Eugene Leung

The role of F(18)-fluorodeoxyglucose positron emission tomography in guiding diagnosis and management in patients with known or suspected cardiac sarcoidosis.

Cardiac sarcoidosis (CS) has gained significant interest in recent years with the emergence of advanced imaging modalities such as MRI and F18-fluorodeoxyglucose-positron emission tomography (FDG-PET) as modalities to aid in the diagnosis of this condition. CS remains a difficult condition to diagnose, particularly in cases of isolated cardiac involvement and it can present with a broad spectrum of clinical syndromes. Furthermore, the appropriate management of these patients remains controversial. FDG-PET has a potential role not only in diagnosis of CS but also in directing further therapies, facilitating the decision to start immunosuppression and monitoring the response to it. In this article, we discuss when to consider FDG-PET, outline the current optimal patient preparation and scanning protocols and then, using case examples, discuss the use of FDG-PET in follow-up of patients with known or suspected CS. We also outline how PET can influence management decisions in these patients.

Is There an Association Between Clinical Presentation and the Location and Extent of Myocardial Involvement of Cardiac Sarcoidosis as Assessed by 18F- Fluorodoexyglucose Positron Emission Tomography?

Background— Positron emission tomography using 18F-Fluorodeoxyglucose (FDG) is an emerging modality for diagnosis of cardiac sarcoidosis (CS). We compared the location and degree of FDG uptake in CS patients presenting with either advanced atrioventricular block (AVB) or ventricular tachycardia (VT). Methods and Results— We included consecutive patients who presented with either AVB or VT with a diagnosis of CS. A cohort of patients with clinically silent CS was included as controls. FDG activity was quantified as standardized uptake values (SUV) and both the overall mean left ventricular (LV) SUV as well as the Maximum Mean Segmental SUV was recorded for each patient. Receiver operator characteristic (ROC) analysis was performed to identify cutoff SUV values that best identified patients with VT. A total of 27 patients with CS were included (13 females; mean age, 56±8 years; 8 VT, 12 AVB, and 7 controls). Both mean LV SUV and Max SUV in CS patients presenting with VT were significantly higher compared with those with AVB (mean SUV: VT median 5.33, range 4.7–9.35 versus AVB median 2.48, range 0.86–8.59, P=0.016; max SUV: VT median 11.07, range 9.24–14.4 versus AVB median 5.63, range 3.42–15.71, P=0.005) and compared with controls. There was no significant difference in SUV values between AVB patients and controls. ROC analysis for identification of patients with VT showed AUCs of 0.93 and 0.895 for a mean LV SUV of >3.42 and a max SUV >8.56, respectively (P<0.001). Conclusions— CS patients with VT displayed significantly higher FDG uptake when compared with those with AVB and asymptomatic controls. Further prospective studies are required to evaluate this finding.

Atrioventricular Block as the Initial Manifestation of Cardiac Sarcoidosis in Middle-Aged Adults

Atrioventricular block (AVB) can be caused by several conditions, including cardiac sarcoidosis (CS). The prevalence of CS causing this presentation in a North American population has not been investigated and was the purpose of this study.

Prevalence of Cardiac Sarcoidosis in Patients Presenting with Monomorphic Ventricular Tachycardia

Sarcoidosis is a granulomatous disease of unknown etiology, which involves the heart in 5–25% of cases. Although ventricular tachycardia (VT) has been reported as the first presentation of sarcoidosis, its prevalence has not previously been investigated. In this prospective study, we sought to systematically investigate the prevalence of cardiac sarcoidosis (CS) in patients presenting with monomorphic VT (MMVT) and no previous history of sarcoidosis.

Arrhythmias in cardiac sarcoidosis: diagnosis and treatment.

