Cardiotoxicity In Cancer Patients Research Articles

Cardiotoxicity in Cancer Patients: The Prevalence, Risk Factors, and Cardioprotective Measures in a Cancer Centre in Saudi Arabia.

Chemotherapy-related cardiotoxicity can exhibit several patterns of functional, structural, and vascular complications. This study aims to identify the patterns and the factors associated with cardiotoxicity in cancer patients. A retrospective cross-sectional analysis of 96 adult cancer patients undergoing anticancer therapy was investigated at King Khalid Hospital in Najran, Saudi Arabia, from May 2022 to April 2023. The data on patient and cancer characteristics, treatment, and outcomes were collected and analyzed. Factors associated with cardiotoxicity were investigated through univariate analyses using odds ratio (OR) and 95% confidence interval (CI). Among the 96 cancer patients in the study, cardiotoxicity occurred in 12 individuals (12.5%). The mean age was 57.0 ± 13.3 years (range: 32-81 years), with 32 (33.3%) being above 65 years. The most common comorbidities were diabetes (n=48; 50%), followed by hypertension (n=32; 33.3%), and dyslipidemia (n=20; 20.8%). The most common cancers were gastrointestinal cancer (n=32; 33.3%), followed by breast cancer (n=22; 22.9%) and lymphoma (n=14; 14.6%). Females were disproportionately affected (64.6%), with 57.3% of them in the metastatic stage. The majority of patients (90.6%) had normal ejection fraction before chemotherapy initiation. In univariate analysis, current smoking (OR: 7.00; 95%CI: 1.94-25.25, p= 0.003), history of percutaneous cardiac intervention (OR: 40.24; 95%CI: 1.80-896.26, p= 0.019), diabetes (OR: 6.05; 95%CI: 1.24-29.32, p= 0.025), renal failure (OR: 8.20; 95%CI: 0.91-74.88, p= 0.046), dyslipidemia (OR: 5.00; 95 CI: 1.38-18.32, p=0.012), anthracycline use (OR: 18.33; 95%CI: 4.36-126.55, p <0.001), trastuzumab use (OR: 25.00; 95%CI: 6.25-129.86, p < 0.001), and increased chemotherapy cycles number (> 10 cycles) (OR: 73.00; 95%CI: 8.56- 622.36, p < 0.001) were associated with cardiotoxicity. Additionally, beta-blocker use was associated with lower rates of cardiotoxicity (OR: 0.17; 95%CI: 0.036-0.84, p= 0.029). The incidence of cardiotoxicity among cancer patients treated with chemotherapy is modest, difficult to predict, and independent of baseline cardiac systolic functions. Factors associated with cardiotoxicity include smoking, history of percutaneous cardiac intervention, diabetes, renal failure, dyslipidemia, anthracycline or trastuzumab use, and increased chemotherapy cycle numbers. A combination of various anticancer drugs and chemotherapy may dramatically raise the risk of cardiotoxicity in cancer patients. As a result, patients receiving high-risk cardiotoxic drugs should be monitored with caution to avoid drug-related cardiotoxicity. Furthermore, proactive treatment techniques aiming at reducing the possible cardiotoxic effects of anticancer therapy are critical.

Protective effects of arbutin against doxorubicin-induced cardiac damage.

Doxorubicin is an effective antineoplastic agent but has limited clinical application because of its cumulative toxicities, including cardiotoxicity. Cardiotoxicity causes lipid peroxidation, genetic impairment, oxidative stress, inhibition of autophagy, and disruption of calcium homeostasis. Doxorubicin-induced cardiotoxicity is frequently tried to be mitigated by phytochemicals, which are derived from plants and possess antioxidant, anti-inflammatory, and anti-apoptotic properties. Arbutin, a natural antioxidant found in the leaves of the bearberry plant, has numerous pharmacological benefits, including antioxidant, anti-bacterial, anti-hyperglycemic, anti-inflammatory, and anti-tumor activity. The study involved male Wistar rats divided into three groups: a control group, a group treated with doxorubicin (20mg/kg) to induce cardiac toxicity, a group treated with arbutin (100mg/kg) daily for two weeks before doxorubicin administration. After treatment, plasma and heart tissue samples were collected for analysis. The samples were evaluated for oxidative stress parameters, including superoxide dismutase, malondialdehyde, and catalase, as well as for cardiac biomarkers, including CK, CK-MB, and LDH. The heart tissues were also analyzed using molecular (TNF-α, IL-1β and Caspase 3), histopathological and immunohistochemical methods (8-OHDG, 4 Hydroxynonenal, and dityrosine). The results showed that arbutin treatment was protective against doxorubicin-induced oxidative damage by increasing SOD and CAT activity and decreasing MDA level. Arbutin treatment was similarly able to reverse the inflammatory response caused by doxorubicin by reducing TNF-α and IL-1β levels and also reverse the apoptosis by decreasing caspase-3 levels. It was able to prevent doxorubicin-induced cardiac damage by reducing cardiac biomarkers CK, CK-MB and LDH levels. In addition to all these results, histopathological analyzes also show that arbutin may be beneficial against the damage caused by doxorubicin on heart tissue. The study suggests that arbutin has the potential to be used to mitigate doxorubicin-induced cardiotoxicity in cancer patients.

