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

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.

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.

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 specimens confirmed non-caseous necrotic chronic granulomatous inflammation (Figure 4). Tuberculosis, fungal, and general bacterial cultures were negative. The levels of hs-cTnT repeatedly increased. CMR examination revealed unevenly increased signals in the middle segment, lateral wall, and posterior wall of the left ventricle in the Triple IR sequence, along with delayed enhancement within the myocardium and at the local epicardium (Figure 5). The diagnosis was pulmonary sarcoidosis and cardiac sarcoidosis. Following glucocorticoid therapy, follow-up CMR imaging revealed improvements in the patient's condition (Figure 6). Concurrently, the patient's hs-cTnT levels gradually returned to normal ranges (Figure 7). These observations support the utility of hs-cTnT as both a screening marker for myocardial involvement in asymptomatic sarcoidosis and a response indicator to inform adjustments to treatment regimens.

Systematic monitoring of treatment-naive patients with asymptomatic sarcoidosis enables early detection of cardiac involvement, allowing timely therapeutic intervention that significantly improves long-term clinical outcomes.

Figure 1: The electrocardiogram showing sinus rhythm, heart rate 94 beats per min, right deviation of the electrical axis +99°, no ST or T wave changes. Please click here to view a larger version of this figure.

Figure 2: 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. Please click here to view a larger version of this figure.

Figure 3: Bronchoscopy of lymph nodes. Bronchoscopy in groups (A) 7 and (B) 4R showed enlarged lymph nodes. Please click here to view a larger version of this figure.

Figure 4: The pathological examination of lymph nodes. The pathological examination of lymph nodes in groups (A) 7 and (B) 4R suggested non-caseous necrotic chronic granulomatous inflammation. Please click here to view a larger version of this figure.

Figure 5: CMR Triple IR Sequence Shows Unevenly Increased Signals in Left Ventricular Middle/Posterior Walls and Myocardial-Epicardial Delayed Enhancement. Please click here to view a larger version of this figure.

Figure 6: The CMR examination showing improved delayed enhancement compared to before. Please click here to view a larger version of this figure.

Figure 7: Patient's hs-cTnT levels gradually decreased to normal range after treatment initiation. Please click here to view a larger version of this figure.

Table 1: Summary of patient characteristics and clinical features of cases of cardiac sarcoidosis in the literature. Please click here to download this Table.

SUPPLEMENTARY FILE: The changes in the patient's hs-cTnT levels following the initiation of glucocorticoid therapy on June 19, 2024. The file contains the hs-cTnT concentration data corresponding to different time points. Through these data, it can be clearly observed that the patient's hs-cTnT levels gradually decreased and eventually returned to the normal range. Please click here to download this File.

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 for diagnosis. However, due to the focal nature of the disease, the sensitivity of endomyocardial biopsy is approximately 25% from unselected RV biopsies, and therefore a negative biopsy does not necessarily rule out CS^12,13,14. Cardiac magnetic resonance and 18F-fluorodeoxyglucose positron emission tomography have high sensitivity and specificity in the diagnosis of cardiac sarcoidosis, but radiation exposure and high cost have hindered their routine use and repeated application^1,6. Following the identification of abnormalities on cardiac contrast-enhanced magnetic resonance imaging (CE-MRI), we recommended that the patient undergo further assessments, including PET-CT and endomyocardial biopsy. However, the patient declined these examinations due to concerns about radiation exposure (related to PET-CT), potential risks of endomyocardial biopsy, and financial constraints.

Cardiac sarcoidosis (CS) is predominantly diagnosed clinically. Per Heart Rhythm Society (HRS) criteria, biopsy-confirmed extra-cardiac sarcoidosis plus either rhythm abnormalities (advanced AVB, sustained VT on ECG/Holter) or LV dysfunction (LVEF <40% on echocardiography/CMR) and/or compatible advanced imaging (cardiac PET/CMR) supports a high probability of CS. The World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) criteria align closely with the HRS, while the Japanese Circulation Society (JCS) uses major/minor criteria and does not require biopsy-proven extra-cardiac sarcoidosis^6,15. Based on this, a highly probable diagnosis of cardiac sarcoidosis was established for the patient following a multidisciplinary discussion, taking into account the patient's electrocardiogram (ECG) findings, results of cardiac contrast-enhanced magnetic resonance imaging (CE-MRI), and past medical history of pulmonary sarcoidosis. The diagnosis could be confirmed by the improvement in relevant examination results after glucocorticoid therapy.

CS is associated with poor prognosis and requires early diagnosis and treatment. Currently, clinical screening mainly relies on electrocardiogram and echocardiography, and for patients with asymptomatic sarcoidosis, the positive rate is low due to the limited positive results of symptoms. In this case, the patient had been diagnosed with pulmonary sarcoidosis for 3 years. As the patient remained asymptomatic, no treatment was initiated, and the patient was followed up regularly. During the current follow-up, repeated mild elevations in hs-cTnT levels were detected, prompting further workup with CMR imaging, which ultimately confirmed a diagnosis of CS. Following treatment per the standard protocol, the patient's hs-cTnT levels showed a sustained decline and returned to the normal range. The level of hs-cTnT reflects the severity of persistent myocardial injury. It is elevated in many patients with heart failure and has prognostic value for the risk of cardiac events, independent of left ventricular function or BNP levels^16,17,18. Some studies have reported that the level of hs-cTnT in patients with CS is usually elevated^7,8,19. To evaluate the relationship between hs-cTnT and CS, we searched for articles in PUBMED and Web of Science using the terms "high-sensitivity troponin, troponin" and "cardiac sarcoidosis, sarcoidosis", excluding non-English, only abstracts, conference reports, a total of 12 articles were selected (Table 1).

