of CPR led to higher score representing greater
risk. There was a strong, almost linear correlation between CSS
Derivation of the novel Cardiogenic points and mortality rate as shown in Figure 1; and the novel
Shock Score CSS showed a good fit between predicted and observed mortality
The derivation cohort consisted of 1308 patients with CS. Base- (Figure 2). An overview of MCS therapy frequencies depending
line characteristics of the overall cohort as well as stratified by on SCAI stages and CSS categories, respectively, is given in
Table 2 Multivariable Cox regression model for 30-day mortality and derived Cardiogenic Shock Score
Variable HR per SD (95% CI) p-value Category CSS points

...........................................................................................................................................
Age 1.41 (1.30–1.53) <0.001 ≤60 years 0
61–70 years 2
71–80 years 3
>80 years 4
Female sex 1.09 (1.01–1.18) 0.019 Female 1
Male 0
Absence of AMI 1.09 (1.00–1.17) 0.037 Absence of AMI 1
AMI 0
Systolic blood pressure 0.88 (0.80–0.96) 0.0056 <90 mmHg 1
≥90 mmHg 0
Heart rate 0.87 (0.80–0.95) 0.0027 <100 bpm 1
≥100 bpm 0
pH 0.81 (0.73–0.91) <0.001 <7.0 2
7.0–7.35 1
>7.35 0
Lactate 1.45 (1.30–1.62) <0.001 <4 mmol/L 0
4–8 mmol/L 1
>8 mmol/L 4
Glucose 0.91 (0.82–1.00) 0.047 <200 mg/dl 1
≥200 mg/dl 0
CPR
No CPR 1.06 (0.95–1.19) 0.28 No CPR 0
CPR <30 min Reference CPR <30 min 0
CPR ≥30 min 1.19 (1.08–1.30) <0.001 CPR ≥30 min 2
Refractory cardiac arrest 1.38 (1.26–1.52) <0.001 Refractory cardiac arrest 3
AMI, acute myocardial infarction; CI, confidence interval; CPR, cardiopulmonary resuscitation; CSS, Cardiogenic Shock Score; HR, hazard ratio; SD, standard deviation.
Comparison of the novel Cardiogenic

.............................................................................
Shock Score to established risk scores

