病例报告

一例表现为肌钙蛋白轻度升高的心脏结节病：病例报告及文献综述

DOI：

10.3791/69381

⸱

2025年12月12日

1Department of Respiratory and Critical Care Medicine, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University

本文内容

摘要

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本研究报道了一例无症状且未经治疗的肺结节病患者，其常规心脏筛查结果正常，但因反复出现高敏心肌肌钙蛋白T（hs-cTnT）升高，通过心脏磁共振成像（CMR）确诊为心脏结节病。via 常规hs-cTnT筛查有助于早期发现心脏受累，及时治疗，并改善预后。

摘要

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心脏结节病（CS）是全身性结节病的一种罕见并发症，可单独发生或与全身性结节病同时出现。其临床表现从无症状的心肌肉芽肿到心律失常、心力衰竭或心源性猝死不等，显著增加了结节病相关的死亡率。早期诊断和治疗CS至关重要，尤其对于全身性结节病症状有限的患者。在已确诊全身性结节病的患者中，心脏结节病（CS）常表现为临床隐匿型，通常在全身性结节病初次发病数年后才显现。迄今为止，尚无明确证据支持血清生物标志物在CS筛查中的有效性，关于其在CS诊断和临床管理中作用的数据仍十分有限。我们报告一例无症状且未接受治疗的肺结节病患者，其高敏心肌肌钙蛋白T（hs-cTnT）多次出现轻度升高，但心电图和超声心动图均无异常。最终通过心脏磁共振（CMR）检查确诊为心脏结节病，经免疫抑制治疗后患者各项指标改善。我们进行了文献检索，以评估hs-cTnT作为CS筛查工具的有效性，为临床实践中CS的管理提供参考依据。

引言

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结节病是一种可累及多个器官的全身性肉芽肿性疾病，其患病率因地区而异1。在北美，结节病的患病率估计为每10万人中有141至160例，而在亚洲，以日本人群中的发病率最高1,2。在心脏结节病（CS）人群中，性别差异始终存在，且种族可能在其中起一定作用。值得注意的是，日本的CS队列研究一致报告女性患病率较高，而早期欧洲和美国的研究则普遍显示男性占主导地位1,3 。CS是一种相对罕见的并发症，与心源性猝死风险增加相关1。尽管高达30%的系统性结节病患者可能存在心脏受累，但仅有5%的患者表现出明显的心脏症状，如传导阻滞、心力衰竭或心源性猝死1,2,4,5。临床上诊断较为困难，CS的诊断需结合多种影像学技术，如心电图、经胸超声心动图、心脏磁共振（CMR）、氟脱氧葡萄糖（FDG）正电子发射断层扫描（PET）以及心内膜心肌活检（EMB）和组织病理学检查。电生理检查、FDG-PET或CMR引导下的心内膜心肌活检可将诊断敏感性提高至约50%6。鉴于心源性猝死的风险，对结节病患者进行心脏受累的筛查至关重要。然而，目前尚无统一且易于重复的生物标志物用于早期识别心脏受累。但近期研究表明，高敏心肌肌钙蛋白T（hs-cTnT）可能作为结节病患者亚临床心肌损伤的敏感指标7,8。健康成年人hs-cTnT的参考上限约为0.014 ng/mL，在早期或局限性心脏结节病患者中，多次报道其轻度升高至0.02–0.05 ng/mL范围内9。然而，临床医生必须谨慎解读hs-cTnT数值。肾功能不全、心肌炎或其他系统性炎症状态可能导致假阳性升高。因此，将hs-cTnT作为筛查工具时，应结合CMR或FDG-PET等高级影像学技术，以确认心肌炎症的存在8。本文报道一例47岁中国女性患者，其在体检发现纵隔淋巴结肿大后三年被诊断为肺结节病。近期肺部CT复查提示纵隔淋巴结较前略有增大。住院期间多次检测显示hs-cTnT水平轻度升高。心电图和超声心动图结果均正常。全面的心脏磁共振成像结果符合心脏结节病表现。给予泼尼松龙和吗替麦考酚酯片治疗后，hs-cTnT水平持续下降并恢复至正常范围。复查肺部CT及心脏磁共振成像均显示较前改善。

病例报告
一名47岁女性患有慢性乙型肝炎已有10年，长期规律服用恩替卡韦分散片5 mg，每日一次。患者否认有高血压、糖尿病、冠心病或慢性肾病病史，且无结节病家族史。入院时，患者初始生命体征如下：血压113/77 mmHg，心率80次/分钟，呼吸频率18次/分钟，环境空气下血氧饱和度为98%。心血管系统和肺部体格检查未见异常。

