Jasper Tromp1, B Daan Westenbrink2, Wouter Ouwerkerk3, Dirk J van Veldhuisen2, Nilesh J Samani4, Piotr Ponikowski5, Marco Metra6, Stefan D Anker7, John G Cleland8, Kenneth Dickstein9, Gerasimos Filippatos10, Pim van der Harst2, Chim C Lang11, Leong L Ng4, Faiez Zannad12, Aelko H Zwinderman3, Hans L Hillege2, Peter van der Meer2, Adriaan A Voors13. 1. Department of Cardiology, University of Groningen, Groningen, the Netherlands; National Heart Centre Singapore, Singapore; Duke-NUS Medical School, Singapore, Singapore. 2. Department of Cardiology, University of Groningen, Groningen, the Netherlands. 3. Department of Epidemiology, Biostatistics & Bioinformatics, Academic Medical Center, Amsterdam, the Netherlands. 4. Department of Cardiovascular Sciences, University of Leicester, and NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, United Kingdom. 5. Department of Heart Diseases, Wroclaw Medical University, and Cardiology Department, Military Hospital, Wroclaw, Poland. 6. Institute of Cardiology, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy. 7. Division of Cardiology and Metabolism-Heart Failure, Cachexia & Sarcopenia, Department of Cardiology (CVK), and Berlin-Brandenburg Center for Regenerative Therapies (BCRT), at Charité University Medicine, Berlin, Germany. 8. Robertson Centre for Biostatistics, Institute of Health and Wellbeing, University of Glasgow, Glasgow Royal Infirmary, Glasgow, United Kingdom. 9. University of Bergen, Stavanger University Hospital, Stavanger, Norway. 10. National and Kapodistrian University of Athens, School of Medicine, Department of Cardiology, Heart Failure Unit, Athens University Hospital Attikon, Athens, Greece. 11. Division of Molecular & Clinical Medicine, University of Dundee, Dundee, United Kingdom. 12. Inserm CIC 1433, Université de Lorrain, CHU de Nancy, Nancy, France. 13. Department of Cardiology, University of Groningen, Groningen, the Netherlands. Electronic address: a.a.voors@umcg.nl.
Abstract
BACKGROUND: Information on the pathophysiological differences between heart failure with reduced ejection fraction (HFrEF) versus heart failure with preserved ejection fraction (HFpEF) is needed OBJECTIVES: The purpose of this study was to establish biological pathways specifically related to HFrEF and HFpEF. METHODS: The authors performed a network analysis to identify unique biomarker correlations in HFrEF and HFpEF using 92 biomarkers from different pathophysiological domains in a cohort of 1,544 heart failure (HF) patients. Data were independently validated in 804 patients with HF. Networks were enriched with existing knowledge on protein-protein interactions and translated into biological pathways uniquely related to HFrEF, HF with a midrange ejection fraction, and HFpEF. RESULTS: In the index cohort (mean age 74 years; 34% female), 718 (47%) patients had HFrEF (left ventricular ejection fraction [LVEF] <40%) and 431 (27%) patients had HFpEF (LVEF ≥50%). A total of 8 (12%) correlations were unique for HFrEF and 6 (9%) were unique to HFpEF. Central proteins in HFrEF were N-terminal B-type natriuretic peptide, growth differentiation factor-15, interleukin-1 receptor type 1, and activating transcription factor 2, while central proteins in HFpEF were integrin subunit beta-2 and catenin beta-1. Biological pathways in HFrEF were related to DNA binding transcription factor activity, cellular protein metabolism, and regulation of nitric oxide biosynthesis. Unique pathways in patients with HFpEF were related to cytokine response, extracellular matrix organization, and inflammation. Biological pathways of patients with HF with a midrange ejection fraction were in between HFrEF and HFpEF. CONCLUSIONS: Network analysis showed that biomarker profiles specific for HFrEF are related to cellular proliferation and metabolism, whereas biomarker profiles specific for HFpEF are related to inflammation and extracellular matrix reorganization. (The BIOlogy Study to TAilored Treatment in Chronic Heart Failure [BIOSTAT-CHF]; EudraCT 2010-020808-29).
BACKGROUND: Information on the pathophysiological differences between heart failure with reduced ejection fraction (HFrEF) versus heart failure with preserved ejection fraction (HFpEF) is needed OBJECTIVES: The purpose of this study was to establish biological pathways specifically related to HFrEF and HFpEF. METHODS: The authors performed a network analysis to identify unique biomarker correlations in HFrEF and HFpEF using 92 biomarkers from different pathophysiological domains in a cohort of 1,544 heart failure (HF) patients. Data were independently validated in 804 patients with HF. Networks were enriched with existing knowledge on protein-protein interactions and translated into biological pathways uniquely related to HFrEF, HF with a midrange ejection fraction, and HFpEF. RESULTS: In the index cohort (mean age 74 years; 34% female), 718 (47%) patients had HFrEF (left ventricular ejection fraction [LVEF] <40%) and 431 (27%) patients had HFpEF (LVEF ≥50%). A total of 8 (12%) correlations were unique for HFrEF and 6 (9%) were unique to HFpEF. Central proteins in HFrEF were N-terminal B-type natriuretic peptide, growth differentiation factor-15, interleukin-1 receptor type 1, and activating transcription factor 2, while central proteins in HFpEF were integrin subunit beta-2 and catenin beta-1. Biological pathways in HFrEF were related to DNA binding transcription factor activity, cellular protein metabolism, and regulation of nitric oxide biosynthesis. Unique pathways in patients with HFpEF were related to cytokine response, extracellular matrix organization, and inflammation. Biological pathways of patients with HF with a midrange ejection fraction were in between HFrEF and HFpEF. CONCLUSIONS: Network analysis showed that biomarker profiles specific for HFrEF are related to cellular proliferation and metabolism, whereas biomarker profiles specific for HFpEF are related to inflammation and extracellular matrix reorganization. (The BIOlogy Study to TAilored Treatment in Chronic Heart Failure [BIOSTAT-CHF]; EudraCT 2010-020808-29).
Authors: Sunyoung Jang; Oluseye Ogunmoroti; Chiadi E Ndumele; Di Zhao; Vishal N Rao; Oluwaseun E Fashanu; Martin Tibuakuu; James D Otvos; Eve-Marie Benson; Pamela Ouyang; Erin D Michos Journal: Circ Heart Fail Date: 2020-07-28 Impact factor: 8.790
Authors: Michael S Sabbah; Ahmed U Fayyaz; Simon de Denus; G Michael Felker; Barry A Borlaug; Surendra Dasari; Rickey E Carter; Margaret M Redfield Journal: Circ Heart Fail Date: 2020-07-29 Impact factor: 8.790
Authors: Sanjiv J Shah; Barry A Borlaug; Dalane W Kitzman; Andrew D McCulloch; Burns C Blaxall; Rajiv Agarwal; Julio A Chirinos; Sheila Collins; Rahul C Deo; Mark T Gladwin; Henk Granzier; Scott L Hummel; David A Kass; Margaret M Redfield; Flora Sam; Thomas J Wang; Patrice Desvigne-Nickens; Bishow B Adhikari Journal: Circulation Date: 2020-03-23 Impact factor: 29.690