Abstract
OBJECTIVES: The aim of this study was to investigate whether patients with systolic heart failure (HF) and abnormal thyroid function are at increased risk for death. BACKGROUND: Thyroid hormone homeostasis is vital to the optimal functioning of the cardiovascular system, but an independent prognostic effect of thyroid abnormalities in patients with HF has not been established. METHODS: In SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial), which randomized patients with ischemic or nonischemic HF to placebo or amiodarone or implantable cardioverter-defibrillator therapy, thyroid-stimulating hormone (TSH) was measured at baseline and at 6-month intervals throughout the 5-year study. RESULTS: Of 2,225 patients, the majority (87%) had normal TSH levels (0.3 to 5.0 μU/ml) at baseline, 12% had values suggestive of hypothyroidism, and 1% had values consistent with hyperthyroidism. Compared with euthyroid patients, those hypothyroid at baseline were older and included more women and Caucasians (all p values <0.05). Over the median follow-up period of 45.5 months, among patients euthyroid at baseline, 89 developed abnormally low TSH levels, and 341 developed abnormally high values. Patients randomized to amiodarone (median dose 300 mg) had an elevated risk for developing abnormal TSH levels compared with implantable cardioverter-defibrillator therapy or placebo (p < 0.0001). Patients with baseline or new-onset abnormal thyroid function had a higher mortality than those with normal thyroid function, even after controlling for other known mortality predictors (hazard ratio: 1.58; 95% confidence interval: 1.29 to 1.94; p < 0.0001 for hypothyroid; hazard ratio: 1.85; 95% confidence interval: 1.21 to 2.83; p = 0.0048 for hyperthyroid). Implantable cardioverter-defibrillator benefit did not vary with thyroid function. CONCLUSIONS: Abnormal thyroid function in patients with symptomatic HF and ejection fractions ≤35% is associated with significantly increased risk for death, even after controlling for known mortality predictors.