HIGH RISK OF MALIGNANT VENTRICULAR ARRHYTHMIAS IN CARDIAC SARCOIDOSIS ASSOCIATED WITH FAILURE TO SUPPRESS MYOCARDIAL INFLAMMATION ASSESSED BY FDG-PET SCANNING

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.

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MYOCARDIAL INFLAMMATION/FIBROSIS DETECTION BY PULSE-CANCELLATION ECHOCARDIOGRAPHY IN PATIENTS WITH CARDIAC SARCOIDOSIS-CORRELATION WITH FDG-PET

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(19)32101-1 ◽

2019 ◽

Vol 73 (9) ◽

pp. 1495 ◽

Cited By ~ 1

Author(s):

Lane Zhang ◽

Steven Fein ◽

Ping Lu ◽

Fantauzzi John ◽

David Steckman ◽

...

Keyword(s):

Fdg Pet ◽

Cardiac Sarcoidosis ◽

Myocardial Inflammation

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Utility of updated diagnositc criteria to detect isolated cardiac sarcoidosis

European Heart Journal ◽

10.1093/ehjci/ehaa946.2146 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

K Sato ◽

M Yamamoto ◽

T Ishizu ◽

M Ieda

Keyword(s):

Diagnostic Criteria ◽

Clinical Diagnosis ◽

Fdg Pet ◽

Cardiac Involvement ◽

Cardiac Sarcoidosis ◽

Histological Finding ◽

Left Ventricular ◽

Myocardial Inflammation ◽

Histologic Diagnosis ◽

Anti Inflammatory

Abstract Background Prior study reported around one-third of cardiac sarcoidosis (CS) are considered as isolated CS. Detection of CS is challenging due to the limited sensitivity of endomyocardial biopsy and applicability of guidelines, especially in patients without extra-cardiac involvement. Existing diagnostic criteria by Japanese Ministry of health and Welfare (JMHW) or Heart Rhythm Society (HRS) require the presence of extra-cardiac sarcoidosis for clinical diagnosis, isolated CS is not diagnosable in the absence of a positive histological finding. Recently, Japanese Society of Cardiology (JCS) updated diagnostic criteria for CS, which provides the pathway to diagnose isolated CS. Purpose We aimed to assess the reliability of the updated CS guideline in diagnosing CS compared to the prior guidelines. Methods We retrospectively identified 162 consecutive patients who underwent FDG-PET for suspected CS from 2012 through 2019. According to the updated JCS diagnostic criteria, patients were classified as histologic diagnosis of CS, clinical diagnosis of CS, or isolated CS (Figure A). We compared the association between diagnostic criteria and response with anti-inflammatory therapy. Results The JCS criteria classified 24 patients (15%) as having clinical CS, 4 (3%) as histological diagnosis of CS, and 21 (13%) as isolated CS. The JMHW criteria defined 22 patients (14%) as having CS (clinical 11%, histological 3%) and HRS criteria classified 11 patients (7%) as having CS (clinical 4%, histological 3%). Extra-cardiac involvement was detected in 36 patients (22%) with 8% of histological confirmation. Among the 126 patients without extra-cardiac involvement, prevalence of cardiac involvement was higher in isolated CS (P<0.05 for all). Compared with clinical diagnosis group, patients with isolated CS showed higher incident of regional wall motion abnormality (WMA) or left ventricular (LV) dysfunction (p=0.023). In the subgroup of 45 patients with serial FDG-PET evaluation, only updated CS criteria was associate with improvement in myocardial inflammation by FDG-PET (p<0.001). Conclusions Updated JCS diagnostic criteria detects CS patients with active myocardial inflammation which require anti-inflammatory therapy regardless of extra-cardiac involvement better than the prior guidelines. Diagnostic criteria for CS Funding Acknowledgement Type of funding source: None

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A prospective study of 18FDG PET in the prediction of relapse in patients with high risk clinical stage I (CS1) non-seminomatous germ cell cancer (NSGCT): MRC study TE22

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.4520 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 4520-4520 ◽

Cited By ~ 2

Author(s):

R. Huddart ◽

M. O’Doherty ◽

A. Padhani ◽

G. Rustin ◽

G. Mead ◽

...

