Incremental Prognostic Value of Hippocampal Metabolic Activity for Sudden Cardiac Death in Patients With Heart Failure With Reduced Ejection Fraction

Abstract

Background: Hippocampal injury is linked to cognitive impairment and cardiac events in patients with heart failure with reduced ejection fraction. However, the predictive value of hippocampal metabolic activity (HMA) for sudden cardiac death (SCD) and the underlying mechanisms remain unclear. This study aimed to evaluate the independent and incremental predictive value of HMA over myocardial scar for SCD-related events in patients with heart failure with reduced ejection fraction and to explore the potential mechanism.

Methods: This prospective study included 270 patients with heart failure with reduced ejection fraction undergoing gated single-photon emission computed tomography and brain/cardiac ¹⁸F-fluorodeoxyglucose positron emission tomography. HMA and myocardial scarring were evaluated. The independent and incremental predictive values of HMA for SCD-related events were explored via the log-rank test, Cox model, C statistic, global χ² test, and net reclassification improvement. Mediation analysis was used to examine the direct and indirect effects of HMA on SCD-related events by setting left ventricular electrical instability as a mediator.

Results: Overall, 34 (12.6%; median follow-up, 4.3 years) patients experienced SCD-related events. Functional myocardial scarring and HMA were strongly associated with SCD-related events (all P<0.01). HMA resulted in significant incremental improvements in prognostic value (χ² increased by 6.598), discrimination (C statistics of 0.760 versus 0.715), and reclassification (net reclassification improvement, 25.6%) for SCD-related events. HMA was associated with SCD-related events via corrected QT interval.

Conclusions: Functional myocardial scarring and HMA had strong independent prognostic value in the risk stratification of SCD-related events in patients with heart failure with reduced ejection fraction. Additionally, HMA had incremental prognostic value based on myocardial scarring. HMA impairment may induce SCD-related events, partly mediated by corrected QT interval.

Keywords: 18F‐FDG PET/CT; heart failure; hippocampus; myocardial scarring; sudden cardiac death.