Multimodality imaging in cardiac sarcoidosis: A case series of diverse phenotypes

INTRODUCTION

Sarcoidosis refers to a systemic inflammatory disease characterized by non-caseating granulomas in multiple organs. Cardiac sarcoidosis (CS) features non-specific clinical manifestations, which accounts for approximately 5% of patients with sarcoidosis, and low sensitivity of endomyocardial biopsy, which is often overlooked in clinical settings.^[1] However, cardiac involvement considerably influences prognosis, which makes the diagnosis of CS particularly challenging.^[2-4] With the wide development of cardiac magnetic resonance (CMR) and positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG), CS has garnered increased attention from clinical physicians.^[5,6]

The clinical manifestations of CS are diverse and mainly include arrhythmia, heart failure, and sudden cardiac death.^[7] Given that the prognosis of CS depends on phenotype and other factors, an early and precise diagnosis is necessary. Given the great mimicker of CS, some patients with CS are underdiagnosed and misdiagnosed. The use of multimodal imaging results is crucial to improving the sensitivity of CS diagnosis.^[8,9] Therefore, we present multimodality imaging findings from four cases with various CS phenotypes confirmed through endomyocardial biopsy at our hospital.

CASE SERIES

DISCUSSION

In our study, 4 patients with CS had arrhythmia and/or cardiac insufficiency as the main clinical manifestations, and they were easily misdiagnosed as other cardiomyopathies in clinical practice. This finding suggests that multimodal imaging techniques play various important roles in the diagnosis of cardiac nodules.

Modalities, such as echocardiography, CT, CMR, and PET, are highly valuable for the assessing of myocardial involvement in sarcoidosis. Echocardiography is the preferred initial choice, and it can be used to identify abnormal wall motion and reduced ejection fraction, although the findings are not definitive for diagnosis. Chest CT is well recognized for its capability to characterize enlarged lymph nodes in the mediastinum and hilar. However, this procedure is limited in facilitating the early diagnosis of CS.

PET can detect both cardiac and extracardiac inflammation and is valuable for monitoring therapy and predicting patient outcomes. Patients with CS display focal FDG uptake of the myocardium. A “hot spot” of ¹⁸F-FDG-PET with a perfusion defect serves as a hallmark in the detection of CS.^[10] A recent meta-analysis reported PET sensitivity and specificity at 84% and 83%, respectively.^[11] Absent FDG uptake combined with abnormal perfusion indicates end-stage myocardial scarring, as illustrated by the imaging of the patient 3. A mismatch pattern and right ventricle uptake are important predictors of cardiac events.^[12,13] The widespread application of these findings is constrained by the variability in methodologies and differences in interpretation approaches.^[14]

For patients suspected of having CS, multiparametric CMR imaging can reveal not only cardiac anatomy and function but also myocardial edema and fibrosis. The inflammatory phase of CS is marked by granulomatous infiltration, which may lead to focal myocardial thickness and wall motion abnormalities as observed in cine CMR. Myocardial edema is readily detected in T₂-weighted imaging [Figures 1 and 2]. LGE is considered the principal magnetic resonance imaging technique for CS identification, with a reported sensitivity of 75–100% and a specificity of 77–85%.^[15] Although CS can affect any part of the myocardium, it typically involves the basal segments of the left ventricle and the right ventricle side of the septum.^[16,17] In chronic disease, granulomatous infiltration results in substantial myocardial fibrosis and scarring [Figures 3 and 4]. In addition, risk stratification and prediction of adverse outcomes in patients with CS can be achieved through the quantitative assessment of the degree of LGE intensification.^[18] In this case series, we have highlighted the importance of clear identification of the various phenotypes of CS, which include dilated cardiomyopathy-like, hypertrophic cardiomyopathy-like, arrhythmogenic, and other non-specific inflammatory cardiomyopathy. Each phenotype carries distinct diagnostic challenges, treatment strategies, and prognostic implications. Arrhythmogenic phenotypes may require implantable cardioverter defibrillator implantation to prevent sudden cardiac death, and dilated phenotypes primarily focus on heart failure management. CMR and PET can visualize the different stages of CS, which suggests the possibility of personalized treatment plans and different clinical outcomes for patients.

