Imaging Cardiac Innervation in Hereditary Transthyretin (ATTRm) Amyloidosis: A Marker for Neuropathy or Cardiomyopathy in Case of Heart Failure?

Overview

Journal J Nucl Cardiol

Specialty Cardiology & Vascular Diseases

Date 2018 Oct 31

PMID 30374850

Citations 5

Authors

Daphne L Jonker

Bouke P C Hazenberg

Hans L A Nienhuis

Riemer H J A Slart

Andor W J M Glaudemans

Walter Noordzij

Affiliations

Soon will be listed here.

Abstract

Background: Nuclear imaging modalities using Iodine-metaiodobenzylguanidine (I-MIBG) and bone seeking tracers identify early cardiac involvement in ATTRm amyloidosis patients. However, little is known whether results from I-MIBG scintigraphy actually correlate to markers for either cardiac autonomic neuropathy or cardiomyopathy.

Methods: All TTR mutation carriers and ATTRm patients who underwent both I-MIBG and Technetium-hydroxymethylene diphosphonate (Tc-HDP) scintigraphy were included. Cardiomyopathy was defined as NT-proBNP > 365 ng/L, and cardiac autonomic neuropathy as abnormal cardiovascular reflexes at autonomic function tests. Late I-MIBG heart-to-mediastinum ratio (HMR) < 2.0 or wash-out > 20%, and any cardiac Tc-HDP uptake were considered as abnormal.

Results: 39 patients (13 carriers and 26 ATTRm patients) were included in this study. Patients with cardiomyopathy, with or without cardiac autonomic neuropathy, had lower late HMR than similar patients without cardiomyopathy [median 1.1 (range 1.0-1.5) and 1.5(1.2-2.6) vs 2.4 (1.4-3.8) and 2.5 (1.5-3.7), respectively, P < 0.001]. Late HMR and wash-out (inversely) correlated with NT-proBNP r = - 0.652 (P < 0.001) and r = 0.756 (P < 0.001), respectively. Furthermore, late HMR and wash-out (inversely) correlated with cardiac Tc-HDP uptake r = - 0.663 (P < 0.001) and r = 0.617 (P < 0.001), respectively.

Conclusion: In case of heart failure, I-MIBG scintigraphy reflects cardiomyopathy rather than cardiac autonomic neuropathy in ATTRm patients and TTR mutation carriers. I-MIBG scintigraphy may already be abnormal before any cardiac bone tracer uptake is visible.

Citing Articles

Exploring Cardiac Sympathetic Denervation in Transthyretin-Mediated Hereditary Amyloidosis (ATTRv): Insights from I-mIBG Scintigraphy.

De Feo M, Cambieri C, Galosi E, Frantellizzi V, Chimenti C, Luigetti M Diagnostics (Basel). 2025; 15(4).

PMID: 40002660 PMC: 11854682. DOI: 10.3390/diagnostics15040508.

Cardiovascular autonomic failure in hereditary transthyretin amyloidosis and TTR carriers is an early and progressive disease marker.

Chiaro G, Stancanelli C, Koay S, Vichayanrat E, Sander L, Ingle G Clin Auton Res. 2024; 34(3):341-352.

PMID: 38769233 DOI: 10.1007/s10286-024-01038-z.

Electrophysiological Manifestations of Cardiac Amyloidosis: State-of-the-Art Review.

Hartnett J, Jaber W, Maurer M, Sperry B, Hanna M, Collier P JACC CardioOncol. 2021; 3(4):506-515.

PMID: 34729522 PMC: 8543134. DOI: 10.1016/j.jaccao.2021.07.010.

Circulating microRNAs Profile in Patients With Transthyretin Variant Amyloidosis.

Vita G, Aguennouz M, Polito F, Oteri R, Russo M, Gentile L Front Mol Neurosci. 2020; 13:102.

PMID: 32655365 PMC: 7325132. DOI: 10.3389/fnmol.2020.00102.

Clinical and echocardiographic characteristics of individuals aged 75/76 years old with screening-detected elevated NT-proBNP levels.

Al-Khalili F, Kemp-Gudmundsdottir K, Svennberg E, Fredriksson T, Frykman V, Friberg L Open Heart. 2020; 7(1):e001200.

PMID: 32153793 PMC: 7046938. DOI: 10.1136/openhrt-2019-001200.

References

Mankad A, Shah K . Transthyretin Cardiac Amyloidosis. Curr Cardiol Rep. 2017; 19(10):97. DOI: 10.1007/s11886-017-0911-5. View

Klaassen S, Tromp J, Nienhuis H, van der Meer P, van den Berg M, Blokzijl H . Frequency of and Prognostic Significance of Cardiac Involvement at Presentation in Hereditary Transthyretin-Derived Amyloidosis and the Value of N-Terminal Pro-B-Type Natriuretic Peptide. Am J Cardiol. 2017; 121(1):107-112. DOI: 10.1016/j.amjcard.2017.09.029. View

Galat A, Rosso J, Guellich A, Van Der Gucht A, Rappeneau S, Bodez D . Usefulness of (99m)Tc-HMDP scintigraphy for the etiologic diagnosis and prognosis of cardiac amyloidosis. Amyloid. 2015; 22(4):210-20. DOI: 10.3109/13506129.2015.1072089. View

