Miller, P. Elliott

Background The pathophysiology of CS is complex and is associated with increased inflammation and impaired vascular tone. Corticosteroids are recommended in septic shock and have been proposed as a potential treatment for other types of shock. Objectives We sought to evaluate the clinical outcomes associated with early corticosteroid use in patients with cardiogenic shock (CS). Methods Using a nationally representative database including over 1000 hospitals, we identified adults ≥18 years of age admitted from 2015–2023 with a diagnosis of CS. Patients with adrenal insufficiency, chronic rheumatologic conditions, COVID-19 infection and acute COPD exacerbation were excluded. Using inverse probability treatment weighting (IPTW), we assessed for the association of receiving early corticosteroids (within the first 2 days of admission) versus no early corticosteroids and in-hospital mortality. Results Of the 167,721 identified patients with CS, the mean (SD) age was 65.5 (±15.2) years and 35.0% were women. A total of 13.2% received any corticosteroid within the first 2 days of admission. The most common corticosteroid was hydrocortisone (73.9%). Mortality for those receiving and not receiving early corticosteroids was 48.8% and 29.6% ( p < 0.001), respectively. After IPTW, early corticosteroid use remained associated with a 3.1% (95% confidence interval [CI]: 2.4% to 3.8%, p < 0.001) higher mortality. Among patients with CS and concomitant sepsis, 27.6% received early corticosteroids, which was similarly associated with a higher mortality (weighted mean 5.8% [95% CI: 4.6% to 7.0%, p < 0.001]). Conclusions Approximately 1 in 7 patients with CS received corticosteroids early during their admission, which was associated with higher in-hospital mortality.

Background Patients with cardiohepatic syndrome are at higher risk of adverse outcomes in the cardiac intensive care unit. We hypothesized that cardiohepatic syndrome phenotypes would exhibit differences in their clinical and transthoracic echocardiogram hemodynamic profiles, portending a higher risk of mortality. Methods We included unique CICU patients with an admission diagnosis of heart failure from 2007 to 2018 with available data for 1 or more admission liver function tests. Echocardiographic variables were extracted from patients who had a transthoracic echocardiogram within 1 day of admission. We assigned patients to 1 of 4 mutually exclusive cardiohepatic syndrome phenotype groups: normal, hepatocellular, cholestasis, and combined. Results We included 3992 CICU patients; 2483 had an available transthoracic echocardiogram. Patients with cholestasis had more right ventricular systolic dysfunction and congestion, whereas those with hepatocellular injury had more left ventricular systolic dysfunction and poor forward flow; hemodynamics and biventricular function were worst in the combined group. In‐hospital mortality occurred in 14.6% and was higher for patients with cholestasis or hepatocellular injury, especially those with greater extent/severity and worse biventricular function or poor hemodynamics. After adjustment, only the group with hepatocellular injury (adjusted odds ratio [OR], 1.35 [95% CI, 1.04–1.75], P =0.03) and the combined group (adjusted OR, 1.75 [95% CI, 1.30–2.34], P <0.001) remained at higher risk. One‐year mortality was highest in the combined group (adjusted hazard ratio [HR], 1.29 [95% CI, 1.10–1.51], P =0.002). Conclusions Cardiohepatic syndrome phenotypes are associated with distinct echocardiographic profiles. Patients with the combined cardiohepatic syndrome phenotype were at highest risk of mortality, particularly if this was combined with poor cardiac function.

OBJECTIVES: To investigate whether severe hyperoxia predisposes to end-organ complications and whether these complications contribute to in-hospital mortality among cardiogenic shock (CS) patients supported in venoarterial extracorporeal membrane oxygenation (VA-ECMO). DESIGN: Adult patients with CS from the Extracorporeal Life Support Organization Registry between 2010 and 2023 were categorized into normoxia (Pao 2 60–150 mm Hg), mild hyperoxia (Pao 2 151–300 mm Hg), and severe hyperoxia (Pao 2 > 300 mm Hg) based on their Pao 2 at 24 hours. The primary outcome was in-hospital mortality. End-organ complications were analyzed using multivariate logistic regression models, and causal mediation analysis was performed to estimate the direct and indirect effects of hyperoxia on mortality. SETTING: Multicenter, multinational prospective cohort study. PATIENTS: Adults with CS supported on VA-ECMO. INTERVENTIONS: Partial pressure of oxygen at 24 hours after VA-ECMO cannulation. MEASUREMENTS/MAIN RESULTS: A total of 10,541 patients were included (normoxia: 48.4%, mild hyperoxia: 30.0%, severe hyperoxia: 21.5%). There was higher in-hospital mortality in patients with severe hyperoxia (71.7%, adjusted OR [aOR]: 2.17; 95% CI, 1.19–2.50) and mild hyperoxia (63.8%, aOR: 1.34; 95% CI, 1.19–1.50) compared normoxia (52.7%; referent group). Severe hyperoxia was associated with more end-organ complications, which incrementally predicted higher mortality (aOR: 1.42; 95% CI, 1.25–1.61). Mediation analysis demonstrated that hyperoxia primary exerted a direct effect on mortality (86%), with contributions from neurologic (3.1%), hepatic (3.9%), renal (3.5%), and bleeding (2.3%) complications. CONCLUSIONS: Severe hyperoxia in patients with CS receiving VA-ECMO is associated with increased mortality and more end-organ complications. However, most of the effect of severe hyperoxia on mortality occurs via direct effects, independent of end-organ complications. These findings highlight the potential direct toxicity of hyperoxia and underscore the need for strategies to optimize oxygen delivery in this critically ill population.

