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BACKGROUND: The STRONG-HF trial showed that high-intensity care (HIC) consisting of rapid up-titration of guideline-directed medical therapy (GDMT) and close follow-up reduced all-cause death or heart failure (HF) readmission at 180 days compared to usual care (UC). We hypothesized that significant differences in patient characteristics, management, and outcomes over the enrolment period may exist. METHODS: Two groups of the 1,078 patients enrolled in STRONG-HF were created according to the order of enrolment within center. The early group consisted of the first 10 patients enrolled at each center (N = 342) and the late group consisted of the following patients (N = 736). RESULTS: Late enrollees were younger, had more frequently reduced ejection fraction, slightly lower NT-proBNP and creatinine levels compared with early enrollees. The primary outcome occurred less frequently in early compared to late enrollees (15% vs. 21%, aHR 0.65, 95% CI 0.42-0.99, P = .044). No treatment-by-enrolment interaction was seen in respect to the average percentage of optimal dose of GDMT after randomization, which was consistently higher in early and late patients randomized to HIC compared to UC. The higher use of renin-angiotensin-inhibitors in the HIC arm was more pronounced in the late enrollees both after randomization (interaction-P = .013) and at 90 days (interaction-P < .001). No interaction was observed for safety events. Patients randomized late to UC displayed a trend toward more severe outcomes (26% vs. 16%, P = .10), but the efficacy of HIC showed no interaction with the enrolment group (aHR 0.77, 95% CI 0.35-1.67 in early and 0.58, 95% CI 0.40-0.83 in late enrollees, adjusted interaction-P = .51) with similar outcomes in the HIC arm in late and early enrollees (16% vs. 13%, P = .73). CONCLUSIONS: Late enrollees have different clinical characteristics and higher event rates compared to early enrollees. GDMT implementation in the HIC arm robustly achieved similar doses with consistent efficacy in early and late enrollees, mitigating the higher risk of adverse outcome in late enrollees. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03412201.
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Insuficiência Cardíaca , Volume Sistólico , Humanos , Masculino , Feminino , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/terapia , Idoso , Pessoa de Meia-Idade , Volume Sistólico/fisiologia , Peptídeo Natriurético Encefálico/sangue , Resultado do Tratamento , Fatores de Tempo , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Fragmentos de Peptídeos/sangue , Causas de Morte/tendências , Readmissão do Paciente/estatística & dados numéricos , Antagonistas de Receptores de Angiotensina/uso terapêuticoRESUMO
BACKGROUND: The use of sodium-glucose cotransporter-2 inhibitors (SGLT2is) in Veterans Affairs (VA) patients hospitalized with heart failure (HF) has not been reported previously. METHODS: VA electronic health record data were used to identify patients hospitalized for HF (primary or secondary diagnosis) from 01/2019-11/2022. Patients with SGLT2i allergy, advanced/end-stage chronic kidney disease (CKD) or advanced HF therapies were excluded. We identified factors associated with discharge SGLT2i prescriptions for patients hospitalized due to HF in 2022. We also compared SGLT2i and angiotensin receptor-neprilysin inhibitor (ARNI) prescription rates. Hospital-level variations in SGLT2i prescriptions were assessed via the median odds ratio. RESULTS: A total of 69,680 patients were hospitalized due to HF; 10.3% were prescribed SGLT2i at discharge (4.4% newly prescribed, 5.9% continued preadmission therapy). SGLT2i prescription increased over time and was higher in patients with HFrEF and primary HF. Among 15,762 patients hospitalized in 2022, SGLT2i prescription was more likely in patients with diabetes (adjusted odds ratio [aOR] 2.27; 95% confidence interval [CI]: 2.09-2.47) and ischemic heart disease (aOR 1.14; 95% CI: 1.03-1.26). Patients with increased age (aOR 0.77 per 10 years; 95% CI: 0.73-0.80) and lower systolic blood pressure (aOR 0.94 per 10 mmHg; 95% CI: 0.92-0.96) were less likely to be prescribed SGLT2i, and SGLT2i prescription was not more likely in patients with CKD (aOR 1.07; 95% CI 0.98-1.16). The adjusted median odds ratio suggested a 1.8-fold variation in the likelihood that similar patients at 2 random VA sites were prescribed SGLT2i (range 0-21.0%). In patients with EF ≤ 40%, 30.9% were prescribed SGLT2i while 26.9% were prescribed ARNI (P < 0.01). CONCLUSION: One-tenth of VA patients hospitalized for HF were prescribed SGLT2i at discharge. Opportunities exist to reduce variation in SGLT2i prescription rates across hospitals and to promote its use in patients with CKD and older age.
