Skip to main content

Advertisement

SpringerLink
Log in

Regional myocardial sympathetic denervation precedes the development of left ventricular systolic dysfunction in chronic Chagas’ cardiomyopathy

  • Original Article
  • Published:
Journal of Nuclear Cardiology Aims and scope

Abstract

Background

Regional myocardial sympathetic denervation is a conspicuous and early disorder in patients with chronic Chagas’ cardiomyopathy (CCC), potentially associated to the progression of myocardial dysfunction

Objective

To evaluate in a longitudinal study the association between the presence and the progression of regional myocardial sympathetic denervation with the deterioration of global and segmental left ventricular dysfunction in CCC.

Methods

18 patients with CCC were submitted at initial evaluation and after 5.5 years to rest myocardial scintigraphy with 123Iodo-metaiodobenzylguanidine and 99mTc-sestamibi and to two-dimensional echocardiography to assess myocardial sympathetic denervation, extent of fibrosis, and the left ventricular ejection fraction (LVEF) and wall motion abnormalities.

Results

In the follow-up evaluation, compared to the initial one, we observed a significant decrease in LVEF (56 ± 11 to 49% ± 12; P = .01) and increased summed defects scores in the myocardial innervation scintigraphy (15 ± 10 to 20 ± 9; P < .01). The presence of regional myocardial sympathetic denervation in ventricular regions of viable non-fibrotic myocardium presented an odds ratio of 4.25 for the development of new wall motion abnormalities (P = .001).

Conclusion

Regional and global myocardial sympathetic denervation is a progressive derangement in CCC. In addition, the regional denervation is topographically associated with areas of future development of regional systolic dysfunction in patients with CCC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Hotez PJ, Molyneux DH, Fenwick A, Kumaresan J, Sachs SE, Sachs JD. Control of neglected tropical diseases. N Engl J Med 2007;357:1018‐27.

    Article  CAS  Google Scholar 

  2. Bern C, Montgomery SP. An estimate of the burden of Chagas disease in the United States. Clin Infect Dis 2009;49:e52‐4.

    Article  Google Scholar 

  3. Gascon J, Bern C, Pinazo MJ. Chagas disease in Spain, the United States and other non-endemic countries. Acta Trop 2010;115:22‐7.

    Article  Google Scholar 

  4. Koberle F. Chagas’ disease and Chagas’ syndromes: the pathology of American trypanosomiasis. Adv Parasitol 1968;6:63‐116.

    Article  CAS  Google Scholar 

  5. de Souza MM, Andrade SG, Barbosa AA Jr, Macedo Santos RT, Alves VA, Andrade ZA. Trypanosoma cruzi strains and autonomic nervous system pathology in experimental Chagas disease. Mem Inst Oswaldo Cruz 1996;91:217‐24.

    Article  Google Scholar 

  6. Machado CR, Caliari MV, de Lana M, Tafuri WL. Heart autonomic innervation during the acute phase of experimental American trypanosomiasis in the dog. Am J Trop Med Hyg 1998;59:492‐6.

    Article  CAS  Google Scholar 

  7. Simoes MV, Pintya AO, Bromberg-Marin G, Sarabanda AV, Antloga CM, Pazin-Filho A, et al. Relation of regional sympathetic denervation and myocardial perfusion disturbance to wall motion impairment in Chagas’ cardiomyopathy. Am J Cardiol 2000;86:975‐81.

    Article  CAS  Google Scholar 

  8. Miranda CH, Figueiredo AB, Maciel BC, Marin-Neto JA, Simoes MV. Sustained ventricular tachycardia is associated with regional myocardial sympathetic denervation assessed with 123I-metaiodobenzylguanidine in chronic Chagas cardiomyopathy. J Nucl Med 2011;52:504‐10.

    Article  CAS  Google Scholar 

  9. Gadioli LP, Miranda CH, Pintya AO, de Figueiredo AB, Schmidt A, Maciel BC, et al. The severity of ventricular arrhythmia correlates with the extent of myocardial sympathetic denervation, but not with myocardial fibrosis extent in chronic Chagas cardiomyopathy: Chagas disease, denervation and arrhythmia. J Nucl Cardiol 2018;25:75‐83.

    Article  Google Scholar 

  10. Pazin-Filho A, Romano MM, Almeida-Filho OC, Furuta MS, Viviani LF, Schmidt A, et al. Minor segmental wall motion abnormalities detected in patients with Chagas’ disease have adverse prognostic implications. Braz J Med Biol Res 2006;39:483‐7.