Purpose of review Sarcoidosis is a granulomatous disease of unclear cause and variable presentation. Cardiac involvement can result in life-threatening conditions including heart block, ventricular tachycardia, sudden cardiac death, and heart failure. There is no consensus on the diagnosis and management of cardiac sarcoidosis and a practical update is needed to provide clinicians with guidance. Recent findings Three recent studies have described cardiac manifestations as the first presentation of sarcoidosis. In one study, cardiac sarcoidosis was found to be the underlying cause in 19% of adults aged less than 55 years presenting with new onset unexplained atrioventricular block. Also, there are increasing reports of patients with isolated cardiac sarcoidosis (i.e., without sarcoid in other organs). Finally, advances in imaging have enhanced our ability to detect myocardial involvement and perhaps follow response to treatment. Summary Cardiac sarcoidosis should be considered in patients aged less than 55 years presenting with unexplained atrioventricular block and in patients with idiopathic cardiomyopathy and sustained ventricular tachycardia. Much remains to be learned about the condition, including the role of steroids and devices in treatment, and the place of advanced imaging in following the response to treatment. Collaborative multicenter studies are required to answer these important clinical questions.

Positron Emission Tomography and Single-Photon Emission Computed Tomography Imaging in the Diagnosis of Cardiac Implantable Electronic Device InfectionCLINICAL PERSPECTIVE: A Systematic Review and Meta-Analysis

Background— The use of cardiac implantable electronic devices (CIED) is increasing, and their associated infections result in significant morbidity and mortality. The introduction of better cardiac imaging techniques could be useful for diagnosing this condition and guiding therapy. Our objective was to systematically assess the diagnostic accuracy of Fluor-18-fluorodeoxyglucose positron emission tomography and computed tomography, labeled leukocyte scintigraphy (LS), and Gallium-67 citrate scintigraphy for the diagnosis of CIED infection. Methods and Results— A systematic review of the literature and meta-analysis on the use of all 3 modalities in CIED infection were conducted. Pooled sensitivity, specificity, and summary receiver operating characteristic curves of each imaging modalities were determined. The literature search identified 2493 articles. A total of 13 articles (11 studies for 18F-FDG PET-CT and 2 for LS), met the inclusion criteria. No studies for 67Ga citrate scintigraphy met the inclusion criteria. The pooled sensitivity of 18F-FDG PET-CT for the diagnosis of CIED infection was 87% (95% CI, 82%–91%) and pooled specificity was 94% (95% CI, 88%–98%). The summary receiver operating characteristic curve analysis demonstrated good overall accuracy, with an area under the curve of 0.935. There were insufficient data to do a meta-analysis for LS, but both studies reported sensitivity above 90% and specificity of 100%. Conclusions— Both 18F-FDG PET-CT and LS yield high sensitivity, specificity, and accuracy, and thus seem to be useful for the diagnosis of CIED infection, based on robust data for 18F-FDG PET-CT but limited data for LS. When available,18F-FDG PET-CT may be preferred.

Inter- and Intra- observer agreement of FDG-PET/CT image interpretation in patients referred for assessment of Cardiac Sarcoidosis

Recent studies have reported the usefulness of 18F-FDG PET in aiding with the diagnosis and management of patients with cardiac sarcoidosis (CS). However, image interpretation of 18F-FDG PET for CS is sometimes challenging. We sought to investigate the inter- and intraobserver agreement and explore factors that led to important discrepancies between readers. Methods: We studied consecutive patients with no significant coronary artery disease who were referred for assessment of CS. Two experienced readers masked to clinical information, imaging reports, independently reviewed 18F-FDG PET/CT images. 18F-FDG PET/CT images were interpreted according to a predefined standard operating procedure, with cardiac 18F-FDG uptake patterns categorized into 5 patterns: none, focal, focal on diffuse, diffuse, and isolated lateral wall or basal uptake. Overall image assessment was classified as either consistent with active CS or not. Results: One hundred scans were included from 71 patients. Of these, 46 underwent 18F-FDG PET/CT with a no-restriction diet (no-restriction group), and 54 underwent 18F-FDG PET/CT with a low-carbohydrate, high-fat and protein-permitted diet (low-carb group). There was agreement of the interpretation category in 74 of 100 scans. The κ-value of agreement among all 5 categories was 0.64, indicating moderate agreement. For overall clinical interpretation, there was agreement in 93 of 100 scans (κ = 0.85). When scans were divided into the preparation groups, there was a trend toward higher agreement in the low-carb group versus the no-restriction group (80% vs. 67%, P = 0.08). Regarding the overall clinical interpretation, there was also a trend toward greater agreement in the low-carb group versus the no-restriction group (96% vs. 89%, P = 0.08). Conclusion: The interobserver agreement of cardiac 18F-FDG uptake image patterns was moderate. However, agreement was better regarding overall interpretation of CS. Detailed prescan dietary preparation seemed to improve interobserver agreement.