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BACKGROUND: Differences in demographics, risk factors, and clinical characteristics may contribute to variations in men and women in terms of the prevalence, clinical setting, and outcomes associated with worsening heart failure (WHF) events. We sought to describe sex-based differences in the epidemiology, clinical characteristics, and outcomes associated with WHF events across clinical settings. METHODS AND RESULTS: We examined adults diagnosed with HF from 2010 to 2019 within a large, integrated health care delivery system. Electronic health record data were accessed for hospitalizations, emergency department (ED) visits and observation stays, and outpatient encounters. WHF was identified using validated natural language processing algorithms and defined as ≥1 symptom, ≥2 objective findings (including ≥1 sign), and ≥1 change in HF-related therapy. Incidence rates and associated outcomes for WHF were compared across care setting by sex. We identified 1,122,368 unique clinical encounters with a diagnosis code for HF, with 124,479 meeting WHF criteria. These WHF encounters existed among 102,116 patients, of whom 48,543 (47.5%) were women and 53,573 (52.5%) were men. Women experiencing WHF were older and more likely to have HF with preserved ejection fraction compared with men. The clinical settings of WHF were similar among women and men: hospitalizations (36.8% vs 37.7%), ED visits or observation stays (11.8% vs 13.4%), and outpatient encounters (4.4% vs 4.9%). Women had lower odds of 30-day mortality after an index hospitalization (adjusted odds ratio 0.88, 95% confidence interval 0.83-0.93) or ED visit or observation stay (adjusted odds ratio 0.86, 95% confidence interval 0.75-0.98) for WHF. CONCLUSIONS: Women and men contribute similarly to WHF events across diverse clinical settings despite marked differences in age and left ventricular ejection fraction.
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Insuficiência Cardíaca , Sistema de Aprendizagem em Saúde , Humanos , Feminino , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Masculino , Idoso , Pessoa de Meia-Idade , Fatores Sexuais , Progressão da Doença , Estudos Retrospectivos , Hospitalização/estatística & dados numéricos , Fatores de Risco , Idoso de 80 Anos ou mais , Incidência , Serviço Hospitalar de Emergência , Volume Sistólico/fisiologiaAssuntos
Aldeído Redutase , Cardiomiopatias Diabéticas , Humanos , Aldeído Redutase/antagonistas & inibidores , Aldeído Redutase/metabolismo , Cardiomiopatias Diabéticas/tratamento farmacológico , Inibidores Enzimáticos/uso terapêutico , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Ischemic cardiomyopathy (ICM) is the most common underlying etiology of heart failure in the United States and is a significant contributor to deaths due to cardiovascular disease worldwide. The diagnosis and management of ICM has advanced significantly over the past few decades, and the evidence for medical therapy in ICM is both compelling and robust. This contrasts with evidence for coronary revascularization, which is more controversial and favors surgical approaches. This review will examine landmark clinical trial results in detail as well as provide a comprehensive overview of the current epidemiology, diagnostic approaches, and management strategies of ICM.