诊断、评估与治疗方案
该患者的最终诊断为肺结节病和心脏结节病。初始实验室检查结果（全血细胞计数、生化血清谱、心肌酶谱、B型利钠肽（BNP）、肿瘤标志物）均正常，hs-cTnT为0.036 ng/mL（正常范围<0.014 ng/mL），血管紧张素转换酶（ACE）为84.2 U/L。心电图显示窦性心律，心率94次/分钟，电轴右偏+99°，无ST段或T波改变（图1），超声心动图未见异常。入院后行胸部增强CT检查，显示肺门及纵隔多发淋巴结肿大，部分支气管受压变窄，双肺肺门附近多处阻塞性炎性改变（图2）。支气管镜检查发现7组和4R组淋巴结肿大（图3）。7组和4R组淋巴结病理检查提示非干酪性坏死性慢性肉芽肿性炎症（图4）。结核、真菌及普通细菌培养均为阴性。患者心脏磁共振检查在Triple IR序列上显示左心室壁中段及后壁信号不均匀增强，心肌内及心外膜下局部区域延迟强化（图5），符合心脏结节病表现。

出院时，患者开始服用泼尼松龙 40 mg（0.75 mg/kg/d），并定期接受心内科和呼吸科医生的随访。一个月后，高敏心肌肌钙蛋白T（hs-cTnT）水平较之前下降，3个月后恢复至正常范围。心脏磁共振检查（图6）显示延迟强化较前改善。目前采用泼尼松龙 5 mg 每日一次联合吗替麦考酚酯 0.5 g 每日两次进行维持治疗。本病例提示，即使肺部结节病患者无明显症状，也可能存在心肌受累。高敏心肌肌钙蛋白T可作为早期筛查工具，有助于实现早期诊断和早期治疗，同时可作为评估后续治疗效果及预后的指标。

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方案

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This study is in accordance with the Declaration of Helsinki. The study was approved by the Medical Ethics Committee of the Fourth Affiliated Hospital of School of Medicine ,Zhejiang University (K2025173).

1. Patient selection

NOTE: Included in this study was a 47-year-old patient with a 3-year confirmed history of pulmonary sarcoidosis, undergoing reassessment of mediastinal lymph node enlargement found on follow-up CT.

  1. Verify absence of acute systemic or cardiopulmonary symptoms such as fever, cough, chest tightness, or chest pain. Record demographic data (age, sex, BMI) and relevant medical history.
  2. Document existing comorbidities and medications.1
    NOTE: The patient confirmed chronic hepatitis B, managed with oral entecavir 5 mg once daily for over 10 years.
  3. Exclude other comorbidities, including hypertension, diabetes mellitus, coronary artery disease, and chronic kidney disease.
  4. Record baseline vital signs: Blood pressure: 113/77 mmHg; heart rate: 80 beats/min; respiratory rate: 18 breaths/min; oxygen saturation: 98% in ambient air.
  5. Conduct a systemic physical examination focusing on the cardiac and pulmonary systems.

2. Laboratory assessment

  1. Collect 5 mL of venous blood using a serum separator tube.
  2. Centrifuge the sample at 2,000 x g for 10 min at room temperature (22-25 °C).
  3. Perform biochemical analysis using an electrochemiluminescence immunoassay analyzer. Complete blood count, liver and kidney function, electrolytes, coagulation profile, BNP, and tumor markers (CEA, NSE, SCC, CYFRA 21-1, ProGRP).
  4. Measure high-sensitivity cardiac troponin T (hs-cTnT) by electrochemiluminescence immunoassay (ECLIA) on the immunoassay platform.
    1. Analytical sensitivity: 3 ng/L; upper reference limit: 14 ng/L (0.014 ng/mL). Observed value: 0.036 ng/mL.
  5. Quantify angiotensin-converting enzyme (ACE) using an enzymatic colorimetric assay; observed value: 84.2 U/L.

