Sudden cardiac death remains a significant clinical challenge in the management of heart failure with reduced ejection fraction (HFrEF), a condition where the heart’s main chamber cannot pump normally. While clinicians routinely use electrocardiograms (ECGs) to identify electrical delays, this strategy has inherent limitations for predicting sudden cardiac death. Consequently, the precise relationship between systemic inflammation, heart rhythm changes, and sudden death risk remains poorly understood.
To address this knowledge gap, a substudy of the VICTORIA trial recently published in JACC: Advances, evaluated 4,391 patients with HFrEF and recent decompensation who had both valid baseline biomarker data and core-lab-adjudicated QT intervals. The study investigated whether circulating inflammatory biomarkers (proteins, cytokines, and cellular markers in the blood that signal underlying systemic inflammation) could improve the prediction of sudden cardiac death risk beyond conventional ECG parameters.
The researchers found that the inflammation marker high-sensitivity C-reactive protein (hsCRP) was a strong, independent predictor of sudden cardiac death, contributing an additional 16% prognostic value beyond established clinical risk factors. Conversely, standard ECG metrics showed unexpected, paradoxical patterns though, likely related to overcorrection of the standard formulas for certain electrical timing differences. Crucially, the data indicates that inflammation drives sudden death through biological pathways entirely separate from standard electrical delays.
While these findings are still early and may not apply to all heart failure patients, this study identifies valuable avenues for future, real-world risk assessment in HFrEF. Ultimately, these insights highlight a promising therapeutic strategy, suggesting that targeted anti-inflammatory interventions could play a key role in preventing sudden cardiac death among vulnerable populations.
The CVC ECG Core Laboratory played a pivotal role in this study through their expert analysis and data contributions. Conducted on behalf of the VICTORIA Study Group, this research was led by Haran Yogasundaram, MD, and co-authored by CVC members Wendimagegn Alemayehu, PhD; Eric Ly, BHK; Tracy Temple, BScN, RN; Roopinder Sandhu, MD, MPH; Cynthia Westerhout, PhD; and Paul W. Armstrong, MD. Additional collaborators were Christopher deFilippi, MD and Christopher O’Connor, MD (Inova Heart and Vascular Institute) and Adriaan Voors, MD, PhD (University of Groningen).
