Durable left ventricular assist devices (dLVAD) remain a lifesaving therapy in patients with stage D heart failure that is refractory to conventional medical therapies. Owing to improvements in technology and patient outcomes, the number of patients supported with dLVADs has increased over the past decade. Despite this growing population, there are few resources for cardiovascular intensivists that integrate epidemiology, diagnostic workup and multidisciplinary medical management of acute emergencies in patients supported with dLVADs.

BACKGROUND:Despite widespread statin use, atherosclerotic cardiovascular disease remains a leading cause of morbidity and mortality worldwide. Monoclonal antibodies targeting circulating proprotein convertase subtilisin-kexin type 9 (PCSK9) substantially reduce low-density lipoprotein cholesterol (LDL-C) levels and cardiovascular events. However, the requirement for self-administration every 2 to 4 weeks may limit adherence to treatment. Inclisiran, a first-in-class small interfering ribonucleic acid (siRNA) therapy targeting hepatic PCSK9 production, has several potential advantages over the anti-PCSK9 monoclonal antibodies, principally longer duration of action. To date, however, the efficacy and safety of inclisiran have not been proven in a cardiovascular outcomes trial. METHODS:The ORION-4 study is the first large-scale clinical outcomes trial of an siRNA therapy, aiming to assess the efficacy and safety of inclisiran among participants with pre-existing atherosclerotic cardiovascular disease. The primary assessment is an intention-to-treat comparison of the effect of inclisiran sodium 300 mg (equivalent to 284 mg inclisiran), given by subcutaneous injection at randomization, at approximately 3 months and then approximately every 6 months thereafter, on major adverse cardiovascular events (MACE), defined as the composite of coronary death, myocardial infarction, fatal or nonfatal ischemic stroke, or urgent coronary revascularization. Participants will be followed until the median time since randomization is at least 5 years and at least 1,700 participants have a recorded adjudicated MACE. With a planned sample size of ∼15,000 participants, ORION-4 was designed to have >99% power to detect a relative reduction in the primary outcome of about 1 quarter, while also providing an opportunity to assess efficacy in different subgroups as well as on secondary outcomes of interest. RESULTS:Between 2019 and 2023 a total of 16,124 participants were randomized in the UK and the US. The mean (SD) age was 70 (8) years and 30% were female. At baseline, 78% had a history of coronary heart disease, 22% of ischemic stroke, 15% of revascularization for peripheral arterial disease, and 23% had diabetes mellitus. 85% were on statin therapy (53% high intensity statin, 29% moderate and 3% low intensity statins). Overall, baseline mean (SD) LDL-C was 96 (32) mg/dL, and was similar among participants on high- and moderate/low-intensity statin regimens (87 [27] mg/dL and 93 [26] mg/dL respectively), with higher levels in those receiving no statin therapy (133 [33] mg/dL). Follow-up will complete during 2026 and results will be available in early 2027. INTERPRETATION:Inclisiran potentially offers a scalable lipid-lowering treatment, either alone or in combination with other agents. ORION-4 will evaluate the clinical efficacy of inclisiran, and provide a robust assessment of the safety of prolonged use of an siRNA therapeutic. TRIAL REGISTRATION:The trial is registered at ClinicalTrials.gov (NCT03705234) and the EU Clinical Trials Register (EudraCT Number: 2017-005066-22).

Regional cardiogenic shock (CS) response systems are strong in concept but remain inconsistently implemented in the United States, with persistent heterogeneity in shock classification, mechanical circulatory support (MCS) deployment, hemodynamic monitoring, and transfer pathways. In California, these challenges are magnified by geography and fragmented hospital networks. The inaugural CALShock conference, convened in Los Angeles in February 2025 by the California Chapter of the American College of Cardiology, brought together multidisciplinary experts to synthesize emerging evidence and operational strategies for scalable improvements to shock systems of care. Key themes included routine use of shared classification and phenotyping frameworks, streamlined shock team activation and escalation workflows, transport as essential infrastructure, standardized prevention and management of MCS-related complications with clear exit strategies, broader registry participation, and integration of survivorship and post-discharge planning into comprehensive shock care. We describe the conference framework as a replicable model for other states and regions seeking to advance cardiogenic shock systems of care.