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Cardiomiopatias , Doença da Artéria Coronariana , Insuficiência Cardíaca , Isquemia Miocárdica , Humanos , Estados Unidos , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/cirurgia , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/terapia , Cardiomiopatias/diagnóstico , Cardiomiopatias/etiologia , Cardiomiopatias/terapia , Tomada de Decisão Clínica , Resultado do Tratamento , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/cirurgiaRESUMO
BACKGROUND: Timely heart failure (HF) diagnosis can lead to earlier intervention and reduced morbidity. Among historically marginalized patients, new-onset HF diagnosis is more likely to occur in acute care settings (emergency department or inpatient hospitalization) than outpatient settings. Whether inequity within outpatient clinician practices affects diagnosis settings is unknown. METHODS: We determined the setting of incident HF diagnosis among Medicare fee-for-service beneficiaries between 2013 and 2017. We identified sociodemographic and medical characteristics associated with HF diagnosis in the acute care setting. Within each outpatient clinician practice, we compared acute care diagnosis rates across sociodemographic characteristics: female versus male sex, non-Hispanic White versus other racial and ethnic groups, and dual Medicare-Medicaid eligible (a surrogate for low income) versus nondual-eligible patients. Based on within-practice differences in acute diagnosis rates, we stratified clinician practices by equity (high, intermediate, and low) and compared clinician practice characteristics. RESULTS: Among 315â 439 Medicare patients with incident HF, 173â 121 (54.9%) were first diagnosed in acute care settings. Higher adjusted acute care diagnosis rates were associated with female sex (6.4% [95% CI, 6.1%-6.8%]), American Indian (3.6% [95% CI, 1.1%-6.1%]) race, and dual eligibility (4.1% [95% CI, 3.7%-4.5%]). These differences persisted within clinician practices. With clinician practice adjustment, dual-eligible patients had a 4.9% (95% CI, 4.5%-5.4%) greater acute care diagnosis rate than nondual-eligible patients. Clinician practices with greater equity across dual eligibility also had greater equity across sex and race and ethnicity and were more likely to be composed of predominantly primary care clinicians. CONCLUSIONS: Differences in HF diagnosis rates in the acute care setting between and within clinician practices highlight an opportunity to improve equity in diagnosing historically marginalized patients.
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Insuficiência Cardíaca , Medicare , Humanos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/etnologia , Insuficiência Cardíaca/epidemiologia , Feminino , Masculino , Estados Unidos/epidemiologia , Idoso , Padrões de Prática Médica/estatística & dados numéricos , Disparidades em Assistência à Saúde/etnologia , Idoso de 80 Anos ou mais , Planos de Pagamento por Serviço PrestadoRESUMO
BACKGROUND: Recent evidence suggests that acetazolamide may be beneficial as an adjunctive diuretic therapy in patients with acute decompensated heart failure (HF). We aim to pool all the studies conducted until now and provide updated evidence regarding the role of acetazolamide as adjunctive diuretic in patients with acute decompensated HF. METHODS: PubMed/Medline, Cochrane Library, and Scopus were searched from inception until July 2023, for randomized and nonrandomized studies evaluating acetazolamide as add-on diuretic in patients with acute decompensated HF. Data about natriuresis, urine output, decongestion, and the clinical signs of congestion were extracted, pooled, and analyzed. Data were pooled using a random effects model. Results were presented as risk ratios (RRs), odds ratios (ORs), or weighted mean differences (WMD) with 95% confidence intervals (95% CIs). Certainty of evidence was assessed using the grading of recommendation, assessment, development, and evaluation (GRADE) approach. A P value of < 0.05 was considered significant in all cases. RESULTS: A total of 5 studies (n = 684 patients) were included with a median follow-up time of 3 months. Pooled analysis demonstrated significantly increased natriuresis (MD 55.07, 95% CI 35.1-77.04, P < 0.00001; I2 = 54%; moderate certainty), urine output (MD 1.04, 95% CI 0.10-1.97, P = 0.03; I2 = 79%; moderate certainty) and decongestion [odds ratio (OR) 1.62, 95% CI 1.14-2.31, P = 0.007; I2 = 0%; high certainty] in the acetazolamide group, as compared with controls. There was no significant difference in ascites (RR 0.56, 95% CI 0.23-1.36, P = 0.20; I2 = 0%; low certainty), edema (RR 1.02, 95% CI 0.52-2.0, P = 0.95; I2 = 45%; very low certainty), raised jugular venous pressure (JVP) (RR 0.86, 95% CI 0.63-1.17, P = 0.35; I2 = 0%; low certainty), and pulmonary rales (RR 0.82, 95% CI 0.44-1.51, P = 0.52; I2 = 25%; low certainty) between the two groups. CONCLUSIONS: Acetazolamide as an adjunctive diuretic significantly improves global surrogate endpoints for decongestion therapy but not all individual signs and symptoms of volume overload. SYSTEMATIC REVIEW REGISTRATION: This systematic review was prospectively registered on the PROSPERO ( https://www.crd.york.ac.uk/PROSPERO/ ), registration number CRD498330.
