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Background: The effectiveness of glucagon-like peptide-1 receptor agonists (GLP1Ras) for prevention of heart failure (HF) in patients with type 2 diabetes (T2DM) without HF and for risk of death in patients with T2DM with HF has not been fully elucidated in routine clinical practice., Methods: Using the real-world global electronic medical record TriNetX database, individuals with T2DM and with or without HF who initiated either GLP1Ras or sitagliptin from 2017 to 2020 were retrospectively analyzed. In individuals with T2DM without HF, the primary outcome was a composite of all-cause mortality and a new diagnosis of HF within three years. In individuals with T2DM with HF, the primary outcome was all-cause mortality within three years. Propensity-score (PS) matching was used to adjust for over 100 baseline characteristics., Results: A total of 65,598 individuals with T2DM without HF starting a GLP1Ras were PS matched with 65,598 starting sitagliptin. GLP1Ras were associated with a lower incidence of the composite endpoint (10.5 % versus 11.8 %, hazard ratio [HR] 0.82, [0.80-0.85], p < 0.001), mortality (HR 0.66 [0.63-0.69]) and new diagnosis of HF (HR 0.92 [0.88-0.96]). There were 6002 individuals in each group matched for T2DM and HF. Mortality was lower in the GLP1Ras group (17.6 % versus 22.8 %, HR 0.70 [0.65-0.76], p < 0.001). Results were consistent across subgroups., Conclusions: In this global real-world data analysis, GLP1Ra use was associated with a lower risk of death and HF in individuals with T2DM without HF, and lower risk of death in those with HF., Competing Interests: Declaration of competing interest Yu Horiuchi received honoraria from TriNetX, Nippon Boehringer Ingelheim, Ono Pharmaceutical Company, AstraZeneca, Kyowa Kirin, Sanofi and Eli Lilly Japan. Nicholas Wettersten received grants from Department of Veterans Affairs National Institutes of Health, consulting fees from Guidepoint and honoraria from San Diego Heart Failure Symposium. Masahiko Asami received honoraria from Astellas, Daiichi Sankyo, AstraZeneca and Kyowa Kirin. Kazuyuki Yahagi received honoraria from Daiichi Sankyo and Nippon Boehringer Ingelheim. Hitomi Yuzawa received honoraria from Daiichi Sankyo. Kota Komiyama received honoraria from Astellas, Daiichi Sankyo, Ono Pharmaceutical and Kowa. Jun Tanaka received honoraria from Eli Lilly Japan, Novo Nordisk and Daiichi Sankyo. Jiro Aoki received honoraria from Daiichi Sankyo, Ono Pharmaceutical and Kowa, and has stock of Eli Lilly and Novo Nordisk. Kengo Tanabe received honoraria from Eli Lilly Japan, Novo Nordisk, Daiichi Sankyo, Ono Pharmaceutical, Industry, AstraZeneca and Kowa., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Improving congestion with diuretic therapy is crucial in the treatment of heart failure (HF). However, despite the use of loop diuretics, diuresis may be inadequate and congestion persists, which is known as diuretic resistance. Diuretic resistance and residual congestion are associated with a higher risk of rehospitalization and mortality. Causes of diuretic resistance in HF include diuretic pharmacokinetic changes, renal hemodynamic perturbations, neurohumoral activations, renal tubular remodeling, and use of nephrotoxic drugs as well as patient comorbidities. Combination diuretic therapy (CDT) has been advocated for the treatment of diuretic resistance. Thiazides, acetazolamides, tolvaptan, mineralocorticoid receptor antagonist, and sodium-glucose co-transporter-2 inhibitors are among the candidates, but none of these treatments has yet demonstrated significant diuretic efficacy or improved prognosis. At present, it is essential to identify and treat the causes of diuretic resistance in individual patients and to use CDT based on a better understanding of the characteristics of each drug to achieve adequate diuresis. Further research is needed to effectively assess and manage diuretic resistance and ultimately improve patient outcomes., Competing Interests: Declaration of competing interest Dr. Horiuchi received a speaking fee from AstraZeneca, Eli Lilly, and Otsuka Pharmaceutical. Dr. Wettersten has nothing to disclose., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Proenkephalin (PENK) is a novel biomarker of kidney function associated with cardiovascular risk in patients with cardiovascular disease. Its association with cardiovascular outcomes in ambulatory individuals is less described. In an observational study of 199 ambulatory Veterans enrolled from April to September 2010, we assessed PENK's association with major adverse cardiac events (MACE - cardiovascular death, heart failure [HF] hospitalization, myocardial infarction [MI], or