Supplementary Material for: Clinical and Pathophysiologic Insights of Free triiodothyronine/Free thyroxine Ratio in Patients with Heart Failure with Preserved Ejection Fraction: Data from the NETDiamond Cohort

<b><i>Background:</i></b> Thyroid dysfunction is common in patients with heart failure (HF). Impaired conversion of free T4 (FT4) into free T3 (FT3) is thought to occur in these patients, decreasing the availability of FT3 and contributing to HF progression. In HF with preserved ejection fraction (HFpEF), it is not known whether changes in conversion of thyroid hormones (THs) are associated with clinical status and outcomes. <b><i>Objectives:</i></b> The objective of this study was to evaluate the association of FT3/FT4 ratio and TH with clinical, analytical, and echocardiographic parameters, as well as their prognostic impact in individuals with stable HFpEF. <b><i>Methods:</i></b> We evaluated 74 HFpEF participants of the NETDiamond cohort without known thyroid disease. We performed regression modeling to study the associations of TH and FT3/FT4 ratio with clinical, anthropometric, analytical, and echocardiographic parameters, and survival analysis to evaluate associations with the composite of diuretic intensification, urgent HF visit, HF hospitalization, or cardiovascular death over a median follow-up of 2.8 years. <b><i>Results:</i></b> The mean age was 73.7 years and 62% were men. The mean FT3/FT4 ratio was 2.63 (standard deviation: 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 = −5.60 kg per FT3/FT4 unit, <i>p</i> = 0.034), higher pulmonary arterial systolic pressure (PASP) (β = −10.26 mm Hg per FT3/FT4 unit, <i>p</i> = 0.002), and lower left ventricular ejection fraction (LVEF) (β = 3.60% per FT3/FT4 unit, <i>p</i> = 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, <i>p</i> = 0.041). <b><i>Conclusions:</i></b> 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 diuretic intensification, urgent HF visits, HF hospitalization, or cardiovascular death. These findings suggest that decreased FT4 to FT3 conversion might be a mechanism associated with HFpEF progression.

背景：甲状腺功能异常在心力衰竭（heart failure, HF）患者中十分常见。此类患者被认为存在游离甲状腺素（free T4, FT4）向游离三碘甲状腺原氨酸（free T3, FT3）的转化受损情况，该过程会降低FT3的可利用度，并推动心力衰竭进展。在射血分数保留型心力衰竭（heart failure with preserved ejection fraction, HFpEF）患者中，甲状腺激素（thyroid hormones, THs）的转化变化是否与临床状态及预后相关，目前尚不明确。
研究目的：本研究旨在评估稳定型射血分数保留型心力衰竭患者的FT3/FT4比值与甲状腺激素的关联，及其与临床、实验室及超声心动图参数的相关性，并分析其预后价值。
研究方法：本研究纳入了NETDiamond队列中74名无已知甲状腺疾病的射血分数保留型心力衰竭参与者。通过回归建模分析甲状腺激素及FT3/FT4比值与临床、人体测量学、实验室及超声心动图参数的关联，并采用生存分析评估中位随访2.8年期间，受试者出现利尿剂强化治疗、紧急心力衰竭就诊、心力衰竭住院或心血管死亡复合终点的相关性。
研究结果：受试者平均年龄为73.7岁，男性占比62%。平均FT3/FT4比值为2.63（标准差：0.43）。FT3/FT4比值较低的受试者更易出现肥胖及心房颤动。较低的FT3/FT4比值与更高的体脂量（β=-5.60kg/FT3/FT4单位，p=0.034）、更高的肺动脉收缩压（pulmonary arterial systolic pressure, PASP）（β=-10.26mmHg/FT3/FT4单位，p=0.002）以及更低的左心室射血分数（left ventricular ejection fraction, LVEF）（β=3.60%/FT3/FT4单位，p=0.008）相关。较低的FT3/FT4比值与更高的心力衰竭复合终点风险相关（风险比（hazard ratio, HR）=2.50，95%置信区间（confidence interval, CI）:1.04–5.88，FT3/FT4每降低1单位，p=0.041）。
研究结论：在射血分数保留型心力衰竭患者中，较低的FT3/FT4比值与更高的体脂量、更高的肺动脉收缩压以及更低的左心室射血分数相关。较低的FT3/FT4比值可预测受试者出现利尿剂强化治疗、紧急心力衰竭就诊、心力衰竭住院或心血管死亡的风险更高。上述研究结果提示，FT4向FT3的转化受损可能是与射血分数保留型心力衰竭进展相关的机制之一。