Cardiac Sympathetic Hyperactivity after Chemotherapy: Early Sign of Cardiotoxicity?

Abstract

BackgroundChemotherapy with anthracyclines and trastuzumab can cause cardiotoxicity. Alteration of cardiac adrenergic function assessed by metaiodobenzylguanidine labeled with iodine-123 (123I-mIBG) seems to precede the drop in left ventricular ejection fraction.ObjectiveTo evaluate and to compare the presence of cardiovascular abnormalities among patients with breast cancer undergoing chemotherapy with anthracyclines and trastuzumab, and only with anthracycline.MethodsPatients with breast cancer were analyzed clinical, laboratory, electrocardiographic and echocardiographic and cardiac sympathetic activity. In scintigraphic images, the ratio of 123I-mIBG uptake between the heart and mediastinum, and the washout rate were calculated. The variables were compared between patients who received anthracyclines and trastuzumab (Group 1) and only anthracyclines (Group 2).ResultsTwenty patients, with mean age 57 ± 14 years, were studied. The mean left ventricular ejection fraction by echocardiography was 67.8 ± 4.0%. Mean washout rate was 28.39 ± 9.23% and the ratio of 123I-mIBG uptake between the heart and mediastinum was 2.07 ± 0.28. Of the patients, 82% showed an increased in washout rate, and the ratio of 123I-mIBG uptake between the heart and mediastinum decreased in 25%. Concerning the groups, the mean washout rate of Group 1 was 32.68 ± 9.30% and of Group 2 was 24.56 ± 7.72% (p = 0,06). The ratio of 123I-mIBG uptake between the heart and mediastinum was normal in all patients in Group 2, however, the Group 1, showed 50% the ratio of 123I-mIBG uptake between the heart and mediastinum ≤ 1.8 (p = 0.02).ConclusionIn women with breast cancer undergoing chemotherapy, assessment of cardiac sympathetic activity with 123I-mIBG appears to be an early marker of cardiotoxicity. The combination of chemotherapy showed higher risk of cardiac adrenergic hyperactivity.

Precision Cardio-Oncology

“…In one study of rats treated with anthracycline, PET imaging with 18 F-DHMT, a marker of reactive oxygen species, revealed an elevation in cardiac superoxide production at 4 wk after treatment, compared with a decrease in LVEF on echocardiography detectable only at 6 wk after treatment (44). In one human study of 20 breast cancer patients treated with either anthracycline and trastuzumab or anthracycline alone, the ratio of 123 I-metaiodobenzylguanidine uptake between the heart and mediastinum on scintigraphic images decreased in 25% of patients, and the washout rate increased in 82% of patients compared with matched controls, demonstrating the potential utility MIBG 5 metaiodobenzylguanidine; BMIPP 5 β-methyl-p-iodophenylpentadecanoic acid; HER2 5 human epidermal growth factor receptor 2; MMP 5 matrix metalloproteinases of 123 I-metaiodobenzylguanidine as a marker of cardiac sympathetic activity and cardiotoxicity (45). However, in a more recent study of 89 asymptomatic patients previously treated with anthracyclines, neither the heart-to-mediastinum ratio nor the washout rate was able to discriminate anthracycline-exposed patients from controls (46).…”

Atualização da Diretriz Brasileira de Cardiologia Nuclear – 2020

“…323 O uso potencial da imagem adrenérgica cardíaca na monitoração dos efeitos cardiotóxicos pelos quimioterápicos tem sido debatido. [368][369][370] Há evidências que a redução da captação cardíaca de MIBG-123 I precede a deterioração da fração de ejeção. 371 Estudo recente mostrou que após 1 ano do tratamento com antracíclico, a RC/M tardia foi o mais robusto parâmetro da cintilografia com MIBG-123 I. Este índice correlacionou-se com variáveis ecocardiográficas convencionais e com os índices globais de strain radial e longitudinal, além da dosagem de galectina 3 em pacientes com câncer de mama tratados com antracíclicos.…”

Breakthroughs in modern cancer therapy and elusive cardiotoxicity: Critical research‐practice gaps, challenges, and insights

“…Among those radiotracers, the norepinephrine analog Imetaiodobenzylguanidine (IMIBG) is FDA approved and the most commonly used agent. This agent can be used to investigate the activity of norepinephrine, which is the predominant neurotransmitter of the sympathetic nervous system . The discovery and application of agents such as IMIBG are absolutely needed in clinical nuclear imaging to provide better prognostic risk stratification, which, in heart failure, may include innervation imaging (sympathetic imaging), because this imaging modality provides more accurate information than conventional markers and mechanistic insights that drive therapeutic decisions .…”

“…This agent can be used to investigate the activity of norepinephrine, which is the predominant neurotransmitter of the sympathetic nervous system. [267][268][269] The discovery and application of agents such as 123 IMIBG are absolutely needed in clinical nuclear imaging to provide better prognostic risk stratification, which, in heart failure, may include innervation imaging (sympathetic imaging), because this imaging modality provides more accurate information than conventional markers and mechanistic insights that drive therapeutic decisions. 258,259,267 A reduced 123 IMIBGmyocardial uptake or higher washout rate can predict cardiac adverse events.…”

“…258,259,267 A reduced 123 IMIBGmyocardial uptake or higher washout rate can predict cardiac adverse events. 123,267 IMIBG imaging is more sensitive than decreased LVEF, which has been frequently used in the clinic, 268 because a decrease in LVEF is a late manifestation of cardiotoxicity. 252 Moreover, with the imaging modality, it is also possible to predict whether LVEF recovery will occur.…”