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PET/CT Evaluation of Cardiac Sarcoidosis

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PET/CT Evaluation of Cardiac Sarcoidosis PET/CT Evaluation of Cardiac Sarcoidosis John P. Bois, MDa,*, Daniele Muser, MDb,1, Panithaya Chareonthaitawee, MDa KEYWORDS Cardiac sarcoidosis Positron emission tomography Fluorine-18 deoxyglucose KEY POINTS Sarcoidosis can involve the heart at with resultant significant morbidity and mortality. PET/CT is the most accurate method by which to diagnose cardiac sarcoidosis. Patient preparation prior to the PET/CT cardiac sarcoid study is critical to ensure diagnostic images are obtained. PET/CT detection of both active inflammation and scar has diagnostic, prognostic, and therapeutic importance. Ongoing areas of research include the use of PET to quantify the extent of myocardial inflammation and the discrepancies in myocardial blood flow in the cardiac sarcoidosis population. INTRODUCTION experiencing spontaneous remission and the remaining one-third developing either a stable or The increasing implementation of advanced car- progressive course.3 diovascular imaging in the form of cardiac PET/ The rate of cardiac involvement by sarcoidosis, CT has had a significant impact on the manage- otherwise termed CS, is variable and ranges ment of cardiac sarcoidosis (CS), one that con- from 20% to 75%.4,5 Furthermore, CS accounts tinues to evolve. Sarcoidosis is characterized for one-fourth of sarcoid-related mortality in the histologically by the presence of noncaseating United States and upward of 85% of death attrib- granulomas, with a predilection for the pulmonary uted to sarcoidosis in the Japanese population.4,6 system but with the ability to involve nearly every The high rate of involvement of the cardiovascular organ. Although the development of sarcoidosis system by sarcoidosis coupled with the potential is believed the sequelae of an exaggerated im- lethal outcomes has rendered accurate and timely mune or inflammatory response to an inciting in- diagnosis of this disease entity as imperative to fectious or environmental trigger, the specific patient care. Unfortunately, the prompt recogni- etiology of this disease remains elusive. The exact tion of CS itself may be elusive, with both tradi- prevalence of sarcoidosis is unknown but tends to tional imaging techniques as well as invasive be highest in women ages 25 years to 44 years 1,2 endomyocardial biopsies often providing a low (100 in 100,000) and in African Americans. There diagnostic yield.6 Consequently, there have been is also a geographic predilection for the develop- focused efforts to enhance or to develop noninva- ment of sarcoidosis, with some regions within the sive imaging techniques that not only detect CS United States reporting rates as high as 330 in 2 but also potentially provide therapeutic and prog- 100,000 patients. The course of the disease is nostic information for the treating clinician. Car- variable, with approximately two-thirds of patients diac PET/CT has emerged as a leading modality Conflict of Interest: The authors have no disclosures. a Department of Cardiovascular Diseases, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA; b Cardiovascular Division, Hospital of The University of Pennsylvania, Philadelphia, PA, USA 1 Present address: Via Pallanza 101, Udine 33100, Italy. * Corresponding author. E-mail address: [email protected] PET Clin 14 (2019) 223–232 https://doi.org/10.1016/j.cpet.2018.12.004 1556-8598/19/Ó 2018 Elsevier Inc. All rights reserved. pet.theclinics.com 224 Bois et al by which to begin to address these issues for the PATIENT PREPARATION FOR CARDIAC PET/CT CS patient population. FOR CARDIAC SARCOIDOSIS Optimal patient preparation is essential when us- INDICATIONS FOR CARDIAC PET/CT FOR ing fluorine-18 deoxyglucose (18F-FDG) PET/CT CARDIAC SARCOIDOSIS to evaluate for CS. The predilection for 18F-FDG The limited size of investigational studies involving accumulation within inflamed tissues, in particular the CS population and the lack of available pro- macrophages, is the pathophysiologic underpin- spective data have resulted in the inability to formu- ning of 18F-FDG PET/CT CS imaging. It is impera- late evidence-based guidelines to determine which tive, therefore, that physiologic myocardial uptake patients warrant PET/CT imaging for the assess- of 18F-FDG be suppressed to identify areas of ment of CS.7,8 The traditional diagnostic guideline pathologic involvement in a manner tht is both ac- for the detection of CS, as outlined by the Japanese curate and reproducible.11 Consequently, several Ministry of Health, Labour and Welfare, did not methods have been developed to achieve sup- include PET/CT imaging.6 The more contemporary pression of physiologic 18F-FDG uptake. guidelines, as proposed by the Heart Rhythm Soci- Cardiac myocyte metabolism is a dynamic and ety in 2014 and the revised Japanese Society of complex process that involves selective uses of Cardiac Sarcoidosis in 2017, did include PET/CT variable fuel sources, including free fatty acids, as a component of the diagnostic algorithm.9,10 glucose, and ketones.12 Which substrate is prefer- The surmised