[(18)F]-NaF PET/CT Identifies Active Calcification in Carotid Plaque.

Although macroscopic calcium deposits in atherosclerotic plaques impart stability, microcalcific deposits can amplify mechanical stress in the fibrous cap by 600 kPa [(1)][1]. Blood flow, stress, and tension between calcified and noncalcified tissue can increase the risk of plaque rupture. It is

[18F]-Fluorodeoxyglucose PET/CT imaging as a marker of carotid plaque inflammation: Comparison to immunohistology and relationship to acuity of events

BACKGROUND [18F]-fluorodeoxyglucose (18FDG) uptake imaged with positron emission tomography (PET) and computed tomography (CT) may serve as a biomarker of plaque inflammation. This study evaluated the relationship between carotid plaque 18FDG uptake and a) intraplaque expression of macrophage and macrophage-like cellular CD68 immunohistology; b) intraplaque inflammatory burden using leukocyte-sensitive CD45 immunohistology; c) symptomatic patient presentation; d) time from last cerebrovascular event. METHODS 54 patients scheduled for carotid endarterectomy underwent 18FDG PET/CT imaging. Maximum 18FDG uptake (SUVmax) and tissue-to-blood ratio (TBRmax) was measured for carotid plaques. Quantitative immunohistological analysis of macrophage-like cell expression (CD68) and leukocyte content (CD45) was performed. RESULTS 18FDG uptake was related to CD68 macrophage expression (TBRmax: r = 0.51, p < 0.001), and total-plaque leukocyte CD45 expression (TBRmax: r = 0.632, p = 0.009, p < 0.001). 18FDG TBRmax uptake in carotid plaque associated with patient symptoms was greater than asymptomatic plaque (3.58 ± 1.01 vs. 3.13 ± 1.10, p = 0.008). 18FDG uptake differed between an acuity threshold of <90 days and >90 days (SUVmax:3.15 ± 0.87 vs. 2.52 ± 0.45, p = 0.015). CONCLUSIONS In this CAIN cohort, 18FDG uptake imaged with PET/CT serves a surrogate marker of intraplaque inflammatory macrophage, macrophage-like cell and leukocyte burden. 18FDG uptake is greater in plaque associated with patient symptoms and those with recent cerebrovascular events. Future studies are needed to relate 18FDG uptake and disease progression.

How common is isolated cardiac sarcoidosis? Extra-cardiac and cardiac findings on clinical examination and whole-body 18F–fluorodeoxyglucose positron emission tomography

BACKGROUND Sarcoidosis is a systemic inflammatory disease which can involve nearly any organ. Clinically manifest cardiac involvement occurs in perhaps 5% of patients with sarcoidosis. The reported prevalence of isolated cardiac sarcoidosis (CS) varies widely with reported rates of 27-54%. The explanation for this variability is likely multi-factorial but perhaps mostly related to the diagnostic method(s) for assessing extra-cardiac involvement. The primary aim of this study was to assess the rate of isolated CS in a homogeneous, prospectively recruited cohort of patients with clinically manifest CS, using whole body FDG PET-CT imaging as a gold standard. A secondary aim was to describe the extent and distribution of extra-cardiac sarcoidosis at the time of first presentation of clinically manifest CS. METHODS Patients were prospectively recruited at the time of first presentation with cardiac symptoms. All patients underwent whole-body and cardiac 18F-FDG PET-CT. All patients were examined for presence of skin sarcoidosis and were assessed by an ophthalmologist. RESULTS 31 patients were included (mean age 56±8years, 17 female, 100% Caucasian). Patients had limited extra-cardiac involvement (mean of 2.2 organs) however using the most precise definition, only 1/31 (3.2%) patients had isolated CS. There were marked differences in right ventricular (RV) and atrial involvement between patients presenting with CS as first presentation compared to patients presenting initially with extra-cardiac disease. CONCLUSIONS Most patients had limited extra-cardiac involvement at the time of presentation of manifest CS however, isolated CS, using the proposed gold standard, was only observed in one patient.