Assessment of Cardiac Sympathetic Activity by Nuclear Medicine: Many Clinical Benefits but Weak Recommendation

Scintigraphy/methods; Single photon emission computed tomography/methods; Nuclear Medicine; 123I-mIBG

The autonomous nervous system (ANS) regulates important cardiac functions, including heart rate, ventricular contractility, QT interval and systemic vascular resistance. ANS dysfunction, known as dysautonomia, can lead to many clinical manifestations, some of them severe and debilitating.¹ Dysautonomia is often underdiagnosed and detected at late stages, due to its wide phenotypic variability and the poor familiarity of the physicians with the disease, leading to higher cardiovascular mortality and morbidity.²

The diagnostic and prognostic potential of nuclear cardiology in the assessment of the ANS has increased. In addition, there is growing evidence that the use of scintigraphy in the evaluation of cardiac innervation can help in cardiovascular risk stratification, therapy selection, and evaluation of potential benefits of new therapeutic approaches.³ , ⁴ However, there is increasing need for physicians with experience with this method, and hence, scientific studies that synthesize and discuss its applications, advantages, and disadvantages would contribute to the effective implementation in clinical practice.⁵

In this issue, Brito et al.⁴ present an interesting review on the use of scintigraphic imaging in the assessment of autonomic innervation in cardiac diseases. The article provides an overview of the use of nuclear medicine and different radiotracers in various clinical settings. Despite the unquestionable potentiality of the technique for a non-invasive, objective, imaging diagnosis of cardiac dysautonomia, each section of the review presents clear limitations for its routine recommendation. The authors point out problems involved in the standardization, low availability, and high cost of the method as the main challenges to be overcome.

Among the scintigraphic techniques addressed in the review, we believe that the cardiac 123I-metaiodobenzylguanidine (¹²³I-mIBG) scintigraphy is the most feasible for practical application. Its implementation in clinical practice would help in solving the issue of underdiagnosing of dysautonomia, and in promoting better medical care for these patients. However, for this purpose, all those limitations should be overcome.

The study is a review of the literature and presents, in a didactic way, the main clinical applications of scintigraphy in the study of cardiac autonomic denervation. The use of this technique started in the early 80s, i.e., 41 years of experience have been accumulated ( Figure 1 ). Undoubtedly, cardiac scintigraphy with ¹²³I-mIBG and its parameters – the late heart-to-mediastinum ratio (HMR) of ¹²³I-mIBG uptake and its clearance rate – is the most supported by currently available data.⁶ Results of these indexes indicate, respectively, the integrity of presynaptic terminals and the adrenergic tone.⁷

Figure 1
– Timeline of the use of cardiac 123I-metaiodobenzylguanidine (123I-mIBG) scintigraphy in different clinical settings. Created with biorender.com.

Figure 2 summarizes the clinical settings that would most benefit from cardiac ¹²³I-mIBG scintigraphy. In heart failure a reduced HMR is an independent marker of mortality and a predictive marker of arrhythmic events.⁸ Besides, observational studies have shown its applicability in cardiac resynchronization therapy⁹ and cardiac defibrillator implantation,¹⁰ focusing on refining the indication criteria for these expensive therapies and making them more cost-effective.

Figure 2
– Main clinical applications of cardiac 123I-metaiodobenzylguanidine (123I-mIBG) scintigraphy. Created with biorender.com.

Other applications include cardiovascular risk stratification in Chagas cardiomyopathy, hypertrophic cardiomyopathy, Takotsubo cardiomyopathy, early detection of cardiotoxicity, cardiac amyloidosis, and dysautonomia secondary to neurodegenerative diseases and diabetes mellitus, as well as therapeutical monitoring in several cardiac conditions.⁴ , ⁵ , ¹¹ , ¹² In many of these situations, mapping of myocardial denervated areas can help in the identification of arrhythmogenic foci and prediction of arrhythmic events,⁸ and consequently in better establishing patient risk and appropriate therapy. In addition, monitoring of recovery from myocardial injury by cardiac ¹²³I-mIBG scintigraphy helps in the evaluation of therapy effectiveness.⁴

However, despite the well-established pathophysiological foundation and numerous studies supporting the benefits of scintigraphy in the evaluation of cardiac sympathetic activity, the scientific community still recommends the development of large prospective randomized clinical trials before including the method in clinical guidelines.¹¹

The main limitations of the method, discussed in the article, are the scarcity of cost-effectiveness data, the high cost of the technique, poor familiarity of physicians with the method, and the lack of multicenter studies evaluating the role of cardiac ¹²³I-mIBG scintigraphy in each of the clinical conditions above mentioned. In addition, the technique as well as the interpretation results (or cutoff points) in different clinical settings still need standardization.⁶ The overcoming of these limitations will advance the use of nuclear imaging in dysautonomia and its full implementation in clinical practice.

