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4. Clinical Correlates and Prognostic Impact of Cognitive Dysfunction in Patients With Heart Failure and Preserved Ejection Fraction: Insights From PARAGON-HF

Author

Shen, Li, Dewan, Pooja, Ferreira, João Pedro, Cunningham, Jonathan W., Jhund, Pardeep S., Anand, Inder S., Chandra, Alvin, Chiang, Lu-May, Claggett, Brian, Desai, Akshay S., Gong, Jianjian, Lam, Carolyn S. P., Lefkowitz, Martin P., Maggioni, Aldo P., Martinez, Felipe, Packer, Milton, Redfield, Margaret M., Rouleau, Jean L., van Veldhuisen, Dirk J., Zannad, Faiez, Zile, Michael R., Solomon, Scott D., and McMurray, John J. V.

Published
2024
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5. Implications of worsening renal function before hospitalization for acute heart failure

Author

Wettersten, Nicholas, Duff, Stephen, Horiuchi, Yu, Veldhuisen, Dirk J, Mueller, Christian, Filippatos, Gerasimos, Nowak, Richard, Hogan, Christopher, Kontos, Michael C, Cannon, Chad M, Müeller, Gerhard A, Birkhahn, Robert, Taub, Pam, Vilke, Gary M, McDonald, Kenneth, Mahon, Niall, Nuñez, Julio, Briguori, Carlo, Passino, Claudio, Maisel, Alan, Murray, Patrick T, and Ix, Joachim H

Subjects
Kidney Disease, Heart Disease, Clinical Research, Cardiovascular, Patient Safety, Renal and urogenital, Humans, Kidney, Creatinine, Acute Disease, Biomarkers, Heart Failure, Hospitalization, Acute heart failure, Acute kidney injury, Cardiorenal syndrome, Cardiorespiratory Medicine and Haematology
Abstract

AimsKidney 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 resultsWe 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.ConclusionsAdmission 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.

Published
2023

6. Long term safety and outcomes after atrial shunting for heart failure with preserved or mildly reduced ejection fraction: 5-year and 3-year follow-up in the REDUCE LAP-HF I and II trials

Author

Litwin, Sheldon E., Komtebedde, Jan, Borlaug, Barry A., Kaye, David M., Hasenfuβ, Gerd, Kawash, Rami, Hoendermis, Elke, Hummel, Scott L., Cikes, Maja, Gustafsson, Finn, Chung, Eugene S., Mohan, Rajeev C., Sverdlov, Aaron L., Swarup, Vijendra, Winkler, Sebastian, Hayward, Christopher S., Bergmann, Martin W., Bugger, Heiko, McKenzie, Scott, Nair, Ajith, Rieth, Andreas, Burkhoff, Daniel, Cutlip, Donald E., Solomon, Scott D., van Veldhuisen, Dirk J., Leon, Martin B., and Shah, Sanjiv J.

Published
2024
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7. Effect of Sacubitril/Valsartan on Cognitive Function in Patients With Heart Failure With Preserved Ejection Fraction: A Prespecified Analysis of PARAGON-HF

Author

Dewan, Pooja, Shen, Li, Pedro Ferreira, João, Jhund, Pardeep S., Anand, Inder S., Chandra, Alvin, Chiang, Lu-May, Claggett, Brian, Desai, Akshay S., Gong, Jianjian, Lam, Carolyn S.P., Lefkowitz, Martin P., Maggioni, Aldo P., Martinez, Felipe, Packer, Milton, Redfield, Margaret M., Rouleau, Jean L., van Veldhuisen, Dirk J., Zannad, Faiez, Zile, Michael R., Solomon, Scott D., and McMurray, John J.V.

