A Case of Cardiac Sarcoidosis Presenting with a Low-level Elevation of Troponin: Case Report and Literature Review

Summary

This study reports an asymptomatic, untreated pulmonary sarcoidosis patient with normal routine cardiac screening, who was diagnosed with cardiac sarcoidosis via cardiac magnetic resonance (CMR) due to recurrent high-sensitivity cardiac troponin T(hs-cTnT) elevation. Routine hs-cTnT screening facilitates early detection of cardiac involvement, timely treatment, and improved prognosis.

Abstract

Cardiac sarcoidosis (CS) is a rare complication of systemic sarcoidosis, which can occur independently or concurrently with systemic sarcoidosis. The clinical manifestations range from asymptomatic myocardial granulomas to arrhythmias, heart failure, or cardiogenic sudden death, significantly increasing the mortality rate associated with sarcoidosis. Early diagnosis and treatment of CS is crucial, especially for patients with limited symptoms of systemic sarcoidosis. In patients with confirmed systemic sarcoidosis, cardiac sarcoidosis (CS) frequently exhibits a clinically silent phenotype, typically manifesting several years subsequent to the initial onset of systemic sarcoidosis manifestations. To date, no definitive evidence substantiates the utility of serum biomarkers for CS screening, and data regarding their efficacy in CS diagnosis and clinical management remain limited. We report a case of an asymptomatic, untreated patient with pulmonary sarcoidosis, who repeatedly had mild elevation of high-sensitivity cardiac troponin T(hs-cTnT), with no abnormalities in electrocardiogram or echocardiography. Eventually, Cardiac Magnetic Resonance (CMR) examination confirmed the diagnosis of cardiac sarcoidosis, and the patient's indicators improved after immunosuppressant treatment. We conducted a literature search to evaluate the effectiveness of hs-cTnT as a screening tool for CS, providing a reference for the management of CS in clinical practice.

Introduction

Sarcoidosis is a systemic granulomatous disease that can affect multiple organs, and its prevalence varies by region¹. In North America, the prevalence of sarcoidosis is estimated to be 141-160 cases per 100,000 people, with the highest incidence among Japanese people in Asia^1,2. Sex-related disparities in the cardiac sarcoidosis (CS) population are consistently documented, with ethnicity likely playing a contributing role. Notably, Japanese CS cohorts consistently report a higher prevalence in women, while earlier European and American studies uniformly demonstrate a male predominance^1,3. CS is a relatively rare complication associated with an increased risk of sudden cardiac death¹. Although up to 30% of patients with systemic sarcoidosis may have cardiac involvement, only 5% of patients have obvious cardiac symptoms such as conduction block, heart failure, or sudden cardiac death^1,2,4,5. Diagnosis in clinical practice is challenging, and the diagnosis of CS requires the combination of various imaging techniques, such as electrocardiogram, transthoracic echocardiography, CMR, fluorodeoxyglucose (FDG)-positron emission tomography (PET), and endomyocardial biopsy (EMB) and histopathology. Electrophysiological studies, FDG-PET, or cardiac magnetic resonance (CMR)-guided endomyocardial myocardial biopsy can increase the diagnostic sensitivity to approximately 50%⁶. Given the risk of sudden cardiac death, screening for cardiac involvement is crucial in patients with sarcoidosis. However, there is currently no unified or easily reproducible screening biomarker for early identification of cardiac involvement. Recent studies, however, have suggested that high-sensitivity cardiac troponin T (hs-cTnT) may serve as a sensitive marker of subclinical myocardial injury in sarcoidosis patients^7,8. The upper reference limit for hs-cTnT in healthy adults is approximately 0.014 ng/mL, and mild elevations within the range of 0.02-0.05 ng/mL have been repeatedly reported among patients with early or limited cardiac sarcoidosis⁹. Nevertheless, clinicians must interpret hs-cTnT values cautiously. False-positive elevations can occur in renal dysfunction, myocarditis, or other systemic inflammatory conditions. Therefore, the use of hs-cTnT as a screening tool should be combined with advanced imaging techniques such as CMR or FDG-PET for confirmation of myocardial inflammation⁸. In this case, we present a 47-year-old Chinese female who was diagnosed with pulmonary sarcoidosis three years after a physical examination revealed enlarged mediastinal lymph nodes. Recent re-examination of lung CT indicated that the mediastinal lymph nodes had slightly increased in size compared to before. During hospitalization, the levels of hs-cTnT were slightly elevated multiple times. The electrocardiogram and echocardiogram were normal. The results of comprehensive cardiovascular magnetic resonance imaging were consistent with cardiac sarcoidosis. Prednisolone and mycophenolate mofetil tablets were administered. The levels of hs-cTnT continued to decrease to the normal range. Re-examination of lung CT and cardiac magnetic resonance imaging showed improvement compared to before.

Case Presentation
A 47-year-old female had chronic hepatitis B for 10 years and was taking Entecavir Dispersible Tablets 5 mg once daily regularly. The patient denied a history of hypertension, diabetes mellitus, coronary heart disease, or chronic kidney disease, and reported no family history of sarcoidosis. On admission, the patient's initial vital signs were as follows: blood pressure 113/77 mmHg, heart rate 80 beats per min, respiratory rate 18 breaths per min, and oxygen saturation in ambient air 98%. Physical examination of the cardiovascular and pulmonary systems showed no abnormalities.