Ponikowski P, Voors A, Anker S, Bueno H, Cleland J, Coats A . 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special.... Eur Heart J. 2016; 37(27):2129-2200. DOI: 10.1093/eurheartj/ehw128. View

Delahaye N, Dinanian S, Slama M, Mzabi H, Samuel D, Adams D . Cardiac sympathetic denervation in familial amyloid polyneuropathy assessed by iodine-123 metaiodobenzylguanidine scintigraphy and heart rate variability. Eur J Nucl Med. 1999; 26(4):416-24. DOI: 10.1007/s002590050406. View

Ruberg F, Berk J . Transthyretin (TTR) cardiac amyloidosis. Circulation. 2012; 126(10):1286-300. PMC: 3501197. DOI: 10.1161/CIRCULATIONAHA.111.078915. View

Stats M, Stone J . Varying levels of small microcalcifications and macrophages in ATTR and AL cardiac amyloidosis: implications for utilizing nuclear medicine studies to subtype amyloidosis. Cardiovasc Pathol. 2016; 25(5):413-7. DOI: 10.1016/j.carpath.2016.07.001. View

Noordzij W, Glaudemans A, Slart R, Dierckx R, Hazenberg B . Clinical use of differential nuclear medicine modalities in patients with ATTR amyloidosis. Amyloid. 2012; 19(4):208-11. DOI: 10.3109/13506129.2012.717993. View

Delahaye N, Le Guludec D, Dinanian S, Delforge J, Slama M, Sarda L . Myocardial muscarinic receptor upregulation and normal response to isoproterenol in denervated hearts by familial amyloid polyneuropathy. Circulation. 2001; 104(24):2911-6. DOI: 10.1161/hc4901.100380. View

10.

Bokhari S, Shahzad R, Castano A, Maurer M . Nuclear imaging modalities for cardiac amyloidosis. J Nucl Cardiol. 2013; 21(1):175-84. PMC: 4302756. DOI: 10.1007/s12350-013-9803-2. View

11.

Piekarski E, Chequer R, Algalarrondo V, Eliahou L, Mahida B, Vigne J . Cardiac denervation evidenced by MIBG occurs earlier than amyloid deposits detection by diphosphonate scintigraphy in TTR mutation carriers. Eur J Nucl Med Mol Imaging. 2018; 45(7):1108-1118. DOI: 10.1007/s00259-018-3963-x. View

12.

Falk R, Dubrey S . Amyloid heart disease. Prog Cardiovasc Dis. 2010; 52(4):347-61. DOI: 10.1016/j.pcad.2009.11.007. View

13.

Slart R, Glaudemans A, Hazenberg B, Noordzij W . Imaging cardiac innervation in amyloidosis. J Nucl Cardiol. 2017; 26(1):174-187. PMC: 6394628. DOI: 10.1007/s12350-017-1059-9. View

14.

Gillmore J, Maurer M, Falk R, Merlini G, Damy T, Dispenzieri A . Nonbiopsy Diagnosis of Cardiac Transthyretin Amyloidosis. Circulation. 2016; 133(24):2404-12. DOI: 10.1161/CIRCULATIONAHA.116.021612. View

15.

Bokhari S, Castano A, Pozniakoff T, Deslisle S, Latif F, Maurer M . (99m)Tc-pyrophosphate scintigraphy for differentiating light-chain cardiac amyloidosis from the transthyretin-related familial and senile cardiac amyloidoses. Circ Cardiovasc Imaging. 2013; 6(2):195-201. PMC: 3727049. DOI: 10.1161/CIRCIMAGING.112.000132. View

16.

Noordzij W, Glaudemans A, Longhi S, Slart R, Lorenzini M, Hazenberg B . Nuclear imaging for cardiac amyloidosis. Heart Fail Rev. 2014; 20(2):145-54. DOI: 10.1007/s10741-014-9463-6. View

17.

Sousa M, Cardoso I, Fernandes R, Guimaraes A, Saraiva M . Deposition of transthyretin in early stages of familial amyloidotic polyneuropathy: evidence for toxicity of nonfibrillar aggregates. Am J Pathol. 2001; 159(6):1993-2000. PMC: 1850610. DOI: 10.1016/s0002-9440(10)63050-7. View

18.

Gertz M, Comenzo R, Falk R, Fermand J, Hazenberg B, Hawkins P . Definition of organ involvement and treatment response in immunoglobulin light chain amyloidosis (AL): a consensus opinion from the 10th International Symposium on Amyloid and Amyloidosis, Tours, France, 18-22 April 2004. Am J Hematol. 2005; 79(4):319-28. DOI: 10.1002/ajh.20381. View

19.

Damy T, Deux J, Moutereau S, Guendouz S, Mohty D, Rappeneau S . Role of natriuretic peptide to predict cardiac abnormalities in patients with hereditary transthyretin amyloidosis. Amyloid. 2013; 20(4):212-20. DOI: 10.3109/13506129.2013.825240. View

20.

Wang A, Fealey R, Gehrking T, Low P . Patterns of neuropathy and autonomic failure in patients with amyloidosis. Mayo Clin Proc. 2008; 83(11):1226-30. PMC: 2842947. DOI: 10.4065/83.11.1226. View