Advanced imaging plays an important role in the diagnosis and management of cardiac sarcoidosis (CS). Cardiac magnetic resonance (CMR) is the recommended initial test in most clinical scenarios given its diagnostic and prognostic value.1,2 CS is unlikely in a patient whose CMR has no late gadolinium enhancement (LGE) present or only nonspecific right ventricular (RV) insertion point LGE.3 In situations where CMR cannot be performed safely or with adequate quality, fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is used as the initial test in the evaluation of a patient with left ventricular systolic dysfunction, high-grade atrioventricular block, or ventricular tachycardia (VT). FDG PET/CT is known to have high sensitivity for the diagnosis of CS, but low specificity, in part because of nonspecific myocardial FDG uptake.4 Some patterns of FDG uptake, such as diffuse myocardial uptake or lateral wall uptake,5 are known to be nonspecific; however, other patterns are less well known. We aimed to describe these patterns in a cohort of patients with a low likelihood of sarcoidosis from our FDG PET/CT registry who underwent CMR that did not show pathologic LGE within 12 months of FDG PET/CT imaging. These patients subsequently received a diagnosis of nonischemic cardiomyopathy (left ventricular ejection fraction [LVEF] <50%) or idiopathic cardiac disease, including atrial or ventricular arrhythmia, frequent premature ventricular complexes, high-grade atrioventricular block, or heart failure, all with a normal LVEF (≥50%). The study was approved by the Mass General Brigham Institutional Review Board and conducted in accordance with institutional guidelines.
We studied all consecutive patients referred to our center for technetium-99m perfusion single-photon emission computed tomography and FDG PET/CT for suspected CS (after dietary preparation of at least 2 meals the day before) from June 2006 to November 2023 who underwent CMR within 12 months of FDG PET/CT imaging and had no LGE or only RV insertion point LGE on their CMR images. Patients with biopsy-proven CS or extracardiac sarcoidosis (diagnosed before or after advanced imaging), suspected myocarditis, genetic cardiomyopathy, and ischemic cardiomyopathy were excluded. We then described and quantified the patterns of abnormal perfusion and myocardial FDG uptake in these patients by using previously described methods.4 Patients were followed up for sudden cardiac death, sustained VT (duration more than 30 seconds), appropriate implantable cardioverter-defibrillator (ICD) therapy, VT ablation, or placement of an ICD or upgrade from a permanent pacemaker to an ICD because of VT. All events occurred at least 30 days after advanced imaging. Follow-up advanced imaging was also reviewed where available.
The final cohort included 41 patients (mean age 51.6 ± 14.3 years; 68% male; 83% White; mean LVEF 40.9% ± 15.4%; 73% with no LGE; 27% with only RV insertion point LGE) with nonischemic cardiomyopathy and 39 patients (mean age 51.5 ± 15.0 years; 67% male; 82% White; mean LVEF 63.0% ± 6.2%; 90% with no LGE; 10% with only RV insertion point LGE) with idiopathic cardiac disease. Among all 80 patients, 0 (0%) had FDG uptake suggestive of extracardiac inflammation, 9 (11%) had abnormal myocardial perfusion, 56 (70%) had no focal FDG uptake, and 6 (8%) had diffuse FDG uptake. The patterns of the remaining 18 (23%) patients are shown in Figure 1. Nine (50%) of the 18 patients had lateral wall FDG uptake, 4 (22%) had lateral wall uptake with concomitant basal septal uptake, 3 (17%) had lateral wall uptake with concomitant basal septal and apical uptake, and 2 (11%) had basal anterior or anteroseptal uptake. Only 1 (6%) of these patients had perfusion-metabolic mismatch (basal anterior). Twenty-two of the 80 patients (28%) underwent genetic testing, and none had a pathogenic or likely pathogenic variant identified. Over a median follow-up of 4.9 years (Q1-Q3: 2.4–7.2 years), 2 patients had ICD therapy delivered, 1 had a permanent pacemaker upgraded to an ICD in response to VT, 1 underwent VT ablation, and 1 had an ICD placed for atrial fibrillation with torsades de pointes. None of these patients had any myocardial FDG uptake on FDG PET/CT. A total of 13 patients underwent repeat CMR (n = 6), FDG PET/CT (n = 5), or both (n = 2). One of the 8 follow-up CMR studies had subendocardial LGE in a coronary distribution, and the remainder had no LGE. Among the 7 follow-up FDG PET/CT studies, 3 had no focal FDG uptake (2 previously had diffuse FDG uptake and 1 previously had no focal FDG uptake), 2 had persistent diffuse FDG uptake, and 2 had persistent lateral wall FDG uptake.