Diagnosis, Assessment, and Plan
The final diagnosis for this patient is pulmonary sarcoidosis and cardiac sarcoidosis.The initial laboratory test results (complete blood count, chemical blood profile, myocardial enzyme spectrum, B-type natriuretic peptide (BNP), tumor marker) were normal, with hs-cTnT at 0.036 ng/mL (normal range is <0.014 ng/mL), angiotensin-converting enzyme(ACE) at 84.2 U/L. The electrocardiogram showed sinus rhythm, heart rate 94 beats per minute, right deviation of the electrical axis +99°, no ST or T wave changes (Figure 1), and no abnormalities in echocardiography. After admission, a comprehensive pulmonary enhanced CT scan revealed multiple enlarged lymph nodes at the pulmonary hilum and along the mediastinum, with some bronchi being compressed and narrowed. There were multiple obstructive inflammatory changes near the pulmonary hilum in both lungs (Figure 2). Bronchoscopy in groups 7 and 4R showed enlarged lymph nodes (Figure 3). The pathological examination of lymph nodes in groups 7 and 4R suggested non-caseous necrotic chronic granulomatous inflammation (Figure 4). Tuberculosis, fungi, and general bacterial cultures were negative. The patient's cardiac magnetic resonance examination showed unevenly increased signals in the middle segment of the left ventricular wall and posterior wall on the Triple IR sequence, with delayed enhancement within the myocardium and locally beneath the epicardium (Figure 5), which was consistent with cardiac sarcoidosis.

At discharge, she began to take 40 mg of prednisolone (0.75 mg/kg/d), and received regular follow-ups from cardiologists and pulmonologists. One month later, the hs-cTnT level decreased compared to before, and it returned to the normal range after 3 months. The cardiac magnetic resonance examination (Figure 6) showed improved delayed enhancement compared to before. Currently, prednisolone 5 mg QD is combined with mycophenolate mofetil 0.5 g BID for maintenance. This case indicates that even patients with pulmonary nsarcoidosis without obvious symptoms may have myocardial involvement. High-sensitivity cardiac troponin T can serve as an early screening tool to enable early diagnosis and early treatment, and also act as an indicator for assessing subsequent therapeutic efficacy and prognosis.

Protocol

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.

Results

No arrhythmia signs were observed in the electrocardiogram (Figure 1). No abnormalities were found in the echocardiogram. The enhanced CT scan of the lungs indicated enlarged lymph nodes in the mediastinum and at the lung hilum, as well as pulmonary shadows adjacent to the two lung hilums (Figure 2). Bronchoscopy examination suggested enlarged lymph nodes in groups 7 and 4R (Figure 3). Histological examination of the biopsy specimen...

Discussion

Cardiac sarcoidosis affects all layers of the heart, mainly affecting the myocardium, and is a serious complication of systemic sarcoidosis¹⁰. Approximately 5% of sarcoidosis patients have clinical manifestations of heart diseases, but autopsy studies suggest that the prevalence may be higher, ranging from 20% to 30%¹¹. People are increasingly recognizing that the heart of sarcoidosis patients is prone to being affected. Histological confirmation of CS is the gold standard ...

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Elecsys Troponin T hs	Roche Diagnostics Gmbh	2025061700	Used for detecting high-sensitivity troponin levels
Gadopentetate Dimeglumine Injection	Guangzhou Kangchen Pharmaceutical Co., Ltd.	YBH05822024	Used for completing enhanced magnetic resonance examination
GE MAC 5500 HD system	GE Healthcare	MAC 5500 HD	High-performance digital ECG system with high-definition waveform and advanced analysis capabilities for clinical dia
Lohexol Injection	General Electric Pharmaceuticals (Shanghai) Co., Ltd.	1206945	Used for completing enhanced CT examination
Olympus BX53 microscope.	Olympus	BX53	A research-grade upright microscope for various techniques including brightfield, darkfield, fluorescence, and polarization. Commonly used in pathology and cell biology.
Olympus NA-201SX-4022	Olympus / Beckman Coulter*	AU480	A modular, medium-throughput clinical chemistry analyzer for routine tests like glucose, liver, and renal function. (*Note: Olympus clinical business was acquired by Beckman Coulter.)
Philips EPIQ 7C	Philips	EPIQ 7C	High-end cardiovascular ultrasound system with superior image quality and advanced quantification tools, primarily for echocardiography.
Roche Cobas e801 analyzer	Roche	cobas e 801	High-throughput, automated immunoassay module for tumor markers, hormones, infectious diseases. A core module of the cobas 8000 series.
Roche Elecsys platform	Roche	Elecsys	The brand name for Roche's electrochemiluminescence technology platform. The "catalog number" is specific to individual reagent tests.
Siemens MAGNETOM Avanto	Siemens Healthineers	MAGNETOM Avanto	A 1.5T MRI system known for high gradient performance, Tim (Total imaging matrix) coil technology, and broad clinical applications.
Siemens SOMATOM Definition Flash	Siemens Healthineers	SOMATOM Definition Flash	A dual-source CT scanner renowned for its extremely fast scanning speed ("Flash" spiral mode) and low radiation dose.