CARDIAC AMYLOIDOSIS with bone PYP Scintigraphic

cardiac amyloidosis with bone pyp scintigraphic

1. CARDIAC amyloidosis 99mTechnetium- Pyrophosphate Imaging for Transthyretin Cardiac Amyloidosis

2. INTRODUCTION cardiac amyloidosis Clinical disorder caused by extracellular deposition of insoluble fibrils formed from misfolded light chain/ transthyretin (TTR) proteins.

3. INTRODUCTION cardiac amyloidosis Mechanism: bone-seeking radiotracers accumulate in the myocardium of patients with cardiac amyloidosis remains unclear but may be related to high calcium levels in amyloidosis. Moreover, the mechanism by which 99mTc-PYP distinguishes ATTR from AL amyloidosis remains to be elucidated. Few hypothesis : 99mTc-PYP may bind TTR amyloid fibrils more intensely than AL fibrils as a result of higher calcium containing compounds in ATTR hearts. Mechanism of myocardial enhancement in ATTR subjects proposes that the intensity of 99mTc-PYP binding relates to the duration over which amyloid deposition has occurred in the affected tissue.

4. In AL patients, fibrils tend to accumulate over shorter time periods than in ATTR patients, whose disease course is typically more indolent. Characteristics of amyloidogenic fibrils in patients with ATTR cardiac amyloid may differ from those of AL amyloid thereby resulting in higher levels of 99mTc-PYP uptake.

5. patient selection Heart failure unexplained increase in left ventricular wall thickness. age > 60 years with unexplained heart failure with preserved ejection fraction. Elderly males unexplained neuropathy bilateral carpal tunnel syndrome atrial arrhythmias in the absence of usual risk factors, and signs/symptoms of heart failure. Evaluation of cardiac involvement in individuals with known or suspected familial amyloidosis. Diagnosis of cardiac ATTR amyloidosis in individuals with CMR or echocardiography consistent with cardiac amyloidosis. Patients with suspected cardiac ATTR amyloidosis and contraindications to CMR such as renal insufficiency or an implantable cardiac device .

6. radiopharmaceutical Tc-99m pyrophosphate (99mTc-PYP) Dosage for adult: 370 - 740 Mbq intravenously ( 5-15 mci) PREPARATION • No specific preparation is required. CONTRAINDICATION Pregnancy Breastfeeding

7. scan acquisition Planar imaging at 1H and 3H post injection For visual interpretation and quantification of the degree of myocardial uptake by heart-to-lung ratio or comparison to rib uptake. Cardiac or chest SPECT and planar images are obtained one hour/3 hours post-injection of 99mTc-PYP. Field Of View (FOV) must include chest extending from the lower neck to upper abdomen, ensure the heart and lung is in view Whole body planar imaging may be helpful to identify uptake of 99mTc- PYP in the shoulder and hip girdles (a specific sign of systemic ATTR amyloidosis)

8. SPECT imaging may be helpful to To avoid overlap of bone uptake To distinguish blood pool activity from myocardial activity To assess the distribution of myocardial 99m Tc-PYP uptake in individuals with positive planar scans To identify 99m Tc-PYP uptake in the interventricular septum (commonly involved in amyloidosis) To quantify the degree of myocardial uptake by comparison to rib uptake.

9. Quantifying Myocardial 99mTc-PYP Uptake There are two approaches ; Quantitative Myocardial-to-Contralateral lung uptake ratio at 1 hour Semi-quantitative: visual comparison to bone (rib) uptake at 3 hours

10. 1. Quantitative Myocardial to Contralateral lung uptake ratio at 1 hour Circular target regions of interest (ROI) are drawn over the heart on the planar images and are mirrored over the contralateral chest to account for background and ribs Total and absolute mean counts are measured in each ROI A heart-to-contralateral lung (H/CL) ratio is calculated as the fraction of heart ROI mean counts to contralateral chest ROI mean counts H/CL ratios of ≥ 1.5 at one hour are classified as ATTR positive H/CL ratios of < 1.5 at one hour are classified as ATTR negative

11. 2. Semi-quantitative: visual comparison to bone (rib) uptake at 3 hours Cardiac uptake of 99mTc-PYP is evaluated using a semi-quantitative visual scoring method in relation to bone (rib) uptake. Visual scores of greater than or equal to 2 on planar or SPECT images at 3 hours are classified as ATTR positive, and scores of less than 2 as ATTR negative. While grade 2 or 3 or H/CL >1.5 uptake is strongly suggestive of ATTR amyloidosis, any degree of 99mTc-PYP uptake can also be seen in AL amyloidosis, and as such a complete evaluation is warranted to exclude this diagnosis. In clinical practice both semi-quantitative visual scoring and H/CL are used.

12. interpretation Myocardial 99mTc-PYP uptake patterns are categorized as absent, focal, diffuse or focal and diffuse. Scans with focal 99mTc-PYP uptake could represent rib fracture or previous myocardial infarction. Following a myocardial infarction, myocardial 99mTc-PYP uptake may be positive for up to 7 days and rarely may remain persistently positive.

13. CONCLUSION An overall interpretation of the findings into categories of 1) Not suggestive of ATTR amyloidosis: A semi-quantitative visual score of 0 or H/CL ratio < 1. 2) Strongly suggestive of ATTR amyloidosis: A semi-quantitative visual score of 2 or 3 or H/CL ratio >1.5. 3) Equivocal for ATTR amyloidosis: A semi-quantitative visual score of 1 or H/CL ratio 1-1.5. Equivocal results could represent AL amyloid or early TTR amyloid. Any degree of 99mTc-PYP uptake can also be seen in AL amyloidosis, and as such a complete evaluation is warranted to exclude this diagnosis. If echo/CMR are strongly positive, and 99mTc-PYP negative, consider further evaluation including endomyocardial biopsy

14. REFERENCES: ASNC Practice Points: 99mTechnetium-Pyrophosphate Imaging for Transthyretin Cardiac Amyloidosis. Bokhari S, Castano A, Pozniakoff T, Deslisle S, Latif F, Maurer MS. (99m)Tc- pyrophosphate scintigraphy for differentiating light-chain cardiac amyloidosis from the transthyretin-related familial and senile cardiac amyloidoses . Circ Cardiovasc Imaging 2013;6:195-201. Hutt DF, Quigley AM, Page J, Hall ML, Burniston M, Gopaul D et al. Utility and limitations of 3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy in systemic amyloidosis. Eur Heart J Cardiovasc Imaging 2014;15:1289-98.

15. thank you