Clinical Course and Outcomes of Cardiogenic Shock in COVID-19 : Insights from COVID-19 Critical Care Consortium

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Obonyo, Silvia Mariani, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7096750/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Aim: Cardiogenic shock (CS) is a life-threatening condition observed in patients with severe heart diseases. Although COVID-19 is known to cause cardiac complications, the epidemiology and outcomes of CS in COVID-19 patients have not been characterised. This study aimed to describe the prevalence, clinical course, mortality, and patient characteristics associated with CS in COVID-19 patients admitted to intensive care units (ICUs). Methods: We retrospectively analysed the Cardiac Sub-study database of the COVID-19 Critical Care Consortium. Local physicians diagnosed CS at ICU admission based on persistent hypotension combined with evidence of low cardiac output and elevated filling pressures. We also evaluated the applicability of the Society for Cardiovascular Angiography and Interventions (SCAI) CS staging system for mortality prediction. Results: Among 780 patients, 74 (9.5%) were diagnosed with CS, and their 30-day mortality rate was significantly higher than that of patients without CS (56.8% vs 33.4%; P <0.001). The common cardiac complications in patients with CS were arrhythmia (58.1%), congestive heart failure (35.1%), and myocardial infarction (18.9%). On multivariable analysis, history of ventricular arrhythmia was the sole independent factor associated with CS complication (odds ratio 3.9; 95% confidence interval [CI], 1.6–9.5). Among patients with CS, 43 were classified into SCAI stages C/D, and 31 into stage E. Stage E was associated with significantly higher mortality (74.2% vs. 44.2%; hazard ratio 2.2; 95% CI, 1.4-4.0). Conclusion: CS was observed in 9.5% of critically ill COVID-19 cases, which was significantly associated with elevated mortality. SCAI staging effectively stratified mortality risk in this population. Health sciences/Cardiology Health sciences/Diseases Health sciences/Medical research Health sciences/Risk factors arrhythmia COVID mortality SARS-CoV-2 SCAI Figures Figure 1 CLINICAL PERSPECTIVS CS was observed in 9.5% of COVID-19 cases admitted to the ICU and was associated with significantly higher mortality compared to those without CS. A medical history of previous VT/VF was an independent predictor of CS complications. The SCAI staging system was applicable to this population, indicating that worsening conditions after ICU admission were associated with an even higher mortality risk. INTRODUCTION Cardiogenic shock (CS) is a life-threatening condition observed in severe cardiac diseases ( 1 ). In this context, a dysfunctional heart fails to maintain adequate cardiac output, leading to hemodynamics collapses, and patients progress to death without intensive pharmacologic or mechanical circulatory support (MCS) ( 2 ). Recently, its pathophysiology has been actively discussed ( 3 ) leading to a new classification system based on mortality risk and clinical characteristics ( 4 ). The Society for Cardiovascular Angiography and Interventions (SCAI) CS classification is one such risk prediction model, and its utility has been validated primarily in CS related to acute myocardial infarction (AMI) and heart failure (HF) ( 5 , 6 ). COVID-19 has been linked to various cardiac complications ( 7 ). Viral-induced direct myocardial injury, along with indirect damage via excessive inflammation, alteration in endothelial function, and microthrombi, can cause severe cardiovascular disorders ( 8 – 11 ). A large cohort study from the U.S. reported that AMI, HF, and myocarditis were observed in 5.5%, 5.4%, and 0.3% of all adult patients hospitalized with SARS-CoV-2 infection, respectively ( 7 ). Pathophysiological studies have further demonstrated microthrombi and myocyte necrosis in 35% of collected heart samples, highlighting the substantial cardiac impact of COVID-19 ( 9 – 11 ). All these heart diseases potentially progress to CS, and thus, identifying predictors and outlining epidemiological data could assist clinicians in providing effective critical care, as demonstrated in AMI-related and HF-related CS ( 12 ). However, data on CS in this cohort remains limited, and the applicability of SCAI CS staging has not been broadly assessed outside AMI and HF cohorts. The COVID-19 Critical Care Consortium (CCCC) registry is one of the largest global datasets on COVID-19 in intensive care units (ICUs) ( 13 , 14 ). This study aimed to describe the characteristics and clinical course of CS in patients with COVID-19, and to assess the applicability of SCAI staging, using data from the CCCC registry. METHODS Study Design: The CCCC registry is an international database enrolling COVID-19 patients requiring intensive care in 459 ICUs across 50 countries. In this registry, we used the Cardiac Sub-study dataset, which focused on data related to cardiac diseases. The study design has been described in a previous publication (Trial registration ACTRN12620000421932) ( 13 ). This study protocol was reviewed under the National Mutual Acceptance scheme by the Alfred Health Human Research Ethics Committee on February 27, 2020 (Project: 62066, Local reference: 108/20), and the study was conducted in accordance with both the protocols, the Declaration of Helsinki, and the Principles of Good Clinical Practice. All participating hospitals obtained local approval from their human research ethics committee prior to data collection; and a waiver of informed consent was granted in all cases. Detailed information on the local ethics committee/institutional review board is included in the Supplemental Digital Content (Ethics Approval Number). All data related to patient backgrounds, presentation, treatment, and outcomes were gathered from the electronic case report form. The University of Queensland received clinical data from the data custodians via data sharing agreements. Study Population: This analysis included consecutive patients ≥ 18 years of age enrolled in the CCCC Cardiac Sub-study dataset from March 2020 to January 2022 (n = 1,155). Cases with missing data on CS and CA were excluded. Variable Definitions: In the CCCC Cardiac Sub-study database, the diagnosis of CS was adjudicated by clinicians at each hospital at ICU admission based on persistent hypotension—specifically, systolic blood pressure (BP) < 90 mmHg or mean BP < 65 mmHg—and evidence of low cardiac output and elevated filling pressures. Cardiac arrest (CA) was defined as sudden and unexpected cessation of cardiac activity with no normal breathing and no signs of circulation. MCS included 1) venoarterial extracorporeal membrane oxygenator (V-A ECMO), 2) micro axial flow pump, and 3) intra-aortic balloon pumping. Based on the previous papers ( 5 , 6 ), the SCAI CS staging was defined as follows: Stage C - CS without CA or MCS from 24 hours after ICU admission through a 30-day period; Stage D - MCS initiation after 24 hours of ICU admission through 30 days; Stage E - CA after 24 hours of ICU admission through 30 days. Deterioration in lactate level or hemodynamic parameters and increasing vasopressor/inotropes use were not considered in this staging model owing to a lack of data after 24 hours of ICU admission. Other definitions are described in Supplementary Table 1. Outcomes: The primary outcome was 30-day all-cause mortality. Data on MCS therapy, CA incidence, hospital stay, discharge, and in-hospital mortality were collected to describe the patient's clinical course. All included patients were followed for 90 days or until death in hospital or hospital discharge. Statistical Analysis: Baseline characteristics, clinical parameters and outcome were summarized descriptively for all eligible patients, stratified by confirmed CS status (CS vs. No CS). Categorical variables were summarized as frequencies and percentages, while continuous variables were summarized using medians and interquartile range (IQR: Q1 to Q3) for consistency. The clinical course of patients with CS was described with a stacked probability plot up to 90 days after ICU admission. Observed mortality stratified by SCAI stage was visualized by Kaplan-Meier survival curves. Evidence of differences in survival curves was assessed using the log-rank test and hazard ratios (HRs) of the association between SCAI stage and 30-day and 90-day mortality were estimated by a Cox proportional hazards model. Associations between patient-level characteristics with CS incidence and 30-day mortality were examined using logistic regression. Model parameters in fitted models were summarized as an odds ratio (OR) and 95% confidence interval (CI). Wald hypothesis tests for model parameters assessed evidence for statistically significant associations, assuming a 5% level of statistically significant. Variance inflation factors were calculated to assess multicollinearity in multivariable regression models. Analyses were carried out using R version 4.4.1 software (R Foundation for Statistical Computing, Vienna, Austria). RESULTS Baseline characteristics: Of 1,155 patients, 375 were excluded because of missing data on CS (n = 358) or CA (n = 17), and the data of 780 patients were analysed (Graphical Abstract A). Of patients included (n = 780), 74 cases were diagnosed with CS (9.5%) at ICU admission. Included population age was 58.0 [48.0–67.0], and 38.3% (n = 299) was female (Table 1 ). Patients of White and Asian ethnicity and sites in Asia Pacific and North America accounted for most parts of the study population. Further, 99.5% of the entire cohort was admitted in 2020 or 2021, and the number of admissions gradually declined during 2021 (Supplementary Fig. 1). At baseline, calcium channel blocker, beta-blocker, and renin-angiotensin system inhibitors were prescribed to 8.8% (n = 69), 12.9% (n = 101) and 11.8% (n = 92) of all patients, respectively. In the CS group, a history of ischemic heart disease (23.0% vs 20.0%), congestive HF (25.7% vs. 15.9%), and ventricular arrhythmia (16.2% vs. 8.4%) was observed more frequently compared to the no CS group. Vaccination with at least one dose was reported in 13.5% of no CS patients and 10.8% of CS patients, respectively. Table 1 Baseline Characteristics Median and interquartile range: n; median (IQR). The number in parentheses represents the percentage (%). All patients n = 780 No CS n = 706 CS n = 74 Age (median [IQR]) 58.0 [48.0–67.0] 58.0 [48.0–67.0] 60.0 [49.0–66.0] Female (%) 299.0 (38.3) 273.0 (38.7) 26.0 (35.1) BMI kg/m (median [IQR]) 28.7 [24.8–33.2] 28.9 [24.8–33.2] 28.6 [25.1–34.7] Ethnicity Aboriginal (%) 9.0 (1.2) 9.0 (1.3) 0.0 (0.0) Asian (%) 270.0 (34.6) 248.0 (35.1) 22.0 (29.7) Arab (%) 109.0 (14.0) 103.0 (14.6) 6.0 (8.1) Black (%) 52.0 (6.7) 46.0 (6.5) 6.0 (8.1) White (%) 252.0 (32.3) 219.0 (31.0) 33.0 (44.6) Other (%) 33 (4.2) 27 (3.8) 6 (8.1) Geographic Region Africa (%) 17 (2.2) 16 (2.3) 1 (1.4) Asia (%) 352 (45.1) 326 (46.2) 26 (35.1) Europe (%) 62 (7.9) 60 (8.5) 2 (2.7) Latin America and the Caribbean (%) 60 (7.7) 39 (5.5) 21 (28.4) Northern America (%) 289 (37.1) 265 (37.5) 24 (32.4) Admission Era 2020 (%) 457 (58.6) 403 (57.1) 54 (73.0) 2021 (%) 319 (40.9) 299 (42.4) 20 (27.0) 2022 (%) 4 (0.5) 4 (0.6) 0 (0.0) Existing Comorbidities Smoking (%) 159 (20.4) 137 (19.4) 22 (29.7) Diabetes (%) 243 (31.2) 216 (30.6) 27 (36.5) Hypertension (%) 421 (54.0) 380 (53.8) 41 (55.4) Chronic pulmonary disease (%) 64 (8.2) 58 (8.2) 6 (8.1) Chronic kidney disease (%) 117 (15.0) 105 (14.9) 12 (16.2) Malignant neoplasm (%) 24 (3.1) 23 (3.3) 1 (1.4) Medication Calcium channel blocker (%) 69 (8.8) 68 (9.6) 1 (1.4) Beta-blocker (%) 101 (12.9) 94 (13.3) 7 (9.5) ACEi/ARB (%) 92 (11.8) 83 (11.8) 9 (12.2) Diuretic (%) 97 (12.4) 88 (12.5) 9 (12.2) Cardiac Disease History Ischemic heart disease (%) 158 (20.3) 141 (20.0) 17 (23.0) Congestive heart failure (%) 131 (16.8) 112 (15.9) 19 (25.7) Ventricular arrhythmia (%) 71 (9.1) 59 (8.4) 12 (16.2) Previously implanted device (%) 13 (1.7) 9 (1.3) 4 (5.4) Congenital heart disease (%) 13 (1.7) 12 (1.7) 1 (1.4) Pre-existing cardiomyopathy (%) 22 (2.8) 17 (2.4) 5 (6.8) Presence of prosthetic valve (%) 3 (0.4) 2 (0.3) 1 (1.4) Recent ACS (within 6 months) (%) 54 (6.9) 46 (6.5) 8 (10.8) Vaccination One or more doses received (%) 103 (13.2) 95 (13.5) 8 (10.8) CS, cardiogenic shock; IQR, interquartile range; BMI, body mass index; ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker, ACS, acute coronary syndrome. In-hospital course: Data on presentation within 24 hours of ICU admission was missing for between 437 and 580 patients. In this limited population, the mean values of C-reactive protein (144.8 vs. 82.6mg/L) and Troponin I (0.15 vs. 0.03 ng/ml) were higher in patients with CS (Supplementary Table 2). CS cases more frequently received intensive therapeutic interventions, including ≥ 2 vasoactive drugs (17.6% vs. 9.1%), and renal replacement therapy (16.2% vs. 8.8%), compared to those without CS (Table 2 ). MCS was used for 8 cases in the CS group. Table 2 Treatment During ICU Stay The number in parentheses represents the percentage (%). All patients n = 780 No CS n = 706 CS n = 74 ≥ 2 vasoactive agents (%) 77 (9.9) 64 (9.1) 13 (17.6) Mechanical ventilation (%) 472 (60.5) 414 (58.6) 58 (78.4) Renal replacement therapy (%) 74 (9.5) 62 (8.8) 12 (16.2) ECMO V-V ECMO 175 (22.4) 154 (21.8) 21 (28.4) V-A ECMO 6 (0.8) 1 (0.1) 5 (6.8) Conversion V-V → V-A 2 (0.3) 0 (0.0) 2 (2.7) Dual lumen + single cannula V-V ECMO 20 (2.6) 20 (2.8) 0 (0.0) Cardiac assist device mAFP 1 (0.1) 0 (0.0) 1 (1.4) IABP 4 (0.5) 0 (0.0) 4 (5.4) Among patients with CS, V-A ECMO was used in 5 patients, mAFP in 1 patient, and IABP in 4 patients. The single mAFP case and 1 of the 4 IABP cases also received V-A ECMO therapy. Overall, 8 patients underwent MCS. The breakdown is as follows: • V-A ECMO alone: n = 3 • V-A ECMO + mAFP: n = 1 • V-A ECMO + IABP: n = 1 • IABP alone: n = 3 CS, cardiogenic shock; ECMO, extracorporeal membrane oxygenation; V-V, venovenous; V-A, venoarterial; mAFP, micro axial flow pump; IABP, intra-aortic balloon pumping. Over half of the CS group (58.1%; n = 43/74) developed atrial/ventricular arrhythmia requiring antiarrhythmics or device therapy, followed by congestive HF (35.1%; n = 26/74) and AMI (18.9%; n = 14/74; Table 3 and Graphical Abstract B). Myocarditis (8.1%) and takotsubo syndrome (1.4%) were also reported. CS group more frequently experienced acute respiratory distress syndrome (ARDS; 81.1% vs. 62.5%), acute kidney injury (AKI; 74.3% vs. 42.2%), disseminated intravascular coagulation (DIC; 23.0% vs. 11.3%), bacteremia (43.2% vs. 18.8%), and bleeding events (16.2% vs. 7.4%), compared to the cohort without CS. Pulmonary embolism, stroke, and liver dysfunction were observed in both groups at comparable prevalence rates. Table 3 Complications During ICU Stay The number in parentheses represents the percentage (%). All patients n = 780 No CS n = 706 CS n = 74 Cardiac complication AMI 78 (10.0) 64 (9.1) 14 (18.9) Congestive HF 130 (16.7) 104 (14.7) 26 (35.1) Cardiac arrhythmia 168 (21.5) 125 (17.7) 43 (58.1) Myocarditis/Pericarditis 7 (0.9) 1 (0.1) 6 (8.1) Endocarditis 7 (0.9) 6 (0.8) 1 (1.4) Takotsubo syndrome 1 (0.1) 0 (0.0) 1 (1.4) Other organ complications ARDS 501 (64.2) 441 (62.5) 60 (81.1) Pulmonary embolism 39 (5.0) 35 (5.0) 4 (5.4) Pleural effusion 145 (18.6) 123 (17.4) 22 (29.7) Stroke/CVA 22 (2.8) 20 (2.8) 2 (2.7) Meningitis/Encephalitis 5 (0.6) 4 (0.6) 1 (1.4) AKI 353 (45.3) 298 (42.2) 55 (74.3) Liver dysfunction 74 (9.5) 65 (9.2) 9 (12.2) Coagulation disorder/DIC 97 (12.4) 80 (11.3) 17 (23.0) Bacteremia 165 (21.2) 133 (18.8) 32 (43.2) Hemorrhage 64 (8.2) 52 (7.4) 12 (16.2) CS, cardiogenic shock; AMI, acute myocardium infarction; HF, heart failure; ARDS, acute respiratory distress syndrome; CVA, cerebrovascular accident; DIC, disseminated intravascular coagulation; AKI, acute kidney injury. Factors associated with cardiogenic shock complication: History of ventricular arrhythmia (ventricular tachycardia (VT)/ventricular fibrillation (VF)) was the sole independent factor associated with CS in our multivariable logistic regression analysis (OR 3.9; 95% CI, 1.6–9.5; Table 4 ). The factors included in this analysis were previously reported to be associated with the incidence of cardiac complications in COVID-19 (age, gender, unvaccinated, history of heart disease) ( 7 , 15 ). No multicollinearity was observed among the variables, with all showing low variance inflation factors (< 2.0), as detailed in Supplementary Table 3. Table 4 Multivariable Logistic Regression Output for Cardiogenic Shock with Site and Era as Random Effects Parameter OR 95% CI P value Age, years 0.99 0.97–1.02 0.616 Female 0.92 0.49–1.73 0.798 Unvaccinated 1.07 0.55–2.09 0.850 Known Ischemic Heart Disease 0.88 0.33–2.40 0.807 Known Congestive HF 0.77 0.29–2.04 0.591 Known Arrhythmia (VT/VF) 3.89 1.60–9.47 0.003 Recent ACS (within 6 months) 2.96 0.94–9.28 0.063 OR, odds ratio; CI, confidence interval: HF, heart failure; VT, ventricular tachycardia; VF, ventricular fibrillation; ACS, acute coronary syndrome. Mortality and SCAI CS staging: The 30-day mortality rate in the total population was 35.6% (n = 278/780), with rates of 56.8% (n = 42/74) and 33.4% (n = 236/706) for patients with and without CS, respectively ( P < 0.001; Graphical Abstract C). All patients with CS were classified into SCAI stage C (n = 41), D (n = 2), and E (n = 31), and their mortality rates were 43.9%, 50.0%, and 74.2%, respectively (Supplementary Table 4). Due to the small number of patients in Stage D, stages C and D were combined for analysis. SCAI stage E showed a significantly higher 30-day mortality risk compared to stage C/D (HR 2.2; 95% CI, 1.4-4.0). Kaplan-Meier survival analysis for 90 days, presented in Graphical Abstract D, also showed significantly higher mortality in stage E (83.9% vs. 72.1%; HR: 3.6; 95% CI: 1.4–10.4). A higher proportion of patients in Stage E were female (41.9% [n = 13/31] vs. 30.2% [n = 13/43]) and Asian (48.4% [n = 15/31] vs. 16.3% [n = 7/43]) compared to those in Stage C/D. Additionally, patients in Stage E were relatively younger (median age: 57.0 years [IQR, 46.5–65.5] vs. 61.0 years [IQR, 50.0–67.5]) (Supplementary Table 5). The stacked probability plot (Fig. 1 ) shows the probability of the following six events (ICU admission without CA or MCS, MCS placement, incidence of CA, hospitalization out of ICU, discharge, and death) after ICU admission. The 90-day mortality was 64.9% (n = 48/74). The most common cause of death in patients with CS was multiorgan failure, followed by cardiac death and respiratory failure (Supplementary Fig. 2). Factors associated with mortality in cardiogenic shock The univariable analysis for 30-day mortality in CS group (Supplementary Table 6) was carried out to clarify the impact of potential confounders on mortality in the CS group because we suspected that the high prevalence of bacteremia (43.2%, n = 32/74) and bleeding events (16.2%, n = 12/74) in the CS group compromised hemodynamic status as septic shock or hemorrhage shock and led to high mortality. However, bacteremia (HR 0.62; 95% CI 0.24–1.56) and hemorrhage (HR 2.55; 95% CI 0.68–12.31) did not have a significant association with mortality in univariable analysis. Further, MCS use during ICU stay (n = 8) and unvaccinated status were not associated with mortality, whereas SCAI stage E was associated with mortality in CS cases (HR 3.6; 95%CI: 1.4–10.4). DISCUSSION This study demonstrated that CS prevalence in COVID-19 patients admitted to ICU was 9.5%. A history of ventricular arrhythmia (VT/VF) was associated with a 3.9-fold increased risk of complicating CS. Furthermore, 30-day mortality in patients with CS was 56.8%, significantly higher than that of patients without CS (33.4%). Patients with CS classified as SCAI stage E had the highest mortality, with a 2.2-fold and 3.6-fold increased risk of death at 30 and 90 days, respectively, compared to those in stage C/D. Incidence of CS in COVID-19 population The CS prevalence rate in our study was higher than that observed in the general ICU population (2.17%) ( 16 ), comparable to the rates in AMI populations (5–10%) ( 17 , 18 ), and slightly lower than the 14.7% reported from cardiac ICUs ( 19 ). These findings suggest that COVID-19 is not only associated with cardiac complications but also linked to an increased incidence of CS. The multivariable analysis in the present study showed a history of VT/VF was statistically associated with CS. The possible explanation for this observation is that pre-existing injury in the myocardium was stimulated by a hyperadrenergic state in COVID-19 infection and served as a substrate of arrhythmia, eventually leading to shock. Indeed, more than half of CS cases presented arrhythmia requiring antiarrhythmics or device intervention, supporting the evidence that arrhythmia can be particularly influential for CS incidence in patients with COVID-19. Although underlying cardiovascular disease, age, gender, and unvaccinated have been reported as factors associated with cardiac complications in COVID-19 ( 20 ), none were significantly related to CS complications in our study. This suggests that CS in COVID-19 may not primarily result from newly developed cardiac injury, such as AMI or myocarditis, but rather from additional damage or stimulation affecting pre-existing myocardial injury or an underlying excitable myocardium, such as arrhythmia or worsening HF. Mortality in COVID-19 with CS The 30-day mortality rate in the CS group was 56.8%. Considering that the same rate reported in AMI-CS was 27–51% ( 21 ), this percentage was high. The conceivable reason for this is the baseline high mortality in the critically ill COVID-19 population. Between the 2020 and 2021 pandemic, the reported mortality rate for COVID-19 cases admitted ICU was 41.6% ( 22 ), while the mortality rate of total patients in our study was similarly high at 35.6%. On top of this already high baseline mortality, the presence of CS was expected to further worsen patient outcomes. The incidence of bacteremia (43.2%) and bleeding (16.2%) was higher among patients in the CS group compared to those without CS. “Mixed CS”, the combined pathophysiology of cardiogenic and either/both distributive and hypovolemic shock, has been linked to an increased mortality risk ( 23 ). In the context of COVID-19, this mixed pathophysiology may be more common due to the nature of the infection and compromised coagulation. Moreover, our findings indicate that a greater proportion of patients in the CS group developed multiorgan failure, including AKI and DIC, underscoring the severity of CS in this population. SCAI CS staging system SCAI staging is currently employed in a variety of clinical settings and has shown excellent predictive value for mortality ( 4 ). However, its applicability outside of AMI and HF cohorts remains underexplored 5 . The current study found Stage E was associated with a 3.9-fold higher risk of 90-day mortality and 2.2-fold higher risk of 30-day mortality in CS group, supporting its relevance in this population and further underscoring the prognostic significance of progressing to an extreme stage. The definition of each stage varies across the studies ( 4 ). In the updated edition, SCAI classification describes stages D and E as the deterioration following the initial treatment ( 24 ) and thus, we incorporated the deterioration after 24 hours of ICU admission into Stage D and E sorting as recent studies ( 5 , 6 ). Our findings further emphasize the importance of early therapeutic interventions before the patient's condition deteriorates, for patients presenting with CS, including those with COVID-19. Utilization of temporary mechanical circulation support Lastly, our study revealed limited utilization of MCS in patients with CS, with only 8 out of 74 patients receiving it, although that in general CS populations reported at 13.9–16.0% ( 25 ). V-V ECMO was initiated in 21 patients but converted to V-A ECMO in only 2 cases. Although data on MCS use in COVID-19 remain sparse, early pandemic literature similarly reports limited application of V-A ECMO ( 26 ). Several factors may explain these low utilization rates, including concerns that artificial devices could exacerbate infections, resource shortages during the pandemic, and guideline-based contraindications to ECMO for high-risk patients with comorbidities ( 27 ). According to previous reports in pandemic, patients treated with V-A ECMO often had significant comorbidities and faced extremely high mortality rates, ranging from 75–100% ( 27 ). Given the particularly severe nature of CS in COVID-19, the reversibility of the underlying pathophysiology and the potential efficacy of MCS remain uncertain. While indications for MCS and the specific cohorts who benefit have been explored in AMI-related CS ( 