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Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, reduces cardiovascular death and worsening heart failure in patients with chronic heart failure and reduced ejection fraction. Early initiation during an acute heart failure (AHF) hospitalization may facilitate decongestion, improve natriuresis, and facilitate safe transition to a beneficial outpatient therapy for both diabetes and heart failure. The objective is to assess the efficacy and safety of initiating dapagliflozin within the first 24 hours of hospitalization in patients with AHF compared to usual care. DICTATE-AHF is a prospective, multicenter, open-label, randomized trial enrolling a planned 240 patients in the United States. Patients with type 2 diabetes hospitalized with hypervolemic AHF and an estimated glomerular filtration rate of at least 30 mL/min/1.73m2 are eligible for participation. Patients are randomly assigned 1:1 to dapagliflozin 10 mg once daily or structured usual care until day 5 or hospital discharge. Both treatment arms receive protocolized diuretic and insulin therapies. The primary endpoint is diuretic response expressed as the cumulative change in weight per cumulative loop diuretic dose in 40 mg intravenous furosemide equivalents. Secondary and exploratory endpoints include inpatient worsening AHF, 30-day hospital readmission for AHF or diabetic reasons, change in NT-proBNP, and measures of natriuresis. Safety endpoints include the incidence of hyper/hypoglycemia, ketoacidosis, worsening kidney function, hypovolemic hypotension, and inpatient mortality. The DICTATE-AHF trial will establish the efficacy and safety of early initiation of dapagliflozin during AHF across both AHF and diabetic outcomes in patients with diabetes.

We aim to validate the diagnostic performance of the first fully automatic, electronic heart failure (HF) identification algorithm and evaluate the implementation of an HF Dashboard system with 2 components: real-time identification of decompensated HF admissions and accurate characterization of disease characteristics and medical therapy. We constructed an HF identification algorithm requiring 3 of 4 identifiers: B-type natriuretic peptide >400 pg/mL; admitting HF diagnosis; history of HF International Classification of Disease, Ninth Revision, diagnosis codes; and intravenous diuretic administration. We validated the diagnostic accuracy of the components individually (n = 366) and combined in the HF algorithm (n = 150) compared with a blinded provider panel in 2 separate cohorts. We built an HF Dashboard within the electronic medical record characterizing the disease and medical therapies of HF admissions identified by the HF algorithm. We evaluated the HF Dashboard's performance over 26 months of clinical use. Individually, the algorithm components displayed variable sensitivity and specificity, respectively: B-type natriuretic peptide >400 pg/mL (89% and 87%); diuretic (80% and 92%); and International Classification of Disease, Ninth Revision, code (56% and 95%). The HF algorithm achieved a high specificity (95%), positive predictive value (82%), and negative predictive value (85%) but achieved limited sensitivity (56%) secondary to missing provider-generated identification data. The HF Dashboard identified and characterized 3147 HF admissions over 26 months. Automated identification and characterization systems can be developed and used with a substantial degree of specificity for the diagnosis of decompensated HF, although sensitivity is limited by clinical data input.

Aims Most proteomic analyses in patients with heart failure (HF) focus on the stable ambulatory setting; pathways that drive acute decompensated heart failure (ADHF) are largely uncharacterized. We aimed to examine the associations of cardiometabolic proteins with HF rehospitalization, mortality and diuretic response in patients with ADHF. Methods The Mechanisms of Diuretic Resistance Cohort comprised patients hospitalized for ADHF at Yale New Haven Hospital from 2015 to 2020. We quantified 369 serum proteins and evaluated their associations with rehospitalization, mortality or diuretic response, using individual and combined biomarkers. Models adjusted for sociodemographic/lifestyle factors, comorbidities and clinical factors. For individual biomarker models, significant proteins were those with a false‐discovery rate q‐value (FDRq) <1%, while combined biomarker models used a penalized cross‐validated log‐likelihood method to reduce false positives. Results Of 401 patients enrolled, median age was 65 years; 36% were female. Six (C1QTNF1, CTSD, FCN2, SERPINA12, TFRC and TNFRSF10C) were associated with increased risk of HF rehospitalization [hazard ratio (HR) ranging from 1.2 to 1.35 per standard deviation (SD) protein concentration] while one (SDC1) was associated with decreased risk (HR = 0.77 per SD protein concentration). Three (CDH1, FABP6 and TNC) were associated with mortality (HR ranging from 1.35 to 1.64 per SD protein concentration). Three (MMP7, PGLYRP1 and REN) were associated with reduced diuretic response (% Estimate ranging from −12.2% to −18.6% per SD protein concentration). Among all proteins, those associated with lower diuretic response correlated with greater mortality risk [Spearman r = −0.63 (95% confidence interval: −0.56, −0.69)]. Conclusions Several proteins with known associations with cardiometabolic disease were associated with poor outcomes or reduced diuretic response. They have known roles in inflammatory, metabolic and cardiac or kidney remodelling pathways and may point to novel pathways in ADHF that warrant investigation as potential prognostic tools and targets for intervention.