Abstract This prespecified AZALEA-TIMI 71 analysis showed that prior oral anticoagulation (OAC) experience indicates bleeding risk in atrial fibrillation. The factor XI inhibitor abelacimab reduced bleeding regardless of prior OAC experience, with potentially greater absolute benefit among OAC-naïve patients. This trial was registered at www.ClinicalTrials.gov as NCT04755283.

BACKGROUND:The paucity of data to guide selection of specific vasoactive agents in patients with cardiogenic shock (CS) may lead to variability in practice patterns. The level of variability and specific factors that are associated with the use of vasoactive medications and inodilators have not been previously described. METHODS:The CCCTN (Critical Care Cardiology Trials Network) is an international, multicenter network of cardiac intensive care units (CICUs) coordinated by the TIMI Study Group. This analysis included CICU admissions for CS from 2019 to 2023. Variation in the use of inodilator treatment (dobutamine/milrinone) was assessed with multivariable mixed-effects logistic modeling. RESULTS:A total of 3282 admissions from 37 CICUs comprised the analysis cohort. The use of vasoactive medications, including inodilator treatment, varied substantially across institutions. Patient-level variables associated with greater use of inodilators included history of heart failure (odds ratio, 1.98 [95% CI, 1.61-2.44]), biventricular failure (1.59 [95% CI, 1.27-2.00]), Society of Cardiovascular Angiography and Interventions stage D (1.34 [95% CI, 1.07-1.68]), valvular disease (1.34 [95% CI, 1.03-1.74]), and male sex (1.23 [95% CI, 1.02-1.49]). Variables associated with less inodilator use included cardiac arrest (0.33 [95% CI, 0.27-0.42]), right ventricular failure (0.50 [95% CI, 0.33-0.73]), Society of Cardiovascular Angiography and Interventions stage E (0.57 [95% CI, 0.41-0.81]), acute myocardial infarction-CS (0.71 [95% CI, 0.56-0.90]), peripheral arterial disease (0.73 [95% CI, 0.54-0.99]), older age (0.77 [95% CI, 0.72-0.83], per 10-year increase), and estimated glomerular filtration rate (0.96 [95% CI, 0.93-0.99], per 10 mL/min per 1.73 m2 increase). No individual measurable institution-level factors (eg, transplant center) were associated with variability in inodilator use. In mixed-effects logistic modeling, 45.7% of variation in inodilator use was attributed to patient-level factors and 22.7% to the random effect of individual CICU centers. Similarly, 35.3% of variation in the use of dobutamine versus milrinone was attributed to patient-level factors and 32.6% to the random effect of individual CICU centers. CONCLUSIONS:There is significant variation in vasoactive treatment and inodilator use in CS. Variation in inodilator use was associated with patient-level factors and with substantial individual CICU practice variation. Such variability underscores the need for additional high-quality evidence to guide vasoactive treatment strategies in CS.

Background Acute kidney injury (AKI) is associated with high morbidity and mortality in critically ill patients. Multicenter analyses describing the epidemiology of AKI in the cardiac intensive care unit (CICU) are scarce. Here, we describe the prevalence, predictors, and outcomes associated with AKI in a contemporary multicenter CICU population. Methods The Critical Care Cardiology Trials Network (CCCTN) is a collaboration of CICUs in North America coordinated by the TIMI Study Group (Boston, MA). We evaluated patient and hospital-level outcomes as a function of creatinine-only Kidney Disease: Improving Global Outcomes (KDIGO) AKI stage within the CCCTN registry. Logistic regression was used to assess associations with in-hospital mortality. Results Among 21 603 admissions, the overall prevalence of AKI was 23.7%, which was composed of KDIGO stage 1: 12.7%, stage 2: 1.7%, and stage 3: 9.2%. A higher prevalence and severity of AKI were seen in patients with baseline kidney disease, hypertension, or diabetes and in admissions with heart failure, cardiogenic shock, and cardiac arrest (P < .001 for all). There was a stepwise increase in hospital mortality across AKI stages (stage 1: 23%, stage 2: 39%, stage 3: 42%; P < .0001). The increased risk of death associated with progressive AKI stage persisted after multivariate adjustment (adjusted OR: stage 1: 2.1, stage 2: 3.7, stage 3: 3.4). Conclusions: AKI occurs in 1 in 4 admissions to the CICU, and a higher AKI stage is incrementally associated with in-hospital mortality, highlighting a need to develop strategies to mitigate AKI and its complications.