    Article  CAS  Google Scholar 

  11. Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging 2015;16:233‐70.

    Article  Google Scholar 

  12. Cerqueira MD, Weissman NJ, Dilsizian V, Jacobs AK, Kaul S, Laskey WK, et al. Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart: A statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association. Circulation 2002;105:539‐42.

    Article  Google Scholar 

  13. Flotats A, Carrio I, Agostini D, Le Guludec D, Marcassa C, Schafers M, et al. Proposal for standardization of 123I-metaiodobenzylguanidine (MIBG) cardiac sympathetic imaging by the EANM Cardiovascular Committee and the European Council of Nuclear Cardiology. Eur J Nucl Med Mol Imaging 2010;37:1802‐12.

    Article  Google Scholar 

  14. Mott KE, Hagstrom JW. The pathologic lesions of the cardiac autonomic nervous system in chronic chagas’ myocarditis. Circulation 1965;31:273‐86.

    Article  CAS  Google Scholar 

  15. Amorim DS, Godoy RA, Manco JC, Tanaka A, Gallo L Jr. Effects of acute elevation in blood pressure and of atropine on heart rate in Chagas’ disease A Preliminary Report. Circulation 1968;38:289‐94.

    Article  CAS  Google Scholar 

  16. Gallo L Jr, Neto JA, Manco JC, Rassi A, Amorim DS. Abnormal heart rate responses during exercise in patients with Chagas’ disease. Cardiology 1975;60:147‐62.

    Article  Google Scholar 

  17. Guzzetti S, Iosa D, Pecis M, Bonura L, Prosdocimi M, Malliani A. Impaired heart rate variability in patients with chronic Chagas’ disease. Am Heart J 1991;121:1727‐34.

    Article  CAS  Google Scholar 

  18. Neto JA, Gallo L Jr, Manco JC, Rassi A, Amorim DS. Postural reflexes in chronic Chagas’s heart disease. Heart rate and arterial pressure responses. Cardiology 1975;60:343‐57.

    Article  CAS  Google Scholar 

  19. Amorim DS, Manco JC, Gallo L Jr, Marin Neto JA. Chagas’ heart disease as an experimental model for studies of cardiac autonomic function in man. Mayo Clin Proc 1982;57:48‐60.

    Google Scholar 

  20. Marin-Neto JA, Bromberg-Marin G, Pazin-Filho A, Simoes MV, Maciel BC. Cardiac autonomic impairment and early myocardial damage involving the right ventricle are independent phenomena in Chagas’ disease. Int J Cardiol 1998;65:261‐9.

    Article  CAS  Google Scholar 

  21. Ribeiro AL, Moraes RS, Ribeiro JP, Ferlin EL, Torres RM, Oliveira E, et al. Parasympathetic dysautonomia precedes left ventricular systolic dysfunction in Chagas disease. Am Heart J 2001;141:260‐5.

    Article  CAS  Google Scholar 

  22. Barizon GC, Simoes MV, Schmidt A, Gadioli LP, Murta Junior LO. Relationship between microvascular changes, autonomic denervation, and myocardial fibrosis in Chagas cardiomyopathy: Evaluation by MRI and SPECT imaging. J Nucl Cardiol 2020;27:434‐44.

    Article  Google Scholar 

  23. Landesmann MC, da Fonseca LM, de Pereira BPB, do Nascimento EM, Rosadodecastro PH, de Souza SA, et al. Iodine-123 metaiodobenzylguanidine cardiac imaging as a method to detect early sympathetic neuronal dysfunction in chagasic patients with normal or borderline electrocardiogram and preserved ventricular function. Clin Nucl Med 2011;36:757‐61.

    Article  Google Scholar 

  24. Kramer CM, Nicol PD, Rogers WJ, Suzuki MM, Shaffer A, Theobald TM, et al. Reduced sympathetic innervation underlies adjacent noninfarcted region dysfunction during left ventricular remodeling. J Am Coll Cardiol 1997;30:1079‐85.

    Article  CAS  Google Scholar 

  25. Sakata K, Mochizuki M, Yoshida H, Nawada R, Ohbayashi K, Ishikawa J, et al. Cardiac sympathetic dysfunction contributes to left ventricular remodeling after acute myocardial infarction. Eur J Nucl Med 2000;27:1641‐9.

