Thyroid Dysfunction in Heart Failure and Cardiovascular Outcomes

BACKGROUND: The effects of thyroid dysfunction in patients with preexisting heart failure have not been adequately studied. We examined the prevalence of thyroid dysfunction and associations with cardiovascular outcomes in a large, prospective cohort of outpatients with preexisting heart failure. METHODS AND RESULTS: We examined associations between thyroid dysfunction and New York Heart Association class, atrial fibrillation, and a composite end point of ventricular assist device placement, heart transplantation, or death in 1365 participants with heart failure enrolled in the Penn Heart Failure Study. Mean age was 57 years, 35% were women, and the majority had New York Heart Association class II (45%) or III (32%) symptoms. More severe heart failure was associated with higher thyroid-stimulating hormone (TSH), higher free thyroxine (FT4), and lower total triiodothyronine (TT3) concentrations (P< 0.001 all models). Atrial fibrillation was positively associated with higher levels of FT4 alone (P= 0.01 all models). There were 462 composite end points over a median 4.2 years of follow-up. In adjusted models, compared with euthyroidism, subclinical hypothyroidism (TSH 4.51-19.99 mIU/L with normal FT4) was associated with an increased risk of the composite end point overall (hazard ratio, 1.82; 95% CI, 1.27-2.61; P= 0.001) and in the subgroup with TSH = 7.00 mIU/L (hazard ratio, 3.25; 95% CI, 1.96-5.39; P< 0.001), but not in the subgroup with TSH 4.51-6.99 mIU/L (hazard ratio, 1.26; 95% CI, 0.78-2.06; P= 0.34). Isolated low T3 was also associated with the composite end point (hazard ratio, 2.12; 95% CI, 1.65-2.72; P< 0.001). CONCLUSIONS: In patients with preexisting heart failure, subclinical hypothyroidism with TSH = 7 mIU/L and isolated low T3 levels are associated with poor prognosis. Clinical trials are needed to explore therapeutic effects of T4 and T3 administration in heart failure.