Active Cardiac Sarcoidosis Research Articles

Cardiac Neuroendocrine Tumor Metastases on 68Ga-DOTATATE PET/CT: Identification and Prognostic Significance.

Neuroendocrine tumor (NET) metastases to the heart are found in 1%-4% of NET patients and have been reported primarily in the form of individual cases. We investigated the prevalence, clinical characteristics, imaging features, and outcomes of NET patients with cardiac metastases on 68Ga-DOTATATE PET/CT. Methods: 68Ga-DOTATATE PET/CT of 490 consecutive patients from a single institution were retrospectively reviewed for sites of metastases. The cumulative cardiovascular event rate and overall survival of patients with cardiac NET metastases (CNMs) were compared with those of a control group of metastatic NET patients without cardiac metastases. In patients with CNMs, the cardiac SUVmax with and without normalization to the myocardial background uptake was compared with a separate cohort of 11 patients with active cardiac sarcoidosis who underwent 68Ga-DOTATATE PET/CT for research purposes. Results: In total, 270 patients with metastatic NETs were identified, 9 (3.3%) of whom had CNMs. All 9 patients had grade 1-2 gastroenteropancreatic NETs, most commonly from the small intestine (7 patients). The control group consisted of 140 patients with metastatic grade 1-2 gastroenteropancreatic NETs. On Kaplan-Meier analysis, there was no significant difference in the risk of cardiovascular adverse events (P = 0.91 on log-rank test) or mortality (P = 0.83) between the metastatic NET patients with and without cardiac metastases. The degree of cardiac DOTATATE uptake was significantly higher in CNMs than in patients with cardiac sarcoidosis without overlap, in terms of both cardiac SUVmax (P = 0.027) and SUVmax-to-myocardial background ratio (P = 0.021). Conclusion: Routine 68Ga-DOTATATE PET/CT can be used to identify CNMs in 3% of patients with metastatic NETs. CNMs do not confer added cardiovascular or mortality risk. A distinguishing feature of CNMs is their high degree of DOTATATE uptake compared with focal myocardial inflammation.

The active papillary muscle sign in 18F-FDG PET/CT cardiac sarcoidosis exams and its relationship with myocardial suppression.

Papillary muscle (PM) activity may demonstrate true active cardiac sarcoidosis (CS) or mimic CS in 18FDG-PET/CT if adequate myocardial suppression (MS) is not achieved. We aim to examine whether PM uptake can be used as a marker of failed MS and measure the rate of PM activity presence in active CS with different dietary preparations. We retrospectively reviewed PET/CTs obtained with three different dietary preparations. Diet-A: 24-h ketogenic diet with overnight fasting (n = 94); Diet-B: 18-h fasting (n = 44); and Diet-C: 72-h daytime ketogenic diet with 3-day overnight fasting (n = 98). Each case was evaluated regarding CS diagnosis (negative, positive, and indeterminant) and presence of PM activity. MaxSUV was measured from bloodpool, liver, and the most suppressed normal myocardium. Linear mixed-effects models were used to compare these factors between those with PM activity and those without. PM activity was markedly lower in the Diet-C group compared with others: Diet-C: 6 (6.1%), Diet-A: 36 (38.3%), and Diet-B: 26 (59.1%) (p < 0.001). MyocardiumMaxSUV was higher, and MyocardiummaxSUV/BloodpoolmaxSUV, MyocardiummaxSUV/LivermaxSUV ratios were significantly higher in the cases with PM activity (p < 0.001). Among cases that used Diet-C and had PM activity, 66.7% were positive and 16.7% were indeterminate. If Diet-A or Diet-B was used, those with PM activity had a higher proportion of indeterminate cases (Diet-A: 61.1%, Diet-B: 61.5%) than positive cases (Diet-A: 36.1%, Diet-B: 38.5%). Lack of PM activity can be a sign of appropriate MS. PM activity is less common with a specific dietary preparation (72-h daytime ketogenic diet with 3-day overnight fasting), and if it is present with this particular preparation, the likelihood that the case being true active CS might be higher than the other traditional dietary preparations.

Characterisation and management of expected and unexpected urgent findings from positron emission tomography with 18F-fluorodeoxyglucose integrated with computed tomography in cardiovascular disease