stroke) and individual outcomes of all-cause mortality, incident HF, and cardiovascular death using Cox regression. We also assessed the association of PENK with left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDd), and left ventricular mass index (LVMi) with linear regression. The mean age was 66 ± 12 years, 99 % were men, and 76 % were White, with median follow-up of 12.7 years. Each two-fold higher PENK was associated with a 73 % higher risk of MACE in unadjusted analysis (HR 1.73; 95 % CI 1.00, 2.99; p = 0.043), though this association lost significance after adjusting for confounders (HR 1.69; 95 % CI 0.90-3.15; p = 0.098). PENK was not associated with all-cause mortality, incident HF or cardiovascular death, although risk estimates were elevated with wide confidence intervals for incident HF and cardiovascular death. PENK was not associated with LVMi or LVEDd but had a non-linear relationship with LVEF with low and high PENK associated with lower LVEF. In conclusion, PENK may be associated with a higher risk of MACE in ambulatory Veterans with diverse health statuses; however, further studies are needed. Abbreviations: PENK: Proenkephalin A; MACE: Major Adverse Cardiac Events., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Dr. Nicholas Wettersten and this work was supported (or supported in part) by Carerr Development Award Number IK CX002105 from the United States (U.S.) Department of Veteans Affairs Clinical Sciences R&D (CSRD) Service. The contents do not represent the view of the U.S. Department of Veterans Affairs or the United States Government.

Background: Worsening renal function (WRF) is common in hospitalized patients being treated for acute heart failure. However, discriminating clinically significant WRF remains challenging. In patients hospitalized with acute heart failure, we evaluated if blood and urine biomarkers of cardiac and kidney dysfunction were associated with adverse outcomes., Methods: We identified 175 of 927 participants in the AKINESIS study (Acute Kidney Neutrophil Gelatinase-Associated Lipocalin Evaluation of Symptomatic Heart Failure Study) who met criteria for stage 1 or 2 Kidney Disease: Improvement Global Outcomes acute kidney injury during the first 3 days of hospitalization. We measured 24 blood and urine biomarkers from specimens collected within 24 hours of meeting acute kidney injury criteria. The primary composite outcome consisted of worsening WRF (higher acute kidney injury stage), need for dialysis, or death at 30 days. Biomarkers' association with the composite outcome was assessed with logistic regression by tertiles and area under the curve (AUC)., Results: Of the 175 participants, 32 (18%) developed the primary composite outcome. Only history of chronic kidney disease was significantly different between those with and without the composite outcome. The highest tertile of plasma Gal-3 (galectin-3) and urine epidermal growth factor were associated with increased odds of the composite outcome compared with the lowest tertile in unadjusted analyses. After adjusting for serum creatinine, systolic blood pressure, and blood urea nitrogen, only the highest tertile of Gal-3 was associated with greater odds of the composite outcome (odds ratio, 4.6 [95% CI, 1.4-16.0). Gal-3 had the highest AUC (0.70 [95% CI, 0.58-0.82]), while epidermal growth factor had a lower AUC (0.63 [95% CI, 0.53-0.74]). Notably, urine biomarkers of kidney tubule injury were not associated with the composite outcome., Conclusions: Tubular injury does not occur in most patients with acute heart failure experiencing WRF, consistent with the functional mechanisms of WRF in this patient population., Registration: URL: https://www.clinicaltrials.gov/study/NCT01291836?term=NCT01291836&rank=1; Unique identifier: NCT01291836., Competing Interests: Dr Maisel previously received grant funding from Abbott Laboratories and Alere Inc. He is the cofounder of Aseptiscope and Imperium. Dr Côté receives consulting fees from GlaxoSmithKline. Dr Ix holds an investigator-initiated research grant from the National Institute of Diabetes and Digestive and Kidney Diseases. He has served on the advisory boards of Akebia, AstraZeneca, and Bayer. He has received travel support from Kidney Disease: Improving Global Outcomes. Dr Murray previously received research funding from Abbott Laboratories and Alere Inc. His institution currently receives research grant funding from Abbott. He receives consulting fees from Novartis, AM-Pharma, and Alexion for serving on clinical trial steering committees. He receives consulting fees from Renibus Therapeutics, Calcimedica, and Bioporto Diagnostics for serving on scientific advisory boards. The other authors report no conflicts.

