Zhang Kathleen W, Miao Jennifer, Mitchell Joshua D, Alvarez-Cardona Jose, Tomasek Kelsey, Su Yan Ru, Gordon Mary, Cornell R Frank, Lenihan Daniel J
Cardio-Oncology Center of Excellence, Division of Cardiology, Washington University School of Medicine, St. Louis, MO.
Department of Internal Medicine, Vanderbilt University Medical Center, Nashville, TN.
JACC CardioOncol. 2020 Mar;2(1):56-66. doi: 10.1016/j.jaccao.2020.01.006. Epub 2020 Mar 17.
Delays in diagnosis of cardiac amyloidosis are common, usually resulting from nonspecific findings on clinical examination and testing. A discriminatory plasma biomarker could result in earlier diagnosis and improve prognosis assessment.
To determine the diagnostic and prognostic utility of hepatocyte growth factor (HGF) in light chain and transthyretin cardiac amyloidosis.
188 patients with cardiac amyloidosis, amyloidosis without cardiac involvement, or symptomatic heart failure with left ventricular hypertrophy (LVH) or reduced ejection fraction (HFrEF) were enrolled prospectively. Serum biomarkers were measured at study enrollment, and all patients with amyloidosis were followed for all-cause mortality, cardiac transplant, or left ventricular assist device implant. Multinomial logistic regression and Kaplan-Meier survival estimates tested the association of biomarker levels with cardiac amyloidosis and clinical outcomes, respectively. Harrell's C-statistic and the likelihood ratio test compared the prognostic accuracy of plasma biomarkers.
HGF was significantly higher in patients with cardiac amyloidosis (p<0.001). An HGF level of 205 pg/mL discriminated cardiac amyloidosis from LVH and HFrEF with 86% sensitivity, 84% specificity, and an area under the curve of 0.88 (95% CI 0.83-0.94). In patients with amyloidosis, elevated HGF levels were associated with worse event-free survival over a median follow-up period of 2.6 years (p<0.001) with incremental prognostic accuracy over NT-proBNP and troponin-T (p<0.001).
HGF discriminates light chain and transthyretin cardiac amyloidosis from patients with symptomatic HF with LVH or HFrEF, and is associated with worse cardiac outcomes. Confirmation of these findings in a larger, multi-center study enrolling confirmed and suspected cases of cardiac amyloidosis is underway.
心脏淀粉样变性的诊断延迟很常见，通常是由于临床检查和检测结果不具有特异性。一种具有鉴别性的血浆生物标志物可实现更早诊断并改善预后评估。
确定肝细胞生长因子（HGF）在轻链和转甲状腺素蛋白心脏淀粉样变性中的诊断和预后价值。
前瞻性纳入188例患有心脏淀粉样变性、无心脏受累的淀粉样变性或有症状性心力衰竭伴左心室肥厚（LVH）或射血分数降低（HFrEF）的患者。在研究入组时测量血清生物标志物，所有淀粉样变性患者均随访全因死亡率、心脏移植或左心室辅助装置植入情况。多项逻辑回归和Kaplan-Meier生存估计分别检验了生物标志物水平与心脏淀粉样变性及临床结局的相关性。Harrell's C统计量和似然比检验比较了血浆生物标志物的预后准确性。
心脏淀粉样变性患者的HGF水平显著更高（p<0.001）。HGF水平为205 pg/mL时，区分心脏淀粉样变性与LVH和HFrEF的灵敏度为86%，特异性为84%，曲线下面积为0.88（95%CI 0.83 - 0.94）。在淀粉样变性患者中，HGF水平升高与中位随访期2.6年的无事件生存期较差相关（p<0.001），其预后准确性高于N末端脑钠肽前体（NT-proBNP）和肌钙蛋白T（p<0.001）。
HGF可区分轻链和转甲状腺素蛋白心脏淀粉样变性与有症状性心力衰竭伴LVH或HFrEF的患者，且与较差的心脏结局相关。一项纳入确诊和疑似心脏淀粉样变性病例的更大规模多中心研究正在对这些发现进行验证。