in the derivation cohort
In the overall cohort, C-indices were 0.677 for IABP-SHOCK
II, 0.683 for CardShock and 0.614 for SCAI. In the sub-cohort
without AMI, IABP-SHOCK II’s C-index was 0.667, CardShock’s
0.669 and SCAI’s 0.624. Finally, in patients with AMI causing CS,
IABP-SHOCK II showed a C-index of 0.675, CardShock 0.689 and
SCAI 0.601.
In comparison, the novel CSS had better discrimination for
predicting 30-day mortality in the overall cohort as well as in
patients with AMI (Figure 3): CSS’s C-index in the overall cohort
was 0.740, 0.734 for patients without AMI and 0.738 for patients
with AMI. Association between SCAI stages and CSS is shown in
online supplementary Tables S2 and S3. CSS’ superiority stratified
by SCAI stages is displayed in Figure 4.
Figure 1 The novel Cardiogenic Shock Score exhibits a nearly
linear association between cumulative shock score points and
relative risk of 30-day mortality in the derivation cohort. External validation of the novel
Cardiogenic Shock Score
online supplementary Tables S4 and S5. MCS devices comprised The Mayo Clinic external validation cohort included 934 patients
veno-arterial extracorporeal membrane oxygenation as well as with a median age of 69.5 years (37.5% female); 59.5% had an acute
Impellas of different generations. Dobutamine and norepinephrine coronary syndrome (online supplementary Table S1). A total of
were used as inotrope and vasopressor, respectively. 355 (38.0%) patients died within 30 days after admission. Median
Figure 2 The plot shows the association between the mortality predicted by the novel Cardiogenic Shock Score (CSS) and the mortality
observed in the derivation as well as in the external validation cohort.
Figure 3 Cardiogenic Shock Score (CSS) superiority in 30-day mortality prediction compared to established scores. This finding was
confirmed in an external validation. AMI, acute myocardial infarction; CS, cardiogenic shock, SCAI, Society for Cardiovascular Angiography and
Interventions.
value of the CSS was 6 (interquartile range 5–8). For prediction of the observed mortality in the external validation cohort (Figures 2
................
30-day mortality, C-indices of the CSS, the IABP-SHOCK II score, and 3; online supplementary Figure S1). C-indices for the CSS were
the CardShock score and the SCAI classification were 0.730, 0.674, 0.733 for patients with acute coronary syndrome and 0.717 with-
0.669 and 0.647, respectively. The CSS had better discrimination out (IABP-SHOCK II: 0.689, 0.656; CardShock: 0.688, 0.688; SCAI:
for 30-day mortality than all the other ones and aligned well with 0.668, 0.617). The CSS had a higher C-index value for 30-day
Figure 4 This diagram demonstrates the Cardiogenic Shock Score (CSS) predictive ability compared to IABP-SHOCK II and CardShock
scores in the derivation cohort even when stratified by the Society for Cardiovascular Angiography and Interventions (SCAI) stages. Stage B
is not displayed (not enough cases).
mortality than the Day 1 SOFA score (0.632), APACHE-III score no reduction in its primary outcome of 30-day all-cause mortal-
.......................................................................................................
(0.680) and APACHE-IV predicted mortality (0.675). CSS’ prognos- ity.36 Use of intra-aortic balloon pump decreased accordingly in the
tic value in each SCAI stage and both cohorts is shown in Figure 5. following years; nevertheless, scientific evidence for the growing
application of veno-arterial extracorporeal membrane oxygenation
and percutaneous ventricular assist devices is even scarcer pending
Discussion currently ongoing trials.2,5,37–39
Importantly, patient selection for all these therapies is a crucial
In this study, we present a novel tool for risk assessment in CS aspect as it is likely that only a specific subgroup of CS patients will
patients irrespective of the underlying cause – the CSS. The CSS is benefit from MCS devices. While patients with mild manifestation
based on readily available point-of-care variables and can therefore of CS might not be sick enough to benefit from MCS devices,
be easily applied in an emergency setting. In the external validation they would still be at risk of life-threatening complications such as
cohort, the CSS has shown superior predictive ability as compared bleeding and ischaemic events.12–14 On the other hand, high-risk
to established risk scores and a good fit between predicted and patients in need of more support might have been excluded
observed mortality. In the future, risk stratification using the novel from MCS device treatment if their CS severity and prognosis
CSS might help to guide treatment decisions and could allow for a was wrongly judged as more favourable with the consequence of
targeted treatment approach in CS. restricting therapy to medical supportive care. This would tilt the
benefit/risk ratio away from MCS devices and might also help to
explain the neutral results of the IABP-SHOCK II trial.
Rationale for risk stratification Accordingly, both the treating physicians as well as researchers of
in cardiogenic shock CS therapies need easy-to-use and reliable risk stratification tools
The prognosis of CS remains dismal despite extensive clinical for their work.18,34 These would strongly facilitate finding the best
and scientific efforts to improve understanding and clinical man- treatment for each patient as a targeted therapy concept including
agement of this condition.1,2 Contemporary non-invasive thera- both invasive (such as MCS) and non-invasive (such as inotropes)
peutic approaches to CS include volume management as well as approaches.
use of vasopressors (specifically norepinephrine) and inotropes to
restore systemic haemodynamics and perfusion.3–5,18,20
In severe CS, medical therapy may be insufficient to restore Established tools for risk stratification
adequate circulation and disrupt the vicious circle of hypoperfu- As a result of this insight, several risk stratification scores have been
