A study published in The Journal of Physiology has revealed that a rare but life-threatening heart condition may not be solely a cardiac disease, but also involves the nervous system—opening the door to new treatment strategies.
The research, led by scientists at the University of Oxford from the Paterson/Li group in DPAG alongside international collaborators, focuses on catecholaminergic polymorphic ventricular tachycardia (CPVT), a genetic disorder that can trigger fatal heart rhythm disturbances, particularly in young people with otherwise healthy hearts.
Traditionally, CPVT has been understood as a disease of heart muscle cells, known as cardiomyocytes. Treatments have therefore largely targeted the heart itself. However, the new study challenges this long-held assumption by showing that the sympathetic nervous system plays a central role in triggering dangerous arrhythmias.
To investigate this, researchers developed advanced laboratory models using human stem cells from patients with CPVT and controls. These were engineered into both heart cells and sympathetic nerve cells in 2D and 3D organoid co-cultures, allowing scientists to recreate and study their interactions in unprecedented detail. The team found that nerve cells derived from CPVT patients were abnormally excitable and showed disrupted calcium signalling—key processes involved in controlling heart rhythm. Crucially, when these diseased nerve cells were combined with otherwise healthy heart cells, they were able to directly trigger arrhythmias.
These findings suggest CPVT should be reclassified as a “neuro-cardiac” disorder, rather than a purely cardiac one. By identifying dysfunction in the nervous system as a driver of disease, the research helps explain why treatments that interrupt nerve signals to the heart, such as cardiac sympathetic denervation surgery, can be effective in some patients.
The study also used advanced techniques including single-cell RNA sequencing to uncover disrupted neurotransmitter pathways in affected nerve cells. This allowed researchers to identify potential molecular targets for new therapies aimed at regulating nerve activity.
The implications of the research are significant. By shifting the focus from the heart alone to the interaction between the heart and nervous system, it opens up new possibilities for treatment, including neuromodulation therapies that specifically target nerve function. Such approaches could complement or even improve upon existing treatments, which include medications like beta-blockers and invasive procedures. In the long term, this could lead to more precise and effective interventions for patients at risk of sudden cardiac death.
This research was supported by the British Heart Foundation, Chinese Academy of Medical Sciences doctoral programme (Oxford) and a Leducq Foundation International Network of Excellence award. It also involved partnerships with industry and academic centres from the USA, China and New Zealand highlighting the collaborative nature of modern biomedical research.
While further studies are needed to translate these findings into clinical treatments, the research represents a major step forward in understanding how the heart and nervous system interact in disease. More broadly, it reflects a growing trend in physiology: recognising that complex conditions often arise from interactions between multiple body systems, rather than a single organ alone. As the authors conclude, redefining CPVT as a neuro-cardiac disorder could reshape both scientific understanding and patient care, potentially saving lives.