Increasing Use of Cardiac PET/CT for Inflammatory and Infiltrative Heart Diseases in Korea

Cardiac positron emission tomography (PET) has many advantages over single photon emission computed tomography, which include lower radiation doses, better image quality and quantitation of absolute myocardial blood flow, and coronary flow reserves.1 Based on its diagnostic and prognostic values, myocardial perfusion imaging with PET has gained its clinical relevance in the management of coronary artery disease.2, 3, 4

The advantage of lower radiation exposure from PET ironically leads to the need for an on-site cyclotron. The requirement of representative short-living radioisotopes (RI) such as O-15 and N-13, the half-lives of which are 3 min and 10 min, respectively, limits its wide spread as the primary imaging study in the clinical fields. A Rb-82 with generator system may provide an answer, which is widely being used in the USA; but it has not been widely accepted in the Asian countries yet. Particularly in Korea, the cost of PET imaging and camera occupation (which is longer than oncology PET imaging) generally exceed the benefit from direct referral for invasive coronary angiography without functional testing. Moreover, the recent announcement of the negative results of the global large-scale prospective ISCHEMIA trial raised active controversies over the usefulness of functional testing itself in the management of coronary artery disease.5

On the other hand, non-perfusion PET using F-18 fluorodeoxyglucose (FDG) is becoming more available in the fields of inflammatory and infiltrative heart diseases. Recently their incidences are increasing in Korea.6 Despite the incremental clinical needs, the traditional diagnostic imaging tools are not sufficiently sensitive or specific to detect the molecular processes underlying these disease entities. To fill the unmet need, the recent clinical guidelines are being modified based on the clinical studies using FDG PET to detect infective endocarditis and cardiac sarcoidosis.7, 8, 9

Despite the usefulness of FDG PET/CT in inflammatory and infiltrative heart diseases, the actual clinical trends have not been elucidated in Korea.10 The purpose of this paper is to investigate the recent trend of cardiac PET/CT usage in Korea, and use of FDG PET/CT for inflammatory and infiltrative heart diseases in the Chonnam National University Hospital (CNUH) and Chonnam National University Hwasun Hospital (CNUHH), and to discuss the further clinical applications of cardiac PET/CT.

The present study showed that the usage of cardiac PET/CT in inflammatory and infiltrative cardiac diseases has increased, which has paralleled the decreasing tendency of myocardial perfusion PET. This trend was mirrored in both domestic database and our institutional database.

The main cause of changing trend of cardiac diseases in Korea is the rapid aging of Korean population. Increases of valvular heart disease and arrhythmia were faster than that of coronary artery diseases. The number of patients with arrhythmia increased 57% in 7 years (from 232,547 in 2010 to 365,461 in 2017). The number of patients with valvular heart disease increased 55% in the same period (from 29,308 in 2010 to 45,581 in 2017). The increasing number is notable in aortic valve disease, which was 88% in the same period (from 14,058 in 2010 to 26,448 in 2017). An increase of patients with coronary artery diseases was only 30% in the same period.6 Non-rheumatic valvular heart diseases became the main cause of valvular heart diseases.12 In the nationwide database, the use of cardiac FDG PET/CT had two phases of rise in number. The first one was mainly based on its use for myocardial viability testing. This trend did not continue as the prospective clinical trials evaluating myocardial viability testing with FDG PET failed to show its value in the decision of revascularization for ischemic heart failure.13, 14 The use of cardiac FDG PET/CT, which was almost used for viability testing, decreased in the late 2000s and early 2010s. Another emerging imaging study, cardiac magnetic resonance (MR) imaging also accelerated the decreasing use of FDG PET in viability testing, taking advantage of the late gadolinium enhancement (LGE) imaging technique.

Recently, inflammatory and infiltrative heart diseases have become the novel targets of cardiac FDG PET/CT. Inflammatory changes follow many pathologic processes including valvular heart diseases and some infiltrative heart diseases such as cardiac sarcoidosis. Infective endocarditis particularly following prosthetic valve insertion is a deadly disease.15 Recently, FDG PET/CT is being increasingly used for detection and treatment response evaluation in inflammatory and infiltrative heart diseases. Clinical and imaging guidelines on such diseases stresses the use of cardiac PET/CT and its genuine values in their recommendations. These disease entities include infective endocarditis (particularly prosthetic valve endocarditis), infected cardiac implantable electronic devices, vascular graft infection, large vessel vasculitis, atherosclerosis and valvular disease, cardiac sarcoidosis, and cardiac amyloidosis.7, 16, 17, 18, 19, 20, 21

Cardiac MR can be a valuable alternative for evaluating inflammatory and infiltrative heart disease.22 The LGE of cardiac MR can detect small myocardial involvement lesions in a patient with cardiac sarcoidosis.23 Therefore, the international expert consensus statement suggests cardiac MR or FDG PET as an advanced imaging technique to patient where cardiac sarcoidosis with abnormal initial screening test results is suspected.24 In addition, the diffuse subendocardial LGE of cardiac MR is the distinct pattern in cardiac amyloidosis.25, 26 Not only the diagnostic impact, but the presence of transmural LGE is also an independent poor prognostic marker of cardiac amyloidosis patients.27

The most important practical consideration for imaging inflammatory and infiltrative heart diseases is suppression of physiologic myocardial FDG uptake. Low-fat high-carbohydrate dietand prolonged fasting for at least for 12 hours were sometimes combined with heparin injection are key factors for suppression of myocardial glucose uptake.7, 16, 17, 18, 19, 20, 21 This imaging technique is well accepted in the Korean community of cardiologists and cardiac surgeons as demonstrated in this paper.

The illustrated case shows that FDG PET/CT clearly shows cardiac involvement of sarcoidosis, and the response to steroid therapy (Fig. 2). Although sarcoidosis mostly involves the lungs, cardiac involvement develops in 25% and becomes major cause of death.28 If the sarcoidosis patient has one or more abnormalities, such as palpitation, syncope, abnormal electrocardiographic or echocardiographic findings, the patient is indicated to undergo imaging studies including FDG PET/CT.24 FDG PET/CT is mandatory when isolated cardiac sarcoidosis is suspected without evidence of systemic involvements.29

This paper has limitations. First of all, the number of cardiac PET/CT is small in authors' institutions and also in Korea. Only data from CNUH and CNUHH was analyzed for inflammatory and infiltrative heart diseases. Analysis of nationwide data is through the use of radiopharmaceutical, which can be reasonably used to assume the application of cardiac PET/CT for inflammatory and infiltrative diseases because FDG is the main radiopharmaceutical for this purpose. Secondly, a comparative analysis with global data was not done. We cited references instead of direct comparison. Despite these limitations we could show an increasing use of cardiac PET/CT for inflammatory and infiltrative heart diseases in Korea. Third, the nationwide survey in Korea is based on voluntary data collection from the domestic institutions, without obligation on strict data quality control. We authors categorized the studies in a highly specific manner, but potential biases during the data input had not been excluded.

In conclusion, cardiac PET/CT tailored for detection of inflammatory processes is useful for both detection and therapy while monitoring inflammatory and infiltrative heart disease. Fusion imaging of PET and CT enhances localization and characterization of even small lesions. Clinical use of cardiac PET/CT for inflammatory and infiltrative heart diseases is increasing in Korea.