Factors associated with Acute Limb Ischemia in Cardiogenic Shock and downstream Clinical Outcomes: Insights from the Cardiogenic Shock Working Group.

BACKGROUND: There are limited data depicting the prevalence and ramifications of acute limb ischemia (ALI) among cardiogenic shock (CS) patients. METHODS: We employed data from the Cardiogenic Shock Working Group (CSWG), a consortium including 33 sites. We constructed a multi-variable logistic regression to examine the association between clinical factors and ALI, we generated another logistic regression model to ascertain the association of ALI with mortality. RESULTS: There were 7,070 patients with CS and 399 (5.6%) developed ALI. Patients with ALI were more likely to be female (40.4% versus 29.4%) and have peripheral arterial disease (13.8% versus 8.3%). Stratified by maximum SCAI shock stage, the rates of ALI were stage B 0.0%, stage C 1.8%, stage D 4.1%, and stage E 10.3%. Factors associated with higher risk for ALI included: peripheral vascular disease OR 2.24 (95% CI: 1.53 - 3.23; p < 0.01) and ≥ 2 mechanical circulatory support (MCS) devices OR 1.66 (95% CI: 1.24 - 2.21, p < 0.01). ALI was highest for VA-ECMO patients (11.6%) or VA-ECMO + IABP/Impella CP (16.6%) yet use of distal perfusion catheters was less than 50%. Mortality was 38.0% for CS patients without ALI but 57.4% for CS patients with ALI. ALI was significantly associated with mortality, adjusted OR 1.40 (95% CI 1.01 - 1.95, p < 0.01). CONCLUSIONS: The rate of ALI was 6% among CS patients. Factors most associated with ALI include peripheral vascular disease and multiple MCS devices. The downstream ramifications of ALI were dire with a considerably higher risk of mortality.

Clinical outcomes among cardiogenic shock patients supported with high-capacity Impella axial flow pumps: A report from the Cardiogenic Shock Working Group.

BACKGROUND: The Impella 5.0 and 5.5 pumps (Abiomed, Danvers, MA) are large-bore transvalvular micro-axial assist devices used in cardiogenic shock (CS) for patients requiring high-capacity flow. Despite their increasing use, real-world data regarding indications, rates of utilization and clinical outcomes with this therapy are limited. The objective of our study was to examine clinical profiles and outcomes of patients in a contemporary, real-world CS registry of patients who received an Impella 5.0/5.5 alone or in combination with other temporary mechanical circulatory support (tMCS) devices. METHODS: The CS Working Group (CSWG) Registry includes patients from 34 US hospitals. For this analysis, data from patients who received an Impella 5.0/5.5 between 2020-2023 were analyzed. Use of Impella 5.0/5.5 with or without additional tMCS therapies, duration of support, adverse events and outcomes at hospital discharge were studied. Adverse events including stroke, limb ischemia, bleeding and hemolysis were not standardized by the registry but reported per individual CSWG Primary Investigator discretion. For those who survived, rates of native heart recovery (NHR) or heart replacement therapy (HRT) including heart transplant (HT), or durable ventricular assist device (VAD) were recorded. We also assessed outcomes based on shock etiology (acute myocardial infarction or MI-CS vs. heart failure-related CS or HF-CS). RESULTS: Among 6,205 patients, 754 received an Impella 5.0/5.5 (12.1%), including 210 MI-CS (27.8%) and 484 HF-CS (64.1%) patients. Impella 5.0/5.5 was used as the sole tMCS device in 32% of patients, while 68% of patients received a combination of tMCS devices. Impella cannulation sites were available for 524/754 (69.4%) of patients, with 93.5% axillary configuration. Survival to hospital discharge for those supported with an Impella 5.0/5.5 was 67%, with 20.4% NHR and 45.5% HRT. Compared to HF-CS, patients with MI-CS supported on Impella 5.0/5.5 had higher in-hospital mortality (45.2% vs 26.2%, p < 0.001) and were less likely to receive HRT (22.4% vs 56.6%, p < 0.001. For patients receiving a combination of tMCS during hospitalization, this was associated with higher rates of limb ischemia (9% vs. 3%, p < 0.01), bleeding (52% vs 33%, p < 0.01), and mortality (38% vs 25%; p < 0.001) compared to Impella 5.0/5.5 alone. Among Impella 5.0/5.5 recipients, the median duration of pump support was 12.9 days (IQR: 6.8-22.9) and longer in patients bridged to HRT (14 days; IQR: 7.7-28.4). CONCLUSIONS: In this multi-center cohort of patients with CS, use of Impella 5.0/5.5 was associated with an overall survival of 67.1% and high rates of HRT. Lower adverse event rates were observed when Impella 5.0/5.5 was the sole support device used. Further study is required to determine whether a strategy of early Impella 5.0/5.5 use for CS improves survival. CONDENSED ABSTRACT: High capacity Impella heart pumps are capable of provide up to 5.5 liter/min of flow while upper body surgical placement allows for ambulation. Patients with advanced cardiogenic shock from acute myocardial infarction or heart failure requiring temporary mechanical circulatory support may benefit from upfront use of Impella 5.5 to improve overall survival, including native heart recovery or successful bridge to durable left ventricular assist device surgery or heart transplantation.

