Effect of carvedilol on silent anthracycline-induced cardiotoxicity assessed by strain imaging: A prospective randomized controlled study with six-month follow-up

Elıtok, Ali; Öz, Fahrettin; Çizgici, Ahmet Yaşar; Kılıç, Leyla; Çiftçi, Rümeysa; Şen, Fatma; Buğra, Zehra; Mercanoğlu, Fehmi; Öncül, Aytaç; Oflaz, Hüseyin

doi:10.5603/cj.a2013.0150

Cited by 104 publications

(94 citation statements)

References 27 publications

(28 reference statements)

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“…The most important finding in the present study was that early administration of carvedilol significantly preserved LV function and inhibited LV remodeling. Our findings strengthen previous work (Kalay et al, 2006;Elitok et al, 2014) and highlight that early administration is essential for protecting against DOX-induced cardiomyopathy. This finding has important preclinical relevance that can be extrapolated to the clinical setting: early provision of carvedilol for chemotherapy patients may be crucial to prevent cardiotoxicity, which in turn preserves heart function and inhibits LV remodeling.…”

Section: Discussionsupporting

confidence: 80%

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Early Administration of Carvedilol Protected against Doxorubicin-Induced Cardiomyopathy

Chen

Chung

Chai

et al. 2015

J Pharmacol Exp Ther

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This study tested for the benefits of early administration of carvedilol as protection against doxorubicin (DOX)-induced cardiomyopathy. Thirty male, adult B6 mice were categorized into group 1 (untreated control), group 2 [DOX treatment (15 mg/every other day for 2 weeks, i.p.], and group 3 [carvedilol (15 mg/kg/d, from day 7 after DOX treatment for 28 days)], and euthanized by day 35 after DOX treatment. By day 35, the left ventricular ejection fraction (LVEF) was significantly lower in group 2 than in groups 1 and 3, and significantly lower in group 3 than in group 1, whereas the left ventricular (LV) end-diastolic and LV endsystolic dimensions showed an opposite pattern to the LVEF among the three groups. The protein expressions of fibrotic (Smad3, TGF-b), apoptotic (BAX, cleaved caspase 3, PARP), DNA damage (g-H2AX), oxidative stress (oxidized protein), mitochondrial damage (cytosolic cytochrome-C), heart failure (brain natriuretic peptide), and hypertrophic (b-MHC) biomarkers of the LV myocardium showed an opposite pattern to the LVEF among the three groups. The protein expressions of antifibrotic (BMP-2, Smad1/5), a-MHC, and phosphorylated-Akt showed an identical pattern to the LVEF among the three groups. The microscopic findings of fibrotic and collagen-deposition areas and the numbers of g-H2AX 1 and 53BP1 1 cells in the LV myocardium exhibited an opposite pattern, whereas the numbers of endothelial cell (CD31 1 , vWF 1 ) markers showed an identical pattern to the LVEF among the three groups. Cardiac stem cell markers (C-kit 1 and Sca-1 1 cells) were significantly and progressively increased from group 1 to group 3. Additionally, the in vitro study showed carvedilol treatment significantly inhibited DOX-induced cardiomyoblast DNA (CD90/ XRCC11 , CD90/53BP1 1 , and r-H2AX 1 cells) damage. Early carvedilol therapy protected against DOX-induced DNA damage and cardiomyopathy.

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Section: Discussionsupporting

confidence: 80%

“…The benefit of carvedilol on preserving heart function has been extensively discussed by numerous clinical observational studies (Kalay et al, 2006;Elitok et al, 2014). The most important finding in the present study was that early administration of carvedilol significantly preserved LV function and inhibited LV remodeling.…”

Section: Discussionsupporting

confidence: 61%

Early Administration of Carvedilol Protected against Doxorubicin-Induced Cardiomyopathy

Chen

Chung

Chai

et al. 2015

J Pharmacol Exp Ther

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“…It can be inferred that the control group was affected by anthracycline-induced cardiotoxicity while carvedilol had a strong cardioprotective effect on the case group. Elitok et al [21] studied 80 patients with breast cancer receiving doxorubicin and showed that LV basal septal and basal lateral systolic strains were significantly reduced in patients that were not treated with carvedilol, which is in line with the results of this study.…”

Section: Discussionsupporting

confidence: 79%

“…Therefore, ejection fraction is not a sensitive parameter with which to evaluate the cardiotoxicity of anthracyclines, and carvedilol did not have an effect on ejection fraction after the chemotherapy either. Elitok et al [21] showed that there is no difference between LVEF in patients who received carvedilol and those who did not. Mukai et al [22] reported that 5 cases of diagnosed anthracycline-induced cardiomyopathy treated by carvedilol had an improvement in LVEF.…”

Section: Discussionmentioning

confidence: 99%

Carvedilol Administration Can Prevent Doxorubicin-Induced Cardiotoxicity: A Double-Blind Randomized Trial

