ABSTRACT

BACKGROUND AND OBJECTIVE: Aflibercept; a decoy receptor for vascular endothelial growth factors (VEGFs) and placental growth factor (PLGF), in combination with FOLFIRI (leucovorin calcium, fluorouracil, irinotecan hydrochloride) chemotherapy regime, was FDA approved in 2012 as second-line salvage chemotherapy for metastatic colorectal cancer (mCRC). This is the first systematic review, and meta-analysis-based evidence to determine the efficacy and safety of Aflibercept plus FOLFIRI regimen pooling randomized controlled trials and single-arm studies.

METHOD: PubMed, Cochrane library, Embase, and Clinical trial.gov were systematically searched for published randomized controlled trials, single-arm studies, and national patient programs on aflibercept plus FOLFIRI chemotherapy for the treatment of mCRC till 11/10/2022.

RESULT: Ten studies met the inclusion criteria comprising 1075 patients for efficacy studies and 2027 patients for safety studies. The pooled prevalences were 18% (95% CI, 5%-37%, p = 0.00) for 12 m PFS and 61% (95% CI, 53-68%, p = 0.00) for 12 m OS. The pooled prevalences were 69% (95% CI, 55-82%, p = 0.00) for any grade 3-4 toxicities, 10% (95% CI, 5-16%, p = 0.00) for grade 3-4 diarrhea, 13% (95% CI, 5-24%, p = 0.00) for grade 3-4 hypertension, 31% (95% CI, 22-40%, p = 0.00) for grade 3-4 neutropenia and 5% (95% CI, 2-7%, p = 0.00) for grade 3-4 venous thromboembolic event.

CONCLUSION: Our meta-analysis shows that the aflibercept plus FOLFIRI combination shows better survival efficacies however; it is also associated with more high-grade adverse events.

PMID:37257732 | DOI:10.1016/j.critrevonc.2023.104034

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PubMed articles on: Cardio-Oncology

Cardiac calcified amorphous tumor in a patient with colon cancer

Clin Case Rep. 2023 Jun 7;11(6):e7491. doi: 10.1002/ccr3.7491. eCollection 2023 Jun.

ABSTRACT

Although one of the most important differential diagnoses of cardiac masses in cancer patients is metastasis from the underlying tumor, it may also be caused by benign etiologies. In this article, we describe cardiac calcified amorphous tumor, which is one of the benign causes of cardiac masses, in a patient with colon cancer.

PMID:37305859 | PMC:PMC10248199 | DOI:10.1002/ccr3.7491

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PubMed articles on: Cardio-Oncology

Chemotherapy-induced cardiotoxicity: a new perspective on the role of Digoxin, ATG7 activators, Resveratrol, and herbal drugs

J Med Life. 2023 Apr;16(4):491-500. doi: 10.25122/jml-2022-0322.

ABSTRACT

Cancer is a major public health problem, and chemotherapy plays a significant role in the management of neoplastic diseases. However, chemotherapy-induced cardiotoxicity is a serious side effect secondary to cardiac damage caused by antineoplastic's direct and indirect toxicity. Currently, there are no reliable and approved methods for preventing or treating chemotherapy-induced cardiotoxicity. Understanding the mechanisms of chemotherapy-induced cardiotoxicity may be vital to improving survival. The independent risk factors for developing cardiotoxicity must be considered to prevent myocardial damage without decreasing the therapeutic efficacy of cancer treatment. This systematic review aimed to identify and analyze the evidence on chemotherapy-induced cardiotoxicity, associated risk factors, and methods to decrease or prevent it. We conducted a comprehensive search on PubMed, Google Scholar, and Directory of Open Access Journals (DOAJ) using the following keywords: "doxorubicin cardiotoxicity", "anthracycline cardiotoxicity", "chemotherapy", "digoxin decrease cardiotoxicity", "ATG7 activators", retrieving 59 articles fulfilling the inclusion criteria. Therapeutic schemes can be changed by choosing prolonged infusion application over boluses. In addition, some agents like Dexrazoxane can reduce chemotherapy-induced cardiotoxicity in high-risk groups. Recent research found that Digoxin, ATG7 activators, Resveratrol, and other medical substances or herbal compounds have a comparable effect on Dexrazoxane in anthracycline-induced cardiotoxicity.

