Thyrotropin Directly Affects Cardiac Electrophysiology and Is Associated With AF Prevalence.

Summary

In a retrospective cohort of 2,311 subclinical hypothyroidism patients, higher TSH levels correlated with greater AF prevalence. Complementary experiments showed TSH directly modulates cardiomyocyte ion channel expression and electrophysiology via TSHR/cAMP/PKA, increasing automaticity and altering action potentials.

Key Findings

• Among 2,311 SH patients, AF prevalence increased with higher TSH (32.1% at 4–10 mU/L vs 44.6% at >10 mU/L).
• TSH altered cardiomyocyte ion channel mRNA/protein expression and increased automaticity in HL-1 and neonatal rat cardiomyocytes.
• Mechanistic pathway implicated TSHR/cAMP/PKA signaling with action potential remodeling confirmed by patch-clamp, optical mapping, and modeling.

Clinical Implications

Consider heightened AF surveillance in subclinical hypothyroidism, especially with TSH >10 mU/L. While causality needs trials, findings support integrating TSH levels into arrhythmia risk stratification and motivate studies of TSH-lowering strategies on AF outcomes.

Limitations

• Retrospective design with potential residual confounding in the clinical association.
• Translational gap from in vitro/rodent cardiomyocytes to human myocardial tissue-level effects.

Future Directions

Prospective studies to validate AF risk across TSH strata and interventional trials testing whether TSH lowering modifies AF incidence/recurrence; human tissue studies to map ion channel remodeling under TSH exposure.