title: Biomarkers of heart failure with normal ejection fraction: a systematic review.
abstract: OBJECTIVE
  Heart failure with normal ejection fraction (HFNEF) is a major and growing public health problem, currently representing half of the heart failure burden. Although many studies have investigated the diagnostic and prognostic value of new biomarkers in heart failure, limited data are available on biomarkers other than natriuretic peptides in HFNEF. We performed a systematic review of epidemiological studies on the associations of biomarkers with the occurrence of HFNEF and with the prognosis of HFNEF patients.
  
  
  RESULTS
  Biomarkers examined most extensively in HFNEF include biomarkers of myocyte stress, inflammation, and extracellular matrix remodelling. Some biomarkers have been shown to be increased to a different extent in HFNEF compared with heart failure with reduced ejection fraction (HFREF). Several biomarkers, including biomarkers of myocyte stress, inflammation, extracellular matrix remodelling, growth differentiation factor 15 (GDF-15), cystatin C, resistin, and galectin-3, were associated with development of HFNEF and with clinical outcomes of HFNEF patients in terms of morbidity and mortality.
  
  
  CONCLUSIONS
  Several biomarkers, including biomarkers of myocyte stress, inflammation, extracellular matrix remodelling, GDF-15, cystatin C, resistin, and galectin-3, appeared to be promising diagnostic and prognostic tools in patients with HFNEF. Investigation of the incremental diagnostic and prognostic value of these biomarkers, or a combination thereof, over established clinical covariates and imaging techniques in large, prospective studies is warranted.
authors.affiliation: Erasmus University Medical Center, Department of Cardiology, Rotterdam, The Netherlands.
authors.forename: Jin M
authors.initials: JM
authors.lastname: Cheng
authors.forename: K Martijn
authors.initials: KM
authors.lastname: Akkerhuis
authors.forename: Linda C
authors.initials: LC
authors.lastname: Battes
authors.forename: Laura C
authors.initials: LC
authors.lastname: van Vark
authors.forename: Hans L
authors.initials: HL
authors.lastname: Hillege
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Paulus
authors.forename: Eric
authors.initials: E
authors.lastname: Boersma
authors.forename: Isabella
authors.initials: I
authors.lastname: Kardys
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D055316:Cystatin C / Q000097:blood*; D016021:Epidemiologic Studies; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D037502:Galectin 3 / Q000097:blood*; D055436:Growth Differentiation Factor 15 / Q000097:blood*; D006333:Heart Failure / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008297:Male; D032383:Myocytes, Cardiac / Q000378:metabolism; D011379:Prognosis; D052243:Resistin / Q000097:blood*; D013318:Stroke Volume
chemical_list: D015415:Biomarkers; D055316:Cystatin C; D037502:Galectin 3; D055436:Growth Differentiation Factor 15; D052243:Resistin
keywords: Biomarker; Heart failure with normal ejection fraction; Prognosis