PMID:37305823 | PMC:PMC10251384 | DOI:10.25122/jml-2022-0322

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PubMed articles on: Cardio-Oncology

Replication of genetic associations of chemotherapy-related cardiotoxicity in the adjuvant NSABP B-31 clinical trial

Front Oncol. 2023 May 25;13:1139347. doi: 10.3389/fonc.2023.1139347. eCollection 2023.

ABSTRACT

BACKGROUND: The cardiotoxic effects of doxorubicin, trastuzumab, and other anticancer agents are well known, but molecular genetic testing is lacking for the early identification of patients at risk for therapy-related cardiac toxicity.

METHODS: Using the Agena Bioscience MassARRAY system, we genotyped TRPC6rs77679196, BRINP1rs62568637, LDB2rs55756123, RAB22Ars707557, intergenic rs4305714, LINC01060rs7698718, and CBR3rs1056892 (V244M) (previously associated with either doxorubicin or trastuzumab-related cardiotoxicity in the NCCTG N9831 trial of anthracycline-based chemotherapy ± trastuzumab) in 993 patients with HER2+ early breast cancer from the NSABP B-31 trial of adjuvant anthracycline-based chemotherapy ± trastuzumab. Association analyses were performed with outcomes of congestive heart failure (N = 29) and maximum decline in left ventricular ejection fraction (LVEF) using logistic and linear regression models, respectively, under an additive model with age, baseline LVEF, and previous use of hypertensive medications as covariates.

RESULTS: Associations of maximum decline in LVEF in the NCCTG N9831 patients did not replicate in the NSABP B-31 patients. However, TRPC6rs77679196 and CBR3rs1056892 were significantly associated with congestive heart failure, p< 0.05, with stronger associations observed in patients treated with chemotherapy only (no trastuzumab) or in the combined analysis of all patients relative to those patients treated with chemotherapy + trastuzumab.

CONCLUSIONS: TRPC6rs77679196 and CBR3rs1056892 (V244M) are associated with doxorubicin-induced cardiac events in both NCCTG N9831 and NSABP B-31. Other variants previously associated with trastuzumab-related decline in LVEF failed to replicate between these studies.

PMID:37305569 | PMC:PMC10248403 | DOI:10.3389/fonc.2023.1139347

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PubMed articles on: Cardio-Oncology

Drug therapy for myocarditis induced by immune checkpoint inhibitors

Front Pharmacol. 2023 May 25;14:1161243. doi: 10.3389/fphar.2023.1161243. eCollection 2023.

ABSTRACT

Immune checkpoint inhibitors (ICIs), including cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death 1 (PD-1), and its ligand 1 (PD-L1), have improved the survival in multiple types of cancers; however, ICIs may cause cardiovascular toxicity. Although rare, ICI-mediated cardiotoxicity is an extremely serious complication with a relatively high mortality. In this review, we discuss the underlying mechanism and clinical manifestations of cardiovascular toxicity induced by ICIs. According to previous studies, multiple signaling pathways are involved in myocarditis induced by ICIs. Further, we summarize the clinical trials of drugs for the treatment of ICI-associated myocarditis. Although these drugs have shown the beneficial effects of alleviating cardiac function and reducing mortality rates, their efficacy is not optimal. Finally, we discuss the therapeutic potential of some novel compounds as well as the underlying mechanisms of their action.

PMID:37305530 | PMC:PMC10248045 | DOI:10.3389/fphar.2023.1161243

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PubMed articles on: Cardio-Oncology

Ambulatory blood pressure monitoring in patients with onco-hematological diseases

Hipertens Riesgo Vasc. 2023 Jun 9:S1889-1837(23)00033-8. doi: 10.1016/j.hipert.2023.05.006. Online ahead of print.

ABSTRACT

Hypertension (HT) is a frequent pathology in patients with active or surviving onco-haematological malignancies. It is estimated that the prevalence of HT in this population ranges between 30 and 70%. The relationship between cancer and HT is multifactorial: common risk factors, neoplasia that cause HT through hormonal secretion, and, especially, chemotherapy drugs that cause HT. Ambulatory blood pressure monitoring (ABPM) is a fundamental tool in the diagnosis and adequate control of blood pressure, avoiding having to suspend or reduce the dose of chemotherapy treatment. In addition, it can help in the diagnosis of autonomic dysfunction related to certain neoplastic pathologies.

