Received: 15 July 2022 | Revised: 27 September 2022 | Accepted: 2 November 2022 DOI: 10.1002/ccd.30484 ORIGINAL ARTICLE ‐ CLINICAL SCIENCE SCAI stage reclassification at 24 h predicts outcome of cardiogenic shock: Insights from the Altshock‐2 registry Nuccia Morici MD, PhD1 | Simone Frea MD2 | Maurizio Bertaina MD3 | Alice Sacco MD4 | Elena Corrada MD5 | Carlotta Sorini Dini MD6 | Martina Briani MD5 | Michele Tedeschi MD7 | Francesco Saia MD8 | Costanza Colombo MD9 | Matteo Rota10 | Fabrizio Oliva MD4 | Mario Iannaccone MD3 | Gaetano M. De Ferrari MD2,11 | Alessandro Sionis MD12 | Navin K. Kapur MD13 | Guido Tavazzi MD14,15 | 16 Federico Pappalardo MD 1 IRCCS S. Maria Nascente ‐ Fondazione Don Carlo Gnocchi ONLUS, Milan, Italy 2 Intensive Cardiac Care Unit, Città della Salute e della Scienza di Torino, Torino, Italy 3 Division of Cardiology, San Giovanni Bosco Hospital, ASL Città di Torino, Torino, Italy 4 Cardiology Department and De Gasperis Cardio Center, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy 5 Humanitas Research Hospital IRCCS Rozzano, Milan, Italy 6 Department of Medical Biotechnologies, Division of Cardiology, University of Siena, Siena, Italy 7 Cardiology Department, Intensive Care Unit, S. Giovanni Di Dio e Ruggi D'Aragona Hospital, Salerno, Italy 8 Cardiology Unit, Cardio‐Thoraco‐Vascular Department, University Hospital of Bologna, Policlinico S. Orsola‐Malpighi, Bologna, Italy 9 Intensive Cardiac Care Unit, Fondazione Policlinico San Matteo Hospital IRCCS, Pavia, Italy 10 Department of Molecular and Translational Medicine, Units of Biostatistics and Biomathematics and Bioinformatics, University of Brescia, Brescia, Italy 11 Department of Medical Sciences, University of Torino, Torino, Italy 12 Intensive Cardiac Care Unit, Cardiology Department, Hospital de la Santa Creu i Sant Pau, IIB‐Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain 13 The CardioVascular Center, Tufts Medical Center, Boston, Massachusetts, USA 14 Department of Clinical‐Surgical, Diagnostic and Paediatric Sciences, Unit of Anaesthesia and Intensive Care, University of Pavia Italy, 15 Anesthesia and Intensive Care, Fondazione Policlinico San Matteo Hospital IRCCS, Anestesia e Rianimazione I, Pavia, Italy 16 Cardiothoracic and Vascular Anesthesia and Intensive Care, AO SS. Antonio e Biagio e Cesare Arrigo, Alessandria, Italy Correspondence Nuccia Morici, MD, PhD, IRCCS S. Maria Abstract Nascente – Fondazione Don Carlo Gnocchi Background: Cardiogenic shock (CS) includes several phenotypes with heterogenous ONLUS, via Alfonso Capecelatro 66, 20149, Milan, Italy. hemodynamic features. Timely prognostication is warranted to identify patients Email: nmorici@dongnocchi.it requiring treatment escalation. We explored the association of the updated Society for Cardiovascular Angiography and Interventions (SCAI) stages classification with in‐hospital mortality using a prospective national registry. Methods: Between March 2020 and February 2022 the Altshock‐2 Registry has included 237 patients with CS of all etiologies at 11 Italian Centers. Patients were This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. © 2022 The Authors. Catheterization and Cardiovascular Interventions published by Wiley Periodicals LLC. 22 | wileyonlinelibrary.com/journal/ccd Catheter Cardiovasc Interv. 2023;101:22–32. MORICI ET AL. | 23 classified according to their admission SCAI stage (assigned prospectively and independently updated according to the recently released version). In‐hospital mortality was evaluated for association with both admission and 24‐h SCAI stages. Results: The overall in‐hospital mortality was 38%. Of the 237 patients included and staged according to the updated SCAI classification, 20 (8%) had SCAI shock stage B, 131 (55%) SCAI stage C, 61 (26%) SCAI stage D and 25 (11%) SCAI stage E. In‐ hospital mortality stratified according to the SCAI classification at 24 h was 18% for patients in SCAI stage B, 27% for SCAI stage C, 63% for SCAI stage D and 100% for SCAI stage E. Both the revised SCAI stages on admission and at 24 h were associated with in‐hospital mortality, but the classification potential slightly increased at 24‐h. After adjusting for age, sex, lactate level, eGFR, CVP, inotropic score and mechanical circulatory support [MCS], SCAI classification at 24 h was an independent predictor of in‐hospital mortality. Conclusions: In the Altshock‐2 registry the utility of SCAI shock stages to identify risk of in‐hospital mortality increased at 24 h after admission. Escalation of treatment (either pharmacological or with MCS) should be tailored to achieve prompt clinical improvement within the first 