Outcomes for Mechanically Ventilated Patients With Acute Myocardial Infarction Admitted to Medical vs Cardiac Intensive Care Units.

Background: Acute myocardial infarction (AMI) remains a common reason for admission to the intensive care unit (ICU). However, there is limited data comparing outcomes for patients with AMI admitted to specific ICUs. Objectives: The purpose of this study was to assess clinical outcomes between patients with AMI requiring invasive mechanical ventilation admitted to the medical ICU (MICU) compared to cardiac (CICU). Methods: We utilized the Vizient Clinical Data Base to identify patients with a primary diagnosis of AMI between October 2015 and December 2019 and requiring invasive mechanical ventilation. Using multivariable logistic regression, we compared clinical outcomes for patients admitted to the MICU vs CICU. Results: We identified 12,639 patients, 25.2% (n = 3,185) of which were admitted to a MICU and 74.8% (n = 9,454) to a CICU. Patients admitted to a CICU were more likely to present with STEMI (57.0% vs 42.8%), cardiogenic shock (46.0% vs 37.4%), and require mechanical circulatory support and vasoactive medications (all, P < 0.001). Median ventilator days were 4 days in both ICUs and not statistically different after multivariable adjustment (P = 0.81). In-hospital mortality was 42.7% compared to 41.3% for MICU vs CICU admissions, respectively (P = 0.15). After multivariable adjustment, CICU admission was associated with lower in-hospital mortality (OR: 0.85, 95% CI: 0.78-0.93, P = 0.001), which persisted when stratified by cardiogenic shock, cardiac arrest, STEMI, largest hospital size (>750 beds), and teaching hospitals (all, P < 0.05). Conclusions: Admission to the CICU, as compared to MICU, was associated with lower in-hospital mortality for patients with AMI. These findings may support optimal triage of critically ill patients with AMI.

Continuum of Preshock to Classic Cardiogenic Shock in the Critical Care Cardiology Trials Network Registry.

BACKGROUND: The prognostic implications of phenotypes along the preshock to cardiogenic shock (CS) continuum remain uncertain. OBJECTIVES: This study sought to better characterize pre- or early shock and normotensive CS phenotypes and examine outcomes compared to those with conventional CS. METHODS: The CCCTN (Critical Care Cardiology Trials Network) is a registry of contemporary cardiac intensive care units. Consecutive admissions (N = 28,703 across 47 sites) meeting specific criteria based on hemodynamic variables, perfusion parameters, and investigator-reported CS were classified into 1 of 4 groups or none: isolated low cardiac output (CO), heart failure with isolated hypotension, normotensive CS, or SCAI (Society of Cardiovascular Angiography and Intervention) stage C CS. Outcomes of interest were in-hospital mortality and incidence of subsequent hypoperfusion among pre- and early shock states. RESULTS: A total of 2,498 admissions were assigned to the 4 groups with the following distribution: 4.8% isolated low CO, 4.4% isolated hypotension, 12.1% normotensive CS, and 78.7% SCAI stage C CS. Overall in-hospital mortality was 21.3% (95% CI: 19.7%-23.0%), with a gradient across phenotypes (isolated low CO 3.6% [95% CI: 1.0%-9.0%]; isolated hypotension 11.0% [95% CI: 6.9%-16.6%]; normotensive CS 17.0% [95% CI 13.0%-21.8%]; SCAI stage C CS 24.0% [95% CI: 22.1%-26.0%]; global P < 0.001). Among those with an isolated low CO and isolated hypotension on admission, 47 (42.3%) and 56 (30.9%) subsequently developed hypoperfusion. CONCLUSIONS: In a large contemporary registry of cardiac critical illness, there exists a gradient of mortality for phenotypes along the preshock to CS continuum with risk for subsequent worsening of preshock states. These data may inform refinement of CS definitions and severity staging.

In a Canine Model of Septic Shock, Cardiomyopathy Occurs Independent of Catecholamine Surges and Cardiac Microvascular Ischemia.