improved diagnostic capabilities of entially used is determined by a combination of the Heart Rhythm Society and the revised Japanese physiologic variables, including substrate avail- Society of Sarcoidosis criteria due to the inclusion ability, myocardial blood flow (MBF), and serum in- of PET/CT have yet to be systematically tested. sulin concentration.13 In the postprandial state, Given the absence of evidence-based guide- increased serum insulin levels result in glucose lines, Chareonthaitawee and colleagues8 have is- transporter 1 and glucose transporter 2 up- sued a joint expert consensus document on regulation, resulting in increased myocyte glucose behalf of the Society of Nuclear Medicine and Mo- uptake.14 One method by which to avoid physio- lecular Imaging (SNMMI) and the American Soci- logic myocyte uptake is instituting a prolonged ety of Nuclear Cardiology (ASNC), which outlines fast. During the fasting state, lipids in lieu of the following 4 patient scenarios for which cardiac glucose become the preferred myocyte substrate PET/CT for the assessment of CS could be and this is particularly the case with prolonged considered: fasting of upward of 18 hours.15 Prior studies have demonstrated that the success rates of fast- and Histologic evidence of extra CS 1ormore ing protocols in suppressing physiologic 18F-FDG abnormal screening results for CS (ECG range from 62% to 90% (Fig. 1).16–19 Unfortu- demonstrating completed left and/or right nately, prolonged fasting often proves laborious, bundle branch block, unexplained Q waves in and the lack of patient compliance is a 2 or more ECG leads, echocardiographic evi- concern.20,21 Furthermore, hypoglycemia poten- dence of regional wall motion abnormalities tially develops with the use of this technique.16 and/or aneurysms, basal septal thinning or A potential alternative to the prolonged fast is depressed left ventricular ejection fraction the implementation of a diet consisting of high fat (<50%), ventricular tachycardia, MR imaging and low carbohydrates. Studies have demon- evidence of midmyocardial inflammation, and, strated that this technique may be superior to fast- lastly, unexplained palpitations or syncope) ing alone.22 Concern again arises, however, New-onset sustained second-degree or third- regarding the ability of patients to adhere to such and degree atrioventricular block age less dietary recommendations due to potential reli- than 60 years old gious or cultural beliefs or due to an inability to Idiopathic sustained ventricular tachycardia tolerate such a diet. Another potential means by Serial studies to assess response to treatment which to increase serum free fatty acid levels is As cardiac PET/CT is further refined, standard- via the use of unfractionated heparin (typically ized, and utilized and as awareness of CS ex- administered dose is 50 U/kg approximately 15 mi- nutes prior to 18F-FDG administration), which stimu- pands, future evidenced-based guidelines may 16,23,24 become available. Until that juncture, however, lates lipolysis. A prior investigation of healthy the aforementioned 4 patient scenarios as outlined volunteers demonstrated that unfractionated hep- by experts in the field provide a useful tool for cli- arin could successfully increase free fatty acid levels without prolonging the partial thrombo- nicians in determining when to order a cardiac 25 PET/CT for the evaluation of CS. plastin time. Subsequent evaluations of the Evaluation of Cardiac Sarcoidosis 225 result, there has been a call to standardize proto- cols and to develop preparation guidelines.11 As a result, both the SNMMI and the ASNC have offi- cially recommended at least 2 high-fat (>35 g) and low-carbohydrate (<3 g) meals a day prior to the anticipated 18F-FDG PET/CT followed by a fast of 4 hours to 12 hours prior to the study, with an alternative a prolonged fast of 18 hours.26 To implement such guidelines, patient education prior to the study is imperative, with materials to facili- tate such a discussion having been previously published.27 Regardless of the exact methodology used to prepare patients for the study, nuclear physicians should be aware of 2 specific patient populations that provide unique challenges. The first is diabetic patients for whom an optimal dietary preparation has not been identified. Insulin-dependent dia- betic patients should continue basal insulin with minimization of rapid-acting insulin. If needed, a sliding scale may be implemented the day before but not the day of the study.8 For non–insulin- dependent patients, oral hypoglycemic agents should be avoided during periods of prescribed fasting.8 Unfortunately, despite extensive efforts to pro- hibit physiologic myocardial 18F-FDG uptake, approximately 30% of potential CS patients have an inconclusive scan, resulting in patient and pro- vider frustration, nondiagnostic exposure to radia- tion, and financial loss (Fig. 2).11,16,20,28–30 Consequently, the development of a radiotracer that does not demonstrate physiologic myocardial uptake and does not require dietary preparation would be of great potential benefit to the PET/CT assessment of the CS population.
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