title: A systems BIOlogy Study to TAilored Treatment in Chronic Heart Failure: rationale, design, and baseline characteristics of BIOSTAT-CHF.
abstract: Despite major improvements in pharmacological and device treatments, heart failure remains a syndrome with high morbidity and mortality, poor quality of life, and high health-care costs. Given the extensive heterogeneity among patients with heart failure, substantial differences in the response to therapy can be expected. We hypothesize that individualized therapy is an essential next step to improve outcomes in patients with heart failure.
  
  
  
  The BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF) included 2516 patients with worsening signs and/or symptoms of heart failure from 11 European countries, who were considered to be on suboptimal medical treatment. Another 1738 patients from Scotland were included in a validation cohort. Overall, both patient cohorts were well matched. The majority of patients were hospitalized for acute heart failure, and the remainder presented with worsening signs and/or symptoms of heart failure at outpatient clinics. Approximately half of the patients were in New York Heart Association class III, and 7% vs 34% of patients of the index vs validation cohort had heart failure with preserved ejection fraction. According to study design, all patients used diuretics, but owing to the inclusion criteria of both cohorts, patients were not on optimal, evidence-based medical therapy. In the follow-up phase, uptitration to guideline-recommended doses was encouraged.
  
  
  
  By using a novel systems biology approach, incorporating demographics, biomarkers, genome-wide analysis, and proteomics, a model that predicts response to therapy will be developed, which should be instrumental in developing alternative therapies for patients with suboptimal response to currently recommended therapies and thus further improve care for patients with heart failure.
authors.affiliation: Department of Cardiology, University of Groningen, Hanzeplein 1, 9713, GZ, Groningen, the Netherlands.
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Voors
authors.affiliation: Innovative Clinical Trials, Department of Cardiology and Pneumology, University Medical Centre Göttingen (UMG), Göttingen, Germany.
authors.forename: Stefan D
authors.initials: SD
authors.lastname: Anker
authors.affiliation: National Heart & Lung Institute, Royal Brompton and Harefield Hospitals, Imperial College, London, UK.
authors.forename: John G
authors.initials: JG
authors.lastname: Cleland
authors.affiliation: University of Bergen, Bergen, Norway.|University of Stavanger, Stavanger, Norway.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Dickstein
authors.affiliation: Department of Cardiology, Heart Failure Unit, Athens University Hospital Attikon, Athens, Greece.
authors.forename: Gerasimos
authors.initials: G
authors.lastname: Filippatos
authors.affiliation: Department of Cardiology, University of Groningen, Hanzeplein 1, 9713, GZ, Groningen, the Netherlands.
authors.forename: Pim
authors.initials: P
authors.lastname: van der Harst
authors.affiliation: Department of Cardiology, University of Groningen, Hanzeplein 1, 9713, GZ, Groningen, the Netherlands.
authors.forename: Hans L
authors.initials: HL
authors.lastname: Hillege
authors.affiliation: School of Medicine Centre for Cardiovascular and Lung Biology, Division of Medical Sciences, University of Dundee, Ninewells Hospital & Medical School, Dundee, UK.
authors.forename: Chim C
authors.initials: CC
authors.lastname: Lang
authors.affiliation: Department of Cardiology, University of Groningen, Hanzeplein 1, 9713, GZ, Groningen, the Netherlands.
authors.forename: Jozine M
authors.initials: JM
authors.lastname: Ter Maaten
authors.affiliation: Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, and NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, LE3 9QP, UK.
authors.forename: Leong
authors.initials: L
authors.lastname: Ng
authors.affiliation: Department of Heart Diseases, Wroclaw Medical University, Poland and Cardiology Department, Military Hospital, Wroclaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Ponikowski
authors.affiliation: Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, and NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, LE3 9QP, UK.
authors.forename: Nilesh J
authors.initials: NJ
authors.lastname: Samani
authors.affiliation: Department of Cardiology, University of Groningen, Hanzeplein 1, 9713, GZ, Groningen, the Netherlands.
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: van Veldhuisen
authors.affiliation: Inserm CIC 1433, Université de Lorrain, CHU de Nancy, Nancy, France.
authors.forename: Faiz
authors.initials: F
authors.lastname: Zannad
authors.affiliation: Department of Epidemiology, Biostatistics and Bioinformatics, Academic Medical Centre, Amsterdam, the Netherlands.
authors.forename: Aeilko H
authors.initials: AH
authors.lastname: Zwinderman
authors.affiliation: Institute of Cardiology, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Metra
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000368:Aged; D000369:Aged, 80 and over; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D002423:Cause of Death; D002908:Chronic Disease; D018450:Disease Progression; D004232:Diuretics / Q000627:therapeutic use*; D005060:Europe; D019317:Evidence-Based Medicine; D005260:Female; D005665:Furosemide / Q000627:therapeutic use; D055106:Genome-Wide Association Study; D023281:Genomics; D006333:Heart Failure / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D009026:Mortality; D017410:Practice Guidelines as Topic; D057285:Precision Medicine; D011446:Prospective Studies; D040901:Proteomics; D049490:Systems Biology
chemical_list: D000319:Adrenergic beta-Antagonists; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D004232:Diuretics; D000451:Mineralocorticoid Receptor Antagonists; D005665:Furosemide
keywords: Heart failure; Individualized treatment; Systems biology; Treatment response