Association Between 3-Iodothyronamine (T1am) Concentrations and Left Ventricular Function in Chronic Heart Failure

J Clin Endocrinol Metab. 2019 Apr 1;104(4):1232-1238. doi: 10.1210/jc.2018-01466.

Abstract

Context: Thyroid hormone metabolites might affect the heart. The endogenous aminergic metabolite 3-iodothyronamine (T1am) reduces left ventricular ejection fraction (LVEF) in rodents.

Objective: To investigate concentration of T1am and its association with LVEF and biomarkers of heart function in patients with chronic heart failure (CHF) without thyroid disease, including patients with cardiac cachexia (nonedematous weight loss >5% over 6 months).

Methods: Cross-sectional study. CHF was characterized by LVEF <45% and symptoms. Three groups were included (n = 19 in each group, matched on age, sex, and kidney function): patients with cachexia (CAC), patients without (non-CAC), and control (C) patients with prior myocardial infarction and LVEF >45%. T1am was measured by a monoclonal antibody-based chemiluminescence immunoassay. N-amino terminal pro-BNP (NT-proBNP) concentrations were also analyzed.

Results: Mean (SD) LVEF: CAC, 32 ± 9%; non-CAC, 38 ± 8%; and C, 60 ± 8% (P < 0.0001). TSH, T4, and T3 levels did not differ between groups and did not correlate to T1am. Serum T1am (nmol/L) concentrations were higher in CHF: CAC (mean ± SD), 12.4 ± 6.6; non-CAC, 9.1 ± 5; and C, 7.3 ± 2.9. A negative association between T1am and LVEF was present after adjusting for sex, age, T3, and estimated glomerular filtration rate (P = 0.03). Further, serum T1am levels tended to be associated with NT-proBNP (P = 0.053).

Conclusion: Serum T1am levels were increased in patients with CHF and numerically highest (although nonsignificant) in patients with cardiac cachexia. Increasing T1am concentrations were independently associated with reduced LVEF, suggesting a direct effect on the human heart.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Cachexia / blood*
  • Cachexia / etiology
  • Chronic Disease
  • Cohort Studies
  • Cross-Sectional Studies
  • Female
  • Heart / physiopathology*
  • Heart Failure / blood
  • Heart Failure / complications
  • Heart Failure / physiopathology*
  • Humans
  • Male
  • Thyronines / blood*
  • Ventricular Function, Left / physiology*

Substances

  • 3-iodothyronamine
  • Biomarkers
  • Thyronines