Keyword(s):

High Risk ◽

Adjuvant Chemotherapy ◽

Relapse Rate ◽

Fdg Pet ◽

Cell Cancer ◽

Pet Scan ◽

Stage I ◽

Pet Scanning ◽

Study Results ◽

Free Rate

4520 Background: High risk stage I NSGCT is characterised by vascular or lymphatic invasion within the primary tumour. This group comprises ∼50% of stage I pts with, (untreated) a relapse rate of 35–40%. Options for the management of such pts include adjuvant chemotherapy, retroperitoneal lymph node dissection (± adjuvant chemotherapy) and surveillance, each achieving similarly high cure rates. An FDG PET scan may be able to aid discrimination between pts without occult metastatic disease, for whom surveillance is an attractive option, and those requiring immediate therapy. Methods: High risk (vascular invasion +ve) CS1 NSGCT pts underwent FDG PET scanning within ∼8 weeks of orchidectomy. PET+ve pts went off study, PET -ve pts were followed on surveillance. The primary outcome measure was the -ve predictive value of PET, defined as the 2-year relapse-free rate (RFR) in pts with a negative PET scan. Assuming a RFR of ∼90%, to exclude a RFR < 80% with 80% power (5% significance), ∼100 PET negative pts were required from ∼135 scanned pts. All baseline CT scans were subject to central review blinded to PET result and relapse status and, in relapsed pts, a retrospective comparison of the CT and PET scan results. Results: Pts were registered between 5/02 and 1/05, when the trial was stopped early by the independent Data Monitoring Committee due to an unacceptably high relapse rate in the PET-ve pts. 116 pts were registered of whom 111 underwent PET scans. 88 pts (79%) were PET-ve; 87 proceeded to surveillance and one requested adjuvant chemotherapy. With median follow-up of 11 months, 33 of the 87 pts on surveillance relapsed for a one-year relapse-free rate of 63% 90% CI (54%, 72%). The PET +ve/relapse rate was 69% in patients with normal markers pre-orchidectomy (n = 36) and 41% in those with raised markers (n = 66). There has been one death (suicide) amongst the PET -ve pts. The radiology and PET scan review will be completed by May 2006. Conclusions: Though PET identified a proportion of pts with disease not detected by CT scan the relapse rate amongst PET -ve pts remains high. The study results therefore suggest that 18FDG PET scanning is not able to identify pts at sufficiently low risk of relapse to replace other treatment options in this setting. No significant financial relationships to disclose.

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18-FDG PET Focal Lesion and Avidity Suppression As Early As Day-7 Post-Induction Chemotherapy Predicts for Superior Outcome in Newly Diagnosed Multiple Myeloma Patients Treated with Total Therapy 3 Trials.

Blood ◽

10.1182/blood.v120.21.2910.2910 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2910-2910

Author(s):

Saad Z Usmani ◽

Sarah Waheed ◽

Alan Mitchell ◽

John Crowley ◽

Antje Hoering ◽

...

Keyword(s):