14,15-Dihydroxyeicosatrienoic acid, a soluble epoxide hydrolase metabolite in blood, is a predictor of anthracycline-induced cardiotoxicity – a hypothesis generating study

BackgroundEarly identification of patients susceptible to chemotherapy-induced cardiotoxicity could lead to targeted treatment to reduce cardiac dysfunction. Rats treated with doxorubicin (DOX), a chemotherapeutic agent, have increased cardiac expression of 14,15-dihydroxyeicosatrienoic acid (14,15-DHET), a bioactive lipid implicated in hypertension and coronary artery disease. However, the utility of 14,15-DHET as plasma biomarkers was not defined. The aim of this study is to investigate if levels of 14,15-DHET are an early blood biomarker to predict the subsequent occurrence of cardiotoxicity in cancer patients after chemotherapy.MethodsH9c2 rat cardiomyocytes were treated with DOX (1 μM) for 2 h and levels of 14,15-DHET in cell media was quantified at 2, 6 or 24 h in media after DOX treatment. Similarly, female Sprague–Dawley rats were treated with DOX for two weeks and levels of 14,15-DHET was assessed in plasma at 48 h and 2 weeks after DOX treatment. Changes in brain natriuretic peptide (BNP) mRNA, an early cardiac hypertrophy process, were determined in the H9c2 cells and rat cardiac tissue. Results were confirmed in human subjects by assessment of levels of 14,15-DHET in plasma of breast cancer patients before and after DOX treatment and left ventricular ejection fraction (LVEF), a clinical marker of cardiotoxicity.ResultsLevels of 14,15-DHET in cell media and rat plasma increased ~ 3-fold and was accompanied with increase in BNP mRNA in H9c2 cells and rat cardiac tissue after DOX treatment. In matched plasma samples from breast cancer patients, levels of 14,15-DHET were increased in patients that developed cardiotoxicity at 3 months before occurrence of LVEF decrease.ConclusionsTogether, these results indicate that levels of 14,15-DHET are elevated prior to major changes in cardiac structure and function after exposure to anthracyclines. Increased levels of 14,15-DHET in plasma may be an important clinical biomarker for early detection of anthracycline-induced cardiotoxicity in cancer patients.

The potentially protective effect of dapagliflozin on the development of cardiotoxicity in cancer patients

Abstract Introduction The clinical trial "DECLARE-TIMI 58" (Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction 58), demonstrated that dapagliflozin, a Sodium glucose cotransporter 2 inhibitor, reduces the composite end point of cardiovascular death/hospitalization for heart failure in a broad population of patients with type 2 diabetes mellitus.Chemotherapy is known for its potetial adverse effects on myocardium.We hypothesized that early initiation of treatment with dapagliflozin could prevent cardiotoxicity . Purpose We aimed to study if dapagliflozin could exert cardioprotective effects in anthracycline,carfilzomib and trastuzumab-induced cardiotoxicity through the analysis of ejection fraction, global longitudinal strain (GLS) of both left and right ventricle. Methods 32 diabetic patients who were diagnosed with cancer at our medical center were randomized (16 dapagliflozin;16 placebo). The groups were well-matched for baseline characteristics (age, diabetes duration, HbA1c, renal and heart function). Our patients, receiving potentially cardiotoxic treatment: 52% were treated with only trastuzumab, 34% were treated with only anthracycline and 14% with carfilzomib. The primary endpoint was the development of cardiotoxicity after treatment with chemotherapy. Cardiotoxicity was defined as a decrease of LVEF by 5% or more to less than 55% in the presence of symptoms of heart failure or an asymptomatic decrease in LVEF by 10% or more to less than 55%. Results In the first trimester of observation compared to baseline, patients treated with dapagliflozin did not show a deterioration of LV GLS [(GLS = −20,2±3,1% vs −19,8±3,1%, p=0,551] .Similarly in the placebo group [(GLS= −23,02±3,6% vs −22,6±3,5%, p=0,572). No significant changes were found in LVEF after treatment with dapagliflozin (57,9±5,6% vs 57,6±6,1%, p=0,733) or the placebo (60,1±5,6% vs 57,8±6,6%, p=0,166).There was a trend in GLS reduction of left ventricle in 2 patients receiving carfilzomib treatment in the placebo group (p=0.058) Conclusions At the best of our knowledge, our study is the first to investigate the early prophylactic use of dapagiflozin in the development of non-ischemic cardiomyopathy in patients receiving anthracycline or trastuzumab,carflilzomib therapies. During the first trimester of observation there was no benefit by dapagliflozin administration but 2 of our patients in the placebo group demonstrated reduction in GLS of left ventricle.