Background: Pathologic antibody mediated rejection (pAMR) evaluation and donor specific antibody (DSA) testing are recommended in the first year after heart transplantation (HTx) in adult patients. Whether DSA testing adds prognostic information to contemporary pAMR surveillance has not been fully studied., Methods: This was a single center study of consecutive endomyocardial biopsies (EMB) performed between November 2010 and February 2023 in adult HTx patients. The primary objective was to evaluate whether DSA testing contributes additional information to pAMR surveillance to better predict overall survival. Secondary endpoints included cardiac allograft dysfunction and loss., Results: A total of 6,033 EMBs from 544 HTx patients were reviewed for the study. The pAMR+/DSA+ group had significantly lower overall survival versus the pAMR-/DSA- group (hazard ratio [HR] = 2.63; 95% confidence interval [CI], 1.35-5.11; p c = 0.013). In the pAMR+/DSA+ group, patients with cardiac allograft dysfunction, compared to those without allograft dysfunction, had significantly lower overall and cardiac survival (p c < 0.001 for both). In contrast, pAMR+/DSA+ and pAMR-/DSA- patients without cardiac allograft dysfunction showed no difference in overall and cardiac survival. Primary graft dysfunction (PGD) was a novel risk factor for development of de novo DSAs (dnDSA) three weeks post-HTx (p = 0.007)., Conclusions: DSA testing as the primary surveillance method can identify high-risk pAMR+/DSA+ patients. Surveillance pAMR testing in the contemporary era may need to be reevaluated. Earlier DSA testing at 10-14 days post-HTx should be considered in PGD patients.

Background: Higher cardiac troponin is associated with worse outcomes in patients with acute heart failure. The significance of repeat measurements over hours remains unclear. We assessed whether a repeat measurement and the Δ between measurements of high-sensitivity cardiac troponin I (hs-cTnI) were associated with outcomes in hypervolemic patients with acute heart failure without acute coronary syndrome., Methods and Results: We analyzed 582 individuals from AKINESIS (Acute Kidney Injury Neutrophil Gelatinase-Associated Lipocalin Evaluation of Symptomatic Heart Failure Study) with hs-cTnI measured ≤12 hours from admission and repeated ≤6 hours thereafter. Associations between hs-cTnI levels and their Δ with short-term (death, intensive care unit admission, receipt of inotropes, or positive pressure ventilation during hospitalization) and long-term (death or heart failure readmission within 1 year) outcomes were assessed. The average age was 69±13 years, 62% were men, 65% were White, 46% had coronary artery disease, and 22% had chest pain. Median hs-cTnI levels were 27 (interquartile range [IQR], 13-62) ng/L initially and 28 (IQR, 14-68) ng/L subsequently, with a Δ of 0 [IQR, -2 to 4] ng/L over 3.4±1 hours. Only the second measurement was associated with short-term outcomes (odds ratio, 1.14 per 2-fold higher [95% CI, 1.02-1.28]). Both individual measurements and the Δ were associated with long-term outcomes (hazard ratios, 1.09, 1.12, and 1.16 for first, second, and Δ, respectively). Associated risk for the first and second measurements were not constant over the year but highest early after being measured and decreased over 1 year., Conclusions: Repeat measurements of hs-cTnI over hours can identify individuals with acute heart failure without acute coronary syndrome at risk for short- and long-term outcomes.