BackgroundCardiac 18F-fluorodeoxyglucose (FDG)-PET-CT plays an important role in the assessment of cardiovascular diseases. Effective management of urgent scan findings facilitates optimal patient care. MethodsWe characterised the management of urgent, expected and unexpected findings in patients referred for cardiac [18F]fluorodeoxyglucose integrated with computed tomography (FDG-PET-CT) at the Royal Brompton Hospital (United Kingdom). Urgent findings are escalated by the reporting physicians/radiologists raising RadAlert notifications to the referring clinician. We characterised the indications and time to management (TTM) between the RadAlert and the resulting management. As controls, we characterised the TTM of 33 urgent findings identified before the RadAlert system was implemented. ResultsOf the 1497 consecutive FDG-PET-CT scans screened (April 2021 to February 2023), 93 RadAlerts were suitable for analysis (TTM 7 days [interquartile range: 2–14]). Expected urgent findings included active cardiac sarcoidosis (56%; TTM 8 days [5–18]), heart transplant rejection (12%; 6 ± 4 days), infective endocarditis (9%; 2 days [1–12]), cardiac device infections (5%; 1 day [0–2]), acute myocarditis (2%; 5 and 14 days) and epicardial mass (1%; 1 day). TTM did not differ significantly between indications (P = 0.06). RadAlert cases had significantly shorter TTM than controls without RadAlert, P = 0.001. After the RadAlerts, 81% of patients had clinical reviews, and 55% had escalation of medical/surgical therapies. Unexpected findings (total N = 45; median TTM 6 days [1–10]) included malignancies (N = 3), infections (N = 2), pneumothorax (N = 1), benign diagnosis (N = 30), unclear diagnosis (N = 5) and 4 findings disappeared on repeat imaging. ConclusionsCardiac FDG-PET-CT identifies expected and unexpected findings in a range of cardiovascular diseases. Serious, unexpected findings are rare and can be effectively escalated by the RadAlert system.

Hybrid Magnetic Resonance Positron Emission Tomography Is Associated With Cardiac-Related Outcomes in Cardiac Sarcoidosis

BackgroundImaging with late gadolinium enhancement (LGE) magnetic resonance (MR) and 18F-fluorodeoxyglucose (18F-FDG) PET allows complementary assessment of myocardial injury and disease activity and has shown promise for improved characterization of active cardiac sarcoidosis (CS) based on the combined positive imaging outcome, MR(+)PET(+). ObjectivesThis study aims to evaluate qualitative and quantitative assessments of hybrid MR/PET imaging in CS and to evaluate its association with cardiac-related outcomes. MethodsA total of 148 patients with suspected CS underwent hybrid MR/PET imaging. Patients were classified based on the presence/absence of LGE (MR+/MR−), presence/absence of 18F-FDG (PET+/PET−), and pattern of 18F-FDG uptake (focal/diffuse) into the following categories: MR(+)PET(+)FOCAL, MR(+)PET(+)DIFFUSE, MR(+)PET(−), MR(−)PET(+)FOCAL, MR(−)PET(+)DIFFUSE, MR(−)PET(−). Further analysis classified MR positivity based on %LGE exceeding 5.7% as MR(+/−)5.7%. Quantitative values of standard uptake value, target-to-background ratio, target-to-normal-myocardium ratio (TNMRmax), and T2 were measured. The primary clinical endpoint was met by the occurrence of cardiac arrest, ventricular tachycardia, or secondary prevention implantable cardioverter-defibrillator (ICD) before the end of the study. The secondary endpoint was met by any of the primary endpoint criteria plus heart failure or heart block. MR/PET imaging results were compared between those meeting or not meeting the clinical endpoints. ResultsPatients designated MR(+)5.7%PET(+)FOCAL had increased odds of meeting the primary clinical endpoint compared to those with all other imaging classifications (unadjusted OR: 9.2 [95% CI: 3.0-28.7]; P = 0.0001), which was higher than the odds based on MR or PET alone. TNMRmax achieved an area under the receiver-operating characteristic curve of 0.90 for separating MR(+)PET(+)FOCAL from non-MR(+)PET(+)FOCAL, and 0.77 for separating those reaching the clinical endpoint from those not reaching the clinical endpoint. ConclusionsHybrid MR/PET image–based classification of CS was statistically associated with clinical outcomes in CS. TNMRmax had modest sensitivity and specificity for quantifying the imaging-based classification MR(+)PET(+)FOCAL and was associated with outcomes. Use of combined MR and PET image–based classification may have use in prognostication and treatment management in CS.

Potential clinical utility of 68Ga-DOTATATE PET/CT for detection and response assessment in cardiac sarcoidosis

BackgroundSomatostatin receptor is expressed in sarcoid granulomas, and preliminary clinical studies have shown that myocardial sarcoidosis can be identified on somatostatin receptor-targeted PET. We examined the potential clinical use of 68Ga-DOTATATE PET/CT for diagnosis and response assessment in cardiac sarcoidosis compared to 18F-FDG PET/CT. MethodsEleven cardiac sarcoidosis patients with 18F-FDG PET/CT were prospectively enrolled for cardiac 68Ga-DOTATATE PET/CT. The two PET/CT studies were interpreted independently and were compared for patient-level and segment-level concordance, as well as for the degree of radiotracer uptake. Follow-up 68Ga-DOTATATE PET/CT was performed in eight patients. ResultsPatient-level concordance was 91%: ten patients had multifocal DOTATATE uptake (active cardiac sarcoidosis) and one patient showed diffuse DOTATATE uptake. Segment-level agreement was 77.1% (Kappa 0.53 ± 0.07). The SUVmax-to-blood pool ratio was lower on 68Ga-DOTATATE PET/CT (3.2 ± 0.6 vs. 4.9 ± 1.5, P = 0.006 on paired t test). Follow-up 68Ga-DOTATATE PET/CT showed one case of complete response and one case of partial response, while 18F-FDG PET/CT showed four cases of response, including three with complete response. ConclusionCompared to 18F-FDG PET/CT, 68Ga-DOTATATE PET/CT can identify active cardiac sarcoidosis with high patient-level concordance, but with moderate segment-level concordance, low signal-to-background ratio, and underestimation of treatment response.

