Efficacy and Safety of Triiodothyronine Treatment in Cardiac Surgery or Cardiovascular Diseases: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background: Low levels of the active thyroid hormone triiodothyronine (T3) in cardiac patients are associated with worse outcomes. The aim of this analysis was to assess if T3 treatment is beneficial and safe in patients undergoing cardiac surgery or those with cardiovascular diseases in whom there is observed or expected reduction in serum T3 levels. Methods: A systematic review and meta-analysis of randomized controlled trials (RCTs) was performed as per the PRISMA guidelines. Pubmed, EMBASE, and Web of Science databases were searched for RCTs published between January 1, 1960 and March 30, 2022 that evaluated the effects of T3 therapy in patients undergoing cardiac surgery or with cardiovascular diseases. The primary outcomes were measures of cardiac function. Weighted mean difference (MD) or relative risk was calculated using a random effects model. PROSPERO registration number CRD42020211966. Results: Of the 3181 full-text articles screened, 34 studies with 2547 participants (number ranging between 13 and 223, mean ages between 0.5 and 73 years, mean percentage of women between 7% and 64%) were included. In 12 RCTs with 1093 adults undergoing cardiac surgery T3 therapy was associated with improvement in cardiac index (MD [95% confidence interval], 0.24 [0.08 to 0.40] L/min/m2, I2 = 74%). The quality of evidence was high to moderate. In 3 RCTs with 188 children undergoing cardiac surgery, 3 RCTs with 131 adult cardiac donors, 3 RCTs with 83 adult patients with heart failure, and 2 RCTs with 89 adults with acute myocardial infarction, T3 therapy did not improve cardiac index or left ventricular function; the quality of evidence ranged from high (pediatric cardiac surgery) to low (other groups). No detrimental effect of T3 therapy was observed on heart rate, risk of in-hospital atrial fibrillation, or mortality. Conclusions: Short-term T3 therapy is safe and trials in adults undergoing cardiac surgical procedures to evaluate longer term clinical endpoints are required. Current data do not support the routine use of T3 therapy in children undergoing cardiac surgery or in cardiac donors. Adequately designed trials are required to determine if T3 therapy improves cardiac function and clinical outcomes in patients with heart failure or acute myocardial infarction.