Multiple Myeloma ◽

High Risk ◽

Induction Chemotherapy ◽

Fdg Pet ◽

Cox Regression ◽

Regression Modeling ◽

Focal Lesion ◽

Additional Information ◽

Pet Scanning

Abstract Abstract 2910 Background: 18-fluorodeoxy-glucose positron emission tomography (18-FDG PET) scanning is increasingly viewed as an important novel imaging tool in the initial workup of multiple myeloma (MM). Recent work from Italian investigators validated our previous report on the prognostic implications of PET scanning in terms of poorer outcome in the presence of higher focal lesion (FL) number, greater FDG uptake intensity, expressed as maximum standardized uptake value (SUVmax) and presence of extramedullary disease. Here, for the first time, we are reporting the prognostic implication of PET-FL and PET-SUVmax suppression after induction chemotherapy as they pertain to survival of patients enrolled in TT3A protocol employing VTD (bortezomib, thalidomide, dexamethasone) and TT3B protocol employing VRD(bortezomib, lenalidomide, dexamethasone), with median follow-up of 78 months and 48 months, respectively. Methods: Imaging parameters included standard metastatic skeletal survey (MBS) delineating the number of osteolytic lesions, STIR-derived MRI-based foal lesion (FL) number (limited to the axial skeleton bone marrow of head, spine, and pelvis). In the absence of FL, diffuse hyper-intense marrow (DHIM) involvement was also annotated1. As for PET scanning, FL number, SUVmax and EMD parameters were captured. PET studies were repeated on day 7 after initiation of the DT-PACE portion of the first induction cycle, prior to first transplant, and prior to maintenance initiation. Imaging data were complete for 429 patients at baseline including 394 with additional information on gene expression profiling (GEP)-derived high-risk. Day-7 PET data were available on 308 and 277 patients, respectively. Cox regression modeling was employed for overall survival (OS), progression free survival (PFS) and complete response duration (CRD). Results: Patient characteristics were fairly comparable among the TT3A and TT3B patients except higher proportions of patients with high-risk features (high beta-2-microglobulin, low albumin, high GEP-derived centrosome index) in TT3B. The number of MBS-OL (>2) adversely affected OS (p=0.0001) and PFS (p=0.005) in TT3A (p=0.0001), PFS (p=0.03) in TT3B with a trend apparent for OS (p=0.06). For CRD, trends were apparent for shorter CRD in the presence of OL >2 in TT3A. In case of baseline PET, results were quite consistent for the 3 endpoints examined and between protocols applied. Thus, patients with 0 or 1–3 FL had equally favorable OS, PFS and, less pronounced in TT3B, CRD. Those with FL >3 fared poorly. Adverse consequences of FL-associated SUVmax >3.9 are apparent for OS, PFS and CRD in TT3A, whereas with TT3B only trends were apparent. Among follow-up imaging, Day-7 PET was the earliest measure. As is apparent in Figure 1, the presence of more than 3 FL imparted shorter OS and PFS in both TT3A and TT3B, with comparable outcomes noted for patients presenting with 0 or 1–3 FL at that time. Similar trends were apparent for CRD with both TT3A and TT3B. Cox regression modeling that considered additional information on day-7 PET results revealed an independent negative impact of day-7 FL>3 in the absence and presence of GEP data for both OS and PFS. Importantly, such information made baseline PET-FL irrelevant for OS and PFS, with MBS-OL >2 remaining in the model for OS, even when GEP data were also analyzed. The other surviving baseline variables included GEP-70-defined high risk for all 3 endpoints examined including CRD, where no imaging parameter emerged as significant. In the case of day-7 PET-SUV max, prognostic significance only applied to OS and PFS in TT3A. Conclusions: The data presented herein, demonstrate that failure of FDG suppression as early as post-induction chemotherapy carries adverse outcome and can serve as prognostic indicators of long-term survival. We have thus established that early PET follow-up scanning can identify further risk discrimination that can be exploited toward therapy change. Disclosures: No relevant conflicts of interest to declare.

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Abstract 17238: Taper With Caution: A Case Report of Treatment Response of a Patient With Cardiac Sarcoidosis to Tapering of Steroid Therapy and Initiation of Methotrexate

Circulation ◽

10.1161/circ.142.suppl_3.17238 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

GAURANGA MAHALWAR ◽

HANAD BASHIR ◽

Jeffery Courson ◽

Anas Alameh

Keyword(s):

Ventricular Tachycardia ◽

Ventricular Arrhythmias ◽

Antiarrhythmic Drugs ◽

Cardiac Sarcoidosis ◽

Sustained Ventricular Tachycardia ◽

Myocardial Inflammation ◽

Prednisone Dose ◽

Pacemaker Placement ◽

Immunosuppression Therapy

Introduction: We present a case of a patient with systemic sarcoidosis with cardiac involvement who presented with palpitations and was noted to be in non-sustained ventricular tachycardia (NSVT) after being tapered down the prednisone dose and being started on methotrexate. Clinical Course: 49-year-old female presented with symptoms of palpitations for 10 day prior to presentation with associated lightheadedness. Her past medical history included cardiac sarcoidosis, atrial tachycardia and complete heart block with a pacemaker placement. Upon checking her remote pacemaker interrogation during the current admission she was found to have recurrent episodes of non-sustained ventricular tachycardia. Patient was diagnosed with sarcoidosis 4 months prior to presentation and was started on 50 mg of prednisone which was tapered down to 30 mg 2 months prior to patient’s presentation due to weight gain along with initiation of methotrexate therapy .Patient was started on amiodarone 200 mg daily with a loading dose of 400 TID while admitted. Her prednisone was increased temporarily and weekly methotrexate was continued. The patient was found to have resolution of symptoms and did not have recurrence of arrhythmia on telemetry. She was upgraded to ICD placement during the same admission and was discharged with follow up. Conclusions: Ventricular tachycardia (VT) resulting from myocardial inflammation is the most common arrhythmia in cardiac sarcoidosis (CS), found in up to 23% of the patients. Antiarrhythmic drugs such as amiodarone are standard treatment for VT in patients with CS. However, corticosteroid therapy has shown to be beneficial for ventricular arrhythmias (VA) as demonstrated in some studies while even worsening ventricular arrhythmias in minority of the patients. In our patient, the tapering of the prednisone dose despite introduction of methotrexate resulted in the recurrence of ventricular tachycardia which eventually resolved with the re-administration of the original dose of prednisone. This indicates that more definitive immunosuppression therapy guidelines are required for patients with CS.

