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Proteomic Biomarkers Are Linked to QTc Interval in Patients With Chronic Heart Failure

Mylène Barry-Loncq de Jong1, Teun B Petersen1,2, Sabrina Abou Kamar1

  • 1Department of Cardiology, Thorax Center, Cardiovascular Institute, Erasmus MC, Rotterdam, the Netherlands.

Proteomics. Clinical Applications
|September 3, 2025
PubMed

Insights

Circulating proteins, including ST2 and angiopoietin-2, are linked to prolonged QTc intervals in heart failure patients. These biomarkers also predict adverse cardiovascular events, offering new insights into heart failure mechanisms.

Area of Science:

  • Cardiology
  • Biomarker Discovery
  • Heart Failure Research

Background:

  • The QTc interval, a measure of cardiac repolarization, is often prolonged in heart failure with reduced ejection fraction (HFrEF).
  • The relationship between specific circulating proteins and QTc interval prolongation in HFrEF remains incompletely understood.
  • Identifying such links may elucidate pathophysiological mechanisms and improve risk stratification in HFrEF.

Purpose of the Study:

  • To investigate the association between a broad panel of circulating cardiovascular proteins and the rate-corrected QT (QTc) interval in HFrEF patients.
  • To determine if these proteins are also associated with adverse cardiovascular outcomes in this population.
  • To explore potential pathophysiological pathways linking protein levels, QTc prolongation, and clinical prognosis.

Main Methods:

  • Analysis of 197 HFrEF patients from the Bio-SHiFT study, all in sinus rhythm at baseline.
  • Measurement of 1105 cardiovascular-related proteins using the Somalogic-SomaScan Assay.
  • Statistical analysis including linear regression for QTc association and Cox regression for outcome prediction, with adjustments for relevant covariates.

Main Results:

  • Eleven biomarkers were significantly associated with QTc interval (FDR < 0.05), including interleukin-1 receptor-like 1 (ST2) and angiopoietin-2.
  • Five biomarkers—ST2, angiopoietin-2, atrial natriuretic factor, insulin-like growth factor-binding protein 7 (IGFBP7), and carbonic anhydrase 4 (CA4)—were significantly associated with adverse cardiovascular outcomes.
  • These proteins are implicated in inflammation, fibrosis, and angiogenesis pathways.

Conclusions:

  • Several circulating cardiovascular proteins are associated with both QTc interval prolongation and adverse cardiovascular events in HFrEF.
  • These findings suggest that inflammation, fibrosis, and angiogenesis pathways may contribute to QTc abnormalities and poor prognosis in HFrEF.
  • The identified biomarkers, particularly ST2, angiopoietin-2, ANF, IGFBP7, and CA4, hold potential as diagnostic and prognostic tools in HFrEF management.
Abstract

Keywords:
HFrEFQT intervalQTcbiomarkersheart failureproteomics

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