Non-Biopsy Diagnosis of Cardiac Transthyretin Amyloidosis

Background: Cardiac transthyretin (ATTR) amyloidosis is a progressive and fatal cardiomyopathy for which several promising therapies are in development. The diagnosis is frequently delayed or missed due to limited specificity of echocardiography and the traditional requirement for histologic confirmation. It has long been recognised that technetium labelled bone scintigraphy tracers can localise to myocardial amyloid deposits and use of this imaging modality for diagnosis of cardiac ATTR amyloidosis has lately been revisited. We conducted a multicentre study to ascertain the diagnostic value of bone scintigraphy in this disease. / Methods and Results: Results of bone scintigraphy and biochemical investigations were analysed from 1217 patients with suspected cardiac amyloidosis referred for evaluation in specialist centers. Among 857 patients with histologically proven amyloid (374 with endomyocardial biopsies), and 360 patients subsequently confirmed to have non amyloid cardiomyopathies, myocardial radiotracer uptake on bone scintigraphy was >99% sensitive and 86% specific for cardiac ATTR amyloid, with 'false positives' almost exclusively from uptake in patients with cardiac AL amyloidosis. Importantly, the combined findings of grade 2 or 3 myocardial radiotracer uptake on bone scintigraphy and absence of a monoclonal protein in serum or urine had a specificity and positive predictive value for cardiac ATTR amyloidosis of 100% (PPV CI 98.0-100). / Conclusions: Bone scintigraphy enables the diagnosis of cardiac ATTR amyloidosis to be made reliably without need for histology in patients who do not have a monoclonal gammopathy. We propose non-invasive diagnostic criteria for cardiac ATTR amyloidosis that are applicable to the majority of patients with this disease

Incidentally detected increased FDG uptake in bowel and its correlation with hystopathological data: our experience in a case series study.

When an intense intestinal FDG accumulation occurs, especially if focal, it can be referred to either physiological intestinal activity or bowel disease, thus leading to a radical change in patient's prognosis. Within a year, we recommended a colonoscopy to 103 of 7365 patients who were subjected to a total body FDG PET/CT. In a case-series study, we re-evaluated the patients and their lesions if already investigated with colonoscopy and biopsy. Only 18 patients were included in our study, but in none of them biopsy was negative and 3 adenocarcinomas, 8 adenomas, 5 inflammatory patterns, 1 hyperplastic polyp and 1 eosinophilic infiltrate were diagnosed. In 16 patients, no suspicion was present and diagnosis was absolutely incidental. Besides, among the three major groups (adenocarcinomas, adenomas and phlogosis), SUVmax values were significantly different. Adenocarcinomas are linked with high SUVmax values (ranging from 8.3 to 20.2) and large size (ranging from 26 to 43 mm). PET/CT sensitivity is low in detecting adenomas, being 71.4% if they are larger than 6 mm and 50% if SUVmax is lower than 4.9. SUVmax values in inflammatory lesions can range from 5.7 to 12. Colorectal cancer is still the second leading cause of cancer death, for this reason in many countries screening programs have been approved and colonoscopy is considered the golden standard. PET/CT cannot be considered as a screening test, but if it incidentally reveals intestinal abnormalities, this data cannot be underestimated and colonoscopy is highly recommended

Role of (11)C-choline PET/CT in the re-staging of prostate cancer patients with biochemical relapse and negative results at bone scintigraphy

AIM: to evaluate the utility of (11)C-choline PET/CT in prostate cancer (PC) patients who have demonstrated a biochemical recurrence and a negative bone scintigraphy (BS). MATERIALS AND METHODS: 123 consecutive PC patients (mean age 67.6 years; range 54-83) with a biochemical relapse (mean PSA value 3.3ng/mL; range 0.2-25.5) after radical prostatectomy (RP) were included in our retrospective study. Patients underwent a BS that resulted negative and a (11)C-choline PET/CT within 4 months from BS (range: 1 day to 4 months; mean: 2.5 months). Validation of results was established by: (1) a positive biopsy, (2) a positive subsequent BS, CT or MR and (3) a normalization of (11)C-choline uptake after systemic therapy or a progression of the disease. RESULTS: (11)C-choline PET/CT was positive in 42/123 patients (34.1%). (11)C-choline PET/CT detected lesions in: bone (10 patients), lymph-nodes (20 patients), bone and lymph nodes (7 patients), bone and lung (1 patient), lymph-nodes and lung (1 patient), local relapse (3 patients). Overall, (11)C-choline PET/CT showed a total of 30 unknown bone lesions in 18/123 (14.6%) patients. CONCLUSION: (11)C-choline PET/CT showed a better sensitivity than BS in patients with biochemical relapse after RP: (11)C-choline PET/CT detected unknown bone lesions in 18/123 (14.6%) patients

Usefulness and limitations of (99m)Tc-3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy in the aetiological diagnosis of amyloidotic cardiomyopathy.