BACKGROUND: High levels of catecholamines are cardiotoxic and associated with stress-induced cardiomyopathies. Using a septic shock model that reproduces the reversible cardiomyopathy seen over 10 days associated with human septic shock, we investigated the effects of catecholamines on microcirculatory perfusion and cardiac dysfunction. METHODS AND RESULTS: Purpose-bred beagles received intrabronchial Staphylococcus aureus (n=30) or saline (n=6). The septic animals were than randomized to epinephrine (1 µg/kg per minute, n=15) or saline (n=15) infusions from 4 to 44 hours. Serial cardiac magnetic resonance imaging, catecholamine levels, and troponins were collected over 92 hours. Serial adenosine-stress perfusion cardiac magnetic resonance imaging was performed on septic animals randomized to receive saline (n=8 out of 15) or epinephrine (n=8 out of 15). High-dose sedation was given to suppress endogenous catecholamine release. Despite catecholamine levels largely remaining within the normal range throughout, by 48 hours, septic animals receiving saline versus nonseptic animals still developed significant worsening of left ventricular ejection fraction, circumferential strain, and ventricular-aortic coupling. In septic animals that received epinephrine versus saline infusions, plasma epinephrine levels increased 800-fold, but epinephrine produced no significant further worsening of left ventricular ejection fraction, circumferential strain, or ventricular-aortic coupling. Septic animals receiving saline had a significant increase in microcirculatory reserve without troponin elevations. Septic animals receiving epinephrine had decreased edema, blunted microcirculatory perfusion, and elevated troponin levels that persisted for hours after the epinephrine infusion stopped. CONCLUSIONS: Cardiac dysfunction during sepsis is not primarily due to elevated endogenous or exogenous catecholamines nor due to decreased microvascular perfusion-induced ischemia. However, epinephrine itself has potentially harmful long-lasting ischemic effects during sepsis including impaired cardiac microvascular perfusion that persists after stopping the infusion.

Cardiac Magnetic Resonance Studies in a Large Animal Model That Simulates the Cardiac Abnormalities of Human Septic Shock.

BACKGROUND: Septic shock is associated with increases in end-diastolic volume (EDV) and decreases in ejection fraction that reverse within 10 days. Nonsurvivors do not develop EDV increases. The mechanism is unknown. METHODS AND RESULTS: Purpose-bred beagles (n=33) were randomized to receive intrabronchial Staphylococcus aureus or saline. Over 96 hours, cardiac magnetic resonance imaging and echocardiograms were performed. Tissue was obtained at 66 hours. From 0 to 96 hours after bacterial challenge, septic animals versus controls had significantly increased left ventricular wall edema (6%) and wall thinning with loss of mass (15%). On histology, the major finding was nonocclusive microvascular injury with edema in myocytes, the interstitium, and endothelial cells. Edema was associated with significant worsening of biventricular ejection fractions, ventricular-arterial coupling, and circumferential strain. Early during sepsis, (0-24 hours), the EDV decreased; significantly more in nonsurvivors (ie, greater diastolic dysfunction). From 24 to 48 hours, septic animals' biventricular chamber sizes increased; in survivors significantly greater than baseline and nonsurvivors, whose EDVs were not different from baseline. Preload, afterload, or heart rate differences did not explain these differential changes. CONCLUSIONS: The cardiac dysfunction of sepsis is associated with wall edema. In nonsurvivors, at 0 to 24 hours, sepsis induces a more severe diastolic dysfunction, further decreasing chamber size. The loss of left ventricular mass with wall thinning in septic survivors may, in part, explain the EDV increases from 24 to 48 hours because of a potentially reparative process removing damaged wall tissue. Septic cardiomyopathy is most consistent with a nonocclusive microvascular injury resulting in edema causing reversible systolic and diastolic dysfunction with more severe diastolic dysfunction being associated with a decreased EDV and death.