Multimodal Imaging of Cancer Therapy-Related Cardiac Dysfunction in Breast Cancer-A State-of-the-Art Review.

This review focuses on multimodality imaging of cardiotoxicity in cancer patients, with the aim of evaluating the effectiveness of different techniques in detecting and monitoring cardiac changes associated with cancer therapy. Eight studies were included in the review, covering various imaging modalities such as cardiac magnetic resonance imaging, echocardiography, and multigated acquisition scanning. Cardiac magnetic resonance imaging emerged as the most definitive modality, offering real-time detection, comprehensive assessment of cardiac function, the ability to detect early myocardial changes, and superior detection of cardiotoxicity when compared to the other imaging modalities. The studies also emphasize the importance of parameters such as left ventricular ejection fraction and global longitudinal strain in assessing cardiac function and predicting cardiotoxicity. Due to the common use of HER2 agents and anthracyclines within the breast cancer population, the LVEF as a critical prognostic measurement for assessing heart health and estimating the severity of left-sided cardiac malfunction is a commonly used endpoint. CTRCD rates differed between imaging modalities, with cardiac MRI the most sensitive. The use of multimodal cardiac imaging remains a nuanced area, influenced by local availability, the clinical question at hand, body habits, and medical comorbidities. All of the imaging modalities listed have a role to play in current care; however, focus should be given to increasing the provision of cardiac MRI for breast cancer patients in the future to optimize the detection of CTRCD and patient outcomes thereafter.

Hyperhomocysteinaemia Promotes Doxorubicin-Induced Cardiotoxicity in Mice.

Doxorubicin, a widely used chemotherapeutic drug in clinical oncology, causes a series of cardiac side effects referred to as doxorubicin-induced cardiotoxicity. Hyperhomocysteinaemia is an independent risk factor for multiple cardiovascular diseases. However, whether hyperhomocysteinaemia contributes to doxorubicin-induced cardiotoxicity is currently unknown. In this study, we explored the pathogenic effects of hyperhomocysteinaemia induced by dietary methionine supplementation (2% wt/wt in rodent chow) in a mouse model of doxorubicin-induced cardiotoxicity. Our data showed that methionine supplementation doubled serum homocysteine levels, inducing mild hyperhomocysteinaemia. Doxorubicin at a cumulative dosage of 25 mg/kg body weight led to significant weight loss and severe cardiac dysfunction, which were further exacerbated by methionine-induced mild hyperhomocysteinaemia. Doxorubicin-induced cardiac atrophy, cytoplasmic vacuolisation, myofibrillar disarray and loss, as well as cardiac fibrosis, were also exacerbated by methionine-induced mild hyperhomocysteinaemia. Additional folic acid supplementation (0.006% wt/wt) prevented methionine-induced hyperhomocysteinaemia and inhibited hyperhomocysteinaemia-aggravated cardiac dysfunction and cardiomyopathy. In particular, hyperhomocysteinaemia increased both serum and cardiac oxidative stress, which could all be inhibited by folic acid supplementation. Therefore, we demonstrated for the first time that hyperhomocysteinaemia could exacerbate doxorubicin-induced cardiotoxicity in mice, and the pathogenic effects of hyperhomocysteinaemia might at least partially correlate with increased oxidative stress and could be prevented by folic acid supplementation. Our study provides preliminary experimental evidence for the assessment of hyperhomocysteinaemia as a potential risk factor for chemotherapy-induced cardiotoxicity in cancer patients.