28 ), Our study in COVID-19-related CS did not demonstrate a mortality benefit associated with MCS use, although study scale was limited. Given the background of infection and the high baseline mortality, even outside the pandemic context, the use of MCS for COVID-19-related CS should be carefully considered. Limitations 1) This is a retrospective analysis, and thus, systemic biases are inevitable. Broader validation in other registry datasets would mitigate the risk of bias. 2) Echocardiographic findings are not included in this study. Detailed cardiac assessment in large-scale COVID-19 cohorts remains scarce, and due to limitations in data collection, this study could not address this gap. 3) Some key data are unavailable, including certain laboratory results, detailed hemodynamic information in the ICU, and clinical course after discharge. The absence of these data prevents a comprehensive characterization of patient profiles, in-hospital presentations, precise SCAI CS staging (based on lactate and BP). CONCLUSION In our Cardiac Sub-study, CS occurred in 9.5% of ICU-admitted COVID-19 cases. A history of ventricular arrhythmia was the only independent factor associated with CS. Furthermore, CS was linked to a higher 30-day mortality rate than that of patients without CS (56.8% vs. 33.4%) and SCAI staging demonstrated its utility in predicting mortality risk in this COVID-19 cohort. Declarations Ethics approval and consent to participate This study protocol was reviewed under the National Mutual Acceptance scheme by the Alfred Health Human Research Ethics Committee on February 27, 2020, and the study was conducted in accordance with both the protocols, the Declaration of Helsinki, and the Principles of Good Clinical Practice. All participating sites obtained approval from their local ethics board and received waivers of informed consent for all patients. Consent for publication All co-authors have approved the current version of the manuscript and consent to its submission to Journal of Intensive Care. Availability of data and material The data that support the findings of this study are available from the Critical Care Consortium COVID-19. Restrictions apply to the availability of these data, which were used under license for the current study and are therefore not publicly available. Data may, however, be obtained from the authors upon reasonable request and with the permission of the Critical Care Consortium COVID-19. Competing interests We declare that the authors have no competing interests as defined by BMC, or other interests that might be perceived to influence the results and/or discussion reported in this paper Funding: The Bill & Melinda Gates Foundation, Grant number INV-034765; Queensland Health; The Prince Charles Hospital Foundation; The Wesley Medical Research; Fisher & Paykel Healthcare; The University of Queensland; The Health Research Board of Ireland. Jacky Y Suen is funded by the Advance Queensland fellowship program, Queensland Government, Australia. Gianluigi Li Bassi is a recipient of the BITRECS fellowship; the “BITRECS” project has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement no. 754550 and from the “La Caixa” Foundation (ID 100010434), under the agreement LCF/PR/GN18/50310006. Author contributions Conceptualization: All authors. Statistical analysis: NW Illustrations and Figures: HN Writing original draft preparation: HN, KS Writing-review and editing: All authors. All authors have read and agreed to the published version of the manuscript. Acknowledgements: We recognize the crucial importance of the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) and Short Period Incidence Study of Severe Acute Respiratory Infection (SPRINT-SARI) networks in developing and expanding the global Coronavirus Disease 2019 Critical Care Consortium (COVID-19– CCC). We thank the generous support we received from the Extracorporeal Life Support Organization and the International Extracorporeal Membrane Oxygenation Network. We owe Li Wenliang, MD from the Wuhan Central Hospital, an eternal debt of gratitude for reminding the world that doctors should never be censored during a pandemic. Finally, we acknowledge all members of the COVID-19–CCC and various collaborators. References Tehrani BN, Truesdell AG, Psotka MA, Rosner C, Singh R, Sinha SS, et al. A Standardized and Comprehensive Approach to the Management of Cardiogenic Shock. JACC: Heart Failure. 2020;8(11):879-91. Zweck E, Thayer KL, Helgestad OKL, Kanwar M, Ayouty M, Garan AR, et al. Phenotyping Cardiogenic Shock. Journal of the American Heart Association. 2021;10(14):e020085. Miller PE, Huber K, Bohula EA, Krychtiuk KA, Pöss J, Roswell RO, et al. Research Priorities in Critical Care Cardiology: JACC Expert Panel. J Am Coll Cardiol. 2023;82(24):2329-37. Naidu SS, Baran DA, Jentzer JC, Hollenberg SM, van Diepen S, Basir MB, et al. SCAI SHOCK Stage Classification Expert Consensus Update: A Review and Incorporation of Validation Studies: This statement was endorsed by the American College of Cardiology (ACC), American College of Emergency Physicians (ACEP), American Heart Association (AHA), European Society of Cardiology (ESC) Association for Acute Cardiovascular Care (ACVC), International Society for Heart and Lung Transplantation (ISHLT), Society of Critical Care Medicine (SCCM), and Society of Thoracic Surgeons (STS) in December 2021. J Am Coll Cardiol. 2022;79(9):933-46. Morici N, Frea S, Bertaina M, Sacco A, Corrada E, Dini CS, et al. SCAI stage reclassification at 24 h predicts outcome of cardiogenic shock: Insights from the Altshock-2 registry. Catheter Cardiovasc Interv. 2023;101(1):22-32. Puri K, Jentzer JC, Spinner JA, Hope KD, Adachi I, Tume SC, et al. Clinical Presentation, Classification, and Outcomes of Cardiogenic Shock in Children. J Am Coll Cardiol. 2024;83(5):595-608. Woodruff RC, Garg S, George MG, Patel K, Jackson SL, Loustalot F, et al. Acute Cardiac Events During COVID-19-Associated Hospitalizations. J Am Coll Cardiol. 2023;81(6):557-69. Sato K, Sinclair JE, Sadeghirad H, Fraser JF, Short KR, Kulasinghe A. Cardiovascular disease in SARS-CoV-2 infection. Clin Transl Immunology. 2021;10(9):e1343. Pellegrini D, Kawakami R, Guagliumi G, Sakamoto A, Kawai K, Gianatti A, et al. Microthrombi as a Major Cause of Cardiac Injury in COVID-19: A Pathologic Study. Circulation. 2021;143(10):1031-42. Giustino G, Pinney SP, Lala A, Reddy VY, Johnston-Cox HA, Mechanick JI, et al. Coronavirus and Cardiovascular Disease, Myocardial Injury, and Arrhythmia: JACC Focus Seminar. Journal of the American College of Cardiology. 2020;76(17):2011-23. Kawakami R, Sakamoto A, Kawai K, Gianatti A, Pellegrini D, Nasr A, et al. Pathological Evidence for SARS-CoV-2 as a Cause of Myocarditis: JACC Review Topic of the Week. J Am Coll Cardiol. 2021;77(3):314-25. Ton V-K, Li S, John K, Li B, Zweck E, Kanwar MK, et al. Serial Shock Severity Assessment Within 72 Hours After Diagnosis. Journal of the American College of Cardiology. 2024;84(11):978-90. Li Bassi G, Suen J, Barnett AG, Corley A, Millar J, Fanning J, et al. Design and rationale of the COVID-19 Critical Care Consortium international, multicentre, observational study. BMJ Open. 2020;10(12):e041417. Rubin R. Global Effort to Collect Data on Ventilated Patients With COVID-19. JAMA. 2020;323(22):2233-4. Akhtar Z, Trent M, Moa A, Tan TC, Fröbert O, MacIntyre CR. The impact of COVID-19 and COVID vaccination on cardiovascular outcomes. Eur Heart J Suppl. 2023;25(Suppl A):A42-a9. Tavazzi G, Tricella G, Garbero E, Zamperoni A, Zanetti M, Finazzi S. Cardiogenic shock in general intensive care unit: a Nationwide prospective analysis of epidemiology and outcome. Eur Heart J Acute Cardiovasc Care. 2024. Aissaoui N, Puymirat E, Delmas C, Ortuno S, Durand E, Bataille V, et al. Trends in cardiogenic shock complicating acute myocardial infarction. Eur J Heart Fail. 2020;22(4):664-72. Samsky MD, Morrow DA, Proudfoot AG, Hochman JS, Thiele H, Rao SV. Cardiogenic Shock After Acute Myocardial Infarction: A Review. Jama. 2021;326(18):1840-50. Berg DD, Bohula EA, van Diepen S, Katz JN, Alviar CL, Baird-Zars VM, et al. Epidemiology of Shock in Contemporary Cardiac Intensive Care Units. Circ Cardiovasc Qual Outcomes. 2019;12(3):e005618. Roth Gregory A, Vaduganathan M, Mensah George A. Impact of the COVID-19 Pandemic on Cardiovascular Health in 2020. Journal of the American College of Cardiology. 2022;80(6):631-40. van Diepen S, Katz JN, Albert NM, Henry TD, Jacobs AK, Kapur NK, et al. Contemporary Management of Cardiogenic Shock: A Scientific Statement From the American Heart Association. Circulation. 2017;136(16):e232-e68. Armstrong RA, Kane AD, Cook TM. Outcomes from intensive care in patients with COVID-19: a systematic review and meta-analysis of observational studies. Anaesthesia. 2020;75(10):1340-9. van Diepen S, Pöss J, Senaratne JM, Gage A, Morrow DA. Mixed Cardiogenic Shock: A Proposal for Standardized Classification, a Hemodynamic Definition, and Framework for Management. Circulation. 2024;150(18):1459-68. Naidu SS, Baran DA, Jentzer JC, Hollenberg SM, Diepen Sv, Basir MB, et al. SCAI SHOCK Stage Classification Expert Consensus Update: A Review and Incorporation of Validation Studies. Journal of the American College of Cardiology. 2022;79(9):933-46. Lang CN, Kaier K, Zotzmann V, Stachon P, Pottgiesser T, von Zur Muehlen C, et al. Cardiogenic shock: incidence, survival and mechanical circulatory support usage 2007-2017-insights from a national registry. Clin Res Cardiol. 2021;110(9):1421-30. MacLaren G, Fisher D, Brodie D. Preparing for the Most Critically Ill Patients With COVID-19: The Potential Role of Extracorporeal Membrane Oxygenation. JAMA. 2020;323(13):1245-6. Shekar K, Badulak J, Peek G, Boeken U, Dalton HJ, Arora L, et al. Extracorporeal Life Support Organization Coronavirus Disease 2019 Interim Guidelines: A Consensus Document from an International Group of Interdisciplinary Extracorporeal Membrane Oxygenation Providers. Asaio j. 2020;66(7):707-21. Thiele H, Møller JE, Henriques JPS, Bogerd M, Seyfarth M, Burkhoff D, et al. Temporary mechanical circulatory support in infarct-related cardiogenic shock: an individual patient data meta-analysis of randomised trials with 6-month follow-up. The Lancet. 2024;404(10457):1019-28. Additional Declarations No competing interests reported. Supplementary Files CardiogenicShockCOVID19tables.docx CardiogenicShockCOVID19graphicalabstract.tif Graphical Abstract. Prevalence and Outcomes of Cardiogenic Shock in COVID-19 Cohort. (A) Between March 2020 and January 2022, 1,155 patients were admitted to the ICU. Of these, 375 were excluded because of insufficient data. Among the 780 patients analyzed, 74 (9.5%) were admitted with a diagnosis of CS and COVID-19. (B) Arrhythmia was observed in over half of all CS cases, followed by congestive HF and AMI. Arrhythmia included both atrial and ventricular arrhythmia requiring additional antiarrhythmics or device therapy. (C) The mortality rate among CS cases was significantly higher than that of patients without CS (56.8% vs. 33.4%; P <0.001). Furthermore, patients in SCAI stage E had substantially higher mortality than other patients with CS (74.2% vs. 44.2%; P <0.001). Because only two patients were classified as SCAI stage D, stages C and D were combined for the mortality analysis. (D) Kaplan-Meier curves for 90-day mortality revealed a significantly worse clinical course for patients in Stage E. CS, cardiogenic shock; ICU, intensive care unit; CA, cardiac arrest; HF, heart failure; AMI, acute myocardial infarction; SCAI, Society for Cardiovascular Angiography and Interventions, HR, hazard ratio; CI, confidence interval. EthicsApprovalNumber.pdf CardiogenicShockCOVID19supplementaryfiles.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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1","display":"","copyAsset":false,"role":"figure","size":154462,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eStacked Probability Plot for patients with Cardiogenic Shock\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe stacked probability plot depicts the state occupation probabilities, allowing for the comparison of six different probabilities at a certain time. Over 90 days, 48 patients (64.9%) died in patients with CS. The terms are defined as follows: 1) “No Cardiac Arrest or MCS” represents ICU stay without the occurrence of CA or MCS therapy, 2) “Cardiac Arrest” indicates the occurrence of CA on that day, 3) “MCS” reflects the proportion of patients with MCS placed on that day, and 4) “Hospitalized” refers to being admitted outside the ICU but remaining in the hospital.