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18Fluorodeoxyglucose Positron Emission Tomography in the Prediction of Relapse in Patients With High-Risk, Clinical Stage I Nonseminomatous Germ Cell Tumors: Preliminary Report of MRC Trial TE22—The NCRI Testis Tumour Clinical Study Group

Journal of Clinical Oncology ◽

10.1200/jco.2006.09.3831 ◽

2007 ◽

Vol 25 (21) ◽

pp. 3090-3095 ◽

Cited By ~ 80

Author(s):

Robert A. Huddart ◽

Michael J. O'Doherty ◽

Anwar Padhani ◽

Gordon J.S. Rustin ◽

Graham M. Mead ◽

...

Keyword(s):

Positron Emission Tomography ◽

High Risk ◽

Germ Cell ◽

Fdg Pet ◽

Clinical Stage ◽

Germ Cell Tumors ◽

Emission Tomography ◽

Positron Emission ◽

Pet Scanning ◽

Nonseminomatous Germ Cell Tumors

Purpose There are several management options for patients with clinical stage I (CS1) nonseminomatous germ cell tumors (NSGCT); this study examined whether an 18fluorodeoxyglucose positron emission tomography (18FDG PET) scan could identify patients without occult metastatic disease for whom surveillance is an attractive option. Methods High-risk (lymphovascular invasion positive) patients with CS1 NSGCT underwent 18FDG PET scanning within 8 weeks of orchidectomy or marker normalization. PET-positive patients went off study; PET-negative patients were observed on a surveillance program. The primary outcome measure was the 2-year relapse-free rate (RFR) in patients with a negative PET scan (the negative predictive value). Assuming an RFR of 90% to exclude an RFR less than 80% with approximately 90% power, 100 PET-negative patients were required; 135 scanned patients were anticipated. Results Patients were registered between May 2002 and January 2005, when the trial was stopped by the independent data monitoring committee due to an unacceptably high relapse rate in the PET-negative patients. Of 116 registered patients, 111 underwent PET scans, and 88 (79%) were PET-negative (61% of preorchidectomy marker–negative patients v 88% of marker-positive patients; P = .002); 87 proceeded to surveillance, and one requested adjuvant chemotherapy. With a median follow-up of 12 months, 33 of 87 patients on surveillance relapsed (1-year RFR, 63%; 90% CI, 54% to 72%). Conclusion Though PET identified some patients with disease not detected by computed tomography scan, the relapse rate among PET negative patients remains high. The results show that 18FDG PET scanning is not sufficiently sensitive to identify patients at low risk of relapse in this setting.

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FDG-PET Scanning Shows Distributed Changes in Cortical Activity Associated with Visual Hallucinations in Eye Disease

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530318666180830112709 ◽

2019 ◽

Vol 19 (1) ◽

pp. 84-89 ◽

Cited By ~ 3

Author(s):

Lütfü Hanoglu ◽

Sultan Yildiz ◽

Tansel Cakir ◽

Taha Hanoglu ◽

Burak Yulug

Keyword(s):

Visual Cortex ◽

Fdg Pet ◽

Underlying Mechanism ◽

Posterior Cingulate Cortex ◽

Eye Disease ◽

Visual Hallucinations ◽

Charles Bonnet Syndrome ◽

Pet Scanning ◽

Inferior Parietal Cortex ◽

Visual Deafferentation

Background and Objective: Charles Bonnet Syndrome (CBS) has been defined as complex visual hallucinations (CVH) due to visual loss. The underlying mechanism of CBS is not clear and the underlying pathophysiology of the visual hallucinations in CBS patients and pure visually impaired patients is still not clear. </P><P> Methods: In our study, we have scanned three patients with eye disease and CBS (VH+) and three patients with eye disease without CBS (VH-) using FDG-PET. Results: Our results showed underactivity in the pons and overactivity in primary right left visual cortex and inferior parietal cortex in VH- patients and underactivity in left Broca, left inf frontal primary visual cortex and anterior and posterior cingulate cortex in VH+ patients relative to the normative 18FFDG PET data that was taken from the database consisting of 50 age-matched healthy adults without neuropsychiatric disorders. Conclusion: From this distributed pattern of activity changes, we conclude that the generation of visual hallucination in CBS is associated with bottom-up and top-down mechanism rather than the generally accepted visual deafferentation-related hyperexcitability theory.

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