Rationale & Objective: Novel approaches to the assessment of kidney disease risk during hypertension treatment are needed because of the uncertainty of how intensive blood pressure (BP) lowering impacts kidney outcomes. We determined whether longitudinal N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurements during hypertension treatment are associated with kidney function decline., Study Design: Prospective observational study., Setting & Participants: 8,005 SPRINT (Systolic Blood Pressure Intervention Trial) participants with NT-proBNP measurements at baseline and 1 year., Exposure: 1-year change in NT-proBNP categorized as a ≥25% decrease, ≥25% increase, or <25% change (stable)., Outcome: Annualized change in estimated glomerular filtration rate (eGFR) and ≥30% decrease in eGFR., Analytical Approach: Linear mixed-effect and logistic regression models were used to evaluate the association of changes in NT-proBNP with subsequent annualized change in eGFR and ≥30% decrease in eGFR, respectively. Analyses were stratified by baseline chronic kidney disease (CKD) status., Results: Compared with stable 1-year NT-proBNP levels, a ≥25% decrease in NT-proBNP was associated with a slower decrease in eGFR in participants with CKD (adjusted difference, 1.09%/y; 95% CI, 0.35-1.83) and without CKD (adjusted difference, 0.51%/y; 95% CI, 0.21-0.81; P = 0.4 for interaction). Meanwhile, a ≥25% increase in NT-proBNP in participants with CKD was associated with a faster decrease in eGFR (adjusted difference, -1.04%/y; 95% CI, -1.72 to -0.36) and risk of a ≥30% decrease in eGFR (adjusted odds ratio, 1.44; 95% CI, 1.06-1.96); associations were stronger in participants with CKD than in participants without CKD (P = 0.01 and P < 0.001 for interaction, respectively). Relationships were similar irrespective of the randomized BP arm in SPRINT (P > 0.2 for interactions)., Limitations: Persons with diabetes and proteinuria >1 g/d were excluded., Conclusions: Changes in NT-proBNP during BP treatment are independently associated with subsequent kidney function decline, particularly in people with CKD. Future studies should assess whether routine NT-proBNP measurements may be useful in monitoring kidney risk during hypertension treatment., Plain-Language Summary: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a biomarker in the blood that reflects mechanical stress on the heart. Measuring NT-proBNP may be helpful in assessing the risk of long-term losses of kidney function. In this study, we investigated the association of changes in NT-proBNP with subsequent kidney function among individuals with and without chronic kidney disease. We found that increases in NT-proBNP are associated with a faster rate of decline of kidney function, independent of baseline kidney measures. The associations were more pronounced in individuals with chronic kidney disease. Our results advance the notion of considering NT-proBNP as a dynamic tool for assessing kidney disease risk., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The reference standard of detecting acute rejection (AR) in adult heart transplant (HTx) patients is an endomyocardial biopsy (EMB). The majority of EMBs are performed in asymptomatic patients. However, the incidence of treated AR compared with EMB complications has not been compared in the contemporary era (2010-current)., Methods: The authors retrospectively analyzed 2769 EMBs obtained in 326 consecutive HTx patients between August 2019 and August 2022. Variables included surveillance versus for-cause indication, recipient and donor characteristics, EMB procedural data and pathological grades, treatment for AR, and clinical outcomes., Results: The overall EMB complications rate was 1.6%. EMBs performed within 1 mo after HTx compared with after 1 mo from HTx showed significantly increased complications (OR, 12.74, P  < 0.001). The treated AR rate was 14.2% in the for-cause EMBs and 1.2% in the surveillance EMBs. We found the incidence of AR versus EMB complications was significantly lower in the surveillance compared with the for-cause EMB group (OR, 0.05, P  < 0.001). We also found the incidence of EMB complications was higher than treated AR in