Unveiling the neural remodelling landscape in heart failure: A new frontier in cardiac arrhythmogenesis research

Heart failure (HF) is a clinical condition that is highly associated with malignant arrhythmias. In recent years, our understanding of HF has evolved to include multiple subtypes and non-cardiomyocyte contributions such as neural remodelling. The neural underpinnings of HF-related arrhythmias have gained a great interest. In this current issue, an interesting study entitled “Autonomic Neuro-cardiac Profile of Electrical, Structural and Neuronal Remodeling in Myocardial Infarction-induced Heart Failure” by Chin et al. [1] sheds light on remodelling within the intrinsic cardiac nervous system (ICNS) in a HF model with reduced ejection fraction post-myocardial infarction (MI).

In this paper, Chin et al. [1] use dual-innervated ex vivo Langendorff rabbit hearts as a model system, to assay the structural and functional alterations of the neural control of the failing heart post-MI. The paper begins by highlighting preclinical and clinical evidence that establishes a causal link between heart rate variability, baroreceptor reflex sensitivity, and fatal ventricular arrhythmias. This evidence tentatively suggests that impaired neuro-cardiac control could be a contributor to arrhythmogenesis in HF. The authors examined the neural network within the heart, specifically the intrinsic cardiac neurons and their ganglia, which regulate cardiac indices on a beat-to-beat basis. Previous work has mostly separately demonstrated either anatomical and functional remodelling of these ganglionic plexi during cardiac pathology without intact sympathetic and parasympathetic input, or in larger animal models [[2], [3], [4], [5]]. This corpus of work indicates a dynamic connection between neural control and cardiac function, and its disruption contributing to arrhythmia in HF or post-MI. Importantly, this paper uniquely combined whole-organ structural and functional approaches to identify ICNS remodelling of chronically infarcted rabbit hearts with increased arrhythmic susceptibility associated with hypersensitivity to sympathetic stimulation and blunted responses to parasympathetic stimulation.

This research marks a milestone by shedding light on neuronal remodelling in HF post-MI. The study identifies differential neuronal enlargement within the ICNS of rabbits in HF, echoing recent studies that highlight morphological changes in ganglia, particularly those with influence over infarcted ventricles [2]. Uniquely, this study's whole-organ approaches unveiled ICNS remodelling only documented in isolated cardiac regions. Additionally, the paper identifies a reduction in neuronal numbers in HF, potentially linked to prior observations of fewer cholinergic neurons within the ICNS post-MI. This reduction could contribute to central vagal attenuation, warranting further investigation into the underlying mechanisms.

Of particular significance is the study's revelation of absent remodelling in the right atrial ganglionic plexus: the region that dominates regulation of heart rate. The lack of neuronal remodelling in this region following MI highlights its neural isolation and protection from injury to ventricular apices. However, the study emphasizes the need for larger sample sizes and detailed phenotyping to validate and expand upon these findings. Chin et al. [1] posit the involvement of the ICNS in offering protection against central neuronal dysregulation during MI, hinting at the potential for targeted therapeutic interventions.

Thus, the paper marks a pioneering step toward understanding the intricate neural changes in the heart occurring in the context of HF. The study opens new avenues for exploring arrhythmogenesis and potential interventions in this critical realm of cardiovascular research. The study will also likely catalyze further investigations and advancements in our understanding of HF-related arrhythmias – especially in the involvement of local intra-cardiac sources of regulatory hormones and their interactions with central neural controllers.

Declaration of competing interest

No financial or personal relationships that may be perceived as influencing their work.