Phenotyping progression of secondary mitral regurgitation in chronic systolic heart failure

Eur J Clin Invest. 2019 Nov;49(11):e13159. doi: 10.1111/eci.13159. Epub 2019 Oct 9.

Abstract

Background: Secondary mitral regurgitation (sMR) drives adverse cardiac remodelling in patients with heart failure with reduced ejection fraction (HFrEF). Progression in severity over time contributes to a transition towards more advanced HF stages. Early identification of patients at risk for sMR progression remains challenging. We therefore sought to assess a broad spectrum of neurohumoral biomarkers in patients with HFrEF to explore their ability to predict progression of sMR.

Methods: A total of 249 HFrEF patients were enrolled. Biomarkers encompassing key neurohumoral pathways in heart failure were sampled at baseline, and sMR progression was assessed over 3 years of follow-up.

Results: Of 191 patients with nonsevere sMR at baseline, 18% showed progressive sMR within three years after study enrolment. Progression of sMR was associated with higher levels of MR-proADM (adj.OR 2.25, 95% CI 1.29-3.93; P = .004), MR-proANP (adj.OR 1.84, 95% CI 1.14-3.00; P = .012), copeptin (adj.OR 1.66, 95% CI 1.04-2.67; P = .035) and CT-pro-ET1 (adj.OR 1.68, 95% CI 1.06-2.68; P = .027) but not with NT-proBNP (P = .54).

Conclusion: Increased plasma levels of neurohumoral cardiac biomarkers are predictors of sMR progression in patients with HFrEF and add easily available incremental prognostic information for risk stratification. Importantly, NT-proBNP was not useful to predict progressive sMR in the present analysis. On the contrary, MR-proANP, primarily produced in the atria, copeptin partly triggered by intra-cardiac and intra-arterial pressures and MR-proADM, a marker of forward failure and peripheral released vasoactive CT-proET1, increase based on a progressive loading burden by sMR and may thus serve as better predictors of sMR progression.

Keywords: HFrEF; neurohumoral marker; sMR; sMR progression.

MeSH terms

  • Adrenomedullin / blood*
  • Aged
  • Atrial Natriuretic Factor / blood*
  • Biomarkers
  • Chronic Disease
  • Disease Progression
  • Echocardiography
  • Endothelin-1 / blood*
  • Female
  • Glycopeptides / blood*
  • Heart Failure, Systolic / blood*
  • Heart Failure, Systolic / complications
  • Heart Failure, Systolic / diagnostic imaging
  • Humans
  • Male
  • Middle Aged
  • Mitral Valve Insufficiency / blood*
  • Mitral Valve Insufficiency / diagnostic imaging
  • Mitral Valve Insufficiency / etiology
  • Natriuretic Peptide, Brain / blood
  • Peptide Fragments / blood*
  • Phenotype
  • Prognosis
  • Protein Precursors / blood*
  • Risk Assessment
  • Stroke Volume

Substances

  • Biomarkers
  • C-terminal proendothelin-1
  • Endothelin-1
  • Glycopeptides
  • Peptide Fragments
  • Protein Precursors
  • copeptins
  • mid-regional pro-adrenomedullin, human
  • midregional pro-atrial natriuretic peptide, human
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • Adrenomedullin
  • Atrial Natriuretic Factor