Published
2024
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9. Systemic oxidative stress associates with disease severity and outcome in patients with new-onset or worsening heart failure

Author

de Koning, Marie-Sophie L. Y., Emmens, Johanna E., Romero-Hernández, Esteban, Bourgonje, Arno R., Assa, Solmaz, Figarska, Sylwia M., Cleland, John G. F., Samani, Nilesh J., Ng, Leong L., Lang, Chim C., Metra, Marco, Filippatos, Gerasimos S., van Veldhuisen, Dirk J., Anker, Stefan D., Dickstein, Kenneth, Voors, Adriaan A., Lipsic, Erik, van Goor, Harry, and van der Harst, Pim

Published
2023
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10. Inflammation and remodeling pathways and risk of cardiovascular events in patients with ischemic heart failure and reduced ejection fraction

Author

Girerd, Nicolas, Cleland, John, Anker, Stefan D, Byra, William, Lam, Carolyn SP, Lapolice, David, Mehra, Mandeep R, van Veldhuisen, Dirk J, Bresso, Emmanuel, Lamiral, Zohra, Greenberg, Barry, and Zannad, Faiez

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Trials and Supportive Activities, Cardiovascular, Clinical Research, Heart Disease, Heart Disease - Coronary Heart Disease, Atrial Remodeling, Biomarkers, Case-Control Studies, Coronary Artery Disease, Death, Sudden, Cardiac, Growth Differentiation Factor 15, Heart Failure, Humans, Inflammation, Myocardial Infarction, Natriuretic Peptide, Brain, Peptide Fragments, Proteomics, Stroke, Stroke Volume, Ventricular Dysfunction, Left
Abstract

Patients with heart failure (HF) and coronary artery disease (CAD) have a high risk for cardiovascular (CV) events including HF hospitalization, stroke, myocardial infarction (MI) and sudden cardiac death (SCD). The present study evaluated associations of proteomic biomarkers with CV outcome in patients with CAD and HF with reduced ejection fraction (HFrEF), shortly after a worsening HF episode. We performed a case-control study within the COMMANDER HF international, double-blind, randomized placebo-controlled trial investigating the effects of the factor-Xa inhibitor rivaroxaban. Patients with the following first clinical events: HF hospitalization, SCD and the composite of MI or stroke were matched with corresponding controls for age, sex and study drug. Plasma concentrations of 276 proteins with known associations with CV and cardiometabolic mechanisms were analyzed. Results were corrected for multiple testing using false discovery rate (FDR). In 485 cases and 455 controls, 49 proteins were significantly associated with clinical events of which seven had an adjusted FDR  0.20). When adding the biomarkers significantly associated with the above outcome to a clinical model (including NT-proBNP), the C-index increase was 0.057 (0.033-0.082), p

Published
2022

16. Atrial Fibrillation Burden and Atrial Shunt Therapy in Heart Failure With Preserved Ejection Fraction

Author

Patel, Ravi B., Reddy, Vivek Y., Komtebedde, Jan, Wegerich, Stephan W., Sekaric, Jadranka, Swarup, Vijay, Walton, Antony, Laurent, Gabriel, Chetcuti, Stanley, Rademann, Matthias, Bergmann, Martin, McKenzie, Scott, Bugger, Heiko, Bruno, Raphael Romano, Herrmann, Howard C., Nair, Ajith, Gupta, Deepak K., Lim, Scott, Kapadia, Samir, Gordon, Robert, Vanderheyden, Marc, Noel, Thomas, Bailey, Steven, Gertz, Zachary M., Trochu, Jean-Noël, Cutlip, Donald E., Leon, Martin B., Solomon, Scott D., van Veldhuisen, Dirk J., Auricchio, Angelo, and Shah, Sanjiv J.

Published
2023
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17. Conducting clinical trials in heart failure during (and after) the COVID-19 pandemic: an Expert Consensus Position Paper from the Heart Failure Association (HFA) of the European Society of Cardiology (ESC)

Author

Anker, Stefan D, Butler, Javed, Khan, Muhammad Shahzeb, Abraham, William T, Bauersachs, Johann, Bocchi, Edimar, Bozkurt, Biykem, Braunwald, Eugene, Chopra, Vijay K, Cleland, John G, Ezekowitz, Justin, Filippatos, Gerasimos, Friede, Tim, Hernandez, Adrian F, Lam, Carolyn SP, Lindenfeld, JoAnn, McMurray, John JV, Mehra, Mandeep, Metra, Marco, Packer, Milton, Pieske, Burkert, Pocock, Stuart J, Ponikowski, Piotr, Rosano, Giuseppe MC, Teerlink, John R, Tsutsui, Hiroyuki, Van Veldhuisen, Dirk J, Verma, Subodh, Voors, Adriaan A, Wittes, Janet, Zannad, Faiez, Zhang, Jian, Seferovic, Petar, and Coats, Andrew JS