Exploring the Utility of Cardiovascular Magnetic Resonance Radiomic Feature Extraction for Evaluation of Cardiac Sarcoidosis.

The aim of this study is to explore the utility of cardiac magnetic resonance (CMR) imaging of radiomic features to distinguish active and inactive cardiac sarcoidosis (CS). Subjects were classified into active cardiac sarcoidosis (CSactive) and inactive cardiac sarcoidosis (CSinactive) based on PET-CMR imaging. CSactive was classified as featuring patchy [18F]fluorodeoxyglucose ([18F]FDG) uptake on PET and presence of late gadolinium enhancement (LGE) on CMR, while CSinactive was classified as featuring no [18F]FDG uptake in the presence of LGE on CMR. Among those screened, thirty CSactive and thirty-one CSinactive patients met these criteria. A total of 94 radiomic features were subsequently extracted using PyRadiomics. The values of individual features were compared between CSactive and CSinactive using the Mann-Whitney U test. Subsequently, machine learning (ML) approaches were tested. ML was applied to two sub-sets of radiomic features (signatures A and B) that were selected by logistic regression and PCA, respectively. Univariate analysis of individual features showed no significant differences. Of all features, gray level co-occurrence matrix (GLCM) joint entropy had a good area under the curve (AUC) and accuracy with the smallest confidence interval, suggesting it may be a good target for further investigation. Some ML classifiers achieved reasonable discrimination between CSactive and CSinactive patients. With signature A, support vector machine and k-neighbors showed good performance with AUC (0.77 and 0.73) and accuracy (0.67 and 0.72), respectively. With signature B, decision tree demonstrated AUC and accuracy around 0.7; Conclusion: CMR radiomic analysis in CS provides promising results to distinguish patients with active and inactive disease.

Quantitative myocardial T2 mapping adds value to Japanese circulation society diagnostic criteria for active cardiac sarcoidosis.

Noninvasive identification of active myocardial inflammation in patients with cardiac sarcoidosis plays a key role in management but remains elusive. T2 mapping is a proposed solution, but the added value of quantitative myocardial T2 mapping for active cardiac sarcoidosis is unknown. Retrospective cohort analysis of 56 sequential patients with biopsy-confirmed extracardiac sarcoidosis who underwent cardiac MRI for myocardial T2 mapping. The presence or absence of active myocardial inflammation in patients with CS was defined using a modified Japanese circulation society criteria within one month of MRI. Myocardial T2 values were obtained for the 16 standard American Heart Association left ventricular segments. The best model was selected using logistic regression. Receiver operating characteristic curves and dominance analysis were used to evaluate the diagnostic performance and variable importance. Of the 56 sarcoidosis patients included, 14 met criteria for active myocardial inflammation. Mean basal T2 value was the best performing model for the diagnosis of active myocardial inflammation in CS patients (pR2 = 0.493, AUC = 0.918, 95% CI 0.835-1). Mean basal T2 value > 50.8ms was the most accurate threshold (accuracy = 0.911). Mean basal T2 value + JCS criteria was significantly more accurate than JCS criteria alone (AUC = 0.981 vs. 0.887, p = 0.017). Quantitative regional T2 values are independent predictors of active myocardial inflammation in CS and may add additional discriminatory capability to JCS criteria for active disease.

Abstract 14627: Angiotensin-Neprilysin Inhibition in Cardiac Sarcoidosis

Introduction: Sacubitril/Valsartan is an established treatment for heart failure patients with reduced ejection fraction (HFrEF). However, there is a paucity of data on its use in patients with cardiac sarcoidosis (CS). Hypothesis To establish the beneficial role of Sacubitril/Valsartan in cardiac sarcoidosis. Methods All consecutive CS patients taking Sacubitril/Valsartan were identified from our database from 2016 to 2022. They were followed up for at least 6 months with serial echocardiography. Data regarding symptoms and echocardiographic parameters were compared using Wilcoxon signed rank test. Results A total of 30 CS patients taking Sacubitril/Valsartan were identified (mean age: 56.73±11.63 years old). The diagnosis of CS was determined in all patients by a multi-disciplinary team. Patients were male predominant (73.3%). The prevalence of smoking, diabetes, hypertension and ischaemic heart disease was 20%, 10%, 10% and 3.3% respectively. Beta-blockers, mineralocorticoid receptor antagonists, prednisolone, implantable cardioverter defibrillator and cardiac resynchronisation therapy (defibrillator) were present in 93.3%, 96.7%, 53.3%, 16.7% and 56.7% patients respectively. At the time of diagnosis, 24 (80%) patients were found to have active cardiac sarcoidosis on cardiac PET. At 6-months following the commencement of Sacubitril/Valsartan, there was a significant improvement in LV ejection fraction (38.77±10.26% vs 32.87±9.30%, p&lt;0.001), LV end-systolic diameter (4.89±1.06cm vs 5.14±1.07cm, p=0.013) and New York Heart Association class (1.6±0.55 vs 2.0±0.52, p=0.001). During the median follow up of 24.9 months, the composite end-point of death and cardiac transplantation was reached in 3 (10%) patients (3 deaths and 0 cardiac transplantation). The patients experiencing at least one sustained ventricular arrhythmia (or aborted sudden cardiac death) decreased from 9 to 7 (p=0.21), the mean prednisolone dose was also comparable (11.56±4.42 vs 10.28±3.71, p=0.50) and none of the patients stopped Sacubitril/Valsartan. Conclusions Sacubitril/Valsartan in cardiac sarcoidosis patients with HFrEF is associated with at least short-term improvements in LV remodelling and functional status.