PMID:37302940 | DOI:10.1016/j.hipert.2023.05.006

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PubMed articles on: Cardio-Oncology

COVID-19 severity and cardiovascular outcomes in SARS-CoV-2-infected patients with cancer and cardiovascular disease

Transl Oncol. 2023 Jun 2;34:101709. doi: 10.1016/j.tranon.2023.101709. Online ahead of print.

ABSTRACT

BACKGROUND: Data regarding outcomes among patients with cancer and co-morbid cardiovascular disease (CVD)/cardiovascular risk factors (CVRF) after SARS-CoV-2 infection are limited.

OBJECTIVES: To compare Coronavirus disease 2019 (COVID-19) related complications among cancer patients with and without co-morbid CVD/CVRF.

METHODS: Retrospective cohort study of patients with cancer and laboratory-confirmed SARS-CoV-2, reported to the COVID-19 and Cancer Consortium (CCC19) registry from 03/17/2020 to 12/31/2021. CVD/CVRF was defined as established CVD or no established CVD, male ≥ 55 or female ≥ 60 years, and one additional CVRF. The primary endpoint was an ordinal COVID-19 severity outcome including need for hospitalization, supplemental oxygen, intensive care unit (ICU), mechanical ventilation, ICU or mechanical ventilation plus vasopressors, and death. Secondary endpoints included incident adverse CV events. Ordinal logistic regression models estimated associations of CVD/CVRF with COVID-19 severity. Effect modification by recent cancer therapy was evaluated.

RESULTS: Among 10,876 SARS-CoV-2 infected patients with cancer (median age 65 [IQR 54-74] years, 53% female, 52% White), 6253 patients (57%) had co-morbid CVD/CVRF. Co-morbid CVD/CVRF was associated with higher COVID-19 severity (adjusted OR: 1.25 [95% CI 1.11-1.40]). Adverse CV events were significantly higher in patients with CVD/CVRF (all p<0.001).interaction

CONCLUSIONS: Co-morbid CVD/CVRF is associated with higher COVID-19 severity among patients with cancer, particularly those not receiving active cancer therapy. While infrequent, COVID-19 related CV complications were higher in patients with comorbid CVD/CVRF. (COVID-19 and Cancer Consortium Registry [CCC19]; NCT04354701).

PMID:37302348 | PMC:PMC10235676 | DOI:10.1016/j.tranon.2023.101709

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PubMed articles on: Cardio-Oncology

Adverse Cardiovascular Events Associated With Cyclin-Dependent Kinase 4/6 Inhibitors in Patients With Metastatic Breast Cancer

J Am Heart Assoc. 2023 Jun 10:e029361. doi: 10.1161/JAHA.123.029361. Online ahead of print.

ABSTRACT

Background Cyclin-dependent kinase (CDK) 4 and 6 inhibitors have significantly improved survival in patients with hormone receptor-positive metastatic breast cancer. There are few data regarding the epidemiology of cardiovascular adverse events (CVAEs) with these therapies. Methods and Results Using the OneFlorida Data Trust, adult patients without prior cardiovascular disease who received at least 1 CDK4/6 inhibitor were included in the analysis. CVAEs identified from International Classification of Diseases, Ninthand Tenth Revisions(ICD-9/10) codes included hypertension, atrial fibrillation(AF)/atrial flutter (AFL), heart failure/cardiomyopathy, ischemic heart disease, and pericardial disease. Competing risk analysis (Fine-Gray model) was used to determine the association between CDK4/6 inhibitor therapy and incident CVAEs. The effect of CVAEs on all-cause death was studied using Cox proportional hazard models. Propensity-weight analyses were performed to compare these patients to a cohort of patients treated with anthracyclines. A total of 1376 patients treated with CDK4/6 inhibitors were included in the analysis. CVAEs occurred in 24% (35.9 per 100 person-years). CVAEs were slightly higher in patients who received CKD4/6 inhibitors compared with anthracyclines (P=0.063), with higher death rate associated with the development of AF/AFL or cardiomyopathy/heart failure in the CDK4/6 group. The development of cardiomyopathy/heart failure and AF/AFL was associated with increased all-cause death (adjusted hazard ratio [HR], 4.89 [95% CI, 2.98-8.05]; and 5.88 [95% CI, 3.56-9.73], respectively). Conclusions CVAEs may be more common with CDK4/6 inhibitors than previously recognized, with increased death rates in these patients who develop AF/AFL or heart failure. Further research is needed to definitively determine cardiovascular risk associated with these novel anticancer treatments.