Subjects
Clinical Research, Patient Safety, Clinical Trials and Supportive Activities, Cardiovascular, Heart Disease, Prevention, Good Health and Well Being, Betacoronavirus, COVID-19, Clinical Trials as Topic, Coronavirus Infections, Europe, Heart Failure, Humans, Informed Consent, Pandemics, Patient Selection, Pneumonia, Viral, Research Design, SARS-CoV-2, Heart failure, Clinical trials, Coronavirus, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Cardiovascular System & Hematology
Abstract

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has important implications for the safety of participants in clinical trials and the research staff caring for them and, consequently, for the trials themselves. Patients with heart failure may be at greater risk of infection with COVID-19 and the consequences might also be more serious, but they are also at risk of adverse outcomes if their clinical care is compromised. As physicians and clinical trialists, it is our responsibility to ensure safe and effective care is delivered to trial participants without affecting the integrity of the trial. The social contract with our patients demands no less. Many regulatory authorities from different world regions have issued guidance statements regarding the conduct of clinical trials during this COVID-19 crisis. However, international trials may benefit from expert guidance from a global panel of experts to supplement local advice and regulations, thereby enhancing the safety of participants and the integrity of the trial. Accordingly, the Heart Failure Association of the European Society of Cardiology on 21 and 22 March 2020 conducted web-based meetings with expert clinical trialists in Europe, North America, South America, Australia, and Asia. The main objectives of this Expert Position Paper are to highlight the challenges that this pandemic poses for the conduct of clinical trials in heart failure and to offer advice on how they might be overcome, with some practical examples. While this panel of experts are focused on heart failure clinical trials, these discussions and recommendations may apply to clinical trials in other therapeutic areas.

Published
2020

19. Galectin-3, Acute Kidney Injury and Myocardial Damage in Patients With Acute Heart Failure

Author

HORIUCHI, YU, WETTERSTEN, NICHOLAS, VAN VELDHUISEN, DIRK J., MUELLER, CHRISTIAN, FILIPPATOS, GERASIMOS, NOWAK, RICHARD, HOGAN, CHRISTOPHER, KONTOS, MICHAEL C., CANNON, CHAD M., MÜELLER, GERHARD A., BIRKHAHN, ROBERT, TAUB, PAM, VILKE, GARY M., MCDONALD, KENNETH, MAHON, NIALL, NUÑEZ, JULIO, BRIGUORI, CARLO, PASSINO, CLAUDIO, DUFF, STEPHEN, MAISEL, ALAN, and MURRAY, PATRICK T.

Published
2023
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23. A comprehensive analysis of the effects of rivaroxaban on stroke or transient ischaemic attack in patients with heart failure, coronary artery disease, and sinus rhythm: the COMMANDER HF trial

Author

Mehra, Mandeep R, Vaduganathan, Muthiah, Fu, Min, Ferreira, João Pedro, Anker, Stefan D, Cleland, John GF, Lam, Carolyn SP, van Veldhuisen, Dirk J, Byra, William M, Spiro, Theodore E, Deng, Hsiaowei, Zannad, Faiez, and Greenberg, Barry

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Clinical Research, Brain Disorders, Neurosciences, Stroke, Clinical Trials and Supportive Activities, Heart Disease, Cardiovascular, Heart Disease - Coronary Heart Disease, Patient Safety, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Aged, Brain Ischemia, Case-Control Studies, Coronary Artery Disease, Double-Blind Method, Drug Therapy, Combination, Factor Xa Inhibitors, Female, Heart Failure, Hemorrhage, Humans, Incidence, Ischemic Attack, Transient, Male, Middle Aged, Myocardial Infarction, Placebos, Platelet Aggregation Inhibitors, Rivaroxaban, Stroke Volume, Heart failure, Oral anticoagulation, Thrombotic, Transient ischaemic attack, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Cardiovascular System & Hematology, Cardiovascular medicine and haematology, Clinical sciences
Abstract

