ArticleEuropean journal of heart failure2022
Liver tests and outcomes in heart failure with reduced ejection fraction: findings from DAPA-HF.
Article in European journal of heart failure, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT03036124. Cited by 17 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure With Reduced Ejection Fraction
Open the trial in the graphWho cites it
17 citing papers in PubMed, 33 citations in OpenAlex.
- Association Between Gut Microbiota Dysbiosis and Bilirubin Metabolism Dysregulation in Children with Heart Failure.Journal of cardiovascular translational research · 2026Article
- Prognostic characteristics of preoperative serum total bilirubin concentration in myxomatous mitral valve disease in dogs undergoing mitral valve repair.Journal of veterinary internal medicine · 2026Article
- Transforming Toxicity into Therapy: Exploring Bilirubin's Benefits and Its Molecular Role in Cardiac Health and Disease.Biomolecules · 2026Review
- Association between noninvasive hepatic fibrosis indices and heart failure mortality.Medicine · 2026Observational
- Organ cross-talk: molecular mechanisms, biological functions, and therapeutic interventions for diseases.Signal transduction and targeted therapy · 2026Review
- Noninvasive Hemodynamic Characterization of Cardiohepatic Syndrome in the Cardiac Intensive Care Unit.Journal of the American Heart Association · 2025Observational
- The Role of MCPIP1 in Macrophage Polarization and Cardiac Function Post-Myocardial Infarction.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Prediction of Kidney Function Improvement After Heart Transplantation.Biomedicines · 2025Article
- 2024 update in heart failure.ESC heart failure · 2025Review
- Hepatic Biomarker Abnormalities in the Cardiac Intensive Care Unit: Proposed Criteria for Cardiohepatic Syndrome.JACC. Advances · 2025Article
- Hepatic function markers as prognostic factors in patients with acute kidney injury undergoing continuous renal replacement therapy.Renal failure · 2024Article
- Correlation of the FIB-4 Liver Biomarker Score with the Severity of Heart Failure.Medicina (Kaunas, Lithuania) · 2024Article
- Circulating mitochondria promoted endothelial cGAS-derived neuroinflammation in subfornical organ to aggravate sympathetic overdrive in heart failure mice.Journal of neuroinflammation · 2024Article
- The Liver in Heart Failure: From Biomarkers to Clinical Risk.International journal of molecular sciences · 2023Review
- Prognostic Value of the AST/ALT Ratio versus Bilirubin in Patients with Cardiogenic Shock.Journal of clinical medicine · 2023Article
- A novel clinical prediction scoring system of high-altitude pulmonary hypertension.Frontiers in cardiovascular medicine · 2023Article
- Genetically determined serum bilirubin level and the risk of heart failure: A mendelian randomization study.Frontiers in genetics · 2023Article
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22 authors at 14 institutions in 11 countries.
Funding
Abstract
aimsReflecting both increased venous pressure and reduced cardiac output, abnormal liver tests are common in patients with severe heart failure and are associated with adverse clinical outcomes. We aimed to investigate the prognostic significance of abnormal liver tests in ambulatory patients with heart failure with reduced ejection fraction (HFrEF), explore any treatment interaction between bilirubin and sodium-glucose cotransporter 2 (SGLT2) inhibitors and examine change in liver tests with SGLT2 inhibitor treatment. METHODS AND
resultsWe explored these objectives in the Dapagliflozin And Prevention of Adverse outcomes in Heart Failure (DAPA-HF) trial, with focus on bilirubin. We calculated the incidence of cardiovascular death or worsening heart failure by bilirubin tertile. Secondary cardiovascular outcomes were examined, along with the change in liver tests at the end-of-study visit. Baseline bilirubin was available in 4720 patients (99.5%). Participants in the highest bilirubin tertile (T3) have more severe HFrEF (lower left ventricular ejection fraction, higher N-terminal pro-B-type natriuretic peptide [NT-proBNP] and worse New York Heart Association class), had a greater burden of atrial fibrillation but less diabetes. Higher bilirubin (T3 vs. T1) was associated with worse outcomes even after adjustment for other predictive variables, including NT-proBNP and troponin T (adjusted hazard ratio for the primary outcome 1.73 [95% confidence interval 1.37-2.17], p < 0.001; and 1.52 [1.12-2.07], p = 0.01 for cardiovascular death). Baseline bilirubin did not modify the benefits of dapagliflozin. During follow-up, dapagliflozin had no effect on liver tests.
conclusionBilirubin concentration was an independent predictor of worse outcomes but did not modify the benefits of dapagliflozin in HFrEF. Dapagliflozin was not associated with change in liver tests. CLINICAL
trial registrationClinicalTrials.gov NCT03036124.
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