Cardiac Magnetic Resonance Studies in a Large Animal Model that Simulates the Cardiac Abnormalities of Human Septic Shock.

Background: Septic shock, in humans and in our well-established animal model, is associated with increases in biventricular end diastolic volume (EDV) and decreases in ejection fraction (EF). These abnormalities occur over 2 days and reverse within 10 days. Septic non-survivors do not develop an increase in EDV. The mechanism for this cardiac dysfunction and EDV differences is unknown. Methods: Purpose-bred beagles randomized to receive intrabronchial Staphylococcus aureus (n=27) or saline (n=6) were provided standard ICU care including sedation, mechanical ventilation, and fluid resuscitation to a pulmonary arterial occlusion pressure of over 10mmHg. No catecholamines were administered. Over 96h, cardiac magnetic resonance imaging, echocardiograms, and invasive hemodynamics were serially performed, and laboratory data was collected. Tissue was obtained at 66h from six septic animals. Results: From 0-96h after bacterial challenge, septic animals vs. controls had significantly increased left ventricular wall edema (6%) and wall thinning with loss of mass (15%) which was more pronounced at 48h in non-survivors than survivors. On histology, edema was located predominantly in myocytes, the interstitium, and endothelial cells. Edema was associated with significantly worse biventricular function (lower EFs), ventricular-arterial coupling, and circumferential strain. In septic animals, from 0-24h, the EDV decreased from baseline and, despite cardiac filling pressures being similar, decreased significantly more in non-survivors. From 24-48h, all septic animals had increases in biventricular chamber sizes. Survivors biventricular EDVs were significantly greater than baseline and in non-survivors, where biventricular EDVs were not different from baseline. Preload, afterload, or HR differences did not explain these differential serial changes in chamber size. Conclusion: Systolic and diastolic cardiac dysfunction during sepsis is associated with ventricular wall edema. Rather than differences in preload, afterload, or heart rate, structural alterations to the ventricular wall best account for the volume changes associated with outcome during sepsis. In non-survivors, from 0-24h, sepsis induces a more severe diastolic dysfunction, further decreasing chamber size. The loss of left ventricular mass with wall thinning in septic survivors may, in part explain, the EDV increases from 24-48h. However, these changes continued and even accelerated into the recovery phase consistent with a reparative process rather than ongoing injury.

Complex Heart-Lung Ventilator Emergencies in the CICU.

This review aims to enhance the comprehension and management of cardiopulmonary interactions in critically ill patients with cardiovascular disease undergoing mechanical ventilation. Highlighting the significance of maintaining a delicate balance, this article emphasizes the crucial role of adjusting ventilation parameters based on both invasive and noninvasive monitoring. It provides recommendations for the induction and liberation from mechanical ventilation. Special attention is given to the identification of auto-PEEP (positive end-expiratory pressure) and other situations that may impact hemodynamics and patients' outcomes.

Modes of Death in Patients with Cardiogenic Shock in the Cardiac Intensive Care Unit: A Report from the Critical Care Cardiology Trials Network.

BACKGROUND: There are limited data on how patients with cardiogenic shock (CS) die. METHODS: The Critical Care Cardiology Trials Network is a research network of cardiac intensive care units coordinated by the Thrombolysis In Myocardial Infarction (TIMI) Study Group (Boston, MA). Using standardized definitions, site investigators classified direct modes of in-hospital death for CS admissions (October 2021 to September 2022). Mutually exclusive categories included 4 modes of cardiovascular death and 4 modes of noncardiovascular death. Subgroups defined by CS type, preceding cardiac arrest (CA), use of temporary mechanical circulatory support (tMCS), and transition to comfort measures were evaluated. RESULTS: Among 1068 CS cases, 337 (31.6%) died during the index hospitalization. Overall, the mode of death was cardiovascular in 82.2%. Persistent CS was the dominant specific mode of death (66.5%), followed by arrhythmia (12.8%), anoxic brain injury (6.2%), and respiratory failure (4.5%). Patients with preceding CA were more likely to die from anoxic brain injury (17.1% vs 0.9%; P < .001) or arrhythmia (21.6% vs 8.4%; P < .001). Patients managed with tMCS were more likely to die from persistent shock (P < .01), both cardiogenic (73.5% vs 62.0%) and noncardiogenic (6.1% vs 2.9%). CONCLUSIONS: Most deaths in CS are related to direct cardiovascular causes, particularly persistent CS. However, there is important heterogeneity across subgroups defined by preceding CA and the use of tMCS.

