Transthyretin Amyloidosis Cardiomyopathy in Greece: Clinical Insights from the National Referral Center.

BACKGROUND: Clinical characteristics and outcomes of patients with transthyretin amyloidosis cardiomyopathy (ATTR-CM) vary by region, necessitating the acquisition of country-specific evidence for proper management. METHODS: This is an observational study including sequential patients presenting in the Amyloidosis Reference Center of Greece, from 01/2014 to 12/2022. ATTR-CM was diagnosed by positive scintigraphy and exclusion of light-chain amyloidosis or positive biopsy typing. Genetic testing was performed in all cases. RESULTS: One-hundred and nine ATTR-CM patients were included (median age, 81 years) of which 15 carried TTR mutations (27% Val30Met). Most patients (82%) presented with heart failure and 59% with atrial fibrillation, while 10% had aortic stenosis. Importantly, 78 (71.6%) had clinically significant extracardiac manifestations (45% musculoskeletal disorder, 40% peripheral neuropathy and 33% gastrointestinal symptoms). Sixty-five (60%) received disease-specific treatment with tafamidis. Estimated median survival was 48 months; advanced NYHA class, National Amyloidosis Center stage, eGFR<45 ml/kg/1.73m2, NT-pro-BNP>5000 pg/mL were associated with worse survival, while tafamidis treatment was associated with improved survival in patients with IVS≥ 12 mm. DISCUSSION: These are the first data describing the characteristics, management, and outcomes of patients with ATTR-CM in Greece, which could influence local guidelines. SHORT TITLE: Transthyretin cardiomyopathy in Greece.

Imaging of cardiac amyloidosis by (99m)Tc-PYP scintigraphy.

OBJECTIVE: Cardiac amyloidosis (CA) is an underestimated and underdiagnosed cause of cardiac insufficiency. Despite being often considered as a solitary entity attributable to extracellular deposition of fibrillary proteins, there exist at least two different pathophysiologic backgrounds, with different clinical course and treatment. a) In light-chain cardiac amyloidosis (immunoglobulin light-chain amyloidosis-AL) the fibrils consist of light-chain immunoglobulins produced by a clonal plasma cell population in bone marrow. b) In CA related to transthyretin (transthyretin-related amyloidosis - ATTR), whether familial amyloid cardiomyopathy or senile systemic amyloidosis, monomers or dimers of the normally tetrameric protein of transthyretin are deposited in the myocardium. Today, definitive diagnosis of cardiac amyloid disease is based on endomyocardial biopsy in conjunction with immunohistochemical parameters or, in ambiguous cases, with mass spectroscopy. Several radiotracers have been hitherto tried in the detection of CA. SUBJECTS AND METHODS: In this pilot study technetium-99m pyrophosphate ((99m)Tc-PYP) was administered to patients suffering from CA, aiming to differentiate scintigraphically between AL and ATTR. Twelve patients (8 males, aged [mean±SD] 70,6±13,2y; 4 females, aged 65,7±9,9y) were enrolled for the discrimination between AL and ATTR. Diagnosis was confirmed by biopsy combined with the clinical and laboratory evaluation of the patients. Myocardial scintigraphy (planar and tomographic imaging) was conducted at 1, 2 and/or 3h after intravenous administration of 555-925MBq (99m)Tc-PYP. Myocardial radiotracer uptake was evaluated optically and also by a semiquantitative method. Two regions of interest (ROI) were drawn: one over the heart and another over the contralateral hemithorax, to calculate the corresponding heart-to-contralateral (H/CL) count ratio. According to established reference standards, a cut-off H/CL value of 1.5 best discriminates between the two conditions. (99m)Tc-PYP scintigraphy revealed diffuse intense myocardial uptake upon visual evaluation that was also verified semi-quantitatively in 6 patients, all of which had ATTR. Faint or no myocardial tracer uptake was found in 4 patients who were diagnosed with AL. Two AL patients had a borderline positive scan on visual evaluation but their H/CL ratios did not exceed the value of 1.5. In three patients, we also attempted scintigraphy with the tracer pentavalent (99m)Tc-dimercaptosuccinic acid. Results and possible mechanisms of uptake are discussed. The sensitivity and specificity of scintigraphy with (99m)Tc-PYP was high, albeit the small number of patients. IN CONCLUSION: These preliminary results are compatible with current international literature, and demonstrate that scintigraphy with (99m)Tc-PYP may prove a simple, non-invasive and widely available method in the identification of patients with the ATTR subtype, thus optimizing therapeutic decisions.

Detection and credibility of sentinel node in vulvar cancer: a single institutional study and short review of literature.

PURPOSE: To evaluate the detectability and credibility of sentinel lymph node (SLN) in vulvar cancer. METHODS: With Tc99m-nanocolloid and methylene blue, we identified SLNs in 34 patients. In 27 cases both tracers were used, while in 7 only blue dye was used. Completion lymphadenectomy was performed in all patients. SLNs and non-SLNs were sent separately for pathologic evaluation. RESULTS: At least one SLN was identified in all patients. Detection rate per groin was not significantly higher in the combined versus blue dye only technique (42/50 vs. 10/14, p = 0.43). 99m-Tc was not superior to blue dye in detecting SLN (42/50 vs. 50/64, p = 0.65). Midline location of the tumor did not seem to negatively affect the procedure. Four false negatives were observed in three patients with tumors >4 cm. Negative predictive value of SLN was 100% for grade I tumors ≤ 4 cm in patients ≤ 71 years. CONCLUSION: Tc-99m does not seem to be superior to methylene blue in the detection of SLN in vulvar cancer. Patients of younger age with small, well-differentiated tumors appear to be the most suitable candidates for lymphatic mapping.