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Randomized Controlled Trial
. 2013 Feb;1(1):48-55.
doi: 10.1016/j.jchf.2012.10.004.

Thyroid function in heart failure and impact on mortality

Judith E Mitchell, Anne S Hellkamp, Daniel B Mark, Jill Anderson, George W Johnson, Jeanne E Poole, Kerry L Lee, Gust H Bardy
Randomized Controlled Trial

Thyroid function in heart failure and impact on mortality

Judith E Mitchell et al. JACC Heart Fail. 2013 Feb.

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.

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Figures

Figure 1
Figure 1. Distribution of Baseline TSH Values
Intervals on the right side of the graph include a wider range of values due to sparseness of the data. Very low thyroid-stimulating hormone (TSH) values include hypothyroid patients on thyroid replacement therapy as well as true hyperthyroid patients.
Figure 2
Figure 2. Median TSH Values Over Time
(A) All patients and by randomized treatment. (B) By New York Heart Association (NYHA) functional class and heart failure etiology subgroups. ICD = implantable cardioverter-defibrillator; TSH = thyroid-stimulating hormone.
Figure 3
Figure 3. Distribution of Thyroid Function Groups Over Follow-Up
Abnormal thyroid groups at each point include patients in those groups at baseline as well as new-onset patients whose onset occurred before the end of that year. (A) All patients. (B) By randomized treatment. ICD = implantable cardioverter-defibrillator.
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