24 h after admission. Registra- tion: http://www.clinicaltrials.gov; Unique identifier: NCT04295252. KEYWORDS cardiogenic shock, heart failure, SCAI stages 1 | INTRODUCTION 2 | M A T E R I A L S AN D M E T H O D S Cardiogenic shock (CS) is the most severe form of acute heart The Altshock‐2 Registry is a multicenter prospective data collection failure, characterized by life‐threatening end‐organ hypoperfusion (ClinicalTrials. gov Identifier: NCT04295252), part of the Italian resulting from low cardiac output.1 Given the high short‐term Altshock‐2 program. Recruitment started on 2 March 2020 with 11 mortality of these patients and the need for developing dedicated Italian Centers contributing to patients' enrolment (Supporting CS teams and systems of care to provide timely interventions,2–7 it Information: Appendix Table 1). Five of the 11 have active heart is of utmost importance to optimize clinical phenotyping and transplant and LVAD programs, whereas 3 have only an LVAD implement dedicated outcome research. Since its original defini- program. This study was approved by the Local Ethics Committee of tion, the Society for Cardiovascular Angiography and Interventions Milano Area 3 of the ASST Grande Ospedale Metropolitano Niguarda (SCAI) stages classification has been widely used for risk (Piazza Ospedale Maggiore 3, 20162). In accordance to the EU stratification upon patient's admission across the whole spectrum Regulation 536/2014, all competent patients provided written of CS.8 A clinical expert consensus group has recently redefined informed consent, whereas consent was waived for patients who the SCAI classification using a 3‐axis model which focuses on a real were not competent on admission. The study was conducted in time assignment of the SCAI shock stage and includes an analysis accordance with ethical principles based on Helsinki's Declaration,10 9 of serial changes over time. International Conference on Harmonization for Good Clinical The Altshock‐2 registry has been designed to include the Practice, and the current ethical rules. The Strengthening the full spectrum of consecutive “real world” CS patients and to Reporting of Observational Studies in Epidemiology Guidelines collect data on etiology, clinical presentation, pharmacological (STROBE) were followed for reporting the findings.11 treatments, use of mechanical circulatory support (MCS) and The Society for SCAI shock stages were prospectively assigned outcome. Accordingly, all patients were prospectively staged upon admission and at 24 h by physician assessment according to the according to SCAI shock stages upon admission and at 24 h. We original definition released in 2019,8 without study‐specific criteria. A aimed to assess whether the updated SCAI shock stage further refinement of the patients' shock stage was independently classification can more accurately identify patients at risk for performed by two researchers (N. M. and D. B.) during data analysis in‐hospital mortality. using the updated SCAI shock stages classification.9 24 | MORICI ET AL. Clinical, laboratory, procedural, pharmacological and follow‐up stages are reflected also by significantly higher values of SAPS data of all consecutive patients enrolled were collected and (simplified acute physiology score) and SOFA (sequential organ failure registered in an electronic case report form provided through the assessment) in stages D and E. RedCap platform. The primary outcome was in‐hospital mortality. Only 42 patients (18%) were monitored using a Swan‐Ganz catheter. No significant differences emerged across SCAI shock stages for left ventricular ejection fraction (LVEF) and end diastolic 2.1 | Data analysis volume (LVEDV), aortic (AR) and mitral regurgitation (MR), tricuspid annular plane systolic excursion (TAPSE) and systolic pulmonary No formal sample size calculation was used to plan enrolment in the artery pressure. registry since the goal was to obtain participation of all eligible patients. Quantitative variables are summarized using medians and quartiles (Q1 and Q3) whereas categorical variables are presented as 3.2 | Pharmacological and mechanical support counts and percentages. Comparisons of patients' characteristics across SCAI shock stages were carried out using the χ2 test—or the Table 3 describes pharmacological and mechanical treatments Fisher exact test when expected frequencies were less than 5—for stratified according to the updated SCAI classification on admission. categorical variables and the one‐way analysis of variance for Mechanical ventilation before intensive care unit admission was more continuous variables. Bar charts were used to graphically synthetize often used in patients with SCAI shock stages D and E. The inotropic SCAI shock stage distribution and SCAI‐stratified in hospital‐ score significantly differs (p < 0.001) across SCAI shock stages, being mortality. 