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Background: Patients with pre-existing heart failure (HF) are likely at higher risk for adverse outcomes in coronavirus disease-2019 (COVID-19), but data on this population are sparse., Objectives: This study described the clinical profile and associated outcomes among patients with HF hospitalized with COVID-19., Methods: This study conducted a retrospective analysis of 6,439 patients admitted for COVID-19 at 1 of 5 Mount Sinai Health System hospitals in New York City between February 27 and June 26, 2020. Clinical characteristics and outcomes (length of stay, need for intensive care unit, mechanical ventilation, and in-hospital mortality) were captured from electronic health records. For patients identified as having a history of HF by International Classification of Diseases-9th and/or 10th Revisions codes, manual chart abstraction informed etiology, functional class, and left ventricular ejection fraction (LVEF)., Results: Mean age was 63.5 years, and 45% were women. Compared with patients without HF, those with previous HF experienced longer length of stay (8 days vs. 6 days; p < 0.001), increased risk of mechanical ventilation (22.8% vs. 11.9%; adjusted odds ratio: 3.64; 95% confidence interval: 2.56 to 5.16; p < 0.001), and mortality (40.0% vs. 24.9%; adjusted odds ratio: 1.88; 95% confidence interval: 1.27 to 2.78; p = 0.002). Outcomes among patients with HF were similar, regardless of LVEF or renin-angiotensin-aldosterone inhibitor use., Conclusions: History of HF was associated with higher risk of mechanical ventilation and mortality among patients hospitalized for COVID-19, regardless of LVEF., Competing Interests: Author Relationship With Industry Dr. Alvarez-Garcia received a mobility grant from Private Foundation Daniel Bravo Andreu (Spain). Dr. Rivas-Lasarte received a “Magda Heras” mobility grant from Spanish Society of Cardiology (Spain). Dr. Mitter has received personal fees from Abbott Laboratories, Cowen & Co., and the Heart Failure Society of America. Dr. Nadkarni has received grants, personal fees, and nonfinancial support from Renalytix AI; has received nonfinancial support from Pensieve Health; and has received personal fees from AstraZeneca, Variant Bio, BioVie, and GLG Consulting, outside the submitted work. Dr. Fayad has received grants from Daiichi-Sankyo, Amgen, Bristol Myers Squibb, and Siemens Healthineers; has received personal fees from Alexion, GlaxoSmithKline, and Trained Therapeutix Discovery, outside the submitted work; and holds patents licensed to Trained Therapeutix Discovery. Dr. Lala has received personal fees from Zoll, outside the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Introduction: Effective tacrolimus (TAC) dosing is hampered by complex pharmacokinetics and significant patient variability. The gut microbiome, a key mediator of endotoxemia, inflammation and oxidative stress in advanced heart failure (HF) patients, is a possible contributor to interindividual variations in drug efficacy. The effect of alterations in the gut microbiome on TAC dosing requirements after heart transplant (HT) has not been explored., Methods: We enrolled 24 patients (mean age = 55.8 ±2.3 years) within 3 months post-HT. Biomarkers of endotoxemia ((lipopolysaccharide (LPS)), inflammation (tumor necrosis factor-α (TNF-α)) and oxidative stress (8,12-iso-Isoprostane F-2alpha-VI) were measured in 16 blood samples. 22 stool samples were analyzed using 16S rRNA sequencing. TAC dose and serum trough level were measured at the time of stool and blood collection. TAC doses were reported in mg/kg/day and as level-to-dose (L/D) ratio, and categorized as ≤ vs. > median., Results: The median TAC dose was 0.1 mg/kg/day and L/D ratio was 100.01. Above the median daily weight-based TAC dose was associated with higher gut microbial alpha diversity (p = 0.03); similarly, TNF-α and 8,12-iso-Isoprostane F-2alpha-VI levels were lower and LPS levels were higher in the above median TAC group, although these findings were only marginally statistically significant and dependent on BMI adjustment. We observed n = 37 taxa to be significantly enriched among patients with > median TAC dose (all FDR<0.05), several of which are potential short-chain fatty acid producers with anti-inflammatory properties, including taxa from the family Subdoligranulum., Conclusions: Our pilot study observed gut microbial alpha diversity to be increased while inflammation and oxidative stress were reduced among patients requiring higher TAC doses early after HT., Competing Interests: Dr. Colombo Consultant, Abbott, no honoraria. Research Grant, Abbott. Dr. Naka Consultant, Abbott, Hourly base reimbursement. The sum of payment does not exceed $5000/year. Consultant, CryoLife, Hourly base reimbursement. The sum of payment does not exceed $5000/year. The rest of the co-authors have no competing interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials.