SpringerLink
Log in

Autonomic denervation, myocardial hypoperfusion and fibrosis may predict ventricular arrhythmia in the early stages of Chagas cardiomyopathy

  • ORIGINAL ARTICLE
  • Published:
Journal of Nuclear Cardiology Aims and scope

Abstract

Background

Sudden cardiac death (SCD) can be the first clinical event of Chagas heart disease (CHD). However, current guidelines contain no clear recommendation for early cardioverter-defibrillator implantation. Using imaging modalities, we evaluated associations among autonomic denervation, myocardial hypoperfusion, fibrosis and ventricular arrhythmia in CHD.

Methods and results

Twenty-nine patients with CHD and preserved left ventricular function underwent 123I-metaiodobenzylguanidine (MIBG) scintigraphy, 99mTc-methoxyisobutylisonitrile (MIBI) myocardial perfusion and cardiac magnetic resonance imaging (MRI). They were divided into arrhythmic (≥ 6 ventricular premature complexes/h and/or non-sustained ventricular tachycardia on 24-hour Holter, n = 15) and non-arrhythmic (< 6 ventricular premature complexes/h and no ventricular tachycardia; n = 14) groups. The arrhythmic group had higher denervation scores from MIBG imaging (23.2 ± 18.7 vs 5.6 ± 4.9; P < .01), hypoperfusion scores from MIBI SPECT (4.7 ± 6.8 vs 0.29 ± 0.6: P = .02), innervation/perfusion mismatch scores (18.5 ± 17.5 vs 5.4 ± 4.8; P = .01) and fibrosis by late gadolinium enhancement on MRI (14.3% ± 13.5% vs 4.0% ± 2.9%; P = .04) than the non-arrhythmic group.

Conclusion

These imaging parameters were associated with ventricular arrhythmia in early CHD and may enable risk stratification and the implementation of primary preventive strategies for SCD.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

Abbreviations

CHD:

Chagas heart disease

ECV:

Extracellular volume

GLS:

Global longitudinal strain

ICD:

Implantable cardioverter-defibrillator

LGE:

Late gadolinium enhancement

MIBI:

Sestamibi

123I-MIBG:

Iodine-123-metaiodobenzylguanidine

MRI:

Magnetic resonance imaging

SCD:

Sudden cardiac death

SPECT:

Single photon emission computed tomography

References

  1. mondiale de la Santé O, World Health Organization. Chagas disease in Latin America: An epidemiological update based on 2010 estimates. Releve Epidemiol Hebd 2015;90:33‐43.

    Google Scholar 

  2. Rassi A, Rassi A, Marin-Neto JA. Chagas disease. Lancet Lond Engl 2010;375:1388‐402.

    Article  Google Scholar 

  3. Dias JCP, Ramos AN, Gontijo ED, Luquetti A, Shikanai-Yasuda MA, Coura JR. [Brazilian Consensus on Chagas Disease, 2015]. Epidemiol E Serv Saude Rev Sist Unico Saude Bras 2016;25:7‐86.

    Google Scholar 

  4. Muñoz-Saravia SG, Haberland A, Wallukat G, Schimke I. Chronic Chagas’ heart disease: A disease on its way to becoming a worldwide health problem: Epidemiology, etiopathology, treatment, pathogenesis and laboratory medicine. Heart Fail Rev 2012;17:45‐64.

    Article  PubMed  Google Scholar 

  5. Antinori S, Galimberti L, Bianco R, Grande R, Galli M, Corbellino M. Chagas disease in Europe: A review for the internist in the globalized world. Eur J Intern Med 2017;43:6‐15.

    Article  PubMed  Google Scholar 

  6. Rassi A, Rassi SG, Rassi A. Sudden death in Chagas’ disease. Arq Bras Cardiol 2001;76:75‐96.

    Article  PubMed  Google Scholar 

  7. de Souza ACJ, Salles G, Hasslocher-Moreno AM, de Sousa AS, Alvarenga Americano do Brasil PE, Saraiva RM, et al. Development of a risk score to predict sudden death in patients with Chaga’s heart disease. Int J Cardiol 2015;187:700‐4.

    Article  PubMed  Google Scholar 

  8. Baroldi G, Oliveira SJ, Silver MD. Sudden and unexpected death in clinically “silent” Chagas’ disease. A hypothesis. Int J Cardiol 1997;58:263‐8.

    Article  CAS  PubMed  Google Scholar 

  9. Sternick EB, Martinelli M, Sampaio R, Sampaio RC, Gerken LM, Teixeira RA, et al. Sudden cardiac death in patients with chagas heart disease and preserved left ventricular function. J Cardiovasc Electrophysiol 2006;17:113‐6.

    Article  PubMed  Google Scholar 

  10. Senra T, Ianni BM, Costa ACP, Mady C, Martinelli-Filho M, Kalil-Filho R, et al. Long-term prognostic value of myocardial fibrosis in patients with Chagas cardiomyopathy. J Am Coll Cardiol 2018;72:2577‐87.

    Article  PubMed  Google Scholar 

  11. Volpe GJ, Moreira HT, Trad HS, Wu KC, Braggion-Santos MF, Santos MK, et al. Left ventricular scar and prognosis in chronic Chagas cardiomyopathy. J Am Coll Cardiol 2018;72:2567‐76.

    Article  PubMed  Google Scholar 

  12. Landesmann MCP, da Fonseca LMB, de Pereira B, do Nascimento EM, Rosado-de-Castro PH, de Souza SAL, 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  PubMed  Google Scholar 

  13. 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  PubMed  Google Scholar 

  14. Barizon GC, Simões 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  PubMed  Google Scholar 

  15. Moll-Bernardes RJ, Rosado-de-Castro PH, Camargo GC, Mendes FSNS, Brito ASX, Sousa AS. New imaging parameters to predict sudden cardiac death in Chagas disease. Trop Med Infect Dis 2020;5:E74.

    Article  Google Scholar 

  16. Denes P, Gillis AM, Pawitan Y, Kammerling JM, Wilhelmsen L, Salerno DM. Prevalence, characteristics and significance of ventricular premature complexes and ventricular tachycardia detected by 24-hour continuous electrocardiographic recording in the Cardiac Arrhythmia Suppression Trial CAST Investigators. Am J Cardiol 1991;68:887‐96.

    Article  CAS  PubMed  Google Scholar 

  17. Fine NM, Tandon S, Kim HW, Shah DJ, Thompson T, Drangova M, et al. Validation of sub-segmental visual scoring for the quantification of ischemic and nonischemic myocardial fibrosis using late gadolinium enhancement MRI. J Magn Reson Imaging 2013;38:1369‐76.

    Article  PubMed  Google Scholar 

  18. 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. Int J Cardiovasc Imaging 2002;18:539‐42.

    PubMed  Google Scholar 

  19. Flotats A, Carrió I, Agostini D, Le Guludec D, Marcassa C, Schäfers 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  PubMed  Google Scholar 

  20. Marin-Neto JA, Cunha-Neto E, Maciel BC, Simões MV. Pathogenesis of chronic Chagas heart disease. Circulation 2007;115:1109‐23.

    Article  PubMed  Google Scholar 

  21. Koberle F. Chagas disease: A disease of the peripheral autonomic nervous system. Wien Klin Wochenschr 1956;68:333‐9.

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  23. Marin-Neto JA, Bromberg-Marin G, Pazin-Filho A, Simões 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  PubMed  Google Scholar 

  24. 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  PubMed  Google Scholar 

  25. Miranda CH, Figueiredo AB, Maciel BC, Marin-Neto JA, Simões 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  PubMed  Google Scholar 

  26. Nunes MCP, Badano LP, Marin-Neto JA, Edvardsen T, Fernández-Golfín C, Bucciarelli-Ducci C, et al. Multimodality imaging evaluation of Chagas disease: An expert consensus of Brazilian Cardiovascular Imaging Department (DIC) and the European Association of Cardiovascular Imaging (EACVI). Eur Heart J Cardiovasc Imaging 2018;19:459‐60.

    Article  PubMed  Google Scholar 

  27. Hiss FC, Lascala TF, Maciel BC, Marin-Neto JA, Simões MV. Changes in myocardial perfusion correlate with deterioration of left ventricular systolic function in chronic Chagas’ cardiomyopathy. JACC Cardiovasc Imaging 2009;2:164‐72.

    Article  PubMed  Google Scholar 

  28. Rossi MA, Tanowitz HB, Malvestio LM, Celes MR, Campos EC, Blefari V, et al. Coronary microvascular disease in chronic Chagas cardiomyopathy including an overview on history, pathology, and other proposed pathogenic mechanisms. PLoS Negl Trop Dis 2010;4:e674.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Marin-Neto JA, Simões MV, Rassi JA. Pathogenesis of chronic Chagas cardiomyopathy: The role of coronary microvascular derangements. Rev Soc Bras Med Trop 2013;46:536‐41.

    Article  PubMed  Google Scholar 

  30. Gadioli LP, Miranda CH, Marin-Neto JA, Volpe GJ, Filho ACLB, Filho AP, et al. Regional myocardial sympathetic denervation precedes the development of left ventricular systolic dysfunction in chronic Chagas’ cardiomyopathy. J Nucl Cardiol 2022. https://doi.org/10.1007/s12350-021-02869-3.

    Article  PubMed  Google Scholar 

  31. Dae MW, O’Connell JW, Botvinick EH, Chin MC. Acute and chronic effects of transient myocardial ischemia on sympathetic nerve activity, density, and norepinephrine content. Cardiovasc Res 1995;30:270‐80.

    Article  CAS  PubMed  Google Scholar 

  32. White JA, Patel MR. The role of cardiovascular MRI in heart failure and the cardiomyopathies. Magn Reson Imaging Clin N Am 2007;15:541-564 vi.