surveillance EMBs., Conclusions: The yield of surveillance EMBs has declined in the contemporary era, with a higher incidence of EMB complications compared with detected AR. The risk of EMB complications was highest within 1 mo after HTx. Surveillance EMB protocols in the contemporary era may need to be reevaluated., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Body mass index (BMI) is a known confounder for natriuretic peptides, but its influence on other biomarkers is less well described. We investigated whether BMI interacts with biomarkers' association with prognosis in patients with acute heart failure (AHF)., Methods and Results: B-type natriuretic peptide (BNP), high-sensitivity cardiac troponin I (hs-cTnI), galectin-3, serum neutrophil gelatinase-associated lipocalin (sNGAL), and urine NGAL were measured serially in patients with AHF during hospitalization in the AKINESIS (Acute Kidney Injury Neutrophil gelatinase-associated lipocalin Evaluation of Symptomatic Heart Failure) study. Cox regression analysis was used to determine the association of biomarkers and their interaction with BMI for 30-day, 90-day and 1-year composite outcomes of death or HF readmission. Among 866 patients, 21.2%, 29.7% and 46.8% had normal (18.5-24.9 kg/m 2 ), overweight (25-29.9 kg/m 2 ) or obese (≥ 30 kg/m 2 ) BMIs on admission, respectively. Admission values of BNP and hs-cTnI were negatively associated with BMI, whereas galectin-3 and sNGAL were positively associated with BMI. Admission BNP and hs-cTnI levels were associated with the composite outcome within 30 days, 90 days and 1 year. Only BNP had a significant interaction with BMI. When BNP was analyzed by BMI category, its association with the composite outcome attenuated at higher BMIs and was no longer significant in obese individuals. Findings were similar when evaluated by the last-measured biomarkers and BMIs., Conclusions: In patients with AHF, only BNP had a significant interaction with BMI for the outcomes, with its association attenuating as BMI increased; hs-cTnI was prognostic, regardless of BMI., Competing Interests: Disclosures CM has previously received grant funding and other support from Abbott Laboratories and Alere and research support and speaker/consulting honoraria from several diagnostic companies by Roche, Singulex, and Sphingotec. CMC's institution has received research support from Abbott Laboratories and Alere. RB has received grant funding from Alere. AM has previously received grant funding from Abbott Laboratories and Alere. PTM has received research funding from Abbott Laboratories and Alere. PTM's institution receives funding from Abbott Laboratories. All other authors declare no conflicts of interest., (Copyright © 2023. Published by Elsevier Inc.)

Background: The reference standard of detecting acute rejection (AR) in adult heart transplant (HTx) patients is an endomyocardial biopsy (EMB). The majority of EMBs are performed in asymptomatic patients. However, the benefit of diagnosing and treating AR compared to the risk of EMB complications has not been compared in the contemporary era (2010-current)., Methods: The authors retrospectively analyzed 2,769 EMB obtained in 326 consecutive HTx patients between August 2019 and August 2022. Variables included surveillance versus for cause indication, recipient and donor characteristics, EMB procedural data and pathologic grades, treatment for AR, and clinical outcomes., Results: The overall EMB complication rate was 1.6%. EMBs performed within 1 month after HTx compared to after 1 month from HTx showed significantly increased complications (OR = 12.74, p < 0.001). The treated AR rate was 14.2% in the for cause EMBs and 1.2% in the surveillance EMBs. We found the benefit/risk ratio was significantly lower in the surveillance compared to the for cause EMB group (OR = 0.05, p < 0.001). We also found the benefit to be lower than risk in surveillance EMBs., Conclusions: The yield of surveillance EMBs has declined, while for cause EMBs continued to demonstrate a high benefit/risk ratio. The risk of EMB complications was highest within 1 month after HTx. Surveillance EMB protocols in the contemporary era may need to be re-evaluated.

