Usefulness of 18F-FDG PET in Diagnosing Cardiac Sarcoidosis
Sarcoidosis is a multisystem granulomatous disorder of unknown etiology. The number of patients with cardiac involvement is considered to be limited, but cardiac sarcoidosis is a very serious and unpredictable aspect of sarcoidosis resulting in conduction-system abnormalities and heart failure. The severity of cardiac involvement depends on the extent and location of the granulomatous lesions.
When establishing a diagnosis, 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) is a useful tool to detect active inflammatory lesions associated with sarcoidosis. The heart uses different energy sources including free fatty acids (FFA), glucose, and others. The 18F-FDG is an analog of glucose, and for the precise evaluation of the extent and severity of cardiac involvement, recent studies have focused on reducing physiological myocardial 18F-FDG uptake. Long fasting and dietary modification, such as observing a low-carbohydrate or high-fat diet, are the recommended regimens for preparations to make a precise evaluation. The FFA level before the PET scan could be a predictor of the success to the suppression of the physiological 18F-FDG accumulation.
With 18F-FDG PET therapy monitoring or risk stratification based on quantitative 18F-FDG accumulation becomes possible. The quantification of the volume and intensity of 18F-FDG uptake could assist in predicting the clinical outcomes and in evaluating the efficiency of steroid treatments.
This report provides a summary of the usefulness of 18F-FDG PET in its current status as a diagnostic modality for cardiac sarcoidosis.
KeywordsCardiac sarcoidosis Positron emission tomography Fluorodeoxyglucose
Sarcoidosis is a multisystem granulomatous disorder of unknown etiology. It is characterized by noncaseating, epithelioid granulomas. Typically, young or middle-aged adults are affected. In Japan, the annual incidence ranges from 1 to 2 cases per 100,000 of the population. The bilateral hilar and mediastinal lymph nodes, lungs, skin, musculoskeletal system, and eyes are well known to be involved in lesions. Essentially all organs, including the heart, may potentially be involved [1, 2].
Sarcoidosis patient treatment generally follows a favorable clinical course. However, about 30 % of patients suffer chronically or experience recurrence. Granulomas forming in an organ can affect how the organ functions and be a cause of signs and symptoms. Especially, prognosis is related to the presence of cardiac lesions .
The frequency of cardiac involvement varies and is significantly influenced by ancetstry. In Japan over 25 % of cases with sarcoidosis experience symptomatic cardiac involvement, whereas in the USA and Europe, only about 5 % of cases present cardiac involvement. Autopsy studies in the USA have shown the frequency of cardiac involvement to be about 20 %, whereas autopsy studies in Japan have shown a frequency above 50 % [4, 5, 6].
16.2 Diagnostic Criteria for Cardiac Sarcoidosis
Histologic analysis of operative or endomyocardial biopsy specimens could be the irrefutably best standard in diagnosing cardiac sarcoidosis. However, it is not feasible to perform endomyocardial biopsies on all suspected regions, and myocardial biopsies tend to have lower sensitivity in the diagnosis of cardiac sarcoidosis. Therefore, the Japanese Ministry of Health and Welfare (JMHW) guidelines for diagnostic imaging have been used as the diagnostic standard since early times . The JMHW criteria include both the histologic and the clinical diagnosis groups. For the clinical diagnosis group, the positive findings of electrocardiography, echocardiography, and 67Ga scintigraphy are the major criteria; minor criteria include findings of electrocardiography, echocardiography, perfusion images, and cardiac magnetic resonance images. Among the criteria, 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) is not included in the 2006 criteria; it is only noted as a comment that abnormal 18F-FDG accumulation in the heart is a diagnostically useful finding. However, the usefulness of 18F-FDG PET has been increasingly recognized; the Japanese health insurance system approved it for detection of inflammation sites in cardiac sarcoidosis on April 2012. Recently, the Heart Rhythm Society of the USA also proposed the diagnosis and management of cardiac sarcoidosis with 18F-FDG PET and MRI recommended for the evaluation of cardiac sarcoidosis, if there is a cardiac history and abnormality in the electrocardiogram or echocardiography in sarcoidosis patients .
16.3 Cardiac Metabolism
16.4 18F-FDG Uptake Patterns in Evaluations of Cardiac Sarcoidosis
16.5 Preparation for the 18F-FDG PET to Evaluate Cardiac Lesions
16.6 Location of the 18F-FDG Uptake
Cardiac sarcoidosis provoked the conduction disturbance such as atrioventricular block. There is a relationship between electrocardiogram abnormalities and myocardial 18F-FDG uptake. In particular, the focal 18F-FDG uptake in the interventricular septum in cardiac sarcoidosis is associated with atrioventricular blockage. Therefore, to identify the location of the 18F-FDG uptake is an important issue of potentially great benefit in treatment planning .
The 18F-FDG uptake due to inflammation in the LV wall is sometimes difficult to distinguish from the physiological uptake. On the other hand, the physiological uptake in the right ventricle (RV) is less common and less intense. Therefore, although less frequent of the sarcoidosis involvement, the 18F-FDG uptake in the RV due to cardiac sarcoidosis may be useful in diagnosing in sarcoidosis .
16.7 Relationship Between 18F-FDG Accumulation and Activity of Sarcoidosis
The significant 18F-FDG accumulation in cardiac sarcoidosis is caused by active inflammatory changes involving activated inflammatory cells like neutrophils, macrophages, and lymphocytes , and the 18F-FDG uptake may reflect an active inflammation condition. This makes 18F-FDG PET useful both for the detection of cardiac sarcoidosis as well as for monitoring the treatment response and early recurrence .
Observations from 18F-FDG PET images are a useful diagnostic tool to detect active inflammatory lesions associated with cardiac sarcoidosis. For a precise evaluation of the extent and severity of cardiac involvement, long fasting and dietary modifications, such as observing a low-carbohydrate or a high-fat diet, are recommended approaches to reduce physiological myocardial 18F-FDG uptake. The FFA level before the PET data acquisition could be a predictor for success in the suppression of physiological 18F-FDG accumulation. Such 18F-FDG PET images also enable therapy monitoring or risk stratification based on the quantitative accumulation determination. The quantification of the volume and intensity of 18F-FDG uptake may also help predict the clinical outcomes and evaluate the efficiency of steroid treatment.
This study was supported in part by grants from the Innovation Program of the Japan Science and Technology Agency and a Hokkaido Heart Association Grant for Research.
- 9.Manabe O, Yoshinaga K, Ohira H, et al. The effects of 18-h fasting with low-carbohydrate diet preparation on suppressed physiological myocardial (18)F-fluorodeoxyglucose (FDG) uptake and possible minimal effects of unfractionated heparin use in patients with suspected cardiac involvement sarcoidosis. J Nucl Cardiol. 2015. Aug. [Epub ahead of print]Google Scholar
Open Access This chapter is distributed under the terms of the Creative Commons Attribution-Noncommercial 2.5 License (http://creativecommons.org/licenses/by-nc/2.5/) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
The images or other third party material in this chapter are included in the work’s Creative Commons license, unless indicated otherwise in the credit line; if such material is not included in the work’s Creative Commons license and the respective action is not permitted by statutory regulation, users will need to obtain permission from the license holder to duplicate, adapt or reproduce the material.