Training Paradigms in Critical Care Cardiology: A Scoping Review of Current Literature.

Background: Over the past decade there has been increasing interest in critical care medicine (CCM) training for cardiovascular medicine (CV) physicians either in isolation (separate programs in either order [CV/CCM], integrated critical care cardiology [CCC] training) or hybrid training with interventional cardiology (IC)/heart failure/transplant (HF) with targeted CCC training. Objective: To review the contemporary landscape of CV/CCM, CCC, and hybrid training. Methods: We reviewed the literature from 2000-2022 for publications discussing training in any combination of internal medicine CV/CCM, CCC, and hybrid training. Information regarding training paradigms, scope of practice and training, duration, sequence, and milestones was collected. Results: Of the 2,236 unique citations, 20 articles were included. A majority were opinion/editorial articles whereas two were surveys. The training pathways were classified into - (i) specialty training in both CV (3 years) and CCM (1-2 years) leading to dual American Board of Internal Medicine (ABIM) board certification, or (ii) base specialty training in CV with competencies in IC, HF or CCC leading to a non-ABIM certificate. Total fellowship duration varied between 4-7 years after a three-year internal medicine residency. While multiple articles commented on the ability to integrate the fellowship training pathways into a holistic and seamless training curriculum, few have highlighted how this may be achieved to meet competencies and standards. Conclusions: In 20 articles describing CV/CCM, CCC, and hybrid training, there remains significant heterogeneity on the standardized training paradigms to meet training competencies and board certifications, highlighting an unmet need to define CCC competencies.

Prognostic performance of the IABP-SHOCK II Risk Score among cardiogenic shock subtypes in the critical care cardiology trials network registry.

BACKGROUND: Risk stratification has potential to guide triage and decision-making in cardiogenic shock (CS). We assessed the prognostic performance of the IABP-SHOCK II score, derived in Europe for acute myocardial infarct-related CS (AMI-CS), in a contemporary North American cohort, including different CS phenotypes. METHODS: The critical care cardiology trials network (CCCTN) coordinated by the TIMI study group is a multicenter network of cardiac intensive care units (CICU). Participating centers annually contribute ≥2 months of consecutive medical CICU admissions. The IABP-SHOCK II risk score includes age > 73 years, prior stroke, admission glucose > 191 mg/dl, creatinine > 1.5 mg/dl, lactate > 5 mmol/l, and post-PCI TIMI flow grade < 3. We assessed the risk score across various CS etiologies. RESULTS: Of 17,852 medical CICU admissions 5,340 patients across 35 sites were admitted with CS. In patients with AMI-CS (n = 912), the IABP-SHOCK II score predicted a >3-fold gradient in in-hospital mortality (low risk = 26.5%, intermediate risk = 52.2%, high risk = 77.5%, P < .0001; c-statistic = 0.67; Hosmer-Lemeshow P = .79). The score showed a similar gradient of in-hospital mortality in patients with non-AMI-related CS (n = 2,517, P < .0001) and mixed shock (n = 923, P < .001), as well as in left ventricular (<0.0001), right ventricular (P = .0163) or biventricular (<0.0001) CS. The correlation between the IABP-SHOCK II score and SOFA was moderate (r2 = 0.17) and the IABP-SHOCK II score revealed a significant risk gradient within each SCAI stage. CONCLUSIONS: In an unselected international multicenter registry of patients admitted with CS, the IABP- SHOCK II score only moderately predicted in-hospital mortality in a broad population of CS regardless of etiology or irrespective of right, left, or bi-ventricular involvement.