AimsStroke is often a devastating event among patients with heart failure with reduced ejection (HFrEF). In COMMANDER HF, rivaroxaban 2.5 mg b.i.d. did not reduce the composite of first occurrence of death, stroke, or myocardial infarction compared with placebo in patients with HFrEF, coronary artery disease (CAD), and sinus rhythm. We now examine the incidence, timing, type, severity, and predictors of stroke or a transient ischaemic attack (TIA), and seek to establish the net clinical benefit of treatment with low-dose rivaroxaban.Methods and resultsIn this double-blind, randomized trial, 5022 patients who had HFrEF(≤40%), elevated natriuretic peptides, CAD, and who were in sinus rhythm were treated with rivaroxaban 2.5 mg b.i.d. or placebo in addition to antiplatelet therapy, after an episode of worsening HF. The primary neurological outcome for this post hoc analysis was time to first event of any stroke or TIA. Over a median follow-up of 20.5 (25th-75th percentiles 20.0-20.9) months, 150 all-cause stroke (127) or TIA (23) events occurred (ischaemic stroke in 82% and haemorrhagic stroke in 11% of stroke events). Overall, 47.5% of first-time strokes were either disabling (16.5%) or fatal (31%). Prior stroke, low body mass index, geographic region, and the CHA2DS2-VASc score were predictors of stroke/TIA. Rivaroxaban significantly reduced the primary neurological endpoint of all-cause stroke or TIA compared with placebo by 32% (1.29 events vs. 1.90 events per 100 patient-years), adjusted for the time from index HF event to randomization and stratified by geographic region (adjusted hazard ratio 0.68, 95% confidence interval 0.49-0.94), with a number needed to treat of 164 patients per year to prevent one stroke/TIA event. The principal safety endpoint of fatal bleeding or bleeding into a critical space, occurred at a similar rate on rivaroxaban and placebo (0.44 events vs. 0.55 events per 100 patient-years).ConclusionsPatients with HFrEF and CAD are at risk for stroke or TIA in the period following an episode of worsening heart failure in the absence of atrial fibrillation. Most strokes are of ischaemic origin and nearly half are either disabling or fatal. Rivaroxaban at a dose of 2.5 mg b.i.d. reduced rates of stroke or TIA compared with placebo in this population.Trial registrationCOMMANDER HF (A Study to Assess the Effectiveness and Safety of Rivaroxaban in Reducing the Risk of Death, Myocardial Infarction, or Stroke in Participants with Heart Failure and Coronary Artery Disease Following an Episode of Decompensated Heart Failure); ClinicalTrials.gov NCT01877915.

Published
2019

24. Heart failure with normal LVEF in BIOSTAT-CHF

Author

Baumhove, Lukas, Tromp, Jasper, Figarska, Sylwia, van Essen, Bart J., Anker, Stefan D., Dickstein, Kenneth, Cleland, John G., Lang, Chim C., Filippatos, Gerasimos, Ng, Leong L., Samani, Nilesh J., Metra, Marco, van Veldhuisen, Dirk J., Lam, Carolyn S.P., Voors, Adriaan A., and van der Meer, Peter

Published
2022
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27. Decongestion, kidney injury and prognosis in patients with acute heart failure

Author

Horiuchi, Yu, Wettersten, Nicholas, van Veldhuisen, Dirk J., Mueller, Christian, Filippatos, Gerasimos, Nowak, Richard, Hogan, Christopher, Kontos, Michael C., Cannon, Chad M., Müeller, Gerhard A., Birkhahn, Robert, Taub, Pam, Vilke, Gary M., Barnett, Olga, McDonald, Kenneth, Mahon, Niall, Nuñez, Julio, Briguori, Carlo, Passino, Claudio, Duff, Stephen, Maisel, Alan, and Murray, Patrick T.

Published
2022
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28. Heart failure with improved versus persistently reduced left ventricular ejection fraction: A comparison of the BIOSTAT‐CHF (European) study with the ASIAN‐HF registry.