Pathophysiology, diagnosis and management of right ventricular failure: A state of the art review of mechanical support devices.

The function of the right ventricle (RV) is to drive the forward flow of blood to the pulmonary system for oxygenation before returning to the left ventricle. Due to the thin myocardium of the RV, its function is easily affected by decreased preload, contractile motion abnormalities, or increased afterload. While various etiologies can lead to changes in RV structure and function, sudden changes in RV afterload can cause acute RV failure which is associated with high mortality. Early detection and diagnosis of RV failure is imperative for guiding initial medical management. Echocardiographic findings of reduced tricuspid annular plane systolic excursion (<1.7) and RV wall motion (RV S' <10 cm/s) are quantitatively supportive of RV systolic dysfunction. Medical management commonly involves utilizing diuretics or fluids to optimize RV preload, while correcting the underlying insult to RV function. When medical management alone is insufficient, mechanical circulatory support (MCS) may be necessary. However, the utility of MCS for isolated RV failure remains poorly understood. This review outlines the differences in flow rates, effects on hemodynamics, and advantages/disadvantages of MCS devices such as intra-aortic balloon pump, Impella, centrifugal-flow right ventricular assist devices, extracorporeal membrane oxygenation, and includes a detailed review of the latest clinical trials and studies analyzing the effects of MCS devices in acute RV failure.

American Heart Association Cardiogenic Shock Registry: Design and Implementation.

BACKGROUND: Cardiogenic shock is a morbid complication of heart disease that claims the lives of more than 1 in 3 patients presenting with this syndrome. Supporting a unique collaboration across clinical specialties, federal regulators, payors, and industry, the American Heart Association volunteers and staff have launched a quality improvement registry to better understand the clinical manifestations of shock phenotypes, and to benchmark the management patterns, and outcomes of patients presenting with cardiogenic shock to hospitals across the United States. METHODS: Participating hospitals will enroll consecutive hospitalized patients with cardiogenic shock, regardless of etiology or severity. Data are collected through individual reviews of medical records of sequential adult patients with cardiogenic shock. The electronic case record form was collaboratively designed with a core minimum data structure and aligned with Shock Academic Research Consortium definitions. This registry will allow participating health systems to evaluate patient-level data including diagnostic approaches, therapeutics, use of advanced monitoring and circulatory support, processes of care, complications, and in-hospital survival. Participating sites can leverage these data for onsite monitoring of outcomes and benchmarking versus other institutions. The registry was concomitantly designed to provide a high-quality longitudinal research infrastructure for pragmatic randomized trials as well as translational, clinical, and implementation research. An aggregate deidentified data set will be made available to the research community on the American Heart Association's Precision Medicine Platform. On March 31, 2022, the American Heart Association Cardiogenic Shock Registry received its first clinical records. At the time of this submission, 100 centers are participating. CONCLUSIONS: The American Heart Association Cardiogenic Shock Registry will serve as a resource using consistent data structure and definitions for the medical and research community to accelerate scientific advancement through shared learning and research resulting in improved quality of care and outcomes of shock patients.

