Endocrine Abstracts

Introduction: Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome with high mortality, for which there are few disease modifying therapeutics. Thyroid axis dysfunction is common in heart failure (HF) and may contribute to the pathogenesis of HFpEF. However, the association of thyroid hormones (TH) with the clinical status of HFpEF patients and their prognostic impact in this syndrome are not clear.

Methods: We evaluated 93 participants with stable HFpEF followed in our centre. We categorized participants according to TH tertiles. A cross-sectional analysis was performed to analyse associations of TH with clinical parameters, and B-type natriuretic peptide (BNP) and high-sensitivity troponin I (hs-TnI) levels. Ordered logistic and linear regression models were used. Associations between TH and a composite endpoint of diuretic intensification, HF hospitalization or all-cause death were assessed using Cox proportional hazard models. These analyses were adjusted for clinically relevant variables.

Results: The mean age of the participants was 73.9 years and 46% were women. Half (51%) had a NYHA class II. In comparison to participants with free T3 (FT3) levels in the upper tertile (2.74 – 3.5 pg/ml), participants with FT3 levels in the lower tertile (1.86 - 2.44 pg/ml) had a higher prevalence of orthopnea (OR= 5.57 [1.14 - 27.16]; P=0.034) and higher levels of BNP (= 0.53 [0.02–1.03]; P=0.041). On the other hand, participants with free T4 (FT4) levels in the lower tertile (0.72 – 0.98 ng/dl) had a trend for a lower prevalence of orthopnea (OR=0.28 [0.07 – 1.06]; P=0.061) and lower levels of hs-TnI (=-0.41 [-0.82 – 0.00]; P=0.050), comparing with participants with FT4 levels in the upper tertile (1.10– 1.65 ng/dl). Over a median of 1037 days of follow-up, 48 persons had at least one of the events included in the composite endpoint. Participants with FT3/FT4 ratio levels in the lower tertile had a higher risk of the composite outcome (HR=2.19 [1.01 – 4.76]; P=0.047), comparing with participants with FT3/FT4 ratio levels in the upper tertile.

Conclusions: Lower levels of FT3 and higher levels of FT4 are associated with a worse clinical status. A lower FT3/FT4 ratio at baseline is associated with increased risk of a combined outcome of diuretic intensification, HF hospitalization or all-cause mortality. These results lead us to the hypothesis that FT4 to FT3 conversion might be impaired in patients with HFpEF. This impairment could be an important player in the progression of the disease.