Left atrial to coronary sinus shunting for treatment of heart failure with mildly reduced or preserved ejection fraction: The ALT FLOW Early Feasibility Study 1-year results.

AIMS: Patients with heart failure and mildly reduced or preserved ejection fraction have limited therapeutic options. The ALT-FLOW Early Feasibility Study evaluated safety, haemodynamics and outcomes for the APTURE transcatheter shunt system, a novel left atrium to coronary sinus shunt in these patients. METHODS AND RESULTS: Safety and shunt implantation success was evaluated for all 116 enrolled patients. An analysis population of implanted patients with a left ventricular ejection fraction (LVEF) >40% (n = 95) was chosen to assess efficacy via paired comparison between baseline and follow-up haemodynamic (3 and 6 months), and echocardiographic, clinical and functional outcomes (6 months and 1 year). Health status and quality of life outcomes were assessed using the Kansas City Cardiomyopathy Questionnaire overall summary score (KCCQ-OSS). The primary safety endpoint, major adverse cardiac, cerebral, and renal events, and reintervention through 30 days, occurred in 3/116 patients (2.6%). All implanted shunts were patent at 1 year. In patients with LVEF >40%, the mean (95% confidence interval) reduction in exercise pulmonary capillary wedge pressure (PCWP) at 20 W was -5.7 (-8.6, -2.9) mmHg at 6 months (p < 0.001). At baseline, 8% had New York Heart Association class I-II status and improved to 68% at 1 year (p < 0.001). KCCQ-OSS at baseline was 39 (35, 43) and improved at 6 months and 1 year by 25 (20-30) and 27 (22-32) points, respectively (both p < 0.0001). No adverse changes in haemodynamic and echocardiographic indices of right heart function were observed at 1 year. Overall, the reduction in PCWP at 20 W and improvement in KCCQ-OSS in multiple subgroups were consistent with those observed for the entire population. CONCLUSIONS: In patients with heart failure and LVEF >40%, the APTURE shunt demonstrated an acceptable safety profile with significant sustained improvements in haemodynamic and patient-centred outcomes, underscoring the need for further evaluation of the APTURE shunt in a randomized trial.

Early Serial Assessment of Aggregate Vasoactive Support and Mortality in Cardiogenic Shock: Insights From the Critical Care Cardiology Trials Network Registry.

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; Ptrend <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 (Ptrend <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]; Pinteraction <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.

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.

Interhospital Variation in Admissions Managed With Critical Care Therapies or Invasive Hemodynamic Monitoring in Tertiary Cardiac Intensive Care Units: An Analysis From the Critical Care Cardiology Trials Network Registry.

BACKGROUND: Wide interhospital variations exist in cardiovascular intensive care unit (CICU) admission practices and the use of critical care restricted therapies (CCRx), but little is known about the differences in patient acuity, CCRx utilization, and the associated outcomes within tertiary centers. METHODS: The Critical Care Cardiology Trials Network is a multicenter registry of tertiary and academic CICUs in the United States and Canada that captured consecutive admissions in 2-month periods between 2017 and 2022. This analysis included 17 843 admissions across 34 sites and compared interhospital tertiles of CCRx (eg, mechanical ventilation, mechanical circulatory support, continuous renal replacement therapy) utilization and its adjusted association with in-hospital survival using logistic regression. The Pratt index was used to quantify patient-related and institutional factors associated with CCRx variability. RESULTS: The median age of the study population was 66 (56-77) years and 37% were female. CCRx was provided to 62.2% (interhospital range of 21.3%-87.1%) of CICU patients. Admissions to CICUs with the highest tertile of CCRx utilization had a greater burden of comorbidities, had more diagnoses of ST-elevation myocardial infarction, cardiac arrest, or cardiogenic shock, and had higher Sequential Organ Failure Assessment scores. The unadjusted in-hospital mortality (median, 12.7%) was 9.6%, 11.1%, and 18.7% in low, intermediate, and high CCRx tertiles, respectively. No clinically meaningful differences in adjusted mortality were observed across tertiles when admissions were stratified by the provision of CCRx. Baseline patient-level variables and institutional differences accounted for 80% and 5.3% of the observed CCRx variability, respectively. CONCLUSIONS: In a large registry of tertiary and academic CICUs, there was a >4-fold interhospital variation in the provision of CCRx that was primarily driven by differences in patient acuity compared with institutional differences. No differences were observed in adjusted mortality between low, intermediate, and high CCRx utilization sites.

