Cases in Tc99m-PYP Evaluation of ATTR Cardiac Amyloidosis: Interpretation and Reporting

Overview: This webinar will provide an overview of best practices and specific case examples associated with the interpretation and reporting of Tc99m-PYPfor evaluation of patients suspected of having ATTR Cardiac Amyloidosis. This program will feature Drs. Jamieson Bourque, Edward Miller, Brett Sperry and Saurabh Malhotra.

Moderator: Jamieson Bourque, MD, MHS, FASNC

  1. Introduction and overview of interpretation and reporting – Jamieson Bourque, MD, MHS, FASNC
  2. Cases and associated practical points in interpretation and reporting – Jamieson Bourque, MD, MHS, FASNC Edward Miller, MD, PhD, FASNC Brett Sperry, MD, Saurabh Malhotra, MD, MPH, FASNC
  3. Expert Panel discussion – All Faculty

Overall goal:
The overall goal of this educational initiative is to increase knowledge and awareness of the appropriate interpretation and reporting of Tc-99m PYP imaging. Imaging physicians need to understand how to perform, process, interpret, and report Tc-99m PYP imaging in appropriate patients and understand what can lead to false positive and false negative studies so that the right patients can be referred in a timely manner to amyloid experts for treatment and management.

Learning Objectives:

  • Ensure correct acquisition and processing of Tc-99m PYP imaging in work-up of cardiac amyloid patients
  • Describe the appropriate components of report on Tc-99m PYP imaging
  • Apply a structured approach to interpret Tc99m-PYP images for ATTR cardiac amyloidosis
  • Assemble a comprehensive Tc99m-PYP report using best practices and ASNC standardized reporting guidelines  

Acknowledgement of Commercial Support
This activity is supported by a grant from Pfizer.

Need statement:
Transthyretin cardiomyopathy, ATTR-CM, is caused by the accumulation of misfolded transthyretin amyloid fibrils in the heart, leads to dysrhythmias and heart failure. [Ruberg 2012a] Diagnosis often occurs late in the disease and prognosis is poor. [Ruberg 2012a; Ruberg 2012b] Transthyretin amyloidosis has 2 main subtypes, hereditary/mutant ATTR caused by a hereditary amino acid mutation in the transthyretin molecule and senile or wild-type ATTR seen mostly in patients with advancing age. [Falk 2011] Deposition of amyloid in the heart, irrespective of the type, can lead to diastolic dysfunction and congestive heart failure and ATTR-CM is an increasingly recognized etiology of heart failure with preserved ejection fraction (HFpEF). [ Vranian 2015] Traditional therapies for heart failure provide systematic treatment but do not address the underlying disease, and in some instances, may even be detrimental. Hence early and accurate diagnosis is of critical importance.

Lack of awareness and suspicion of cardiac amyloidosis, and the fact that the clinical presentation often overlaps with other more common cardiovascular diseases including hypertrophic cardiomyopathy, hypertensive heart disease, aortic stenosis, leads to missed and/or delayed diagnosis. [White 2016] The limited specificity of echocardiography and the traditional requirement for histologic confirmation, preceding the use of Tc-99m PYP to make a confirmed diagnosis, also delays accurate diagnosis. 

Non-invasive imaging and new therapies in development have the potential to improve the long-term prognosis of patients with ATTR-CM. Clinicians need to distinguish the signs and symptoms of cardiac amyloidosis from other cardiovascular diseases, provide early and accurate diagnosis differentiating the subtype, and understand both current and emerging treatments to optimize patient care and limit organ damage. Early diagnosis and treatment of cardiac amyloidosis are essential in treating the disease before irreversible organ damage occurs and improving long-term patient outcomes. [Ruberg 2012a; Maurer 2017] 

Both SPECT and planar Tc-99m PYP imaging are sensitive and specific approaches to non-invasively differentiate AL-CA from ATTR-CM. [Bokhari 2013; Castano 2016; Bokhari 2018] Scans show intense myocardial uptake in both wtATTR and hATTR, compared to none/minimal uptake in AL-CA. [Bokhari 2013] A multicenter study in 1498 patients showed a positive predictive value of 100% for ATTR-CM in patients with an echocardiogram or CMR consistent with or suggestive of CA, and absence of monoclonal protein.[Gillmore 2017] A meta-analysis of six selected studies, 529 patients, showed a sensitivity of 92.2% and specificity of  95.4% for bone scintigraphy in diagnosing ATTR-CM. [Osborne 2016] 

Assessment of planar scans involves semi-quantitative visual scoring of 0-3 and a quantitative ratio of heart-to-contralateral (H/CL) regions-of-interest. However, use of planar imaging alone, can lead to an inaccurate diagnosis. SPECT imaging improves the diagnostic accuracy and efficiency of Tc-99m PYP imaging. [Masri 2020] Blood pool increases the visual score and heart-to-contralateral ratio on planar images resulting in false positive studies. Blood pool clearance is critical for an accurate diagnosis. In patients with a semiquantitative visual score of I or 2 and (H/CL) ratio between 1.3 and 1.9, SPECT imaging should be performed.  SPECT imaging at 1 hour in these patients was shown to be an efficient, cost-effective approach. [Masri 2020] 

Tc-99m PYP can non-invasively identify most patients with ATTR-CM. Optimized and standardized protocols are critical to ensure consistent and accurate data. Imagers need to understand how to perform and interpret Tc-99m PYP scans to provide high quality diagnostic information to ensure timely and appropriate referral and improve patient outcomes. 

