Why Low Carb Diet Before Pet Scan – Comparison of the Effects of Three Different Dietary Modifications on Myocardial Inhibition by 18F-FDG PET/CT Evaluation in Patients with Suspected Cardiac Sarcoidosis
Can Özütemiz, Yasemin Koksel, Jerry W. Froelich, Nathan Rubin, Maneesh Bhargava, Henri Roukoz, Rebecca Cogswell, Jeremy Markowitz, David M. Perlman, and Daniel Steinberger
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3 Division of Pulmonary, Allergy, Intensive Care, and Sleep Medicine, University of Minnesota Department of Medicine, Minneapolis, MN; and
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There is no definitive literature-based dietary recommendation for myocardial suppression in the setting of cardiac sarcoidosis (SCC).
F-FDG PET/CT. Our aim is to compare 3 different dietary preparations to achieve the best myocardial inhibition and LV diagnosis. Methods: We retrospectively reviewed and compared 3 dietary supplements used in our institution. Since 2014 March to 2019 December. three different diets were applied: a 24-hour ketogenic diet with an overnight fast (
= 98). Interpretation of the original reports was recorded and an independent radiologist (observer) retrospectively re-evaluated each case for diagnosis of CV (negative, positive, indeterminate) and myocardial inhibition (complete, failed, partial). Interobserver agreement was analyzed. We measured SUVmax from the blood pool, the liver, and the most suppressed normal myocardium. Results: We found better myocardial inhibition with the 72-hour formulation, as indicated by higher blood pool-to-myocardium and liver-to-myocardium ratios (
< 0.001). Myocardial inhibition rates for the 72-hour ketogenic diet, 24-hour ketogenic diet, and 18-hour fasting formulations were as follows: complete myocardial inhibition 96.9%, 68.1%, and 52.3%, respectively; failed myocardial inhibition, 0%, 23.4%, and 25%, respectively; and partial myocardial inhibition, 3.1%, 8.5%, and 22.7%, respectively.
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< 0.001). The 72-hour preparation had significantly fewer equivocal and positive studies. CS diagnostic rates of 72-hour ketogenic diet, 24-hour ketogenic diet and 18-hour fasting preparations were negative – 82.7%, 52.1% and 27.3%, respectively; uncertain, 2.0%, 24.5%, and 40.9%, respectively; and positive in 15.3%, 23.4% and 31.8%, respectively (
0.88). Conclusion: A 72-hour daily ketogenic diet with 3 days of overnight fasting produces significantly better myocardial inhibition compared to a 24-hour ketogenic diet with overnight fasting and 18-hour fasting.
Cardiac sarcoid (CS) is difficult to diagnose. The clinical presentation can vary from asymptomatic to ventricular tachycardia, high-grade atrioventricular block, or heart failure (1, 2). The gold standard for diagnosis is endomyocardial biopsy. However, it is invasive, prone to false-negative results due to sampling errors, and has a low sensitivity for CS compared to autopsy (3). Therefore, non-invasive imaging methods, cardiac MRI and cardiology
F-FDG PET/CT (cPET/CT) is often used when screening or symptoms suggest cardiac involvement. Although both methods have limitations, they ultimately proved to be complementary because they measure different pathological processes (3–8).
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The main limitation of cPET/CT is related to physiological glucose metabolism in the myocardium. Normal healthy myocardium uses a combination of free fatty acids and glucose for energy under normal conditions. Thus, inhibition of physiological myocardial uptake is necessary to distinguish myocardial inflammation from normal physiological myocardial activity. This is achieved by changing the metabolism of the myocardium from the use of glucose to the use of free fatty acids (9). Several different nutritional and pharmacological modifications have been proposed to achieve this goal. However, there is no standardized approach, with protocols varying from institution to institution (3, 4, 7, 9–16). More recently, the Society for Nuclear Medicine and Molecular Imaging (SNMMI) and the American Society of Nuclear Cardiology (ASNC) jointly reported consensus guidelines for appropriate dietary modification in the evaluation of CS, including the following 2 options (3). First, the day before the test, the patient eats at least 2 high-fat (>35 g), low-carbohydrate (<3 g) meals and does not eat for at least 4-12 hours. Second, the patient did not eat for more than 18 hours before the test. Despite these attempts, a recent large review of the literature concluded that “a definitive recommendation for diet preparation is not possible based on the current evidence; however, readability appears to improve with lower carbohydrate intake during preparation” (10).
Metabolism of F-FDG. The first 2 methods were similar to the aforementioned consensus guidelines. The third method, a new nutritional protocol, involved a 72-hour continuous ketogenic diet with 3 days of overnight fasting. Our aim was to compare the effects of 3 different dietary modifications on cPET/CT in patients with suspected KS.