Prognostic value of coronary atherosclerosis and CAC score for the risk of chemotherapy-related cardiac dysfunction (CTRCD): The protocol of ANTEC study.

Cardiological complications of oncological treatment, including the most serious one, heart failure, constitute a significant and still unsolved clinical problem. A history of dyslipidemia and complications of atherosclerosis, including coronary artery disease, are established risk factors for cardiotoxicity in cancer patients. In recent years, a protective effect of statin treatment on the development of heart failure in cancer patients has been observed. This protocol describes a study aiming to assess the prognostic value of coronary atherosclerosis burden and the CAC score on the onset of cardiac dysfunction associated with cancer therapy. ANTEC (Atherosclerosis iN chemoTherapy-rElated Cardiotoxicity) is a single-site, prospective, observational study to evaluate the influence of the coronary atherosclerosis and CAC score assessed by computed tomography on the development of left ventricular systolic dysfunction in cancer patients with at least moderate cardiotoxicity risk. A group of 80 patients diagnosed with cancer prior to high-dose anthracycline chemotherapy (doxorubicin ≥ 240 mg / m2 body weight or epirubicin ≥ 600 mg / m2 body weight), without a history of heart failure and coronary artery disease, will be included in the study. Patient follow-up is planned for 12 months. In all patients, coronary computed tomographic angiography (CCTA) will be performed once at the beginning of the study. The primary endpoint is the onset of cancer therapy-related cardiovascular toxicity, defined as mild, moderate, severe and very severe according to ESC 2022 Cardio-oncology guidelines. During follow up, echocardiography with GLS assessment will be performed every three months. Additionally, new biomarkers of atherosclerosis (IL-6, MPO, TNF-alpha) will be measured every 6 months. The study registration identifier on clinicaltrials.gov is NCT05118178. This study is listed on cinicaltrials.gov with identifier NCT05118178.

Cooperative sensing of mitochondrial DNA by ZBP1 and cGAS promotes cardiotoxicity

Mitochondrial DNA (mtDNA) is a potent agonist of the innate immune system; however, the exact immunostimulatory features of mtDNA and the kinetics of detection by cytosolic nucleic acid sensors remain poorly defined. Here, we show that mitochondrial genome instability promotes Z-form DNA accumulation. Z-DNA binding protein 1 (ZBP1) stabilizes Z-form mtDNA and nucleates a cytosolic complex containing cGAS, RIPK1, and RIPK3 to sustain STAT1 phosphorylation and type I interferon (IFN-I) signaling. Elevated Z-form mtDNA, ZBP1 expression, and IFN-I signaling are observed in cardiomyocytes after exposure to Doxorubicin, a first-line chemotherapeutic agent that induces frequent cardiotoxicity in cancer patients. Strikingly, mice lacking ZBP1 or IFN-I signaling are protected from Doxorubicin-induced cardiotoxicity. Our findings reveal ZBP1 as a cooperative partner for cGAS that sustains IFN-I responses to mitochondrial genome instability and highlight ZBP1 as a potential target in heart failure and other disorders where mtDNA stress contributes to interferon-related pathology.

Redefining the Incidence and Profile of Fluoropyrimidine-Associated Cardiotoxicity in Cancer Patients: A Systematic Review and Meta-Analysis.

The cardiac toxicity that occurs during administration of anti-tumor agents has attracted increasing concern. Fluoropyrimidines have been used for more than half a century, but their cardiotoxicity has not been well clarified. In this study, we aimed to assess the incidence and profile of fluoropyrimidine-associated cardiotoxicity (FAC) comprehensively based on literature data. A systematic literature search was performed using PubMed, Embase, Medline, Web of Science, and Cochrane library databases and clinical trials on studies investigating FAC. The main outcome was a pooled incidence of FAC, and the secondary outcome was specific treatment-related cardiac AEs. Random or fixed effects modeling was used for pooled meta-analyses according to the heterogeneity assessment. PROSPERO registration number: (CRD42021282155). A total of 211 studies involving 63,186 patients were included, covering 31 countries or regions in the world. The pooled incidence of FAC, by meta-analytic, was 5.04% for all grades and 1.5% for grade 3 or higher. A total of 0.29% of patients died due to severe cardiotoxicities. More than 38 cardiac AEs were identified, with cardiac ischemia (2.24%) and arrhythmia (1.85%) being the most frequent. We further performed the subgroup analyses and meta-regression to explore the source of heterogeneity, and compare the cardiotoxicity among different study-level characteristics, finding that the incidence of FAC varied significantly among different publication decades, country/regions, and genders. Patients with esophagus cancer had the highest risk of FAC (10.53%), while breast cancer patients had the lowest (3.66%). The treatment attribute, regimen, and dosage were significantly related to FAC. When compared with chemotherapeutic drugs or targeted agents, such a risk was remarkably increased (χ2 = 10.15, p < 0.01; χ2 = 10.77, p < 0.01). The continuous 5-FU infusion for 3-5 consecutive days with a high dosage produced the highest FAC incidence (7.3%) compared with other low-dose administration patterns. Our study provides comprehensive global data on the incidence and profile of FAC. Different cancer types and treatment appear to have varying cardiotoxicities. Combination therapy, high cumulative dose, addition of anthracyclines, and pre-existing heart disease potentially increase the risk of FAC.