Research Priorities in Critical Care Cardiology: JACC Expert Panel.

Over the last several decades, the cardiac intensive care unit (CICU) has seen a substantial evolution in the patient population, comorbidities, and diagnoses. However, the generation of high-quality evidence to manage these complex and critically ill patients has been slow. Given the scarcity of clinical trials focused on critical care cardiology (CCC), CICU clinicians are often left to extrapolate from studies that either exclude or poorly represent the patient population admitted to CICUs. The lack of high-quality evidence and limited guidance from society guidelines has led to significant variation in practice patterns for many of the most common CICU diagnoses. Several barriers, both common to critical care research and unique to CCC, have impeded progress. In this multinational perspective, we describe key areas of priority for CCC research, current challenges for investigation in the CICU, and essential elements of a path forward for the field.

Prognostic significance of haemodynamic parameters in patients with cardiogenic shock.

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.

Pulmonary Artery Catheter Use and Mortality in the Cardiac Intensive Care Unit.

BACKGROUND: The appropriate use of pulmonary artery catheters (PACs) in critically ill cardiac patients remains debated. OBJECTIVES: The authors aimed to characterize the current use of PACs in cardiac intensive care units (CICUs) with attention to patient-level and institutional factors influencing their application and explore the association with in-hospital mortality. METHODS: The Critical Care Cardiology Trials Network is a multicenter network of CICUs in North America. Between 2017 and 2021, participating centers contributed annual 2-month snapshots of consecutive CICU admissions. Admission diagnoses, clinical and demographic data, use of PACs, and in-hospital mortality were captured. RESULTS: Among 13,618 admissions at 34 sites, 3,827 were diagnosed with shock, with 2,583 of cardiogenic etiology. The use of mechanical circulatory support and heart failure were the patient-level factors most strongly associated with a greater likelihood of the use of a PAC (OR: 5.99 [95% CI: 5.15-6.98]; P < 0.001 and OR: 3.33 [95% CI: 2.91-3.81]; P < 0.001, respectively). The proportion of shock admissions with a PAC varied significantly by study center ranging from 8% to 73%. In analyses adjusted for factors associated with their placement, PAC use was associated with lower mortality in all shock patients admitted to a CICU (OR: 0.79 [95% CI: 0.66-0.96]; P = 0.017). CONCLUSIONS: There is wide variation in the use of PACs that is not fully explained by patient level-factors and appears driven in part by institutional tendency. PAC use was associated with higher survival in cardiac patients with shock presenting to CICUs. Randomized trials are needed to guide the appropriate use of PACs in cardiac critical care.

Multidisciplinary Critical Care Management of Electrical Storm: JACC State-of-the-Art Review.

Electrical storm (ES) reflects life-threatening cardiac electrical instability with 3 or more ventricular arrhythmia episodes within 24 hours. Identification of underlying arrhythmogenic cardiac substrate and reversible triggers is essential, as is interrogation and programming of an implantable cardioverter-defibrillator, if present. Medical management includes antiarrhythmic drugs, beta-adrenergic blockade, sedation, and hemodynamic support. The initial intensity of these interventions should be matched to the severity of ES using a stepped-care algorithm involving escalating treatments for higher-risk presentations or recurrent ventricular arrhythmias. Many patients with ES are considered for catheter ablation, which may require the use of temporary mechanical circulatory support. Outcomes after ES are poor, including frequent ES recurrences and deaths caused by progressive heart failure and other cardiac causes. A multidisciplinary collaborative approach to the management of ES is crucial, and evaluation for heart transplantation or palliative care is often appropriate, even for patients who survive the initial episode.

Inflammation and DKK1-induced AKT activation contribute to endothelial dysfunction following NR2F2 loss.