Mechanical Preload Reduction: Harnessing a Cornerstone of Heart Failure Management to Improve Clinical Outcomes.

Decongestion is a cornerstone therapeutic goal for those presenting with decompensated heart failure. Current approaches to clinical decongestion include reducing cardiac preload, which is typically limited to diuretics and hemofiltration. Several new technologies designed to mechanically reduce cardiac preload are in development. In this review, we discuss the pathophysiology of decompensated heart failure; the central role of targeting cardiac preload; emerging mechanical preload reduction technologies; and potential application of these devices.

Reperfusion Injury in Patients With Acute Myocardial Infarction: JACC Scientific Statement.

Despite impressive improvements in the care of patients with ST-segment elevation myocardial infarction, mortality remains high. Reperfusion is necessary for myocardial salvage, but the abrupt return of flow sets off a cascade of injurious processes that can lead to further necrosis. This has been termed myocardial ischemia-reperfusion injury and is the subject of this review. The pathologic and molecular bases for myocardial ischemia-reperfusion injury are increasingly understood and include injury from reactive oxygen species, inflammation, calcium overload, endothelial dysfunction, and impaired microvascular flow. A variety of pharmacologic strategies have been developed that have worked well in preclinical models and some have shown promise in the clinical setting. In addition, there are newer mechanical approaches including mechanical unloading of the heart prior to reperfusion that are in current clinical trials.

Innovating to resolve the pressure-oxygenation-paradox created by VA-ECMO could improve outcomes for acute myocardial infarction and cardiogenic shock.

VA-ECMO use is growing exponentially. Recent data shows no clinical benefit with routine use of VA-ECMO in acute myocardial infarction and shock, however clinical experience with ECMO is growing. Two key variables that may impact outcomes with ECMO in acute myocardial infarction and shock include it's effect on systemic pressure and oxygenation. We define the pressure-oxygenaton paradox of ECMO as a potential new avenue for therapeutic discovery.

Left ventricular unloading in patients supported with veno-arterial extra corporeal membrane oxygenation; an international EuroELSO survey.

INTRODUCTION: Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) improves end-organ perfusion in cardiogenic shock but may increase afterload, which can limit cardiac recovery. Left ventricular (LV) unloading strategies may aid cardiac recovery and prevent complications of increased afterload. However, there is no consensus on when and which unloading strategy should be used. METHODS: An online survey was distributed worldwide via the EuroELSO newsletter mailing list to describe contemporary international practice and evaluate heterogeneity in strategies for LV unloading. RESULTS: Of 192 respondents from 43 countries, 53% routinely use mechanical LV unloading, to promote ventricular recovery and/or to prevent complications. Of those that do not routinely unload, 65% cited risk of complications as the reason. The most common indications for unplanned unloading were reduced arterial line pulsatility (68%), pulmonary edema (64%) and LV dilatation (50%). An intra-aortic balloon pump was the most frequently used device for unloading followed by percutaneous left ventricular assist devices. Echocardiography was the most frequently used method to monitor the response to unloading. CONCLUSIONS: Significant variation exists with respect to international practice of ventricular unloading. Further research is required that compares the efficacy of different unloading strategies and a randomized comparison of routine mechanical unloading versus unplanned unloading.

Guide to Lung-Protective Ventilation in Cardiac Patients.

