CME TTR Amyloidosis Confirming a Diagnosis Mo Mori rie A Gert - PowerPoint PPT Presentation

CME TTR Amyloidosis Confirming a Diagnosis Mo Mori rie A Gert rtz, z, MD MD: Ma Mayo Clinic

When to Suspect TTR Amyloidosis Family History Carpal Tunnel Cardiomyopathies Conceição et al. J Peripher Nerv Syst. 2016;21(1):5-9.

Red Flags • Reduction in longitudinal strain with apical sparing • Discrepancy between left ventricular thickness and QRS voltage • Atrioventricular block in the presence of increased left ventricular wall thickness • Echocardiographic hypertrophic phenotype with associated infiltrative features • Marked extracellular volume expansion, abnormal nulling time for the myocardium or diffuse late gadolinium enhancement on CMR • Symptoms of polyneuropathy and/or dysautonomia • History of bilateral carpal tunnel syndrome • Mild increase in troponin levels on repeated occasions Witteles et al JACC Heart failure 2019; 7: 709-16

Diagnosis Tissue biopsy • Common tissues biopsied include subcutaneous fatty tissue of the abdominal wall, kidney, skin, gastric, or rectal mucosa, sural nerve tissue, retinaculum and peritendinous fat obtained at carpal tunnel surgery, tissue from the salivary gland, and endomyocardial tissue Congo red staining of amyloid • The gold standard Bone scintigraphy • Use of myocardial radiotracer uptake on bone scintigraphy may also eliminate the need for biopsy in patients with cardiac ATTR amyloidosis Amyloid typing • Immunohistochemistry and immunofluorescence • Proteomics can be utilized for amyloidosis typing • Mass spectrometry Ando Y et al. Orphanet J Rare Dis 2013, 8:31; Leung N et al. Blood 2012;120:3206-3213; Castaño A et al . J Nucl Cardiol 2016;23:1355-1363; Gilmore JD et al. Circulation 2016; 133: 2404-12

Bone scintigraphy with 99m Tc-DPD/HMDP/PYP B C A D TTR HCM HCM Control Quarta CC et al JACC Cv Img 2012;5:755-8.

Bone scintigraphy with 99m Tc-DPD/HMDP/PYP Grade 0 Grade 1 Grade 2 to 3 Serum immunofixation + Urine Immunofixation + serum free light chain assay (Freelite) Monoclonal protein present? No Yes Yes No Yes No Need specialized assessment Cardiac Cardiac ATTR Review/request for Diagnosis : AL/ATTR amyloidosis CMR Histological confirmation and typing amyloidosis of amyloid unlikely TTR genotyping Cardiac amyloidosis Variant ATTR Wild-Type ATTR (AL/AApoAI/ATTR/other) amyloidosis amyloidosis

Diagnostic Tools ECHO MRI Scintigraphy BNP Other Suspicion +++ ++ + (TTR) + Definite diagnosis + ++ +++ (TTR) - Etiologic diagnosis +/- +? +++ +/- RBP4 Early diagnosis + ? ++ (TTR) +/? Functional eval +++ ++ + (MIBG) - Prognosis + ++ + +++ 6MWT Amyloiditic burden + ++ +? - Response to Tx + + ? +++? 6MWT?