Author

Cao, Thong Huy, Tay, Wan Ting, Jones, Donald J.L., Cleland, John G.F., Tromp, Jasper, Emmens, Johanna Elisabeth, Teng, Tiew‐Hwa Katherine, Chandramouli, Chanchal, Slingsby, Oliver Charles, Anker, Stefan D., Dickstein, Kenneth, Filippatos, Gerasimos, Lang, Chim C., Metra, Marco, Ponikowski, Piotr, Samani, Nilesh J., Van Veldhuisen, Dirk J., Zannad, Faiez, Anand, Inder S., and Lam, Carolyn S.P.

Subjects
BUNDLE-branch block, VENTRICULAR ejection fraction, HEART failure patients, HEART failure, HEART diseases
Abstract

Aims: We investigated the prevalence, clinical characteristics, and prognosis of patients with heart failure (HF) with improved ejection fraction (HFimpEF). Methods and results: We used data from BIOSTAT‐CHF including patients with a left ventricular ejection fraction (LVEF) ≤40% at baseline who had LVEF re‐assessed at 9 months. HFimpEF was defined as a LVEF >40% and a LVEF ≥10% increase from baseline at 9 months. We validated findings in the ASIAN‐HF registry. The primary outcome was a composite of time to HF rehospitalization or all‐cause mortality. In BIOSTAT‐CHF, about 20% of patients developed HFimpEF, that was associated with a lower primary event rate of all‐cause mortality (hazard ratio [HR] 0.52, 95% confidence interval [CI] 0.28–0.97, p = 0.040) and the composite endpoint (HR 0.46, 95% CI 0.30–0.70, p < 0.001) compared with patients who remained in persistent HF with reduced ejection fraction (HFrEF). The findings were similar in the ASIAN‐HF (HR 0.40, 95% CI 0.18–0.89, p = 0.024, and HR 0.29, 95% CI 0.17–0.48, p < 0.001). Five independently common predictors for HFimpEF in both BIOSTAT‐CHF and ASIAN‐HF were female sex, absence of ischaemic heart disease, higher LVEF, smaller left ventricular end‐diastolic and end‐systolic diameter at baseline. A predictive model combining only five predictors (absence of ischaemic heart disease and left bundle branch block, smaller left ventricular end‐systolic and left atrial diameter, and higher platelet count) for HFimpEF in the BIOSTAT‐CHF achieved an area under the curve of 0.772 and 0.688 in the ASIAN‐HF (due to missing left atrial diameter and platelet count). Conclusions: Approximately 20–30% of patients with HFrEF improved to HFimpEF within 1 year with better clinical outcomes. In addition, the predictive model with clinical predictors could more accurately predict HFimpEF in patients with HFrEF. [ABSTRACT FROM AUTHOR]

Published
2024
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29. Increase of serum pancreatic enzymes during hospitalization for acute heart failure.

Author

Vijver, Marlene A.T., Dams, Olivier C., ter Maaten, Jozine M., Beldhuis, Iris E., Damman, Kevin, Voors, Adriaan A., Verdonk, Robert C., and van Veldhuisen, Dirk J.

Subjects
PANCREATIC enzymes, PEPTIDES, VENTRICULAR ejection fraction, HEART failure, LIPASES
Abstract

Aims: Acute heart failure (AHF) is associated with end‐organ dysfunction. The effect of AHF on the pancreas has not been studied. We aim to evaluate serum markers of pancreatic damage during hospitalization for AHF. Methods and results: In data from the Pragmatic Urinary Sodium‐based treatment algoritHm in Acute Heart Failure (PUSH‐AHF) study, amylase and lipase values were extracted from available serum samples at baseline, and at 24 and 72 h after hospitalization. The differences between pancreatic enzymes between timepoints were evaluated using the Friedman test. Associations with N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) were tested using linear regression analysis. The study population consisted of 274 patients. Mean age was 73 ± 11 years, and 117 (43%) were women. Mean left ventricular ejection fraction (LVEF) was 38 ± 14%; 53 (19%) patients had HF with a preserved LVEF (≥50%). At baseline, median amylase and lipase were within normal range (47 [33–63] U/L and 30 [21–44] U/L, respectively). Both enzymes significantly increased in the first 72 h (P‐value for trend <0.001); mean change was 9 ± 22 U/L for amylase, and 10 ± 22 U/L for lipase. Moreover, NT‐proBNP at baseline showed a positive correlation with mean change in pancreatic enzymes in 72 h (P = 0.02 for amylase and P = 0.006 for lipase). Conclusion: Patients admitted for AHF exhibited a significant increase in serum values of pancreatic enzymes in the first 72 h, suggesting that an episode of AHF affects the pancreatic tissue. This rise in pancreatic enzymes was associated with HF severity, as reflected by NT‐proBNP. [ABSTRACT FROM AUTHOR]

