Low systemic levels of free triiodothyronine (fT3) may be associated with adverse cardiovascular functionality and prognostic outcomes in subjects with cardiovascular disease.[1-4]
Low T3 syndrome is a type of non-thyroidal illness (NTI) where impaired hepatic deiodinase activity results in inhibition of peripheral thyroxine (T4) to triiodothyronine (T3) conversion, despite initially normal thyroid hormone secretion. It can progress in severity to dysregulation of thyroid hormone metabolism and poor peripheral tissue response.[2,5]
The presence of low T3 syndrome in several types of cardiovascular disease, including acute myocardial infarction, heart failure and chronic heart disease, is thought to be associated with the genomic and non-genomic roles that thyroid hormones play in the maintenance of cardiac and vascular health.[1-3,5]
Specific functions that fT3 is involved in are cardiac contractility, output and heart rate, vascular and coronary artery resistance, and cardiac after-load. These are via mechanisms including regulation of calcium reuptake, modulation of mitochondrial function, thermogenesis and haemodynamic effects.[1,2,6]
Several recent studies have explored the diagnostic significance of NTI syndrome (NTIS) and T3 in patients with cardiovascular disease.[1,3,4]
Wang et al investigated the prevalence and prognostic value of NTIS in patients with cardiovascular disease in a systemic review and meta-analysis. In an assessment of 41 studies, a pooled random-effect meta-analysis and hazard ratio analysis was performed for all-cause mortality, cardiac mortality and major adverse cardiovascular events (MACE).
The prevalence of NTIS in cardiovascular patients was 21.7% (95% CI 18.4-25.3%), with a sub-group assessment observing that NTIS was present in 24.5% of subjects with heart failure, 18.9% in acute myocardial infarction (MI) and 17.1% in acute coronary syndrome.
The study also observed an independent association between NTIS and increased risk of all-cause mortality (HR=2.52, 95% CI 1.87-3.40, P<0.001) and cardiac mortality (HR=2.06, 95% CI 1.58-2.69, P<0.001), and that NTIS was an independent predictor of MACE in cardiovascular patients (HR=1.73, 95% CI 1.32-2.26, P<0.001).
A separate retrospective study aimed to determine the clinical predictive value of T3 in patients hospitalised for acute heart failure. In 137 patients, without thyroid disease, levels of both total and fT3 were tested on admission and assessed against several clinical outcomes.
Low levels of fT3 correlated with an increased number of days in hospital (median 11 v 7 days p<0.001), higher rates of intensive care unit admission (31.8% v 16.9%, p 0.047) and a trend towards increased invasive mechanical ventilation required (9% v 1.4% p 0.056). The authors concluded that low T3 was predictive of worse clinical patient outcomes in acute heart failure.
Another study also found that fT3 was a useful prognostic tool in subjects with acute decompensated heart failure (ADHF). In an analysis of 270 patients hospitalised for ADHF between 2007-2012, levels of TSH, fT3 and fT4 were measured 48 hours following admission.
fT3 was found to be a more accurate prognostic marker than TSH and fT4, with the receiver operating characteristic (ROC) curve analysis demonstrating it had the most favourable performance (area under ROC curve 0.791, sensitivity 85%, specificity 72%). Other findings were that low fT3 levels were independently associated with higher in-hospital mortality (OR 14.4) and probability of 1-year total death compared with patients with normal fT3.
These studies indicate that low fT3 levels are associated with poorer outcomes in patients with cardiovascular disease and may be a useful risk analysis tool in this population. Further study is required to confirm the prevalence and diagnostic specifics of thyroid hormones and fT3 to improve clinical outcomes in cardiovascular patient groups.
- Okayama D, Minami Y, Kataoka S, et al. Thyroid function on admission and outcome in patients hospitalized for acute decompensated heart failure. J Cardiol 2015;66:205-211. [Full Text]
- Dan GA. Thyroid hormones and the heart. Heart Fail Rev 2016;21:357-359. [Full Text]
- Rothberger GD, Gadhvi S, Michelakis N, et al. Usefulness of serum triiodothyronine (T3) to predict outcomes in patients hospitalized with acute heart failure. Am J Cardiol 2016: S0002-9149(16)31819-7. [Abstract]
- Wang B, Lui S, Yao Q, et al. Non-thyroidal illness syndrome in patients with cardiovascular diseases: a systematic review and meta-analysis. Int J Cardiol 2017;226:1-10. [Full Text]
- Mancini A, Di Segni C, Raimondo S, et al. Thyroid hormones, oxidative stress and inflammation. Mediators of Inflammation 2016;2016:article ID 6757154. [Full Text]
- Kishi T. Free triiodothyronine, not thyroid stimulating hormone, should be focused on for risk stratification in acute decompensated heart failure. J Cardiol 2015;66:201-202. [Full Text]