Anthracycline-induced cardiotoxicity — are we about to clear this hurdle?

Anthracyclines have contributed significantly to remarkable improvements in overall survival and are regarded as the most effective cytostatic drug for cancer treatment in various malignancies. However, anthracyclines are a significant cause of acute and chronic cardiotoxicity in cancer patients, and long-term cardiotoxicity can lead to death in about one-third of patients. Several molecular pathways have been implicated in the development of anthracycline-induced cardiotoxicity, although the underlying mechanisms of some molecular pathways are not fully elucidated. It is now generally believed that anthracycline-induced reactive oxygen species (resulting from intracellular metabolism of anthracyclines) and drug-induced inhibition of topoisomerase II beta are the key mechanisms responsible for the cardiotoxicity. To prevent cardiotoxicity, several strategies are being followed: (i) angiotensin-converting enzyme inhibitors, sartans, beta-blockers, aldosterone antagonists, and statins; (ii) iron chelators; and (iii) by development of new anthracycline derivatives with little or no cardiotoxicity. This review will discuss clinically evaluated doxorubicin analogues that were developed as potentially non-cardiotoxic anticancer agents and include recent development of a novel liposomal anthracycline (L-Annamycin) for the treatment of soft-tissue sarcoma metastatic to the lung and acute myelogenous leukaemia.

Ellagic acid inhibits mitochondrial fission protein Drp-1 and cell proliferation in cancer.

Anthracyclines such as doxorubicin (Dox) are widely used to treat a variety of adult and childhood cancers, however, a major limitation to many of these compounds is their propensity for inducing heart failure. A naturally occurring polyphenolic compound such as Ellagic acid (EA) has been shown by our laboratory to mitigate the cardiotoxic effects of Dox, however, the effects of EA on cancer cell viability have not been established. In this study, we explored the effects of EA alone and in combination with Dox on cancer cell viability and tumorigenesis. Herein, we show that EA induces cell cycle exit and reduces proliferation in colorectal cancer (HCT116) and breast adenocarcinoma cells (MCF7). We show that EA promotes cell cycle exit by a mechanism that inhibits mitochondrial dynamics protein Drp-1. EA treatment of HCT116 and MCF7 cells resulted in a hyperfused mitochondrial morphology that coincided with mitochondrial perturbations including loss of mitochondrial membrane potential, impaired respiratory capacity. Moreover, impaired mitochondrial function was accompanied by a reduction in cell cycle and proliferation markers, CDK1, Ki67, and Cyclin B. This resulted in a reduction in proliferation and widespread death of cancer cells. Furthermore, while Dox treatment alone promoted cell death in both HCT116 and MCF7 cancer cell lines, EA treatment lowered the effective dose of Dox to promote cell death. Hence, the findings of the present study reveal a previously unreported anti-tumor property of EA that impinges on mitochondrial dynamics protein, Drp-1 which is crucial for cell division and tumorigenesis. The ability of EA to lower the therapeutic threshold of Dox for inhibiting cancer cell growth may prove beneficial in reducing cardiotoxicity in cancer patients undergoing anthracycline therapy.

