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Abstract

The incidence of acute myeloid leukemia (AML) increases with age. Intensive induction chemotherapy containing cytarabine and an anthracycline has been part of the upfront and salvage treatment of AML for decades. Anthracyclines are associated with a significant risk of cardiotoxicity (especially anthracycline-related left ventricular dysfunction [ARLVD]). In the older adult population, the higher prevalence of cardiac comorbidities and risk factors may further increase the risk of ARLVD. In this article of the Young International Society of Geriatric Oncology group, we review the prevalence of ARLVD in patients with AML and factors predisposing to ARLVD, focusing on older adults when possible. In addition, we review the assessment of cardiac function and management of ARLVD during and after treatment. It is worth noting that only a minority of clinical trials focus on alternative treatment strategies in patients with mildly declined left ventricular ejection fraction or at a high risk for ARLVD. The limited evidence for preventive strategies to ameliorate ARLVD and alternative strategies to anthracycline use in the setting of cardiac comorbidities are discussed. Based on extrapolation of findings from younger adults and nonrandomized trials, we recommend a comprehensive baseline evaluation of cardiac function by imaging, cardiac risk factors, and symptoms to risk stratify for ARLVD. Anthracyclines remain an appropriate choice for induction although careful risk-stratification based on cardiac disease, risk factors, and predicted chemotherapy-response are warranted. In case of declined left ventricular ejection fraction, alternative strategies should be considered.

PMID: 32097461 [PubMed - as supplied by publisher]

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pubmed: tutte cardiotoxicity...

Corrigendum to "The cardiotoxicity effect of different chemotherapeutic regimens in Iraqi patients with breast cancer: A follow up study" [Heliyon 5 (8) (August 2019) e02194].


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Corrigendum to "The cardiotoxicity effect of different chemotherapeutic regimens in Iraqi patients with breast cancer: A follow up study" [Heliyon 5 (8) (August 2019) e02194].


Heliyon. 2020 Feb;6(2):e03398


Authors: Anber ZNH, Saleh BOM, Al-Rawi SA


Abstract

[This corrects the article DOI: 10.1016/j.heliyon.2019.e02194.].

PMID: 32095649 [PubMed - in process]

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Aconitine induces cardiomyocyte damage by mitigating BNIP3-dependent mitophagy and the TNFα-NLRP3 signalling axis.


//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--media.wiley.com-assets-7388-69-wiley-full-text.png Related Articles

Aconitine induces cardiomyocyte damage by mitigating BNIP3-dependent mitophagy and the TNFα-NLRP3 signalling axis.


Cell Prolif. 2020 Jan;53(1):e12701


Authors: Peng F, Zhang N, Wang C, Wang X, Huang W, Peng C, He G, Han B


Abstract

OBJECTIVES: Aconitine, the natural product extracted from Aconitum species, is widely used for the treatment of various diseases, including rheumatism, arthritis, bruises, fractures and pains. However, many studies have reported cardiotoxicity and neurotoxicity caused by aconitine, but the detailed mechanism underlying aconitine's effect on these processes remains unclear.

MATERIALS AND METHODS: The effects of aconitine on the inflammation, apoptosis and viability of H9c2 rat cardiomyocytes were evaluated by flow cytometry, Western blot, RNA sequencing and bioinformatics analysis.

RESULTS: Aconitine suppressed cardiomyocyte proliferation and induced inflammation and apoptosis in a dose- and time-dependent manner. These inflammatory damages could be reversed by a TNFα inhibitor and BNIP3-mediated mitophagy. Consistent with the in vitro results, overexpression of BNIP3 in heart tissue partially suppressed the cardiotoxicity of aconitine by inhibiting apoptosis and the NLRP3 inflammasome.

CONCLUSIONS: Our findings lay a foundation for the application of a TNFα inhibitor and BNIP3 to aconitine-induced cardiac toxicity prevention and therapy, thereby demonstrating potential for further investigation.

PMID: 31657084 [PubMed - indexed for MEDLINE]

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pubmed: tutte cardiotoxicity...