Acute heart failure hospitalizations complicated by diuretic resistance are associated with worse outcomes. Yet, quantification of the frequency and accompanying risk from loop diuretic resistance is limited by the absence of a comprehensive definition with universal clinical application. Herein, we outline limitations of the current metrics used to identify and define diuretic resistance. We discuss the best available methods to identify and prognosticate outcomes in diuretic resistance. We propose a mechanism-based classification system of diuretic resistance by anatomical location as follows: pre-nephron resistance, pre-loop of Henle resistance, loop of Henle resistance, and post-loop of Henle resistance. Within this paradigm, we compare and contrast historical beliefs of resistance mechanisms with current literature specific to patients with heart failure. We recommend a treatment pathway to restore diuretic efficacy with a literature review of the various combination diuretic strategies and ongoing clinical trials that may impact current best practices.

Introduction Diuretic resistance is a common complication impairing decongestion during hospitalization for acute decompensated heart failure (ADHF). The current understanding of diuretic resistance mechanisms in ADHF is based upon extrapolations from other disease states and healthy volunteers. However, accumulating evidence suggests that the dominant mechanisms in other populations have limited influence on diuretic response in ADHF. Additionally, the ability to rapidly and reliably diagnose diuretic resistance is inadequate using currently available tools. Aims The Mechanisms of Diuretic Resistance (MDR) Study is designed to rigorously investigate the mechanisms of diuretic resistance and develop tools to rapidly predict diuretic response in a prospective cohort hospitalized with ADHF. Methods Study assessments occur serially during the ADHF hospitalization and after discharge. Each assessment includes a supervised 6‐hour urine collection with baseline blood and timed spot urine collections following loop diuretic administration. Patient characteristics, medications, physical exam findings, and both in‐hospital and post‐discharge HF outcomes are collected. Patients with diuretic resistance are eligible for a randomized sub‐study comparing an increased loop diuretic dose with combination diuretic therapy of loop diuretic plus chlorothiazide. Conclusions The Mechanisms of Diuretic Resistance Study will establish a prospective patient cohort and biorepository to investigate the mechanisms of diuretic resistance and urine biomarkers to rapidly predict loop diuretic resistance.

Background/ObjectivesObesity is associated with a lower mortality risk among patients with heart failure (HF). Whether this obesity paradox applies to all-cause hospitalizations is unknown. We aimed to investigate the association between body mass index (BMI) and 30-day all-cause readmissions following HF hospitalization.Subjects/MethodsWe retrospectively evaluated 2252 HF hospital admissions of Centers of Medicare Services beneficiaries from an academic medical center. We classified obesity using established BMI categories. All 30-day postdischarge readmission to all hospitals and mortality events were documented. We evaluated 30-day postdischarge unplanned, all-cause readmission and death in the total cohort, propensity-matched cohort, and by ejection fraction (EF).ResultsAn Overweight-Obese BMI (BMI ≥ 25 kg/m2) was paradoxically associated with a lower mortality rate than a Normal BMI (18.5–24.9 kg/m2) (5.0% vs 8.5%, p = 0.0018). In contrast, an Overweight-Obese BMI was associated with a 29% (95% CI: 1.03–1.63) increased relative risk of all-cause readmission compared with a Normal BMI (23.2% vs 18.9%, p = 0.0288), which was consistent across obesity severity subgroups. Among 966 matched admissions, an Overweight-Obese BMI retained higher readmission risk compared with a Normal BMI (25.1% vs 17.2%, p = 0.003). After matching, readmissions remained higher for Overweight-Obese vs Normal BMI in admissions with reduced EF (25.7% vs 17.8%, p = 0.032) and preserved EF (23.0% vs 15.0%, p = 0.048). No difference in the percentage of readmissions for HF (40%) or noncardiovascular causes (45%) existed between Overweight-Obese and Normal BMI groups.ConclusionsDespite a lower mortality risk, increased BMI is associated with increased all-cause hospital readmission rates in an elderly HF population which persists after propensity matching.

