Cardiac sarcoidosis-state of the art review

Abstract

Sarcoidosis is a multi-system inflammatory disorder of unknown etiology resulting in formation of non-caseating granulomas. Cardiac involvement-which is associated with worse prognosis-has been detected in approximately 25% of individuals based on autopsy or cardiac imaging studies. Nevertheless, the diagnosis of cardiac sarcoidosis is challenging due to the low yield of endomyocardial biopsy, and the limited accuracy of various clinical criteria. Thus, no gold standard diagnostic criterion exists. This review will summarize the pathophysiology, diagnosis, and treatment of cardiac sarcoidosis with a focus on advanced cardiovascular imaging, We review the evidence to support a role for cardiac magnetic resonance (CMR) imaging in the initial evaluation of selected patients with suspected cardiac sarcoidosis, with cardiac positron emission tomography (PET) as an alternative or complementary initial diagnostic test in a subgroup of patients in whom CMR may be contra-indicated or when CMR is negative with continued clinical concern for myocardial inflammation. In addition to the diagnostic value of these tests, CMR and PET are also useful in identifying patients who have higher risk of adverse events such as ventricular tachycardia or death, in whom preventive therapies such as defibrillators should be more strongly considered. Although no randomized controlled trials for treatment of cardiac sarcoidosis exist, immunosuppressive therapy is often used. We review emerging evidence regarding the use of cardiac PET to identify and quantity the amount of myocardial inflammation as well as to guide the use of immunotherapy. Future studies are needed to determine the benefit of imaging guided therapies aimed at improving patient outcomes.

Keywords: Cardiac sarcoidosis; cardiac MRI; cardiac positron emission tomography (cardiac PET); review.

Figure 1

A 67-year-old man without known sarcoidosis presented with abnormal chest X-ray after evaluation for a cough. A prior transbronchial biopsy was inconclusive. Evaluation demonstrated normal ECG, Holter monitor with brief episodes of non-sustained ventricular tachycardia, and globally hypokinetic left ventricular systolic function (LVEF 44%). CMR (black background) images with LGE demonstrated diffuse patchy hyperenhancement in the basal and mid ventricle in a non-ischemic pattern in addition to transmural enhancement in the thinned apical lateral wall. Corresponding cardiac PET (white background) demonstrated focal (basal lateral and apical anterior and lateral) on diffuse uptake. Transbronchial biopsy was repeated showing non-caseating granulomas (lower right, at low power 40× and high power 200×), consistent with pulmonary sarcoidosis. CT images of the chest had no coronary calcium that would have indicated significant calcified coronary artery disease. Histology images courtesy of Dr. Patrick Malafronte, Department of Pathology, Walter Reed National Military Medical Center. CMR, cardiac magnetic resonance; LGE, late gadolinium enhancement; PET, positron emission tomography.

Figure 2

Serial FDG PET exams showing change in inflammation. The results of three serial studies over 25 months from a 46-year-old man with cardiac sarcoidosis treated with corticosteroids are shown. The color maps demonstrate the intensity of FDG uptake in a sagittal view. The grayscale images demonstrate serial perfusion images using 82-rubidium (top) and metabolism images using FDG (bottom) in three distinct axes at approximately the same location. For each scan, the measurements of LV ejection fraction, SUV maximum and SUV volumes are displayed. Adapted from (18). FDG PET, fluorodeoxyglucose positron emission tomography; SUV, standardized uptake values.

Figure 3

Use of CMR and 18F-FDG PET for the diagnosis and monitoring of cardiac sarcoidosis. Patients with normal CMR are unlikely to have significant cardiac involvement and may be monitored clinically. Select patients with high clinical suspicion of cardiac sarcoidosis and normal CMR might be considered for ¹⁸F-FDG PET. CMR may be preferable to ¹⁸F-FDG PET as a first line test to minimize ionizing radiation, although local institutional expertise may influence test choice. Patients with inflammation by ¹⁸F-FDG PET should be considered for anti-inflammatory therapy and repeat ¹⁸F-FDG PET imaging in 3–6 months to evaluate response to therapy. EF, ejection fraction; CMR, cardiac magnetic resonance; ¹⁸F-FDG PET, ¹⁸F-fluorodeoxyglucose positron emission tomography; ICD, implantable cardiac defibrillator.

Figure 4

Co-registration of separately acquired cardiac CMR, left panel with cardiac PET, right panel. The CMR was notable for a region of focal late gadolinium enhancement in the basal anterolateral wall. PET was significant for active inflammation in the same area in addition to an area of less intense inflammation in the basal anteroseptum that did not have significant LGE. CMR, cardiac magnetic resonance; PET, positron emission tomography; LGE, late gadolinium enhancement.