Early Detection and Monitoring of Cancer Chemotherapy-Related Left Ventricular Dysfunction by Imaging Methods.


//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--www.scielo.br-img-scielo.gif //www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--www.ncbi.nlm.nih.gov-corehtml-pmc-pmcgifs-pubmed-pmc.png Related Articles

Early Detection and Monitoring of Cancer Chemotherapy-Related Left Ventricular Dysfunction by Imaging Methods.


Arq Bras Cardiol. 2019 03;112(3):309-316


Authors: Ribeiro ML, Jorge AJL, Nacif MS, Martins WA


PMID: 30916206 [PubMed - indexed for MEDLINE]

27 February 2020

15:48

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Combined cardio-protective ability of syringic acid and resveratrol against isoproterenol induced cardio-toxicity in rats via attenuating NF-kB and TNF-α pathways.


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Combined cardio-protective ability of syringic acid and resveratrol against isoproterenol induced cardio-toxicity in rats via attenuating NF-kB and TNF-α pathways.


Sci Rep. 2020 Feb 25;10(1):3426


Authors: S M, Shaik AH, E MP, Al Omar SY, Mohammad A, Kodidhela LD


Abstract

The study was conducted to evaluate the cardio-protective activity of combination (COMB) of syringic acid (SA) and resveratrol (RV) against isoproterenol (ISO) induced cardio-toxicity in rats. Rats were pre-treated orally with SA (50 mg/kg), RV (50 mg/kg) and combination of SA (25 mg/kg) and RV (25 mg/kg) along with positive control gallic acid (50 mg/kg) for 30 days. The effects of ISO on cardiac markers, lipid profile and lipid peroxidation marker, anti-oxidant enzymes and m-RNA expression of nuclear factor-kappa B (NF-kB) and tumor necrosis factor-α (TNF-α) were observed along with histopathological observations of simple and transmission electron microscopes (TEM). Serum creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH) and alkaline phosphatase were significantly increased while cardiac tissue CK-MB, LDH, superoxide dismutase and catalase were significantly decreased in ISO administered rats, which also exhibited a significant increase in total cholesterol, triglycerides, low density lipoprotein cholesterol, very low density lipoprotein cholesterol and thiobarbutyric acid reactive substances and significant decrease in high density lipoprotein cholesterol in serum and heart. The m-RNA levels of inflammatory markers NF-kB and TNF-α were significantly increased in ISO treated rats. COMB Pre-treatment significantly reversed the ISO actions. Histopathological studies of simple and TEM were also co-related with the above biochemical parameters. Docking studies with NF-kB were also performed. Evidence has shown for the first time in this approach that COMB pre-treatment ameliorated ISO induced cardio-toxicity in rats and revealed cardio-protection.

PMID: 32099011 [PubMed - in process]

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Variability in echocardiography and MRI for detection of cancer therapy cardiotoxicity.


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Variability in echocardiography and MRI for detection of cancer therapy cardiotoxicity.


Heart. 2020 Feb 25;:


Authors: Lambert J, Lamacie M, Thampinathan B, Altaha MA, Esmaeilzadeh M, Nolan M, Fresno CU, Somerset E, Amir E, Marwick TH, Wintersperger BJ, Thavendiranathan P


Abstract

OBJECTIVES: To compare variability of echocardiographic and cardiovascular magnetic resonance (CMR) measured left ventricular (LV) function parameters and their relationship to cancer therapeutics-related cardiac dysfunction (CTRCD).

METHODS: We prospectively recruited 60 participants (age: 49.8±11.6 years), 30 women with human epidermal growth factor receptor 2-positive breast cancer (15 with CTRCD and 15 without CTRCD) and 30 healthy volunteers. Patients were treated with anthracyclines and trastuzumab. Participants underwent three serial CMR (1.5T) and echocardiography studies at ~3-month intervals. Cine-CMR for LV ejection fraction (LVEF), myocardial tagging for global longitudinal strain (GLS) and global circumferential strain (GCS), two-dimensional (2D) echocardiography for strain and LVEF and three-dimensional (3D) echocardiography for LVEF measurements were obtained. Temporal, interobserver and intraobserver variability were calculated as the coefficient of variation and as the SE of the measurement (SEM). Minimal detected difference (MDD) was defined as 2xSEM.