Sources:
Ruberg FL, Berk JL. Transthyretin (TTR) cardiac amyloidosis. Circulation. 2012a;126:1286-1300.
Ruberg FL, Maurer MS, Judge DP, et al. Prospective evaluation of the morbidity and mortality of wild-type and V1221 mutant transthyretin amyloid cardiomyopathy: The Transthyretin Amyloidosis Cardiac Study (TRACS). Am Heart J. 2012b;164:222-228.
Falk RH. Cardiac amyloidosis: a treatable disease, often overlooked. Circulation. 2011;124:1079–1085.
Vranian MN, Sperry BW, Valent J, Hanna M. Emerging advances in the management of cardiac amyloidosis. Curr Cardiol Rep. 2015;17:100.
White JA, Fine NM. Recent advances in cardiovascular imaging relevant to the management of patients with suspected cardiac amyloidosis. Curr Cardiol Rep. 2016;18:77.
Maurer M, Elliott P, Comenzo R, Semigran M, Rapezzi C. Addressing common questions encountered in the diagnosis and management of cardiac amyloidosis. Circulation. 2017;135:1357-1377.

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 amyloidosis. Circ Cardiovasc Imaging. 2013; 6:195–201.
Castano A, Haq M, Narotsky DL, et al. Multicenter study of planar technetium 99m pyrophosphate cardiac imaging: predicting survival for patients with ATTR cardiac amyloidosis. JAMA Cardiol. 2016;1:880-889.
Bokhari S, Morgenstern R, Weinberg R, et al. Standardization of 99m technetium pyrophosphate imaging methodology to diagnose TTR cardiac amyloidosis. J Nucl Cardiol. 2018;25:181-190.
Gillmore JD, Maurer MS, Falk RH. Nonbiopsy diagnosis of cardiac transthyretin amyloidosis. Circulation. 2016;133:2404–2412
Osborne MT, Erthal F, Craig J, Beanlands R, Di Carli MF. Technetium-99m pyrophosphate SPECT for TTR amyloid. May 2016. www.acc.org/education-and-meetings/patient-case-quizzes/technetium-99m-pyrophosphate-spect-for-ttr-amyloid. Accessed April 25, 2019.
Masri A, Bukhari S, Ahmad S, et al. Efficient 1-Hour technetium-99m pyrophosphate imaging protocol for the diagnosis of transthyretin cardiac amyloidosis. Circ Cardiovasc Imaging. 2020 Feb;13(2):e010249. Epub 2020 Feb 17.

References

  1. Alexander KM, Singh A, Falk RH. Novel pharmacotherapies for cardiac amyloidosis. Pharmacol Ther. 2017;180:129-138.
     
  2. Bokhari S, Morgenstern R, Weinberg R, Kinkhabwala M, Panagiotou D, Castano A, DeLuca A, Kontak A, Jin Z, Maurer MS. Standardization of 99mTechnetium pyrophosphate imaging methodology to diagnose TTR cardiac amyloidosis. J Nucl Cardiol. 2018;25:181–190.

  3. Castano A, Haq M, Narotsky DL, et al. Multicenter study of planar technetium 99m pyrophosphate cardiac imaging. Predicting survival for patients with ATTR cardiac amyloidosis. JAMA Cardiol. 2016;1:880-889.
     
  4. Donnelly JP, Hanna M. Cardiac amyloidosis: An update on diagnosis and treatment. Cleve Clin J Med. 2017 Dec;84(12 Suppl 3):12-26.
     
  5. Dorbala, S., Ando, Y., Bokhari, S. et al. ASNC/AHA/ASE/EANM/HFSA/ISA/SCMR/SNMMI expert consensus recommendations for multimodality imaging in cardiac amyloidosis: Part 1 of 2—evidence base and standardized methods of imaging. J. Nucl. Cardiol. 26, 2065–2123 (2019). https://doi.org/10.1007/s12350-019-01760-6
     
  6. Dorbala, S., Ando, Y., Bokhari, S. et al. ASNC/AHA/ASE/EANM/HFSA/ISA/SCMR/SNMMI expert consensus recommendations for multimodality imaging in cardiac amyloidosis: Part 2 of 2—Diagnostic criteria and appropriate utilization. J. Nucl. Cardiol. (2019). https://doi.org/10.1007/s12350-019-01761-5
     
  7. Falk RH. Cardiac Amyloidosis: A treatable disease, often overlooked. Circulation 2011;124:1079–1085.
     
  8. Gillmore JD, Maurer MS, Falk RH, Merlini G, Damy T, Dispenzieri A, Wechalekar AD, Berk JL, Quarta CC, Grogan M, Lachmann HJ, Bokhari S, Castano A, Dorbala S, Johnson GB, Glaudemans AWJM, Rezk T, Fontana M, Palladini G, Miliani P, Guidalotti PL, Flatman K, Lane T, Vonberg FW, Whelan CJ, Moon JC, Ruberg FL, Miller EJ, Hutt DF, Hazenberg BP, Rapezzi C, Hawkins PN. Nonbiopsy diagnosis of cardiac transthyretin amyloidosis. Circulation 2016;133(24):2404-2412.
     