Markers of glomerular disease, estimated glomerular filtration rate (eGFR) and albuminuria, are associated with cardiac structural abnormalities and incident cardiovascular disease (CVD). We aimed to determine whether biomarkers of kidney tubule injury, function, and systemic inflammation are associated with cardiac structural abnormalities. Among 393 Multi-Ethnic Study of Atherosclerosis participants without diabetes, CVD, or chronic kidney disease, we assessed the association of 12 biomarkers of kidney tubule injury, function, and systemic inflammation with the left ventricular mass/volume ratio (LVmvr) and left ventricular ejection fraction (LVEF) on cardiac magnetic resonance imaging using linear regression. The average age was 60 ± 10 years; 48% were men; mean eGFR was 96±16 ml/min/1.73 m 2 ; mean LVmvr was 0.93±0.18 g/ml, and mean LVEF was 62±6%. Each twofold greater concentration of plasma soluble urokinase plasminogen activator receptor was associated with a 0.04 g/ml (95% confidence interval [CI] 0.01 to 0.08 g/ml) higher LVmvr and 2.1% (95% CI 0.6 to 3.5%) lower LVEF, independent of risk factors for CVD, eGFR, and albuminuria. Each twofold greater plasma monocyte chemoattractant protein 1 was associated with higher LVmvr with a similar coefficient to that of plasma soluble urokinase plasminogen activator receptor. Each twofold greater concentration of plasma chitinase-3-like protein 1 and urine alpha-1-microglobulin was associated with a 1.1% (95% CI 0.4 to 1.7%) and 1.2% (95% CI 0.2 to 2.2%) lower LVEF, respectively. In conclusion, abnormal kidney tubule health may lead to cardiac dysfunction above and beyond eGFR and albuminuria., Competing Interests: Disclosures Dr. Gutierrez receives grant funding and honoraria from Amgen and Akebia. He receives honoraria from AstraZeneca, Reata, and Ardelyx and serves on a Data Monitoring Committee for QED Therapeutics. Dr. Bonventre is cofounder and holds equity in Goldfinch Bio and Autonomous Medical Devices, is coinventor on KIM-1 patents assigned to Mass General Brigham, and has received consulting income and/or equity from Cadent, Renalytix, Sarepta, and Seagen and laboratory support from Kantum Pharma. He has equity in Pacific Biosciences, DxNow, and MediBeacon. Dr. Bonventre's interests were reviewed and are managed by BWH and MGB in accordance with their conflict-of-interest policies. Dr. Kimmel is a coeditor with Mark Rosenberg of Chronic Renal Disease Academic Press and a coeditor with Daniel Cukor and Scott D. Cohen of Psychosocial Aspects of Chronic Kidney Disease Academic Press. Dr. Shlipak is on advisory boards and receives honoraria from Bayer, Boehringer-Ingelheim, Astra-Zeneca. He receives grant support from Bayer. Dr. Ix has grant support from Baxter International. He is on advisory boards for Akebia, AstraZeneka, Ardelyx, Alpha Young, and Bayer. He serves on a Data and Safety Monitoring Board from Sanifit International. The remaining authors have no conflicts of interest to declare., (Published by Elsevier Inc.)

Background: Galectin-3, a biomarker of inflammation and fibrosis, can be associated with renal and myocardial damage and dysfunction in patients with acute heart failure (AHF)., Methods and Results: We retrospectively analyzed 790 patients with AHF who were enrolled in the AKINESIS study. During hospitalization, patients with galectin-3 elevation (> 25.9 ng/mL) on admission more commonly had acute kidney injury (assessed by KDIGO criteria), renal tubular damage (peak urine neutrophil gelatinase-associated lipocalin [uNGAL] > 150 ng/dL) and myocardial injury (≥ 20% increase in the peak high-sensitivity cardiac troponin I [hs-cTnI] values compared to admission). They less commonly had ≥ 30% reduction in B-type natriuretic peptide from admission to last measured value. In multivariable linear regression analysis, galectin-3 was negatively associated with estimated glomerular filtration rate and positively associated with uNGAL and hs-cTnI. Higher galectin-3 was associated with renal replacement therapy, inotrope use and mortality during hospitalization. In univariable Cox regression analysis, higher galectin-3 was associated with increased risk for the composite of death or rehospitalization