Abstract Funding Acknowledgements None. Background Hyperoxemia (a high PaO2, i.e. &gt;200-300 mmHg) has been associated with adverse outcomes in general critical care settings as well as in acute cardiovascular care conditions. The association between hyperoxemia and mortality has not been characterized in the heterogeneous population admitted to the cardiac intensive care unit (CICU). We aimed to examine the association between hyperoxemia on CICU admission with in-hospital mortality. Methods We retrospectively analyzed Mayo Clinic CICU patients from January 2007 to April 2018. PaO2 closest on admission was analyzed as a continuous variable (per 100 mmHg) and categorized as: 60-100 mmHg (51.9%), 101-150 mmHg (28.6%), 151-200 mmHg (10.6%), 201-300 mmHg (6.4%), and &gt;300 mmHg (2.5%). Those without PaO2 on admission and those with hypoxemia were excluded. The primary outcome was all-cause in-hospital mortality evaluated using logistic regression, after adjusting for age, Charlson Comorbidity Index, M-CARS, and use of IMV and NIPPV. Results A total of 3,368 patients were included (median 70.3 years, 39.4% women). Admission diagnoses included ACS (37.0%, with 19.8% STEMI), HF (67.8%), shock (33.0%) and cardiac arrest (25.3%). Median admission PaO2 was 99 (IQR 78, 136) mmHg, with no difference in median PaO2 between hospital survivors and inpatient deaths (99 versus 98, p = 0.38). A J-shaped relationship was observed between admission PaO2 and in-hospital mortality (Figure A), with slightly higher mortality below 100 mmHg and incrementally higher mortality above this threshold (esp. at &gt;200 mmHg). The incremental association between higher PaO2 and mortality (adjusted OR 1.17 per 100 mmHg higher, 95% CI 1.01-1.34, P = 0.03) was focused in the highest PaO2 group (i.e., &gt;300 mmHg; Figure B). Conclusion Hyperoxia (esp. PaO2 &gt;300 mmHg) on CICU admission is associated with increased in-hospital mortality, demonstrating a J-shaped association with an inflection point of lowest mortality around 100 mmHg. Further studies are warranted to assess if specific oxygen targets influence outcomes in critically ill cardiac patients.

BACKGROUND: Associations of early changes in vasoactive support with cardiogenic shock (CS) mortality remain incompletely defined. METHODS: The Critical Care Cardiology Trials Network is a multicenter registry of cardiac intensive care units. Patients admitted with CS (2018–2023) had vasoactive dosing assessed at 4 and 24 hours from cardiac intensive care unit admission and quantified by the vasoactive-inotropic score (VIS). Prognostic associations of VIS at both time points, as well as change in VIS from 4 to 24 hours, were examined. Interaction testing was performed based on mechanical circulatory support status. RESULTS: Among 3665 patients, 82% had a change in VIS <10, with 7% and 11% having a ≥10-point increase and decrease from 4 to 24 hours, respectively. The 4 and 24-hour VIS were each associated with cardiac intensive care unit mortality (13%–45% and 11%–73% for VIS <10 to ≥40, respectively; P trend <0.0001 for each). Stratifying by the 4-hour VIS, changes in VIS from 4 to 24 hours had a graded association with mortality, ranging from a 2- to >4-fold difference in mortality comparing those with a ≥10-point increase to ≥10-point decrease in VIS ( P trend <0.0001). The change in VIS alone provided good discrimination of cardiac intensive care unit mortality (C-statistic, 0.72 [95% CI, 0.70–0.75]) and improved discrimination of the 24-hour Sequential Organ Failure Assessment score (0.72 [95% CI, 0.69–0.74] to 0.76 [95% CI, 0.74–0.78]) and the clinician-assessed Society for Cardiovascular Angiography and Interventions shock stage (0.72 [95% CI, 0.70–0.74] to 0.77 [95% CI, 0.75–0.79]). Although present in both groups, the mortality risk associated with VIS was attenuated in patients managed with versus without mechanical circulatory support (odds ratio per 10-point higher 24-hour VIS, 1.36 [95% CI, 1.23–1.49] versus 1.84 [95% CI, 1.69–2.01]; P interaction <0.0001). CONCLUSIONS: Early changes in the magnitude of vasoactive support in CS are associated with a gradient of risk for mortality. These data suggest that early VIS trajectory may improve CS prognostication, with the potential to be leveraged for clinical decision-making and research applications in CS.