Importance:Older age is a strong risk factor for bleeding with currently available anticoagulants. Factor XI (FXI) inhibition may offer a safer anticoagulant strategy in this population. Objective:To evaluate the safety of the novel FXI inhibitor abelacimab vs rivaroxaban by age in patients with atrial fibrillation (AF). Design, Setting, and Participants:The randomized clinical trial AZALEA-TIMI 71 randomized patients with AF to receive 1 of 2 subcutaneous abelacimab doses (90 mg or 150 mg monthly) or oral rivaroxaban (20 mg daily, dose reduction to 15 mg). This prespecified analysis of the phase 2b AZALEA-TIMI 71 trial evaluated bleeding risk by age, analyzed continuously and categorically (<75 vs ≥75 years). The trial was conducted from March 2021 to September 2023; data analysis was performed from February to May 2025. Interventions:Monthly subcutaneous abelacimab (90 or 150 mg) or daily oral rivaroxaban (20/15 mg). Main Outcomes and Measures:The primary end point was the composite of major or clinically relevant nonmajor (CRNM) bleeding. Results:Among 1287 patients randomized, 715 (55.6%) were male and 572 (44.4%) were female; there were 625 patients (49%) 75 years or older. Compared with younger patients, those 75 years or older had lower body mass index (28 vs 32), were less likely to be taking antiplatelet therapy at baseline (17% vs 32%), and were more likely to have creatinine clearance 50 mL/min or less (33% vs 8%). Both abelacimab doses were associated with significantly less major or CRNM bleeding compared with rivaroxaban in those 75 years or older (hazard ratio [HR], 0.32; 95% CI, 0.17-0.60; and HR, 0.40; 95% CI, 0.22-0.73; for abelacimab, 90 and 150 mg, vs rivaroxaban, respectively) and in those younger than 75 years (HR, 0.28; 95% CI, 0.12-0.61; and HR, 0.35; 95% CI, 0.17-0.70; P for interaction, .85 and .84, respectively). Patients 75 years or older tended to derive greater absolute risk reductions with abelacimab (7.1 and 6.2 per 100 patient-years for abelacimab, 90 and 150 mg, vs rivaroxaban, respectively) than those younger than 75 years (4.7 and 4.2 per 100 patient-years, respectively). When modeled continuously, bleeding risk tended to increase with age in the rivaroxaban group but remained stable in the abelacimab group (P for interaction, .33). Conclusions and Relevance:This study found that abelacimab consistently reduced bleeding compared with rivaroxaban regardless of age, with the potential for a greater absolute reduction in bleeding with older age. FXI inhibition with abelacimab may become a particularly attractive option in older patients with AF and higher bleeding risk. The results of ongoing phase 3 trials are necessary to establish the efficacy and benefit-to-risk ratio of abelacimab. Trial Registration:ClinicalTrials.gov Identifier: NCT04755283.

