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

Conceição et al. J Peripher Nerv Syst. 2016;21(1):5-9.

When to Suspect TTR Amyloidosis

Family History Carpal Tunnel Cardiomyopathies

Witteles et al JACC Heart failure 2019; 7: 709-16

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

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

A B C D

Quarta CC et al JACC Cv Img 2012;5:755-8.

TTR HCM HCM Control

Bone scintigraphy with 99mTc-DPD/HMDP/PYP

Grade 2 to 3 Grade 1 Grade 0 No Yes Yes No Yes No Cardiac amyloidosis (AL/AApoAI/ATTR/other) TTR genotyping Need specialized assessment for Diagnosis : Histological confirmation and typing

• f amyloid

Cardiac ATTR amyloidosis Wild-Type ATTR amyloidosis Variant ATTR amyloidosis Serum immunofixation + Urine Immunofixation + serum free light chain assay (Freelite) Monoclonal protein present? Review/request CMR

Bone scintigraphy with 99mTc-DPD/HMDP/PYP

Cardiac AL/ATTR amyloidosis unlikely

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?

Diagnostic Tools