Impact of cardiac resynchronisation therapy in patients with cardiac sarcoidosis

Abstract Background Implantation of a device is usually required in cardiac sarcoidosis (CS) patients presenting with advanced conduction abnormalities or ventricular arrhythmias. A cardiac resynchronisation therapy (CRT) device is often chosen in patients with concomitant left ventricular systolic impairment. The role of CRT in CS is not well established. Purpose To describe the cohort of CS patients with CRT device in situ in our hospital focusing on the short-term effect in serial echocardiography and long-term outcomes on morbidity and mortality. Methods All consecutive CS patients with a CRT device in situ were identified in our CS database (2005–2022). A confident CS diagnosis was provided after review of all relevant clinical and imaging baseline data in our CS multi-disciplinary meeting and a consensus decision for CRT-D implantation was made based on international guidelines. All patients were followed up for at least 6 months with serial echocardiography. Serial data regarding symptoms, rhythm disturbance and echocardiographic parameters were obtained and comparisons were performed using Wilcoxon signed rank test. Results A total of 51 CS patients with CRT-D were identified (mean age: 57±10 years old). Patients were male predominant (64.7%) and Caucasian in origin (86.2%). Extra-cardiac sarcoidosis was confirmed histologically in 33 (64.7%) patients. The prevalence of smoking, diabetes, hypertension and ischaemic heart disease was 27.5%, 21.6%, 49.0% and 7.8% respectively. At the time of device implantation or during follow-up, 43 (84.3%) patients were found to have active cardiac sarcoidosis on cardiac PET. Post CRT implantation there was a significant difference in LV ejection fraction (35.9±15.0% vs 42.2±14.1%, p&amp;lt;0.001), LV end-systolic diameter (4.90±1.46 cm vs 4.62±1.32 cm, p=0.012) and LV end-diastolic diameter (5.99±1.18 cm vs 5.66±1.06 cm, p&amp;lt;0.001). No significant changes were observed in the right ventricular function (p=0.09) and severity of mitral regurgitation (p=0.40). There was one patient who experienced acute heart failure decompensation admission within six months of CRT-D implantation. The New York Heart Association (NYHA) class improved in 26 patients (51.0%), worsened in 4 (7.8%) patients and remained the same in 21 (41.2%) patients at 6 months post CRT-implantation. During the mean follow up of 47.6 months, the composite end-point of death and cardiac transplantation was reached in 9 (17.6%) patients (8 deaths and 1 cardiac transplantation). 5 patients had major complications including a large haematoma, a small atrio-septal defect, haemothorax, device associated endocarditis and lead fracture. Minor wound infections were seen in 3 patients and 4 patients received inappropriate shock or anti-tachycardia pacing. Conclusions CRT in cardiac sarcoidosis patients is associated with short-term improvement in LV remodelling and functional status but over a four year follow up, morbidity and mortality are common. Funding Acknowledgement Type of funding sources: None.

Increased 18F-fluorodeoxyglucose uptake in the cardiac atria: an evidence for increased atrial inflammation in patients with atrial fibrillation?

Abstract Funding Acknowledgements Type of funding sources: None. Background Atrial inflammation and fibrotic remodelling underlie the pathophysiology of atrial cardiomyopathy, which is associated with the development of atrial fibrillation (AF) and atrial flutter (AFL). 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) has been used to detect inflammatory processes. Recent studies have revealed an increased FDG-uptake in the atria of patients with AF, but also in patients with diagnosis of cardiac sarcoidosis with ventricular inflammation. Purpose This study aimed to assess the capability of PET/CT to detect and quantify the degree of atrial inflammation (FDG-uptake) in a population with dedicated cardiac FDG-PET/CT. Methods We investigated 101 patients suspected of sarcoidosis (57±12 years, 72% male) who underwent 18F-FDG PET/CT scan with dedicated cardiac specific preparation (heparin infusion, 12 hours fasting, and high-fat low-carbohydrate diet). We excluded patients with active ventricular cardiac sarcoidosis or undergoing high-dose immunosuppressive therapy (prednisolone ≥20mg/day or prednisolone combined with other immunotherapy like methotrexate). We measured the maximum standardized uptake value (SUVmax) in atrial myocardium and mean standardized uptake value (SUVmean) in blood pool and calculated the target-to-background ratio (TBR) of SUVmax in atrial myocardium to SUVmean in blood pool. All medical records, ECG data on arrhythmia type and diagnosis of systemic sarcoidosis (with absence of ventricular involvement) were used for the analysis. Sarcoidosis was diagnosed based on the criteria established in 2006 by the Japanese Ministry of Health and Welfare. The collected data were sorted according to presence of arrhythmia and systemic sarcoidosis and TBR of each group were compared. Results AF or AFL was found in 30/101 patients. Systemic sarcoidosis was found in 37/101 patients. Patients with known AF/AFL had significantly increased TBR within the atrial tissue compared to those without AF/AFL: (median: 1.26, 1st-3rd quartile: 1.20-1.33) versus (median: 1.22, 1st-3rd quartile: 1.14-1.25; p = 0.004; figure A). Arrhythmia-associated atrial inflammation was consistently observed, independently of presence of concomitant systemic sarcoidosis (figure B). Patients with both atrial arrhythmias and systemic sarcoidosis had the highest atrial inflammation level, as identified by TBR (figure B). Conclusion Development of atrial fibrillation or flutter is associated with an increased atrial FDG-uptake as metabolic marker of atrial inflammation. The level of atrial inflammation is further enhanced by additional presence of systemic sarcoidosis.