The incidence of acute respiratory insufficiency has continued to increase among patients admitted to modern-day cardiovascular intensive care units. Positive pressure ventilation (PPV) remains the mainstay of treatment for these patients. Alterations in intrathoracic pressure during PPV has distinct effects on both the right and left ventricles, affecting cardiovascular performance. Lung-protective ventilation (LPV) minimizes the risk of further lung injury through ventilator-induced lung injury and, hence, an understanding of LPV and its cardiopulmonary interactions is beneficial for cardiologists.

Body Mass Index and Mortality in Cardiogenic Shock.

We explored the association of body mass index (BMI) with mortality in cardiogenic shock (CS). Using the Cardiogenic Shock Working Group registry, we assessed the impact of BMI on mortality using restricted cubic splines in a multivariable logistic regression model adjusting for age, gender, and race. We also assessed mortality, device use, and complications in BMI categories, defined as underweight (<18.5 kg/m2), normal (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), obese (30-39.9 kg/m2), and severely obese (>40 kg/m2) using univariable logistic regression models. Our cohort had 3,492 patients with CS (mean age = 62.1 ± 14 years, 69% male), 58.0% HF-related CS (HF-CS), and 27.8% acute myocardial infarction (AMI) related CS. Body mass index was a significant predictor of mortality in multivariable regression using restricted cubic splines (p < 0.0001, p = 0.194 for nonlinearity). When stratified by categories, patients with healthy weight had lower mortality (29.0%) than obese (35.1%, p = 0.003) or severely obese (36.7%, p = 0.01). In HF-CS cohort, the healthy weight patients had the lowest mortality (21.7%), whereas it was higher in the underweight (37.5%, p = 0.012), obese (29.2%, p = 0.003), and severely obese (29.9%, p = 0.019). There was no difference in mortality among BMI categories in AMI-CS.

Comparison of Mixed Venous Oxygen Saturation and Premembranous Venous Oxygen Saturation in Patients on Peripheral Venous-Arterial Extracorporeal Membrane Oxygenation.

In patients on veno-arterial extracorporeal membrane oxygenation (ECMO) premembranous venous oxygen saturation (Spm-vO2) is continuously displayed on the ECMO console. However, the concordance between Spm-vO2 and mixed venous oxygen saturation (SvO2) remains largely unexplored. Our single-center retrospective study included adult patients who had paired SvO2 and Spm-vO2 readings within 15 minutes of each other, on peripherally cannulated Vf ivc-A ECMO and a pulmonary artery using catheter (PAC). The 82 pairs of observations showed a mean difference of 11.37% (95% limits of agreement -6.0 to 28.74, p < 0.001) between Spm-vO2 and SvO2. Although the two values correlated with each other (r = 0.51, p < 0.01), the difference between the paired measurements was larger at lower values of SvO2 (3.72 ± 6.38% when SvO2 >80%, 11.79±7.46% when SvO2 between 60% and 80%, and 18.81±12.09% when SvO2 <60%). The equation SvO2 = 1.2* Spm-vO2 - 28.03 was obtained by Passing Bablok regression. Cardiac index calculated by Spm-vO2 and SvO2 differed by 0.8L/minute/m2 (95% limits of agreement -0.52 to 2.17, p < 0.001). In peripheral VA-ECMO, Spm-vO2 is consistently higher than SvO2, with more discordance at lower saturation levels. Using Spm-vO2 to estimate cardiac output using Fick method yields inaccurate results.

Superiority of a Silk Surgical Site Wound Closure Device Over Synthetic Dressings.