References

• ¹
  Rocha EA, Mehta N, Távora-Mehta MZP, Roncari CF, Cidrão AA de L, Elias J. Disautonomia: Uma Condição Esquecida – Parte 1. Arq Bras Cardiol. 2021;116(4):814–35. doi:10.36660/abc.20200420.
• ²
  Arrais Rocha E, Mehta N, Zildany Pinheiro Távora-Mehta M, Ferreira Roncari C, Alves de Lima Cidrão A, Elias Neto J. Disautonomia: Uma Condição Esquecida – Parte II. Arq Bras Cardiol. 2021;116(5):981–98. d0i:10.36660/abc.20200422.
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  Brito AX de, Glavam A, Bronchtein AI, Rosado-de-Castro PH. Autonomic Innervation Evaluation in Cardiac Disease. Int J Cardiovasc Sci. 2021; 34(6):702-713.
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  MastrocolaE L, Amorim BJ, Vitola JV, Soares Brandão MC, Grossman GB, Souza Leão Lima RSL, et al. Atualização da Diretriz Brasileira de Cardiologia Nuclear – 2020. Arq Bras Cardiol. 2020;114(2):325–428. doi:10.36660/abc.20200087.
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  Rocha ET da, Alves WEFM, Verschure DO, Verberne HJ. The use of Cardiac 123I-mIBG Scintigraphy in Clinical Practice: The Necessity to Standardize! Int J Cardiovasc Sci. 2017;30(6):533–41.
• ⁷
  Flotats A, Carrió I, Agostini D, Le Guludec D, Marcassa C, Schaffers M, et al. Proposal for standardization of123I-metaiodobenzylguanidine (MIBG) cardiac sympathetic imaging by the EANM Cardiovascular Committee and the European Council of Nuclear Cardiology. Eur J Nucl Med Mol Imaging. 2010;37(9):1802–12. doi:10.1007/s00259-010-1491-4.
• ⁸
  Jacobson AF, Senior R, Cerqueira MD, Wong ND, Thomas GS, Lopez VA, et al. Myocardial iodine-123 meta-iodobenzylguanidine imaging and cardiac events in heart failure. Results of the prospective ADMIRE-HF (AdreView Myocardial Imaging for Risk Evaluation in Heart Failure) study. J Am Coll Cardiol. 2010;55(20):2212–21. doi: 10.1016/j.jacc.2010.01.014.
• ⁹
  Nishioka SA, D’Orio Filho MM, Brandão SC, C. Giorgi MC, Vieira MLC, Costa R, et al. Cardiac sympathetic activity pre and postresynchronization therapy evaluated by 123I-MIBGmyocardial scintigraphy. J Nucl Cardiol. 2007;14(6):852-9. doi:10.1016/j.nuclcard.2007.08.004.
• ¹⁰
  Arora R, Ferrick KJ, Nakata T, Kaplan RC, Rozengarten M, Latif F, et al. I-123 MIBG imaging and heart rate variability analysis to predict the need for an implantable cardioverter defibrillator. J Nucl Cardiol. 2003;10(2):121–31. doi: 10.1067/mnc.2003.2.
• ¹¹
  Travin MI. Current Clinical Applications and Next Steps for Cardiac Innervation Imaging. Curr Cardiol Rep. 2017;19(1):1-11. doi:10.1007/s11886-017-0817-2.
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  Guimarães SLP, Soares B SC, Andrade LR, Maia RJ, Markman Filho B. Cardiac sympathetic hyperactivity after chemotherapy: early sign of cardiotoxicity? Arq Bras Cardiol. 2015 Sep 1;105(3):228–34. doi: 10.5935/abc.20150075.

• Editorial related to the article: Autonomic Innervation Evaluation in Cardiac Disease

Publication Dates

• Publication in this collection
  10 Mar 2023
• Date of issue
  Nov-Dec 2021