Evaluating the association between hybrid magnetic resonance positron emission tomography and cardiac-related outcomes in cardiac sarcoidosis

Objectives: To evaluate an extended hybrid MR/PET imaging strategy in cardiac sarcoidosis (CS) employing qualitative and quantitative assessment of PET tracer uptake, and to evaluate its association with cardiac-related outcomes. Background: Invasive endomyocardial biopsy is the gold standard to diagnose CS, but it has poor sensitivity due to the patchy distribution of disease. Imaging with hybrid late gadolinium enhancement (LGE) MR and 18F-fluorodexyglucose (18F-FDG) PET allows simultaneous assessment of myocardial injury and disease activity and has shown promise for improved diagnosis of active CS based on the combined positive imaging outcome, MR(+)PET(+). Methods: 148 patients with suspected CS were enrolled for hybrid MR/PET imaging. Patients were classified based on presence/absence of LGE (MR+/MR-), presence/absence of 18F-FDG (PET+/PET-), and pattern of 18F-FDG uptake (focal/diffuse) into the following categories: MR(+)PET(+)FOCAL, MR(+)PET(+)DIFFUSE, MR(+)PET(-), MR(-)PET(+)FOCAL, MR(-)PET(+)DIFFUSE, MR(-)PET(-). Patients classified as MR(+)PET(+)FOCAL were designated as having active CS [aCS(+)], while all others were considered as having inactive or absent CS and designated aCS(-). Quantitative values of standard uptake value (SUVmax), target-to-background ratio (TBRmax), target-to-normal-myocardium ratio (TNMRmax) and T2 were measured. Occurrence of a cardiac-related clinical outcome was defined as any of the following during the 6-month period after imaging: cardiac arrest, ventricular arrhythmia, complete heart block, need for cardiac resynchronization/defibrillator/pacemaker/monitoring device (CRT-D, ICD/WCD, or ILR). MR/PET imaging results were compared to the presence of the composite clinical outcome. Results: Patients designated aCS(+) had more than 4-fold increased odds of meeting the clinical endpoint compared to aCS(-) (unadjusted odds ratio 4.8; 95% CI 2.0-11.4; p<0.001). TNMRmax achieved an area under the receiver operating characteristic curve of 0.90 for separating aCS(+) from aCS(-). Conclusions: Hybrid MR/PET imaging with an extended image-based classification of CS was statistically associated with clinical outcomes in CS. TNMRmax had high sensitivity and excellent specificity for quantifying the imaging-based classification of active CS.

Cardiac fibroblast activation detected by 68Gallium-FAPI-46 PET/MRI as a sign of chronic activity in cardiac sarcoidosis

In a patient with cardiac sarcoidosis, follow-up FDG-PET suggested complete remission under immunosuppression whereas FAPI-PET demonstrated ongoing fibroblast activation pointing at its potential to monitor chronic activity in sarcoidosis.

Histology of Cardiac Sarcoidosis with Novel Considerations Arranged upon a Pathologic Basis

Sarcoidosis is a rare disease of isolated or diffuse granulomatous inflammation. Although any organs can be affected by sarcoidosis, cardiac sarcoidosis is a fatal disorder, and it is crucial to accurately diagnose it to prevent sudden death due to dysrhythmia. Although endomyocardial biopsy is invasive and has limited sensitivity for identifying granulomas, it is the only modality that yields a definitive diagnosis of cardiac sarcoidosis. It is imperative to develop novel pathological approaches for the precise diagnosis of cardiac sarcoidosis. Here, we aimed to discuss commonly used diagnostic criteria for cardiac sarcoidosis and to summarize useful and novel histopathologic criteria of cardiac sarcoidosis. While classical histologic observations including noncaseating granulomas and multinucleated giant cells (typically Langhans type) are the most important findings, others such as microgranulomas, CD68+ CD163− pro-inflammatory (M1) macrophage accumulation, CD4/CD8 T-cell ratio, Cutibacterium acnes components, lymphangiogenesis, confluent fibrosis, and fatty infiltration may help to improve the sensitivity of endomyocardial biopsy for detecting cardiac sarcoidosis. These novel histologic findings are based on the pathology of cardiac sarcoidosis. We also discussed the principal histologic differential diagnoses of cardiac sarcoidosis, such as tuberculosis myocarditis, fungal myocarditis, giant cell myocarditis, and dilated cardiomyopathy.

Advances in Diagnostic Imaging for Cardiac Sarcoidosis

Sarcoidosis is a systemic granulomatous disease of unknown etiology, and its clinical presentation depends on the affected organ. Cardiac sarcoidosis (CS) is one of the leading causes of death among patients with sarcoidosis. The clinical manifestations of CS are heterogeneous, and range from asymptomatic to life-threatening arrhythmias and progressive heart failure due to the extent and location of granulomatous inflammation in the myocardium. Advances in imaging techniques have played a pivotal role in the evaluation of CS because histological diagnoses obtained by myocardial biopsy tend to have lower sensitivity. The diagnosis of CS is challenging, and several approaches, notably those using positron emission tomography and cardiac magnetic resonance imaging (MRI), have been reported. Delayed-enhanced computed tomography (CT) may also be used for diagnosing CS in patients with MRI-incompatible devices and allows acceptable evaluation of myocardial hyperenhancement in such patients. This article reviews the advances in imaging techniques for the evaluation of CS.

Stable Extent of Recurrently Active Cardiac and Cutaneous Sarcoidosis

Background: Recurrent or persistently active sarcoidosis is a risk factor for permanent organ damage. Whether this damage is due to accumulated focal injuries or progressive disease extent is not known, as the natural history of chronic inflammation in sarcoidosis is poorly characterized. The objective of this study is to determine the pattern of disease in recurrently active sarcoidosis.Methods: We identified patients with recurrent cardiac sarcoidosis (N = 21) retrospectively from an imaging database, and with recurrent cutaneous sarcoidosis (N = 17) from a prospective registry. The longitudinal patterns of cardiac sarcoidosis were established by findings on cardiac positron emission tomography scans, and of cutaneous sarcoidosis by the validated Cutaneous Sarcoidosis Activity and Morphology Instrument clinical scoring system. Patterns of recurrent disease were compared to baseline findings.Results: Recurrent sarcoidosis occurred in a nearly identical pattern and distribution as baseline disease, and spread of disease was rarely observed for both cardiac and cutaneous sarcoidosis: 97% of heart segments positive on recurrence scans were positive on baseline scans, and only one new region of facial disease was observed. In some cases, recurrence followed years of apparent remission.Discussion: Across phenotypes, and across a long period of follow-up, the extent of sarcoidosis was stable in spite of fluctuations in disease activity. For patients with a demonstrated history of recurrent disease affecting critical organs, our findings support the need for long-term follow-up.

The usefulness of repeated CMR and FDG PET/CT in the diagnosis of patients with initial possible cardiac sarcoidosis

Background Cardiac sarcoidosis (CS) diagnosis is usually based on advanced imaging techniques and multidisciplinary evaluation. Diagnosis is classified as definite, probable, possible or unlikely. If diagnostic confidence remains uncertain, cardiac imaging can be repeated. The objective is to evaluate the usefulness of repeated cardiac magnetic resonance imaging (CMR) and fluorodeoxyglucose positron emission tomography (FDG PET/CT) for CS diagnosis in patients with an initial “possible” CS diagnosis. Methods We performed a retrospective cohort study in 35 patients diagnosed with possible CS by our multidisciplinary team (MDT), who received repeated CMR and FDG PET/CT within 12 months after diagnosis. Imaging modalities were scored on abnormalities suggestive for CS and classified as CMR+/PET+, CMR+/PET−, CMR−/PET+ and CMR−/PET−. Primary endpoint was final MDT diagnosis of CS. Results After re-evaluation, nine patients (25.7%) were reclassified as probable CS and 16 patients (45.7%) as unlikely CS. Two patients started immunosuppressive treatment after re-evaluation. At baseline, eleven patients (31.4%) showed late gadolinium enhancement (LGE) on CMR (CMR+) and 26 (74.3%) patients showed myocardial FDG-uptake (PET+). At re-evaluation, nine patients (25.7%) showed LGE (CMR+), while 16 patients (45.7%) showed myocardial FDG-uptake (PET+). When considering both imaging modalities together, 82.6% of patients with CMR−/PET+ at baseline were reclassified as possible or unlikely CS, while 36.4% of patients with CMR+ at baseline were reclassified as probable CS. Three patients with initial CMR−/PET+ showed LGE at re-evaluation. Conclusion Repeated CMR and FDG PET/CT may be useful in establishing or rejecting CS diagnosis, when initial diagnosis is uncertain. However, clinical relevance has to be further determined.