Neurometabolism and Ventricular Dyssynchrony in Patients With Heart Failure and Reduced Ejection Fraction

The brain coordinates the heart through the autonomic nervous system (ANS). Numerous mediator signals along the brain-heart axis interact with the neuronal-metabolic system in heart failure (HF). Disturbances in cardio-neural interactions influence the disease progression in patients with HF. The purpose of this study was to investigate the interactome between ANS-associated neurometabolism and ventricular dyssynchrony in patients with heart failure with reduced ejection fraction (HFrEF). Further, we studied the association of neurometabolism with major arrhythmic events (MAEs). A total of 197 patients with HFrEF who underwent gated single-photon emission computed tomography myocardial perfusion imaging and the brain 18F-fluorodeoxyglucose positron emission tomography/computed tomography were prospectively enrolled. Relationships between the brain metabolism and MAEs were assessed using Cox models and mediation analyses. Finally, metabolic central autonomic networks were constructed and statistically compared between patients with and without MAEs. In total, 35 (17.8%) patients experienced MAEs during a median follow-up of 3.1 years. In patients with HFrEF (age 58 years [IQR: 50-64 years], left ventricular ejection fraction: 20.0% [IQR: 15.0%-25.0%]), glucose hypometabolism in the insula, hippocampus, amygdala, cingulate gyrus, and caudate nucleus were independent predictors for MAEs (all P < 0.05). Cerebral hypometabolism was related to ventricular dyssynchrony, which was the predominant risk factor of MAEs. Additionally, patients who experienced MAEs presented hypoconnectivity in the metabolic central autonomic network compared with those without MAEs (P < 0.05). We found an interaction of the neuronal metabolic-ventricular dyssynchronization axis in HF, which might be related to MAEs. This new brain-heart axis could expand our understanding of the distinct pathomechanisms of HFrEF.