Chemotherapy-induced Cardiotoxicity In Patients Research Articles

Molecular genetic markers of chemotherapy-induced cardiotoxicity in patients with oncohematological diseases (review)

Cardiotoxicity of anticancer therapy is a severe adverse cardiovascular event affecting the survival of cancer patients. Modern methods for diagnosing cardiotoxicity allow to identify already occurred myocardial transformations, accompanied by symptoms of heart failure and are not predict and detect early changes in the heart tissue during treatment. Recently, increasing attention is paid to the search for molecular genetic markers, a single identification of which before starting treatment will make possible to determining the risks of cardiotoxicity and change treatment taking into account individual genetic characteristics. At the same time, most research on the effect of allelic variants of genes on cardio-vascular complications relate to chemotherapy of solid tumors. The review considered possible prognostic genetic variants of cardiotoxicity induced by chemotherapy in patients with the hematopoietic and lymphatic malignancies.

CHANGES IN MYOCARDIAL BIOELECTRIC ACTIVITY IN PATIENTS WITH PROGRESSIVE MYLTIPLE MYELOMA

Introduction. Long-termed oncohematological course with periods of progression and remission of multiple myeloma, an increase in the cumulative dose of cytostatic drugs usually lead to a growing risk of chemotherapy-induced cardiotoxicity in patients with high cardiac risks. The aim of this study is to investigate changes in myocardial bioelectric activity of patients with progression of multiple myeloma and concomitant ischemic heart disease. Materials and methods. 42 patients with multiple myeloma were examined. The patients were divided into groups according to presence of concomitant coronary heart disease: І (n=15) included patients with multiple myeloma without concomitant cardiovascular diseases; II (n=27) involved patients with multiple myeloma and concomitant coronary heart disease. The patients were assessed before chemotherapy. We analyzed general and biochemical blood count findings. Based on Holter electrocardiography monitoring findings, we assessed heart rate, PQ interval, corrected QT interval. Results: Grade 3 and 4 of anaemia were detected only in the group of patients with multiple myeloma and concomitant coronary heart disease, in 4 (14,80%) and in 1 (3,70%) patients, respectively. Serum creatinine level above 177 μmol / l was found in 1 (6%) patient in the group I and in 2 (7%) patients in the group II. An inverse correlation was found between creatinine levels and erythrocyte counts in patients with multiple myeloma and concomitant coronary heart disease (R=-0,58, p<0,05). Rhythm disorders were found in 3 (20%) patients with multiple myeloma without cardiovascular diseases and in 8 (29.6%) patients with multiple myeloma with concomitant ischemic heart disease, conduction disorders was found in 5 (33%) patients in group I and in 14 (52%) patients in group II. Tendency in increasing the incidence of myocardial bioelectrical activity has been found out in case of concomitant coronary heart disease.

Statin Use Can Attenuate the Decline in Left Ventricular Ejection Fraction and the Incidence of Cardiomyopathy in Cardiotoxic Chemotherapy Recipients: A Systematic Review and Meta-Analysis.

There is insufficient evidence about the cardioprotective effects of statins against chemotherapy-induced cardiomyopathy. The MEDLINE and EMBASE databases were searched from inception to March 2021 for studies that reported the mean left ventricular ejection fraction (LVEF) before and after chemotherapy and the incidence of chemotherapy-induced cardiotoxicity in patients who received concurrent statin therapy and those who received chemotherapy alone. A random effects meta-analysis was performed to obtain the pooled weighted mean difference (WMD) and the 95% confidence interval (CI) for the mean final LVEF and the mean LVEF change, and the pooled odds ratio (OR) and the 95% CI of the incidence of chemotherapy-induced cardiomyopathy. Seven studies with 3042 patients were included in this meta-analysis (statin group: 1382 patients received concurrent statin with chemotherapy; control group: 1660 patients received chemotherapy alone). Patients in the control group had a more significant decline in LVEF (WMD = −6.08%, 95% CI: −8.55 to −3.61, p < 0.001) compared to those in the statin group. Additionally, the statin group had a significantly lower incidence of chemotherapy-induced cardiomyopathy compared to the control group (OR = 0.41, 95% CI = 0.28–0.60, p < 0.001). Consequently, our study showed a significant reduction in the incidence of chemotherapy-induced cardiomyopathy and the degree of LVEF decline in patients in the statin group compared to those in the control group.

