ABSTRACT

BACKGROUND: Cyclophosphamide (CP) is a commonly used chemotherapeutic and immunosuppressive alkylating agent. However, cardiac adverse effects of CP interfere with its clinical benefit. Cardio-oncology research is currently an important issue and finding effective cardiopreserving agents is a critical need. For the first time, we aimed to detect if dapagliflozin (DAP) could ameliorate CP-induced cardiac injury and investigated the role of hypoxia inducible factor α (HIF1α)/vascular endothelial growth factor (VEGF)/endothelial nitric oxide synthase (eNOS) pathway.

METHODS: Forty male Wistar albino rats were included in the current model. Studied groups are: control group; CP-induced cardiotoxicity group; CP group treated with DAP; CP group treated with DAP and administered a nitric oxide synthase inhibitor; nitro-ω-L-arginine (L-NNA) before DAP to explore the role of eNOS.

RESULTS: Our data revealed that CP could induce cardiac damage as manifested by significant increases in cardiac enzymes, blood pressure, malondialdehyde (MDA), tumor necrosis factor alpha (TNFα), HIF1α, sodium glucose co-transporter 2 (SGLT2) and cleaved caspase-3 levels with toxic histopathological changes. However, there are significant decreases in reduced glutathione (GSH), total antioxidant capacity (TAC), VEGF, and eNOS. On the opposite side, co-administration of DAP showed marked improvement of CP-induced cardiac damage that may be due to its ability to inhibit SGLT2, antioxidant, anti-inflammatory and anti-apoptotic properties. Results showed decreasing the cardioprotective effect of DAP on administration of L-NNA, reflecting the critical effect of eNOS in mediating such protection.

CONCLUSION: DAP could reduce CP cardiotoxicity based upon its ability to modulate SGLT2 and HIF1α/VEGF/eNOS signaling pathway.

PMID:37526264 | DOI:10.1177/09603271231193392

09:46

PubMed articles on: Cardio-Oncology

Statins as preventive therapy for anthracycline cardiotoxicity: A meta-analysis of randomized controlled trials

Int J Cardiol. 2023 Jul 30:131219. doi: 10.1016/j.ijcard.2023.131219. Online ahead of print.

ABSTRACT

BACKGROUND: Cardiotoxicity occurs in 5-20% of cancer patients who receive anthracyclines. The aim of this study was to pool all the randomized controlled trials (RCTs) investigating the cardio-protective role of statins in patients treated with anthracyclines.

METHODS: PubMed and Scopus electronic databases were scanned for eligible studies up to May 3rd, 2023. A total of 5 RCTs with 808 patients were included. Efficacy endpoints were the rate of anthracycline-mediated cardiotoxicity, the incidence of hospitalization for heart failure (HF), left ventricular ejection fraction (LVEF) value after anthracycline treatment, and ∆LVEF calculated as the difference in LVEF before and after anthracycline therapy. Safety endpoints [i.e., the incidence of muscle pain and serious adverse events (SAE)] were also assessed.

RESULTS: On pooled analysis, the statin-treated group had a lower incidence of cardiotoxicity compared to the placebo group [risk ratio (RR) 0.52, 95% confidence Interval (CI) 0.33-0.83, P = 0.01; I2 = 0%], as well as higher mean LVEF [Mean difference (MD) 1.88, 95% CI 0.66-3.1, P < 0.01; I2 = 57.3%)] and a more favorable ∆LVEF during follow-up (MD 2.38, 95% CI -0.03 - +4.79, P = 0.05; I2 = 99%), despite no significant difference in terms of hospitalization for HF and rate of adverse events. Of note, severe heterogeneity affected the analyses for both LVEF and ΔLVEF.

CONCLUSIONS: The current meta-analysis of all RCTs conducted so far shows an overall beneficial effect of statins on the risk of anthracyclines induced cardiotoxicity and LVEF preservation. No difference was observed in the rate of HF hospitalization. . More powered RCTs are needed to fully investigate the impact of statins on prognosis in patients receiving anthracyclines therapy.

PMID:37527752 | DOI:10.1016/j.ijcard.2023.131219

09:46

PubMed articles on: Cardio-Oncology

Neopetroside-B alleviates doxorubicin-induced cardiotoxicity via mitochondrial protection

Biomed Pharmacother. 2023 Jul 29;165:115232. doi: 10.1016/j.biopha.2023.115232. Online ahead of print.

ABSTRACT

Doxorubicin, a member of the anthracycline family, is a widely prescribed anticancer chemotherapy drug. Unfortunately, cumulative doses of doxorubicin can cause mitochondrial dysfunction, leading to acute or chronic cardiotoxicity. This study demonstrated that Neopetroside-B (NPS-B) protects cardiomyocytes in the presence of doxorubicin. NPS-B improved mitochondrial function in cardiomyocytes by increasing ATP production and oxygen consumption rates. On the other hand, NPS-B negatively influenced cancer cell lines by increasing reactive oxygen species. We analyzed NPS-B-influenced metabolites (VIP > 1.0; AUC>0.7; p < 0.05) and proteins (FC > 2.0) and constructed metabolite-protein enrichment, which showed that NPS-B affected uracil metabolism and NAD-binding proteins (e.g., aldehyde dehydrogenase and glutathione reductase) in cardiomyocytes. However, for the cancer cells, NPS-B decreased the NAD+/NADH balance, impairing cell viability. In a xenograft mouse model treated with doxorubicin, NPS-B reduced cardiac fibrosis and improved cardiac function. NPS-B may be a beneficial intervention to reducing doxorubicin-induced cardiotoxicity with anticancer effects.

