High-sensitivity cardiac troponin T and NT-proBNP for ruling-in and ruling-out of cardiac amyloidosis
High-sensitivity cardiac troponin T and NT-proBNP for ruling-in and ruling-out of cardiac amyloidosis
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高敏心肌肌钙蛋白 T 和 NT-proBNP 用于判定和排除心脏淀粉样变性
DOI：
10.1093/ehjci/ehaa946.2112
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发表时间：
2020
影响因子：
39.3
通讯作者：
G. Vergaro
中科院分区：
文献类型：
--
作者：
V. Castiglione;A. Aimo;C. Prontera;S. Masotti;V. Chubuchny;D. Genovesi;A. Barison;M. Nicol;A. Cohen;D. Logeart;C. Passino;M. Emdin;G. Vergaro
心脏淀粉样变性（CA）是由错误折叠的蛋白质在细胞外沉积成不溶性淀粉样纤维引起的，2种最常见的形式是甲状腺素运载蛋白（ATTR）和免疫球蛋白轻链（AL）淀粉样变性。心肌肌钙蛋白和利钠肽的慢性升高在CA中很常见，并预示着更差的预后。CA的心脏损害的生物标志物的诊断率研究较少。
本研究旨在评价高敏心肌肌钙蛋白T（hs-cTnT）和B型利钠肽前体N末端组分（NT-proBNP）在诊断CA中的纳入/排除价值。
我们研究了275例连续患者，这些患者转诊至意大利（n=184）和法国（n=91）的两个三级中心，由于存在浆细胞恶液质或不明原因的左心室（假性）肥大而临床怀疑为CA。结合影像学技术（超声心动图、心脏磁共振、二磷酸盐造影）和活检检查的提示性特征，证实了CA。所有患者均接受了完整的基线表征，包括hs-cTnT和NT-proBNP。分别选择对应于阴性似然比10的生物标志物值<0.1 or a positive likelihood ratio >作为CA的排除和纳入截止值。
在161例（59%）患者中证实了CA，这些患者患有AL淀粉样变性（n=96，60%）或ATTR淀粉样变性（n=65，40%）。在评价时，97例（35%）患者（34例CA vs. 63例对照，p=0.112）因失代偿性心力衰竭住院。CA患者的hs-cTnT（65 ng/L [44-122] vs. 31 [18-42]，p<0.001）和NT-proBNP（4260 ng/L [2006-8911] vs. 1199 [468-3357]，p<0.001）高于非CA患者。hs-cTnT和NT-proBNP的曲线下面积（AUC）值分别为0.832和0.744（差异p=0.002）。两种生物标志物的组合（AUC=0.836）改善了对NT-proBNP（p=0.004）的区分，但未改善对hs-cTnT（p=0.423）的区分。选择hs-cTnT值<15 ng/L（灵敏度= 100%，阴性预测值= 100%，真阴性=13，假阴性=0）和NT-proBNP <550 ng/L（灵敏度= 98%，阴性预测值= 89%，真阴性=33，假阴性=4）作为排除临界值。hs-cTnT水平≥80 ng/L（特异性= 96%，阳性预测值= 93%，真阳性=71，假阳性=5）是判定淀粉样变性的最佳标准，而NT-proBNP无纳入临界值。hs-cTnT值≥80或<15 ng/dL可有效排除89例（32%）患者。
血浆hs-cTnT和NT-proBNP对疑似CA患者有诊断价值。单独hs-cTnT水平<15或≥80 ng/L可能有助于排除或确认多达三分之一接受疾病诊断筛查的患者的CA诊断。
图1
资金来源类型：无
Cardiac amyloidosis (CA) is caused by the extracellular deposition of misfolded proteins into insoluble amyloid fibrils, the 2 most common forms being transthyretin (ATTR) and immunoglobulin light chain (AL) amyloidosis. Chronic elevation of cardiac troponins and natriuretic peptides is common in CA and predicts worse outcome. The diagnostic yield of biomarkers of cardiac damage for CA has been less investigated.
We aimed to evaluate the ruling-in/out values for the diagnosis of CA of high-sensitivity cardiac troponin T (hs-cTnT) and of N-terminal fraction of pro-B-type natriuretic peptide (NT-proBNP).
We studied 275 consecutive patients referred to two tertiary Centers in Italy (n=184) and France (n=91) with the clinical suspicion of CA due to the presence of a plasma cell dyscrasia or an unexplained left ventricular (pseudo)hypertrophy. CA was confirmed by the combination of suggestive features on imaging techniques (echocardiography, cardiac magnetic resonance, diphosphonate scintigraphy) and biopsy examination. All patients underwent a full baseline characterization including hs-cTnT and NT-proBNP. Biomarkers values corresponding to a negative likelihood ratio <0.1 or a positive likelihood ratio >10 were respectively chosen as rule-out and rule-in cut-offs for CA.
CA was confirmed in 161 (59%) patients, who had either AL amyloidosis (n=96, 60%) or ATTR amyloidosis (n=65, 40%). At time of evaluation, 97 (35%) patients (34 CA vs. 63 controls, p=0.112) were hospitalized for decompensated heart failure. Patients with CA showed higher hs-cTnT (65 ng/L [44–122] vs. 31 [18–42], p<0.001) and NT-proBNP (4260 ng/L [2006–8911] vs. 1199 [468–3357], p<0.001) than those without CA. The area under the curve (AUC) values for hs-cTnT and NT-proBNP were 0.832 and 0.744 respectively (p=0.002 for the difference). The combination of the two biomarkers (AUC=0.836) improved discrimination over NT-proBNP (p=0.004), but not over hs-cTnT (p=0.423). A hs-cTnT value <15 ng/L (sensitivity=100%, negative predictive value=100%, true negatives=13, false negatives=0) and a NT-proBNP <550 ng/L (sensitivity=98%, negative predictive value=89%, true negatives=33, false negatives=4) were selected as rule-out cut-offs. A hs-cTnT level ≥80 ng/L (specificity=96%, positive predictive value=93%, true positives=71, false positives=5) was optimal for ruling in amyloidosis, while no rule-in cut-off could be selected for NT-proBNP. hs-cTnT values of either ≥80 or <15 ng/dL could effectively rule-in/out 89 (32%) patients.
Plasma hs-cTnT and NT-proBNP have diagnostic value in patients with suspected CA. Stand-alone hs-cTnT levels <15 or ≥80 ng/L may help to exclude or confirm the diagnosis of CA in up to one third of patients undergoing a diagnostic screening for the disease.
Figure 1
Type of funding source: None