Abstract 14901: Risk Factors for Cardiotoxicity in Cancer Patients Receiving Immune Checkpoint Inhibitors: A Systematic Review With Meta-Analysis

Introduction Although immune checkpoint inhibitors (ICI) have reshaped the treatment landscape for cancer patients, they carry potential risk for the development of cardiovascular adverse events (CVAEs). Objectives We attempted to identify risk factors for CVAEs in cancer patients receiving ICI. Methods Two investigators (C.H.H. and Y.C.) independently reviewed Medline, PubMed, and Embase from inception to May 20, 2022 to identify high quality studies. We included randomized controlled trials, prospective or retrospective cohorts that reported the risks factors for any new onset or worsening CVAEs, including cardiomyopathy, arrhythmia, heart failure, acute coronary syndrome, myocarditis, and pericarditis, in cancer patients receiving ICI. Two investigators (E.A. and M.A.) independently extracted data from included studies. Any discrepancy was resolved through discussion with senior reviewers (K.Y.C and M.N.). We performed random-effects meta-analyses on risk factors for CVAEs after the initiation of ICI. We used I-statistics (I 2 ) to quantify the statistical heterogeneity. Results 12 observational studies involving 21,912 patients (CVAEs=2,897) of any cancers were included for final qualitative and quantitative analyses. 11 covariates, including age, gender, body mass index, ever-smoking history, hypertension, type II diabetes, coronary artery disease (CAD), congestive heart failure, chronic kidney disease (CKD), chronic obstructive pulmonary disease, and stroke, were available for the meta-analyses. Our meta-analyses (Table 1) demonstrated that male gender, hypertension, CAD, and CKD were associated with increased odds for the development of CVAEs in patients taking ICI. Conclusions In conclusion, male gender, hypertension, CAD, and CKD were identified as significant risk factors for CVAEs in patients taking ICI. Evidence supports a strategy of proper optimization of risk factors before, during, and after the ICI treatment.

Cardioprotective Strategies from Cardiotoxicity in Cancer Patients: A Comprehensive Review.

Cardiotoxicity is a significant complication of chemotherapeutic agents in cancer patients. Cardiovascular incidents including LV dysfunction, heart failure (HF), severe arrhythmias, arterial hypertension, and death are associated with high morbidity and mortality. Risk stratification of cancer patients prior to initiation of chemotherapy is crucial, especially in high-risk patients for cardiotoxicity. The early identification and management of potential risk factors for cardiovascular side effects seems to contribute to the prevention or minimization of cardiotoxicity. Screening of cancer patients includes biomarkers such as cTnI and natriuretic peptide and imaging measurements such as LV function, global longitudinal strain, and cardiac MRI. Cardioprotective strategies have been investigated over the last two decades. These strategies for either primary or secondary prevention include medical therapy such as ACE inhibitors, ARBs, b-blockers, aldosterone antagonists, statins and dexrazoxane, physical therapy, and reduction of chemotherapeutic dosages. However, data regarding dosages, duration of medical therapy, and potential interactions with chemotherapeutic agents are still limited. Collaboration among oncologists, cardiologists, and cardio-oncologists could establish management cardioprotective strategies and approved follow-up protocols in patients with cancer receiving chemotherapy.

Cardioprotective effect of Chinese herbal medicine for anthracycline-induced cardiotoxicity in cancer patients: A meta-analysis of prospective studies.

Background:To assess the benefits and harmful effects of Chinese herbal medicine (CHM) formulations in preventing anthracyclines (ANT)-induced cardiotoxicity.Method:The Cochrane Library, Pubmed and EMBASE databases were electronically searched for relevant randomized controlled trials (RCTs) published till December 2021 in English or Chinese-language, in addition to manual searches through the reference lists of the selected papers, and the Chinese Conference Papers Database. Data was extracted by 2 investigators independently.Result:Seventeen RCTs reporting 11 different CHMs were included in this meta-analysis. The use of CHM reduced the occurrence of clinical heart failure (RR 0.48, 95% CI 0.39 to 0.60, P < .01) compared to the control group. Data on subclinical heart failure in terms of LVEF values showed that CHM reduced the occurrence of subclinical heart failure (RR 0.47, 95% CI 0.35 to 0.62, P < .01) as well.Conclusion:CHM is an effective and safe cardioprotective intervention that can potentially prevent ANT-induced cardiotoxicity. However, due to the insufficient quality of the included trials, our results should be interpreted with cautious.