NR2F2 is expressed in endothelial cells (ECs) and Nr2f2 knockout produces lethal cardiovascular defects. In humans, reduced NR2F2 expression is associated with cardiovascular diseases including congenital heart disease and atherosclerosis. Here, NR2F2 silencing in human primary ECs led to inflammation, endothelial-to-mesenchymal transition (EndMT), proliferation, hypermigration, apoptosis-resistance, and increased production of reactive oxygen species. These changes were associated with STAT and AKT activation along with increased production of DKK1. Co-silencing DKK1 and NR2F2 prevented NR2F2-loss-induced STAT and AKT activation and reversed EndMT. Serum DKK1 concentrations were elevated in patients with pulmonary arterial hypertension (PAH) and DKK1 was secreted by ECs in response to in vitro loss of either BMPR2 or CAV1, which are genetic defects associated with the development of PAH. In human primary ECs, NR2F2 suppressed DKK1, whereas its loss conversely induced DKK1 and disrupted endothelial homeostasis, promoting phenotypic abnormalities associated with pathologic vascular remodeling. Activating NR2F2 or blocking DKK1 may be useful therapeutic targets for treating chronic vascular diseases associated with EC dysfunction.NEW & NOTEWORTHY NR2F2 loss in the endothelial lining of blood vessels is associated with cardiovascular disease. Here, NR2F2-silenced human endothelial cells were inflammatory, proliferative, hypermigratory, and apoptosis-resistant with increased oxidant stress and endothelial-to-mesenchymal transition. DKK1 was induced in NR2F2-silenced endothelial cells, while co-silencing NR2F2 and DKK1 prevented NR2F2-loss-associated abnormalities in endothelial signaling and phenotype. Activating NR2F2 or blocking DKK1 may be useful therapeutic targets for treating vascular diseases associated with endothelial dysfunction.

Characteristics, therapies, and outcomes of In-Hospital vs Out-of-Hospital cardiac arrest in patients presenting to cardiac intensive care units: From the critical care Cardiology trials network (CCCTN).

BACKGROUND: Cardiac arrest (CA) is a common reason for admission to the cardiac intensive care unit (CICU), though the relative burden of morbidity, mortality, and resource use between admissions with in-hospital (IH) and out-of-hospital (OH) CA is unknown. We compared characteristics, care patterns, and outcomes of admissions to contemporary CICUs after IHCA or OHCA. METHODS: The Critical Care Cardiology Trials Network is a multicenter network of tertiary CICUs in the US and Canada. Participating centers contributed data from consecutive admissions during 2-month annual snapshots from 2017 to 2021. We analyzed characteristics and outcomes of admissions by IHCA vs OHCA. RESULTS: We analyzed 2,075 admissions across 29 centers (50.3% IHCA, 49.7% OHCA). Admissions with IHCA were older (median 66 vs 62 years), more commonly had coronary disease (38.3% vs 29.7%), atrial fibrillation (26.7% vs 15.6%), and heart failure (36.3% vs 22.1%), and were less commonly comatose on CICU arrival (34.2% vs 71.7%), p < 0.001 for all. IHCA admissions had lower lactate (median 4.3 vs 5.9) but greater utilization of invasive hemodynamics (34.3% vs 23.6%), mechanical circulatory support (28.4% vs 16.8%), and renal replacement therapy (15.5% vs 9.4%); p < 0.001 for all. Comatose IHCA patients underwent targeted temperature management less frequently than OHCA patients (63.3% vs 84.9%, p < 0.001). IHCA admissions had lower unadjusted CICU (30.8% vs 39.0%, p < 0.001) and in-hospital mortality (36.1% vs 44.1%, p < 0.001). CONCLUSION: Despite a greater burden of comorbidities, CICU admissions after IHCA have lower lactate, greater invasive therapy utilization, and lower crude mortality than admissions after OHCA.

