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Abstract

AIMS: Data regarding the cardiac toxicity of cabozantinib lacks. The aim of our study was to assess the risk of cabozantinib-related cardiotoxicity in mRCC patients.

METHODS: We performed a multicentre prospective study on mRCC patients treated with cabozantinib between October 2016 and November 2017. Transthoracic echocardiogram and plasma biomarkers assay were assessed at baseline, 3 and 6 months after cabozantinib initiation.

RESULTS: The study population included 22 mRCC patients. At baseline, 9.1% had a reduced left ventricular ejection fraction (LVEF), but none had a left ventricular systolic dysfunction. Patients with baseline reduced LVEF did not show further significant LVEF modification after 3 months. After 6 months, only 1 had an LVEF decline >10% compared to baseline, resulting in LV systolic dysfunction. At baseline, 64.7% and 27.3% of patients had elevated precursor brain natriuretic peptide (proBNP) and high-sensitivity troponin I (hsTnI), respectively. Among patients with basal normal proBNP and hsTnI, none had elevated values at 3 and 6 months. No correlation was found between basal elevated proBNP and basal reduced LVEF (P = .29), and between elevated proBNP and reduced LVEF after 6 months (P = .37). Similarly, we found no correlations between elevated hsTnI and reduced LVEF or elevated proBNP at baseline (P = .47; P = .38), at 3 (P = .059; P = .45) and after 6 months (P = .72; P = 1.0).

CONCLUSIONS: This prospective study revealed a modest risk of developing left ventricular systolic dysfunction related to cabozantinib. A lack of correlation between elevated cardiac biomarkers and reduced LVEF at different time-points was detected. Assessments of the cardiac function should be reserved at the occurrence of clinical symptoms.

PMID: 30740760 [PubMed - indexed for MEDLINE]

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Detection of anthracycline-induced cardiotoxicity using perfusion-corrected 99mTc sestamibi SPECT.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--www.nature.com-images-lo_npg.gif //www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--www.ncbi.nlm.nih.gov-corehtml-pmc-pmcgifs-pubmed-pmc.png Related Articles

Detection of anthracycline-induced cardiotoxicity using perfusion-corrected 99mTc sestamibi SPECT.

Sci Rep. 2019 01 18;9(1):216

Authors: Safee ZM, Baark F, Waters ECT, Veronese M, Pell VR, Clark JE, Mota F, Livieratos L, Eykyn TR, Blower PJ, Southworth R

Abstract

By the time cardiotoxicity-associated cardiac dysfunction is detectable by echocardiography it is often beyond meaningful intervention. 99mTc-sestamibi is used clinically to image cardiac perfusion by single photon emission computed tomography (SPECT) imaging, but as a lipophilic cation its distribution is also governed by mitochondrial membrane potential (ΔΨm). Correcting scans for variations in perfusion (using a ΔΨm-independent perfusion tracer such as (bis(N-ethoxy-N-ethyldithiocarbamato)nitrido 99mTc(V)) (99mTc-NOET) could allow 99mTc-sestamibi to be repurposed to specifically report on ΔΨm as a readout of evolving cardiotoxicity. Isolated rat hearts were perfused within a γ-detection apparatus to characterize the pharmacokinetics of 99mTc-sestamibi and 99mTc-NOET in response to mitochondrial perturbation by hypoxia, ionophore (CCCP) or doxorubicin. All interventions induced 99mTc-sestamibi washout; hypoxia from 24.9 ± 2.6% ID to 0.4 ± 6.2%, CCCP from 22.8 ± 2.5% ID to -3.5 ± 3.1%, and doxorubicin from 23.0 ± 2.2% ID to 17.8 ± 0.7, p < 0.05.< 0.05)),

PMID: 30659226 [PubMed - indexed for MEDLINE]

16 April 2020

14:12

Cardiotoxicity News

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Investigation of cardiovascular protective effect of Shenmai injection by network pharmacology and pharmacological evaluation.

BMC Complement Med Ther. 2020 Apr 15;20(1):112

Authors: Li L, Yang D, Li J, Niu L, Chen Y, Zhao X, Oduro PK, Wei C, Xu Z, Wang Q, Li Y

Abstract

BACKGROUND: Shenmai injection (SMI) has been used in the treatment of cardiovascular disease (CVD), such as heart failure, myocardial ischemia and coronary heart disease. It has been found to have efficacy on doxorubicin (DOX)-induced cardiomyopathy. The aims of this study were to explore the underlying molecular mechanisms of SMI treatment on CVD by using network pharmacology and its protective effect on DOX-induced cardiotoxicity by in vitro and in vivo experiment based on network pharmacology prediction.