  9. Maurer MS, Elliott P, Comenzo R, Semigran M, Rapezzi C. Addressing common questions encountered in the diagnosis and management of cardiac amyloidosis. Circulation 2017;135:1357-1377.
     
  10. Maurer MS, Schwartz JH, Gundapaneni B, Elliott PM, Merlini G, Waddington-Cruz M, Kristen AV, Grogan M, Witteles R, Day T, Drachman BM, Shah SJ. Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy. N Eng J Med. 2018; 379:1007-1016.
     
  11. Ruberg FL and Berk JL. Transthyretin (TTR) cardiac amyloidosis. Circulation 2012;126:1286-1300.
     
  12. Ruberg FL, Maurer MS, Judge DP, Zeldenrust S, Skinner M, Kim AY, Falk RH, Cheung KN, Patel AR, Pano A, Packman J, Grogan DR. Prospective evaluation of the morbidity and mortality of wild-type and V122I mutant transthyretin amyloid cardiomyopathy: The Transthyretin Amyloidosis Cardiac Study (TRACS).  Am Heart J. 2012;164:222-228.
     
  13. Siddiqi OK, Ruberg FL. Cardiac amyloidosis: An update on pathophysiology, diagnosis, and treatment. Trends Cardiovasc Med. 2018;28:10-21.
     
  14. Vranian MN, Sperry BW, Valent J, Hanna M. Emerging advances in the management of cardiac amyloidosis. Curr Cardiol Rep. 2015;17:100.
     
  15. White JA and Fine NM. Recent advances in cardiovascular imaging relevant to the management of patients with suspected cardiac amyloidosis. Curr Cardiol Rep. 2016;18:77.

Jamieson M. Bourque, MD, MHS, FASNC - Moderator
Associate Professor of Medicine and Radiology
Medical Director of Nuclear Cardiology and the Stress Laboratory
Medical Director of Culpeper Cardiology
University of Virginia Health System
Charlottesville, VA 

Edward J. Miller, MD, PhD, FASNC - Presenter
Associate Professor of Medicine and Radiology in the Section of Cardiovascular Medicine
Director, Nuclear Cardiology, Cardiovascular Medicine
Director, Cardiology Fellowship Program, Cardiovascular Medicine
Yale School of Medicine
New Haven, CT 

Saurabh Malhotra, MD, MPH, FASNC – Presenter
Director of Advanced Cardiac Imaging Cook County Health
Associate Professor of Medicine Rush Medical College
John H. Stroger Hospital of Cook County
Chicago, IL 

Brett W. Sperry, MD – Presenter
Cardiology, Advanced Heart Failure/Transplant Cardiology
Assistant Professor of Medicine, University of Missouri–Kansas City
Co-director of the Cardiac Amyloidosis Program
Saint Luke’s Mid America Heart Institute
Kansas City, MO 

Planners
Jamieson M. Bourque, MD, MHS
Linda Giering, ASNC Staff
Joe Reyes, ASNC Staff

The following faculty planners, reviewers, editors, question writers and staff reported no financial relationships:
Linda Giering, ASNC staff
Joe Reyes, ASNC staff
 

The following faculty planners, reviewers, editors, question writers and staff reported financial relationships:
Jamieson M. Bourque, MD, MHS, FASNC: Pfizer, GE Healthcare, Locus Health
Edward J Miller, MD, PhD, FASNC: Bracco, Pfizer, GE Healthcare, Alnylam, Eidos
Saurabh Malhotra, MD, MPH, FASNC: Pfizer, Akcea Therapeutics
Brett W Sperry, MD: Alnylam, Novartis 

Off Label Use
Presentations may include discussion of drugs or devices, or uses of drugs or devices, that have not been approved by the Food and Drug Administration (FDA) or have been approved by the FDA for specific uses only. The FDA has stated that it is the responsibility of the physician to determine the FDA clearance status of each drug or device he or she wishes to use in clinical practice. ASNC is committed to the free exchange of medical education. Inclusion of any discussion in this program, including discussion on off-label uses, does not imply an endorsement by ASNC of the uses, products or techniques presented.  Presenters are required to disclose to the learners, if there is any off-label usage within the presentation.

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Webinar
08/21/2020 at 12:00 PM (EDT)   |  60 minutes
08/21/2020 at 12:00 PM (EDT)   |  60 minutes