RESULTS: Patients with CTRCD demonstrated larger mean temporal changes in all parameters compared with those without: 2D-LVEF: 4.6% versus 2.8%; 3D-LVEF: 5.2% vs 2.3%; CMR-LVEF: 6.6% versus 2.7%; 2D-GLS: 1.9% versus 0.7%, 2D-GCS: 2.5% versus 2.2%; CMR-GCS: 2.7% versus 1.6%; and CMR-GLS: 2.1% versus 1.4%, with overlap in 95% CI for 2D-LVEF, 2D-GCS, CMR-GLS and CMR-GCS. The respective mean temporal variability/MDD in healthy volunteers were 3.3%/6.5%, 1.8%/3.7%, 2.2%/4.4%, 0.8%/1.5%, 1.9%/3.7%, 1.8%/3.6% and 1.4%/2.8%. Although the mean temporal variability in healthy volunteers was lower than the mean temporal changes in CTRCD, at the individual level, 2D-GLS, 3D-LVEF and CMR-LVEF had the least overlap. 2D-GLS and CMR-LVEF had the lowest interobserver/intraobserver variabilities.

CONCLUSION: Temporal changes in 3D-LVEF, 2D-GLS and CMR LVEF in patients with CTRCD had the least overlap with the variability in healthy volunteers; however, 2D-GLS appears to be the most suitable for clinical application in individual patients.

PMID: 32098808 [PubMed - as supplied by publisher]

28 February 2020

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Glycyrrhiza glabra (Licorice) root extract attenuates doxorubicin-induced cardiotoxicity via alleviating oxidative stress and stabilising the cardiac health in H9c2 cardiomyocytes.


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Glycyrrhiza glabra (Licorice) root extract attenuates doxorubicin-induced cardiotoxicity via alleviating oxidative stress and stabilising the cardiac health in H9c2 cardiomyocytes.


J Ethnopharmacol. 2020 Feb 24;:112690


Authors: Upadhyay S, Mantha AK, Dhiman M


Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Doxorubicin (DOX) is an effective anti-neoplastic drug, however; it has downside effects on cardiac health and other vital organs. The herbal remedies used in day to day life may have a beneficial effect without disturbing the health of the vital organs. Glycyrrhiza glabra L. is a ligneous perennial shrub belonging to Leguminosae/Fabaceae/Papilionaceae family growing in Mediterranean region and Asia and widespread in Turkey, Italy, Spain, Russia, Syria, Iran, China, India and Israel. Commonly known as mulaithi in north India, G. glabra has glycyrrhizin, glycyrrhetic acid, isoliquiritin, isoflavones, etc., which have been reported for several pharmacological activities such as anti-demulcent, anti-ulcer, anti-cancer, anti-inflammatory and anti-diabetic.

AIM OF THE STUDY: The objective of the present study is to investigate the interaction between the molecular factors like PPAR-α/γ and SIRT-1 during cardiac failure arbitrated by DOX under in vitro conditions and role of Glycyrrhiza glabra (Gg) root extract in alleviating these affects.

MATERIALS AND METHODS: In the present study, we have examined the DOX induced responses in H9c2 cardiomyocytes and investigated the role of phytochemical Glycyrrhiza glabra in modulating these affects. MTT assay was done to evaluate the cell viability, Reactive Oxygen Species (ROS)/Reactive Nitrogen Species (RNS) levels, mitochondrial ROS, mitochondrial membrane potential was estimated using fluorescent probes. The oxidative stress in terms of protein carbonylation, lipid peroxidation and DNA damage was detected via spectrophotometric methods and immune-fluorescence imaging. The cardiac markers and interaction between SIRT-1 and PPAR-α/γ was measured using Real-Time PCR, Western Blotting and Co-immunoprecipitation based studies.