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Acetazolamida , Diuréticos , Insuficiência Cardíaca , Acetazolamida/uso terapêutico , Acetazolamida/administração & dosagem , Humanos , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Diuréticos/uso terapêutico , Diuréticos/administração & dosagem , Quimioterapia Combinada , Doença Aguda , Ensaios Clínicos Controlados Aleatórios como Assunto , Inibidores da Anidrase Carbônica/uso terapêutico , Inibidores da Anidrase Carbônica/administração & dosagemRESUMO
AIMS: Worsening heart failure (WHF) events occurring in non-inpatient settings are becoming increasingly recognized, with implications for prognostication. We evaluate the performance of a natural language processing (NLP)-based approach compared with traditional diagnostic coding for non-inpatient clinical encounters and left ventricular ejection fraction (LVEF). METHODS AND RESULTS: We compared characteristics for encounters that did vs. did not meet WHF criteria, stratified by care setting [i.e. emergency department (ED) and observation stay]. Overall, 8407 (22%) encounters met NLP-based criteria for WHF (3909 ED visits and 4498 observation stays). The use of an NLP-derived definition adjudicated 3983 (12%) of non-primary HF diagnoses as meeting consensus definitions for WHF. The most common diagnosis indicated in these encounters was dyspnoea. Results were primarily driven by observation stays, in which 2205 (23%) encounters with a secondary HF diagnosis met the WHF definition by NLP. CONCLUSIONS: The use of standard claims-based adjudication for primary diagnosis in the non-inpatient setting may lead to misclassification of WHF events in the ED and overestimate observation stays. Primary diagnoses alone may underestimate the burden of WHF in non-hospitalized settings.
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BACKGROUND: Heart failure (HF) is a leading cause of hospitalization in the United States. Decongestion remains a central goal of inpatient management, but contemporary decongestion practices and associated weight loss have not been well characterized nationally. OBJECTIVES: This study aimed to describe contemporary inpatient diuretic practices and clinical predictors of weight loss in patients hospitalized for HF. METHODS: The authors identified HF hospitalizations from 2015 to 2022 in a U.S. national database aggregating deidentified patient-level electronic health record data across 31 geographically diverse community-based health systems. The authors report patient characteristics and inpatient weight change as a primary indicator of decongestion. Predictors of weight loss were evaluated using multivariable models. Temporal trends in inpatient diuretic practices, including augmented diuresis strategies such as adjunctive thiazides and continuous diuretic infusions, were assessed. RESULTS: The study cohort included 262,673 HF admissions across 165,482 unique patients. The median inpatient weight loss was 5.3 pounds (Q1-Q3: 0.0-12.8 pounds) or 2.4 kg (Q1-Q3: 0.0-5.8 kg). Discharge weight was higher than admission weight in 20% of encounters. An increase of ≥0.3 mg/dL in serum creatinine from admission to inpatient peak occurred in >30% of hospitalizations and was associated with less weight loss. Adjunctive diuretic agents were utilized in <20% of encounters but were associated with greater weight loss. CONCLUSIONS: In a large-scale U.S. community-based cohort study of HF hospitalizations, estimated weight loss from inpatient decongestion remains highly variable, with weight gain observed across many admissions. Augmented diuresis strategies were infrequently used. Comparative effectiveness trials are needed to establish optimal strategies for inpatient decongestion for acute HF.
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Diuréticos , Insuficiência Cardíaca , Hospitalização , Redução de Peso , Humanos , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Feminino , Masculino , Idoso , Diuréticos/uso terapêutico , Diuréticos/administração & dosagem , Hospitalização/estatística & dados numéricos , Estados Unidos/epidemiologia , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Estudos de CoortesRESUMO
Background: The eligibility and potential benefit of transcatheter edge-to-edge repair (TEER) in addition to guideline-directed medical therapy to treat moderate-severe or severe secondary mitral regurgitation (MR) has not been reported in a contemporary heart failure (HF) population. Methods: Eligibility for TEER based on Food and Drug Administration (FDA) labeling: (1) HF symptoms, (2) moderate-severe or severe MR, (3) left ventricular ejection fraction (LVEF) 20% to 50%, (4) left ventricular end-systolic dimension 7.0 cm, and (5) receiving GDMT (blocker + angiotensin-converting enzyme inhibitor/angiotensin receptor blocker). The proportion (%) of patients eligible for TEER. The hypothetical number needed to treat to prevent or postpone adverse outcomes was estimated using relative risk reductions from published hazard ratios in the registration trial and the observed event rates. Results: We identified 50,841 adults with HF and known LVEF. After applying FDA criteria, 2461 patients (4.8%) were considered eligible for transcatheter mitral valve replacement (FDA+), with the vast majority of patients excluded (FDA-) based on a lack of clinically significant MR (N = 47,279). FDA+ patients had higher natriuretic peptide levels and were more likely to have a prior HF hospitalization compared to FDA- patients. Although FDA+ patients had a more dilated left ventricle and lower LVEF, median (25th-75th) left ventricular end-systolic dimension (cm) was low at 4.4 (3.7-5.1) and only 30.8% had severely reduced LVEF. FDA+ patients were at higher risk of HF-related morbidity and mortality. The estimated number needed to treat to potentially prevent or postpone all-cause hospitalization was 4.4, 8.8 for HF hospitalization, and 5.3 for all-cause death at 24 months in FDA+ patients. Conclusions: There is a low prevalence of TEER eligibility based on FDA criteria primarily due to absence of moderate-severe or severe MR. FDA+ patients are a high acuity population and may potentially derive a robust clinical benefit from TEER based on pivotal studies. Additional research is necessary to validate the scope of eligibility and comparative effectiveness of TEER in real-world populations.