Clinician and Algorithmic Application of the 2019 and 2022 Society of Cardiovascular Angiography and Intervention Shock Stages in the Critical Care Cardiology Trials Network Registry.

BACKGROUND: Algorithmic application of the 2019 Society of Cardiovascular Angiography and Intervention (SCAI) shock stages effectively stratifies mortality risk for patients with cardiogenic shock. However, clinician assessment of SCAI staging may differ. Moreover, the implications of the 2022 SCAI criteria update remain incompletely defined. METHODS: The Critical Care Cardiology Trials Network is a multicenter registry of cardiac intensive care units (CICUs). Between 2019 and 2021, participating centers (n=32) contributed at least a 2-month snapshot of consecutive medical CICU admissions. In-hospital mortality was assessed across 3 separate staging methods: clinician assessment, Critical Care Cardiology Trials Network algorithmic application of the 2019 SCAI criteria, and a revision of the Critical Care Cardiology Trials Network application using the 2022 SCAI criteria. RESULTS: Of 9612 admissions, 1340 (13.9%) presented with cardiogenic shock with in-hospital mortality of 35.2%. Both clinician and algorithm-based staging using the 2019 SCAI criteria identified a stepwise gradient of mortality risk (stage C-E: 19.0% to 83.7% and 14.6% to 52.2%, respectively; Ptrend<0.001 for each). Clinician assignment of SCAI stages identified higher risk patients compared with algorithm-based assignment (stage D: 49.9% versus 29.3%; stage E: 83.7% versus 52.2%). Algorithmic application of the 2022 SCAI criteria, with incorporation of the vasoactive-inotropic score, more closely approximated clinician staging (mortality for stage C-E: 21.9% to 70.5%; Ptrend<0.001). CONCLUSIONS: Both clinician and algorithm-based application of the 2019 SCAI stages identify a stepwise gradient of mortality risk, although clinician-staging may better allocate higher risk patients into advanced SCAI stages. Updated algorithmic staging using the 2022 SCAI criteria and vasoactive-inotropic score further refines risk stratification.

Outcomes of Patients With Primary Cardiac Diagnoses Admitted to Cardiac vs Noncardiac Intensive Care Units.

BACKGROUND: Demographics in cardiac intensive care units (CICUs) have evolved, with increased prevalence of noncardiac critical illnesses. OBJECTIVES: This study compares outcomes of patients with primary cardiac diagnoses admitted to CICUs vs those of patients with primary cardiac diagnoses admitted to noncardiac ICUs. METHODS: The Cerner Health Facts Database was queried to identify adults with primary cardiac diagnoses admitted to ICUs within 48 hours of presentation between 2009 and 2014. Only hospitals with multiple ICUs including a CICU were studied. Information on ICU staffing was not available. A univariate analysis of ICU type (model 1) and multivariate analyses incorporating patient- and hospital-level variables (model 2) and concurrent, noncardiac, ICU-level diagnoses (model 3) were utilized to assess the impact of ICU type on inpatient mortality. RESULTS: Of 16,163 encounters across 14 hospitals, 8,499 (52.6%) were admitted to CICUs and 7,664 (47.4%) to noncardiac ICUs. Univariate analysis (model 1) demonstrated increased mortality in noncardiac ICUs compared to CICUs (odds ratio [OR]: 1.47, 95% CI: 1.32-1.64; P < 0.0001). This risk dissipated (OR: 1.04, 95% CI: 0.91-1.18; P = 0.56) after controlling for patient- and hospital-level variables (model 2). Inclusion of concurrent, noncardiac, ICU-level diagnoses (model 3) lead to a reversal with decreased mortality in noncardiac ICUs (OR: 0.86, 95% CI: 0.76-0.98; P = 0.03). CONCLUSIONS: In this historical cohort study evaluating CICU outcomes prior to the evolution of proposed staffing and care model modernization, survival of cardiac patients with concurrent, noncardiac critical illnesses may have been better with the expertise available in general system ICUs. These results may support contemporary efforts to increase the capacity to manage noncardiac critical illnesses in CICUs.