19 (Q1−Q3, 9.0−30.5) in SCAI stage B and 40 (Q1−Q3, 26.5−57.0) in The paired t‐test was used to assess any difference in selected SCAI stage E. Conversely, sodium nitroprusside was used in 47% of variables (lactates, estimated Glomerular Filtration Rate and central patients with SCAI shock stage B as compared to one patient only venous pressure) between measurements on admission and at 24 h. (4.2%) with SCAI stage E. Overall, 144 (62%) patients received a The association between SCAI shock stages on admission, by temporary MCS device. prospective physician assessment as well as for further refinement according to the updated criteria, and at 24 h with in‐hospital mortality was quantified in terms of Odd Ratio (OR) and its 95% 3.3 | SCAI classification stages confidence interval (CI). The latter was also assessed in a multi- variable fashion adjusting for selected variables. Figure 1 describes the SCAI shock classification upon admission, by All analyses were performed using R version 4.1.2 (R Foundation prospective physician assessment as well as for further refinement for Statistical Computing). according to the updated criteria, and at 24‐h. For what regards the updated SCAI shock classification on admission, 20 (8%) patients had a SCAI stage B, while 131 (55%), 61 (26%) and 25 (11%) patients had SCAI 3 | RESULTS stages C, D, and E, respectively. Such updated classification restaged 41 (17%) patients, 8 (3%) of whom with SCAI stage B, 20 (8%) with SCAI 3.1 | Study population characteristics stage C, 7 (3%) with SCAI stage D and 6 (2.5%) with SCAI stage E. At 24 h, 202 out of 237 patients (85%) had a SCAI assessment: 15 (7%) A total of 237 patients were hospitalized with confirmed diagnosis of SCAI stage A, 28 (19%) SCAI stage B, 102 (50%) SCAI stage C, 35 (17%) CS between March 2020 and February 2022. The baseline SCAI stage D and 12 (6%) SCAI stage E. Worth note, 42% of the SCAI B characteristics of the study population are described in Table 1. patients worsened their classification at 24 h compared to the admission The median age was 65 years (Q1−Q3, 55−74 years) and 77% were evaluation, whereas only 8.3% improved (Figure 2, Figure 3). Although male. One‐hundred‐and‐one patients (43%) were admitted for CS statistical significance is not achieved, a 100% and 50% increase in related to acute myocardial infarction (AMI), 88 patients (37%) had median values of lactates and central venous pressure (CPV) has been acutely decompensated heart failure (ADHF) and 48 patients (20%) observed at 24 h for SCAI B patients who worsened their status presented with other diagnoses. (Supporting Information: Appendix Table 2). Patients with SCAI shock stage B were younger (median age 56 Supporting Information: Appendix Figure 1 shows the SCAI years, Q1−Q3, 49−65 years) than those with higher stages, and were shock stages classification in the Altshock‐2 registry and in other mainly admitted with ADHF‐CS etiology (55%). recent international studies. Table 2 reports clinical presentation, laboratory parameters, invasive monitoring, hemodynamic, and echocardiographic findings on admission. Forty‐seven patients (31%) suffered cardiac arrest, the 3.4 | In‐hospital outcome proportion being significantly different (p < 0.001) among SCAI shock stages (21% vs. 33% vs. 79% in SCAI stage C, D, and E, respectively). Ninety patients died (38%) in‐hospital, with a statistically significant Hypoperfusion and multiorgan failure in more advanced SCAI shock (p < 0.001) higher rate in SCAI stages D and E. Mortality rates MORICI ET AL. | 25 TABLE 1 Baseline characteristics of patients according to the Society for Cardiovascular Angiography and Interventions (SCAI) classification Characteristic Admission updated SCAI shock stages Demographics Overall N = 237a B N = 20a C N = 131a D N = 61a E N = 25a p Valueb Age, years 65.0 (55.0−74.0) 56.0 (49.2−65.0) 66.0 (56.0−74.5) 66.0 (58.0−76.0) 63.0 (48.0−72.0) 0.031 BMI 25.9 (23.0‐28.5) 26.1 (23.1−29.2) 25.7 (23.1−27.7) 27.0 (23.1−29.4) 25.7 (22.8–27.8) 0.6 Sex 0.2 F 54 (23%) 4 (20%) 24 (18%) 17 (28%) 9 (36%) M 183 (77%) 16 (80%) 107 (82%) 44 (72%) 16 (64%) Medical History COVID‐19 14 (6.3%) 2 (11%) 7 (5.9%) 4 (6.7%) 1 (4.2%) 0.8 Hypertension 142 (60%) 8 (40%) 80 (61%) 38 (62%) 16 (64%) 0.3 Diabetes 73 (31%) 6 (30%) 41 (31%) 24 (39%) 2 (8.0%) 0.029 Smoking 63 (27%) 7 (35%) 35 (27%) 15 (25%) 6 (24%) 0.8 Dyslipidemia 100 (42%) 11 (55%) 49 (37%) 31 (51%) 9 (36%) 0.2 Prior PCI 51 (22%) 2 (10%) 28 (21%) 13 (22%) 8 (32%) 0.4 Prior CABG 20 (8.4%) 0 (0%) 11 (8.4%) 7 (11%) 2 (8.0%) 0.5 Stroke or TIA 13 (5.5%) 0 (0%) 9 (6.9%) 4 (6.6%) 0 (0%) 0.5 Peripheral artery disease 40 (17%) 0 (0%) 23 (18%) 12 (20%) 5 (20%) 0.14 Atrial fibrillation 66 (28%) 6 (30%) 36 (27%) 21 (34%) 3 (12%) 0.2 CKD 59 (25%) 5 (25%) 35 (27%) 17 (28%) 2 (8.0%) 0.2 Anemia 32 (14%) 1 (5.0%) 17 (13%) 12 (20%) 2 (8.0%) 0.3 Liver disease 12 (5.1%) 0 (0%) 5 (3.8%) 5 (8.2%) 2 (8.0%) 0.4 Thyroid disease 37 (16%) 2 (10%) 18 (14%) 12 (20%) 5 (20%) 0.6 Cancer 25 (11%) 0 (0%) 16 (12%) 7 (11%) 2 (8.0%) 0.4 Prior EF 39.0 (22.0,55.0) 32.5 (23.2,51.2) 35.0 (21.2,55.0) 40.0 (25.0,55.0) 40.0 (32.0,55.0) 0.6 Waiting list for HT 10 (4.2%) 0 (0%) 9 (6.9%) 0 (0%) 1 (4.0%) 0.11 Etiology 0.13 AMI 101 (43%) 6 (30%) 51 (39%) 29 (48%) 15 (60%) ADHF 88 (37%) 11 (55%) 54 (41%) 19 (31%) 4 (16%) Other 48 (20%) 3 (15%) 26 (20%) 13 (21%) 6 (24%) Drug history Betablocker 106 (46%) 7 (37%) 65 (50%) 24 (41%) 10 (42%) 0.5 ACE‐I 42 (18%) 2 (11%) 25 (19%) 11 (19%) 4 (17%) 0.9 ARB 24 (10%) 1 (5.0%) 15 (12%) 4 (6.8%) 4 (17%) 0.5 Loop diuretics 94 (40%) 10 (50%) 57 (44%) 21 (36%) 6 (25%) 0.2 MRA 59 (25%) 7 (35%) 35 (27%) 13 (22%) 4 (17%) 0.5 Calcium antagonist 27 (12%) 0 (0%) 16 (12%) 7 (12%) 4 (17%) 0.3 Oral anticoagulant 60 (26%) 7 (35%) 34 (26%) 18 (31%) 1 (4.2%) 0.034 Ivabradine 6 (2.6%) 0 (0%) 4 (3.1%) 2 (3.4%) 0 (0%) >0.9 Sacubitril/Valsartan 29 (12%) 2 (10%) 19 (15%) 5 (8.5%) 3 (12%) 0.7 SAPT 78 (34%) 3 (15%) 46 (36%) 20 (34%) 9 (38%) 0.3 (Continues) 26 | MORICI ET AL. TABLE 1 (Continued) Characteristic Admission updated SCAI shock stages Demographics Overall N = 237a B N = 20a C N = 131a D N = 61a E N = 25a p Valueb DAPT 22 (9.5%) 2 (10%) 11 (8.6%) 6 (10%) 3 (12%) 0.8 Oral antidiabetics 40 (17%) 6 (30%) 24 (19%) 8 (14%) 2 (8.3%) 0.2 Insulin therapy 25 (11%) 4 (20%) 16 (13%) 5 (8.6%) 0 (0%) 0.12 Abbreviations: ACE‐I, Angiotensin‐convertin enzyme inhibitor; ADHF, acutely decompensated heart failure; AMI, acute myocardial infarction cardiogenic shock; ARB, Angiotensin receptor blocker; BMI, body mass index; CABG, coronary artery bypass graft; CKD, chronic kidney disease; DAPT, Dual antiplatelet therapy; EF, ejection fraction; HT, heart transplant; MRA, mineralcorticoid receptor antagonist; PCI, percutaneous coronary intervention; SAPT, Single antiplatelet therapy; TIA, transient ischemic attack. a Data are presented as n (%) for categorical variables and median (25%, 75% percentiles) for continuous variables. b Derived through χ2 or Fisher's exact test (frequencies < 5) for categorical variables and one‐way analysis of variance for continuous variables. stratified according to SCAI classification upon admission and at 24 h Baran et al.12 prospectively validated the SCAI shock staging in a are described in Figure 3, while Supporting Information: Appendix series of 166 consecutive single center patients; several of them Figure 2 shows the mortality rate according to SCAI shock suffered from lung failure and required VV ECMO. They similarly classification upon admission and at 24 h assessment in the showed that demographics, hemodynamics, LVEF and laboratory Altshock‐2 registry and in other recent international studies. values do not correlate with the SCAI stage and that the 24 h The SCAI classification prospectively assessed by the physician reassessment improves mortality prediction. This was true regardless taking care of the patient upon admission as well as the updated SCAI of intervention, either circulatory support or medical management classification are significantly associated with in‐hospital mortality. alone, underlining the importance of timely treatment. According to the latter, a statistically significant increased risk of in‐ Our registry is in line with this report12 in suggesting that the hospital mortality was detected in patients with SCAI shock stage D treatment of CS should be timely and aggressive, as it should be able (OR 3.29, 95% CI 1.17−9.94, p = 0.03) as compared to SCAI shock to quickly restore the hemodynamic status of the sickest patients. stage B. The risk magnitude increased at 24 h; compared to SCAI This concept is consistent with the improved prognostication of the shock stage A, patients classified as SCAI shock stage D had an OR of 24‐h classification, which takes into account the results of the early 23.7 (95% CI 4.05−455, p = 0.004), while all patients classified with phase management. This finding is novel and further applies to SCAI SCAI shock stage E died before discharge (Supporting Information: B patients which deteriorate in half of cases within 24 h using Appendix Table 