PMID:37301767 | DOI:10.1161/JAHA.123.029361

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PubMed articles on: Cardio-Oncology

Vernonia amygdalina Ethanol Extract Protects against Doxorubicin-Induced Cardiotoxicity via TGFβ, Cytochrome c, and Apoptosis

Molecules. 2023 May 24;28(11):4305. doi: 10.3390/molecules28114305.

ABSTRACT

Doxorubicin (DOX) has been extensively utilized in cancer treatment. However, DOX administration has adverse effects, such as cardiac injury. This study intends to analyze the expression of TGF, cytochrome c, and apoptosis on the cardiac histology of rats induced with doxorubicin, since the prevalence of cardiotoxicity remains an unpreventable problem due to a lack of understanding of the mechanism underlying the cardiotoxicity result. Vernonia amygdalinaethanol extract (VAEE) was produced by soaking dried Vernonia amygdalinaleaves in ethanol. Rats were randomly divided into seven groups: K- (only given doxorubicin 15 mg/kgbw), KN (water saline), P100, P200, P400, P4600, and P800 (DOX 15 mg/kgbw + 100, 200, 400, 600, and 800 mg/kgbw extract); at the end of the study, rats were scarified, and blood was taken directly from the heart; the heart was then removed. TGF, cytochrome c, and apoptosis were stained using immunohistochemistry, whereas SOD, MDA, and GR concentration were evaluated using an ELISA kit. In conclusion, ethanol extract might protect the cardiotoxicity produced by doxorubicin by significantly reducing the expression of TGF, cytochrome c, and apoptosis in P600 and P800 compared to untreated control K- (p < 0.001). These findings suggest that Vernonia amygdalinamay protect cardiac rats by reducing the apoptosis, TGF, and cytochrome c expression while not producing the doxorubicinol as doxorubicin metabolite. In the future, Vernonia amygdalinacould be used as herbal preventive therapy for patient administered doxorubicin to reduce the incidence of cardiotoxicity.

PMID:37298779 | PMC:PMC10254146 | DOI:10.3390/molecules28114305

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PubMed articles on: Cardio-Oncology

Toll-like Receptor 4 Inflammatory Perspective on Doxorubicin-Induced Cardiotoxicity

Molecules. 2023 May 24;28(11):4294. doi: 10.3390/molecules28114294.

ABSTRACT

Doxorubicin (Dox) is one of the most frequently used chemotherapeutic drugs in a variety of cancers, but Dox-induced cardiotoxicity diminishes its therapeutic efficacy. The underlying mechanisms of Dox-induced cardiotoxicity are still not fully understood. More significantly, there are no established therapeutic guidelines for Dox-induced cardiotoxicity. To date, Dox-induced cardiac inflammation is widely considered as one of the underlying mechanisms involved in Dox-induced cardiotoxicity. The Toll-like receptor 4 (TLR4) signaling pathway plays a key role in Dox-induced cardiac inflammation, and growing evidence reports that TLR4-induced cardiac inflammation is strongly linked to Dox-induced cardiotoxicity. In this review, we outline and address all the available evidence demonstrating the involvement of the TLR4 signaling pathway in different models of Dox-induced cardiotoxicity. This review also discusses the effect of the TLR4 signaling pathway on Dox-induced cardiotoxicity. Understanding the role of the TLR4 signaling pathway in Dox-induced cardiac inflammation might be beneficial for developing a potential therapeutic strategy for Dox-induced cardiotoxicity.

PMID:37298770 | PMC:PMC10254273 | DOI:10.3390/molecules28114294

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PubMed articles on: Cardio-Oncology

Feasibility of a Virtual Educational Programme for Behaviour Change in Cardiac Patients from a Low-Resource Setting

Int J Environ Res Public Health. 2023 May 24;20(11):5934. doi: 10.3390/ijerph20115934.