Published
2024
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30. IL‐17 is associated with disease severity and targetable inflammatory processes in heart failure.

Author

Baumhove, Lukas, van Essen, Bart J., Dokter, Martin M., Zijlstra, Sietske N., Deiman, Frederik E., Laman, Jon D., Lang, Chim C., Verstappen, Gwenny M.P.J., van Veldhuisen, Dirk J., van der Meer, Peter, Bomer, Nils, and Voors, Adriaan A.

Subjects
FIBROBLAST growth factors, IMMUNOREGULATION, HEART failure, HEART fibrosis, PEPTIDES
Abstract

Aims: Heart failure (HF) is recognized as an inflammatory disease in which cytokines play an important role. In animal HF models, interleukin‐17A (IL‐17) has been linked to deterioration of cardiac function and fibrosis, whereas knock‐out of IL‐17 showed beneficial cardiac effects. However, there is limited evidence of IL‐17 involvement in patients with HF. This study aims to investigate the clinical characteristics, outcomes, and pathophysiological processes associated with circulating IL‐17 concentrations in patients with HF. Methods and results: IL‐17 was measured by ELISA in 2082 patients diagnosed with HF along with 363 circulating proteins using proximity extension assay technology for differential expression and pathway analysis. Data were validated in an independent cohort of 1737 patients with HF. Patients with elevated IL‐17 concentrations had more severe HF, as reflected by more frequent current or previous hospitalizations for HF, higher New York Heart Association functional class (NYHA) and higher levels of N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP). High IL‐17 concentrations were independently associated with an increased risk of hospitalization for HF and mortality. In both cohorts, the most strongly up‐regulated proteins in patients with high IL‐17 were fibroblast growth factor 21 (FGF‐21), interleukin‐6 (IL‐6), C‐X‐C motif chemokine ligand 13 (CXCL13), tumour necrosis factor receptor superfamily member 6B (TNFRSF6B) and interleukin‐1 receptor antagonist (IL‐1RA). Pathway over‐representation analysis showed increased activity of pathways related to lymphocyte‐mediated immunity, leukocyte activation and regulation of the immune response. Conclusions: In patients with HF, elevated IL‐17 concentrations indicate more severe HF and increased activity of inflammatory processes known to be involved in the pathophysiology of HF. IL‐17 might hold potential for identifying and targeting inflammation in HF. [ABSTRACT FROM AUTHOR]

Published
2024
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31. Atrial shunt device for heart failure with preserved and mildly reduced ejection fraction (REDUCE LAP-HF II): a randomised, multicentre, blinded, sham-controlled trial