\u003c/p\u003e\n\u003cp\u003eCS, cardiogenic shock; CA, cardiac arrest; MCS, mechanical circulatory support; ICU, intensive care unit.\u003c/p\u003e","description":"","filename":"CardiogenicShockCOVID19figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-7096750/v1/2cf97f31fe08ca43492073ab.png"},{"id":101754204,"identity":"37fb620c-8fe1-47f6-aa8c-037c2c333263","added_by":"auto","created_at":"2026-02-03 10:42:02","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1272766,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7096750/v1/4f78a893-b449-474f-b2a5-942bc92b325b.pdf"},{"id":92152698,"identity":"f2db2df6-36c1-4f49-86dc-9b5d91d14ba1","added_by":"auto","created_at":"2025-09-25 08:29:21","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":49041,"visible":true,"origin":"","legend":"","description":"","filename":"CardiogenicShockCOVID19tables.docx","url":"https://assets-eu.researchsquare.com/files/rs-7096750/v1/e156fc3bbd79fd5d5f4b4ea3.docx"},{"id":92152975,"identity":"9f571fc9-0811-47d7-94f8-4ad72e056e6f","added_by":"auto","created_at":"2025-09-25 08:37:21","extension":"tif","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":102192,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eGraphical Abstract. Prevalence and Outcomes of Cardiogenic Shock in COVID-19 Cohort.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(A) Between March 2020 and January 2022, 1,155 patients were admitted to the ICU. Of these, 375 were excluded because of insufficient data. Among the 780 patients analyzed, 74 (9.5%) were admitted with a diagnosis of CS and COVID-19.\u003c/p\u003e\n\u003cp\u003e(B) Arrhythmia was observed in over half of all CS cases, followed by congestive HF and AMI. Arrhythmia included both atrial and ventricular arrhythmia requiring additional antiarrhythmics or device therapy.\u003c/p\u003e\n\u003cp\u003e(C) The mortality rate among CS cases was significantly higher than that of patients without CS (56.8% vs. 33.4%; \u003cem\u003eP\u003c/em\u003e \u0026lt;0.001). Furthermore, patients in SCAI stage E had substantially higher mortality than other patients with CS (74.2% vs. 44.2%; \u003cem\u003eP\u003c/em\u003e \u0026lt;0.001). Because only two patients were classified as SCAI stage D, stages C and D were combined for the mortality analysis.\u003c/p\u003e\n\u003cp\u003e(D) Kaplan-Meier curves for 90-day mortality revealed a significantly worse clinical course for patients in Stage E.\u003c/p\u003e\n\u003cp\u003eCS, cardiogenic shock; ICU, intensive care unit; CA, cardiac arrest; HF, heart failure; AMI, acute myocardial infarction; SCAI, Society for Cardiovascular Angiography and Interventions, HR, hazard ratio; CI, confidence interval.\u003c/p\u003e","description":"","filename":"CardiogenicShockCOVID19graphicalabstract.tif","url":"https://assets-eu.researchsquare.com/files/rs-7096750/v1/286ee414ac1ff04c6a1e980f.tif"},{"id":92152703,"identity":"5b325e6b-2f50-47bd-ad45-61e40c918ee2","added_by":"auto","created_at":"2025-09-25 08:29:21","extension":"pdf","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":440843,"visible":true,"origin":"","legend":"","description":"","filename":"EthicsApprovalNumber.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7096750/v1/2037576aadb5b0e52a8e8cd0.pdf"},{"id":92152710,"identity":"3707172f-40d8-4e3b-92fb-24bd73088105","added_by":"auto","created_at":"2025-09-25 08:29:21","extension":"docx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":107228,"visible":true,"origin":"","legend":"","description":"","filename":"CardiogenicShockCOVID19supplementaryfiles.docx","url":"https://assets-eu.researchsquare.com/files/rs-7096750/v1/e9a956ceaeee31c3dbcbd045.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Clinical Course and Outcomes of Cardiogenic Shock in COVID-19 : Insights from COVID-19 Critical Care Consortium","fulltext":[{"header":"CLINICAL PERSPECTIVS","content":"\u003col\u003e\n \u003cli\u003eCS was observed in 9.5% of COVID-19 cases admitted to the ICU and was associated with significantly higher mortality compared to those without CS.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eA medical history of previous VT/VF was an independent predictor of CS complications.\u003c/li\u003e\n \u003cli\u003eThe SCAI staging system was applicable to this population, indicating that worsening conditions after ICU admission were associated with an even higher mortality risk.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"INTRODUCTION","content":"\u003cp\u003eCardiogenic shock (CS) is a life-threatening condition observed in severe cardiac diseases (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). In this context, a dysfunctional heart fails to maintain adequate cardiac output, leading to hemodynamics collapses, and patients progress to death without intensive pharmacologic or mechanical circulatory support (MCS) (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Recently, its pathophysiology has been actively discussed (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) leading to a new classification system based on mortality risk and clinical characteristics (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). The Society for Cardiovascular Angiography and Interventions (SCAI) CS classification is one such risk prediction model, and its utility has been validated primarily in CS related to acute myocardial infarction (AMI) and heart failure (HF) (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eCOVID-19 has been linked to various cardiac complications (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Viral-induced direct myocardial injury, along with indirect damage via excessive inflammation, alteration in endothelial function, and microthrombi, can cause severe cardiovascular disorders (\u003cspan additionalcitationids=\"CR9 CR10\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). A large cohort study from the U.S. reported that AMI, HF, and myocarditis were observed in 5.5%, 5.4%, and 0.3% of all adult patients hospitalized with SARS-CoV-2 infection, respectively (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Pathophysiological studies have further demonstrated microthrombi and myocyte necrosis in 35% of collected heart samples, highlighting the substantial cardiac impact of COVID-19 (\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). All these heart diseases potentially progress to CS, and thus, identifying predictors and outlining epidemiological data could assist clinicians in providing effective critical care, as demonstrated in AMI-related and HF-related CS (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). However, data on CS in this cohort remains limited, and the applicability of SCAI CS staging has not been broadly assessed outside AMI and HF cohorts.\u003c/p\u003e\u003cp\u003eThe COVID-19 Critical Care Consortium (CCCC) registry is one of the largest global datasets on COVID-19 in intensive care units (ICUs) (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). This study aimed to describe the characteristics and clinical course of CS in patients with COVID-19, and to assess the applicability of SCAI staging, using data from the CCCC registry.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy Design:\u003c/h2\u003e\u003cp\u003eThe CCCC registry is an international database enrolling COVID-19 patients requiring intensive care in 459 ICUs across 50 countries. In this registry, we used the Cardiac Sub-study dataset, which focused on data related to cardiac diseases. The study design has been described in a previous publication (Trial registration ACTRN12620000421932) (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). This study protocol was reviewed under the National Mutual Acceptance scheme by the Alfred Health Human Research Ethics Committee on February 27, 2020 (Project: 62066, Local reference: 108/20), and the study was conducted in accordance with both the protocols, the Declaration of Helsinki, and the Principles of Good Clinical Practice. All participating hospitals obtained local approval from their human research ethics committee prior to data collection; and a waiver of informed consent was granted in all cases. Detailed information on the local ethics committee/institutional review board is included in the \u003cb\u003eSupplemental Digital Content (Ethics Approval Number).\u003c/b\u003e\u003c/p\u003e\u003cp\u003eAll data related to patient backgrounds, presentation, treatment, and outcomes were gathered from the electronic case report form. The University of Queensland received clinical data from the data custodians via data sharing agreements.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eStudy Population:\u003c/h3\u003e\n\u003cp\u003eThis analysis included consecutive patients\u0026thinsp;\u0026ge;\u0026thinsp;18 years of age enrolled in the CCCC Cardiac Sub-study dataset from March 2020 to January 2022 (n\u0026thinsp;=\u0026thinsp;1,155). Cases with missing data on CS and CA were excluded.\u003c/p\u003e\n\u003ch3\u003eVariable Definitions:\u003c/h3\u003e\n\u003cp\u003eIn the CCCC Cardiac Sub-study database, the diagnosis of CS was adjudicated by clinicians at each hospital at ICU admission based on persistent hypotension\u0026mdash;specifically, systolic blood pressure (BP)\u0026thinsp;\u0026lt;\u0026thinsp;90 mmHg or mean BP\u0026thinsp;\u0026lt;\u0026thinsp;65 mmHg\u0026mdash;and evidence of low cardiac output and elevated filling pressures. Cardiac arrest (CA) was defined as sudden and unexpected cessation of cardiac activity with no normal breathing and no signs of circulation. MCS included 1) venoarterial extracorporeal membrane oxygenator (V-A ECMO), 2) micro axial flow pump, and 3) intra-aortic balloon pumping. Based on the previous papers (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e), the SCAI CS staging was defined as follows: Stage C - CS without CA or MCS from 24 hours after ICU admission through a 30-day period; Stage D - MCS initiation after 24 hours of ICU admission through 30 days; Stage E - CA after 24 hours of ICU admission through 30 days. Deterioration in lactate level or hemodynamic parameters and increasing vasopressor/inotropes use were not considered in this staging model owing to a lack of data after 24 hours of ICU admission.\u003c/p\u003e\u003cp\u003eOther definitions are described in Supplementary Table\u0026nbsp;1.\u003c/p\u003e\n\u003ch3\u003eOutcomes:\u003c/h3\u003e\n\u003cp\u003eThe primary outcome was 30-day all-cause mortality. Data on MCS therapy, CA incidence, hospital stay, discharge, and in-hospital mortality were collected to describe the patient's clinical course. All included patients were followed for 90 days or until death in hospital or hospital discharge.\u003c/p\u003e\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003eStatistical Analysis:\u003c/h2\u003e\u003cp\u003eBaseline characteristics, clinical parameters and outcome were summarized descriptively for all eligible patients, stratified by confirmed CS status (CS vs. No CS). Categorical variables were summarized as frequencies and percentages, while continuous variables were summarized using medians and interquartile range (IQR: Q1 to Q3) for consistency. The clinical course of patients with CS was described with a stacked probability plot up to 90 days after ICU admission. Observed mortality stratified by SCAI stage was visualized by Kaplan-Meier survival curves. Evidence of differences in survival curves was assessed using the log-rank test and hazard ratios (HRs) of the association between SCAI stage and 30-day and 90-day mortality were estimated by a Cox proportional hazards model. Associations between patient-level characteristics with CS incidence and 30-day mortality were examined using logistic regression. Model parameters in fitted models were summarized as an odds ratio (OR) and 95% confidence interval (CI). Wald hypothesis tests for model parameters assessed evidence for statistically significant associations, assuming a 5% level of statistically significant. Variance inflation factors were calculated to assess multicollinearity in multivariable regression models.\u003c/p\u003e\u003cp\u003eAnalyses were carried out using R version 4.4.1 software (R Foundation for Statistical Computing, Vienna, Austria).