Top

Published in:

01-02-2017 | Original Article

Assessment of late anthracycline-induced cardiotoxicity by ¹²³I-mIBG cardiac scintigraphy in patients treated during childhood and adolescence

Authors: Marcelo José dos Santos, MD, PhD, Euclides Timóteo da Rocha, MD, PhD, Hein J. Verberne, MD, PhD, Eduardo Tinois da Silva, MS, Davi Casale Aragon, MS, José Soares Junior, MD, PhD

Published in: Journal of Nuclear Cardiology | Issue 1/2017

Abstract

Purpose

The goal of this study was to evaluate late cardiotoxic effects of anthracyclines (ATC) by evaluating cardiac sympathetic activity in a cohort of asymptomatic patients previously treated with ATC for childhood cancers.

Methods

We studied 89 asymptomatic patients previously treated with ATC with a normal echocardiogram (49 men and 40 women) and a control group of 40 healthy individuals (26 men and 14 women). Both groups underwent planar myocardial ¹²³I-meta-iodobenzylguanidine scintigraphy (¹²³I-mIBG). From these images, the early and late heart-to-mediastinum (H/M) ratio and washout rate (WR) were assessed.

Results

The mean survival at the time of the ¹²³I-mIBG scintigraphy was 5.3 ± 3.4 years. Patients treated with ATC had a lower but clinical normal left ventricular ejection fraction (LVEF) compared to controls (60.44 ± 6.5 vs 64.1 ± 6.0%, P < 0.01). Both the late H/M ratio and WR were not able to discriminate ATC treated patients from controls. The cumulative ATC dose was the only independent predictor of the LVEF, explaining approximately 12% of the variation in LVEF (P = 0.01).

Conclusions

Although the pathophysiology behind ATC cardiotoxicity is most likely multifactorial, myocardial sympathetic activity is not associated with a reduction in LVEF 5-years after completion of chemotherapy.

Lipshultz SE, Adams MJ. Cardiotoxicity after childhood cancer: Beginning with the end in mind. J Clin Oncol 2010;28:1276-81.CrossRefPubMed

Jacobson AF, Travin MI. Impact of medications on mIBG uptake, with specific attention to the heart: Comprehensive review of the literature. J Nucl Cardiol 2015;22:980-93.CrossRefPubMed

Visscher H, Ross CJ, Rassekh SR, Barhdadi A, Dubé M-P, Al-Saloos H, et al. Pharmacogenomic prediction of anthracycline-induced cardiotoxicity in children. J Clin Oncol 2012;30:1422-8.CrossRefPubMed

Lipshultz SE, Colan SD, Gelber RD, Perez-Atayde AR, Sallan SE, Sanders SP. Late cardiac effects of doxorubicin therapy for acute lymphoblastic leukemia in childhood. N Engl J Med 1991;324:808-15.CrossRefPubMed

Panjrath GS, Jain D. Monitoring chemotherapy-induced cardiotoxicity: Role of cardiac nuclear imaging. J Nucl Cardiol 2006;13:415-26.CrossRefPubMed

Hong RA, Iimura T, Sumida KN, Eager RM. Cardio-oncology/onco-cardiology. Clin Cardiol 2010;33:733-7.CrossRefPubMed

Schwartz RG, Jain D, Storozynsky E. Traditional and novel methods to assess and prevent chemotherapy-related cardiac dysfunction noninvasively. J Nucl Cardiol 2013;20:443-64.CrossRefPubMed

Wexler LH, Andrich MP, Venzon D, Berg SL, Weaver-McClure L, Chen CC, et al. Randomized trial of the cardioprotective agent ICRF-187 in pediatric sarcoma patients treated with doxorubicin. J Clin Oncol 1996;14:362-72.CrossRefPubMed

Aggarwal A, Esler MD, Socratous F, Kaye DM. Evidence for functional presynaptic alpha-2 adrenoceptors and their down-regulation in human heart failure. J Am Coll Cardiol 2001;37:1246-51.CrossRefPubMed

10.

Carrió I. Cardiac neurotransmission imaging. J Nucl Med 2001;42:1062-76.PubMed

11.

Chirumamilla A, Travin MI. Cardiac applications of ¹²³I-mIBG imaging. Semin Nucl Med 2011;41:374-87.CrossRefPubMed

12.

Corbett JR, Akinboboye OO, Bacharach SL, Borer JS, Botvinick EH, DePuey EG, et al. Equilibrium radionuclide angiocardiography. J Nucl Cardiol 2006;13:e56-79.CrossRefPubMed

13.

Agostini D, Carrio I, Verberne HJ. How to use myocardial ¹²³I-MIBG scintigraphy in chronic heart failure. Eur J Nucl Med Mol Imaging 2009;36:555-9.CrossRefPubMed

14.

Flotats A, Carrió I, Agostini D, Guludec D, Marcassa C, Schaffers 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.CrossRefPubMed

15.