Purpose We previously reported in a small series of patients that 99mTc-3, 3-diphosphono-1, 2-propanodicarboxylic acid ( 99mTc-DPD) scintigraphy tested positive in transthyretin-related (TTR) (both mutant and wild-type) but not in primary (AL) amyloidotic cardiomyopathy (AC). We extended our study to a larger cohort of patients with AC. Methods We evaluated (1) 45 patients with TTR-related AC (28 mutant and 17 wild-type), (2) 34 with AL-related AC and (3) 15 non-affected controls. Myocardial uptake of 99mTc-DPD (740 MBq i.v.) was semiquantitatively and visually assessed at 5 min and at 3 h. Results Heart retention (HR) and heart to whole-body retention ratio (H/WB) of late 99mTc-DPD uptake were higher among TTR-related AC (HR 7.8%; H/WB 10.4) compared with both unaffected controls (HR 3.5%; H/WB 5.7; p< 0.0001) and AL-related AC (HR 4.0%; H/WB 6.1; p< 0.0001). For the diagnosis of TTR-related AC, positive and negative predictive accuracy of visual scoring of cardiac retention were: 80 and 100% (visual score ≥1); 88 and 100% (visual score ≥2); and 100 and 68% (visual score = 3). At adjusted linear regression analysis, TTR aetiology turned out to be the only positive predictor of increasing 99mTc-DPD uptake in terms of both HR [β 2.5, 95% confidence interval (CI) 1.5-3.5; p<0.0001] and H/WB (β 3.5, 95% CI 2.1-4.9; p<0.0001). Conclusion While 99mTc-DPD scintigraphy was confirmed to be useful for differentiating TTR from AL-related AC, diagnostic accuracy was lower than previously reported due to a mild degree of tracer uptake in about one third of AL patients. 99mTc-DPD scintigraphy can provide an accurate differential diagnosis in cases of absent or intense uptake evaluated by visual score

Evaluation of mosaic pattern areas in HRCT with Min-IP reconstructions in patients with pulmonary hypertension: could this evaluation replace lung perfusion scintigraphy?

To discuss the respective role of perfusion scintigraphy and Min-IP HRCT reconstruction in the evaluation of oligemic areas in patients with pulmonary hypertension. Abstract Purpose: The aim of this study is to evaluate a possible correlation between areas of lung attenuation, found in minimum intensity projection (Min-IP) reconstruction images performed with high resolution computed tomography without contrast medium (HRCT), and areas of lung perfusion alteration, found in lung perfusion scintigraphy (LPS). Materials and methods: Two independent radiologists, unaware of LPS results, evaluated retrospectively a group of 113 patients affected by pulmonary hypertension (HP) of different aetiology. These have been examined in a period of two years in our centre both by spiral computed tomography (CT) with and without contrast-medium and by LPS. The final diagnosis was determined on clinical data, right heart catheterisation and contrast enhanced CT in angiographic phase (CTPA). We reconstructed the Min-IP images of lung parenchyma in all the cases both in HRCT without contrast-medium, and in contrast enhanced CT in angiographic phase (CTPA) in axial, sagittal and coronal planes. The obtained images were qualitatively graded into three categories of pulmonary attenuation: homogeneous, inhomogeneous with non-segmental patchy defects, inhomogeneous with segmental defects. The same criteria of classification were used also for LPS images. In the group of patients with chronic thromboembolic pulmonary hypertension (CTEPH) we also compared the number of areas of lung attenuation found in Min-IP images in HRCT without contrast-medium, and their exact localization, with not perfused areas in LPS. Gold standard for the diagnosis of pulmonary embolism was spiral contrast enhanced CT in angiographic phase (CTPA). Results: In all cases we found exact correspondence between the Min-IP images in HRCT with and without contras agent. The attenuation pattern seen on Min-IP images was concordant with those of LPS in 96 out of 113 patients (85%). In the remaining 17 cases (15%) it was discordant: in 12 cases inhomogeneous in Min-IP images (7 with non-segmental patchy defects, 5 with segmental defects) and homogeneous in LPS, in 5 cases inhomogeneous (1 with non-segmental patchy defects, 4 with segmental defects) in LPS images and homogeneous in Min-IP. In a general view, Min-IP reconstruction without contrast-medium showed a sensitivity of 100% and specificity of 96.1%, positive predictive value (PPV) of 92.3% and negative predictive value (NPV) of 100%, to recognize a pattern of lung attenuation inhomogeneous with segmental defects correspondent to a chronic thromboembolic condition, no false negative cases and three false positive cases; on the other hand LPS, on its own, showed a sensitivity of 91.67% and specificity of 93.51%, positive predictive value (PPV) of 86.84% and negative predictive value (NPV) of 96%, 3 false negative cases and 5 false positive cases. Conclusion: Min-IP obtained in HRCT without contrast-medium and in CTPA were equivalent. Min-IP images generally showed a higher sensitivity and specificity than LPS in the evaluation of lung perfusion regarding patients with pulmonary hypertension caused by different etiology, particularly in CTEPH patients. These results can be completed with the evaluation of HRCT and CTPA basal scans, providing more informations than ventilation/perfusion lung scintigraphy. HRCT images integrated by Min-IP reconstruction can represent the first step in the diagnostic algorithm of patients affected by dyspnoea and pulmonary hypertension of unknown causes, reserving the use of contrast-medium only in selected patients and reducing the patients' X-ray-expositio

Selecrive myocardial uptake of 99mTc-DPD in transthyretin-related amyloidosis: implication for recognition of cardia involvement and differential diagnosis with AL amyloidosis.

