Low tri-iodothyronine syndrome improves the risk prediction for mortality in patients with acute heart failure: A prospective observational cohort study

Background and Objective: Clinical studies have suggested that low tri-iodothyronine (T3) syndrome negatively affects the clinical outcomes of patients with acute heart failure (AHF). The aim of this prospective cohort study was to evaluate the effect of low T3 syndrome in terms of prognosis and risk-predictive potential in AHF. Methods: A prospective observational cohort study was conducted from April 2012 to August 2016 in Nanjing, China. All clinical baseline characteristics were retrieved from electronic medical records. Low T3 syndrome was defined by a low free T3 level (<3.1 pM) accompanied by a normal thyroid-stimulating hormone level. The association between the free T3 level and mortality and the incremental risk prediction were estimated in Cox regression adjusted models. Results: In total, 312 patients with AHF for whom detailed thyroid hormone profiles were available were prospectively enrolled. Seventy-two patients exhibited low T3 syndrome. Over a median follow-up period of 35 months, 121 cumulative deaths occurred. Cardiovascular death was observed in 94 patients. After extensive adjustment for confounders, the low T3 syndrome-associated hazard ratios (95% confidence intervals) were 1.74 (1.16–2.61, P = 0.007) for all-cause mortality and 1.90 (1.21–2.98, P = 0.005) for cardiovascular mortality. The restricted cubic splines suggested a negative linear relationship between the free T3 level and mortality risk. Considering reclassification, adding low T3 syndrome to the fully adjusted model improved the risk prediction for all-cause mortality (integrated discrimination improvement [IDI]: 2.0%, P = 0.030; net reclassification improvement [NRI]: 8.9%, P = 0.232) and cardiovascular mortality (IDI: 2.5%, P = 0.030; NRI: 21.3%, P = 0.013). Conclusions: Low T3 syndrome reclassified risk prediction for mortality beyond traditional risk factors for patients with AHF.