    Article  CAS  Google Scholar 

  26. Sisson JC, Shapiro B, Meyers L, Mallette S, Mangner TJ, Wieland DM, et al. Metaiodobenzylguanidine to map scintigraphically the adrenergic nervous system in man. J Nucl Med 1987;28:1625‐36.

    CAS  Google Scholar 

  27. Sisson JC, Wieland DM, Sherman P, Mangner TJ, Tobes MC, Jacques S Jr. Metaiodobenzylguanidine as an index of the adrenergic nervous system integrity and function. J Nucl Med 1987;28:1620‐4.

    CAS  Google Scholar 

  28. Bellotti G, Bocchi EA, de Moraes AV, Higuchi ML, Barbero-Marcial M, Sosa E, et al. In vivo detection of Trypanosoma cruzi antigens in hearts of patients with chronic Chagas’ heart disease. Am Heart J 1996;131:301‐7.

    Article  CAS  Google Scholar 

  29. Machado CR, Ribeiro AL. Experimental American trypanomiasis in rats: sympathetic denervation, parasitism and inflammatory process. Mem Inst Oswaldo Cruz 1989;84:549‐56.

    Article  CAS  Google Scholar 

  30. Nakahara T, Hashimoto J, Suzuki T, Fujii H, Kubo A. Completely inverse images in dual-isotope SPECT with Tl-201 and I-123 MIBG in a patient with myocarditis. Ann Nucl Med 2001;15:277‐80.

    Article  CAS  Google Scholar 

  31. Dae MW, De Marco T, Botvinick EH, O’Connell JW, Hattner RS, Huberty JP, et al. Scintigraphic assessment of MIBG uptake in globally denervated human and canine hearts–implications for clinical studies. J Nucl Med 1992;33:1444‐50.

    CAS  Google Scholar 

  32. Imamura Y, Ando H, Mitsuoka W, Egashira S, Masaki H, Ashihara T, et al. Iodine-123 metaiodobenzylguanidine images reflect intense myocardial adrenergic nervous activity in congestive heart failure independent of underlying cause. J Am Coll Cardiol 1995;26:1594‐9.

    Article  CAS  Google Scholar 

  33. Barber MJ, Mueller TM, Henry DP, Felten SY, Zipes DP. Transmural myocardial infarction in the dog produces sympathectomy in noninfarcted myocardium. Circulation 1983;67:787‐96.

    Article  CAS  Google Scholar 

  34. Dae MW, Herre JM, O’Connell JW, Botvinick EH, Newman D, Munoz L. Scintigraphic assessment of sympathetic innervation after transmural versus nontransmural myocardial infarction. J Am Coll Cardiol 1991;17:1416‐23.

    Article  CAS  Google Scholar 

  35. Matsunari I, Schricke U, Bengel FM, Haase HU, Barthel P, Schmidt G, et al. Extent of cardiac sympathetic neuronal damage is determined by the area of ischemia in patients with acute coronary syndromes. Circulation 2000;101:2579‐85.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Cardiology, Medical School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil

    Leonardo Pippa Gadioli, Carlos Henrique Miranda, José Antonio Marin-Neto, Gustavo Jardim Volpe, Antonio Carlos Leite Barros Filho, Antonio Pazin Filho, Antonio Osvaldo Pintya, Alexandre Baldini de Figueiredo & Marcus Vinicius Simões

Authors
  1. Leonardo Pippa Gadioli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Carlos Henrique Miranda
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. José Antonio Marin-Neto
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gustavo Jardim Volpe
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Antonio Carlos Leite Barros Filho
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Antonio Pazin Filho
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Antonio Osvaldo Pintya
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Alexandre Baldini de Figueiredo
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Marcus Vinicius Simões
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marcus Vinicius Simões.

Ethics declarations

Disclosures

The authors have indicated that they have no financial conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

The authors of this article have provided a PowerPoint file, available for download at SpringerLink, which summarizes the contents of the paper and is free for re-use at meetings and presentations. Search for the article DOI on SpringerLink.com.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PPTX 8328 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gadioli, L.P., Miranda, C.H., Marin-Neto, J.A. et al. Regional myocardial sympathetic denervation precedes the development of left ventricular systolic dysfunction in chronic Chagas’ cardiomyopathy. J. Nucl. Cardiol. 29, 3166–3176 (2022). https://doi.org/10.1007/s12350-021-02869-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12350-021-02869-3

Keywords

Search

Navigation