Contains fulltext : 215796.pdf (publisher's version ) (Open Access)Radboud University, 23 januari 2020Promotor : Levinson, S.C. Co-promotor : Meyer, A.S.XIV, 207 p

Usefulness and limitations of 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy in the aetiological diagnosis of amyloidotic cardiomyopathy.

PURPOSE: We previously reported in a small series of patients that (99m)Tc-3,3-diphosphono-1,2-propanodicarboxylic acid ((99m)Tc-DPD) scintigraphy tested positive in transthyretin-related (TTR) (both mutant and wild-type) but not in primary (AL) amyloidotic cardiomyopathy (AC). We extended our study to a larger cohort of patients with AC. METHODS: We evaluated (1) 45 patients with TTR-related AC (28 mutant and 17 wild-type), (2) 34 with AL-related AC and (3) 15 non-affected controls. Myocardial uptake of (99m)Tc-DPD (740 MBq i.v.) was semiquantitatively and visually assessed at 5 min and at 3 h. RESULTS: Heart retention (HR) and heart to whole-body retention ratio (H/WB) of late (99m)Tc-DPD uptake were higher among TTR-related AC (HR 7.8%; H/WB 10.4) compared with both unaffected controls (HR 3.5%; H/WB 5.7; p < 0.0001) and AL-related AC (HR 4.0%; H/WB 6.1; p < 0.0001). For the diagnosis of TTR-related AC, positive and negative predictive accuracy of visual scoring of cardiac retention were: 80 and 100% (visual score ≥1); 88 and 100% (visual score ≥2); and 100 and 68% (visual score = 3). At adjusted linear regression analysis, TTR aetiology turned out to be the only positive predictor of increasing (99m)Tc-DPD uptake in terms of both HR [β 2.5, 95% confidence interval (CI) 1.5-3.5; p < 0.0001] and H/WB (β 3.5, 95% CI 2.1-4.9; p < 0.0001). CONCLUSION: While (99m)Tc-DPD scintigraphy was confirmed to be useful for differentiating TTR from AL-related AC, diagnostic accuracy was lower than previously reported due to a mild degree of tracer uptake in about one third of AL patients. (99m)Tc-DPD scintigraphy can provide an accurate differential diagnosis in cases of absent or intense uptake evaluated by visual score

Defining the diagnosis in echocardiographically suspected senile systemic amyloidosis.

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Role of (99m)Tc-DPD scintigraphy in diagnosis and prognosis of hereditary transthyretin-related cardiac amyloidosis

OBJECTIVES: In a cohort of patients with hereditary transthyretin-related amyloidosis (ATTR), we aimed to assess the role of (99m)Tc-3,3-diphosphono-1,2-propanodicarboxylic acid ((99m)Tc-DPD) in detecting myocardial amyloid infiltration across a wide spectrum of cardiac involvement and in predicting major adverse cardiac events (MACE). BACKGROUND: Hereditary transthyretin-related amyloidosis is a challenging and underdiagnosed condition where both early diagnosis and prognosis remain problematic. METHODS: We evaluated 63 patients with ATTR: 40 with and 23 without echocardiographically diagnosed amyloidotic cardiomyopathy (AC). Myocardial uptake of (99m)Tc-DPD scintigraphy was semiquantitatively and visually assessed at 5 min and 3 h. RESULTS: All patients with AC showed moderate-to-severe myocardial tracer uptake (i.e., visual score ≥2). Within the subgroup without AC, only 4 patients (with Ala36Pro, Gly47Ala, Thr49Ala, and Glu89Gln transthyretin mutations) showed myocardial tracer uptake and abnormal heart/whole body retention (H/WB) values: in all these cases endomyocardial biopsies showed amyloidotic infiltration. The H/WB was positively correlated with left ventricular (LV) mean wall thickness (Pearson's r=0.695, p12 mm in combination with H/WB >7.5 was associated with the highest event rate. CONCLUSIONS: In ATTR, (99m)Tc-DPD scintigraphy can identify myocardial infiltration across a wide spectrum of morphologic/functional cardiac involvement, allowing an early diagnosis of the disease (even before the appearance of echocardiographic abnormalities). The (99m)Tc-DPD myocardial uptake is a prognostic determinant of "cardiac" outcome in ATTR, either alone or in combination with LV wall thickness