This Health Insurance Portability and Accountability Act-compliant retrospective study was approved by the Institutional Review Board (STUDY00005814) and therefore did not require written informed consent. All dedicated cPET/CT for CS since 2012. month of January. until 2019 December, received at the University of Minnesota for initial diagnosis or follow-up to assess response to treatment were collected into a PACS folder. During this time, three different dietary preparations were used. Diet-A (24-hour ketogenic diet) has been used since 2012. month of January. until 2018 February, Diet-B (18-hour fasting) from 2018 March to 2018 September, Diet-C (72-hour ketogenic diet with 3-day overnight fast) from 2018 September. until 2019 December. (Table 1).
Our goal was to compare an equal number of reviews for each diet. However, Diet-B was given for a limited time, so this group had less cPET/CT than the Diet-A and Diet-C groups. We found 98 studies on Diet-C. Therefore, the most recent 98 studies using Diet-A in 2018 were selected. in February, but 4 were subsequently excluded due to lack of image processing in the PET/CT viewer. Finally, a total of 236 cPET/CTs from 160 unique patients were included (Diet-A: 94 studies with 70 patients; Diet-B: 44 studies with 39 patients; Diet-C: 98 studies with 86 patients). Of the 160 subjects, 128 (80%) followed only 1 unique diet and 32 (20%) followed more than one type of diet.
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In addition to dietary changes, smoking was restricted for 6 hours and exercise was restricted for 24 hours prior to cPET/CT. If patients had diabetes, blood glucose levels must be less than 200 mg/dL and insulin was restricted for 6 hours prior to the study. cPET/CT was rescheduled if the above criteria were not met.
The researcher obtained the following information from the electronic medical records: date of examination, patient’s age, gender, body mass index, injected dose.
F-FDG, blood glucose immediately before cPET/CT, type of diet, adherence to the diet, and whether retesting was performed for non-adherence to the diet. All cPET/CTs were initially reported by 2 independent nuclear radiologists. The reports were retrospectively reviewed by the investigator and classified into 3 categories according to the presence of CS: active inflammation by CS = positive, no active inflammation by CS = negative and indeterminate, and myocardial inhibition into complete inhibition, partial inhibition, and failure inhibition.
All included cases were retrospectively evaluated by a single nuclear radiologist (observer). Qualitative and quantitative evaluation was performed using the SyngoVia MMoncology and MIcardiology applications. Each study was reformatted in oblique axial/coronal/sagittal planes according to the anatomical orientation of the heart (Figure 1) using PET emissions and CT images. In particular, in cases where the myocardium is heterogeneous or completely inhibited, the anatomical orientation of the heart is corrected according to the CT appearance. Quantitatively, blood pool-maxSUV (from the mediastinal descending thoracic aorta), liver-maxSUV (from the right lobe of the liver), myocardium-maxSUV (from the most suppressed part of the left ventricle) and lesion-maxSUV (from the most depressed).
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F-FDG – passionate part of the myocardium if active CS is suspected). Bloodpool-maxSUV/myocardium-maxSUV and liver-maxSUV/myocardium-maxSUV ratios were calculated.
A 62-year-old woman with inferior wall motion abnormalities, arrhythmia, and old external PET/CT presented with suspected KS. A previous endomyocardial biopsy was negative; there were no pathological or imaging signs of sarcoidosis elsewhere in the body. Based on the clinical findings, the patient was considered to have a possible CS and was referred for PET/CT. The first PET/CT was obtained while following Diet-B (above:
F-FDG/PET) which is reported as active CS with complete myocardial inhibition. However, the secondary outcome of partial suppression was assessed by the observer as indeterminate. The patient subsequently received steroids and was followed up with Diet-C (bottom). This time, both report and observer agreed that there was complete suppression without an active CS. Although it is possible that this putative case of KS responded to treatment, it is also possible that the initial interpretation was incorrect and the patient received unnecessary treatment.
Qualitatively, the presence of myocardial inhibition was visually categorized into 3 groups: if no physiological uptake was perceived, it was categorized as complete inhibition; if the uptake was heterogeneous without a typical mismatch pattern and the appearance did not suggest early active disease, it was categorized as partial suppression; and if diffuse uptake was present, it was categorized as failed inhibition. The presence of KS was assessed qualitatively according to 2 literature-based criteria. The first analysis consisted of 6 categories according to the SNMMI–ASNC guidelines: 1, normal; 2, diffuse nonspecific; 3, focal acquisition without mismatch
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N-ammonia, indicating early active disease; 4, focal uptake with mismatch pattern representing active disease; 5, focal uptake with mismatch pattern mixed with no
F-FDG is an avid perfusion defect representing the scar (3). The second analysis consisted of 4 categories according to Lu et al.: 1, normal; 2, annular diffuse uptake at the base is considered a negative CS; 3. absorption of the focus is considered a positive KS; 4, diffuse myocardial uptake is considered uncertain (7). To allow comparison of interobserver variability of radiology report and observer, these analyzes were stratified according to the SNMMI–ASNC classification – category 1 + 6 = negative; Category 2 = not specified; Category 3+
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