Diagnostic Accuracy of Advanced Imaging in Cardiac Sarcoidosis

Abstract

Background The diagnostic yield of cardiac sarcoidosis (CS) by endomyocardial biopsy is limited. Fluorodeoxyglucose (FDG) positron emission tomography (PET) and cardiac magnetic resonance imaging (MRI) may facilitate noninvasive diagnosis, but the accuracy of this approach is not well defined. We aimed to correlate findings from FDG PET and cardiac MRI with histological findings from explanted hearts of patients who underwent cardiac transplantation. Methods We analyzed the explanted heart histology for all patients who underwent cardiac transplant at our center from April 2008 to July 2018 and had pretransplant FDG PET (n=18) or cardiac MRI (n=31). The likelihood of CS based on FDG PET or cardiac MRI was categorized in a blinded fashion using a previously published method. RESULTS: Using a CS probable cutoff for FDG PET resulted in a sensitivity of 100.0% (95% CI, 54.1%-100.0%) and a specificity of 33.3% (95% CI, 9.9%-65.1%). Three of the 9 CS probable by FDG PET cases were found to be arrhythmogenic cardiomyopathy. The test characteristics of cardiac MRI are more challenging to comment on using our data as there was only one confirmed case of CS on post-transplant histological assessment. Of the 8 CS highly probable or probable cases by cardiac MRI, 3 were found to be dilated cardiomyopathy, and 2 were found to be end-stage hypertrophic cardiomyopathy. Conclusions FDG PET and cardiac MRI can help facilitate the diagnosis of CS in patients with advanced heart failure with a high degree of sensitivity but lower specificity.

Keywords: biopsy; cardiomyopathy; heart failure; sarcoidosis; transplantation.

Figure 1.. Example fluorodeoxyglucose positron emission tomography images and histology images of a case of cardiac sarcoidosis.

A. Short axis (SA), horizontal long axis (HLA), and vertical long axis (VLA) ^99mTc-sestamibi myocardial perfusion SPECT and FDG PET imaging showing perfusion defects with FDG uptake in the mid and basal anteroseptal and inferoseptal segments (arrows). This study was deemed CS highly probable given the mismatched defects. B. Coronal PET (left) and PET/CT whole body FDG imaging showing anteroseptal and inferoseptal myocardial uptake, as well as multiple FDG-avid bilateral mediastinal, bilateral hilar, and upper abdominal lymph nodes. C. Gross photograph of four-chamber view of the explanted heart showing diffuse involvement of the myocardium by sarcoid (arrows). The right ventricle is extensively involved, as is the interventricular septum, with more patchy involvement of the left ventricle. D. Photomicrograph of H&E stained section showing myocardium with a non-necrotizing granuloma containing abundant giant cells. There is fibrosis and a lymphocytic infiltrate at the periphery of the granuloma. (200X original magnification)

Figure 2.. Example fluorodeoxyglucose positron emission tomography images and histology images of a case of arrhythmogenic cardiomyopathy.

A. Short axis (SA), horizontal long axis (HLA), and vertical long axis (VLA) ^99mTc-sestamibi myocardial perfusion SPECT and FDG PET imaging showing a medium-sized perfusion defect in the apical anterior, septal, and inferior walls, as well as the left ventricular apex. There is also a small-sized perfusion defect in the basal inferolateral wall (arrows). There is FDG uptake in the apical lateral wall and the mid and basal anterolateral walls (arrows). While this pattern of FDG uptake is generally considered a normal variant, its association with perfusion defects in the absence of obstructive CAD was deemed abnormal and categorized as CS probable. B. Coronal PET (left) and PET/CT whole body FDG imaging showing anterolateral wall myocardial uptake, and the absence of abnormal extracardiac FDG uptake. C. Gross photograph of four chamber view of the explanted heart showing fatty replacement of the right ventricular free wall characteristic of AC (arrow). An automatic implantable cardioverter-defibrillator lead is seen in the right heart along with evidence of an apically placed left ventricular assist device. D. Photomicrograph of H&E stained section demonstrating transmural fibrofatty infiltration of the right ventricular free wall without other significant pathology. Occasional islands of viable myocardium remain. (40X original magnification)

Figure 3.. Example cardiac magnetic resonance imaging images and histology images of a case of cardiac sarcoidosis.

A. Short axis cardiac MRI images showing numerous large, focal areas of prominent LGE in the lateral, inferolateral, inferoseptal, and anteroseptal segments of the left ventricle as well as LGE of the right ventricular wall. Direct and contiguous extension of LGE across the interventricular septum into the right ventricle is seen in both images (arrows). This study was deemed CS highly probable given the pattern and location of the LGE. B. Gross photograph of four chamber view of the explanted heart showing patchy fibrosis of the left ventricular free wall, apex and basal interventricular septum characteristic of myocardial involvement by sarcoid (arrow). C. Photomicrograph of H&E stained section showing myocardium with a non-necrotizing granuloma containing abundant giant cells. There is a lymphocytic infiltrate at the periphery of the granuloma. (200X original magnification)

Figure 4.. Example cardiac magnetic resonance imaging images and histology images of a case of dilated cardiomyopathy.

A. Short axis cardiac MRI images showing direct and contiguous extension of LGE across the interventricular septum into the right ventricle and focal LGE of basal right ventricular insertions points (arrows). This study was deemed CS highly probable given the pattern and location of the LGE. B. Gross photograph of four chamber view of the explanted heart showing biventricular dilation and hypertrophy characteristic of DCM. There is evidence of an apically placed left ventricular assist device. C. Photomicrograph of H&E stained section demonstrating myocyte hypertrophy and interstitial fibrosis without inflammation or other significant pathology. (200X original magnification)