Multimodality Approach for Surveillance of Cardiac Sarcoidosis After Heart Transplantation Based on a Case Series

<h3>Purpose</h3> Cardiac sarcoidosis is an inflammatory, granulomatous disease of a progressive nature, which may clinically present as sudden death, arrhythmias, or heart failure (HF). When advanced, heart transplantation (HT) emerges as a therapeutic option. The post-transplant outcomes of this patients, regarding survival and rejections, seem to be similar to those related to other etiologies. However, the involvement of multiple organs by the disease and its reactivation potential is a concern regarding its recurrence in the transplanted heart, but its diagnosis, screening and immunosuppression strategy in this scenario are still little explored in the literature. <h3>Methods</h3> We retrospectively reviewed the clinical course of 4 patients with cardiac sarcoidosis who underwent HT between 2014 and 2021. <h3>Results</h3> We followed 4 female patients submitted to HT due to sarcoidosis. The first one transplanted in 2014, aged 32 years, and reativated sarcoidosis after 1 year, diagnosed by cardiac magnetic resonance imaging (MRI) compatible with inflammatory cardiomyopathy and died in 2017 of a non-cardiac cause. Second patient transplanted in 2020, aged 55 years, had high troponin levels also after 1 year post HT, with no evidence of rejection - subsequently, underwent cardiac PET/CT with accentuated diffuse uptake, received treatment with increased steroid dose, with an improvement in the marker after. The third, transplanted in 2021 aged 50 years, presented cardiac MRI after 1 month with a non-ischemic late mesoepicardial enhancement and PET/CT with moderate FDG uptake in the corresponding region suggestive of active cardiac sarcoidosis, using corticosteroids in increased dose for a while, showing improvement in the control PET/CT pattern. Finally, fourth patient transplanted in 2015, aged 40, with no evidence of reactivation of the disease so far, but due to sarcoidosis diagnosis previous to HT, she has always received higher doses of steroids. <h3>Conclusion</h3> There are few reports of recurrence of sarcoidosis after heart transplantation, which makes management of these cases challenging. An integrated approach that includes advanced imaging methods, routine serial endomyocardial biopsies, and serum biomarkers may be useful in monitoring this patients after HT, giving early diagnosis and treatment, which may be lifesaving given it´s potential fatal prognosis.

Exploring the Utility of Radiomic Feature Extraction to Improve the Diagnostic Accuracy of Cardiac Sarcoidosis Using FDG PET.

BackgroundThis study aimed to explore the radiomic features from PET images to detect active cardiac sarcoidosis (CS).MethodsForty sarcoid patients and twenty-nine controls were scanned using FDG PET-CMR. Five feature classes were compared between the groups. From the PET images alone, two different segmentations were drawn. For segmentation A, a region of interest (ROI) was manually delineated for the patients' myocardium hot regions with standardized uptake value (SUV) higher than 2.5 and the controls' normal myocardium region. A second ROI was drawn in the entire left ventricular myocardium for both study groups, segmentation B. The conventional metrics and radiomic features were then extracted for each ROI. Mann-Whitney U-test and a logistic regression classifier were used to compare the individual features of the study groups.ResultsFor segmentation A, the SUVmin had the highest area under the curve (AUC) and greatest accuracy among the conventional metrics. However, for both segmentations, the AUC and accuracy of the TBRmax were relatively high, >0.85. Twenty-two (from segmentation A) and thirty-five (from segmentation B) of 75 radiomic features fulfilled the criteria: P-value < 0.00061 (after Bonferroni correction), AUC >0.5, and accuracy >0.7. Principal Component Analysis (PCA) was conducted, with five components leading to cumulative variance higher than 90%. Ten machine learning classifiers were then tested and trained. Most of them had AUCs and accuracies ≥0.8. For segmentation A, the AUCs and accuracies of all classifiers are >0.9, but k-neighbors and neural network classifiers were the highest (=1). For segmentation B, there are four classifiers with AUCs and accuracies ≥0.8. However, the gaussian process classifier indicated the highest AUC and accuracy (0.9 and 0.8, respectively).ConclusionsRadiomic analysis of the specific PET data was not proven to be necessary for the detection of CS. However, building an automated procedure will help to accelerate the analysis and potentially lead to more reproducible findings across different scanners and imaging centers and consequently improve standardization procedures that are important for clinical trials and development of more robust diagnostic protocols.