Records in Medical Records as Important Elements in the Identification and Treatment of Cardiotoxicity in Cancer Patients

Records in Medical Records as Important Elements in the Identification and Treatment of Cardiotoxicity in Cancer Patients

Effect of arterial hypertension on quality of life and anxiety in middle-aged patients with breast cancer

BACKGROUND: Arterial hypertension is one of the key risk factors for the development of cardiotoxicity in cancer patients. The importance for patients with left breast cancer is due to the possibility of the heart getting into the radiation area during treatment. The use of a method for assessing the quality of life and symptoms of anxiety can help improve treatment in such patients by increasing the interaction between a physician and a patient.&#x0D; AIM: The aim of the study is to assess the quality of life and the level of anxiety in patients with breast cancer, depending on the presence of arterial hypertension.&#x0D; MATERIALS AND METHODS: 67 patients with HER2neu negative cancer of the left breast have been examined. The average age is 42 (47; 63). All the patients after radical mastectomy and a course of chemotherapy with the inclusion of doxorubicin in a cumulative dose of no more than 360 mg/m2 have been hospitalized for 3D conformal radiation therapy. The first group included 32 patients with grade III comorbid hypertension; the second group included 35 patients without hypertension. The examination included an assessment of the status of an oncological patient according to the ECOG scale, echocardiography with an assessment of diastolic function, determination of the level of reactive and personal anxiety according to the Spielberger Khanin scale and quality of life using the SF-36 questionnaire.&#x0D; RESULTS: In the group of the patients with combined hypertension, left ventricular hypertrophy has been detected in 48 % of cases. In the patients of both groups with preserved ejection fraction, type I diastolic dysfunction has been detected (E/A 1): in the patients of the first group in 59.4 % of cases, in the patients of the second 31.4 % of cases. The difference obtained is due to the effect of hypertension on the left ventricular relaxation disorder. The level of reactive anxiety was significantly higher in the patients of the first group and amounted to 43.8 (41.2; 46.2) versus 38.4 (32.7; 42.6) points in the second group. The level of personal anxiety was high in the patients of both groups, which can be explained by the predominant influence of cancer. In the patients of both groups, there was a decrease in indicators according to the SF-36 questionnaire on all scales. The most significant changes have been obtained on the scales of physical functioning, role-based physical functioning, pain, vitality and general health. Cancer patients with concomitant hypertension rated their health status lower, while they are more likely to note a decrease in daily role activity as a result of their emotional state.&#x0D; CONCLUSIONS: The data obtained indicate that arterial hypertension has a significant negative effect on the level of reactive anxiety and quality of life indicators of breast cancer patients, which is of great importance in the formation of a patient-oriented approach to the therapeutic support of specific treatment in such patients.

BOT-5 Chrysanthemum morifolium extract improves doxorubicin-induced cardiomyopathy by suppressing apoptosis in mouse heart

Background: Doxorubicin is widely used for the treatment of various malignant tumors. However, doxorubicin causes cumulative and dose-dependent cardiotoxicity, ranging from occult changes in myocardial structure and function to severe cardiomyopathy and congestive heart failure. Since this problem affects the QOL and survival of cancer patients, solutions for this problem are urgently needed. Recently, it has been reported that Chrysanthemum morifolium extracts (CME) have antioxidant and anti-inflammatory activities. The purpose of this study is to clarify whether CME decreases doxorubicin-induced cardiotoxicity and prevents the development of heart failure. Methods and Results: H9C2 cardiomyoblast cells were treated with CME (0.3, 1 mg/mL) for 2 hours and then stimulated with doxorubicin. After 24 hours incubation, surviving cells were evaluated by MTT assay. CME dose-dependently decreased doxorubicin-induced cardiotoxicity in H9C2 cells. Western blotting showed that CME significantly suppressed doxorubicin-induced increases in four markers of apoptosis: p53, phosphorylated p53, and cleaved caspase-9 and -3. Next, to investigate the effects of CME on doxorubicin-induced cardiomyopathy in vivo, C57BL6 mice were orally administered with CME (400 mg/kg/day) or vehicle daily from 2 days before doxorubicin treatment and then treated once intraperitoneally with doxorubicin (20 mg/kg). The survival ratio of the CME-treated group was significantly higher than that of the vehicle-treated group. Echocardiographic analysis at 7 days after doxorubicin stimulation revealed that CME had significantly improved doxorubicin-induced left ventricular systolic dysfunction. Apoptotic cells in mouse heart tissue were detected by TUNEL assay, which showed that CME significantly suppressed doxorubicin-induced apoptosis. Discussion: These results indicate that CME decreases doxorubicin-induced cardiotoxicity both in vitro and in vivo, suggesting that CME might possess the therapeutic potency to reduce doxorubicin-induced cardiotoxicity in cancer patients. Further studies are required to assess the effectiveness of CME for preventing doxorubicin-induced heart failure in clinical settings.

