Jozine M Ter Maaten, Daan Kremer, Biniyam G Demissei1, Joachim Struck2, Andreas Bergmann2, Stefan D Anker3,4, Leong L Ng5,6, Kenneth Dickstein7,8, Marco Metra9, Nilesh J Samani5,6, Simon P R Romaine5,6, John Cleland10, Nicolas Girerd11, Chim C Lang12, Dirk J van Veldhuisen1, Adriaan A Voors1. 1. Department of Cardiology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands. 2. Sphingotec GmbH, Hennigsdorf, Germany. 3. Department of Cardiology (CVK), and Berlin-Brandenburg Center for Regenerative Therapies (BCRT), German Centre for Cardiovascular Research (DZHK) partner site Berlin, Charité Universitätsmedizin, Berlin, Germany. 4. Department of Cardiology and Pneumology, University Medical Center Göttingen (UMG), Göttingen, Germany. 5. Department of Cardiovascular Sciences, University of Leicester, Leicester, UK. 6. NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK. 7. University of Bergen, Bergen, Norway. 8. Stavanger University Hospital, Stavanger, Norway. 9. Department of Medical and Surgical Specialties, Institute of Cardiology, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy. 10. National Heart & Lung Institute, Royal Brompton & Harefield Hospitals, Imperial College, London, UK. 11. Inserm CIC1433, Université de Lorrain, CHU de Nancy, Nancy, France. 12. Division of Molecular and Clinical Medicine, School of Medicine, University of Dundee, Ninewells Hospital & Medical School, Dundee, UK.
Abstract
BACKGROUND: Secretion of adrenomedullin (ADM) is stimulated by volume overload to maintain endothelial barrier function, and higher levels of biologically active (bio-) ADM in heart failure (HF) are a counteracting response to vascular leakage and tissue oedema. This study aimed to establish the value of plasma bio-ADM as a marker of congestion in patients with worsening HF. METHODS AND RESULTS: The association of plasma bio-ADM with clinical markers of congestion, as well as its prognostic value was studied in 2179 patients with new-onset or worsening HF enrolled in BIOSTAT-CHF. Data were validated in a separate cohort of 1703 patients. Patients with higher plasma bio-ADM levels were older, had more severe HF and more signs and symptoms of congestion (all P < 0.001). Amongst 20 biomarkers, bio-ADM was the strongest predictor of a clinical congestion score (r2 = 0.198). In multivariable regression analysis, higher bio-ADM was associated with higher body mass index, more oedema, and higher fibroblast growth factor 23. In hierarchical cluster analysis, bio-ADM clustered with oedema, orthopnoea, rales, hepatomegaly and jugular venous pressure. Higher bio-ADM was independently associated with impaired up-titration of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers after 3 months, but not of beta-blockers. Higher bio-ADM levels were independently associated with an increased risk of all-cause mortality and HF hospitalization (hazard ratio 1.16, 95% confidence interval 1.06-1.27, P = 0.002, per log increase). Analyses in the validation cohort yielded comparable findings. CONCLUSIONS: Plasma bio-ADM in patients with new-onset and worsening HF is associated with more severe HF and more oedema, orthopnoea, hepatomegaly and jugular venous pressure. We therefore postulate bio-ADM as a congestion marker, which might become useful to guide decongestive therapy.
BACKGROUND: Secretion of adrenomedullin (ADM) is stimulated by volume overload to maintain endothelial barrier function, and higher levels of biologically active (bio-) ADM in heart failure (HF) are a counteracting response to vascular leakage and tissue oedema. This study aimed to establish the value of plasma bio-ADM as a marker of congestion in patients with worsening HF. METHODS AND RESULTS: The association of plasma bio-ADM with clinical markers of congestion, as well as its prognostic value was studied in 2179 patients with new-onset or worsening HF enrolled in BIOSTAT-CHF. Data were validated in a separate cohort of 1703 patients. Patients with higher plasma bio-ADM levels were older, had more severe HF and more signs and symptoms of congestion (all P < 0.001). Amongst 20 biomarkers, bio-ADM was the strongest predictor of a clinical congestion score (r2 = 0.198). In multivariable regression analysis, higher bio-ADM was associated with higher body mass index, more oedema, and higher fibroblast growth factor 23. In hierarchical cluster analysis, bio-ADM clustered with oedema, orthopnoea, rales, hepatomegaly and jugular venous pressure. Higher bio-ADM was independently associated with impaired up-titration of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers after 3 months, but not of beta-blockers. Higher bio-ADM levels were independently associated with an increased risk of all-cause mortality and HF hospitalization (hazard ratio 1.16, 95% confidence interval 1.06-1.27, P = 0.002, per log increase). Analyses in the validation cohort yielded comparable findings. CONCLUSIONS: Plasma bio-ADM in patients with new-onset and worsening HF is associated with more severe HF and more oedema, orthopnoea, hepatomegaly and jugular venous pressure. We therefore postulate bio-ADM as a congestion marker, which might become useful to guide decongestive therapy.
Authors: Eva M Boorsma; Jozine M Ter Maaten; Kevin Damman; Wilfried Dinh; Finn Gustafsson; Steven Goldsmith; Daniel Burkhoff; Faiez Zannad; James E Udelson; Adriaan A Voors Journal: Nat Rev Cardiol Date: 2020-05-15 Impact factor: 32.419
Authors: Henrike Arfsten; Georg Goliasch; Philipp E Bartko; Suriya Prausmüller; Georg Spinka; Anna Cho; Johannes Novak; Julia Mascherbauer; Helmuth Haslacher; Guido Strunk; Martin Hülsmann; Noemi Pavo Journal: ESC Heart Fail Date: 2021-03-20
Authors: Jozine M Ter Maaten; Pieter Martens; Kevin Damman; Kenneth Dickstein; Piotr Ponikowski; Chim C Lang; Leong L Ng; Stefan D Anker; Nilesh J Samani; Gerasimos Filippatos; John G Cleland; Faiez Zannad; Hans L Hillege; Dirk J van Veldhuisen; Marco Metra; Adriaan A Voors; Wilfried Mullens Journal: Clin Res Cardiol Date: 2020-01-30 Impact factor: 5.460
Authors: Fraser M Curran; U Bhalraam; Mohapradeep Mohan; Jagdeep S Singh; Stefan D Anker; Kenneth Dickstein; Alexander S Doney; Gerasimos Filippatos; Jacob George; Marco Metra; Leong L Ng; Colin N Palmer; Nilesh J Samani; Dirk J van Veldhuisen; Adriaan A Voors; Chim C Lang; Ify R Mordi Journal: ESC Heart Fail Date: 2021-05-16
Authors: Oscar H M Lundberg; Maria Lengquist; Martin Spångfors; Martin Annborn; Deborah Bergmann; Janin Schulte; Helena Levin; Olle Melander; Attila Frigyesi; Hans Friberg Journal: Crit Care Date: 2020-11-04 Impact factor: 9.097
Authors: Marko Kumric; Tina Ticinovic Kurir; Josko Bozic; Duska Glavas; Tina Saric; Bjørnar Marcelius; Domenico D'Amario; Josip A Borovac Journal: Card Fail Rev Date: 2021-06-12