Levothyroxine fails to improve cardiac function in mild subclinical hypothyroidism

Treatment with levothyroxine appears to have no significant impact on systolic and diastolic heart function in older adults with mild subclinical hypothyroidism as compared with placebo, results of a study have shown.

Swiss participants aged ≥65 years with subclinical hypothyroidism (thyroid-stimulating hormone [TSH] 4.60-19.99 mIU/L; free thyroxine level within reference range) who participated in a trial nested within the TRUST trial were randomized to either levothyroxine (starting dose of 50 µg daily) to achieve TSH normalization or placebo.

The primary outcomes were left ventricular ejection fraction for systolic function and the ratio between mitral peak velocity of early filling to early diastolic mitral annular velocity (E/e’ ratio) for diastolic function. Secondary outcomes were the following: e’ lateral/septal, left atrial volume index, and systolic pulmonary artery pressure.

At the end of the trial, 185 participants (mean age, 74.1 years; 47 percent women) underwent echocardiography. The mean TSH decreased from 6.35 to 3.55 mIU/L in patients taking levothyroxine (n=96) but remained elevated at 5.29 mIU/L in those who received placebo (n=89) after a median treatment duration of 18.4 months.

No significant adjusted between-group differences were observed for the mean left ventricular ejection fraction (62.7 percent vs 62.5 percent; difference, 0.4 percent, 95 percent confidence interval [CI], –1.8 percent to 2.5 percent; p=0.72) and the E/e’ ratio (10.6 vs 10.1; difference, 0.4, 95 percent CI, –0.7 to 1.4; p=0.47).

There were also no differences seen for the secondary diastolic function parameters or for interaction according to sex, baseline TSH, pre-existing heart failure, and treatment duration (p>0.05).

“Subclinical hypothyroidism has been associated with heart failure,” the investigators noted.