Previous reports have indicated that FDG-PET can reflect the activity of inflammation in cardiac tissues and the involvement of epithelioid cell granulomas²⁰. A study retrospectively analyzed the serum levels of hs-cTnT, ACE, lysozyme, BNP, left ventricular ejection fraction (LVEF), and FDG-PET data in patients with CS, finding that hs-cTnT is a reliable indicator for evaluating the activity of cardiac sarcoidosis: the sensitivity and specificity were 87.5% and 75.0%, respectively, and the positive predictive value (PPV) and negative predictive value (NPV) were 87.5% and 75.0%. Moreover, hs-cTnT had a good correlation with ACE and lysozyme, but no correlation with BNP or LVEF. For example, patients with low hs-cTnT, high BNP, and low EF might be in the terminal stage of cardiac sarcoidosis. At the same time, the combination of high hs-cTnT, low BNP, and preserved EF might indicate that the disease is in the early and active stage⁹.The main treatment drug for sarcoidosis is glucocorticoid. However, there is currently no clear evidence-based basis for the optimal dosage and duration of glucocorticoid treatment. The total treatment course and the rate of dose reduction vary from patient to patient^1,21. Studies have suggested that hs-cTnT is associated with worse left ventricular function, higher incidence of atrioventricular conduction block, and heart failure. Moreover, after glucocorticoid treatment, the level of hs-cTnT decreases compared to before treatment, indicating that hs-cTnT can reflect the activity and severity of inflammatory myocardial injury in CS and can be used as a marker to evaluate the treatment response during glucocorticoid treatment. Even if patients do not have obvious clinical symptoms of cardiac dysfunction, this is helpful for timely adjustment of the treatment plan to reduce the risk of disease recurrence and progression⁸.

Hs-cTnT can also serve as a biomarker for evaluating the prognosis of CS. A study analyzed patients with CS in the chronic stage who were undergoing treatment. According to the hs-cTnT levels, the patients were divided into two groups. The patients with high hs-cTnT had a higher rate of cardiogenic mortality than those in the normal hs-cTnT group. The patients in the hs-cTnT group had a higher rate of cardiogenic death, ventricular fibrillation, persistent ventricular tachycardia, or hospitalization due to heart failure than those in the normal hs-cTnT group. The proportion of patients with hs-cTnT experiencing cardiac events within 2 years was ≥ 50%. Patients with high hs-cTnT levels had a higher probability of experiencing major cardiovascular adverse events, and even a slight increase in cTnT levels could lead to cardiac events. This indicates that hs-cTnT is an effective biomarker for evaluating the prognosis of CS²². Another study found that NT-proBNP, hs-cTnT, and serum creatinine, when analyzed as continuous variables, were respectively associated with the composite endpoint of left ventricular assist device implantation, heart transplantation, or death²³. Some studies have reviewed 512 patients diagnosed with CS. The research results suggested that among patients with hs-cTnT levels, the male prevalence was higher, the symptoms of heart failure were more severe, EF was lower, BNP levels were higher, and hs-cTnT levels were significantly associated with a higher incidence of major cardiovascular adverse events⁹.

A retrospective analysis was conducted on the clinical data of 132 patients with systemic sarcoidosis. Kaplan-Meier survival analysis and Cox proportional hazards model were used to evaluate the relationship between cardiovascular events and prognosis. Results showed that 28 patients experienced cardiovascular events. The patients in the event group had more severe symptoms of heart failure, a higher incidence of ventricular tachycardia, and higher serum hs-cTnT values [0.025 (0.017 - 0.044) compared with 0.011 (0.007 - 0.019) ng/mL, p < 0.001], and the left ventricular ejection fraction was lower than that of the non-myocardial infarction group. Even if the patients were not diagnosed with cardiac involvement at the time of enrollment, these trends could still be observed. Multivariate analysis showed that hs-cTnT was an independent biomarker for predicting cardiac events (hs-cTnT > 0.014 ng/mL: HR: 7.31, 95% confidence interval: 2.20 to 24.28, p < 0.001). The results indicated that hs-cTnT is a useful biomarker for predicting cardiovascular events in patients with sarcoidosis, even in those who did not have cardiac involvement at the initial assessment, and after using glucocorticoid treatment ²⁴. ShoKazui et al. aimed to assess whether the longitudinal levels of hs-cTnT were associated with adverse events in patients with CS. They examined the longitudinal hs-cTnT data of 63 patients with CS who had been treated with prednisolone. The patients were divided into two groups based on the median area under the hs-cTnT curve. The primary adverse events were persistent ventricular tachycardia or ventricular fibrillation, worsening of heart failure, and cardiogenic sudden death (SCD). During the median follow-up period of 30.4 months, a total of 463 cTnT measurements were collected. The study found that a higher area under the hs-cTnT curve was significantly associated with an increased incidence of major adverse events (P = 0.027). Changes in hs-cTnT levels before and 1 month after glucocorticoid treatment were not related to adverse events (P values were 0.179, 0.096, and 0.95, respectively). The study demonstrated that longitudinal hs-cTnT levels were associated with adverse cardiac events in patients with CS. Continuous measurement of hs-cTnT in CS patients is helpful for the early identification of high-risk patients²⁵.

Most research results indicate that the elevation of hs-cTnT is associated with the severity and poor prognosis of cardiac sarcoidosis, and it can be used to guide the reduction of medication and personalized adjustment of the treatment course during glucocorticoid therapy. Currently, there are no studies on using hs-cTnT as a screening method for CS. This case report indicates that hs-cTnT can be used as an indicator to screen for myocardial involvement, especially when there are no obvious cardiac-related symptoms and no significant abnormalities in a conventional electrocardiogram or echocardiography. However, further verification with a larger sample size is needed.