sion, end-organ damage (including the myocardium itself) and sys- proposed in the recent years.40 Most recognized among them are
temic inflammatory response.16,17 MCS devices address this need the IABP-SHOCK II score as well as the CardShock deriving from
for further cardiac output augmentation, although their supporting the respective trials. These scores were created to estimate risk
evidence is limited and mostly based on smaller or observational of short-term mortality or serious adverse events.21,22
studies with heterogeneous conclusions.2,10,11,15 The most recog- Once again, though, patient selection proves to be a matter of
nized trial in this field was the IABP-SHOCK II trial, which showed concern. The IABP-SHOCK II trial enrolled only patients with AMI
Figure 5 The Cardiogenic Shock Score (CSS) was categorised as high (>6 points) versus low (≤6 points) based on the median CSS value
and 30-day survival in these groups was stratified by the Society for Cardiovascular Angiography and Interventions (SCAI) stages. This figure
highlights that CSS adds extra risk stratification information for patients in each SCAI stage. Stage B is not displayed (not enough cases).
as the cause of CS (AMI-CS) and therefore excluded all CS patients which are readily available in the emergency setting would be more
............................................................
with other causes.21 On the other hand, the CardShock trial was useful.
not restricted to AMI-CS, but AMI accounted for disproportion- These concerns were already addressed by introducing the
ately >80% of CS cases enrolled.22 rather novel SCAI classification.24 We aimed to demonstrate,
Just recently, CLIP, a novel mortality predicting score composed though, that CSS could provide a more granular risk prediction
of cystatin C, interleukin-6, lactate and N-terminal pro-B-type compared to SCAI in this cohort.
natriuretic peptide was presented, which could outperform the
IABP-SHOCK II score as well as the Simplified Acute Physiology
Score II.41 However, biomarker data were acquired from patients of The novel Cardiogenic Shock Score
the CULPRIT-SHOCK trial and therefore may lack generalisability There are four major advantages of the novel CSS in comparison
to non-AMI-CS patients or patients with AMI-CS and a single to the aforementioned risk stratification tools. First, the CSS was
coronary lesion; furthermore, not all of these biomarkers are derived in a cohort of 1308 patients and validated in another 934
routinely obtained for all patients in clinical practice.3 patients, as compared to 480 patients in IABP-SHOCK II and 219
Another issue with the already established scores is the lim- patients in CardShock.22,36 Second, the underlying cohort was not
ited availability of the underlying parameters (such as coronary preselected for AMI-CS and included a nearly 1:1 ratio of patients
flow after revascularisation for the IABP-SHOCK II score or the with AMI-CS versus non-AMI-CS (Table 1). This is a strength of our
biomarkers needed for the CLIP score) in the initial phase of treat- study as it is known that non-AMI causes of CS18 are also linked
ment. Therapeutic decision making in critical ill patients needs to high mortality but less well investigated.2,42 Third, CSS provided
to be addressed in a timely manner, and a more delayed risk a better risk prediction for 30-day mortality as compared to the
stratification approach is less appealing. Thus, easy-to-use tools IABP-SHOCK II and CardShock scores and the SCAI classification
in the overall cohort as well as the AMI and non-AMI sub-groups. therapy decisions). Based on the added value of combining the
........................................................................................................................................................................
Fourth, CSS is based on parameters which are all available at the CSS with the SCAI CS classification in this study, MCS application
‘point of care’ and therefore can be assessed very early during the might be guided by both in the future, e.g. targeting a specific CSS
treatment course. This aspect emphasizes the advantage of the CSS risk level within a specific SCAI CS class with a dedicated MCS
in clinical practice and allows it to be a criterion for enrolment in device.
future CS trials. Besides, it could facilitate implementation in clinical
practice – a critical aspect of risk stratification tools.43 Finally,
in the external validation cohort, the CSS has shown superior Limitations
predictive ability as compared to established risk scores. While Despite its large sample size and the validation in an external
there was a good fit between predicted and observed mortality, cohort, the novel CSS was built on retrospective, observational
the maximum relative risk ratios varied between the derivation data. It is therefore impossible to rule out unmeasured confound-
and validation cohorts, limiting its performance as a multiplier ing. Furthermore, the variables used for our and the other tested
of risk. scores were not harmonized between the derivation and the val-
The CSS’ added value to the SCAI classification should be idation cohort, which might have influenced the results. Because
highlighted here. It is essential to note that the SCAI classification our goal was to incorporate only data that are available at initial
was not designed as a stand-alone risk score, but rather as a presentation, we did not have extensive biomarker or haemody-
tool to identify different stages of CS severity. In this study, the namic data. Additionally, despite its large sample size, this study
CSS provided accurate risk prediction across all SCAI CS classes, was based on two cohorts from two tertiary care centres and gen-
outperforming the IABP-SHOCK II and CardShock scores in the eralisability to other hospitals in other healthcare systems might
derivation as well as in the validation cohort (Figure 4). Additionally, be limited. Besides, none of the tested risk scores had very good