FIGURE 1. Patterns, Frequency, and Quantification of Nonspecific Focal Myocardial FDG Uptake.
FDG = fluorodeoxyglucose; max = maximum; SUV = standardized uptake value.
In conclusion, the data from our study suggest that in addition to diffuse myocardial FDG uptake and lateral wall myocardial FDG uptake, focal basal anterior/anteroseptal, basal septal, or apical FDG uptake in the absence of perfusion-metabolic mismatch or FDG-avid extracardiac disease should raise suspicion for nonspecific uptake likely from inadequate suppression of physiologic FDG uptake in patients referred for FDG PET/CT for evaluation of suspected CS. Interpretation with beta-hydroxybutyrate testing5 or repeat imaging with prolonged dietary preparation (more than 2 meals the day before) may help improve diagnostic certainty.
What is the clinical question being addressed?
What are common patterns of nonspecific FDG uptake in patients with a low likelihood of sarcoidosis?
What is the main finding?
In a cohort of patients with a low likelihood of sarcoidosis who underwent CMR without pathologic LGE within 1 year of FDG PET/CT, in addition to diffuse uptake and lateral wall uptake, nonspecific patterns included focal basal anterior/anteroseptal, basal septal, and apical FDG uptake.
Acknowledgments
Dr Hankinson has received funding from the National Institutes of Health (grant number T32HL094301–15). Dr Desai has received grants and personal fees from AstraZeneca, Alnylam, and Novartis; and personal fees from Abbott, Amgen, Biofourmis, Boston Scientific, Boehringer Ingelheim, Corvidia, DalCor Pharma, Relypsa, Regeneron, and Merck Sharp and Dohme, outside of the submitted work. Dr Stewart has received support from the Kenneth L. Baughman Master Clinician Scholar Program in Cardiovascular Medicine at Brigham and Women’s Hospital; and has served as a consultant (clinical events committee) for Procyrion. Dr Lakdawala has received unrestricted funding on LMNA heart disease from the O’Hare Family Foundation, Pfizer, and Bristol Myers Squibb; and modest consulting incomes from Pfizer, Bristol Myers Squibb, Nuevocore, Alexion, Bayer, Cytokinetics, Sarepta, and Tenaya. Dr Givertz has served as a consultant and/or on an advisory board for Merck Sharp and Dohme; and has received institutional research support from Abbott Vascular, Endotronix, and Natera. Dr Tedrow has received consulting, research, speaker, and advisory board honoraria from Boston Scientific, Biosense Webster, and Abbott Medical. Dr Sauer has served as a paid consultant to Biosense Webster, Boston Scientific, AtriCure, Abbott, and Sanofi. Dr Blankstein has received funding grants from Amgen and Novartis. Dr Di Carli has received funding grants from Gilead Sciences, Sun Pharmaceuticals, and Amgen; has served as a consultant and/or advisor to Sanofi, MedTrace Pharma, and Valo Health. Dr Divakaran has received support from a Khoury Innovation Award from the Brigham and Women’s Hospital Heart and Vascular Center and a Master Clinician Scholar Award from the Department of Medicine at Brigham and Women’s Hospital.
Footnotes
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.
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