CARDIAC AMYLOIDOSIS IMAGING ERIC MARTIN MD
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1 CARDIAC AMYLOIDOSIS IMAGING ERIC MARTIN MD
2 DISCLOSURES Bayer Dalcor Pharma UK LTD Harvard Clinical Research Institute Heartflow Inc. NIH Vascular Dynamics Employee-Iowa Heart Center/Mercy-Des Moines
3 BACKGROUND Amyloidosis is a heterogeneous group of diseases Localized or systemic deposition of insoluble extracellular fibrillary proteins in organs and tissues Clinical manifestation is based on organ involved and type of precursor protein (AL or ATTR) Systemic involvement usually fatal (1 per 1,000 deaths) 3,000 new US cases annually
4 AMYLOID SUBTYPES AA- rarely affects the heart AL ATTR 1) Familial (mutant, ATTRm) 2) Senile (wild-type, ATTRw) Aβ2M- also rarely affects the heart
5 AL Amyloidosis ~ 1in 100,000 Cardiac involvement in ~ 50% 25% shows CHF AF and conduction abnormalities are common Cardiac involvement has poor prognosis Median survival of 6-12 months
6 ATTRw Amyloidosis- Wild Type Genetically normal Senile Non-hereditary Most commonly in males >70 y/o
7 ATTRm Amyloidosis- Mutant Genetically Abnormal Familial (Autosomal Dominant) Seen in all ages >100 mutations 3-4% of US African-Americans have Val122Ile mutation
8 European Cardiology Review, 2015; 10 (2):113 7
9 European Cardiology Review, 2015; 10 (2):113 7
10
11 Rodney H. Falk et al. JACC 2016;68: American College of Cardiology Foundation
12 AL Amyloidosis Rodney H. Falk et al. JACC 2016;68: American College of Cardiology Foundation
13 Rodney H. Falk et al. JACC 2016;68: American College of Cardiology Foundation
14 American College of Cardiology Foundation Rodney H. Falk et al. JACC 2016;68:
15 American College of Cardiology Foundation Rodney H. Falk et al. JACC 2016;68:
16 Rodney H. Falk et al. JACC 2016;68: American College of Cardiology Foundation
17 Rodney H. Falk et al. JACC 2016;68: American College of Cardiology Foundation
18 American College of Cardiology Foundation Rodney H. Falk et al. JACC 2016;68:
19 USUAL SUSPECTS CHF with LVH and at least Gr II diastolic dysfunction Typical CMR findings on CMR - Diffuse Late Gadolinium Enhancement - ECV expansion - Characteristic T-1 relaxation time
20 99m Tc-PYP IMAGING Ability to specifically identify ATTR cardiac amyloidosis non-invasively
21 PATIENT SELECTION CHF and unexplained LVH African-americans >60y/o w/ CHF and LVH (>12mm) >60y/o HFpEF Individuals, especially elderly males, w/ CHF and unexplained neuropathy, bilateral CTS, atrial arrhythmias in the absence of usual risk factors Individuals with known or suspected Familial Amyloidosis
22 PATIENT SELECTION Dx Cardiac ATTR in individuals w/ CMR or Echo consistent with cardiac amyloidosis Patients w/ suspected ATTR and contraindications to CMR such as renal insufficiency or cardiac devices
23 DOSIMETRY 99M Tc-PYP 15mCi Total Body Effective Dose= 3.2mSv
24 IMAGING PROCEDURE SPECT and Planar images are obtained 1 hr after 99mTc-PYP injection PLANAR IMAGING: - useful for visual interpretation - quantification of heart to lung ratio
25 IMAGING PROCEDURE SPECT IMAGING: - Avoid overlap of bone uptake - Distinguish blood pool from myocardial activity - Assess distribution of myocardial uptake especially in interventricular septum. - Quantify degree of myocardial uptake by comparison to rib uptake
26 IMAGE INTERPRETATION Anterior and lateral planar images and reconstructed SPECT images are reviewed Quantitative: Heart to Lung ratio in 1 hour Semi-quantitative: Visual comparison to rib uptake in 3 hours
27 QUANTITATIVE
28 QUANTITATIVE H/L RATIO =/> 1.5 (POSITIVE) H/L RATIO <1.5 (NEGATIVE)
29 Mean heart-to-contralateral ratio according to amyloid subtype. Sabahat Bokhari et al. Circ Cardiovasc Imaging. 2013;6: Copyright American Heart Association, Inc. All rights reserved.
30 SEMI-QUANTITATIVE
31 SEMI-QUANTITATIVE GRADE Grade 0 Grade 1 Grade 2 Grade 3 MYOCARDIAL 99MTc-PYP UPTAKE No uptake or Normal Bone uptake Uptake less than rib uptake Uptake equal to rib uptake Uptake greater than rib uptake with mild or absent rib uptake Visual score of =/> 2 are considered ATTR positive
32 INTERPRETATION CAVEATS Focal tracer uptake could represent rib fracture or recent MI Recent MI can remain positive for 7 days and rarely thereafter Any degree of uptake can be seen in AL amyloidosis and as such a complete evaluation is warranted
33 TREATMENTS Often unresponsive to diuretics at normal dosages No data on prognostic benefit of ACEI CCB and Digoxin are potentially toxic Best to avoid BB due to high incidence of CHB
34 AL Suppress immunoglobulin light chain production CVD (Cyclophosphamide, Velcade, Dexamethasone)
35 TTR Hepatic TTR Production Inhibition TTR Stabilization -Tafamadis (Vyndaquel) -Diflunisal Increase TTR Clearance -Doxycycline
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