ABSTRACT

Patient education is an integral part of recovery from a critical cardiac life event and a core component of cardiac rehabilitation (CR) programmes. This study addressed the feasibility of a virtual educational programme for behaviour change in CR patients from a low-resource setting in Brazil. Cardiac patients from a CR programme closed due to the pandemic received a 12-week virtual educational intervention (WhatsApp messages and bi-weekly calls from healthcare providers). Acceptability, demand, implementation, practicality, and limited efficacy were tested. Overall, 34 patients and 8 healthcare providers agreed to participate. The intervention was considered practical and acceptable by the participants, who reported a satisfaction median of 9.0 (7.4-10.0)/10 (patients) and 9.8 (9.6-10.0)/10 (providers). The main difficulties in carrying out the intervention activities were related to technology, motivation to self-learning, and a lack of in-person orientation. All the patients reported that the information included in the intervention was aligned with their information needs. The intervention was associated with changes in exercise self-efficacy, sleep quality, depressive symptoms, and performance of high-intensity physical activity. In conclusion, the intervention was considered feasible to educate cardiac patients from a low-resource setting. It should be replicated and expanded to support patients that face barriers to onsite CR participation. Challenges related to technology and self-learning should be addressed.

PMID:37297538 | PMC:PMC10252834 | DOI:10.3390/ijerph20115934

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PubMed articles on: Cardio-Oncology

Cardiovascular Complications of Pan-Cancer Therapies: The Need for Cardio-Oncology

Cancers (Basel). 2023 Jun 5;15(11):3055. doi: 10.3390/cancers15113055.

ABSTRACT

It is more likely that a long-term survivor will have both cardiovascular disease and cancer on account of the progress in cancer therapy. Cardiotoxicity is a well-recognized and highly concerning adverse effect of cancer therapies. This side effect can manifest in a proportion of cancer patients and may lead to the discontinuation of potentially life-saving anticancer treatment regimens. Consequently, this discontinuation may adversely affect the patient's survival prognosis. There are various underlying mechanisms by which each anticancer treatment affects the cardiovascular system. Similarly, the incidence of cardiovascular events varies with different protocols for malignant tumors. In the future, comprehensive cardiovascular risk assessment and clinical monitoring should be considered for cancer treatments. Baseline cardiovascular evaluation risk should be emphasized prior to initiating clinical therapy in patients. Additionally, we highlight that there is a need for cardio-oncology to avoid or prevent cardiovascular side effects. Cardio-oncology service is based on identifying cardiotoxicity, developing strategies to reduce these toxicities, and minimizing long-term cardiotoxic effects.

PMID:37297017 | PMC:PMC10252624 | DOI:10.3390/cancers15113055

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PubMed articles on: Cardio-Oncology

The Role of the Cardiac Biomarkers in the Renal Cell Carcinoma Multidisciplinary Management

Diagnostics (Basel). 2023 May 30;13(11):1912. doi: 10.3390/diagnostics13111912.

ABSTRACT

Renal cell carcinoma, an aggressive malignancy, is often incidentally diagnosed. The patient remains asymptomatic to the late stage of the disease, when the local or distant metastases are already present. Surgical treatment remains the choice for these patients, although the plan must adapt to the characteristics of the patients and the extension of the neoplasm. Systemic therapy is sometimes needed. It includes immunotherapy, target therapy, or both, with a high level of toxicity. Cardiac biomarkers have prognosis and monitoring values in this setting. Their role in postoperative identification of myocardial injury and heart failure already have been demonstrated, as well as their importance in preoperative evaluation from the cardiac point of view and the progression of renal cancer. The cardiac biomarkers are also part of the new cardio-oncologic approach to establishing and monitoring systemic therapy. They are complementary tests for assessment of the baseline toxicity risk and tools to guide therapy. The goal must be to continue the treatment as long as possible with the initiation and optimisation of the cardiological treatment. Cardiac atrial biomarkers are reported to have also antitumoral and anti-inflammatory properties. This review aims to present the role of cardiac biomarkers in the multidisciplinary management of renal cell carcinoma patients.

PMID:37296764 | PMC:PMC10253077 | DOI:10.3390/diagnostics13111912

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PubMed articles on: Cardio-Oncology

Prognostic Factors for Cardiotoxicity among Children with Cancer: Definition, Causes, and Diagnosis with Omics Technologies

Diagnostics (Basel). 2023 May 26;13(11):1864. doi: 10.3390/diagnostics13111864.