BACKGROUND:Contemporary data characterizing older adults admitted to cardiac intensive care units (CICUs) across diverse indications are limited. OBJECTIVES:The objective of the study was to describe the clinical characteristics, critical care therapies, and in-hospital outcomes of older patients admitted to the CICU compared with younger adults. METHODS:The Critical Care Cardiology Trials Network is a multicenter, international registry of CICUs. Between 2017 and 2024, participating centers contributed annual ≥2-month snapshots of consecutive medical CICU admissions. Admissions were categorized into 4 age groups: <65, 65-<75, 75-<85, and ≥85 years. Outcomes included CICU and in-hospital mortality and length of stay. Multivariable models adjusted for sex, illness severity (SOFA score), lactate, and kidney function. RESULTS:Among 35,265 admissions from 50 sites, 44%, 27%, 21%, and 9% were aged <65, 65-<75, 75-<85, and ≥85 years, respectively. Acute coronary syndrome was the most common admission diagnosis among all age groups. Patients aged ≥85 years had the lowest use of mechanical circulatory support (5.5%), which consisted exclusively of intra-aortic balloon pumps. Relative to patients <65 years, adjusted ORs of in-hospital mortality were 1.53 (1.40-1.67) for 65-<75 years, 1.83 (1.67-2.01) for 75-<85 years, and 1.95 (1.72-2.22) for ≥85 years. Among cardiac arrest patients the increase in mortality with age was steeper, reaching 3.09 (2.24-4.26) for patients ≥85 years. CONCLUSIONS:Patients ≥85 years in contemporary CICUs experience survival comparable to those aged 75-<85 years, except in the setting of cardiac arrest. These findings support consideration of factors beyond chronological age in CICU triage and treatment decisions.

Early detection of cardiovascular disease and implementation of evidence-based treatments can reduce cardiovascular morbidity and mortality. Medical algorithms and decision-making tools provide a compelling option for screening, risk prediction, and treatment management. Such digital tools have the potential to aid both healthcare professionals and patients, providing support to decrease unwarranted diagnostic and treatment variability while guiding personalized care, with the overall objective of improving clinical outcomes. However, incorporating digital tools in healthcare settings is challenging, and evidence the required to support their adoption and understand the limitations can be lacking. A multinational panel of expert cardiologists and emergency physicians across North America, Europe, and Oceania gathered to deliberate on the current landscape of digital tools and medical algorithms, drawing on prior clinical experiences and knowledge of country-specific regulations. In this viewpoint, the evidence to support and guide the adoption of digital tools in cardiovascular clinical practice and the necessary components for successful integration into clinical workflows were discussed. Digital tools must be developed with the needs of the healthcare professionals, other relevant stakeholders (eg, administration personnel), and patients in mind to give them the best chance of widespread adoption. Academia, industry, and regulatory bodies should work together to cultivate and accelerate the implementation of digital tools in healthcare. The considerations discussed here may help decision makers to determine if a digital tool has the components necessary to integrate into the clinical workflow successfully.

Cardiogenic shock is defined by inadequate blood flow to vital organs because of cardiac insufficiency and is often, but not always, manifest by hypotension. In an effort to mitigate end-organ hypoperfusion and modulate blood pressure, medical management with vasoactive agents is the initial strategy in virtually all patients with cardiogenic shock. This clinical primer describes the pharmacologic profiles of the currently used vasoactive agents and available comparative effectiveness data, reviews the pathophysiology of the most common phenotypic forms of cardiogenic shock, and provides a strategic framework for vasoactive agent selection and titration that integrates the pharmacology, pathophysiology, and hemodynamic derangements that define each shock phenotype. The practice-based approach to vasopressor selection strategy for the management of cardiogenic shock outlines the following steps: first, emergently protect the mean arterial pressure; then, define the hemodynamic phenotype of cardiogenic shock and identify (and address, in parallel) potential etiologies and contributors; next, set additional hemodynamic goals beyond mean arterial pressure; last, tailor pharmacotherapy through iterative assessments of perfusion and ongoing hemodynamic derangements.