\u003c/p\u003e\u003c/div\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\u003ch2\u003eBaseline characteristics:\u003c/h2\u003e\u003cp\u003eOf 1,155 patients, 375 were excluded because of missing data on CS (n\u0026thinsp;=\u0026thinsp;358) or CA (n\u0026thinsp;=\u0026thinsp;17), and the data of 780 patients were analysed (Graphical Abstract A). Of patients included (n\u0026thinsp;=\u0026thinsp;780), 74 cases were diagnosed with CS (9.5%) at ICU admission. Included population age was 58.0 [48.0\u0026ndash;67.0], and 38.3% (n\u0026thinsp;=\u0026thinsp;299) was female (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Patients of White and Asian ethnicity and sites in Asia Pacific and North America accounted for most parts of the study population. Further, 99.5% of the entire cohort was admitted in 2020 or 2021, and the number of admissions gradually declined during 2021 (Supplementary Fig.\u0026nbsp;1). At baseline, calcium channel blocker, beta-blocker, and renin-angiotensin system inhibitors were prescribed to 8.8% (n\u0026thinsp;=\u0026thinsp;69), 12.9% (n\u0026thinsp;=\u0026thinsp;101) and 11.8% (n\u0026thinsp;=\u0026thinsp;92) of all patients, respectively. In the CS group, a history of ischemic heart disease (23.0% vs 20.0%), congestive HF (25.7% vs. 15.9%), and ventricular arrhythmia (16.2% vs. 8.4%) was observed more frequently compared to the no CS group. Vaccination with at least one dose was reported in 13.5% of no CS patients and 10.8% of CS patients, respectively.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003e\u003cb\u003eBaseline Characteristics\u003c/b\u003e Median and interquartile range: n; median (IQR). The number in parentheses represents the percentage (%).\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAll patients\u003c/p\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;780\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNo CS\u003c/p\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;706\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eCS\u003c/p\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;74\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge (median [IQR])\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e58.0 [48.0\u0026ndash;67.0]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e58.0 [48.0\u0026ndash;67.0]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e60.0 [49.0\u0026ndash;66.0]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e299.0 (38.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e273.0 (38.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e26.0 (35.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBMI kg/m (median [IQR])\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e28.7 [24.8\u0026ndash;33.2]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e28.9 [24.8\u0026ndash;33.2]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e28.6 [25.1\u0026ndash;34.7]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eEthnicity\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAboriginal (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9.0 (1.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9.0 (1.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAsian (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e270.0 (34.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e248.0 (35.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e22.0 (29.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eArab (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e109.0 (14.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e103.0 (14.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6.0 (8.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBlack (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e52.0 (6.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e46.0 (6.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6.0 (8.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWhite (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e252.0 (32.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e219.0 (31.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e33.0 (44.6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOther (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e33 (4.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e27 (3.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6 (8.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eGeographic Region\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAfrica (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e17 (2.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16 (2.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1 (1.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAsia (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e352 (45.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e326 (46.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e26 (35.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEurope (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e62 (7.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e60 (8.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2 (2.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLatin America and the Caribbean (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e60 (7.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e39 (5.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e21 (28.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNorthern America (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e289 (37.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e265 (37.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e24 (32.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAdmission Era\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2020 (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e457 (58.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e403 (57.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e54 (73.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2021 (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e319 (40.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e299 (42.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e20 (27.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2022 (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (0.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (0.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eExisting Comorbidities\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSmoking (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e159 (20.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e137 (19.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e22 (29.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiabetes (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e243 (31.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e216 (30.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e27 (36.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHypertension (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e421 (54.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e380 (53.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e41 (55.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChronic pulmonary disease (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e64 (8.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e58 (8.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6 (8.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChronic kidney disease (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e117 (15.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e105 (14.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12 (16.2)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMalignant neoplasm (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e24 (3.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e23 (3.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1 (1.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMedication\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCalcium channel blocker (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e69 (8.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e68 (9.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1 (1.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBeta-blocker (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e101 (12.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e94 (13.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7 (9.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eACEi/ARB (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e92 (11.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e83 (11.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e9 (12.2)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiuretic (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e97 (12.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e88 (12.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e9 (12.2)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCardiac Disease History\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIschemic heart disease (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e158 (20.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e141 (20.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e17 (23.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCongestive heart failure (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e131 (16.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e112 (15.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e19 (25.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVentricular arrhythmia (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e71 (9.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e59 (8.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12 (16.2)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePreviously implanted device (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13 (1.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9 (1.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4 (5.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCongenital heart disease (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13 (1.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12 (1.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1 (1.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePre-existing cardiomyopathy (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e22 (2.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e17 (2.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5 (6.8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePresence of prosthetic valve (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (0.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (0.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1 (1.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRecent ACS (within 6 months) (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e54 (6.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e46 (6.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8 (10.8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eVaccination\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOne or more doses received (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e103 (13.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e95 (13.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8 (10.8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eCS, cardiogenic shock; IQR, interquartile range; BMI, body mass index; ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker, ACS, acute coronary syndrome.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eIn-hospital course:\u003c/h3\u003e\n\u003cp\u003eData on presentation within 24 hours of ICU admission was missing for between 437 and 580 patients. In this limited population, the mean values of C-reactive protein (144.8 vs. 82.6mg/L) and Troponin I (0.15 vs. 0.03 ng/ml) were higher in patients with CS (Supplementary Table\u0026nbsp;2).\u003c/p\u003e\u003cp\u003eCS cases more frequently received intensive therapeutic interventions, including\u0026thinsp;\u0026ge;\u0026thinsp;2 vasoactive drugs (17.6% vs. 9.1%), and renal replacement therapy (16.2% vs. 8.8%), compared to those without CS (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). MCS was used for 8 cases in the CS group.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003e\u003cb\u003eTreatment During ICU Stay\u003c/b\u003e The number in parentheses represents the percentage (%).