Verberne HJ, Somsen GA, van Eck-Smit BL. ¹²³I-meta-iodobenzylguanidine in patients with chronic heart failure: Technical aspects, conceptual issues, and future prospects. Nucl Med Commun 2009;30:411-4.CrossRefPubMed

16.

van der Pal HJ, van Dalen EC, Hauptmann M, Kok WE, Caron HN, van den Bos C, et al. Cardiac function in 5-year survivors of childhood cancer: A long-term follow-up study. Arch Intern Med 2010;170:1247.PubMed

17.

Olmos R, Bokkel Huinink W, Hoeve R, Van Tinteren H, Bruning P, Van Vlies B, et al. Assessment of anthracycline-related myocardial adrenergic derangement by [¹²³I] metaiodobenzylguanidine scintigraphy. Eur J Cancer 1995;31:26-31.CrossRef

18.

Clements IP, Garcia EV, Chen J, Folks RD, Butler J, Jacobson AF. Quantitative iodine-123-metaiodobenzylguanidine (MIBG) SPECT imaging in heart failure with left ventricular systolic dysfunction: Development and validation of automated procedures in conjunction with technetium-99m tetrofosmin myocardial perfusion SPECT. J Nucl Cardiol 2015. doi:10.1007/s12350-015-0097-4.PubMed

19.

Paiva MG, Petrilli AS, Moises VA, Macedo CR, Tanaka C, Campos O. Cardioprotective effect of dexrazoxane during treatment with doxorubicin: A study using low-dose dobutamine stress echocardiography. Pediatr Blood Cancer 2005;45:902-8.CrossRefPubMed

20.

Yeh ET, Bickford CL. Cardiovascular complications of cancer therapy incidence, pathogenesis, diagnosis, and management. J Am Coll Cardiol 2009;53:2231-47.CrossRefPubMed

21.

Carrio I, Estorch M, Berna L, Germa JR, Alonso C, Ojeda B, et al. Assessment of anthracycline-induced myocardial damage by quantitative indium 111 myosin-specific monoclonal antibody studies. Eur J Nucl Med 1991;18:806-12.CrossRefPubMed

22.

Carrio I, Lopez-Pousa A, Estorch M, Duncker D, Berna L, Torres G, et al. Detection of doxorubicin cardiotoxicity in patients with sarcomas by indium-111-antimyosin monoclonal antibody studies. J Nucl Med 1993;34:1503-7.PubMed

23.

Jiji RS, Kramer CM. Non-invasive imaging and monitoring cardiotoxicity of cancer therapeutic drugs. J Nucl Cardiol 2012;19:377-88.CrossRefPubMedPubMedCentral

24.

Braunwald E. Biomarkers in heart failure. N Engl J Med 2008;358:2148-59.CrossRefPubMed

25.

Seta Y, Shan K, Bozkurt B, Oral H, Mann DL. Basic mechanisms in heart failure: The cytokine hypothesis. J Cardiac Fail 1996;2:243-9.CrossRef

26.

Ky B, French B, Ruparel K, Sweitzer NK, Fang JC, Levy WC, et al. The vascular marker soluble fms-like tyrosine kinase 1 is associated with disease severity and adverse outcomes in chronic heart failure. J Am Coll Cardiol 2011;58:386-94.CrossRefPubMedPubMedCentral

27.

Takeishi Y, Sukekawa H, Sakurai T, Saito H, Nishimura S, Shibu T, et al. Noninvasive identification of anthracycline cardiotoxicity: Comparison of 123I-MIBG and 123I-BMIPP imaging. Ann Nucl Med 1994;8:177-82.CrossRefPubMed

Title: Assessment of late anthracycline-induced cardiotoxicity by 123I-mIBG cardiac scintigraphy in patients treated during childhood and adolescence
Authors: Marcelo José dos Santos, MD, PhD
Euclides Timóteo da Rocha, MD, PhD
Hein J. Verberne, MD, PhD
Eduardo Tinois da Silva, MS
Davi Casale Aragon, MS
José Soares Junior, MD, PhD
Publication date: 01-02-2017
Publisher: Springer US
Published in: Journal of Nuclear Cardiology / Issue 1/2017
Print ISSN: 1071-3581
Electronic ISSN: 1532-6551
DOI: https://doi.org/10.1007/s12350-015-0309-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Assessment of late anthracycline-induced cardiotoxicity by ¹²³I-mIBG cardiac scintigraphy in patients treated during childhood and adolescence

Abstract

Purpose

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2017

A useful and easy to develop combined stress test for myocardial perfusion imaging: Regadenoson and isometric exercise, preliminary results

Cardiovascular risk stratification after renal transplant: Is SPECT-MPI the answer?

Purposeful Imaging: Goals for ASNC in 2017

Hybrid CCTA/SPECT myocardial perfusion imaging findings in patients with anomalous origin of coronary arteries from the opposite sinus and suspected concomitant coronary artery disease

2014 ESC/ESA guidelines on noncardiac surgery: Cardiovascular assessment and management

Effect of Bayesian-penalized likelihood reconstruction on [13N]-NH3 rest perfusion quantification