it correlated strongly with 30-day survival across all SCAI CS discrimination, highlighting the potential for further refinement
classes, demonstrating the added value of combining the CSS and of risk stratification tools in CS; we hypothesize that the high
the SCAI CS classification (Figure 5). In this way, the CSS may baseline mortality risk of CS populations poses challenges in the
function as a ‘risk modifier’ providing additional risk stratification separation of higher-risk from lower-risk patients. Furthermore,
when added to the SCAI classification. the adjustment of IABP-SHOCK II and CardShock scores to our
The prognostic superiority of CSS may be explained by the above database (e.g. because of unavailable TIMI flow grades) could have
described differences. The comparable C-indices of IABP-SHOCK affected their C-index. Moreover, C-statistics might not always be
II between the AMI and the non-AMI groups is surprising given the best discrimination measure as they do not take distribution
that the latter was developed in AMI patients only.36 CardShock into account.45 The baseline mortality rate in the derivation cohort
included AMI and non-AMI patients, yet it performed minimally was higher than in many contemporary CS populations, including
better.22 It is unexpected that AMI increased the CardShock score the validation cohort. While the substantial differences between
while decreasing the CSS, suggesting different effects on risk in the derivation and validation cohorts are of potential concern,
these disparate cohorts. AMI as a protective factor in CSS might be the similar performance of the CSS in these CS populations with
explained by its addressability with coronary intervention, whereas different characteristics may support its external validity. Finally,
AMI may be associated with more severe CS conferring higher application of scores like CSS for risk stratification remains rather
risk when this is not accounted for adequately.2,3 Of note, sev- informative at this point, as their impact on decision making has yet
eral studies have likewise indicated higher short-term mortality in to be evaluated.
non-AMI CS, although different definitions/populations might pro-
vide different results on this.29,42,44 It is also notable that tachycardia
and hyperglycaemia were paradoxically associated with lower risk, Conclusion
potentially because these abnormalities reflect a patient’s ability to
In this study, we present a novel tool for risk assessment in CS
respond to physiologic stress.
patients irrespective of the underlying cause – the CSS. The CSS
Finally, higher CSS might demand more intensive treatments like
is uniquely based on few readily available point-of-care variables
MCS (if positive results in the ongoing randomised controlled trials
and can therefore be easily applied in an emergency setting. The
confirm the efficacy of these treatments). In this regard, it will
CSS has shown superior predictive ability in the external validation
be interesting to see if the novel CSS shows an interaction with
cohort as compared to established scores and a good fit between
the potentially effective treatments, e.g. higher efficacy in certain
predicted and observed mortality. In the future, the novel CSS
score ranges, including futility for very high scores. Today, MCS
might help to guide treatment decisions in a timely manner and
application appears to be dependent on SCAI stages (with higher
could allow for a ‘targeted treatment approach’ in CS as well as
stages indicating worse outcomes and thus higher willingness to
facilitate patient selection for enrolment to trials.
implement MCS devices), which reflects the SCAI classification’s
role as a tool to identify different CS classes (online supplementary
Table S4). On the other hand, the opposite is true for CSS with
higher scores correlating with lower MCS application rates (online
Supplementary Information
supplementary Table S5). This might be explicable by CSS’ status as Additional supporting information may be found online in the
a clinically not yet established risk score (and thus not yet driving Supporting Information section at the end of the article.
Acknowledgement ventricular assist device versus intra-aortic balloon pumping for treatment of car-
........................................................................................................................................................................
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patients with acute myocardial infarction complicated by cardiogenic shock. JAMA.
Siemens Healthineers, outside the submitted work. P.K. reports 2020;323:734–45.
non-financial support from European Union, British Heart Foun- 14. Amin AP, Spertus JA, Curtis JP, Desai N, Masoudi FA, Bach RG, et al. The evolving
landscape of Impella use in the United States among patients undergoing percu-
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German Centre of Cardiovascular Research, outside the submit- 2020;141:273–84.
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2016012783 issued and has received research support for basic, et al. Left ventricular unloading is associated with lower mortality in cardio-
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European J of Heart Fail - 2022 - Beer - Early Risk Stratification in Patients With Cardiogenic Shock Irrespective of The

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European Journal of Heart Failure (2022) 24, 657–667 RESEARCH ARTICLE

Early risk stratification in patients with

Introduction trials enrolling unselected patients with shock due to AMI.2,6–11

Furthermore, criticism regarding the use of MCS in CS is centred

Derivation of the novel Cardiogenic External validation cohort

Table 1 Baseline characteristics

All (n = 1308) Non-AMI-CS (n = 672) AMI-CS (n = 636)

Variable HR per SD (95% CI) p-value Category CSS points

Comparison of the novel Cardiogenic

Shock Score to established risk scores

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