Stable Extent of Recurrently Active Cardiac and Cutaneous Sarcoidosis.

Background: Recurrent or persistently active sarcoidosis is a risk factor for permanent organ damage. Whether this damage is due to accumulated focal injuries or progressive disease extent is not known, as the natural history of chronic inflammation in sarcoidosis is poorly characterized. The objective of this study is to determine the pattern of disease in recurrently active sarcoidosis.Methods: We identified patients with recurrent cardiac sarcoidosis (N = 21) retrospectively from an imaging database, and with recurrent cutaneous sarcoidosis (N = 17) from a prospective registry. The longitudinal patterns of cardiac sarcoidosis were established by findings on cardiac positron emission tomography scans, and of cutaneous sarcoidosis by the validated Cutaneous Sarcoidosis Activity and Morphology Instrument clinical scoring system. Patterns of recurrent disease were compared to baseline findings.Results: Recurrent sarcoidosis occurred in a nearly identical pattern and distribution as baseline disease, and spread of disease was rarely observed for both cardiac and cutaneous sarcoidosis: 97% of heart segments positive on recurrence scans were positive on baseline scans, and only one new region of facial disease was observed. In some cases, recurrence followed years of apparent remission.Discussion: Across phenotypes, and across a long period of follow-up, the extent of sarcoidosis was stable in spite of fluctuations in disease activity. For patients with a demonstrated history of recurrent disease affecting critical organs, our findings support the need for long-term follow-up.

Abstract 10664: Quantitative T2 Mapping to Diagnose Cardiac Sarcoidosis and Predict Incident Heart Failure

Introduction/Hypothesis: Myocardial native T2 quantification using cardiac magnetic resonance (CMR) may be helpful to diagnose active cardiac sarcoidosis and predict prognosis without the need for IV gadolinium. Methods: At a large academic institution, 66 consecutive patients with biopsy-proven pulmonary sarcoidosis underwent CMR for evaluation of active cardiac sarcoidosis (CS) from January 2017 to January 2020. Of these, 56 patients were identified who fit inclusion criteria. Active clinical CS was defined according to the Japanese Ministry of Health and Welfare criteria for diagnosis of CS. Quantitative T2 mapping of all AHA myocardial segments was evaluated and incident heart failure (HF) was recorded. A power calculation was performed beforehand which suggested n &gt; 50 was adequate. Results: The best fit model to identify active clinical CS was the mean T2 value of the basal segments (AUC 0.902, 95% CI 0.821-0.983; see Figure 1). Mean basal T2 &gt;51 ms was the optimal cutoff with accuracy of 91.1%, sensitivity of 71.4%, and specificity of 97.6%. T2 &gt;49 ms was the most sensitive cutoff (92.9%) with a negative predictive value of 96.2%. The best fit model to predict incident HF was the average T2 value of the basal segments (AUC 0.830, 95% 0.702-0.959). For every 1 ms increase in T2 value, there was a 41% increased risk for incident HF (odds ratio 1.41 95% CI 1.12-1.92, p=0.013). Conclusion: Measurement of mean basal myocardial T2 values efficiently identified patients with active clinical cardiac sarcoidosis and predicted incident heart failure. Quantitative T2 mapping is highly sensitive and specific for the diagnosis.

T2-weighted short-tau-inversion-recovery imaging reflects disease activity of cardiac sarcoidosis

ObjectiveWe investigated the diagnostic performance of semi-quantitative hyperintensity on T2-weighted short-tau-inversion-recovery black-blood (T2W-STIR-BB) images in identifying active cardiac sarcoidosis (CS) in patients, and compared it with that of 18F-fluoro-2-deoxyglucose positron...

Non-steroidal treatment of cardiac sarcoidosis: A systematic review.

The treatment of active cardiac sarcoidosis (CS) usually involves immunosuppressive therapy, with the goal of preventing inflammation-induced scar formation. In most cases, steroids remain the first-line treatment for CS. However, given the side effect profile of their long-term use, steroid-sparing therapies are increasingly used. There are no published randomized trials of steroid-sparing agents in CS. We sought to do a systematic review to evaluate the current published data on the use of non-steroidal treatments in the management of CS. We searched the Cochrane Library, Ovid Medline, Ovid Embase, PubMed, and Web of Science Core Collection databases from inception of database to August 2020 to identify the effectiveness of biological or synthetic disease-modifying antirheumatic agents (s- and bDMARDs). Secondary objectives include safety profile as well as the change in the average corticosteroid dose after treatment initiation. Twenty-three studies were ultimately selected for inclusion which included a total of 480 cases of CS treated with a range of both s- and bDMARDs. In all included studies, sDMARDs and bDMARDs were studied in combination with steroids or as second or higher-line treatments after therapeutic failure or intolerance to corticosteroid use. Methotrexate (MTX) and infliximab (IFX) were the most common synthetic and biologic DMARDs studied respectively, reported in about 35% of the studies reviewed. The use of steroid-sparing agents was associated with a reduction in the maintenance steroid dose used. In conclusion, steroids will remain as the cornerstone of anti-inflammatory management in patients with CS until trials on the use and safety profile of other immunosuppressive agents are completed and published.