With over 1 million primary heart failure (HF) hospitalizations annually, nearly 80% of patients who present to the emergency department with decompensated HF (DHF) are hospitalized. Short stay units (SSU) present an alternative to hospitalization, yet the effectiveness of the SSU strategy of care is not well known. This study is to determine the effectiveness of a SSU strategy compared with hospitalization in lower-risk patients with DHF. Our primary outcome was a composite of 30-day mortality and re-hospitalization. Key secondary outcomes included 90-day mortality and re-hospitalization, costs, and 30-day days-alive-and-out-of-hospital (DAOOH). This is a systematic review and meta-analysis, following PRISMA guidelines. MEDLINE, EMBASE, CENTRAL, CINAHL, SCOPUS, and Web of Science were searched from inception through February 2024. Either randomized trials or comparative observational studies were included if they compared outcomes between low-risk ED DHF patients admitted to an SSU (defined as an observation unit with expected stay ≤ 48 h) vs. admitted to the hospital. Two authors independently screened all titles and abstracts and then identified full texts for inclusion. Data extraction and risk of bias assessments were performed by two authors in parallel. The primary outcome was a composite of death or readmission within 30 days, reported as relative risk (RR), where a RR < 1 favored the SSU strategy. Secondary outcomes included 90-day mortality and re-hospitalization, costs, and 1-month days-alive-and-out-of-hospital (DAOOH). Of the 467 articles identified by our search strategy, only 3 full text articles were included. In meta-analysis for the primary outcome of 30-day death or readmission, the RR was 0.95 (95% CI = 0.56 to 1.63; I2 = 0%) for patients randomized to SSU vs hospitalization (2 studies, 241 patients). There were only 2 total deaths at 30 days in the 2 studies (total N = 258) which reported 30-day mortality, both in hospitalized patients. Only one study reported 90-day outcomes, showing no significant differences. Costs were lower in the SSU arm from one study, and 30-day DAOOH also favored SSU based on a single randomized trial. Based on very limited evidence, SSU provides similar efficacy for 30-day and 90-day mortality and readmission compared to hospitalization. An SSU strategy appears safe and may be cost effective.

Diuresis to achieve decongestion is a central aim of therapy in patients hospitalized for acute decompensated heart failure (ADHF). While multiple clinical trials have investigated initial diuretic strategies for a designated period of time, there is a paucity of evidence to guide diuretic titration strategies continued until decongestion is achieved. The use of urine chemistries (urine sodium and creatinine) in a natriuretic response prediction equation accurately estimates natriuresis in response to diuretic dosing, but a randomized clinical trial is needed to compare a urine chemistry-guided diuresis strategy with a strategy of usual care. The urinE chemiStry guided aCute heArt faiLure treATmEnt (ESCALATE) trial is designed to test the hypothesis that protocolized diuretic therapy guided by spot urine chemistry through completion of intravenous diuresis will be superior to usual care and improve outcomes over the 14 days following randomization. ESCALATE will randomize and obtain complete data on 450 patients with acute heart failure to a diuretic strategy guided by urine chemistry or a usual care strategy. Key inclusion criteria include an objective measure of hypervolemia with at least 10 pounds of estimated excess volume, and key exclusion criteria include significant valvular stenosis, hypotension, and a chronic need for dialysis. Our primary outcome is days of benefit over the 14 days after randomization. Days of benefit combines patient symptoms captured by global clinical status with clinical state quantifying the need for hospitalization and intravenous diuresis. NCT04481919.

Diuresis to achieve decongestion is a central aim of therapy in patients hospitalized for acute decompensated heart failure (ADHF). While multiple approaches have been tried to achieve adequate decongestion rapidly while minimizing adverse effects, no single diuretic strategy has shown superiority, and there is a paucity of data and guidelines to utilize in making these decisions. Observational cohort studies have shown associations between urine sodium excretion and outcomes after hospitalization for ADHF. Urine chemistries (urine sodium ± urine creatinine) may guide diuretic titration during ADHF, and multiple randomized clinical trials have been designed to compare a strategy of urine chemistry–guided diuresis to usual care. This review will summarize current literature for diuretic monitoring and titration strategies, outline evidence gaps, and describe the recently completed and ongoing clinical trials to address these gaps in patients with ADHF with a particular focus on the utility of urine sodium–guided strategies.