RESULTS: The Glycyrrhiza glabra (Gg) extracts maintained the membrane integrity and improved the lipid homeostasis and stabilized cytoskeletal element actin. Gg phytoextracts attenuated aggravated ROS level, repaired the antioxidant status and consequently, assisted in repairing the DNA damage and mitochondrial function. Further, the expression of hypertrophic markers in the DOX treated cardiomyocytes reconciled the expression factors both at the transcriptional and translational levels after Gg treatment. SIRT-1 mediated pathway and its downstream activator PPAR factors are significant in maintaining the cellular functions. It was observed that the Gg extract allows regaining the nuclear SIRT-1 and PPAR-γ level which was otherwise reduced with DOX treatment in H9c2 cardiomyocytes. The co-immunoprecipitation (Co-IP) documented that SIRT-1 interacts with PPAR-α in the untreated control H9c2 cardiomyocytes whereas DOX treatment interferes and diminishes this interaction however the Gg treatment maintains this interaction. Knocking down SIRT-1 also downregulated expression of PPAR-α and PPAR-γ in DOX treated cells and Gg treatment was able to enhance the expression of PPAR-α and PPAR-γ in SIRT-1 knocked down cardiomyocytes.

CONCLUSIONS: The antioxidant property of Gg defend the cardiac cells against the DOX induced toxicity via; 1) reducing the oxidative stress, 2) maintaining the mitochondrial functions, 3) regulating lipid homeostasis and cardiac metabolism through SIRT-1 pathway and 4) conserving the cardiac hypertrophy and hence preserving t[...]

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he cardiomyocytes health. Therefore, Gg can be recommended as a healthier supplement with DOX towards cancer therapeutics associated cardiotoxicity.

PMID: 32105749 [PubMed - as supplied by publisher]

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Cardiotoxic Profile and Arterial Stiffness of Adjuvant Chemotherapy for Colorectal Cancer.


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Cardiotoxic Profile and Arterial Stiffness of Adjuvant Chemotherapy for Colorectal Cancer.


Cancer Manag Res. 2020;12:1175-1185


Authors: Visvikis A, Kyvelou SM, Pietri P, Georgakopoulos C, Manousou K, Tousoulis D, Stefanadis C, Vlachopoulos C, Pektasides D


Abstract

Background and Purpose: Even though new cancer therapies have improved the overall survival, in some cases they have been associated with adverse effects, including increased cardiotoxicity. The purpose of the present study was to assess the cardiovascular effects of adjuvant chemotherapy for colorectal cancer and mainly the impact on arterial stiffness indices.

Material and Methods: A total of 70 patients with non-metastatic colorectal cancer who were treated either with FOLFOX (n=16) or with XELOX (n=54) adjuvant chemotherapy were included in the study. All patients were subjected to full cardiovascular evaluation at the beginning and the end of chemotherapy. Arterial stiffness was assessed by means of pulse wave velocity (PWV) and augmentation index (Aix) and full laboratory examinations were conducted prior to, and soon after, the termination of chemotherapy.

Results: Patients exhibited significantly higher levels of carotid-radial PWV, carotid femoral RWV and Aix post-chemotherapy (p<0.001);

Conclusion: There is a clear burden in arterial stiffness indices post-adjuvant chemotherapy for colorectal cancer in both chemotherapy groups. This is a finding of important clinical significance, however more prospective studies are required in order to encode the possible mechanisms involved.

PMID: 32104097 [PubMed]

29 February 2020

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Combined effects of berberine and evodiamine on colorectal cancer cells and cardiomyocytes in vitro.


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Combined effects of berberine and evodiamine on colorectal cancer cells and cardiomyocytes in vitro.


Eur J Pharmacol. 2020 Feb 25;:173031


Authors: Guan X, Zheng X, Vong CT, Zhao J, Xiao J, Wang Y, Zhong Z


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