3). After adjusting for age, sex, lactates, eGFR, PVC, contemporary therapeutic approaches. inotropic score and MCS, SCAI classification at 24 h was still an The 100% mortality reported among patients classified as SCAI independent predictor of in‐hospital mortality (Supporting Informa- Stage E at the 24 h evaluation highlights the need of rapid and tion: Appendix Table 4). appropriate mechanical support in the sickest patients to provide any hemodynamic improvement and prompt shock reversal within 24 h. To act accordingly during this limited time‐window, it is essential to 4 | DISC US SION identify reliable markers of clinical deterioration. Although high lactates were associated with SCAI level E, only a minority of SCAI D Our prospective multicenter Altshock‐2 registry provides new insight patients deteriorating over the first 24 h showed an increase in on a real‐world population of patients admitted for CS. We report lactates or a worsening renal function. On the contrary, CVP and that in a CS population with a relevant prevalence of ADHF‐CS inotropic score identified deterioration; however, they were not patients, the SCAI shock stage classification, both in the original found to be independently associated with in‐hospital mortality at definition prospectively assigned and in the updated version refined multivariable analysis. in a retrospective fashion, was associated to in‐hospital mortality. The study found that inotropes are routinely used across all Such classification potential slightly improved, although not signifi- stages of CS with doses increasing with worsening SCAI stages; on cantly, at the 24 h evaluation, as shown by an increased in‐hospital the other hand, the use of MCS and respiratory support did not mortality risk for all SCAI stages. This process of deterioration increase significantly with more advanced SCAI stages. through the SCAI stages is tracked by increasing CVP and inotropic Our work shows some real‐life practices that should be score. considered in the clinical application of the SCAI classification and, This registry shows that SCAI staging is a dynamic process and interestingly, major differences between US and Italy. The use of the suggests that its evaluation 24 h after shock onset is better suited to pulmonary artery catheter was very low and right heart catheteriza- predict mortality, compared with the initial assessment. tion was eventually performed after the initiation of mechanical TABLE 2 Clinical presentation, blood examinations, and monitoring stratified according to the SCAI classification MORICI Admission updated SCAI shock stages Characteristic Overall N = 237a B N = 20a C N = 131a D N = 61a E N = 25a p Valueb ET AL. Clinical presentation Cardiac arrest 47 (31%) 0 (0%) 16 (21%) 16 (33%) 15 (79%) <0.001 Laboratory profile on admission Lactate (nmol/L) 2.8 (1.8−5.9) 1.2 (0.9−1.6) 2.7 (1.8−4.7) 3.3 (2.2−7.1) 11.7 (4.9−16.0) <0.001 Bilirubin (mg/dl) 0.9 (0.5−1.5) 1.0 (0.6−1.2) 1.0 (0.6−1.7) 0.8 (0.5−1.9) 0.5 (0.3−1.0) 0.36 AST (U/L) 113.0 (31.5−426.5) 37.5 (23.8−126.8) 116.5 (27.0−336.2) 88.0 (34.8−435.5) 509.0 (142.0−1394.0) 0.001 ALT (U/L) 73.0 (27.0−220.0) 40.0 (24.0−66.0) 64.0 (25.0−176.0) 79.0 (35.0−203.0) 400.0 (157.0–1314.0) <0.001 INR 1.3 (1.2−1.9) 1.2 (1.1−1.7) 1.3 (1.2−1.8) 1.3 (1.2−1.9) 1.5 (1.2–2.2) 0.39 eGFR (ml/min) 55.0 (34.0−79.0) 82.0 (54.5−96.5) 55.0 (33.5−79.5) 47.0 (29.5−64.8) 62.5 (42.5–81.8) 0.003 NT‐proBNP (ng/l) 8690.5 (4491.5−21,365.2) 8,423.0 (5823.5−10,021.5) 8,674.0 (4223.0−19,546.0) 9,178.0 (3112.0−22,276.0) 26,823.0 (26,823.0−26,823.0) 0.65 BNP (ng/l) 530.0 (196.0−1651.0) 334.0 (169.5−697.5) 1,089.0 (491.0−2015.0) 412.0 (175.8−571.0) 38.0 (16.0−429.5) 0.058 Glycemia (mg/dl) 164.5 (131.2,234.8) 154.5 (130.0−200.5) 160.0 (133.0−204.5) 186.0 (135.2−263.8) 208.0 (118.0−284.0) 0.15 Hemoglobin (g/dl) 126.0 (106.5−144.0) 130.0 (112.5−144.5) 126.5 (108.0−144.0) 126.0 (106.0−144.0) 109.0 (101.0−135.0) 0.20 3 3 Platelet count (10 /mm ) 223.0 (166.0−284.5) 236.0 (180.0−296.5) 233.0 (174.2−292.5) 212.0 (176.0−263.0) 176.0 (132.0−216.0) 0.042 3 3 WBC count (10 /mm ) 12.9 (9.0−17.2) 8.9 (8.2−15.4) 12.4 (9.3−16.2) 14.2 (9.0−19.4) 14.7 (10.4,17.1) 0.31 CRP (mg/dl) 4.0 (1.1−11.2) 3.4 (1.1−6.2) 4.9 (1.5−11.4) 4.5 (1.4−17.3) 0.6 (0.2−2.1) 0.77 SOFA score 7.0 (4.0−9.0) 4.0 (3.0−4.0) 6.0 (4.0−8.8) 8.5 (7.0−10.0) 8.0 (7.0−11.2) <0.001 SAPS 45.0 (34.0−58.0) 32.0 (24.0−41.2) 42.0 (31.0−53.0) 54.5 (40.8−62.2) 62.0 (45.0−71.5) 0.014 Invasive monitoring Arterial pressure 227 (97%) 19 (95%) 125 (96%) 58 (98%) 25 (100%) 0.64 Central venous line 210 (90%) 19 (95%) 116 (89%) 52 (88%) 23 (92%) 0.90 Pulmonary artery catheter 42 (18%) 7 (35%) 26 (20%) 8 (14%) 1 (4.0%) 0.038 Hemodynamic findings on admission MAP (mmHg) 70.0 (60.5−78.0) 70.0 (62.0−77.8) 70.0 (63.0−78.0) 70.5 (63.0−83.0) 57.5 (47.8,70.0) 0.003 SAP (mmHg) 93.0 (82.0−110.0) 89.0 (83.8−105.5) 95.0 (85.0−110.0) 98.0 (84.2−117.5) 78.0 (60.0−100.0) 0.006 HR (bpm) 90.0 (75.0−110.0) 85.0 (74.5−94.5) 90.0 (75.0,110.0) 96.0 (75.0,114.5) 96.0 (83.0,110.0) 0.43 CVP (mmHg) 12.0 (8.0−17.0) 11.0 (9.0−15.0) 12.0 (7.0−16.5) 14.0 (10.0−17.0) 14.0 (11.0−19.0) 0.16 | (Continues) 27 28 TABLE 2 (Continued) | Admission updated SCAI shock stages Characteristic Overall N = 237a B N = 20a C N = 131a D N = 61a E N = 25a p Valueb ScvO2 (%) 61.0 (47.0−71.0) 58.6 (44.5−69.3) 60.1 (45.0−70.0) 68.0 (47.3−72.0) 59.0 (54.2−71.4) 0.56 2 CI (L/min/m ) 2.0 (1.6−2.3) 2.1 (1.5−2.5) 2.0 (1.7−2.4) 1.9 (1.7−2.1) 2.3 (2.3−2.3) 0.95 PAPm (mmHg) 28.0 (25.0−35.0) 34.0 (30.5−38.0) 26.5 (22.8−31.2) 29.0 (28.0−35.0) 25.0 (25.0−25.0) 0.91 PCWP (mmHg) 21.0 (14.0−25.0) 20.0 (15.0−28.0) 21.0 (11.0−25.0) 22.0 (18.8−24.5) 18.0 (18.0−18.0) 0.89 Echocardiographic findings on admission LVEF (%) 20.0 (16.0−30.0) 20.0 (15.0−33.0) 20.0 (18.0−28.0) 22.5 (15.0−35.2) 26.5 (19.2−33.0) 0.71 LVEDV (ml) 163.5 (122.0−223.8) 190.0 (134.8−245.0) 167.5 (130.2−226.5) 121.0 (88.5−208.0) 145.0 (142.5−182.5) 0.87 MR 0.25 None 15 (8.4%) 1 (5.6%) 7 (6.4%) 6 (15%) 1 (10%) 1+/4+ 52 (29%) 3 (17%) 33 (30%) 11 (27%) 5 (50%) 2+/4+ 36 (20%) 2 (11%) 23 (21%) 11 (27%) 0 (0%) 3+/4+ 35 (20%) 5 (28%) 21 (19%) 8 (20%) 1 (10%) 4+/4+ 40 (22%) 7 (39%) 25 (23%) 5 (12%) 3 (30%) AR 0.89 None 114 (67%) 14 (78%) 67 (63%) 26 (67%) 7 (88%) 1+/4+ 32 (19%) 3 (17%) 23 (22%) 5 (13%) 1 (12%) 2+/4+ 18 (11%) 1 (5.6%) 10 (9.4%) 7 (18%) 0 (0%) 3+/4+ 5 (2.9%) 0 (0%) 4 (3.8%) 1 (2.6%) 0 (0%) 4+/4+ 2 (1.2%) 0 (0%) 2 (1.9%) 0 (0%) 0 (0%) TAPSE (mm) 15.0 (12.0−18.0) 15.0 (12.0−20.0) 16.0 (13.0−18.0) 14.0 (11.0−17.0) 15.0 (11.5−19.0) 0.16 Systolic PAP (mmHg) 45.0 (36.0−54.0) 45.5 (33.5−49.8) 45.0 (35.5−55.0) 47.5 (40.0−50.0) 49.5 (40.0−60.5) 0.69 Abbreviations: ALT, alanine aminotransferase; AR, aortic regurgitation; AST, aspartate aminotransferase; BNP, B‐type natriuretic peptide; CI, cardiac index; CRP, C‐reactive protein; CVP, central venous pressure; eGFR, estimated glomerular filtration rate; HR, heart rate; ICU, intensive care unit; INR, international normalized ratio; LVEDV, left ventricular end diastolic volume; LVEF, left ventricular ejection fraction; MAP, mean arterial pressure; MR, mitral regurgitation; NT‐proBNP, N‐terminal proB‐type natriuretic peptide; PAP, pulmonary artery pressure; PCWP, pulmonary capillary wedge pressure; SAP: systolic arterial pressure; SAPS: simplified acute physiology score; ScvO2, central venous oxygen saturation; SOFA, sequential organ failure assessment; TAPSE, tricuspid annular plane systolic excursion; WBC, white blood cell. a Data are presented as n (%) for categorical variables and median (25%, 75% percentiles) for continuous variables. b Derived through χ2 or Fisher's exact test (frequencies < 5) for categorical variables and one‐way analysis of variance for continuous variables. MORICI ET AL. MORICI ET AL. | 29 TABLE 3 Pharmacological and mechanical treatment stratified according to the SCAI classification Admission updated SCAI shock stages Characteristic Overall N = 237a B N = 20a C N = 131a D N = 61a E N = 25a p Valueb Treatments before ICU admission Inotropic/vasopressor support 119 (52%) 7 (39%) 67 (52%) 29 (49%) 16 (67%) 0.3 Noninvasive ventilation 17 (7.4%) 3 (16%) 11 (8.6%) 2 (3.4%) 1 (4.2%) 0.3 Mechanical ventilation 73 (32%) 3 (16%) 28 (22%) 23 (40%) 19 (79%) <0.001 ICU procedures Inotropic/vasopressor support 219 (95%) 19 (95%) 122 (95%) 54 (93%) 24 (96%) >0.9 Epinephrine 124 (58%) 12 (63%) 62 (52%) 37 (70%) 13 (54%) 0.2 Norepinephrine 138 (64%) 8 (42%) 70 (58%) 41 (77%) 19 (79%) 0.006 Levosimendan 81 (38%) 9 (47%) 50 (42%) 16 (30%) 6 (25%) 0.2 Milrinone 13 (6.4%) 3 (16%) 5 (4.5%) 5 (10%) 0 (0%) 0.10 Dobutamine 88 (40%) 9 (47%) 53 (44%) 21 (39%) 5 (21%) 0.2 Dopamine 33 (15%) 4 (21%) 22 (18%) 7 (13%) 0 (0%) 0.070 Sodium nitroprusside 80 (37%) 9 (47%) 54 (45%) 16 (30%) 1 (4.2%) <0.001 Inotropic score 16.0 (10.0,36.5) 19.0 (9.0,30.5) 13.0 (7.0,25.0) 24.0 (13.0,43.5) 40.0 (26.5,57.0) <0.001 Mechanical circulatory support Mechanical circulatory support 144 (62%) 12 (60%) 77 (59%) 37 (63%) 18 (75%) 0.5 IABP 117 (82%) 12 (100%) 69 (90%) 27 (75%) 9 (50%) <0.001 Time from index admission to IABP (days) 1.0 (0.0−3.0) 2.0 (0.5−6.0) 1.0 (0.0−3.8) 0.0 (0.0−1.2) 0.0 (0.0−0.0) 0.3 IABP duration (days) 4.0 (2.3−7.0) 4.0 (1.5−6.2) 4.2 (2.8−8.0) 4.0 (2.4−5.0) 4.0 (0.4−6.5) 0.6 Impella 22 (15%) 2 (17%) 8 (10%) 10 (27%) 2 (11%) 0.12 Impella duration (days) 