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AIM: The TRANSFORM-HF trial demonstrated no significant outcome differences between torsemide and furosemide following hospitalization for heart failure (HF), but may have been impacted by non-adherence to the randomized diuretic. The current study sought to determine the treatment effect of torsemide versus furosemide using an on-treatment analysis inclusive of all randomized patients except those confirmed non-adherent to study diuretic. METHODS AND RESULTS: TRANSFORM-HF was an open-label, pragmatic randomized trial of 2859 patients hospitalized for HF from June 2018 through March 2022. Patients were randomized to a loop diuretic strategy of torsemide versus furosemide with investigator-selected dosage. This post-hoc on-treatment analysis included all patients alive with either known or unknown diuretic status, and excluded patients confirmed to be non-adherent to study diuretic. This modified on-treatment definition was applied separately at time of hospital discharge and 30-day follow-up. All-cause mortality and hospitalization outcomes were assessed over 12 months. Overall, 2570 (89.9%) and 2374 (83.0%) patients were included in on-treatment analyses at discharge and 30-day follow-up, respectively. There was no significant difference in all-cause mortality between torsemide and furosemide in patients on-treatment at discharge (17.5% vs. 17.8%; hazard ratio [HR] 1.01 [95% confidence interval [CI] 0.83-1.22], p = 0.96) and at 30-day follow-up (14.5% vs. 15.0%; HR 1.02 [95% CI 0.81-1.27], p = 0.90). All-cause mortality or all-cause hospitalization was similar between torsemide and furosemide in patients who were on-treatment at discharge (58.3% vs. 61.3%; HR 0.92 [95% CI 0.82-1.03]) and 30-day follow-up (60.9% vs. 64.4%; HR 0.93 [95% CI 0.82-1.05]). In patients who were on-treatment at 30-day follow-up, there were 677 total hospitalizations in the torsemide group and 686 total hospitalizations in the furosemide group (rate ratio 0.99 [95% CI 0.86-1.14], p = 0.87). CONCLUSIONS: In TRANSFORM-HF, a post-hoc on-treatment analysis did not meaningfully differ from the original trial results. Among those deemed compliant with the assigned diuretic, there remained no significant difference in mortality or hospitalization after HF hospitalization with a strategy of torsemide versus furosemide. CLINICAL TRAIL REGISTRATION: ClinicalTrials.gov Identifier: NCT03296813.