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.

Anticoagulation Bridging in Patients With Left Ventricular Assist Device: A Regional Analysis of HeartMate 3 Recipients.

Advances in left ventricular assist device technologies have led to an improvement in pump hemocompatibility and outcomes. Because of concerns of thromboembolic complications in prior generations of left ventricular assist devices, bridging with parenteral anticoagulants was routinely. Management strategies of subtherapeutic INRs and their effects on the current generation of devices deserve review. We performed analysis of the MOMENTUM 3 trial including 6 centers in the mid-America region. Patients with subtherapeutic INRs (INR < 2) occurring after the index admission underwent chart review to determine the management strategies taken by clinicians. Strategies were divided into two groups, bridging or nonbridging. Of the 225 patients included in the analysis, 130 (58%) patients had a total of 235 subtherapeutic international normalized ratio (INR) events. Most (n = 179, 76.2%) of these INRs were not bridged (n = 100 warfarin dose adjustment, n = 79 no change in warfarin dose). Among those INRs (n = 56, 23.8%) treated with bridging, approximately half (n = 30, 53.6%) were treated with subcutaneous agents and other half (n = 26, 46.4%) were treated with intravenous agents. There was no difference in individual outcomes or composite endpoints of death, rehospitalization, CVA, or bleeding events between the groups.

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.

Design and characteristics of the prophylactic intra-operative ventricular arrhythmia ablation in high-risk LVAD candidates (PIVATAL) trial.

BACKGROUND: The use of a Left Ventricular Assist Device (LVAD) in patients with advanced heart failure refractory to optimal medical management has progressed steadily over the past two decades. Data have demonstrated reduced LVAD efficacy, worse clinical outcome, and higher mortality for patients who experience significant ventricular tachyarrhythmia (VTA). We hypothesize that a novel prophylactic intra-operative VTA ablation protocol at the time of LVAD implantation may reduce the recurrent VTA and adverse events postimplant. METHODS: We designed a prospective, multicenter, open-label, randomized-controlled clinical trial enrolling 100 patients who are LVAD candidates with a history of VTA in the previous 5 years. Enrolled patients will be randomized in a 1:1 fashion to intra-operative VTA ablation (n = 50) versus conventional medical management (n = 50) with LVAD implant. Arrhythmia outcomes data will be captured by an implantable cardioverter defibrillator (ICD) to monitor VTA events, with a uniform ICD programming protocol. Patients will be followed prospectively over a mean of 18 months (with a minimum of 9 months) after LVAD implantation to evaluate recurrent VTA, adverse events, and procedural outcomes. Secondary endpoints include right heart function/hemodynamics, healthcare utilization, and quality of life. CONCLUSION: The primary aim of this first-ever randomized trial is to assess the efficacy of intra-operative ablation during LVAD surgery in reducing VTA recurrence and improving clinical outcomes for patients with a history of VTA.

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.

Left Atrial to Coronary Sinus Shunting for Treatment of Symptomatic Heart Failure.

BACKGROUND: Heart failure (HF) is associated with both mortality and a significant decline in health status. Interatrial shunting is increasingly being investigated as a novel therapeutic option. OBJECTIVES: The ALT FLOW Early Feasibility Study was designed to evaluate the safety of the Edwards left atrial to coronary sinus APTURE Transcatheter Shunt System in patients with symptomatic HF. METHODS: A total of 18 centers enrolled patients with symptomatic HF with a pulmonary capillary wedge pressure >15 mm Hg at rest or 25 mm Hg during exercise. RESULTS: Between May 2018 and September 2022, 87 patients underwent attempted APTURE shunt implantation. Mean age was 71 years, and 53% were male. At baseline, mean left ventricular ejection fraction was 59% with 90% of the patients being in NYHA functional class III. Device success was achieved in 78 patients (90%), with no device occlusions or associated adverse events identified after implantation. The primary safety outcome occurred in only 2 patients (2.3%) at 30 days. At 6 months, health status improved: 67% of participants achieved NYHA functional class I to II status, with a 23-point improvement (P < 0.0001; 95% CI: 17-29 points) in the Kansas City Cardiomyopathy Questionnaire overall summary score. Also at 6 months, 20-W exercise pulmonary capillary wedge pressure was 7 mm Hg lower (P < 0.0001; 95% CI: -11 to -4 mm Hg) without change in right atrial pressure or other right heart function indices. CONCLUSIONS: In this single-arm experience, the APTURE Transcatheter Shunt System in patients with symptomatic HF was observed to be safe and resulted in reduction in pulmonary capillary wedge pressure and clinically meaningful improvements in HF symptoms and quality of life indices.

