Nakashima Mitsutaka, Sakuragi Satoru, Miyoshi Toru, Takayama Shin, Kawaguchi Tatsuto, Kodera Nobuhisa, Akai Hiroaki, Koide Yuji, Otsuka Hiroaki, Wada Tadashi, Kawamoto Kenji, Tanakaya Machiko, Katayama Yusuke, Ito Hiroshi
Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Pharmaceutical Sciences Medicine, Dentistry, Okayama, Japan.
Department of Cardiovascular Medicine, National Hospital Organization Iwakuni Clinical Center, 1-1-1 Atagomachi, Iwakuni, Yamaguchi, 740-8510, Japan.
ESC Heart Fail. 2021 Jun;8(3):2240-2247. doi: 10.1002/ehf2.13317. Epub 2021 Mar 24.
Fibrosis-4 index (FIB-4 index), calculated by age, aspartate aminotransferase, alanine aminotransferase, and platelet count, is a simple marker to evaluate liver fibrosis and is associated with right-sided heart failure. However, the clinical relevance of FIB-4 in patients with heart failure with preserved ejection fraction (HFpEF) remains unclear. We investigated the prognostic implication of the FIB-4 index regarding right ventricular dysfunction in patients with HFpEF.
This prospective study included 116 consecutive HFpEF patients (mean age 79 years, 43% male) hospitalized with acute decompensated heart failure. We evaluated the association of the FIB-4 index with right ventricular function determined by tricuspid annular plane systolic excursion (TAPSE) and tricuspid lateral annular systolic velocity (S') before discharge. Cox regression analysis was performed to evaluate the association between the FIB-4 index and major adverse cardiovascular events (MACE) defined as the composite of cardiovascular death, readmission for heart failure, nonfatal myocardial infarction, and nonfatal stroke. FIB-4 index before discharge was significantly lower than that at admission (2.62 [1.92-3.46] and 3.03 [2.05-4.67], median [interquartile range], P < 0.001). Left ventricular ejection fraction, TAPSE, and S' before discharge were 62.7 (55.9-68.6) %, 17.5 ± 4.6 mm (mean ± standard deviation), and 10.0 (8.0-12.0) cm/s, respectively. In multiple linear regression analysis, the FIB-4 index before discharge was inversely correlated with TAPSE (β minus;0.244, P = 0.014) and S' (β -0.266, P = 0.009). During a median follow-up of 736 days, 37 MACE occurred. Multivariate Cox regression analysis revealed that a high FIB-4 index before discharge (per 1 point) was a significant predictor of MACE (hazard ratio 1.270, 95% confidence interval 1.052-1.532) after adjustment for male, serum creatinine, and haemoglobin. Receiver operating characteristic analysis indicated that the optimal cut-off value of FIB-4 index before discharge to predict MACE was 3.11. Kaplan-Meier survival analysis showed that patients with a FIB-4 index before discharge ≥3.11 had a significantly poorer prognosis than patients with FIB-4 index before discharge <3.11 (P = 0.029). Patients with an FIB-4 index ≥3.11 had a 2.202-fold (95% confidence interval 1.110-4.368) increased risk of MACE compared with those with an FIB-4 index <3.11 after adjustment for male, serum creatinine, and haemoglobin.
An increase in the FIB-4 index was associated with right ventricular dysfunction and a higher risk of future MACE in patients with HFpEF.
纤维化-4指数(FIB-4指数)通过年龄、天冬氨酸转氨酶、丙氨酸转氨酶和血小板计数计算得出,是评估肝纤维化的一个简单标志物,且与右心衰竭相关。然而,FIB-4在射血分数保留的心力衰竭(HFpEF)患者中的临床意义仍不明确。我们研究了FIB-4指数对HFpEF患者右心室功能障碍的预后影响。
这项前瞻性研究纳入了116例因急性失代偿性心力衰竭住院的连续性HFpEF患者(平均年龄79岁,43%为男性)。我们评估了出院前FIB-4指数与通过三尖瓣环平面收缩期位移(TAPSE)和三尖瓣外侧环收缩速度(S')确定的右心室功能之间的关联。进行Cox回归分析以评估FIB-4指数与定义为心血管死亡、因心力衰竭再次入院、非致命性心肌梗死和非致命性卒中的复合终点的主要不良心血管事件(MACE)之间的关联。出院前FIB-4指数显著低于入院时(中位数[四分位间距]为2.62[1.92 - 3.46]和3.03[2.05 - 4.67],P < 0.001)。出院前左心室射血分数、TAPSE和S'分别为62.7(55.9 - 68.6)%、17.5 ± 4.6 mm(平均值±标准差)和10.0(8.0 - 12.0)cm/s。在多元线性回归分析中,出院前FIB-4指数与TAPSE(β -0.244,P = 0.014)和S'(β -0.266,P = 0.009)呈负相关。在中位随访736天期间,发生了37例MACE。多变量Cox回归分析显示,在调整男性、血清肌酐和血红蛋白后,出院前高FIB-4指数(每增加1分)是MACE的显著预测因素(风险比1.270,95%置信区间1.052 - 1.532)。受试者工作特征分析表明,出院前FIB-4指数预测MACE的最佳截断值为3.11。Kaplan-Meier生存分析显示,出院前FIB-4指数≥3.11的患者预后明显比出院前FIB-4指数<3.11的患者差(P = 0.029)。在调整男性、血清肌酐和血红蛋白后,FIB-4指数≥3.11的患者发生MACE的风险比FIB-4指数<3.11的患者高2.202倍(95%置信区间1.110 - 4.368)。
FIB-4指数升高与HFpEF患者的右心室功能障碍及未来发生MACE的较高风险相关。