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Furosemida , Insuficiência Cardíaca , Hospitalização , Inibidores de Simportadores de Cloreto de Sódio e Potássio , Torasemida , Humanos , Furosemida/uso terapêutico , Furosemida/administração & dosagem , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/mortalidade , Torasemida/uso terapêutico , Masculino , Feminino , Idoso , Hospitalização/estatística & dados numéricos , Inibidores de Simportadores de Cloreto de Sódio e Potássio/uso terapêutico , Pessoa de Meia-Idade , Resultado do Tratamento , Diuréticos/uso terapêuticoRESUMO
BACKGROUND: Guideline-directed medical therapy (GDMT) decisions may be less affected by single patient variables such as blood pressure or kidney function and more by overall risk profile. In STRONG-HF (Safety, tolerability and efficacy of up-titration of guideline-directed medical therapies for acute heart failure), high-intensity care (HIC) in the form of rapid uptitration of heart failure (HF) GDMT was effective overall, but the safety, tolerability and efficacy of HIC across the spectrum of HF severity is unknown. Evaluating this with a simple risk-based framework offers an alternative and more clinically translatable approach than traditional subgroup analyses. OBJECTIVES: The authors sought to assess safety, tolerability, and efficacy of HIC according to the simple, powerful, and clinically translatable MAGGIC (Meta-Analysis Global Group in Chronic) HF risk score. METHODS: In STRONG-HF, 1,078 patients with acute HF were randomized to HIC (uptitration of treatments to 100% of recommended doses within 2 weeks of discharge and 4 scheduled outpatient visits over the 2 months after discharge) vs usual care (UC). The primary endpoint was the composite of all-cause death or first HF rehospitalization at day 180. Baseline HF risk profile was determined by the previously validated MAGGIC risk score. Treatment effect was stratified according to MAGGIC risk score both as a categorical and continuous variable. RESULTS: Among 1,062 patients (98.5%) with complete data for whom a MAGGIC score could be calculated at baseline, GDMT use at baseline was similar across MAGGIC tertiles. Overall GDMT prescriptions achieved for individual medication classes were higher in the HIC vs UC group and did not differ by MAGGIC risk score tertiles (interaction nonsignificant). The incidence of all-cause death or HF readmission at day 180 was, respectively, 16.3%, 18.9%, and 23.2% for MAGGIC risk score tertiles 1, 2, and 3. The HIC arm was at lower risk of all-cause death or HF readmission at day 180 (HR: 0.66; 95% CI: 0.50-0.86) and this finding was robust across MAGGIC risk score modeled as a categorical (HR: 0.51; 95% CI: 0.62-0.68 in tertiles 1, 2, and 3; interaction nonsignificant) for all comparisons and continuous (interaction nonsignificant) variable. The rate of adverse events was higher in the HIC group, but this observation did not differ based on MAGGIC risk score tertile (interaction nonsignificant). CONCLUSIONS: HIC led to better use of GDMT and lower HF-related morbidity and mortality compared with UC, regardless of the underlying HF risk profile. (Safety, Tolerability and Efficacy of Rapid Optimization, Helped by NT-proBNP testinG, of Heart Failure Therapies [STRONG-HF]; NCT03412201).
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AIMS: Biologically active adrenomedullin (bio-ADM) is a promising marker of residual congestion. The STRONG-HF trial showed that high-intensity care (HIC) of guideline-directed medical therapy (GDMT) improved congestion and clinical outcomes in heart failure (HF) patients. The association between bio-ADM, decongestion, outcomes and the effect size of HIC of GDMT remains to be elucidated. METHODS AND RESULTS: We measured plasma bio-ADM concentrations in 1005 patients within 2 days prior to anticipated discharge (baseline) and 90 days later. Bio-ADM correlated with most signs of congestion, with the exception of rales. Changes in bio-ADM were strongly correlated with change in congestion status from baseline to day 90 (gamma -0.24; p = 0.0001). Patients in the highest tertile of baseline bio-ADM concentrations were at greater risk than patients in the lowest tertile for the primary outcome of 180-day all-cause mortality or HF rehospitalization (hazard ratio [HR] 2.14, 95% confidence interval [CI] 1.42-3.22) and 180-day HF rehospitalization (HR 2.33, 95% CI 1.38-3.94). Areas under the receiver-operating characteristic curves were 0.5977 (95% CI 0.5561-0.6393), 0.5800 (95% CI 0.5356-0.6243), and 0.6159 (95% CI 0.5711-0.6607) for bio-ADM, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and their combination, respectively, suggesting that both bio-ADM and NT-proBNP provided similarly modest discrimination for this outcome. A trend towards better discrimination by combined bio-ADM and NT-proBNP than NT-proBNP alone was found (p = 0.059). HIC improved the primary outcome, irrespective of baseline bio-ADM concentration (interaction p = 0.37). In contrast to NT-proBNP, the 90-day change in bio-ADM did not differ significantly between HIC and usual care. CONCLUSIONS: Bio-ADM is a marker of congestion and predicts congestion at 3 months after a HF hospitalization. Higher bio-ADM was modestly associated with a higher risk of death and early hospital readmission and may have added value when combined with NT-proBNP.