    Article  PubMed  Google Scholar 

  33. Torreão JA, Ianni BM, Mady C, Naia E, Rassi CH, Nomura C, et al. Myocardial tissue characterization in Chagas’ heart disease by cardiovascular magnetic resonance. J Cardiovasc Magn Reson 2015;17:97.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Rochitte CE, Oliveira PF, Andrade JM, Ianni BM, Parga JR, Ávila LF, et al. Myocardial delayed enhancement by magnetic resonance imaging in patients with Chagas’ disease: A marker of disease severity. J Am Coll Cardiol 2005;46:1553‐8.

    Article  PubMed  Google Scholar 

  35. Rossi MA. Patterns of myocardial fibrosis in idiopathic cardiomyopathies and chronic Chagasic cardiopathy. Can J Cardiol 1991;7:287‐94.

    CAS  PubMed  Google Scholar 

  36. Pinheiro MVT, Moll-Bernardes RJ, Camargo GC, Siqueira FP, de Azevedo CF, de Holanda MT, et al. Associations between cardiac magnetic resonance T1 map** parameters and ventricular arrhythmia in patients with Chagas disease. Am J Trop Med Hyg 2020;103:745‐51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Potter E, Marwick TH. Assessment of left ventricular function by echocardiography: The case for routinely adding global longitudinal strain to ejection fraction. JACC Cardiovasc Imaging 2018;11:260‐74.

    Article  PubMed  Google Scholar 

  38. Cho GY, Marwick TH, Kim HS, Kim MK, Hong KS, Oh DJ. Global 2-dimensional strain as a new prognosticator in patients with heart failure. J Am Coll Cardiol 2009;54:618‐24.

    Article  PubMed  Google Scholar 

  39. Azevedo ACA, Barros MVL, Klaboe LG, Edvardsen T, Costa HS, Paixao GMM, et al. Association between myocardial mechanical dispersion and ventricular arrhythmogenicity in chagas cardiomyopathy. Int J Cardiovasc Imaging 2021;37:2727‐34.

    Article  CAS  PubMed  Google Scholar 

  40. Barros MVL, Leren IS, Edvardsen T, Haugaa KH, Carmo AAL, Lage TAR, et al. Mechanical dispersion assessed by strain echocardiography is associated with malignant arrhythmias in Chagas cardiomyopathy. J Am Soc Echocardiogr 2016;29:368‐74.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We thank all of the staff and research assistants at D’Or Institute for Research and Education, Oswaldo Cruz Foundation—Fiocruz, and the patients who took part in this study. We are grateful to Rubem Menna-Barreto for kindly offering the image of Trypanosoma cruzi.

Author information

Authors and Affiliations

  1. D’Or Institute for Research and Education (IDOR), Diniz Cordeiro, 30, Botafogo, Rio de Janeiro, RJ, 22281-100, Brazil

    Adriana Soares Xavier de Brito MD, PhD, Renata Junqueira Moll-Bernardes MD, PhD, Martha Valéria Tavares Pinheiro MD, PhD, Gabriel Cordeiro Camargo MD, PhD, Fabio Paiva Rossini Siqueira MD, Renee Sarmento Oliveira MD, Adriana Pereira Glavam MD, Sergio Altino de Almeida MD, PhD, Paulo Henrique Rosado-de-Castro MD, PhD & Andrea Silvestre de Sousa MD, PhD

  2. Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Av. Brasil, 4365, Manguinhos, Rio de Janeiro, RJ, 21040-360, Brazil

    Marcelo Teixeira de Holanda MD, PhD, Luiz Henrique Conde Sangenis MD, PhD, Fernanda de Souza Nogueira Sardinha Mendes MD, PhD & Andrea Silvestre de Sousa MD, PhD

Authors
  1. Adriana Soares Xavier de Brito MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Renata Junqueira Moll-Bernardes MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Martha Valéria Tavares Pinheiro MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gabriel Cordeiro Camargo MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Fabio Paiva Rossini Siqueira MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Renee Sarmento Oliveira MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Adriana Pereira Glavam MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Sergio Altino de Almeida MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Marcelo Teixeira de Holanda MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Luiz Henrique Conde Sangenis MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Fernanda de Souza Nogueira Sardinha Mendes MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Paulo Henrique Rosado-de-Castro MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Andrea Silvestre de Sousa MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Andrea Silvestre de Sousa MD, PhD.

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.

Funding

This work was supported by the D’Or Institute for Research and Education (IDOR), Rio de Janeiro; Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation (Fiocruz), INOVA (no. VPPCB-007-FIO-18-2-10-30), Rio de Janeiro, Brazil; and the Brazilian National Council for Scientific and Technological Development (CNPq; no. 437025/2018-7).

The authors of this article have provided a PowerPoint file, available for download at SpringerLink, which summarises 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 1842 kb)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

de Brito, A.S.X., Moll-Bernardes, R.J., Pinheiro, M.V.T. et al. Autonomic denervation, myocardial hypoperfusion and fibrosis may predict ventricular arrhythmia in the early stages of Chagas cardiomyopathy. J. Nucl. Cardiol. 30, 2379–2388 (2023). https://doi.org/10.1007/s12350-023-03281-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12350-023-03281-9

Keywords

Search

Navigation