title: Long-term L-Triiodothyronine (T3) treatment in stable systolic heart failure patients: a randomised, double-blind, cross-over, placebo-controlled intervention study.
abstract: BACKGROUND
  Chronic heart failure (HF) is characterized by reduced serum T3 levels and increased activity of the T3 degrading enzyme deiodinase D3. This may result in an intracellular composition of the cardiomyocyte mimicking that of hypothyroidism. Short-term T3-administration to systolic HF patients might be beneficial.
  
  
  OBJECTIVE
  Does long-term treatment with T3 have a beneficial effect on cardiac function and neurohormonal activation in chronic systolic HF patients with serum T3 levels below 1·6 nmol/l?
  
  
  METHODS
  A randomized, double-blind, cross-over, placebo-controlled intervention study with oral T3 treatment twice daily for 3 months. The T3 dose was uptitrated to a final dose avoiding reduced TSH levels.
  
  
  METHODS
  Left-ventricular ejection fraction (LVEF).
  
  
  METHODS
  Cardiac imaging was performed using multiple gated tomographic radionuclide ventriculography (MUGA-SPECT). Neurohormonal stimulation was evaluated by plasma measurements of natriuretic peptides, aldosterone, renin, noradrenalin and copeptin levels. The patients were monitored for potential cardiac arrhythmias at the start of each treatment period.
  
  
  RESULTS
  Thirteen patients completed the protocol. Mean LVEF was 43%, range: 37-52 and serum T3 levels 1·4 nmol/l (0·9-1·6). The T3 dose was 20 μg per day (10-40). TSH levels did not change between groups, whereas serum T3 levels increased in the active arm. Cardiac function as measured by LVEF, end-diastolic and end-systolic volumes and cardiac output did not change during T3-treatment and neither did the neurohormonal profile. There were no side-effects in terms of cardiac arrhythmias and no change in resting heart rate.
  
  
  CONCLUSIONS
  This study does not support the hypothesis that oral T3 treatment might be beneficial to patients with chronic, stable systolic HF with a modest degree of reduced LVEF and low-normal serum T3 concentrations. The study included both functional studies of heart contractility as well as measures of the neurohormonal activation.
authors.affiliation: Department of Medicine, Endocrine Unit, Herlev University Hospital, Herlev, Denmark.
authors.forename: Pernille
authors.initials: P
authors.lastname: Holmager
authors.affiliation: Department of Medicine, Endocrine Unit, Herlev University Hospital, Herlev, Denmark.
authors.forename: Ulla
authors.initials: U
authors.lastname: Schmidt
authors.affiliation: Department of Medicine, Endocrine Unit, Herlev University Hospital, Herlev, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Mark
authors.affiliation: Clinical Physiology and Nuclear Medicine, Glostrup University Hospital, Glostrup, Denmark.
authors.forename: Ulrik
authors.initials: U
authors.lastname: Andersen
authors.affiliation: Department of Cardiology, Frederiksberg Hospital, Frederiksberg, Denmark.
authors.forename: Helena
authors.initials: H
authors.lastname: Dominguez
authors.affiliation: Department of Cardiology, Frederiksberg Hospital, Frederiksberg, Denmark.
authors.forename: Ilan
authors.initials: I
authors.lastname: Raymond
authors.affiliation: Clinical Physiology and Nuclear Medicine, Herlev University Hospital, Herlev, Denmark.
authors.forename: Bo
authors.initials: B
authors.lastname: Zerahn
authors.affiliation: Department of Medicine, Endocrine Unit, Herlev University Hospital, Herlev, Denmark.
authors.forename: Birte
authors.initials: B
authors.lastname: Nygaard
authors.affiliation: Department of Medicine, Endocrine Unit, Herlev University Hospital, Herlev, Denmark.|Faculty of Health Sciences, Copenhagen University, Denmark.
authors.forename: Caroline
authors.initials: C
authors.lastname: Kistorp
authors.affiliation: Department of Medicine, Endocrine Unit, Herlev University Hospital, Herlev, Denmark.|Faculty of Health Sciences, Copenhagen University, Denmark.
authors.forename: Jens
authors.initials: J
authors.lastname: Faber
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001145:Arrhythmias, Cardiac / Q000188:drug therapy; D004311:Double-Blind Method; D005260:Female; D054143:Heart Failure, Systolic / Q000188:drug therapy*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D014284:Triiodothyronine / Q000627:therapeutic use*
chemical_list: D014284:Triiodothyronine