4.9 (2.1−8.0) 7.5 (5.2−9.8) 4.2 (1.9−7.2) 4.9 (2.7−8.7) 2.6 (1.4−3.8) 0.6 ECMO 39 (27%) 3 (25%) 8 (10%) 14 (38%) 14 (78%) <0.001 ECMO duration (days) 4.0 (1.9−10.1) 13.0 (7.4−22.0) 8.5 (5.8−11.6) 6.5 (4.0−12.0) 1.8 (0.5−2.5) 0.004 Respiratory support 158 (68%) 12 (60%) 81 (62%) 45 (78%) 20 (83%) 0.055 Noninvasive ventilation 62 (43%) 5 (56%) 40 (53%) 15 (36%) 2 (11%) 0.005 Mechanical ventilation 118 (76%) 10 (83%) 54 (69%) 35 (78%) 19 (95%) 0.085 Noninvasive ventilation duration (days) 2.0 (1.0−4.0) 1.0 (0.4−1.0) 2.0 (0.9−5.0) 2.0 (1.1−3.6) 1.5 (1.2,1.8) 0.6 Mechanical ventilation duration (days) 5.0 (2.0−10.6) 5.9 (3.0−10.0) 4.5 (2.0−10.0) 8.2 (2.0−18.6) 2.7 (1.1−5.4) 0.067 CRRT 59 (25%) 3 (15%) 27 (21%) 24 (41%) 5 (22%) 0.025 CRRT duration (days) 4.2 (3.0−8.5) 5.0 (4.0−5.4) 6.0 (3.0−9.5) 3.7 (2.0−6.2) 2.4 (0.6−8.7) 0.4 Abbreviations: CRRT, continuous renal replacement therapy; ECMO, ExtraCorporeal Membrane Oxygenation; IABP, intraortic balloon pump. a Data are presented as n (%) for categorical variables and median (25%, 75% percentiles) for continuous variables. b Derived through χ2 or Fisher's exact test (frequencies < 5) for categorical variables and one‐way analysis of variance for continuous variables. support, markedly reducing the applicability of the hemodynamic criteria As far as echocardiography, the data from the Alt Shock2 registry for the SCAI classification and promoting a wider use of the concepts of show that patients suffered from severe LV dysfunction (median hemodynamic failure and hypoperfusion as well as a systematic use of LVEF 20%, Q1−Q3 16−30) without any statistically significant echocardiography. From a pragmatic standpoint, this difference is favored difference according to the SCAI stage; the same was true for other by the distinct infrastructural approach to CS which is mostly based on echocardiographic parameters, such as TAPSE (median 15 mm, input from critical care and cardiology in Italy as opposed to algorithms Q1–Q3 12–18) or estimated systolic PAP (median 45 mmHg, driven by interventional cardiology in the US. Q1−Q3 36−54). Moderate‐severe MR affected almost half of the 30 | MORICI ET AL. F I G U R E 1 SCAI classification upon admission (prospective physician assessment and further refinement according to the updated criteria) and at the 24‐h evaluation in the whole population. SCAI, Society for Cardiovascular Angiography and Interventions. population and that warrants thorough consideration, especially prospective assessment. Third, clinicians applied institutional proto- when considering device selection for MCS. At baseline only mean cols and best practices which might differ across centers. Finally, arterial pressure, lactates and transaminases discriminate between outcome differences across AMI‐CS and ADHF‐CS patients will be SCAI stages. investigated in a separate investigation of the Altshock‐2 registry. Thayer et al.13 showed that CVP is associated with increased Although at time of writing our limited sample did not powerfully mortality and higher SCAI stage and envisioned the need for future allow to draw definitive conclusions, a preliminary analysis did not management protocols calling for early venous decongestion. Taken show a significant interaction effect of CS etiology and updated SCAI 14 together with the data from Schrage, which showed the association score upon admission on in‐hospital mortality. However, mixing the of lactates with mortality, the current data would suggest the two groups of patients may skew the outcome as ADHF‐CS is a opportunity to rapidly treat patients with CS with the aim of reducing chronic disease with a different degree of end organ adaptation. lactates and venous congestion rapidly and ideally within 24 h. Future studies are warranted to identify the best strategies in this regard. 4.2 | Strengths 4.1 | Limitations This is the first registry in Italy to enroll and collect data from patients who are not able to consent, following the endorsement of the Our study has some limitations. First, at the time of writing the legislation and direction from the UE 536/2014/EC. This allowed the Altshock‐2 registry sample size is still limited to allow generalizable enrolment of every consecutive patient, thus markedly reducing findings. The registry started to recruit patients in March 2020, selection bias and increasing the generalization of findings. during the first COVID‐19 pandemic wave, when several of the 11 Participating centers are experienced in MCS and have all North Italian centers who contributed to patients' enrollment were contemporary devices available for clinical use. fully dedicated to manage COVID