Faculty Bibliography

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.

There is limited large, national data investigating the prevalence, characteristics, and outcomes of cardiac arrest (CA) in patients hospitalized for heart failure (HF). The goal of this study was to examine the characteristics, trends, and outcomes of HF hospitalizations complicated by in-hospital CA. We used the National Inpatient Sample to identify all primary HF admissions from 2016 to 2019. Cohorts were built based on the presence of a codiagnosis of CA. Diagnoses were identified using International Classification of Diseases, Tenth Revision, Clinical Modification codes. Associations with CA were then analyzed using multivariate logistic regression. We identified a total of 4,905,564 HF admissions, 56,170 (1.1%) of which had CA. Hospitalizations complicated by CA were significantly more likely to be male, to have coronary artery disease, renal disease, and less likely to be White (p <0.001, all). Age <65 (odds ratio [OR] 1.18, p <0.001), renal disease (OR 2.41, p <0.001), and coronary artery disease (OR 1.26, p <0.001) had higher odds of CA while female gender (OR 0.84, confidence interval [CI] 0.83 to 0.86, p <0.001) or HFpEF (OR 0.49, CI 0.48 to 0.50, p <0.001) had lower odds of CA. Patients with CA had higher inpatient mortality (CA 54.2% vs no CA 2.1%, p <0.001), which persisted after multivariate adjustment (OR 64.8, CI 63.5 to 66.0, p <0.001). CA occurs in >1 in 1,000 HF hospitalizations and remains a prominent and serious event associated with a high mortality. Further research is needed to examine long-term outcomes and mechanical circulatory support utilization with more granularity in HF patients with in-hospital CA.

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.

The Aeson total artificial heart provides right- and left-sided heart replacement for biventricular failure with notable improvements from prior generations. These include enhanced hemocompatibility and autoregulation enabling increased output in response to higher filling pressures. We report the first clinical implantation in the United States as part of an early feasibility study. The patient was successfully bridged to transplant after 5 months of support on the device and has made a full recovery.