An arrhythmogenic metabolite in atrial fibrillation

J Transl Med. 2023 Aug 24;21(1):566. doi: 10.1186/s12967-023-04420-z.


Background: Long-chain acyl-carnitines (ACs) are potential arrhythmogenic metabolites. Their role in atrial fibrillation (AF) remains incompletely understood. Using a systems medicine approach, we assessed the contribution of C18:1AC to AF by analysing its in vitro effects on cardiac electrophysiology and metabolism, and translated our findings into the human setting.

Methods and results: Human iPSC-derived engineered heart tissue was exposed to C18:1AC. A biphasic effect on contractile force was observed: short exposure enhanced contractile force, but elicited spontaneous contractions and impaired Ca2+ handling. Continuous exposure provoked an impairment of contractile force. In human atrial mitochondria from AF individuals, C18:1AC inhibited respiration. In a population-based cohort as well as a cohort of patients, high C18:1AC serum concentrations were associated with the incidence and prevalence of AF.

Conclusion: Our data provide evidence for an arrhythmogenic potential of the metabolite C18:1AC. The metabolite interferes with mitochondrial metabolism, thereby contributing to contractile dysfunction and shows predictive potential as novel circulating biomarker for risk of AF.

Trial registration: NCT02417311.

Keywords: Acyl-carnitine; Atrial fibrillation; Engineered heart tissue; Metabolites; Translational medicine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Atrial Fibrillation*
  • Heart Atria
  • Humans
  • Mitochondria
  • Muscle Contraction
  • Respiration

Associated data