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Figure 1:

Imaging results for a 44-year-old patient during the active inflammation phase. (A) First-degree atrioventricular block and incomplete right bundle branch block were detected. (B-D) Cardiac magnetic resonance (CMR) showed nodular thickening of the right ventricular wall and interventricular septum with T2 high signal intensity in the short-axis geometry corresponding to apparent late gadolinium enhancement (white arrow). (E) Computed tomography result was negative. (F) ¹⁸F-fluorodeoxyglucose (FDG)-positron emission tomography revealed focal FDG update (white arrow). (G-I) CMR was repeated and revealed that a nodular enhancement was smaller than before (white arrow). (J) Endomyocardial biopsy showed the formation of non-caseating inflammatory granuloma in low-magnification hematoxylin-eosin (HE) staining (×10).

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Figure 2:

Imaging results for a 52-year-old woman with a hypertrophic cardiomyopathy-like phenotype of cardiac sarcoidosis. (A) Electrocardiogram showed short-array ventricular tachycardia. (B) Transthoracic echocardiogram revealed enlargement of the right atrium and left and right ventricles. (C-H) Cardiac magnetic resonance unveiled the ventricular septum, right and anterior left ventricles, corresponding to an apparent patchy transmural late gadolinium enhancement (white arrow). (I) Non-caseating epithelioid granulomas were shown on a photomicrograph ((Hematoxylin-eosin HE), x10). (J) CD68 immunostaining highlighted macrophages and giant cells (x10).

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Figure 3:

Imaging findings for a 37-year-old patient in the late phase of cardiac sarcoidosis (CS). (A) First-degree atrioventricular block and abnormal P and Q waves were observed. (B) Computed tomography results were negative. (C-H) Cardiac magnetic resonance (MR) revealed general thinning of the ventricular wall and late gadolinium enhancement in the interventricular septum, right ventricle, and ventricular free walls (white arrow). (I) ¹⁸F-fluorodeoxyglucose-positron emission tomography unveiled fixed perfusion defects corresponding to the affected areas seen in MR imaging. (J) Pathological images displayed the advanced phase of CS, which was characterized primarily by myocardial fibrosis with granulomas and chronic inflammation ((Hematoxylin-eosin HE), x10).

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Figure 4:

Imaging findings for a 57-year-old patient with a dilated cardiomyopathy-like phenotype of cardiac sarcoidosis. (A) Electrocardiogram showed atrial fibrillation. (B) Computed tomography revealed extracardiac lymphadenopathy (white arrow). (C-E) Cardiac magnetic resonance displayed scattered mid myocardial late gadolinium enhancement areas in the basal interventricular septum (white arrow in sub-figures C and E). (F) ¹⁸F-fluorodeoxyglucose (FDG)-positron emission tomography revealed no significant focal FDG update. (G) Photomicrographs illustrated lesions in a heart explant specimen composed of non-caseating epithelioid granulomas ((Hematoxylin-eosin HE), x20).

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Accurate diagnosis of CS presents a challenge due to the overlap of clinical and imaging findings with other infiltrative and inflammatory cardiomyopathies, such as giant cell myocarditis and ALVC. Giant cell myocarditis and CS display similar presentations and are hardly distinguishable; the former progresses rapidly, and the pathology shows the absence of non-caseating granuloma to support the diagnosis.^[19] ALVC is an rare inherited cardiomyopathy characterized by fibrofatty replacement of left ventricle myocytes, and LGE is observed in fibrofatty infiltrated areas.^[20]

CONCLUSION

An effective CS diagnostic approach necessitates the recognition of multimodality imaging features and addressing differential diagnostic challenges. This strategy aids in improving the early diagnosis, optimizing treatment plans, and enhancing the clinical outcomes of CS patients.