Anthracycline Cardiotoxicity: From Bench to Bedside

Gianni, Luca; Herman, Eugene H.; Lipshultz, Steven E.; Minotti, Giorgio; Sarvazyan, Narine; Sawyer, Douglas B.

doi:10.1200/jco.2007.14.9401

Cited by 420 publications

(357 citation statements)

References 110 publications

(119 reference statements)

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“…Several reports have described the incidence and risk of early cardiotoxicity, characterized by reversible depression of contractile function [12]. Late cardiotoxicity is more common [12,13]. Cardiac abnormalities are observed years after DOX administration; they seem to occur independently of cardiac problems that present during initial therapy [14].…”

Section: Introductionmentioning

confidence: 99%

Curcumin Attenuates Doxorubicin-Induced Cardiotoxicity by Inducing Autophagy via the Regulation of JNK Phosphorylation

Katamura¹,

Iwai-Kanai²,

Nakaoka³

et al. 2014

J Clin Exp Cardiolog

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Background and Objective: Doxorubicin (DOX) has been used in cancer therapy for several decades. However, cardiac complications induced by DOX dose-dependently limit the clinical implication at optimal antitumor efficacy. Curcumin (Cur), a natural compound, has been effective as an anticancer agent in various types of cancers. It also protects against cardiac hypertrophy and heart failure, though its effect on cardiomyopathy caused by DOX treatment is unclear. To elucidate the role of curcumin on heart failure, we used the DOX induced cardiomyopathy model and primary cultured cardiac myocytes. Method and Results:Male C57/BL6 mice were randomized to 4 courses of treatment administered for 4 weeks: Phosphate-Buffered Saline (PBS), Cur, DOX, and DOX+Cur. DOX-treated mice exhibited severe cardiac dysfunction, and the mortality was higher than that in PBS-treated mice. In DOX-treated mice, the number of apoptotic cardiac myocytes was higher and the fibrotic areas were larger than in PBS-treated mice. The cardiotoxic effects of DOX were ameliorated by treatment with Cur. In DOX-treated GFP-LC3 transgenic mice, Cur induced autophagy and decreased apoptosis in the heart. Cur also induced autophagy and suppressed DOX-induced apoptosis in neonatal rat cardiac myocytes. Inhibition of autophagy by 3-methyladenine decreased the cardioprotective effect of Cur. Furthermore, Cur decreased c-Jun N-terminal kinase (JNK) phosphorylation, resulting in reduction of apoptosis. The JNK inhibitor SP600125 abolished these effects. Conclusion:Cur protects the heart from DOX-induced cardiotoxicity by inducing autophagy and decreasing cardiomyocyte apoptosis. The mechanism involves JNK-mediated modification of apoptosis. Induction of cardiac autophagy may be a novel therapeutic approach for preventing DOX-induced cardiotoxicity.

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Section: Introductionmentioning

confidence: 99%

Curcumin Attenuates Doxorubicin-Induced Cardiotoxicity by Inducing Autophagy via the Regulation of JNK Phosphorylation

Katamura¹,

Iwai-Kanai²,

Nakaoka³

et al. 2014

J Clin Exp Cardiolog

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“…Early detection of cardiac function abnormality is of paramount importance in patients after www.cardiologyjournal.org anthracycline therapy [12][13][14][15][16]. Anthracyclineinduced cardiomyocytes cell death by apoptosis and myofilament degradation may lead to impaired myocardial deformation as well as systolic dysfunction [17].…”

Section: Discussionmentioning

confidence: 99%

The early variation of left ventricular twisting function in patients with lymphoma received anthracycline therapy assessed by three-dimensional speckle tracking echocardiography

et al. 2017

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± 4.5° vs. 8.8 ± 3.6° vs. 6.0 ± 3.2°; basal rotation: -7.7 ± 3.0° vs. -5.9 ± 2.6° vs. -4.4 ± 2.5°; twist: 20.0 ± 6.4° vs. 14.5 ± 5.1° vs. 9.8 ± 4.5°; torsion: 2.9 ± 0.9°/cm vs. 2.1 ± 0.9°/cm vs. 1.4 ± 0.7°/cm; all p < 0.01). Furthermore, apical-basal rotation delay increased significantly after two cycles as well as after four cycles of the regimen (38.3 ± 67.9 ms vs. 66.7 ± 73.9 ms vs. 92.6 ± 96.9 ms; p < 0.01). Conclusions: LV twisting function deteriorated in the early stage of anthracycline therapy in patients with lymphoma, which could be detected by 3D-STE sensitively. (Cardiol J 2017; 24, 5: 484-494)

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“…However, there is no generally accepted mechanism for how these drugs cause heart failure [26]. A general hypothesis for anthracyclineinduced cardiac toxicity is that some form of cardiac injury occurs with every repeat exposure.…”

Section: Lessons From Oncology -Could Anthracyclines Be Used To Regrementioning

confidence: 99%

How Can we Improve Non-Surgical Septal Reduction for Hypertrophic Obstructive Cardiomyopathy?

Cleator¹,

Kasasbeh²

2016

J Cardiovasc Dis Diagn

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The goal for treatment of medical refractory Hypertrophic Obstructive Cardiomyopathy (HCM) is reduction of the hypertrophied left ventricular septum which obstructs blood flow. A surgical approach consists of an open-heart myomectomy, while the less invasive percutaneous approach involves creating a myocardial infarction by injecting 95 to 100% ethanol through a septal artery, a procedure termed alcohol septal ablation (ASA). Although less invasive than myomectomy, there are several limitations of alcohol septal ablation. The most important appears to be full thickness infarction that is often complicated by heart block and ventricular tachycardia/fibrillation. The ideal therapy for septal hypertrophy would be to find an agent that induces a less severe injury and/or atrophy of the hypertrophied septum. We review several alternative techniques for selective injury of the septum and describe the ideal characteristics of such an ideal agent. Our central hypothesis is that the anthracycline antibiotic such as doxorubicin may be the perfect agent. Anthracycline-based chemotherapies have been used in the treatment of solid and hematological tumors for many years. These agents have known cardiotoxic side effects that are related to cumulative dose which can lead to heart failure. Although the mechanism of action of doxorubicin cardiotoxicity is controversial, it is very clear that these agents cause atrophy of the myocardium, induce apoptosis and necrosis, as well as anti-angiogenic effects. We propose that selectively treating the hypertrophied septum of HCM patients with injection of the anthracycline doxorubicin will lead to superior outcomes compared to ASA.

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Anthracycline Cardiotoxicity: From Bench to Bedside

Cited by 420 publications

References 110 publications

Curcumin Attenuates Doxorubicin-Induced Cardiotoxicity by Inducing Autophagy via the Regulation of JNK Phosphorylation

Curcumin Attenuates Doxorubicin-Induced Cardiotoxicity by Inducing Autophagy via the Regulation of JNK Phosphorylation

The early variation of left ventricular twisting function in patients with lymphoma received anthracycline therapy assessed by three-dimensional speckle tracking echocardiography

How Can we Improve Non-Surgical Septal Reduction for Hypertrophic Obstructive Cardiomyopathy?

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