BACKGROUND: Silk fibroin is an emerging biomaterial with enhanced properties of cellular regeneration, growth and proliferation. The use of a silk fibroin wound dressing has the potential to decrease the incidence of wound healing complications and to improve patient outcomes compared to synthetic dressing alternatives. METHODS: A prospective, randomized, single-blinded clinical trial was conducted on 50 patients who were dressed with a silk fibroin dressing on one side of their body and on the contralateral side with 3M Steri-Strips® after undergoing abdominoplasty, reduction mammaplasty, or brachioplasty procedures. Data was collected over 5 postoperative visits using photographs and an investigator administered questionnaire to monitor erythema, skin irritation, skin discomfort, the need for pharmaceutical intervention, wound dehiscence and mechanical skin injury. A comprehensive 75 patient statistical analysis was conducted combining the results with a previously published study comparing Dermabond® Prineo® to the silk dressing. RESULTS: 20.8% (10/48) of patients were assessed by surgeons as having skin erythema (7-10) on the Steri-Strip® control side and 0% (0/48) on the silk dressing side (p=0.002). The frequency of breast triple point separation in 43 cases was 30.2% (13/43) on the Steri-Strip® side and 9.3% (4/43) on the silk side (p=0.012). 75% (36/48) of patients had partial or total detachment of Steri-Strips® while 0% (0/48) had total detachment of the silk dressing and 18.8% (9/48) had partial detachment of the silk dressing within the first two weeks (p<0.001). CONCLUSION: A silk fibroin wound dressing significantly reduces the incidence of wound healing complications throughout the postoperative period.Clinical Relevance Statement: The adoption of a silk fibroin wound dressing into clinical practice has the potential to improve patient outcomes, decrease medical adhesive related skin injuries and reduce the rate of wound healing complications.

Circulating Proteome Analysis Identifies Reduced Inflammation After Initiation of Hemodynamic Support with Either Veno-Arterial Extracorporeal Membrane Oxygenation or Impella in Patients with Cardiogenic Shock.

In-hospital mortality associated with cardiogenic shock (CS) remains high despite the use of percutaneous assist devices. We sought to determine whether support with VA-ECMO or Impella in patients with CS alters specific components of the plasma proteome. Plasma samples were collected before device implantation and 72 h after initiation of support in 11 CS patients receiving ECMO or Impella. SOMAscan was used to detect 1305 circulating proteins. Sixty-seven proteins were changed after ECMO (18 upregulated and 49 downregulated, p < 0.05), 38 after Impella (10 upregulated and 28 downregulated, p < 0.05), and only eight proteins were commonly affected. Despite minimal protein overlap, both devices were associated with markers of reduced inflammation and increased apoptosis of inflammatory cells. In summary, ECMO and Impella are associated with reduced expression of inflammatory markers and increased markers of inflammatory cell death. These circulating proteins may serve as novel targets of therapy or biomarkers to tailor AMCS use.

Novel Role for Cardiolipin as a Target of Therapy to Mitigate Myocardial Injury Caused by Venoarterial Extracorporeal Membrane Oxygenation.

BACKGROUND: Cardiolipin is a mitochondrial-specific phospholipid that maintains integrity of the electron transport chain (ETC) and plays a central role in myocardial ischemia/reperfusion injury. Tafazzin is an enzyme that is required for cardiolipin maturation. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) use to provide hemodynamic support for acute myocardial infarction has grown exponentially, is associated with poor outcomes, and is under active clinical investigation, yet the mechanistic effect of VA-ECMO on myocardial damage in acute myocardial infarction remains poorly understood. We hypothesized that VA-ECMO acutely depletes myocardial cardiolipin and exacerbates myocardial injury in acute myocardial infarction. METHODS: We examined cardiolipin and tafazzin levels in human subjects with heart failure and healthy swine exposed to VA-ECMO and used a swine model of closed-chest myocardial ischemia/reperfusion injury to evaluate the effect of VA-ECMO on cardiolipin expression, myocardial injury, and mitochondrial function. RESULTS: Cardiolipin and tafazzin levels are significantly reduced in the left ventricles of individuals requiring VA-ECMO compared with individuals without VA-ECMO before heart transplantation. Six hours of exposure to VA-ECMO also decreased left ventricular levels of cardiolipin and tafazzin in healthy swine compared with sham controls. To explore whether cardiolipin depletion by VA-ECMO increases infarct size, we performed left anterior descending artery occlusion for a total of 120 minutes followed by 180 minutes of reperfusion in adult swine in the presence and absence of MTP-131, an amphipathic molecule that interacts with cardiolipin to stabilize the inner mitochondrial membrane. Compared with reperfusion alone, VA-ECMO activation beginning after 90 minutes of left anterior descending artery occlusion increased infarct size (36±8% versus 48±7%; P<0.001). VA-ECMO also decreased cardiolipin and tafazzin levels, disrupted mitochondrial integrity, reduced electron transport chain function, and promoted oxidative stress. Compared with reperfusion alone or VA-ECMO before reperfusion, delivery of MTP-131 before VA-ECMO activation reduced infarct size (22±8%; P=0.03 versus reperfusion alone and P<0.001 versus VA-ECMO alone). MTP-131 restored cardiolipin and tafazzin levels, stabilized mitochondrial function, and reduced oxidative stress in the left ventricle. CONCLUSIONS: We identified a novel mechanism by which VA-ECMO promotes myocardial injury and further identify cardiolipin as an important target of therapy to reduce infarct size and to preserve mitochondrial function in the setting of VA-ECMO for acute myocardial infarction.