Author

Akar, Joseph, Ando, Jiro, Anzai, Toshihisa, Asakura, Masanori, Bailey, Steven, Basuray, Anupam, Bauer, Fabrice, Bergmann, Martin, Blair, John, Cavendish, Jeffrey, Chung, Eugene, Cikes, Maja, Dauber, Ira, Donal, Erwan, Eicher, Jean-Christophe, Fail, Peter, Flaherty, James, Freixa, Xavier, Gafoor, Sameer, Gertz, Zachary, Gordon, Robert, Guazzi, Marco, Guerrero-Miranda, Cesar, Gupta, Deepak, Gustafsson, Finn, Hadadi, Cyrus, Hakemi, Emad, Handoko, Louis, Hass, Moritz, Hausleiter, Jorg, Hayward, Christopher, Hickey, Gavin, Hummel, Scott, Hussain, Imad, Isnard, Richard, Izumi, Chisato, Jondeau, Guillaume, Juneman, Elizabeth, Kinugawa, Koichiro, Kipperman, Robert, Krakowiak, Bartek, Krim, Selim, Larned, Joshua, Lewis, Gregory, Lipsic, Erik, Magalski, Anthony, Mazimba, Sula, Mazurek, Jeremy, McGrady, Michele, Mckenzie, Scott, Mehta, Shamir, Mignone, John, Morsli, Hakim, Nair, Ajith, Noel, Thomas, Orford, James, Parikh, Kishan, Patterson, Tiffany, Penicka, Martin, Petrie, Mark, Pieske, Burkert, Post, Martijn, Raake, Philip, Romero, Alicia, Ryan, John, Saito, Yoshihiko, Sakamoto, Takafumi, Sakata, Yasushi, Samara, Michael, Satya, Kumar, Sindone, Andrew, Starling, Randall, Trochu, Jean-Noël, Upadhya, Bharathi, van der Heyden, Jan, van Empel, Vanessa, Varma, Amit, Vest, Amanda, Wengenmayer, Tobias, Westenfeld, Ralf, Westermann, Dirk, Yamamoto, Kazuhiro, Zirlik, Andreas, Shah, Sanjiv J, Borlaug, Barry A, Chung, Eugene S, Cutlip, Donald E, Debonnaire, Philippe, Fail, Peter S, Gao, Qi, Hasenfuß, Gerd, Kahwash, Rami, Kaye, David M, Litwin, Sheldon E, Lurz, Philipp, Massaro, Joseph M, Mohan, Rajeev C, Ricciardi, Mark J, Solomon, Scott D, Sverdlov, Aaron L, Swarup, Vijendra, van Veldhuisen, Dirk J, Winkler, Sebastian, and Leon, Martin B

Published
2022
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34. Dose-limiting, adverse event–associated bradycardia with β-blocker treatment of atrial fibrillation in the GENETIC-AF trial

Author

Abraham, William T., Piccini, Jonathan P., Dufton, Christopher, Carroll, Ian A., Healey, Jeffrey S., O’Connor, Christopher M., Marshall, Debra, Aleong, Ryan, van Veldhuisen, Dirk J., Rienstra, Michiel, Wilton, Stephen B., White, Michel, Sauer, William H., Anand, Inder S., Huebler, Sophia P., Connolly, Stuart J., and Bristow, Michael R.

Published
2022
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37. Type D personality as a risk factor for adverse outcome in patients with cardiovascular disease: an individual patient data meta-analysis

Author

Lodder, Paul, Wicherts, Jelte M., Antens, Marijn, Albus, Christian, Bessonov, Ivan S., Condén, Emelie, Dulfer, Karolijn, Gostoli, Sara, Grande, Gesine, Hedberg, Pär, Herrmann-Lingen, Christoph, Jaarsma, Tiny, Koo, Malcolm, Lin, Ping, Lin, Tin-Kwang, Meyer, Thomas, Pushkarev, Georgiy, Rafanelli, Chiara, Raykh, Olga I., de Quadros, Alexandre Schaan, Schmidt, Marcia, Sumin, Alexei N., Utens, Elisabeth M.W.J., van Veldhuisen, Dirk J., Wang, Yini, and Kupper, Nina

Published
2023
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38. Rationale and Design of the Groningen Intervention Study for the Preservation of Cardiac Function with Sodium Thiosulfate after St-segment Elevation Myocardial Infarction (GIPS-IV) trial

Author

de Koning, Marie-Sophie LY, van Dorp, Paulien, Assa, Solmaz, Hartman, Minke HT, Voskuil, Michiel, Anthonio, Rutger L, Veen, Duco, Pundziute-Do Prado, Gabija, Leiner, Tim, van Goor, Harry, van der Meer, Peter, van Veldhuisen, Dirk J, Nijveldt, Robin, Lipsic, Erik, and van der Harst, Pim

Published
2022
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41. Mineralocorticoid Receptor Antagonists in Patients With Heart Failure and Impaired Renal Function