ABSTRACT

Improvements in the treatment of childhood cancer have considerably enhanced survival rates over the last decades to over 80% as of today. However, this great achievement has been accompanied by the occurrence of several early and long-term treatment-related complications major of which is cardiotoxicity. This article reviews the contemporary definition of cardiotoxicity, older and newer chemotherapeutic agents that are mainly involved in cardiotoxicity, routine process diagnoses, and methods using omics technology for early and preventive diagnosis. Chemotherapeutic agents and radiation therapies have been implicated as a cause of cardiotoxicity. In response, the area of cardio-oncology has developed into a crucial element of oncologic patient care, committed to the early diagnosis and treatment of adverse cardiac events. However, routine diagnosis and the monitoring of cardiotoxicity rely on electrocardiography and echocardiography. For the early detection of cardiotoxicity, in recent years, major studies have been conducted using biomarkers such as troponin, N-terminal pro b-natriuretic peptide, etc. Despite the refinements in diagnostics, severe limitations still exist due to the increase in the above-mentioned biomarkers only after significant cardiac damage has occurred. Lately, the research has expanded by introducing new technologies and finding new markers using the omics approach. These new markers could be used not only for early detection but also for the early prevention of cardiotoxicity. Omics science, which includes genomics, transcriptomics, proteomics, and metabolomics, offers new opportunities for biomarker discovery in cardiotoxicity and may provide an understanding of the mechanisms of cardiotoxicity beyond traditional technologies.

PMID:37296716 | PMC:PMC10252297 | DOI:10.3390/diagnostics13111864

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PubMed articles on: Cardio-Oncology

Interventional Cardio-Oncology: Unique Challenges and Considerations in a High-Risk Population

Curr Treat Options Oncol. 2023 Jun 10. doi: 10.1007/s11864-023-01110-2. Online ahead of print.

ABSTRACT

Patients with cancer are at risk of developing cardiovascular disease (CVD) including atherosclerotic heart disease (AHD), valvular heart disease (VHD), and atrial fibrillation (AF). Advances in percutaneous catheter-based treatments, including percutaneous coronary intervention (PCI) for AHD, percutaneous valve replacement or repair for VHD, and ablation and left atrial appendage occlusion devices (LAAODs) for AF, have provided patients with CVD significant benefit in the recent decades. However, trials and registries investigating outcomes of these procedures often exclude patients with cancer. As a result, patients with cancer are less likely to undergo these therapies despite their benefits. Despite the inclusion of cancer patients in randomized clinical trial data, studies suggest that cancer patients derive similar benefits of percutaneous therapies for CVD compared with patients without cancer. Therefore, percutaneous interventions for CVD should not be withheld in patients with cancer, as they may still benefit from these procedures.

PMID:37296366 | DOI:10.1007/s11864-023-01110-2

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PubMed articles on: Cardio-Oncology

Cardio-oncology for Pediatric and Adolescent/Young Adult Patients

Curr Treat Options Oncol. 2023 Jun 10. doi: 10.1007/s11864-023-01100-4. Online ahead of print.

ABSTRACT

As chemotherapy continues to improve the lives of patients with cancer, understanding the effects of these drugs on other organ systems, and the cardiovascular system in particular, has become increasingly important. The effects of chemotherapy on the cardiovascular system are a major determinant of morbidity and mortality in these survivors. Although echocardiography continues to be the most widely used modality for assessing cardiotoxicity, newer imaging modalities and biomarker concentrations may detect subclinical cardiotoxicity earlier. Dexrazoxane continues to be the most effective therapy for preventing anthracycline-induced cardiomyopathy. Neurohormonal modulating drugs have not prevented cardiotoxicity, so their widespread, long-term use for all patients is currently not recommended. Advanced cardiac therapies, including heart transplant, have been successful in cancer survivors with end-stage HF and should be considered for these patients. Research on new targets, especially genetic associations, may produce treatments that help reduce cardiovascular morbidity and mortality.

PMID:37296365 | DOI:10.1007/s11864-023-01100-4

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PubMed articles on: Cardio-Oncology

Oxaliplatin-induced cardiotoxicity in mice is connected to the changes in energy metabolism in the heart tissue

bioRxiv. 2023 May 25:2023.05.24.542198. doi: 10.1101/2023.05.24.542198. Preprint.