due to HF and death alone at 1 year. After multivariable adjustment, higher galectin-3 levels were associated only with death., Conclusions: In patients with AHF, higher galectin-3 values were associated with renal dysfunction, renal tubular damage and myocardial injury, and they predicted worse outcomes., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Aims: Kidney function changes dynamically during AHF treatment, but risk factors for and consequences of worsening renal function (WRF) at hospital admission are uncertain. We aimed to determine the significance of WRF at admission for acute heart failure (AHF)., Methods and Results: We evaluated a subgroup of 406 patients from The Acute Kidney Injury Neutrophil gelatinase-associated lipocalin Evaluation of Symptomatic heart failure Study (AKINESIS) who had serum creatinine measurements available within 3 months before and at the time of admission. Admission WRF was primarily defined as a 0.3 mg/dL or 50% creatinine increase from preadmission. Alternative definitions evaluated were a ≥0.5 mg/dL creatinine increase, ≥25% glomerular filtration rate decrease, and an overall change in creatinine. Predictors of admission WRF were evaluated. Outcomes evaluated were length of hospitalization, a composite of adverse in-hospital events, and the composite of death or HF readmission at 30, 90, and 365 days. Biomarkers' prognostic ability for these outcomes were evaluated in patients with admission WRF. One-hundred six patients (26%) had admission WRF. These patients had features of more severe AHF with lower blood pressure, higher BUN, and lower serum sodium concentrations at admission. Higher BNP (odds ratio [OR] per doubling 1.16-1.28, 95% confidence interval [CI] 1.00-1.55) and lower diastolic blood pressure (OR 0.97-0.98, 95% CI 0.96-0.99) were associated with a higher odds for the three definitions of admission WRF. The primary WRF definition was not associated with a longer hospitalization, but alternative WRF definitions were (1.3 to 1.6 days longer, 95% CI 1.0-2.2). WRF across definitions was not associated with a higher odds of adverse in-hospital events or a higher risk of death or HF readmission. In the subset of patients with WRF, biomarkers were not prognostic for any outcome., Conclusions: Admission WRF is common in AHF patients and is associated with an increased length of hospitalization, but not adverse in-hospital events, death, or HF readmission. Among those with admission WRF, biomarkers did not risk stratify for adverse events., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background and Aims: Identifying individuals at elevated risk for mortality, especially from cardiovascular disease, may help guide testing and treatment. Risk factors for mortality differ by sex and race. We investigated the association of growth hormone (GH) with all-cause and cardiovascular mortality in a racially diverse cohort in the United States., Methods: Among an age, sex and race stratified subgroup of 1046 Black and White participants from the REasons for Geographic And Racial Disparities in Stroke (REGARDS) study, 881 had GH available; values were log 2 transformed. Associations with all-cause and cardiovascular mortality were assessed in the whole subgroup, and by sex and race, using multivariable Cox-proportional hazard models and C-index., Results: The mean age was 67.4 years, 51.1% were women, and 50.2% were Black participants. The median GH was 280 (interquartile range 79-838) ng/L. There were 237 deaths and 74 cardiovascular deaths over a mean of 8.0 years. In multivariable Cox analysis, GH was associated with higher risk of all-cause mortality per doubling (hazard ratio [HR] 1.17, 95% confidence interval [CI] 1.09-1.25) and cardiovascular mortality (HR 1.21, 95% CI 1.06-1.37). The association did not differ by sex or race (interaction p > 0.05). The addition of GH to a model of clinical variables significantly improved the C-index compared to clinical model alone for all-cause and cardiovascular death., Conclusions: Higher fasting GH was associated with higher risk of all-cause and cardiovascular mortality and improved risk prediction, regardless of sex or race., (Published by Elsevier B.V.)