Background Oral anticoagulation (OAC) reduces stroke in patients with atrial fibrillation (AF), but increases bleeding. Objectives This study aimed to evaluate an updated version of the Age, Biomarkers, and Clinical history of bleeding in AF (ABC-AF)-bleeding score (2.0) including consideration of OAC type (direct oral anticoagulant [DOAC] or warfarin) and compare its performance with other bleeding risk scores in 25 962 patients from the COMBINE AF cohort. Methods The COMBINE AF biomarker cohort contains individual participant data from patients with AF enrolled in 3 pivotal randomized trials comparing DOACs with warfarin. The biomarkers in the ABC-AF-bleeding score (growth differentiation factor 15, hemoglobin, and troponin-T) were analyzed in baseline samples. The biomarker-based ABC-AF-bleeding score was updated (version 2.0) by incorporating OAC type into the model (DOAC or warfarin). Discrimination was assessed by Harrell C-index and compared with clinically based bleeding scores; HAS-BLED (Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile INR, Elderly, Drugs/alcohol), DOAC, and ORBIT (Older age, Reduced haemoglobin/haematocrit or history of anaemia, Bleeding history, Insufficient renal function, Treatment with antiplatelet agents). Results During follow-up, 1321 patients (5.1%) had an International Society on Thrombosis and Haemostasis major bleeding event, including 480 gastrointestinal, and 248 intracranial hemorrhages. The ABC-AF-bleeding 2.0 risk score showed better discrimination and calibration than the original version and provided superior discrimination than clinical risk scores for all outcomes. The ABC-AF-bleeding score 2.0 C-indices for major bleeding were 0.69 (95% CI, 0.68-0.71); gastrointestinal bleeding, 0.72 (95% CI, 0.69-0.74); and intracranial bleeding, 0.66 (95% CI, 0.63-0.70). The ABC-AF-bleeding score 2.0 also provided consistent superior discrimination in clinically relevant subgroups. Conclusion The updated ABC-AF-bleeding score 2.0 provided better discrimination and calibration for the risk of major bleeding than clinical risk scores, which was consistent across multiple subgroups. These findings support the utility of the ABC-AF-bleeding score for advancing precision medicine in AF.

OBJECTIVES:Lactate is a critical prognostic biomarker in observational studies of cardiac intensive care. In research settings, lactate is an integral component of prognostic models such as the IABP-SHOCK II risk score. However, lactate measurements are frequently missing due to heterogeneous clinical and logistical factors, potentially introducing systematic bias and compromising the validity of epidemiological inferences. In practice, missing lactate values are often replaced by indicator variables or excluded entirely, potentially hampering the analytical validity of research results. We illustrate a methodological framework to address missing lactate values in clinical research settings. STUDY DESIGN AND SETTING:We used data from 17,993 admissions recorded between 2017 and 2021 across 35 cardiac intensive care units participating in the Critical Care Cardiology Trials Network registry to characterize the mechanism of lactate missingness and develop a structured model for multiple imputation (MI). To assess the practical implications of this imputation procedure, we evaluated risk reclassification when using imputed lactate for computing the IABP-SHOCK II risk score. RESULTS:Missingness was associated with patient severity, confirming that the data were not missing completely at random. Identified predictors of lactate missingness were included in the MI model. The inclusion of imputed lactate in the IABP-SHOCK II risk score resulted in significant reclassification of risk, demonstrating the magnitude of bias inherent in naïve imputation (event-specific net reclassification ranging from -0.13% to 2.70% across shock populations). CONCLUSION:Missing lactate measurements are a source of selection and measurement bias in critical care registries. A structured imputation framework mitigates bias and improves the reliability of real-world evidence in cardiovascular epidemiology. PLAIN LANGUAGE SUMMARY:Lactate is a blood marker that helps clinicians assess how sick a patient is and is commonly used in risk prediction tools for patients with cardiogenic shock (CS). However, lactate measurements are often missing in clinical registries because testing practices vary across hospitals and patient groups. When lactate values are missing, researchers often either exclude those patients from analyses or assume that the missing value is low. Both approaches can introduce bias and may lead to inaccurate estimates of patient risk. In this study, we developed and evaluated a structured approach for handling missing lactate values using MI, a statistical method that estimates likely values based on other available clinical information. Using data from the Critical Care Cardiology Trials Network registry, we assessed how accounting for missing lactate affected risk classification in patients with CS. We found that replacing missing lactate values using a principled imputation approach led to meaningful changes in risk classification and identified additional patients at higher risk of death who would not have been recognized using standard approaches. The results were robust across multiple sensitivity analyses. These findings suggest that appropriate handling of missing biomarker data can improve the validity of registry-based research and may lead to more accurate assessment of patient risk when complete data are unavailable.