Cardiogenic shock continues to carry a high mortality rate despite contemporary care, with no breakthrough therapies shown to improve survival over the past few decades. It is a time‐sensitive condition that commonly results in cardiovascular complications and multisystem organ failure, necessitating multidisciplinary expertise. Managing patients with cardiogenic shock remains challenging even in well‐resourced settings, and an important subgroup of patients may require cardiac replacement therapy. As a result, the idea of leveraging the collective cognitive and procedural proficiencies of multiple providers in a collaborative, team‐based approach to care (the “shock team”) has been advocated by professional societies and implemented at select high‐volume clinical centers. A slowly maturing evidence base has suggested that cardiogenic shock teams may improve patient outcomes. Although several registries exist that are beginning to inform care, particularly around therapeutic strategies of pharmacologic and mechanical circulatory support, none of these are currently focused on the shock team approach, multispecialty partnership, education, or process improvement. We propose the creation of a Cardiogenic Shock Team Collaborative—akin to the successful Pulmonary Embolism Response Team Consortium—with a goal to promote sharing of care protocols, education of stakeholders, and discovery of how process and performance may influence patient outcomes, quality, resource consumption, and costs of care.

Abstract Aims Invasive haemodynamic assessment with a pulmonary artery catheter is often used to guide the management of patients with cardiogenic shock (CS) and may provide important prognostic information. We aimed to assess prognostic associations and relationships to end-organ dysfunction of presenting haemodynamic parameters in CS. Methods and results The Critical Care Cardiology Trials Network is an investigator-initiated multicenter registry of cardiac intensive care units (CICUs) in North America coordinated by the TIMI Study Group. Patients with CS (2018–2022) who underwent invasive haemodynamic assessment within 24 h of CICU admission were included. Associations of haemodynamic parameters with in-hospital mortality were assessed using logistic regression, and associations with presenting serum lactate were assessed using least squares means regression. Sensitivity analyses were performed excluding patients on temporary mechanical circulatory support and adjusted for vasoactive-inotropic score. Among the 3603 admissions with CS, 1473 had haemodynamic data collected within 24 h of CICU admission. The median cardiac index was 1.9 (25th–75th percentile, 1.6–2.4) L/min/m2 and mean arterial pressure (MAP) was 74 (66–86) mmHg. Parameters associated with mortality included low MAP, low systolic blood pressure, low systemic vascular resistance, elevated right atrial pressure (RAP), elevated RAP/pulmonary capillary wedge pressure ratio, and low pulmonary artery pulsatility index. These associations were generally consistent when controlling for the intensity of background pharmacologic and mechanical haemodynamic support. These parameters were also associated with higher presenting serum lactate. Conclusion In a contemporary CS population, presenting haemodynamic parameters reflecting decreased systemic arterial tone and right ventricular dysfunction are associated with adverse outcomes and systemic hypoperfusion.

Background: Exposure to hyperoxia, a high arterial partial pressure of oxygen (PaO2), may be associated with worse outcomes in patients receiving extracorporeal membrane oxygenator (ECMO) support. We examined hyperoxia in the Extracorporeal Life Support Organization Registry among patients receiving venoarterial ECMO for cardiogenic shock. Methods: We included Extracorporeal Life Support Organization Registry patients from 2010 to 2020 who received venoarterial ECMO for cardiogenic shock, excluding extracorporeal CPR. Patients were grouped based on PaO2 after 24 hours of ECMO: normoxia (PaO2 60–150 mmHg), mild hyperoxia (PaO2 151–300 mmHg), and severe hyperoxia (PaO2 >300 mmHg). In-hospital mortality was evaluated using multivariable logistic regression. Results: Among 9959 patients, 3005 (30.2%) patients had mild hyperoxia and 1972 (19.8%) had severe hyperoxia. In-hospital mortality increased across groups: normoxia, 47.8%; mild hyperoxia, 55.6% (adjusted odds ratio, 1.37 [95% CI, 1.23–1.53]; P <0.001); severe hyperoxia, 65.4% (adjusted odds ratio, 2.20 [95% CI, 1.92–2.52]; P <0.001). A higher PaO2 was incrementally associated with increased in-hospital mortality (adjusted odds ratio, 1.14 per 50 mmHg higher [95% CI, 1.12–1.16]; P <0.001). Patients with a higher PaO2 had increased in-hospital mortality in each subgroup and when stratified by ventilator settings, airway pressures, acid-base status, and other clinical variables. In the random forest model, PaO2 was the second strongest predictor of in-hospital mortality, after older age. Conclusions: Exposure to hyperoxia during venoarterial ECMO support for cardiogenic shock is strongly associated with increased in-hospital mortality, independent from hemodynamic and ventilatory status. Until clinical trial data are available, we suggest targeting a normal PaO2 and avoiding hyperoxia in CS patients receiving venoarterial ECMO.