Effectiveness and safety of infliximab in cardiac Sarcoidosis

BackgroundImmunosuppressive therapy in active cardiac sarcoidosis (CS) might prevent potential life-threatening complications. Infliximab (IFX) is a tumor necrosis factor alpha monoclonal antibody proven to be effective in refractory extracardiac sarcoidosis. It is sparsely used in CS, because of its association with worsening heart failure in prior studies. The goal of this study is to assess the effectiveness and safety of IFX in CS. Methods and resultsA retrospective, single center cohort study was performed in sarcoidosis patients treated with IFX based on a cardiac indication between January 2016 and March 2019. Patients received IFX intravenously at a dose of 5 mg/kg at week 0, 2, and subsequently every 4 weeks. After every six months, treatment response was evaluated within the multidisciplinary team using FDG-PET/CT, transthoracic echocardiography, biomarkers and device interrogation reports. Responder analysis definitions were based on; dosage of immunosuppressive drugs, improvement in functional class, left ventricular ejection fraction (LVEF) and SUVmax. Twenty-two patients were included (mean age 51.0 SD10.0 years, male 68.2%) with a mean follow-up of 18.9 months (6 to 44 months) of whom 18 (82%) were classified as responders. Median SUVmax on FDG-PET/CT decreased from SUVmax 5.2 [3.7–8.4] to 2.3 [1.4–2.3], p = 0.015. The target-to-background ratio decreased from 3.2 [2.1–5.1] to 1.0 [0.7–2.4], p = 0.002. The median left ventricular (LV) ejection fraction increased from 45.0% [34.0–60.0] to 55.0% [41.0–60.0], p = 0.02. The majority of patients (73%) experienced no side effects and no patients had worsening of heart failure. ConclusionIn this pilot study, patients with refractory CS treated with infliximab, on top of standard of care, had a reduction in inflammation on FDG-PET/CT and an improvement in LV function, without serious adverse events.

Quantitative analysis of myocardial metabolic heterogeneity is superior to visual assessment for the detection of active cardiac sarcoidosis by F-18 FDG PET-CT imaging

Abstract Funding Acknowledgements Type of funding sources: None. Background Myocardial inflammation may occur in the context of a multisystem disease such as sarcoidosis, adversely affecting prognosis. A definitive diagnosis of cardiac sarcoidosis (CS) is essential to implementing life-saving treatment but this is complicated by the invasive nature of endomyocardial biopsy (EMB) and its low accuracy. Positron emission tomography (PET) assists in diagnosis, which relies on visual interpretation of myocardial F-18 FDG uptake. The value of quantitative analysis and its application to clinical practice remain uncertain. Purpose To investigate the power of quantitative F-18 FDG PET-CT imaging analysis for detecting CS in patients with suspected disease. Methods All patients underwent F-18 FDG PET-CT after a 24-hour low-carbohydrate diet and 15-hour fasting as part of their diagnostic work-up for suspected cardiac inflammation. Cardiovascular magnetic resonance acted as gatekeeper to PET-CT in 8 of every 10 scans. Myocardial F-18 FDG uptake was assessed qualitatively and quantitatively using both manually drawn regions of interest and automatic polar maps to measure global and segmental standardised F-18 FDG uptake values (SUV). The coefficient of variation (CoV) was calculated to determine uptake heterogeneity. To confirm diagnosis, follow-up data regarding disease progression, further testing and treatment were collected. To allow for sufficient follow-up time, the first 40 consecutive patients from a prospective registry (n= 214; Sep 2017-Jun 2020) were included. Results A comprehensive clinical picture was obtained successfully in 37 patients (median [IQR], 17 [13.5] months) and a final diagnosis of CS reached in 7 (disease prevalence, 19%). EMB was performed in 2 patients only while 3 underwent PPM/ICD implantation. Significant predictors of CS were fulfilment of Japanese Ministry of Health and Welfare criteria (Wald, 6.44; p = 0.01) and left ventricular dysfunction (Wald 6.72; p = 0.01). Qualitative F-18 FDG PET-CT had a high negative (95%) but low positive (45%) predictive value for CS (sensitivity, 83%; specificity, 77%). F-18 FDG SUV CoV was the strongest imaging predictor (Wald, 6.77; p = 0.009) and was significantly higher in CS than non-CS (CoV median [quartiles], 0.26 [0.21, 0.36] and 0.12 [0.11, 0.14] respectively; p = 0.004). As per ROC curve analysis (AUC, 0.84), a CoV threshold of 0.20 was highly specific (93%) and sensitive (86%) for CS. Conclusion In a referring population with a low prevalence of cardiac sarcoidosis, F-18 FDG PET-CT imaging is sensitive for the detection of myocardial inflammation with active disease unlikely in patients with a negative scan. Quantitative evaluation of metabolic heterogeneity within the myocardium provides a strong, independent marker of active disease and should be considered alongside visual assessment.