\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAll patients\u003c/p\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;780\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNo CS\u003c/p\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;706\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eCS\u003c/p\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;74\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026ge;\u0026thinsp;2 vasoactive agents (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e77 (9.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e64 (9.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e13 (17.6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMechanical ventilation (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e472 (60.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e414 (58.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e58 (78.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRenal replacement therapy (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e74 (9.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e62 (8.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12 (16.2)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eECMO\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eV-V ECMO\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e175 (22.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e154 (21.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e21 (28.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eV-A ECMO\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (0.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (0.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5 (6.8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eConversion V-V \u0026rarr; V-A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (0.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2 (2.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDual lumen\u003c/p\u003e\u003cp\u003e+ single cannula V-V ECMO\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e20 (2.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20 (2.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCardiac assist device\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003emAFP\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (0.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1 (1.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIABP\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (0.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4 (5.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eAmong patients with CS, V-A ECMO was used in 5 patients, mAFP in 1 patient, and IABP in 4 patients. The single mAFP case and 1 of the 4 IABP cases also received V-A ECMO therapy. Overall, 8 patients underwent MCS. The breakdown is as follows:\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u0026bull; V-A ECMO alone: n\u0026thinsp;=\u0026thinsp;3\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u0026bull; V-A ECMO\u0026thinsp;+\u0026thinsp;mAFP: n\u0026thinsp;=\u0026thinsp;1\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u0026bull; V-A ECMO\u0026thinsp;+\u0026thinsp;IABP: n\u0026thinsp;=\u0026thinsp;1\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u0026bull; IABP alone: n\u0026thinsp;=\u0026thinsp;3\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eCS, cardiogenic shock; ECMO, extracorporeal membrane oxygenation; V-V, venovenous; V-A, venoarterial; mAFP, micro axial flow pump; IABP, intra-aortic balloon pumping.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eOver half of the CS group (58.1%; n\u0026thinsp;=\u0026thinsp;43/74) developed atrial/ventricular arrhythmia requiring antiarrhythmics or device therapy, followed by congestive HF (35.1%; n\u0026thinsp;=\u0026thinsp;26/74) and AMI (18.9%; n\u0026thinsp;=\u0026thinsp;14/74; Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e and Graphical Abstract B). Myocarditis (8.1%) and takotsubo syndrome (1.4%) were also reported. CS group more frequently experienced acute respiratory distress syndrome (ARDS; 81.1% vs. 62.5%), acute kidney injury (AKI; 74.3% vs. 42.2%), disseminated intravascular coagulation (DIC; 23.0% vs. 11.3%), bacteremia (43.2% vs. 18.8%), and bleeding events (16.2% vs. 7.4%), compared to the cohort without CS. Pulmonary embolism, stroke, and liver dysfunction were observed in both groups at comparable prevalence rates.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003e\u003cb\u003eComplications During ICU Stay\u003c/b\u003e The number in parentheses represents the percentage (%).\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAll patients\u003c/p\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;780\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNo CS\u003c/p\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;706\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eCS\u003c/p\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;74\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e\u003cp\u003eCardiac complication\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAMI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e78 (10.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e64 (9.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e14 (18.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCongestive HF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e130 (16.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e104 (14.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e26 (35.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCardiac arrhythmia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e168 (21.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e125 (17.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e43 (58.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMyocarditis/Pericarditis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7 (0.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (0.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6 (8.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEndocarditis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7 (0.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (0.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1 (1.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTakotsubo syndrome\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (0.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1 (1.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eOther organ complications\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eARDS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e501 (64.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e441 (62.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e60 (81.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePulmonary embolism\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e39 (5.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e35 (5.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4 (5.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePleural effusion\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e145 (18.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e123 (17.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e22 (29.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStroke/CVA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e22 (2.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20 (2.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2 (2.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMeningitis/Encephalitis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (0.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (0.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1 (1.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAKI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e353 (45.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e298 (42.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e55 (74.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLiver dysfunction\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e74 (9.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e65 (9.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e9 (12.2)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCoagulation disorder/DIC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e97 (12.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e80 (11.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e17 (23.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBacteremia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e165 (21.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e133 (18.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e32 (43.2)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHemorrhage\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e64 (8.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e52 (7.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12 (16.2)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eCS, cardiogenic shock; AMI, acute myocardium infarction; HF, heart failure; ARDS, acute respiratory distress syndrome; CVA, cerebrovascular accident; DIC, disseminated intravascular coagulation; AKI, acute kidney injury.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eFactors associated with cardiogenic shock complication:\u003c/h2\u003e\u003cp\u003eHistory of ventricular arrhythmia (ventricular tachycardia (VT)/ventricular fibrillation (VF)) was the sole independent factor associated with CS in our multivariable logistic regression analysis (OR 3.9; 95% CI, 1.6\u0026ndash;9.5; Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). The factors included in this analysis were previously reported to be associated with the incidence of cardiac complications in COVID-19 (age, gender, unvaccinated, history of heart disease) (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). No multicollinearity was observed among the variables, with all showing low variance inflation factors (\u0026lt;\u0026thinsp;2.0), as detailed in Supplementary Table\u0026nbsp;3.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eMultivariable Logistic Regression Output for Cardiogenic Shock with Site and Era as Random Effects\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eParameter\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOR\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e95% CI\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eP value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge, years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.99\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.97\u0026ndash;1.02\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.616\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.92\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.49\u0026ndash;1.73\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.798\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUnvaccinated\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.07\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.55\u0026ndash;2.09\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.850\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eKnown Ischemic Heart Disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.88\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.33\u0026ndash;2.40\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.807\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eKnown Congestive HF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.77\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.29\u0026ndash;2.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.591\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eKnown Arrhythmia (VT/VF)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e3.89\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.60\u0026ndash;9.47\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.003\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRecent ACS (within 6 months)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2.96\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.94\u0026ndash;9.28\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.063\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eOR, odds ratio; CI, confidence interval: HF, heart failure; VT, ventricular tachycardia; VF, ventricular fibrillation; ACS, acute coronary syndrome.