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Thyroid hormone replacement therapy attenuates atrial remodeling and reduces atrial fibrillation inducibility in a rat myocardial infarction-heart failure model

Zhang, Youhua; Dedkov, Eduard I; Lee, Bianca; Li, Ying; Pun, Khusbu; Gerdes, A Martin
BACKGROUND:Heart failure (HF) is associated with increased atrial fibrillation (AF) risk. Accumulating evidence suggests the presence of myocardial tissue hypothyroidism in HF, which may contribute to HF development. In a recent report we demonstrated that hypothyroidism, like hyperthyroidism, leads to increased AF inducibility. The present study was designed to investigate the effect of thyroid hormone (TH) replacement therapy on AF arrhythmogenesis in HF. METHODS AND RESULTS/RESULTS:Myocardial infarction (MI) was produced in rats by means of coronary artery ligation. Rats with large MIs (>40%) were randomized into L-thyroxine (T4; n = 14) and placebo (n = 15) groups 2 weeks after MI. Rats received 3.3 mg T4 (in 60-day release form) or placebo pellets for 2 months. Compared with the placebo, T4 treatment improved cardiac function and decreased left ventricular internal diameters as well as left atrial diameter. T4 treatment attenuated atrial effective refractory period prolongation (45 ± 1.5 ms in placebo group vs 37 ± 1.6 ms in T4 group; P < .01) and reduced AF inducibility (AF/atrial flutter/tachycardia were inducible in 11/15 rats [73%] in the placebo- vs 4/14 rats [29%] in the T4-treated group; P < .05). Arrhythmia reduction was associated with decreased atrial fibrosis but was not associated with connexin 43 changes. CONCLUSIONS:To our knowledge this is the first study demonstrating that TH replacement therapy in HF attenuates atrial remodeling and reduces AF inducibility after MI-HF. Clinical studies are needed to confirm such benefits in human patients.
PMID: 25305503
ISSN: 1532-8414
CID: 5268072