ArticleHeart rhythm2025
Poincaré plot analysis of electrocardiogram uncovers beneficial effects of omaveloxolone in a mouse model of Friedreich's ataxia.
Article in Heart rhythm, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Dose-dependent exercise promotes the transition from atrial protection to arrhythmogenic vulnerability: the intermediary role of calcium handling instability in substrate remodeling.Frontiers in physiology · 2026Article
- Omaveloxolone, But Not Dimethyl Fumarate, Improves Cardiac Function in Friedreich's Ataxia Mice With Severe Cardiomyopathy.Journal of the American Heart Association · 2025Article
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7 authors.
Funding
Abstract
backgroundFriedreich's ataxia (FA) is a rare inherited neuromuscular disorder whereby most patients die of lethal cardiomyopathy and arrhythmias. Mechanisms leading to arrhythmic events in patients with FA are poorly understood.
objectiveThis study aimed to examine cardiac electrical signal propagation in a mouse model of FA with severe cardiomyopathy and to evaluate effects of omaveloxolone (OMAV), the first Food and Drug Administration-approved therapy.
methodsCardiac-specific MCK-Cre frataxin knockout (FXN-cKO) mice were used to mimic FA cardiomyopathy. In vivo surface electrocardiogram (ECG) recordings, Western blotting, quantitative real-time polymerase chain reaction analysis, and histochemistry were performed.
resultsCharacteristics like long QT syndrome, interatrial block, and ST-segment abnormalities in patients with FA were identified in FXN-cKO mice. FXN-cKO mice exhibited sexual dimorphism in electrical signal propagation and cardiac structural integrity. Untreated FA males showed increased ventricular propagation intervals, whereas females exhibited delayed atrial propagation. OMAV showed no significant therapeutic effect on average ECG time intervals but improved chamber-specific waveforms when aggregated frequency distributions were analyzed. The J wave was absent in FXN-cKO male mice but reappeared with OMAV treatment. Poincaré plots revealed disparate idiopathic arrhythmias with multi-clustering events in individual mice with high incidence in FXN-cKO males. OMAV treatment reduced multi-clustering events to a single cluster; however, autonomic nervous system dysfunction still remained.
conclusionOur study revealed significant electrical propagation disturbances and sexual dimorphism in FXN-cKO mice with severe cardiomyopathy. Poincaré plots identified irregularities in heart rhythm and autonomic nervous system dysfunction. OMAV improved heart function by stabilizing early repolarization and reducing disparate arrhythmias. This work stresses sex-specific ECG interpretations and alternative mathematical approaches for drug testing in FA models.
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