Background: Cardiac troponin (cTn) can be elevated in many patients presenting to the emergency department (ED) with chest pain but without a diagnosis of acute coronary syndrome (ACS). We compared the prognostic significance of cTn in these different populations., Methods: We retrospectively analyzed the CHOPIN study, which enrolled patients who presented to the ED with chest pain. Patients were grouped as ACS, non-ACS cardiovascular disease, noncardiac chest pain and chest pain not otherwise specified (NOS). We examined the prognostic ability of cTnI for the clinical endpoints of mortality and major adverse cardiovascular event (MACE; a composite of acute myocardial infarction, unstable angina, revascularization, reinfarction, and congestive heart failure and stroke) at 180-day follow-up., Results: Among 1982 patients analyzed, 14% had ACS, 21% had non-ACS cardiovascular disease, 31% had a noncardiac diagnosis and 34% had chest pain NOS. cTnI elevation above the 99th percentile was observed in 52, 18, 6 and 7% in these groups, respectively. cTnI elevation was associated with mortality and MACE, and their relationships were more prominent in noncardiac diagnosis and chest pain NOS than in ACS and non-ACS cardiovascular diagnoses for mortality, and in non-ACS patients than in ACS patients for MACE (hazard ratio for doubling of cTnI 1.85, 2.05, 8.26 and 4.14, respectively; P for interaction 0.011 for mortality; 1.04, 1.23, 1.54 and 1.42, respectively; P for interaction <0.001 for MACE)., Conclusion: In patients presenting to the ED with chest pain, cTnI elevation was associated with a worse prognosis in non-ACS patients than in ACS patients., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: In patients with acute heart failure (AHF), the development of worsening renal function with appropriate decongestion is thought to be a benign functional change and not associated with poor prognosis. We investigated whether the benefit of decongestion outweighs the risk of concurrent kidney tubular damage and leads to better outcomes., Methods: We retrospectively analyzed data from the AKINESIS study, which enrolled AHF patients requiring intravenous diuretic therapy. Urine neutrophil gelatinase-associated lipocalin (uNGAL) and B-type natriuretic peptide (BNP) were serially measured during the hospitalization. Decongestion was defined as ≥30% BNP decrease at discharge compared to admission. Univariable and multivariable Cox models were assessed for one-year mortality., Results: Among 736 patients, 53% had ≥30% BNP decrease at discharge. Levels of uNGAL and BNP at each collection time point had positive but weak correlations (r ≤ 0.133). Patients without decongestion and with higher discharge uNGAL values had worse one-year mortality, while those with decongestion had better outcomes regardless of uNGAL values (p for interaction 0.018). This interaction was also significant when the change in BNP was analyzed as a continuous variable (p < 0.001). Although higher peak and discharge uNGAL were associated with mortality in univariable analysis, only ≥30% BNP decrease was a significant predictor after multivariable adjustment., Conclusions: Among AHF patients treated with diuretic therapy, decongestion was generally not associated with kidney tubular damage assessed by uNGAL. Kidney tubular damage with adequate decongestion does not impact outcomes; however, kidney injury without adequate decongestion is associated with a worse prognosis., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Aims: Improving renal function (IRF) is paradoxically associated with worse outcomes in acute heart failure (AHF), but outcomes may differ based on response to decongestion. We explored if the relationship of IRF with mortality in hospitalized AHF patients differs based on successful decongestion., Methods and Results: We evaluated 760 AHF patients from AKINESIS for the relationship between IRF, change in B-type natriuretic peptide (BNP), and 1-year mortality. IRF was defined as a ≥20% increase in estimated glomerular filtration rate (eGFR) relative to admission. Adequate decongestion was defined as a ≥40% decrease in last measured BNP relative to admission. IRF occurred in 22% of patients who had a mean age of 69 years, 58% were men, 72% were white, and median admission eGFR was 49 mL/min/1.73 m 2 . IRF patients had more severe heart failure reflected by lower admission eGFR, higher blood urea nitrogen, lower systolic blood pressure, lower sodium, and higher use of inotropes. IRF patients had higher 1-year mortality (25%) than non-IRF patients (15%) (P < 0.01). However, this relationship differed by BNP trajectory (P-interaction = 0.03). When stratified by BNP change, non-IRF patients and IRF patients with decreasing BNP had lower 1-year mortality than either non-IRF and IRF patients without decreasing BNP. However, in multivariate analysis, IRF was not associated with mortality [adjusted hazard ratio (HR) 1.0, 95% confidence interval (CI) 0.7-1.5] while BNP was (adjusted HR 0.5, 95% CI 0.3-0.7). When IRF was evaluated as transiently occurring or persisting at discharge, again only BNP change was significantly associated with mortality., Conclusion: Improving renal function is associated with mortality in AHF but not independent of other variables and congestion status. Achieving adequate decongestion, as reflected by lower BNP, in AHF is more strongly associated with mortality than IRF., (© 2021 European Society of Cardiology.)