Inflammatory Biomarkers and ECG Repolarization Metrics

BACKGROUND: Sudden cardiac death (SCD) is a leading cause of mortality in heart failure with reduced ejection fraction (HFrEF). Although prolonged corrected QT (QTc) interval is associated with inflammation and SCD, the association between inflammatory biomarkers, electrocardiogram (ECG) repolarization metrics and SCD remains unclear in HFrEF. OBJECTIVES: The objective of the study was to assess the relationship between ECG repolarization intervals, inflammation, and SCD in HFrEF. METHODS: We evaluated 4,391 patients with HFrEF and recent decompensation in the VICTORIA trial who had core lab-adjudicated ECGs and baseline biomarkers. We assessed whether interleukin-6, growth differentiation factor-15, and high-sensitivity C-reactive protein (hsCRP) were associated with SCD and an association between QTc interval prolongation and SCD. JTc interval was also included and defined as QTc minus the QRS duration. Cox proportional hazards and linear regression models were used. RESULTS: JTc interval (HR: 0.97 per 10 ms; 95% CI: 0.94-1.00; P = 0.043), but not QTc interval, was associated with SCD. All 3 biomarkers were associated with increased SCD risk in univariable analysis, but only hsCRP remained significant in multivariable models (HR: 1.20 per doubling; P < 0.001). Growth differentiation factor-15 was independently associated with QTc and JTc intervals. When each inflammatory biomarker was added separately to the covariate-adjusted JTc interval model, hsCRP provided the greatest prognostic value (16% new information; P < 0.001). CONCLUSIONS: Inflammatory biomarkers, particularly hsCRP, are independently associated with SCD in patients with HFrEF and provide prognostic value beyond ECG parameters. These findings suggest that inflammation likely contributes to SCD risk through pathways distinct from repolarization prolongation. Biomarkers such as hsCRP may be useful to incorporate into risk stratification.