Cover Image

Thyrotropin directly affects cardiac electrophysiology and is associated with AF prevalence

BACKGROUND: - Although hyperthyroidism is known to increase the risk of atrial fibrillation (AF), subclinical hypothyroidism (SH) is an often-underreported condition characterized by elevated thyroid-stimulating hormone (TSH) levels and normal free triiodothyronine/free thyroxine (fT3/fT4) levels. T...

Full description

Saved in:
Bibliographic Details
Main Authors: Rahm, Ann-Kathrin (Author) , Wunsch, Maximilian (Author) , Seibold, Dominik (Author) , Kramp, Xenia (Author) , Schöffel, Axel (Author) , Syren, Pascal (Author) , Rivinius, Rasmus (Author) , Mages, Christine (Author) , Pfeiffer, Julia (Author) , Gampp, Heike (Author) , Caspari, Teresa (Author) , Wen, Xin (Author) , Hund, Hauke (Author) , Akın, Ibrahim (Author) , Zhou, Xiao-Bo (Author) , Fan, Xuehui (Author) , Meng, Zenghui (Author) , Yan, Chen (Author) , Li, Yingrui (Author) , Sticht, Carsten (Author) , Ullrich, Nina D. (Author) , Kender, Zoltán (Author) , Heijman, Jordi (Author) , Frey, Norbert (Author) , Thomas, Dierk (Author) , Lugenbiel, Patrick (Author)
Format: Article (Journal)
Language:English
Published: December 2025
In: Circulation. Arrhythmia and electrophysiology
Year: 2025, Volume: 18, Issue: 12, Pages: ?
ISSN:1941-3084
DOI:10.1161/CIRCEP.125.013775
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1161/CIRCEP.125.013775
Verlag, lizenzpflichtig, Volltext: https://www.ahajournals.org/doi/10.1161/CIRCEP.125.013775
Get full text
Author Notes:Ann-Kathrin Rahm, Maximilian N. Wunsch, Dominik Seibold, Xenia C. Kramp, Axel Schöffel, Pascal Syren, Rasmus Rivinius, Christine Mages, Julia Pfeiffer, Heike Gampp, Teresa Caspari, Xin Wen, Hauke Hund, Ibrahim Akin, Xiaobo Zhou, Xuehui Fan, Zenghui Meng, Chen Yan, Yingrui Li, Carsten Sticht, Nina D. Ullrich, Zoltan Kender, Jordi Heijman, Norbert Frey, Dierk Thomas, Patrick Lugenbiel
Description
Summary:BACKGROUND: - Although hyperthyroidism is known to increase the risk of atrial fibrillation (AF), subclinical hypothyroidism (SH) is an often-underreported condition characterized by elevated thyroid-stimulating hormone (TSH) levels and normal free triiodothyronine/free thyroxine (fT3/fT4) levels. This study aimed to clarify the association between SH and AF and to identify potential direct electrophysiological effects of TSH. - METHODS: - We retrospectively included 2311 patients diagnosed with SH between 2007 and 2020 who had an ECG within 7 days of diagnosis. Logistic regression analysis identified factors independently associated with AF in patients with SH. Effects of different TSH doses on ion channel mRNA and protein levels were analyzed in HL-1 and neonatal rat cardiomyocytes. Video analysis with MYOCYTER, patch-clamp, optical mapping, and computational modeling were used to study automaticity and action potential characteristics after TSH application. - RESULTS: - AF was documented more often with higher TSH levels (4-10 mU/L TSH: 32.1% versus >10 mU/L TSH: 44.6%; P<0.0001). Multivariable regression identified elevated TSH levels as an independent risk factor for AF. TSHR (TSH receptors) were confirmed in cardiomyocytes, and exposure to TSH led to changes in ion channel expression levels that promoted action potential prolongation. TSH also increased the beating rate in neonatal rat cardiomyocytes. We identified a TSHR-mediated cascade involving cAMP, PKA (protein kinase A), and CREB (cAMP-responsive element-binding protein) as a potential regulator of cardiomyocyte electrical remodeling leading to the proarrhythmic effects that promote the development of AF. - CONCLUSIONS: - Individuals with SH exhibit an increased prevalence of AF, which is likely in part due to a direct effect of TSH on ion channel expression in cardiomyocytes via the TSHR/cAMP/PKA pathway.
Item Description:Online veröffentlicht: 3. Dezember 2025
Gesehen am 12.02.2026
Physical Description:Online Resource
ISSN:1941-3084
DOI:10.1161/CIRCEP.125.013775

Similar Items