Cardiotoxicity Associated with Chemotherapy Used in Gastrointestinal Tumours.

Cardiotoxicity is a well-recognised side effect of cancer-related therapies with a great impact on outcomes and quality of life in the cancer survivor population. The pathogenesis of chemotherapy-induced cardiotoxicity in patients with gastrointestinal cancers involves various molecular mechanisms, and the combined use of various chemotherapies augments the risk of each drug used alone. In terms of cardiotoxicity diagnosis, novel biomarkers, such as troponins, brain natriuretic peptide (BNP), myeloperoxidases and miRNAs have been recently assessed. Echocardiography is a noninvasive imaging method of choice for the primary assessment of chemotherapy-treated patients to generally evaluate the cardiovascular impact of these drugs. Novel echocardiography techniques, like three-dimensional and stress echocardiography, will improve diagnosis efficacy. Cardiac magnetic resonance (CMR) can evaluate cardiac morphology, function and wall structure. Corroborated data have shown the importance of CMR in the early evaluation of patients with gastrointestinal cancers, treated with anticancer drugs, but further studies are required to improve risk stratification in these patients. In this article, we review some important aspects concerning the cardiotoxicity of antineoplastic drugs used in gastrointestinal cancers. We also discuss the mechanism of cardiotoxicity, the role of biomarkers and the imaging methods used in its detection.

Impact of dyslipidemia and obesity on the incidence of cardiotoxicity in breast cancer patients treated with anthracyclines and Trastuzumab

Cardiovascular diseases and cancer share many risk factors, general population with metabolic syndrome are known to have an increased risk for cardiovascular diseases, Many studies showed a greater risk of cardiotoxicity in breast cancer patients with metabolic syndrome treated with anthracyclines and/or trastuzumab To assess associations between independent metabolic syndrome components: dyslipidemia, obesity and overweight and chemotherapy-induced cardiotoxicity in patients with breast cancer. Four hundred and seventy-three patients treated with sequential anthracyclines and trastuzumab were followed in the cardio-oncology unit from June 2018 to February 2020. Cardiac monitoring included echocardiographic assessment of LV function before chemotherapy and every 12 weeks after. We then evaluated the risk for cardiotoxicity associated with being overweight defined by a body mass index BMI between 25 kg/m 2 and 29,9 kg/m 2 and obesity (BMI ≥ 30 kg/m 2 ) and dylipidemia defined by total cholestrol level > 2 g/l, LDL-cholesterol level over 1.6 g/l or TriGlycerides TG > 1.5 g/l. Among 473 patients, 90 (19,1%) were obese and 146 (31,2%) were considered overweight and 66 (14%) had dyslipidemia. Overall, the mean rate of cardiotoxicity was 9.5%. Multivariate analysis showed that obesity was significantly associated with a higher risk of cardiotoxicity ( P = 0, 042, 95% CI, 0.77–1.68) whereas overweight wasn’t ( P = 0.931, 95% CI, 0.53–0.89). Even though incidence of cardiotoxicity was higher in the dyslipedimic group versus patients without dyslipidemia, no statistically significant correlation was noted between dyslipidemia and cardiotoxicity (RR = 1.33; P = 0.88, 95% CI, 0.6–2.33) Independently a significant association was found between obesity alone and cardiotoxicity. However, dyslipidemia or high body weight solely didn’t display a significant risk for cardiotoxicity alone. These results should be verified by further studies.

A randomized trial to evaluate the impact of exercise-based cardiac rehabilitation for the prevention of chemotherapy-induced cardiotoxicity in patients with breast cancer: ONCORE study protocol

