title: Adaptive cardiovascular hormones in a spectrum of heart failure phenotypes.
abstract: OBJECTIVE
  In heart failure (HF), activation of brain natriuretic peptide (BNP), atrial natriuretic peptide (ANP) and adrenomedullin (ADM) is adaptive. The activation of these peptides in relation to different HF phenotypes such as HF with preserved ejection fraction (HFpEF), reduced ejection fraction (HFrEF) and after left ventricular assist device (LVAD) and heart transplantation (HTx) remains poorly characterized.
  
  
  METHODS
  We measured and compared N-terminal (NT)-proBNP, mid-regional (MR)-proANP and mid-regional (MR)-proADM in 86 patients with HFpEF, 49 patients with HFrEF, 13 patients one year post-LVAD and 22 patients one year post-HTx. We assessed their prognostic impact using Kaplan-Meier analysis and multivariable Cox regression.
  
  
  RESULTS
  In HFpEF, HFrEF, LVAD and HTx, NT-proBNP, median (inter-quartile range), was 1000 (465-2335), 3145 (1475-5190), 1430 (986-2570), and 208 (127-353) pmol/L, p < 0.001. MR-proANP was 313 (192-381), 449 (325-596), 276 (216-305), and 118 (96-163) pmol/L, p < 0.001. MR-proADM was 1.2 (0.9-1.6), 1.3 (0.9-2.0), 0.9 (0.7-1.4), and 0.7 (0.6-0.9) nmol/L, p < 0.001 overall and p = 0.212 HFpEF versus HFrEF. In both HFpEF and HFrEF, NT-proBNP and MR-proANP predicted survival free from HTx or LVAD, independent of age, gender, NYHA class and eGFR, whereas MR-proADM did not.
  
  
  CONCLUSIONS
  Patterns of the cardiomyocyte stress hormones NT-proBNP and MR-proANP suggest that compared to HFrEF, HFpEF may represent milder disease and LVAD and HTx may represent progressive resolution of HF severity. NT-proBNP and MR-proANP independently predicted prognosis in both HFpEF and HFrEF. In contrast, MR-proADM did not distinguish between HFpEF and HFrEF, did not predict prognosis in either, and may be more non-specific in HF.
authors.affiliation: Karolinska Institute, Department of Medicine, Stockholm, Sweden; Karolinska University Hospital, Department of Cardiology, Stockholm, Sweden.
authors.forename: Stanislava
authors.initials: S
authors.lastname: Zabarovskaja
authors.affiliation: Karolinska Institute, Department of Medicine, Stockholm, Sweden; Karolinska University Hospital, Department of Cardiology, Stockholm, Sweden.
authors.forename: Camilla
authors.initials: C
authors.lastname: Hage
authors.affiliation: Karolinska Institute, Department of Medicine, Stockholm, Sweden; Karolinska University Hospital, Department of Cardiology, Stockholm, Sweden.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Linde
authors.affiliation: Département de Cardiologie & CIC-IT U 804, Centre Hospitalier Universitaire de Rennes, France.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Daubert
authors.affiliation: Département de Cardiologie & CIC-IT U 804, Centre Hospitalier Universitaire de Rennes, France.
authors.forename: Erwan
authors.initials: E
authors.lastname: Donal
authors.affiliation: Karolinska Institute, Department of Medicine, Stockholm, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Gabrielsen
authors.affiliation: Karolinska Institute, Department of Medicine, Stockholm, Sweden; Karolinska University Hospital, Department of Cardiology, Stockholm, Sweden.
authors.forename: Linda
authors.initials: L
authors.lastname: Mellbin
authors.affiliation: Karolinska Institute, Department of Medicine, Stockholm, Sweden; Karolinska University Hospital, Department of Cardiology, Stockholm, Sweden. Electronic address: stasia.zab@gmail.com.
authors.forename: Lars H
authors.initials: LH
authors.lastname: Lund
mesh_terms: D000222:Adaptation, Physiological; D053607:Adrenomedullin / Q000097:blood*; D000704:Analysis of Variance; D009320:Atrial Natriuretic Factor / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000401:mortality / Q000601:surgery*; D016027:Heart Transplantation; D006353:Heart-Assist Devices; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D015999:Multivariate Analysis; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D010641:Phenotype; D011379:Prognosis; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012720:Severity of Illness Index; D013318:Stroke Volume / Q000502:physiology*; D016019:Survival Analysis
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D053607:Adrenomedullin; D009320:Atrial Natriuretic Factor
keywords: Heart failure with preserved ejection fraction; Heart transplantation; MR-proADM; MR-proANP; NT-proBNP; Ventricular assist device