Hosseini

et al. 2016

Cardiology

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Objective: The aim of this study is to evaluate the preventive effects of carvedilol on doxorubicin-induced cardiotoxicity. Methods: In this trial, 70 female patients with breast cancer who were candidates to receive doxorubicin were enrolled, from which 30 were selected randomly to receive carvedilol 6.25 mg daily during chemotherapy, with the rest receiving placebo as the control group. Both groups were evaluated 1 week before and 1 week after chemotherapy by measuring the left ventricular ejection fraction and strain/strain rate. Results: Data analysis showed that the case group presented no significant reduction in strain and strain-rate parameters after intervention, while there was a significant reduction in these parameters in the control group (all p values <0.001). Also, the mean differences of strain parameters in the case group were significantly less than in the control group in all evaluated heart walls (basal septal strain, p = 0.005, basal lateral strain, p = 0.001, basal inferior strain, p < 0.001, and basal anterior strain, p < 0.001); the same was true for the strain-rate parameters (the p values for basal septal, basal lateral, basal inferior and basal anterior strain rate were 0.037, 0.037, 0.002 and <0.001, respectively). Conclusion: This study shows that carvedilol can prevent doxorubicin-induced cardiotoxicity. Whether this prophylaxis should be considered as the preferred method needs further investigation.

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“…13 Our patient population was similar to those assessed in previous studies of cardiotoxicity in breast cancer patients, 14,15 suggesting that our data could be used to identify patients at high risk of developing CIC.…”

Section: Discussionmentioning

confidence: 49%

Global and regional patterns of longitudinal strain in screening for chemotherapy-induced cardiotoxicity

Portugal

Branco

Galrinho

et al. 2017

Revista Portuguesa de Cardiologia (English Edition)

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Introduction: Serial echocardiographic assessment of left ventricular ejection fraction (LVEF) is the gold standard in screening for chemotherapy-induced cardiotoxicity (CIC). Measurement of myocardial deformation using speckle tracking enables more detailed assessment of myocardial contractility. The aim of this study was to determine the relationship between global and regional longitudinal strain and CIC. Methods: This was a prospective study of 158 breast cancer patients undergoing chemotherapy with anthracyclines with or without adjuvant trastuzumab who underwent serial monitoring by transthoracic echocardiography with assessment of myocardial deformation. CIC was defined as a decrease in LVEF to <53%. Global longitudinal strain (GLS) was estimated using EchoPAC BT12 software on a GE Vivid E9 cardiac ultrasound system. Patients were classified according to the 2015 ASE/EACVI criteria as having impaired myocardial deformation when GLS was reduced (less negative), with a cutoff of -18%. Results: During a mean follow-up of 5.4 months (1-48 months), the incidence of CIC was 18.9%. A decrease in GLS was observed during follow-up for the entire cohort (baseline GLS -20.1±3.5% vs. -18.7±3.4% at last follow-up assessment, p=0.001). A total of 97 patients (61.4%) were observed to have impaired myocardial deformation (GLS ≥18%) at some point during follow-up. This decrease was more significant in patients who eventually developed CIC (GLS -17.2±2.5%, ଝ Please cite this article as: Portugal G, Moura Branco L, Galrinho A, et al. Importância da deformação longitudinal na deteção da cardiotoxicidade induzida por quimioterapia e na identificação de padrões específicos de afetação segmentar. Rev Port Cardiol. 2017;36:9---15. Resultados: Durante um período de seguimento médio de 5,4 meses (1-48 meses), a incidên-cia de CIT foi de 18,9%. Na população global observou-se uma deterioração significativa do GLS durante o tratamento com quimioterapia (-20,1 ± 3,5% versus 18,7 ± 3,4%, p = 0,001), com compromisso do GLS detetado durante em algum período do seguimento em 61,4% dos doentes. Esta deterioração foi mais marcada no subgrupo de doentes com CIT (GLS: -17,2 ± 2,5%, p = 0,02). Na análise regional da deformação longitudinal, verificou-se compromisso da contractilidade envolvendo preferencialmente os segmentos septais (seis em seis) e parede anterior (dois em três). Por regressão logística multivariada, o compromisso do GLS esteve independentemente associado ao desenvolvimento de CIT (odds ratio 4,88, IC 1,32-18,0, p = 0,017). Conclusões: O compromisso da deformação longitudinal é frequente em doentes submetidos a quimioterapia e mostrou um padrão de distribuição predominante a nível septal e anterior. A degradação da GLS foi um preditor independente de CIT. PALAVRAS-CHAVE

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Effect of carvedilol on silent anthracycline-induced cardiotoxicity assessed by strain imaging: A prospective randomized controlled study with six-month follow-up

Abstract: These results indicate that carvedilol has a protective effect against the cardiotoxicity induced by ANT.

Cited by 104 publications

References 27 publications

Early Administration of Carvedilol Protected against Doxorubicin-Induced Cardiomyopathy

Early Administration of Carvedilol Protected against Doxorubicin-Induced Cardiomyopathy

Carvedilol Administration Can Prevent Doxorubicin-Induced Cardiotoxicity: A Double-Blind Randomized Trial

Global and regional patterns of longitudinal strain in screening for chemotherapy-induced cardiotoxicity

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