Author

Matsumoto, Shingo, primary, Henderson, Alasdair D., additional, Shen, Li, additional, Yang, Mingming, additional, Swedberg, Karl, additional, Vaduganathan, Muthiah, additional, van Veldhuisen, Dirk J., additional, Solomon, Scott D., additional, Pitt, Bertram, additional, Zannad, Faiez, additional, Jhund, Pardeep S., additional, and McMurray, John J.V., additional

Published
2024
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44. Relation of Decongestion and Time to Diuretics to Biomarker Changes and Outcomes in Acute Heart Failure

Author

Horiuchi, Yu, Wettersten, Nicholas, van Veldhuisen, Dirk J., Mueller, Christian, Filippatos, Gerasimos, Nowak, Richard, Hogan, Christopher, Kontos, Michael C., Cannon, Chad M., Müeller, Gerhard A., Birkhahn, Robert, Taub, Pam, Vilke, Gary M., Barnett, Olga, McDonald, Kenneth, Mahon, Niall, Nuñez, Julio, Briguori, Carlo, Passino, Claudio, Maisel, Alan, and Murray, Patrick T.

Published
2021
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45. Potential Utility of Cardiorenal Biomarkers for Prediction and Prognostication of Worsening Renal Function in Acute Heart Failure

Author

HORIUCHI, YU, WETTERSTEN, NICHOLAS, VELDHUISEN, DIRK J. van, MUELLER, CHRISTIAN, FILIPPATOS, GERASIMOS, NOWAK, RICHARD, HOGAN, CHRISTOPHER, KONTOS, MICHAEL C., CANNON, CHAD M., MÜELLER, GERHARD A., BIRKHAHN, ROBERT, TAUB, PAM, VILKE, GARY M., BARNETT, OLGA, McDONALD, KENNETH, MAHON, NIALL, NUÑEZ, JULIO, BRIGUORI, CARLO, PASSINO, CLAUDIO, MAISEL, ALAN, and MURRAY, PATRICK T.

Published
2021
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46. Identifying Subpopulations with Distinct Response to Treatment Using Plasma Biomarkers in Acute Heart Failure: Results from the PROTECT Trial

Author

Liu, Licette CY, Valente, Mattia AE, Postmus, Douwe, O’Connor, Christopher M, Metra, Marco, Dittrich, Howard C, Ponikowski, Piotr, Teerlink, John R, Cotter, Gad, Davison, Beth, Cleland, John GF, Givertz, Michael M, Bloomfield, Daniel M, van Veldhuisen, Dirk J, Hillege, Hans L, van der Meer, Peter, and Voors, Adriaan A

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Cardiovascular, Clinical Research, Heart Disease, Acute Disease, Aged, Biomarkers, Diuretics, Female, Heart Failure, Humans, Male, Xanthines, Acute heart failure, Treatment heterogeneity, Subpopulation treatment effect pattern plot, Rolofylline, Pharmacology and Pharmaceutical Sciences, Cardiovascular System & Hematology, Cardiovascular medicine and haematology, Pharmacology and pharmaceutical sciences
Abstract

BackgroundOver the last 50 years, clinical trials of novel interventions for acute heart failure (AHF) have, with few exceptions, been neutral or shown harm. We hypothesize that this might be related to a differential response to pharmacological therapy.MethodsWe studied the magnitude of treatment effect of rolofylline across clinical characteristics and plasma biomarkers in 2033 AHF patients and derived a biomarker-based responder sum score model. Treatment response was survival from all-cause mortality through day 180.ResultsIn the overall study population, rolofylline had no effect on mortality (HR 1.03, 95% CI 0.82-1.28, p = 0.808). We found no treatment interaction across clinical characteristics, but we found interactions between several biomarkers and rolofylline. The biomarker-based sum score model included TNF-R1α, ST2, WAP four-disulfide core domain protein HE4 (WAP-4C), and total cholesterol, and the score ranged between 0 and 4. In patients with score 4 (those with increased TNF-R1α, ST2, WAP-4C, and low total cholesterol), treatment with rolofylline was beneficial (HR 0.61, 95% CI 0.40-0.92, p = 0.019). In patients with score 0, treatment with rolofylline was harmful (HR 5.52, 95% CI 1.68-18.13, p = 0.005; treatment by score interaction p

Published
2017

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