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Inflammatory Biomarkers and ECG Repolarization Metrics: Sudden Death in Heart Failure With Reduced Ejection Fraction

Haran Yogasundaram1, Wendimagegn Alemayehu1, Eric Ly1

  • 1Canadian VIGOUR Centre, University of Alberta, Edmonton, Alberta, Canada.

JACC. Advances
|June 17, 2026
PubMed

Insights

Inflammatory biomarkers like hsCRP are linked to sudden cardiac death (SCD) in heart failure patients, offering prognostic value beyond ECG measures. This suggests inflammation plays a role in SCD risk distinct from repolarization changes.

Area of Science:

  • Cardiology
  • Biomarkers
  • Sudden Cardiac Death

Background:

  • Sudden cardiac death (SCD) is a major cause of mortality in heart failure with reduced ejection fraction (HFrEF).
  • The link between inflammatory biomarkers, ECG repolarization, and SCD in HFrEF is not fully understood.

Purpose of the Study:

  • To investigate the association between ECG repolarization metrics, inflammatory biomarkers, and SCD in patients with HFrEF.
  • To determine if inflammatory markers provide prognostic information for SCD beyond traditional ECG parameters.

Main Methods:

  • Analysis of 4,391 HFrEF patients from the VICTORIA trial with baseline ECGs and biomarkers.
  • Assessment of interleukin-6, growth differentiation factor-15, and hsCRP in relation to SCD.
  • Utilized Cox proportional hazards and linear regression models, including JTc interval (QTc minus QRS duration).

Main Results:

  • The JTc interval, but not QTc, was associated with SCD risk.
  • High-sensitivity C-reactive protein (hsCRP) was independently associated with increased SCD risk in multivariable models.
  • hsCRP provided the greatest prognostic value when added to the JTc interval model, indicating significant new information.

Conclusions:

  • Inflammatory biomarkers, especially hsCRP, are independently linked to SCD in HFrEF patients.
  • Inflammation appears to contribute to SCD risk via mechanisms separate from repolarization prolongation.
  • hsCRP may enhance risk stratification for SCD in HFrEF.
Abstract

Keywords:
VICTORIA trialheart failure with reduced ejection fractioninflammatory biomarkerssudden cardiac death

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