Novel predictive role for mid-regional proadrenomedullin in moderate to severe aortic stenosis

Heart. 2022 Jul 27;108(16):1319-1327. doi: 10.1136/heartjnl-2021-320707.

Abstract

Objective: We investigated the prognostic significance of selected known and novel circulating biomarkers in aortic stenosis (AS).

Methods: N-terminal pro-BNP (NT-proBNP), high-sensitivity troponin-T (hsTnT), growth differentiation factor-15 (GDF-15), suppression of tumorigenicity-2 (ST2), mid-regional proadrenomedullin (MR-proADM) and mid-regional proatrial natriuretic peptide (MR-proANP) were measured in patients with moderate to severe AS, New York Heart Association (NYHA) class I-II and left ventricular ejection fraction ≥50%, recruited consecutively across five centres from 2011 to 2018. Their ability to predict both primary (all-cause mortality, heart failure hospitalisation or progression to NYHA class III-IV) and secondary (additionally incorporating syncope and acute coronary syndrome) outcomes was determined by competing risk analyses.

Results: Among 173 patients with AS (age 69±11 years, 55% male, peak transaortic velocity (Vmax) 4.0±0.8 m/s), the primary and secondary outcomes occurred in 59 (34%) and 66 (38%), respectively. With aortic valve replacement as a competing risk, the primary outcome was determined consistently by the comorbidity index and each selected biomarker except ST2 (p<0.05), independent of NYHA class, Vmax, LV-global longitudinal strain and serum creatinine. MR-proADM had the highest discriminative value for both primary (subdistribution HR (SHR) 11.3, 95% CI 3.9 to 32.7) and secondary outcomes (SHR 12.6, 95% CI 4.7 to 33.5). Prognostic assessment of dual-biomarker combinations identified MR-proADM plus either hsTnT or NT-proBNP as the best predictive model for both clinical outcomes. Paired biomarker models were not superior to those including MR-proADM as the sole circulating biomarker.

Conclusion: MR-proADM most powerfully portended worse prognosis and should be further assessed as possibly the biomarker of choice for risk stratification in AS.

Keywords: Aortic stenosis; Biomarkers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenomedullin
  • Aged
  • Aged, 80 and over
  • Aortic Valve Stenosis* / diagnosis
  • Atrial Natriuretic Factor
  • Biomarkers
  • Female
  • Heart Failure*
  • Humans
  • Interleukin-1 Receptor-Like 1 Protein
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain
  • Peptide Fragments
  • Prognosis
  • Protein Precursors
  • Stroke Volume
  • Ventricular Function, Left

Substances

  • Biomarkers
  • Interleukin-1 Receptor-Like 1 Protein
  • Peptide Fragments
  • Protein Precursors
  • proadrenomedullin
  • Natriuretic Peptide, Brain
  • Adrenomedullin
  • Atrial Natriuretic Factor