Clinical and pathophysiologic insights of FT3/FT4 ratio in patients with Heart Failure with Preserved Ejection Fraction: data from the NETDiamond cohort

Abstract Purpose Thyroid dysfunction is common in patients with heart failure (HF). Impaired conversion of T4 into T3 is thought to decrease the availability of T3 and contribute to HF progression. In HF with preserved ejection fraction (HFpEF), it is not known whether changes in conversion of thyroid hormones (TH) are associated with clinical status and outcomes. Methods We evaluated 79 HFpEF participants of the NETDiamond cohort without known thyroid disease. We performed regression modelling to study the associations of TH and FT3/FT4 ratio with clinical and echocardiographic parameters, and survival analysis to evaluate associations with the composite of urgent HF visit, HF hospitalization or cardiovascular death, over a median follow-up of 2.8 years. Results The mean age was 73.5 years and 47% were men. The mean FT3/FT4 ratio was 2.63 (SD 0.43). Subjects with lower FT3/FT4 ratio were more likely to be obese and have atrial fibrillation. Lower FT3/FT4 ratio was associated with higher body fat (β=-5.60kg per FT3/FT4 unit, p = 0.034), higher pulmonary arterial systolic pressure (PASP) (β=-10.26mmHg, p = 0.002) and lower left ventricular ejection fraction (LVEF) (β = 3.60%, p = 0.008). Lower FT3/FT4 ratio was associated with higher risk for the composite HF outcome (HR = 2.50, 95%CI 1.04–5.88, per 1-unit decrease in FT3/FT4, p = 0.041). Conclusions In patients with HFpEF, lower FT3/FT4 ratio was associated with higher body fat, higher PASP and lower LVEF. Lower FT3/FT4 predicted a higher risk of urgent HF visit, HF hospitalization or cardiovascular death. These findings suggest that decreased FT4 to FT3 conversion may be associated with HFpEF progression.