METHODS: Network pharmacology method was used to reveal the relationship between ingredient-target-disease and function-pathway of SMI on the treatment of CVD. Chemical ingredients of SMI were collected form TCMSP, BATMAN-TCM and HIT Database. Drugbank, DisGeNET and OMIM Database were used to obtain potential targets for CVD. Networks were visualized utilizing Cytoscape software, and the enrichment analysis was performed using IPA system. Finally, cardioprotective effects and predictive mechanism confirmation of SMI were investigated in H9c2 rat cardiomyocytes and DOX-injured C57BL/6 mice.

RESULTS: An ingredient-target-disease & function-pathway network demonstrated that 28 ingredients derived from SMI modulated 132 common targets shared by SMI and CVD. The analysis of diseases & functions, top pathways and upstream regulators indicated that the cardioprotective effects of SMI might be associated with 28 potential ingredients, which regulated the 132 targets in cardiovascular disease through regulation of G protein-coupled receptor signaling. In DOX-injured H9c2 cardiomyocytes, SMI increased cardiomyocytes viability, prevented cell apoptosis and increased PI3K and p-Akt expression. This protective effect was markedly weakened by PI3K inhibitor LY294002. In DOX-treated mice, SMI treatment improved cardiac function, including enhancement of ejection fraction and fractional shortening.

CONCLUSIONS: Collectively, the protective effects of SMI on DOX-induced cardiotoxicity are possibly related to the activation of the PI3K/Akt pathway, as the downstream of G protein-coupled receptor signaling pathway.

PMID: 32293408 [PubMed - as supplied by publisher]

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Ultrastructural and Echocardiographic Assessment of Chronic Doxorubicin-Induced Cardiotoxicity in Rats.

Arch Razi Inst. 2020 Mar;75(1):55-62

Authors: Babaei H, Razmaraii N, Assadnassab G, Mohajjel Nayebi A, Azarmi Y, Mohammadnejad D, Azami A

Abstract

Doxorubicin (DOX) is one of the secondary metabolites of Streptomyces peucetius var. caesius. It is a common and effective chemotherapeutic agent used for the treatment of different diseases, including lymphoma, leukemia, breast cancer, and solid tumors. However, this medicine causes cardiotoxic side effects, which limit its clinical application. The present study examined the cardiomyopathy induced by DOX via echocardiography and transmission electron microscopy (TEM). The main objective was to evaluate the capacity of echocardiography and TEM as diagnostic tools for DOX-induced cardiotoxicity. Moreover, the correlation between intracellular and functional changes due to cardiotoxicity was assessed in a rat model. Cardiomyopathy was induced in rats by two cumulative doses of DOX. Group I received DOX 12 [i.e., 12 mg/kg, intraperitoneal (IP)] and group II received DOX 15 (i.e., 15 mg/kg, IP) in six equal doses over two weeks. Group III as the control (Ctrl) group received normal saline as a vehicle. Mortality during the study was only observed in the DOX 15 group. The echocardiographic assessments revealed significant changes in ejection fraction, fractional shortening, and heart rate in the groups which received DOX. In addition, severe cardiac arrhythmia was evident in DOX-treated groups. Remarkable adverse effects, such as moderately degenerated cells and inflated mitochondria were observed in the TEM analysis of rat hearts in the DOX groups. The present study indicated that rat models are suitable for investigating DOX-induced cardiomyopathy, especially at the dose of 12 mg/kg. Furthermore, echocardiography and TEM examinations were found to be valuable methods for the determination of cardiotoxicity in rats due to DOX.

PMID: 32292003 [PubMed - in process]

17 April 2020

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Evaluating biomarkers as predictors of cancer therapy cardiotoxicity: all you need is a meta-analysis?

Eur J Heart Fail. 2020 Apr 15;:

Authors: Aimo A, Fabiani I, Emdin M

PMID: 32297460 [PubMed - as supplied by publisher]

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Subclinical Cardiac Dysfunction in Childhood Cancer Survivors on 10-Years Follow-Up Correlates With Cumulative Anthracycline Dose and Is Best Detected by Cardiopulmonary Exercise Testing, Circulating Serum Biomarker, Speckle Tracking Echocardiography, and Tissue Doppler Imaging.

Front Pediatr. 2020;8:123

Authors: Wolf CM, Reiner B, Kühn A, Hager A, Müller J, Meierhofer C, Oberhoffer R, Ewert P, Schmid I, Weil J