Treatment of Acute Myocardial Infarction and Cardiogenic Shock: Outcomes of the RECOVER III Postapproval Study by Society of Cardiovascular Angiography and Interventions Shock Stage.

BACKGROUND: The Society for Cardiovascular Angiography and Interventions proposed a staging system (A-E) to predict prognosis in cardiogenic shock. Herein, we report clinical outcomes of the RECOVER III study for the first time, according to Society for Cardiovascular Angiography and Interventions shock classification. METHODS AND RESULTS: The RECOVER III study is an observational, prospective, multicenter, single-arm, postapproval study of patients with acute myocardial infarction with cardiogenic shock undergoing percutaneous coronary intervention with Impella support. Patients enrolled in the RECOVER III study were assigned a baseline Society for Cardiovascular Angiography and Interventions shock stage. Staging was then repeated within 24 hours after initiation of Impella. Kaplan-Meier survival curve analyses were conducted to assess survival across Society for Cardiovascular Angiography and Interventions shock stages at both time points. At baseline assessment, 16.5%, 11.4%, and 72.2% were classified as stage C, D, and E, respectively. At ≤24-hour assessment, 26.4%, 33.2%, and 40.0% were classified as stage C, D, and E, respectively. Thirty-day survival among patients with stage C, D, and E shock at baseline was 59.7%, 56.5%, and 42.9%, respectively (P=0.003). Survival among patients with stage C, D, and E shock at ≤24 hours was 65.7%, 52.1%, and 29.5%, respectively (P<0.001). After multivariable analysis of impact of shock stage classifications at baseline and ≤24 hours, only stage E classification at ≤24 hours was a significant predictor of mortality (odds ratio, 4.8; P<0.001). CONCLUSIONS: In a real-world cohort of patients with acute myocardial infarction with cardiogenic shock undergoing percutaneous coronary intervention with Impella support, only stage E classification at ≤24 hours was significantly predictive of mortality, suggesting that response to therapy may be more important than clinical severity of shock at presentation.

Delaying reperfusion plus left ventricular unloading reduces infarct size: Sub-analysis of DTU-STEMI pilot study.