Effects of Body Mass Index on Presentation and Outcomes of COVID-19 among Heart Transplant and Left Ventricular Assist Device Patients: A Multi-Institutional Study.

The coronavirus disease 2019 (COVID-19) pandemic continues to pose a significant threat to patients receiving advanced heart failure therapies. The current study was undertaken to better understand the relationship between obesity and outcomes of SARS-CoV-2 infection in patients with a left ventricular assist device (LVAD) or heart transplant. We performed a retrospective review of patients with a heart transplant or LVAD who presented to one of the participating 11 institutions between April 1 and November 30, 2020. Patients were grouped by body mass index (BMI) into obese (BMI ≥ 30 k/m2) and nonobese cohorts (BMI < 30 kg/m2). Multivariable logistic regression models were used to estimate effects of obesity on outcomes of interest. Across all centers, 162 heart transplant and 81 LVAD patients were identified; 54 (33%) and 38 (47%) were obese, respectively. Obese patients tended to have more symptoms at presentation. No differences in rates of hospitalization or ICU admission were noted. Obese patients with LVADs were more likely to require mechanical ventilation (39% vs. 8%, p < 0.05). No differences in renal failure or secondary infection were noted. Mortality was similar among heart transplant patients (11% [obese] vs. 16% [nonobese], p = 0.628) and LVAD patients (12% vs. 15%, p = 1.0). BMI was not associated with increased adjusted odds of mortality, ICU admission, or mechanical ventilation (all p > 0.10). In summary, acute presentations of SARS-CoV-2 among heart transplant and LVAD recipients carry a significantly higher mortality than the general population, although BMI does not appear to impact this. Further studies on the longer-term effects of COVID-19 on this population are warranted.

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.

Left Ventricular Assist Devices: A Primer For the General Cardiologist.

Durable implantable left ventricular assist devices (LVADs) have been shown to improve survival and quality of life for patients with stage D heart failure. Even though LVADs remain underused overall, the number of patients with heart failure supported with LVADs is steadily increasing. Therefore, general cardiologists will increasingly encounter these patients. In this review, we provide an overview of the field of durable LVADs. We discuss which patients should be referred for consideration of advanced heart failure therapies. We summarize the basic principles of LVAD care, including medical and surgical considerations. We also discuss the common complications associated with LVAD therapy, including bleeding, infections, thrombotic issues, and neurologic events. Our goal is to provide a primer for the general cardiologist in the recognition of patients who could benefit from LVADs and in the principles of managing patients with LVAD. Our hope is to "demystify" LVADs for the general cardiologist.

Critical Care Cardiology Trials Network (CCCTN): a cohort profile.

AIMS: The aims of the Critical Care Cardiology Trials Network (CCCTN) are to develop a registry to investigate the epidemiology of cardiac critical illness and to establish a multicentre research network to conduct randomised clinical trials (RCTs) in patients with cardiac critical illness. METHODS AND RESULTS: The CCCTN was founded in 2017 with 16 centres and has grown to a research network of over 40 academic and clinical centres in the United States and Canada. Each centre enters data for consecutive cardiac intensive care unit (CICU) admissions for at least 2 months of each calendar year. More than 20 000 unique CICU admissions are now included in the CCCTN Registry. To date, scientific observations from the CCCTN Registry include description of variations in care, the epidemiology and outcomes of all CICU patients, as well as subsets of patients with specific disease states, such as shock, heart failure, renal dysfunction, and respiratory failure. The CCCTN has also characterised utilization patterns, including use of mechanical circulatory support in response to changes in the heart transplantation allocation system, and the use and impact of multidisciplinary shock teams. Over years of multicentre collaboration, the CCCTN has established a robust research network to facilitate multicentre registry-based randomised trials in patients with cardiac critical illness. CONCLUSION: The CCCTN is a large, prospective registry dedicated to describing processes-of-care and expanding clinical knowledge in cardiac critical illness. The CCCTN will serve as an investigational platform from which to conduct randomised controlled trials in this important patient population.

Anticoagulation and Antiplatelet Therapy for Prevention of Venous and Arterial Thrombotic Events in Critically Ill Patients With COVID-19: COVID-PACT.