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003eMortality and SCAI CS staging:\u003c/h2\u003e\u003cp\u003eThe 30-day mortality rate in the total population was 35.6% (n\u0026thinsp;=\u0026thinsp;278/780), with rates of 56.8% (n\u0026thinsp;=\u0026thinsp;42/74) and 33.4% (n\u0026thinsp;=\u0026thinsp;236/706) for patients with and without CS, respectively (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001; Graphical Abstract C). All patients with CS were classified into SCAI stage C (n\u0026thinsp;=\u0026thinsp;41), D (n\u0026thinsp;=\u0026thinsp;2), and E (n\u0026thinsp;=\u0026thinsp;31), and their mortality rates were 43.9%, 50.0%, and 74.2%, respectively (Supplementary Table\u0026nbsp;4). Due to the small number of patients in Stage D, stages C and D were combined for analysis. SCAI stage E showed a significantly higher 30-day mortality risk compared to stage C/D (HR 2.2; 95% CI, 1.4-4.0). Kaplan-Meier survival analysis for 90 days, presented in Graphical Abstract D, also showed significantly higher mortality in stage E (83.9% vs. 72.1%; HR: 3.6; 95% CI: 1.4\u0026ndash;10.4).\u003c/p\u003e\u003cp\u003eA higher proportion of patients in Stage E were female (41.9% [n\u0026thinsp;=\u0026thinsp;13/31] vs. 30.2% [n\u0026thinsp;=\u0026thinsp;13/43]) and Asian (48.4% [n\u0026thinsp;=\u0026thinsp;15/31] vs. 16.3% [n\u0026thinsp;=\u0026thinsp;7/43]) compared to those in Stage C/D. Additionally, patients in Stage E were relatively younger (median age: 57.0 years [IQR, 46.5\u0026ndash;65.5] vs. 61.0 years [IQR, 50.0\u0026ndash;67.5]) (Supplementary Table\u0026nbsp;5).\u003c/p\u003e\u003cp\u003eThe stacked probability plot (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) shows the probability of the following six events (ICU admission without CA or MCS, MCS placement, incidence of CA, hospitalization out of ICU, discharge, and death) after ICU admission. The 90-day mortality was 64.9% (n\u0026thinsp;=\u0026thinsp;48/74).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe most common cause of death in patients with CS was multiorgan failure, followed by cardiac death and respiratory failure (Supplementary Fig.\u0026nbsp;2).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003eFactors associated with mortality in cardiogenic shock\u003c/h2\u003e\u003cp\u003eThe univariable analysis for 30-day mortality in CS group (Supplementary Table\u0026nbsp;6) was carried out to clarify the impact of potential confounders on mortality in the CS group because we suspected that the high prevalence of bacteremia (43.2%, n\u0026thinsp;=\u0026thinsp;32/74) and bleeding events (16.2%, n\u0026thinsp;=\u0026thinsp;12/74) in the CS group compromised hemodynamic status as septic shock or hemorrhage shock and led to high mortality. However, bacteremia (HR 0.62; 95% CI 0.24\u0026ndash;1.56) and hemorrhage (HR 2.55; 95% CI 0.68\u0026ndash;12.31) did not have a significant association with mortality in univariable analysis. Further, MCS use during ICU stay (n\u0026thinsp;=\u0026thinsp;8) and unvaccinated status were not associated with mortality, whereas SCAI stage E was associated with mortality in CS cases (HR 3.6; 95%CI: 1.4\u0026ndash;10.4).\u003c/p\u003e\u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThis study demonstrated that CS prevalence in COVID-19 patients admitted to ICU was 9.5%. A history of ventricular arrhythmia (VT/VF) was associated with a 3.9-fold increased risk of complicating CS. Furthermore, 30-day mortality in patients with CS was 56.8%, significantly higher than that of patients without CS (33.4%). Patients with CS classified as SCAI stage E had the highest mortality, with a 2.2-fold and 3.6-fold increased risk of death at 30 and 90 days, respectively, compared to those in stage C/D.\u003c/p\u003e\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\u003ch2\u003eIncidence of CS in COVID-19 population\u003c/h2\u003e\u003cp\u003eThe CS prevalence rate in our study was higher than that observed in the general ICU population (2.17%) (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e), comparable to the rates in AMI populations (5\u0026ndash;10%) (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e), and slightly lower than the 14.7% reported from cardiac ICUs (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). These findings suggest that COVID-19 is not only associated with cardiac complications but also linked to an increased incidence of CS.\u003c/p\u003e\u003cp\u003eThe multivariable analysis in the present study showed a history of VT/VF was statistically associated with CS. The possible explanation for this observation is that pre-existing injury in the myocardium was stimulated by a hyperadrenergic state in COVID-19 infection and served as a substrate of arrhythmia, eventually leading to shock. Indeed, more than half of CS cases presented arrhythmia requiring antiarrhythmics or device intervention, supporting the evidence that arrhythmia can be particularly influential for CS incidence in patients with COVID-19.\u003c/p\u003e\u003cp\u003eAlthough underlying cardiovascular disease, age, gender, and unvaccinated have been reported as factors associated with cardiac complications in COVID-19 (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e), none were significantly related to CS complications in our study. This suggests that CS in COVID-19 may not primarily result from newly developed cardiac injury, such as AMI or myocarditis, but rather from additional damage or stimulation affecting pre-existing myocardial injury or an underlying excitable myocardium, such as arrhythmia or worsening HF.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec16\" class=\"Section2\"\u003e\u003ch2\u003eMortality in COVID-19 with CS\u003c/h2\u003e\u003cp\u003eThe 30-day mortality rate in the CS group was 56.8%. Considering that the same rate reported in AMI-CS was 27\u0026ndash;51% (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e), this percentage was high. The conceivable reason for this is the baseline high mortality in the critically ill COVID-19 population. Between the 2020 and 2021 pandemic, the reported mortality rate for COVID-19 cases admitted ICU was 41.6% (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e), while the mortality rate of total patients in our study was similarly high at 35.6%. On top of this already high baseline mortality, the presence of CS was expected to further worsen patient outcomes.\u003c/p\u003e\u003cp\u003eThe incidence of bacteremia (43.2%) and bleeding (16.2%) was higher among patients in the CS group compared to those without CS. \u0026ldquo;Mixed CS\u0026rdquo;, the combined pathophysiology of cardiogenic and either/both distributive and hypovolemic shock, has been linked to an increased mortality risk (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). In the context of COVID-19, this mixed pathophysiology may be more common due to the nature of the infection and compromised coagulation.\u003c/p\u003e\u003cp\u003eMoreover, our findings indicate that a greater proportion of patients in the CS group developed multiorgan failure, including AKI and DIC, underscoring the severity of CS in this population.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec17\" class=\"Section2\"\u003e\u003ch2\u003eSCAI CS staging system\u003c/h2\u003e\u003cp\u003eSCAI staging is currently employed in a variety of clinical settings and has shown excellent predictive value for mortality (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). However, its applicability outside of AMI and HF cohorts remains underexplored\u003csup\u003e5\u003c/sup\u003e. The current study found Stage E was associated with a 3.9-fold higher risk of 90-day mortality and 2.2-fold higher risk of 30-day mortality in CS group, supporting its relevance in this population and further underscoring the prognostic significance of progressing to an extreme stage.\u003c/p\u003e\u003cp\u003eThe definition of each stage varies across the studies (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). In the updated edition, SCAI classification describes stages D and E as the deterioration following the initial treatment (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e) and thus, we incorporated the deterioration after 24 hours of ICU admission into Stage D and E sorting as recent studies (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Our findings further emphasize the importance of early therapeutic interventions before the patient's condition deteriorates, for patients presenting with CS, including those with COVID-19.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec18\" class=\"Section2\"\u003e\u003ch2\u003eUtilization of temporary mechanical circulation support\u003c/h2\u003e\u003cp\u003eLastly, our study revealed limited utilization of MCS in patients with CS, with only 8 out of 74 patients receiving it, although that in general CS populations reported at 13.9\u0026ndash;16.0% (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). V-V ECMO was initiated in 21 patients but converted to V-A ECMO in only 2 cases. Although data on MCS use in COVID-19 remain sparse, early pandemic literature similarly reports limited application of V-A ECMO (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eSeveral factors may explain these low utilization rates, including concerns that artificial devices could exacerbate infections, resource shortages during the pandemic, and guideline-based contraindications to ECMO for high-risk patients with comorbidities (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). According to previous reports in pandemic, patients treated with V-A ECMO often had significant comorbidities and faced extremely high mortality rates, ranging from 75\u0026ndash;100% (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). Given the particularly severe nature of CS in COVID-19, the reversibility of the underlying pathophysiology and the potential efficacy of MCS remain uncertain.\u003c/p\u003e\u003cp\u003eWhile indications for MCS and the specific cohorts who benefit have been explored in AMI-related CS (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e), Our study in COVID-19-related CS did not demonstrate a mortality benefit associated with MCS use, although study scale was limited. Given the background of infection and the high baseline mortality, even outside the pandemic context, the use of MCS for COVID-19-related CS should be carefully considered.\u003c/p\u003e\u003cp\u003e\u003cb\u003eLimitations\u003c/b\u003e 1) This is a retrospective analysis, and thus, systemic biases are inevitable. Broader validation in other registry datasets would mitigate the risk of bias. 2) Echocardiographic findings are not included in this study. Detailed cardiac assessment in large-scale COVID-19 cohorts remains scarce, and due to limitations in data collection, this study could not address this gap. 3) Some key data are unavailable, including certain laboratory results, detailed hemodynamic information in the ICU, and clinical course after discharge. The absence of these data prevents a comprehensive characterization of patient profiles, in-hospital presentations, precise SCAI CS staging (based on lactate and BP).\u003c/p\u003e\u003c/div\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eIn our Cardiac Sub-study, CS occurred in 9.5% of ICU-admitted COVID-19 cases. A history of ventricular arrhythmia was the only independent factor associated with CS. Furthermore, CS was linked to a higher 30-day mortality rate than that of patients without CS (56.8% vs. 33.4%) and SCAI staging demonstrated its utility in predicting mortality risk in this COVID-19 cohort.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study protocol was reviewed under the National Mutual Acceptance scheme by the Alfred Health Human Research Ethics Committee on February 27, 2020, and the study was conducted in accordance with both the protocols, the Declaration of Helsinki, and the Principles of Good Clinical Practice. All participating sites obtained approval from their local ethics board and received waivers of informed consent for all patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll co-authors have approved the current version of the manuscript and consent to its submission to Journal of Intensive Care.