The horse cardiac transcriptome: Moving towards a molecular understanding of atrial fibrillation.
Authors: Haugaard Simon Libak, Nissen Sarah Dalgas, Schneider Mélodie Jil, Birk Jesper Bratz, Carstensen Helena, Hopster-Iversen Charlotte, Altıntaş Ali, Barrès Romain, Kjøbsted Rasmus, Wojtaszewski Jørgen F P, Herum Kate M, Jespersen Thomas, Buhl Rikke
Journal: Equine veterinary journal
Summary
# Editorial Summary Atrial fibrillation in horses often recurs after treatment, likely because the arrhythmia itself triggers lasting changes in heart muscle that perpetuate the condition; this research sought to understand the molecular basis of those changes by sequencing RNA from atrial and ventricular tissue in six horses with naturally occurring persistent AF and six healthy controls, then validating findings against a separate cohort with experimentally induced AF. Rather than the ion channel dysfunction seen in human AF, the equine atria showed marked upregulation of metabolic pathways (particularly fatty acid oxidation and glycolysis), fibrotic gene expression, and myofibrillar remodelling, alongside increased glycogen accumulation in the left atrium and maintained AMPK activity in the right atrium. Chamber-specific transcriptional signatures differed substantially across the four heart chambers, and the molecular profile of naturally occurring AF correlated well with tachypacing-induced AF, suggesting that metabolic remodelling represents a genuine disease consequence rather than an incidental finding. The practical implication is significant: therapeutically targeting atrial metabolic dysfunction and fibrosis—rather than focusing primarily on electrical disturbance—may offer more durable treatment outcomes and reduce recurrence rates in equine AF cases. This shift in thinking moves the field away from rhythm-only interventions towards addressing the underlying tissue changes that sustain the arrhythmia.
Read the full abstract on PubMed
Practical Takeaways
- •Persistent equine AF involves metabolic and structural remodeling rather than primary electrical changes, suggesting that targeting metabolic pathways and fibrosis may improve treatment outcomes beyond current electrical management approaches.
- •Understanding that AF-induced myocardial changes accumulate over 2-12 weeks reinforces the importance of early diagnosis and intervention to prevent irreversible transcriptional changes.
- •Future AF therapies in horses should consider metabolic modulation (fatty acid and glycolytic pathways) and anti-fibrotic strategies alongside conventional antiarrhythmic treatments.
Key Findings
- •Horse cardiac transcriptome shows distinct molecular identities across four chambers with ion channel expression largely similar to humans except for ventricular repolarising potassium channels.
- •Persistent AF was associated with significant upregulation of metabolic, fibrotic and myofibrillar pathways in atria rather than ion channel remodeling.
- •Metabolic remodeling in AF included upregulation of fatty acid and glycolytic pathways, increased left atrial glycogen content, and preserved AMPK activity in right atrium.
- •Transcriptomic profiles of naturally occurring persistent AF correlated well with tachypacing-induced AF, suggesting common molecular mechanisms.