78P Cardiotoxicity in cancer patients treated with immune-checkpoint inhibitors

Immunotherapy (IO) represents one of the most promising therapeutic approaches in systemic cancer treatment. However, its broad clinical application revealed several important cardiovascular side effects which can limit treatment options, decrease patients' prognosis and quality of life. The aim of this study was to assess the prevalence of cardiovascular risk factors (CVRF) and the incidence of cardiovascular events (CVE) in patients treated with IO. This has been little researched, and the information we have is scarce.

Abstract 13232: Prokineticin as a Biomarker of Cardiotoxicity in Cancer Patients

Many anticancer drugs are highly effective for cancer treatments. However, they triggerclinically significant cardiovascular morbidity and in some case mortality. Recently,experimental data support an important protective role of prokineticin-2, a cytokine, againstanthracycline-mediated cardiovascular toxicity. The aim of this study was to examine thelevels of plasma prokineticins (PROK1 and PROK2), and clinically used cardiac biomarkers(Troponin-T, Brain Natriuretic peptide) to assess possible correlations of these cytokines withrisk and severity of cardiotoxicity of cancer treatments. 200 patients with different type oftumor (mostly breast cancer, and ovarian cancer, urinarybladder cancer or other types oftumors), were enrolled. They were scheduled for cancer treatments including anthracyclinesalone, monoclonal antibody-based tyrosine kinase inhibitors TKI alone, a combination ofanthracyclines and TKI, and a combination of both anticancer agents and taxanes. Theexclusion criteria were previous anticancer treatments and cardiovascular pathologies suchashypertension, cardiomyopathy, coronary artery disease, life threatening arrhythmias, andongoing cardiovascular treatments. High-sensitive troponin I (TNI), BNP, PROK1 and PROK2were assessed in the plasma and cardiac systolic function (left ventricular ejection fraction,LVEF) were assessed by ECHO atbaseline and at 3, 6, 12 months after the completion of theoncology treatments. 42/142 patients (33%) showed an increase in TNI during or soon afterthe completion of cancer therapy. All patients (except for2) with an elevated TNI received acardioprotective therapy with enalapril. LVEF gradually and significantly decreased frombaseline during the observational period (P&lt;0.001). This was associated with increased levelsof TNI levels during and soon after cancer treatments. BNP levels remained unaltered. PROK1levels (N=63) had slightly, but not significant increased. PROK2 levels significantly increased(N=63) from baseline. This pilot study confirmed the role of TNI in predicting chemotherapy-mediated cardiotoxicity, and identified for the first time PROK2 as potential biomarker thatmay help to identify patients more prone to develop cardiotoxicity.

Statin use can attenuate the decline in left ventricular ejection fraction during the cardiotoxic chemotherapy: a systemic review and meta-analysis

Abstract Background Antineoplastic medications such as anthracyclines and trastuzumab are effective in treating various hematologic and solid organ malignancies, however an increased risk of cardiotoxicity in patients has been reported. A decline in left ventricular ejection fraction (LVEF) is a common finding in chemotherapy-induced cardiomyopathy and is sometimes irreversible and lethal. Several agents such as beta blockers and angiotensin-converting enzyme (ACE) inhibitors have shown to reduce the chemotherapy-induced cardiotoxicity in cancer patients. The use of statins, however, to prevent chemotherapy-related cardiotoxicity is not as well studied as other cardioprotective agents. In this study, we aimed to investigate the difference in the degree of decline in the LVEF in patients who received concurrent statin during the chemotherapy compared to those who received chemotherapy alone. Methods A systematic search of MEDLINE and EMBASE databases was performed from inception to March 2021 for studies that reported the mean LVEF before and after chemotherapy in patients who received concurrent statin therapy and those who did not receive statin along with the chemotherapy. A random effects meta-analysis was performed to obtain the pooled WMD of LVEF between the intervention (statin with chemotherapy) and the control group (chemotherapy alone) before and after chemotherapy treatments using STATA 16. Results Four studies with a total of 297 patients were included in this meta-analysis. Of the 297 patients, 115 patients were in the intervention group and received statin with chemotherapy, while 182 patients were in the control group and received chemotherapy alone. Baseline mean LVEF had no statistically significant difference between the intervention (statin) and the control (no statin) group, and the WMD was −0.38% (95% CI: −1.27 to 0.51, p=0.342). Upon follow-up, the control group patients showed a significantly greater decline in LVEF, with WMD of −6.08% (95% CI: −8.55 to −3.61, p=0.013), compared to the intervention group. Conclusion Patients who did not receive statin during the chemotherapy period had a greater mean decline in LVEF from baseline compared to that of the control group after the chemotherapy treatments. Funding Acknowledgement Type of funding sources: None.