INTRODUCTION: The STEMI-DTU pilot study tested the early safety and practical feasibility of left ventricular (LV) unloading with a trans-valvular pump before reperfusion. In the intent-to-treat cohort, no difference was observed for microvascular obstruction (MVO) or infarct size (IS) normalized to either the area at risk (AAR) at 3-5 days or total LV mass (TLVM) at 3-5 days We now report a per protocol analysis of the STEMI-DTU pilot study. METHODS: In STEMI-DTU STUDY 50 adult patients (25 in each arm) with anterior STEMI [sum of precordial ST-segment elevation (ΣSTE) ≥4 mm] requiring primary percutaneous coronary intervention (PCI) were enrolled. Only patients who met all inclusion and exclusion criteria were included in this analysis. Cardiac magnetic resonance (CMR) imaging 3-5 days after PCI quantified IS/AAR and IS/TLVM and MVO. Group differences were assessed using Student's t-tests and linear regression (SAS Version-9.4). RESULTS: Of the 50 patients enrolled, 2 died before CMR imaging. Of the remaining 48 patients those without CMR at 3-5 days (n = 8), without PCI of a culprit left anterior descending artery lesion (n = 2), with OHCA (n = 1) and with ΣSTE < 4 mm (n = 5) were removed from this analysis leaving 32/50 (64 %) patients meeting all inclusion and exclusion criteria (U-IR, n = 15; U-DR, n = 17) as per protocol. Despite longer symptom-to-balloon times in the U-DR arm (228 ± 80 vs 174 ± 59 min, p < 0.01), IS/AAR was significantly lower with 30 min of delay to reperfusion in the presence of active LV unloading (47 ± 16 % vs 60 ± 15 %, p = 0.02) and remained lower irrespective of the magnitude of precordial ΣSTE. MVO was not significantly different between groups (1.5 ± 2.8 % vs 3.5 ± 4.8 %, p = 0.15). Among patients who received LV unloading within 180 min of symptom onset, IS/AAR was significantly lower in the U-DR group. CONCLUSION: In this per-protocol analysis of the STEMI-DTU pilot study we observed that LV unloading for 30 min before reperfusion significantly reduced IS/AAR compared to LV unloading and immediate reperfusion, whereas in the ITT cohort no difference was observed between groups. This observation supports the design of the STEMI-DTU pivotal trial and suggests that strict adherence to the study protocol can significantly influence the outcome.

Outcomes of Patients Transferred to Tertiary Care Centers for Treatment of Cardiogenic Shock: A Cardiogenic Shock Working Group Analysis.

BACKGROUND: Consensus recommendations for cardiogenic shock (CS) advise transfer of patients in need of advanced options beyond the capability of "spoke" centers to tertiary/"hub" centers with higher capabilities. However, outcomes associated with such transfers are largely unknown beyond those reported in individual health networks. OBJECTIVES: To analyze a contemporary, multicenter CS cohort with the aim of comparing characteristics and outcomes of patients between transfer (between spoke and hub centers) and nontransfer cohorts (those primarily admitted to a hub center) for both acute myocardial infarction (AMI-CS) and heart failure-related HF-CS. We also aim to identify clinical characteristics of the transfer cohort that are associated with in-hospital mortality. METHODS: The Cardiogenic Shock Working Group (CSWG) registry is a national, multicenter, prospective registry including high-volume (mostly hub) CS centers. Fifteen U.S. sites contributed data for this analysis from 2016-2020. RESULTS: Of 1890 consecutive CS patients enrolled into the CSWG registry, 1028 (54.4%) patients were transferred. Of these patients, 528 (58.1%) had heart failure-related CS (HF-CS), and 381 (41.9%) had CS related to acute myocardial infarction (AMI-CS). Upon arrival to the CSWG site, transfer patients were more likely to be in SCAI stages C and D, when compared to nontransfer patients. Transfer patients had higher mortality rates (37% vs 29%, < 0.001) than nontransfer patients; the differences were driven primarily by the HF-CS cohort. Logistic regression identified increasing age, mechanical ventilation, renal replacement therapy, and higher number of vasoactive drugs prior to or within 24 hours after CSWG site transfer as independent predictors of mortality among HF-CS patients. Conversely, pulmonary artery catheter use prior to transfer or within 24 hours of arrival was associated with decreased mortality rates. Among transfer AMI-CS patients, BMI > 28 kg/m2, worsening renal failure, lactate > 3 mg/dL, and increasing numbers of vasoactive drugs were associated with increased mortality rates. CONCLUSION: More than half of patients with CS managed at high-volume CS centers were transferred from another hospital. Although transfer patients had higher mortality rates than those who were admitted primarily to hub centers, the outcomes and their predictors varied significantly when classified by HF-CS vs AMI-CS.