Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.
Institute of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark.
Front Immunol. 2022 Mar 25;13:841849. doi: 10.3389/fimmu.2022.841849. eCollection 2022.
The aim of this study was to evaluate left ventricular global longitudinal strain (LVGLS), N-terminal pro brain natriuretic peptide (Nt-ProBNP), and Troponin T as non-invasive markers for acute cellular rejection (ACR) diagnosis and severity assessment after heart transplantation (HTx).
We retrospectively included all HTx patients transplanted from 2013 to 2019. At each visit, the patients were subjected to endomyocardial biopsy (EMB), measurement of Nt-ProBNP and Troponin T, and protocoled echocardiography with assessment of LVGLS. Sudden drop in graft function (SDGF) was defined as a drop in LVGLS ≥-2% in combination with either an increase in Troponin T ≥20% or Nt-ProBNP ≥30% compared with levels at the latest visit.
We included 1,436 EMBs from 83 HTx patients. The biopsies were grouped as 0R (n = 857), 1R (n = 538), and ≥2R (n = 41). LVGLS was lower and Troponin T and Nt-ProBNP higher in the 2R group than in the 0R and 1R groups (LVGLS: -12.9 ± 3.8% versus -16.9 ± 3.1% and -16.1 ± 3.3%; Troponin T: 79 [33;230] ng/l versus 27 [13;77] ng/l and 27 [14;68] ng/l; Nt-ProBNP: 4,174 [1,095;9,510] ng/l versus 734 [309;2,210] ng/l and 725 [305;2,082], all p < 0.01). A SDGF was seen at 45 visits of which 19 had ≥2R ACR. EMBs showed ACR in 20 cases without SDGF. Finally, neither was SDGF seen nor did the EMB show rejection in 1,136 cases. Thus, the sensitivity of SDGF for ≥2R ACR detection was 49% (32-65) and specificity 98% (97-99). The positive predictive value (PPV) was 42% (31-55) and the negative predictive value (NPV) 98% (98-99). The diagnostic value improved in a sub-analysis excluding EMBs within 3 months after HTx, clinically interpreted false positive ≥2R ACR cases, and cases with ≥2R ACR who recently (<2 weeks) were treated with intravenous methylprednisolone due to ≥2R ACR (sensitivity 75% (48-93), specificity 97% (96-98), NPV 99% (99-100), and PPV 39% (27-52).
Patients with ≥2R ACR have lower LVGLS and higher Troponin T and Nt-ProBNP than patients without 2R rejection. A non-invasive model combining changes in LVGLS and Troponin T or Nt-ProBNP showed excellent negative predictive value and moderate sensitivity and may be used as a gatekeeper to invasive biopsies after HTx.
本研究旨在评估左心室整体纵向应变（LVGLS）、N 端脑利钠肽前体（Nt-ProBNP）和肌钙蛋白 T 作为心脏移植（HTx）后急性细胞排斥（ACR）诊断和严重程度评估的非侵入性标志物。
我们回顾性纳入了 2013 年至 2019 年间接受 HTx 的所有患者。在每次就诊时，患者均接受心内膜心肌活检（EMB）、Nt-ProBNP 和肌钙蛋白 T 测量以及协议超声心动图检查，并评估 LVGLS。移植物功能突然下降（SDGF）定义为 LVGLS 较最近一次就诊下降≥-2%，同时肌钙蛋白 T 增加≥20%或 Nt-ProBNP 增加≥30%。
我们纳入了 83 例 HTx 患者的 1436 份 EMB。活检分为 0R（n=857）、1R（n=538）和≥2R（n=41）。2R 组的 LVGLS 较低，肌钙蛋白 T 和 Nt-ProBNP 较高（LVGLS：-12.9±3.8%比-16.9±3.1%和-16.1±3.3%；肌钙蛋白 T：79[33；230]ng/l比 27[13；77]ng/l和 27[14；68]ng/l；Nt-ProBNP：4174[1095；9510]ng/l比 734[309；2210]ng/l和 725[305；2082]ng/l，均 p<0.01）。在 45 次就诊中出现了 45 次 SDGF，其中 19 次有≥2R ACR。20 例无 SDGF 的 EMB 显示有 ACR。最后，1136 例既无 SDGF 也无 EMB 显示排斥。因此，SDGF 对≥2R ACR 检测的敏感性为 49%（32-65），特异性为 98%（97-99）。阳性预测值（PPV）为 42%（31-55），阴性预测值（NPV）为 98%（98-99）。在排除 HTx 后 3 个月内的 EMB、临床判断为假阳性≥2R ACR 病例以及因≥2R ACR 而最近（<2 周）接受静脉甲基泼尼松龙治疗的≥2R ACR 病例的亚分析中，诊断价值提高（敏感性 75%（48-93），特异性 97%（96-98），NPV 99%（99-100），PPV 39%（27-52）。
与无 2R 排斥的患者相比，≥2R ACR 患者的 LVGLS 较低，肌钙蛋白 T 和 Nt-ProBNP 较高。一种结合 LVGLS 和肌钙蛋白 T 或 Nt-ProBNP 变化的非侵入性模型显示出良好的阴性预测值和中等的敏感性，可作为 HTx 后侵入性活检的门控。