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are available from the Critical Care Consortium COVID-19. Restrictions apply to the availability of these data, which were used under license for the current study and are therefore not publicly available. Data may, however, be obtained from the authors upon reasonable request and with the permission of the Critical Care Consortium COVID-19.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe declare that the authors have no competing interests as defined by BMC, or other interests that might be perceived to influence the results and/or discussion reported in this paper\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe Bill \u0026amp; Melinda Gates Foundation, Grant number INV-034765; Queensland Health; The Prince Charles Hospital Foundation; The Wesley Medical Research; Fisher \u0026amp; Paykel Healthcare; The University of Queensland; The Health Research Board of Ireland. Jacky Y Suen is funded by the Advance Queensland fellowship program, Queensland Government, Australia. Gianluigi Li Bassi is a recipient of the BITRECS fellowship; the “BITRECS” project has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement no. 754550 and from the “La Caixa” Foundation (ID 100010434), under the agreement LCF/PR/GN18/50310006.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConceptualization: All authors.\u003c/p\u003e\n\u003cp\u003eStatistical analysis: NW\u003c/p\u003e\n\u003cp\u003eIllustrations and Figures: HN\u003c/p\u003e\n\u003cp\u003eWriting original draft preparation: HN, KS\u003c/p\u003e\n\u003cp\u003eWriting-review and editing: All authors.\u003c/p\u003e\n\u003cp\u003eAll authors have read and agreed to the published version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe recognize the crucial importance of the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) and Short Period Incidence Study of Severe Acute Respiratory Infection (SPRINT-SARI) networks in developing and expanding the global Coronavirus Disease 2019 Critical Care Consortium (COVID-19– CCC). We thank the generous support we received from the Extracorporeal Life Support Organization and the International Extracorporeal Membrane Oxygenation Network. We owe Li Wenliang, MD from the Wuhan Central Hospital, an eternal debt of gratitude for reminding the world that doctors should never be censored during a pandemic. Finally, we acknowledge all members of the COVID-19–CCC and various collaborators.\u003cstrong\u003e\u003cem\u003e\u003cbr\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eTehrani BN, Truesdell AG, Psotka MA, Rosner C, Singh R, Sinha SS, et al. A Standardized and Comprehensive Approach to the Management of Cardiogenic Shock. JACC: Heart Failure. 2020;8(11):879-91.\u003c/li\u003e\n\u003cli\u003eZweck E, Thayer KL, Helgestad OKL, Kanwar M, Ayouty M, Garan AR, et al. Phenotyping Cardiogenic Shock. Journal of the American Heart Association. 2021;10(14):e020085.\u003c/li\u003e\n\u003cli\u003eMiller PE, Huber K, Bohula EA, Krychtiuk KA, P\u0026ouml;ss J, Roswell RO, et al. Research Priorities in Critical Care Cardiology: JACC Expert Panel. J Am Coll Cardiol. 2023;82(24):2329-37.\u003c/li\u003e\n\u003cli\u003eNaidu SS, Baran DA, Jentzer JC, Hollenberg SM, van Diepen S, Basir MB, et al. SCAI SHOCK Stage Classification Expert Consensus Update: A Review and Incorporation of Validation Studies: This statement was endorsed by the American College of Cardiology (ACC), American College of Emergency Physicians (ACEP), American Heart Association (AHA), European Society of Cardiology (ESC) Association for Acute Cardiovascular Care (ACVC), International Society for Heart and Lung Transplantation (ISHLT), Society of Critical Care Medicine (SCCM), and Society of Thoracic Surgeons (STS) in December 2021. J Am Coll Cardiol. 2022;79(9):933-46.\u003c/li\u003e\n\u003cli\u003eMorici N, Frea S, Bertaina M, Sacco A, Corrada E, Dini CS, et al. SCAI stage reclassification at 24\u0026thinsp;h predicts outcome of cardiogenic shock: Insights from the Altshock-2 registry. Catheter Cardiovasc Interv. 2023;101(1):22-32.\u003c/li\u003e\n\u003cli\u003ePuri K, Jentzer JC, Spinner JA, Hope KD, Adachi I, Tume SC, et al. Clinical Presentation, Classification, and Outcomes of Cardiogenic Shock in Children. J Am Coll Cardiol. 2024;83(5):595-608.\u003c/li\u003e\n\u003cli\u003eWoodruff RC, Garg S, George MG, Patel K, Jackson SL, Loustalot F, et al. Acute Cardiac Events During COVID-19-Associated Hospitalizations. J Am Coll Cardiol. 2023;81(6):557-69.\u003c/li\u003e\n\u003cli\u003eSato K, Sinclair JE, Sadeghirad H, Fraser JF, Short KR, Kulasinghe A. Cardiovascular disease in SARS-CoV-2 infection. Clin Transl Immunology. 2021;10(9):e1343.\u003c/li\u003e\n\u003cli\u003ePellegrini D, Kawakami R, Guagliumi G, Sakamoto A, Kawai K, Gianatti A, et al. Microthrombi as a Major Cause of Cardiac Injury in COVID-19: A Pathologic Study. Circulation. 2021;143(10):1031-42.\u003c/li\u003e\n\u003cli\u003eGiustino G, Pinney SP, Lala A, Reddy VY, Johnston-Cox HA, Mechanick JI, et al. Coronavirus and Cardiovascular Disease, Myocardial Injury, and Arrhythmia: JACC Focus Seminar. Journal of the American College of Cardiology. 2020;76(17):2011-23.\u003c/li\u003e\n\u003cli\u003eKawakami R, Sakamoto A, Kawai K, Gianatti A, Pellegrini D, Nasr A, et al. Pathological Evidence for SARS-CoV-2 as a Cause of Myocarditis: JACC Review Topic of the Week. J Am Coll Cardiol. 2021;77(3):314-25.\u003c/li\u003e\n\u003cli\u003eTon V-K, Li S, John K, Li B, Zweck E, Kanwar MK, et al. Serial Shock Severity Assessment Within 72 Hours After Diagnosis. Journal of the American College of Cardiology. 2024;84(11):978-90.\u003c/li\u003e\n\u003cli\u003eLi Bassi G, Suen J, Barnett AG, Corley A, Millar J, Fanning J, et al. Design and rationale of the COVID-19 Critical Care Consortium international, multicentre, observational study. BMJ Open. 2020;10(12):e041417.\u003c/li\u003e\n\u003cli\u003eRubin R. Global Effort to Collect Data on Ventilated Patients With COVID-19. JAMA. 2020;323(22):2233-4.\u003c/li\u003e\n\u003cli\u003eAkhtar Z, Trent M, Moa A, Tan TC, Fr\u0026ouml;bert O, MacIntyre CR. The impact of COVID-19 and COVID vaccination on cardiovascular outcomes. Eur Heart J Suppl. 2023;25(Suppl A):A42-a9.\u003c/li\u003e\n\u003cli\u003eTavazzi G, Tricella G, Garbero E, Zamperoni A, Zanetti M, Finazzi S. Cardiogenic shock in general intensive care unit: a Nationwide prospective analysis of epidemiology and outcome. Eur Heart J Acute Cardiovasc Care. 2024.\u003c/li\u003e\n\u003cli\u003eAissaoui N, Puymirat E, Delmas C, Ortuno S, Durand E, Bataille V, et al. Trends in cardiogenic shock complicating acute myocardial infarction. Eur J Heart Fail. 2020;22(4):664-72.\u003c/li\u003e\n\u003cli\u003eSamsky MD, Morrow DA, Proudfoot AG, Hochman JS, Thiele H, Rao SV. Cardiogenic Shock After Acute Myocardial Infarction: A Review. Jama. 2021;326(18):1840-50.\u003c/li\u003e\n\u003cli\u003eBerg DD, Bohula EA, van Diepen S, Katz JN, Alviar CL, Baird-Zars VM, et al. Epidemiology of Shock in Contemporary Cardiac Intensive Care Units. Circ Cardiovasc Qual Outcomes. 2019;12(3):e005618.\u003c/li\u003e\n\u003cli\u003eRoth Gregory A, Vaduganathan M, Mensah George A. Impact of the COVID-19 Pandemic on Cardiovascular Health in 2020. Journal of the American College of Cardiology. 2022;80(6):631-40.\u003c/li\u003e\n\u003cli\u003evan Diepen S, Katz JN, Albert NM, Henry TD, Jacobs AK, Kapur NK, et al. Contemporary Management of Cardiogenic Shock: A Scientific Statement From the American Heart Association. Circulation. 2017;136(16):e232-e68.\u003c/li\u003e\n\u003cli\u003eArmstrong RA, Kane AD, Cook TM. Outcomes from intensive care in patients with COVID-19: a systematic review and meta-analysis of observational studies. Anaesthesia. 2020;75(10):1340-9.\u003c/li\u003e\n\u003cli\u003evan Diepen S, P\u0026ouml;ss J, Senaratne JM, Gage A, Morrow DA. Mixed Cardiogenic Shock: A Proposal for Standardized Classification, a Hemodynamic Definition, and Framework for Management. Circulation. 2024;150(18):1459-68.\u003c/li\u003e\n\u003cli\u003eNaidu SS, Baran DA, Jentzer JC, Hollenberg SM, Diepen Sv, Basir MB, et al. SCAI SHOCK Stage Classification Expert Consensus Update: A Review and Incorporation of Validation Studies. Journal of the American College of Cardiology. 2022;79(9):933-46.\u003c/li\u003e\n\u003cli\u003eLang CN, Kaier K, Zotzmann V, Stachon P, Pottgiesser T, von Zur Muehlen C, et al. Cardiogenic shock: incidence, survival and mechanical circulatory support usage 2007-2017-insights from a national registry. Clin Res Cardiol. 2021;110(9):1421-30.\u003c/li\u003e\n\u003cli\u003eMacLaren G, Fisher D, Brodie D. Preparing for the Most Critically Ill Patients With COVID-19: The Potential Role of Extracorporeal Membrane Oxygenation. JAMA. 2020;323(13):1245-6.\u003c/li\u003e\n\u003cli\u003eShekar K, Badulak J, Peek G, Boeken U, Dalton HJ, Arora L, et al. Extracorporeal Life Support Organization Coronavirus Disease 2019 Interim Guidelines: A Consensus Document from an International Group of Interdisciplinary Extracorporeal Membrane Oxygenation Providers. Asaio j. 2020;66(7):707-21.\u003c/li\u003e\n\u003cli\u003eThiele H, M\u0026oslash;ller JE, Henriques JPS, Bogerd M, Seyfarth M, Burkhoff D, et al. Temporary mechanical circulatory support in infarct-related cardiogenic shock: an individual patient data meta-analysis of randomised trials with 6-month follow-up. The Lancet. 2024;404(10457):1019-28.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"arrhythmia, COVID, mortality, SARS-CoV-2, SCAI","lastPublishedDoi":"10.21203/rs.3.rs-7096750/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7096750/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eAim:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCardiogenic shock (CS) is a life-threatening condition observed in patients with severe heart diseases. Although COVID-19 is known to cause cardiac complications, the epidemiology and outcomes of CS in COVID-19 patients have not been characterised. This study aimed to describe the prevalence, clinical course, mortality, and patient characteristics associated with CS in COVID-19 patients admitted to intensive care units (ICUs).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe retrospectively analysed the Cardiac Sub-study database of the COVID-19 Critical Care Consortium. Local physicians diagnosed CS at ICU admission based on persistent hypotension combined with evidence of low cardiac output and elevated filling pressures. We also evaluated the applicability of the Society for Cardiovascular Angiography and Interventions (SCAI) CS staging system for mortality prediction.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAmong 780 patients, 74 (9.5%) were diagnosed with CS, and their 30-day mortality rate was significantly higher than that of patients without CS (56.8% vs 33.4%; \u003cem\u003eP\u003c/em\u003e\u0026lt;0.001). The common cardiac complications in patients with CS were arrhythmia (58.1%), congestive heart failure (35.1%), and myocardial infarction (18.9%). On multivariable analysis, history of ventricular arrhythmia was the sole independent factor associated with CS complication (odds ratio 3.9; 95% confidence interval [CI], 1.6–9.5). Among patients with CS, 43 were classified into SCAI stages C/D, and 31 into stage E. Stage E was associated with significantly higher mortality (74.2% vs. 44.2%; hazard ratio 2.2; 95% CI, 1.4-4.0).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCS was observed in 9.5% of critically ill COVID-19 cases, which was significantly associated with elevated mortality. SCAI staging effectively stratified mortality risk in this population.\u003c/p\u003e","manuscriptTitle":"Clinical Course and Outcomes of Cardiogenic Shock in COVID-19 : Insights from COVID-19 Critical Care Consortium","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-25 08:29:16","doi":"10.21203/rs.3.rs-7096750/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"7d66a665-bde9-4c3c-9f04-2f66957c4920","owner":[],"postedDate":"September 25th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":55227383,"name":"Health sciences/Cardiology"},{"id":55227384,"name":"Health sciences/Diseases"},{"id":55227385,"name":"Health sciences/Medical research"},{"id":55227386,"name":"Health sciences/Risk factors"}],"tags":[],"updatedAt":"2026-02-03T04:09:39+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-25 08:29:16","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7096750","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7096750","identity":"rs-7096750","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}