3. Electrocardiographic and echocardiographic evaluation

  1. Record a 12-lead ECG using an electrocardiograph at 25 mm/s speed and 10 mm/mV gain.
  2. Evaluate rhythm, axis, and ST-T wave changes; confirm right-axis deviation (+99°) with sinus rhythm.
  3. Perform transthoracic echocardiography on an ultrasound diagnostic system equipped with a 2.5 MHz transducer.
  4. Measure left ventricular ejection fraction (LVEF), wall motion, and valvular function according to ASE 2018 guidelines

4. Chest CT imaging

  1. Conduct contrast-enhanced CT on a computed tomography system scanner.
  2. Set parameters as follows: Tube voltage: 120 kVp; tube current: 100-120 mAs; slice thickness: 1 mm; reconstruction interval: 1 mm.
  3. Administer 80 mL of Iohexol (350 mg I/mL) intravenously at 3.5 mL/s, followed by a 30 mL saline flush.
  4. Acquire images during a breath-hold at full inspiration.
  5. Evaluate the mediastinal and hilar lymph nodes for size, contour, and compression of adjacent bronchi.

5. Bronchoscopy and EBUS-TBNA

  1. Prepare the patient with topical 2% lidocaine aerosol anesthesia and continuous oxygen monitoring.
  2. Insert a convex-probe EBUS bronchoscope through the oral route under moderate sedation (e.g., midazolam 2 mg IV).
  3. Identify lymph node stations 4R and 7 under ultrasound guidance.
  4. Perform transbronchial needle aspiration using a 22-gauge clinical chemistry analyzer needle.
  5. Make 3-4 needle passes per station with negative pressure applied via syringe to collect core tissue.
  6. Immediately fix the specimens in 10% neutral-buffered formalin for 12-24 h at room temperature.

6. Cardiac Magnetic Resonance (CMR) Imaging

  1. Perform CMR using a 1.5 T magnetic resonance imaging system scanner.
  2. Acquire sequences in the following order: Cine SSFP (TR/TE = 3.0/1.5 ms, flip angle = 60°); T2-weighted short-tau inversion recovery (TR/TE = 2,000/80 ms); Triple Inversion Recovery (TR/TE = 700/20 ms).
  3. Inject gadobutrol 0.1 mmol/kg intravenously at 2 mL/s, followed by a 20 mL saline flush.
  4. Acquire late gadolinium enhancement (LGE) images 10-15 min post-contrast using inversion-recovery gradient echo sequences.
  5. Assess for regional delayed enhancement, wall motion abnormality, and myocardial edema consistent with sarcoid infiltration.

7. Histopathology and immunohistochemistry

  1. Embed fixed tissues in paraffin and section at 4 µm thickness using a rotary microtome.
  2. Stain sections with hematoxylin-eosin (H&E) for 8 min at room temperature.
  3. Perform special stains for pathogen exclusion: Ziehl-Neelsen for acid-fast bacilli; Periodic acid-Schiff (PAS) and Gomori methenamine silver (GMS) for fungi.
  4. Mount slides with neutral resin and observe under 400× magnification using an upright research microscope.
  5. Identify non-caseating granulomatous inflammation without necrosis.

8. Treatment protocol

  1. Initiate prednisolone 40 mg/day (0.75 mg/kg/day) orally after breakfast.
  2. Prescribe calcium carbonate 600 mg/day and vitamin D3 800 IU/day as supplements.
  3. In case of gastrointestinal discomfort, administer sucralfate 1 g TID and esomeprazole 20 mg QD.
  4. Schedule follow-up every 2-4 weeks during the initial 3 months.
  5. Taper prednisolone gradually by 5 mg every 2 weeks, guided by hs-cTnT decline and CMR improvement.
  6. Introduce mycophenolate mofetil 0.5 g BID as a steroid-sparing agent after stabilization.
  7. Monitor liver and renal function monthly throughout therapy.

9. Follow-up and monitoring

  1. Reassess hs-cTnT monthly for 3 months, then every 3 months.
  2. Repeat CMR at 3 and 6 months to monitor changes in LGE.
  3. Perform chest CT at 3 months: Station 4R lymph node: 2.37 cm → 0.75 cm; Station 7 lymph node: 2.97 cm → 1.70 cm.
  4. Evaluate ECG and echocardiography at each visit to detect arrhythmia or LV dysfunction.
  5. Maintain therapy with prednisolone 5 mg QD + mycophenolate mofetil 0.5 g BID for long-term remission.
  6. Continue periodic surveillance every 6-12 months.
    NOTE: Normalization of hs-cTnT and regression of myocardial enhancement are indicative of remission.

