Noninvasive Prognostic Biomarkers for Left-Sided Heart Failure as Predictors of Survival in Pulmonary Arterial Hypertension.

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  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: United States NLM ID: 0231335 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1931-3543 (Electronic) Linking ISSN: 00123692 NLM ISO Abbreviation: Chest Subsets: MEDLINE
    • Publication Information:
      Publication: 2016- : New York : Elsevier
      Original Publication: Chicago : American College of Chest Physicians
    • Subject Terms:
      Heart Failure/*complications ; Interleukin-1 Receptor-Like 1 Protein/*blood ; Natriuretic Peptide, Brain/*blood ; Peptide Fragments/*blood ; Pulmonary Arterial Hypertension/*blood ; Ventricular Function, Left/*physiology; Biomarkers/blood ; Enzyme-Linked Immunosorbent Assay ; Female ; Heart Failure/blood ; Heart Failure/physiopathology ; Humans ; Male ; Middle Aged ; Prognosis ; Protein Precursors ; Pulmonary Arterial Hypertension/etiology ; Pulmonary Arterial Hypertension/mortality ; Risk Factors ; Stroke Volume/physiology ; Survival Rate/trends ; United States/epidemiology
    • Abstract:
      Background: Three biomarkers, soluble suppression of tumorigenicity 2 (ST2), galectin 3 (Gal3), and N-terminal brain natriuretic peptide prohormone (NT-proBNP), are approved for noninvasive risk assessment in left-sided heart failure, and small observational studies have shown their prognostic usefulness in heterogeneous pulmonary hypertension cohorts. We examined associations between these biomarkers and disease severity and survival in a large cohort of patients with pulmonary arterial hypertension (PAH) (ie, group 1 pulmonary hypertension). We hypothesized that additive use of biomarkers in combination would improve the prognostic value of survival models.
      Methods: Biomarker measurements and clinical data were obtained from 2,017 adults with group 1 PAH. Associations among biomarker levels and clinical variables, including survival times, were examined with multivariable regression models. Likelihood ratio tests and the Akaike information criterion were used to compare survival models.
      Results: Higher ST2 and NT-proBNP were associated with higher pulmonary pressures and vascular resistance and lower 6-min walk distance. Higher ST2 and NT-proBNP levels were associated with increased risk of death (hazard ratios: 2.79; 95% CI, 2.21-3.53; P < .001 and 1.84; 95% CI, 1.62-2.10; P < .001, respectively). The addition of ST2 to survival models composed of other predictors of survival, including NT-proBNP, significantly improved model fit and predictive capacity.
      Conclusions: ST2 and NT-proBNP are strong, noninvasive prognostic biomarkers in PAH. Despite its prognostic value in left-sided heart failure, Gal3 was not predictive in PAH. Adding ST2 to survival models significantly improves model predictive capacity. Future studies are needed to develop multimarker assays that improve noninvasive risk stratification in PAH.
      (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)
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    • Grant Information:
      P50 HL084946 United States HL NHLBI NIH HHS; F32 HL143835 United States HL NHLBI NIH HHS; R01 HL114910 United States HL NHLBI NIH HHS; R24 HL105333 United States HL NHLBI NIH HHS; R24 HL123767 United States HL NHLBI NIH HHS; R01 HL135114 United States HL NHLBI NIH HHS; T32 HL007534 United States HL NHLBI NIH HHS
    • Contributed Indexing:
      Keywords: biomarkers; heart failure; molecular biology; pulmonary hypertension
    • Accession Number:
      0 (Biomarkers)
      0 (IL1RL1 protein, human)
      0 (Interleukin-1 Receptor-Like 1 Protein)
      0 (Peptide Fragments)
      0 (Protein Precursors)
      0 (pro-brain natriuretic peptide (1-76))
      114471-18-0 (Natriuretic Peptide, Brain)
    • Publication Date:
      Date Created: 20200129 Date Completed: 20210517 Latest Revision: 20210609
    • Publication Date:
      20221213
    • Accession Number:
      PMC7268446
    • Accession Number:
      10.1016/j.chest.2019.12.037
    • Accession Number:
      31987881