Oxygen Supplementation and Hyperoxia in Critically Ill Cardiac Patients: From Pathophysiology to Clinical Practice.

Oxygen supplementation has been a mainstay in the management of patients with acute cardiac disease. While hypoxia is known to be detrimental, the adverse effects of artificially high oxygen levels (hyperoxia) have only recently been recognized. Hyperoxia may induce harmful hemodynamic effects, including peripheral and coronary vasoconstriction, and direct cellular toxicity through the production of reactive oxygen species. In addition, emerging evidence has shown that hyperoxia is associated with adverse clinical outcomes. Thus, it is essential for the cardiac intensive care unit (CICU) clinician to understand the available evidence and titrate oxygen therapies to specific goals. This review summarizes the pathophysiology of oxygen within the cardiovascular system and the association between supplemental oxygen and hyperoxia in patients with common CICU diagnoses, including acute myocardial infarction, heart failure, shock, cardiac arrest, pulmonary hypertension, and respiratory failure. Finally, we highlight lessons learned from available trials, gaps in knowledge, and future directions.

Plasma Cell-Free DNA Predicts Survival and Maps Specific Sources of Injury in Pulmonary Arterial Hypertension.

BACKGROUND: Cell-free DNA (cfDNA) is a noninvasive marker of cellular injury. Its significance in pulmonary arterial hypertension (PAH) is unknown. METHODS: Plasma cfDNA was measured in 2 PAH cohorts (A, n=48; B, n=161) and controls (n=48). Data were collected for REVEAL 2.0 (Registry to Evaluate Early and Long-Term PAH Disease Management) scores and outcome determinations. Patients were divided into the following REVEAL risk groups: low (≤6), medium (7-8), and high (≥9). Total cfDNA concentrations were compared among controls and PAH risk groups by 1-way analysis of variance. Log-rank tests compared survival between cfDNA tertiles and REVEAL risk groups. Areas under the receiver operating characteristic curve were estimated from logistic regression models. A sample subset from cohort B (n=96) and controls (n=16) underwent bisulfite sequencing followed by a deconvolution algorithm to map cell-specific cfDNA methylation patterns, with concentrations compared using t tests. RESULTS: In cohort A, median (interquartile range) age was 62 years (47-71), with 75% female, and median (interquartile range) REVEAL 2.0 was 6 (4-9). In cohort B, median (interquartile range) age was 59 years (49-71), with 69% female, and median (interquartile range) REVEAL 2.0 was 7 (6-9). In both cohorts, cfDNA concentrations differed among patients with PAH of varying REVEAL risk and controls (analysis of variance P≤0.002) and were greater in the high-risk compared with the low-risk category (P≤0.002). In cohort B, death or lung transplant occurred in 14 of 54, 23 of 53, and 35 of 54 patients in the lowest, middle, and highest cfDNA tertiles, respectively. cfDNA levels stratified as tertiles (log-rank: P=0.0001) and REVEAL risk groups (log-rank: P<0.0001) each predicted transplant-free survival. The addition of cfDNA to REVEAL improved discrimination (area under the receiver operating characteristic curve, 0.72-0.78; P=0.02). Compared with controls, methylation analysis in patients with PAH revealed increased cfDNA originating from erythrocyte progenitors, neutrophils, monocytes, adipocytes, natural killer cells, vascular endothelium, and cardiac myocytes (Bonferroni adjusted P<0.05). cfDNA concentrations derived from erythrocyte progenitor cells, cardiac myocytes, and vascular endothelium were greater in patients with PAH with high-risk versus low-risk REVEAL scores (P≤0.02). CONCLUSIONS: Circulating cfDNA is elevated in patients with PAH, correlates with disease severity, and predicts worse survival. Results from cfDNA methylation analyses in patients with PAH are consistent with prevailing paradigms of disease pathogenesis.