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结果

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心电图未见心律失常征象（图1）。超声心动图未发现异常。肺部增强CT扫描显示纵隔及肺门淋巴结肿大，并见邻近双侧肺门的肺部阴影（图2）。支气管镜检查提示第7组和4R组淋巴结肿大（图3）。活检标本的组织学检查证实为非干酪性坏死性慢性肉芽肿性炎症（图4）。结核、真菌及普通细菌培养均为阴性。高敏心肌肌钙蛋白T（hs-cTnT）水平反复升高。心脏磁共振（CMR）检查在Triple IR序列中显示左心室中段侧壁及后壁信号不均匀增强，并伴有心肌内及局部心外膜的延迟强化（图5）。诊断为肺结节病及心脏结节病。经糖皮质激素治疗后，随访CMR影像显示患者病情改善（图6）。同时，患者的hs-cTnT水平逐渐恢复至正常范围（图7）。上述观察结果支持将h...

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讨论

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心脏结节病累及心脏的所有层次，主要影响心肌，是系统性结节病的一种严重并发症10。约5%的结节病患者具有心脏疾病的临床表现，但尸检研究表明其实际患病率可能更高，可达20%至30%11。人们日益认识到结节病患者的心脏容易受累。组织学证实是诊断心脏结节病的金标准。然而，由于该病呈局灶性分布，对未选择性右心室活检而言，心内膜心肌活检的敏感性约为25%，因此阴性活检结果并不能排除心脏结节病的诊断12,13,14。心脏磁共振成像和18F-氟脱氧葡萄糖正电子发射断层扫描在诊断心脏结节病方面具有较高的敏感性和特异性，但辐射暴露和高昂费用限制了它们的常规使用和重复应用1,6。在发现心脏增强磁共振成像（CE-MRI）异常后，我们建议患者进一步接受PET-CT和心...

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披露

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作者无任何利益冲突需要披露。

材料

本文使用的材料清单
姓名公司目录编号评论
Elecsys 高敏肌钙蛋白 TRoche Diagnostics Gmbh2025061700用于检测高敏肌钙蛋白水平
钆喷酸葡胺注射液广州康臣药业有限公司YBH05822024用于完成增强磁共振检查
GE MAC 5500 HD 系统 GE HealthcareMAC 5500 HD高性能数字心电图系统，具备高清波形和先进的分析功能，用于临床诊断
碘海醇注射液通用电气药业（上海）有限公司1206945用于完成增强CT检查
Olympus BX53 显微镜OlympusBX53研究级正置显微镜，适用于明场、暗场、荧光和偏振等多种技术，广泛应用于病理学和细胞生物学领域
Olympus NA-201SX-4022Olympus / Beckman Coulter*AU480模块化中通量临床化学分析仪，用于葡萄糖、肝功能、肾功能等常规检测。（*注：Olympus 临床业务已被 Beckman Coulter 收购）
Philips EPIQ 7C PhilipsEPIQ 7C高端心血管超声系统，具有卓越的图像质量和先进的定量分析工具，主要用于超声心动图检查
Roche Cobas e801 分析仪Rochecobas e 801高通量全自动免疫分析模块，用于肿瘤标志物、激素、传染病等检测，是 cobas 8000 系列的核心模块
Roche Elecsys 平台RocheElecsysRoche 电化学发光技术平台的品牌名称，"货号"针对具体试剂检测项目而定
Siemens MAGNETOM AvantoSiemens HealthineersMAGNETOM Avanto1.5T 磁共振成像系统，以高梯度性能、Tim（全成像矩阵）线圈技术和广泛的临床应用著称
Siemens SOMATOM Definition FlashSiemens HealthineersSOMATOM Definition Flash双源CT扫描仪，以其极快的扫描速度（"Flash"螺旋模式）和低辐射剂量而闻名