BACKGROUND: The efficacy and safety of prophylactic full-dose anticoagulation and antiplatelet therapy in critically ill COVID-19 patients remain uncertain. METHODS: COVID-PACT (Prevention of Arteriovenous Thrombotic Events in Critically-ill COVID-19 Patients Trial) was a multicenter, 2×2 factorial, open-label, randomized-controlled trial with blinded end point adjudication in intensive care unit-level patients with COVID-19. Patients were randomly assigned to a strategy of full-dose anticoagulation or standard-dose prophylactic anticoagulation. Absent an indication for antiplatelet therapy, patients were additionally randomly assigned to either clopidogrel or no antiplatelet therapy. The primary efficacy outcome was the hierarchical composite of death attributable to venous or arterial thrombosis, pulmonary embolism, clinically evident deep venous thrombosis, type 1 myocardial infarction, ischemic stroke, systemic embolic event or acute limb ischemia, or clinically silent deep venous thrombosis, through hospital discharge or 28 days. The primary efficacy analyses included an unmatched win ratio and time-to-first event analysis while patients were on treatment. The primary safety outcome was fatal or life-threatening bleeding. The secondary safety outcome was moderate to severe bleeding. Recruitment was stopped early in March 2022 (≈50% planned recruitment) because of waning intensive care unit-level COVID-19 rates. RESULTS: At 34 centers in the United States, 390 patients were randomly assigned between anticoagulation strategies and 292 between antiplatelet strategies (382 and 290 in the on-treatment analyses). At randomization, 99% of patients required advanced respiratory therapy, including 15% requiring invasive mechanical ventilation; 40% required invasive ventilation during hospitalization. Comparing anticoagulation strategies, a greater proportion of wins occurred with full-dose anticoagulation (12.3%) versus standard-dose prophylactic anticoagulation (6.4%; win ratio, 1.95 [95% CI, 1.08-3.55]; P=0.028). Results were consistent in time-to-event analysis for the primary efficacy end point (full-dose versus standard-dose incidence 19/191 [9.9%] versus 29/191 [15.2%]; hazard ratio, 0.56 [95% CI, 0.32-0.99]; P=0.046). The primary safety end point occurred in 4 (2.1%) on full dose and in 1 (0.5%) on standard dose (P=0.19); the secondary safety end point occurred in 15 (7.9%) versus 1 (0.5%; P=0.002). There was no difference in all-cause mortality (hazard ratio, 0.91 [95% CI, 0.56-1.48]; P=0.70). There were no differences in the primary efficacy or safety end points with clopidogrel versus no antiplatelet therapy. CONCLUSIONS: In critically ill patients with COVID-19, full-dose anticoagulation, but not clopidogrel, reduced thrombotic complications with an increase in bleeding, driven primarily by transfusions in hemodynamically stable patients, and no apparent excess in mortality. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04409834.

End-of-life care in the cardiac intensive care unit: a contemporary view from the Critical Care Cardiology Trials Network (CCCTN) Registry.

AIMS: Increases in life expectancy, comorbidities, and survival with complex cardiovascular conditions have changed the clinical profile of the patients in cardiac intensive care units (CICUs). In this environment, palliative care (PC) services are increasingly important. However, scarce information is available about the delivery of PC in CICUs. METHODS AND RESULTS: The Critical Care Cardiology Trials Network (CCCTN) Registry is a network of tertiary care CICUs in North America. Between 2017 and 2020, up to 26 centres contributed an annual 2-month snapshot of all consecutive medical CICU admissions. We captured code status at admission and the decision for comfort measures only (CMO) before all deaths in the CICU. Of 13 422 patients, 10% died in the CICU and 2.6% were discharged to palliative hospice. Of patients who died in the CICU, 68% were CMO at death. In the CMO group, only 13% were do not resuscitate/do not intubate at admission. The median time from CICU admission to CMO decision was 3.4 days (25th-75th percentiles: 1.2-7.7) and ≥7 days in 27%. Time from CMO decision to death was <24 h in 88%, with a median of 3.8 h (25th-75th 1.0-10.3). Before a CMO decision, 78% received mechanical ventilation and 26% mechanical circulatory support. A PC provider team participated in the care of 41% of patients who died. CONCLUSIONS: In a contemporary CICU registry, comfort measures preceded death in two-thirds of cases, frequently without PC involvement. The high utilization of advanced intensive care unit therapies and lengthy times to a CMO decision highlight a potential opportunity for early engagement of PC teams in CICU.