PMID:37523986 | DOI:10.1016/j.biopha.2023.115232

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11:34

Cardiotoxicity News

PubMed articles on: Cancer & VTE/PE

Thrombophilia Gene Mutations Predict Venous Thromboembolism in Ambulatory Cancer Patients Receiving Chemotherapy

J Thromb Haemost. 2023 Aug 1:S1538-7836(23)00580-9. doi: 10.1016/j.jtha.2023.07.017. Online ahead of print.

ABSTRACT

BACKGROUND: Inherited thrombophilia and cancer both independently increase the risk of venous thromboembolism (VTE). However, whether the increased VTE risk associated with inherited thrombophilia exists in cancer patients is less clear.

OBJECTIVES: Our objective was to determine the influence of inherited thrombophilia on VTE and bleeding risk in moderate-high risk ambulatory cancer patients receiving chemotherapy.

METHODS: We conducted a post-hoc analysis using blood samples from patients enrolled in the AVERT trial to determine if previously recognized thrombophilia gene mutations (Prothrombin FII G20210A, Factor XI, Fibrinogen Gamma, Serpin Family A Member 10, Factor V K858R, Factor XIII, Factor V Leiden (FVL), and ABO blood) were associated with VTE or bleeding during the 7-months after starting chemotherapy. Logistic regression was used comparing heterozygous and homozygous mutations (combined) to wild type. VTE rates, bleeding rates and risk differences for mutations stratified by prophylactic anticoagulation use were calculated.

RESULTS: Of the 447 patients, there were 39 VTE and 39 bleeding events. The odds of VTE were significantly increased with FVL mutation and non-O blood type [OR: 5.2 (95%CI:1.9-14.7) and 2.7 (95%CI:1.2-6.1), respectively]. The use of anticoagulation prophylaxis resulted in complete protection in FVL patients whereas those not receiving anticoagulation had a VTE rate of 119 per 100 patient-years. Lower VTE rates were also observed in non-O blood type patients taking prophylactic anticoagulation. No other thrombophilia genes tested were significantly associated with VTE or bleeding.

CONCLUSIONS: Our results indicate FVL mutation and ABO blood type may be important VTE predictors in cancer patients starting chemotherapy.

PMID:37536569 | DOI:10.1016/j.jtha.2023.07.017

11:34

PubMed articles on: Cancer & VTE/PE

Low-Molecular-Weight Heparin Versus Warfarin in Adult Cancer Patients as a Precision Medicine for Thrombosis: A Systematic Review and Meta-Analysis

Cureus. 2023 Jul 1;15(7):e41268. doi: 10.7759/cureus.41268. eCollection 2023 Jul.

ABSTRACT

Venous thromboembolism (VTE) is a condition often seen in patients diagnosed with cancer and is recognized as a predictor of poor outcomes in these patients. The probability of VTE recurring is generally higher in people with cancer than in those without; hence, addressing this issue is essential when making healthcare decisions. Therefore, our systematic review was primarily designed to compare low-weight- molecular heparin (LMWH) to warfarin in reducing recurrent VTE among cancer patients. However, other outcomes were also evaluated, such as mortality and bleeding events observed more in cancer patients. The selection of relevant articles was carried out using a database search and a manual search, which involved reviewing reference lists of articles eligible for inclusion in the current review. The methodological quality of each included study was then assessed using Cochrane's risk of bias tool in the Review Manager software (RevMan 5.4.1). Additionally, pooled results were examined using the Review Manager software and presented as forest plots. Our search of electronic databases elicited a total of 2163 articles, of which only six were deemed eligible for inclusion and analysis. Data pooled from the six studies demonstrated the effectiveness of LMWH in minimizing the reoccurrence of VTE over warfarin [risk ratio (RR): 0.67; 95% CI: 0.47 - 0.95; p = 0.03]. However, LMWH had a similar effect statistically as warfarin on the major bleeding events (RR: 1.05; 95% CI: 0.62 - 1.77; p = 0.85), minor bleeding events (RR: 0.80; 95% CI: 0.54 - 1.20; p = 0.28), and all-cause mortality (RR: 1.00; 95% CI: 0.88 - 1.13; p = 0.99). While LMWH demonstrated its effectiveness in minimizing the incidence of VTE recurrence over warfarin in cancer patients, it had no statistical difference in terms of mortality or bleeding events when compared to warfarin. Based on our findings, we recommend that LMWH continues to be used as a first-line treatment regimen to mitigate recurrent VTE in cancer patients.

PMID:37533609 | PMC:PMC10390756 | DOI:10.7759/cureus.41268

11:34

PubMed articles on: Cancer & VTE/PE

Direct oral anticoagulants versus aspirin for primary thromboprophylaxis in patients with multiple myeloma undergoing outpatient therapy: A systematic review and updated meta-analysis

Br J Haematol. 2023 Aug 2. doi: 10.1111/bjh.19017. Online ahead of print.