参考文献

$$\rightleftharpoonup{xx}$$ $$\longleftharp{xx}$$, $$\longrightharp{xx}$$,
  1. Sharma, R., et al. Management of cardiac sarcoidosis. Eur Heart J. 45 (30), 2697-2726 (2024).
  2. Tan, J. L., Tan, B. E., Cheung, J. W., Ortman, M., Lee, J. Z. Update on cardiac sarcoidosis. Trends Cardiovasc Med. 33 (7), 442-455 (2023).
  3. Iso, T., et al. Sex differences in clinical characteristics and prognosis of patients with cardiac sarcoidosis. Heart. 109 (18), 1387-1393 (2023).
  4. Van Der Velde, N., et al. Screening for cardiac sarcoidosis: Diagnostic approach and long-term follow-up in a tertiary centre. Neth Heart J. 33 (2), 55-64 (2025).
  5. Bakker, A. L. M., et al. Holter monitoring and cardiac biomarkers in screening for cardiac sarcoidosis. Lung. 203 (1), 10(2024).
  6. Cheng, R. K., et al. Diagnosis and management of cardiac sarcoidosis: A scientific statement from the American Heart Association. Circulation. 149 (21), e1197-e1216 (2024).
  7. Baba, Y., et al. Usefulness of high-sensitive cardiac troponin T for evaluating the activity of cardiac sarcoidosis. Int Heart J. 53 (5), 287-292 (2012).
  8. Kandolin, R., et al. Usefulness of cardiac troponins as markers of early treatment response in cardiac sarcoidosis. Am J Cardiol. 116 (6), 960-964 (2015).
  9. Baba, Y., et al. Prognostic role of high-sensitivity cardiac troponin T in patients with cardiac sarcoidosis: Insights from ILLUMINATE-CS. ESC Heart Fail. 12 (2), 869-878 (2025).
  10. Farina, N., et al. Cardiac sarcoidosis: Clinical insights, diagnosis, and management strategies. Rev Cardiovasc Med. 26 (2), 26605(2025).
  11. Mathai, S. V., Patel, S., Jorde, U. P., Rochlani, Y. Epidemiology, pathogenesis, and diagnosis of cardiac sarcoidosis. Methodist Debakey Cardiovasc J. 18 (2), 78-93 (2022).
  12. Muser, D., et al. Characterization of the electroanatomic substrate in cardiac sarcoidosis: Correlation with imaging findings of scar and inflammation. JACC Clin Electrophysiol. 4 (3), 291-303 (2018).
  13. Bennett, M. K., et al. Evaluation of the role of endomyocardial biopsy in 851 patients with unexplained heart failure from 2000-2009. Circ Heart Fail. 6 (4), 676-684 (2013).
  14. Ardehali, H., et al. A positive endomyocardial biopsy result for sarcoid is associated with poor prognosis in patients with initially unexplained cardiomyopathy. Am Heart J. 150 (3), 459-463 (2005).
  15. Terasaki, F., et al. JCS 2016 guideline on diagnosis and treatment of cardiac sarcoidosis-digest version. Circ J. 83 (11), 2329-2388 (2019).
  16. Aimo, A., et al. Prognostic value of high-sensitivity troponin T in chronic heart failure: An individual patient data meta-analysis. Circulation. 137 (3), 286-297 (2018).
  17. Latini, R., et al. Prognostic value of very low plasma concentrations of troponin T in patients with stable chronic heart failure. Circulation. 116 (11), 1242-1249 (2007).
  18. Arima, N., et al. Prospective multicenter screening with high-sensitivity cardiac troponin T for wild-type transthyretin cardiac amyloidosis in outpatient and community-based settings. Circ J. 89 (1), 24-30 (2024).
  19. Tanada, Y., Sato, Y., Sawa, T., Fujiwara, H., Takatsu, Y. Serial measurement of high-sensitivity cardiac troponin I and N-terminal proB-type natriuretic peptide in a patient presenting with cardiac sarcoidosis. Intern Med. 51 (24), 3379-3381 (2012).
  20. Keijsers, R. G., et al. Imaging the inflammatory activity of sarcoidosis: Sensitivity and inter observer agreement of (67)Ga imaging and (18)F-FDG PET. Q J Nucl Med Mol Imaging. 55 (1), 66-71 (2011).
  21. Sadek, M. M., Yung, D., Birnie, D. H., Beanlands, R. S., Nery, P. B. Corticosteroid therapy for cardiac sarcoidosis: A systematic review. Can J Cardiol. 29 (9), 1034-1041 (2013).
  22. Takaya, Y., et al. Impact of high-sensitivity cardiac troponin T on clinical outcomes in patients with cardiac sarcoidosis. Circ J. 89 (4), 442-449 (2025).
  23. Kolluri, N., et al. Routine laboratory biomarkers as prognostic indicators of cardiac sarcoidosis outcomes. Sarcoidosis Vasc Diffuse Lung Dis. 39 (3), e2022023(2022).
  24. Baba, Y., et al. High-sensitivity cardiac troponin T is a useful biomarker for predicting the prognosis of patients with systemic sarcoidosis regardless of cardiac involvement. Intern Med. 62 (21), 3097-3105 (2023).
  25. Kazui, S., et al. Association of longitudinal cardiac troponin trajectory with adverse events in patients with cardiac sarcoidosis. Int J Cardiol. 389, 131268(2023).

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