patients. In addition, our registry For the first time the updated SCAI classification is implemented collects data from tertiary centers with large experience in CS and in a large series of patients who were prospectively stratified with active transplantation and VAD programs. Secondly, the according to the original version. Expending the SCAI stage updated SCAI stage refinement stratification has been performed classification to 24 h after admission gives an opportunity to have a by two investigators and is not externally validated. However, this trajectory of the impact of hospital treatments to identify the need refinement did not substantially change the prognostic role of the for escalation. MORICI ET AL. | 31 F I G U R E 2 SCAI classification upon admission (prospective physician assessment and further refinement according to the updated criteria) and at the 24‐h evaluation, with SCAI class variations. CVP, central venous pressure; SCAI, Society for Cardiovascular Angiography and Interventions; WRF, worsening renal function. F I G U R E 3 In‐hospital mortality for different SCAI stages upon admission (prospective assessment and updated classification) and at the 24‐h evaluation, in the whole study population. SCAI, Society for Cardiovascular Angiography and Interventions. 32 | MORICI ET AL. 5 | C ONC LUS I ON S 5. Berg DD, Bohula EA, van Diepen S, et al. Epidemiology of shock in contemporary cardiac intensive care units. Circ Cardiovasc Qual Outcomes. 2019;12(3):e005618. doi:10.1161/CIRCOUTCO Using the data of the prospective multicenter Altshock‐2 registry, we MES.119.005618 were able to provide new insights on a all‐comers real‐world 6. Valente S, Marini M, Battistoni I, et al. [Cardiogenic shock is a rare population of patients admitted for CS in Italy. We report the disease: the dedicated network]. G Ital Cardiol (Rome). 2017;18(10): following major findings: (1) the prevalence of ADHF‐CS appears to 719‐726. doi:10.1714/2790.28261 7. Rab T, Ratanapo S, Kern KB, et al. Cardiac shock care centers. J Am Coll be increasing relative to AMICS; (2) the potential for SCAI shock Cardiol. 2018;72(16):1972‐1980. doi:10.1016/j.jacc.2018.07.074 stages to identify the risk of in‐hospital mortality increases at the 24‐ 8. Baran DA, Grines CL, Bailey S, et al. SCAI clinical expert consensus h reassessment rather than upon admission; (3) the deterioration of statement on the classification of cardiogenic shock: this document the SCAI stage is tracked by CVP and inotropic score; (4) timely was endorsed by the American college of cardiology (ACC), the American heart association (AHA), the society of critical care interventions might be deployed as deterioration is captured via the Medicine (SCCM), and the society of thoracic surgeons (STS) in worsening of the SCAI stage. April 2019. Catheter Cardiovasc Interv. 2019;94(1):29‐37. doi:10. 1002/ccd.28329 A C KN O W L E D G M E N T S 9. Naidu SS, Baran DA, Jentzer JC, et al. SCAI SHOCK stage We thank Dr Dario Brunelli for data management and graphical classification expert consensus update: a review and incorporation of validation studies: this statement was endorsed by the American support. college of cardiology (ACC), American college of emergency We thank all the Investigators involved in the Altshock program. physicians (ACEP), American heart association (AHA), european Open access funding provided by BIBLIOSAN. 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 CO NFL I CT OF INTERES T thoracic surgeons (STS) in December 2021. J Am Coll Cardiol. 2022 The authors declare no conflict of interest. 79(9):933‐946. doi:10.1016/j.jacc.2022.01.018 10. World Medical Association. World medical association Declaration D A TA A V A I L A B I L I T Y S T A T E M E N T of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013;310(20):2191‐2194. doi:10.1001/jama.2013. Data will become available to interested investigators, upon submis- 281053 sion of a reasonable research request, approved by the chief 11. Vandenbroucke JP, von Elm E, Altman DG, et al. STROBE Initiative investigators Strengthening the reporting of observational studies in Epidemiol- ogy(STROBE): explanation and elaboration. PLoS Med. 2007;4:e297. doi:10.1371/journal.pmed.0040297 ORCID 12. Baran DA, Long A, Badiye AP, Stelling K. Prospective validation of Nuccia Morici https://orcid.org/0000-0003-1070-8857 the SCAI shock classification: single center analysis. Catheter Maurizio Bertaina http://orcid.org/0000-0001-5727-4107 Cardiovasc Interv. 2020;Dec 96(7):1339‐1347. doi:10.1002/ccd. Alice Sacco http://orcid.org/0000-0002-8150-474X 29319 13. 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