Faculty Bibliography

BACKGROUND/UNASSIGNED:Associations of early changes in vasoactive support with cardiogenic shock (CS) mortality remain incompletely defined. METHODS/UNASSIGNED: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/UNASSIGNED: CONCLUSIONS/UNASSIGNED: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.

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.

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.

BACKGROUND:The European Society of Cardiology (ESC) provided a focused update to the 2021 Guideline for the Management of Heart Failure, now providing a 1A recommendation for intravenous iron in patients with heart failure with reduced ejection fraction (HFrEF) and iron deficiency (ID). However, the findings from randomized controlled trials (RCT) are mixed. This systematic review of RCTs aims to provide an update and synthesize the evidence addressing the association of intravenous iron with patient-based outcomes in patients with HFrEF and ID. METHODS:Any RCT evaluating the effect of intravenous iron in patients with HFrEF and ID was eligible for inclusion. A complete search of the EMBASE and PubMed databases was conducted from inception until 15 September 2023. The primary outcome was the composite of the quality of life (QoL) questionnaires, while the secondary outcomes included first heart failure (HF) hospitalizations and all-cause mortality. Data extraction was performed independently by two reviewers. Data were pooled using a random-effects model. RESULTS:Of the 1035 references, 15 RCTs enrolling 6649 patients were included in this study. Intravenous iron was associated with significant improvement in the composite of QoL (standardized mean difference - 1.36, 95% confidence interval [CI] - 2.24 to - 0.48; p = 0.002), a significant reduction in first HF hospitalizations (hazard ratio [HR] 0.73, 95% CI 0.56-0.95; p = 0.02), and with no change in all-cause mortality (HR 0.90, 95% CI 0.79-1.03; p = 0.12). The certainty of the evidence ranged from moderate to very low. CONCLUSION/CONCLUSIONS:Intravenous iron is possibly associated with improved QoL and reduced HF hospitalizations, without impacting all-cause mortality. These findings not only support the use of intravenous iron in patients with HFrEF but also emphasize the need for well-designed and executed RCTs with granular outcome reporting and powered sufficiently to address the impact of intravenous iron on mortality in patients with HFrEF and ID. REGISTRATION/BACKGROUND:PROSPERO identifier number CRD42023389.

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:= 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.

IMPORTANCE:Left ventricular assist devices (LVADs) enhance quality and duration of life in advanced heart failure. The burden of nonsurgical bleeding events is a leading morbidity. Aspirin as an antiplatelet agent is mandated along with vitamin K antagonists (VKAs) with continuous-flow LVADs without conclusive evidence of efficacy and safety. OBJECTIVE:To determine whether excluding aspirin as part of the antithrombotic regimen with a fully magnetically levitated LVAD is safe and decreases bleeding. DESIGN, SETTING, AND PARTICIPANTS:This international, randomized, double-blind, placebo-controlled study of aspirin (100 mg/d) vs placebo with VKA therapy in patients with advanced heart failure with an LVAD was conducted across 51 centers with expertise in treating patients with advanced heart failure across 9 countries. The randomized population included 628 patients with advanced heart failure implanted with a fully magnetically levitated LVAD (314 in the placebo group and 314 in the aspirin group), of whom 296 patients in the placebo group and 293 in the aspirin group were in the primary analysis population, which informed the primary end point analysis. The study enrolled patients from July 2020 to September 2022; median follow-up was 14 months. INTERVENTION:Patients were randomized in a 1:1 ratio to receive aspirin (100 mg/d) or placebo in addition to an antithrombotic regimen. MAIN OUTCOMES AND MEASURES:The composite primary end point, assessed for noninferiority (-10% margin) of placebo, was survival free of a major nonsurgical (>14 days after implant) hemocompatibility-related adverse events (including stroke, pump thrombosis, major bleeding, or arterial peripheral thromboembolism) at 12 months. The principal secondary end point was nonsurgical bleeding events. RESULTS:Of the 589 analyzed patients, 77% were men; one-third were Black and 61% were White. More patients were alive and free of hemocompatibility events at 12 months in the placebo group (74%) vs those taking aspirin (68%). Noninferiority of placebo was demonstrated (absolute between-group difference, 6.0% improvement in event-free survival with placebo [lower 1-sided 97.5% CI, -1.6%]; P < .001). Aspirin avoidance was associated with reduced nonsurgical bleeding events (relative risk, 0.66 [95% confidence limit, 0.51-0.85]; P = .002) with no increase in stroke or other thromboembolic events, a finding consistent among diverse subgroups of patient characteristics. CONCLUSIONS AND RELEVANCE:In patients with advanced heart failure treated with a fully magnetically levitated LVAD, avoidance of aspirin as part of an antithrombotic regimen, which includes VKA, is not inferior to a regimen containing aspirin, does not increase thromboembolism risk, and is associated with a reduction in bleeding events. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT04069156.

Despite improving outcomes with modern pump technology, left ventricular assist device (LVAD) utilization for patients with end-stage heart failure (HF) has declined significantly in the preceding half-decade. Here, we examine this trend, noting an inherent contradiction in the declining utilization of an improving therapeutic option. We propose a series of provocative questions as a "call to action" for the field of advanced HF to consider both scientifically and clinically, focusing on our evaluation parameters for LVAD candidacy, our approach to dichotomous LVAD vs transplant decisions, and our current management paradigms. We conclude that modernization in these areas to match the advantages of modern pump technology is required to best serve patients with advanced HF.