ACCURACY OF MYOCARDIAL NATIVE T2 FOR THE DIAGNOSIS OF ACTIVE CARDIAC SARCOIDOSIS

SESSION TITLE: Late-breaking Abstract Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: To determine the accuracy of native T2 on cardiac magnetic resonance (CMR) in the diagnosis of active cardiac sarcoidosis when compared to combined clinical diagnosis and cardiac positron emission tomography (PET) as the gold standard. METHODS: 24 patients were identified who had received both cardiac MRI and PET within a 6-month period between May 2017 and May 2020. 6 patients were excluded due to lack of active cardiac sarcoidosis at the time of imaging. T2 and PET American Heart Association (AHA) left ventricular segment mapping was loaded onto polar plots and compared with the gold standard. Statistical analysis was performed in XLSTAT including logistic regression and two-tailed T tests. RESULTS: A total of 18 patients were included in the analyses. Five models were found that adequately predicted the diagnosis of active cardiac sarcoidosis: PET SUV > 2.5 (R2 = 0.132, AUC = 0.722), max SUV (R2 = 0.358, AUC = 0.833), T2 > 55 msec (R2 = 0.294, AUC = 0.722), T2 >59.4 msec (R2 = 0.258, AUC = 0.736), and max T2 (R2 = 0.408, AUC = 0.875). The best model was using max T2 value as a predictor of active cardiac sarcoidosis, which suggested a 95% probability of a positive test at 59.4 msec. The odds ratio for every integer increase in max T2 msec was 2.098 (95% CI 0.92 – 4.78). CONCLUSIONS: The use of T2 imaging is at least as predictive of active cardiac sarcoidosis as PET in three different models. The best fit model was using T2 max. T2 > 55 msec was the most sensitive model (91.7%), while T2 > 59.4 was the most specific (100%). At our institution, the optimal diagnostic threshold lies between these two values. CLINICAL IMPLICATIONS: Quantifiable T2 parameters indicative of active cardiac sarcoid can be coupled with late gadolinium enhancement on CMR to diagnose both active and inactive cardiac sarcoidosis using a single imaging modality. This would ultimately allow for fewer imaging studies and lower patient radiation exposure. DISCLOSURES: Owner/Founder relationship with YellowDot Innovations, LLC Please note: $20001 - $100000 Added 07/16/2020 by Jeremy Burt, source=Web Response, value=Ownership interest No relevant relationships by Jordan Chamberlin, source=Web Response Research Grant relationship with Medtronic Please note: $5001 - $20000 Added 07/16/2020 by Brian Houston, source=Web Response, value=Grant/Research Support No relevant relationships by Ennis James, source=Web Response No relevant relationships by Madison Kocher, source=Web Response No relevant relationships by William Rieter, source=Web Response No relevant relationships by Madalyn Snoddy, source=Web Response No relevant relationships by Natalie Stringer, source=Web Response Grant recipient relationship with Siemens Healthcare Please note: >$100000 Added 07/17/2020 by Akos Varga-Szemes, source=Web Response, value=Grant/Research Support Consultant relationship with Elucid Bioimaging Please note: $5001 - $20000 Added 07/17/2020 by Akos Varga-Szemes, source=Web Response, value=Consulting fee Consultant relationship with Bayer Healthcare Please note: $1001 - $5000 Added 07/17/2020 by Akos Varga-Szemes, source=Web Response, value=Consulting fee No relevant relationships by Jeffrey Waltz, source=Web Response

Cardiac Sarcoidosis multi-center randomized controlled trial (CHASM CS- RCT)

The Cardiac Sarcoidosis Multi-Center Randomized Controlled Trial (CHASM CS-RCT; NCT03593759) is a multicenter randomized controlled trial designed to evaluate the optimal initial treatment strategy for patients with active cardiac sarcoidosis. We hypothesize that (1) a low dose prednisone/methotrexate combination will have non-inferior efficacy to standard dose prednisone and that (2) the low dose prednisone/ methotrexate combination will result in significantly better quality of life than standard dose prednisone, as a result of reduced burden of side effects. Eligible study subjects will have active clinically manifest cardiac sarcoidosis presenting with one or more of the following clinical findings: advanced conduction system disease, significant sinus node dysfunction, non-sustained or sustained ventricular arrhythmia, left ventricular dysfunction or right ventricular dysfunction. Subjects will be randomized in a 1:1 ratio to prednisone 0.5 mg/kg/day for 6 months (maximum dose 30 mg daily) OR to prednisone 20 mg daily for 1 month, then 10 mg daily for 1 month, then 5 mg daily for one month then stop AND methotrexate 15-20 mg once weekly for 6 months. The primary endpoint is summed perfusion rest score on 6-month PET (blinded core-lab review). The summed perfusion rest score is measure of myocardial fibrosis/scar. The design is non-inferiority with a sample size of 97 per group. Given the multiorgan system potential adverse side effects of prednisone, proving noninferiority of an alternate regimen would be sufficient to make the alternative compare favorably to standard dose steroids. This is the first ever clinical trial in cardiac sarcoidosis and thus in addition to the listed goals of the trial, we will also establish a multi-center, multinational cardiac sarcoidosis clinical trials network. Such a collaborative infrastructure will enable a new era of high quality data to guide physicians when treating cardiac sarcoidosis patients.