BackgroundAnthracyclines and monoclonal antibodies against human epidermal growth factor receptor-2 (HER2) are frequently used to treat breast cancer but they are associated with risk of developing cardiotoxicity. Implementation of cardioprotective strategies as part of breast cancer treatment are needed. To date, a limited number of studies have examined the effectiveness of cardiac rehabilitation programs or exercise programs in the prevention of cardiotoxicity through an integral assessment of cardiac function. The ONCORE study proposes an exercise-based cardiac rehabilitation program as a non-pharmacological tool for the management of chemotherapy-induced cardiotoxicity.MethodsThe study protocol describes a prospective, randomized controlled trial aimed to determine whether an intervention through an exercise-based CR program can effectively prevent cardiotoxicity induced by anthracyclines and/or anti-HER2 antibodies in women with breast cancer. Three hundred and forty women with breast cancer at early stages scheduled to receive cardiotoxic chemotherapy will be randomly assigned (1:1) to participation in an exercise-based CR program (intervention group) or to usual care and physical activity recommendation (control group). Primary outcomes include changes in left ventricular ejection fraction and global longitudinal strain as markers of cardiac dysfunction assessed by transthoracic echocardiography. Secondary outcomes comprise levels of cardiovascular biomarkers and cardiopulmonary function through peak oxygen uptake determination, physical performance and psychosocial status. Supervised exercise program-related outcomes including safety, adherence/compliance, expectations and physical exercise in- and out-of-hospital are studied as exploratory outcomes. Transthoracic echocardiography, clinical test and questionnaires will be performed at the beginning and two weeks after completion of chemotherapy.DiscussionThe growing incidence of breast cancer and the risk of cardiotoxicity derived from cancer treatments demand adjuvant cardioprotective strategies. The proposed study may determine if an exercise-based CR program is effective in minimizing chemotherapy-induced cardiotoxicity in this population of women with early-stage breast cancer. The proposed research question is concrete, with relevant clinical implications, transferable to clinical practice and achievable with low risk.Trial registration ClinicalTrials.gov Identifier: NCT03964142. Registered on 28 May 2019. Retrospectively registered. https://clinicaltrials.gov/ct2/show/NCT03964142

P1776 Longitudinal change of regional left ventricular deformation by 2D speckle tracking for chemotherapy-induced cardiotoxicity in patients with breast cancer

Abstract Funding Acknowledgements Japan Agency for Medical Research and Development, Japan Heart Foundation Research Grant Background In breast cancer patients, chemotherapy-induced cardiotoxicity (CIC) may affect deformation in left ventricle segmentation differently over time. Purpose To evaluate longitudinal change of regional LV deformation caused by CIC in patients with breast cancer by 2D speckle tracking echocardiography (STE). Methods From 2017 to 2019, we enrolled 21 women with breast cancer and followed with continuous echocardiographic examination at enrollment (before chemotherapy), 3 months, 6 months, 9 months, and 12 months after chemotherapy at our hospital. We assessed conventional 2D echocardiographic indices and regional LV deformation analyzing longitudinal strain (LS), circumferential strain (CS), and radial strain (RS) by 2D STE. Results During the follow-period, there was no change in BNP (12.3 at baseline vs. 14.7 at 3 months vs. 16.6 at 6 months vs 18.3 at 9 months vs 10.9 pg/ml at 12 months, P = 0.96) and LVEF (62.2 vs. 62.0 vs. 61.2 vs 61.1 vs 62.9%, P = 0.84). However, significant decreases were observed in GLS (-20.3 vs. -19.0 vs. -17.9 vs -17.1 vs -17.7%, P &amp;lt; 0.01), and Troponin T (0.006 vs. 0.018 vs. 0.015 vs 0.009 vs 0.007 ng/ml, P &amp;lt; 0.01) after chemotherapy while there were no difference in global CS (-30.3 vs. - 29.1 vs. -27.0 vs -26.7 vs -28.0%, P = 0.15) and RS (46.8 vs. 47.9 vs. 49.6 vs 42.4 vs 46.3%, P = 0.17). When assessing regional deformation, we observed significant decrease in mid-inferoseptal region LS, mid-anterolateral region LS, mid-anterior region LS and apical-inferior region LS (Figure 1A). Of note, CS was impaired in basal- anterolateral region and mid-anteroseptal region (Figure 1B). However, none of regional RS showed significant difference after chemotherapy. Conclusion These results suggest that BNP and LVEF may not be ideal to detect CIC at early phase, and impaired GLS and increased Troponin T between 3 and 6 months after treatment may be initial signs by CIC. Longitudinal change of regional deformation implied that Mid-wall segmentation was vulnerable by chemotherapy more than other segmentations. Abstract P1776 Figure 1

Effect of Rosuvastatin in Preventing Chemotherapy-Induced Cardiotoxicity in Women With Breast Cancer: A Randomized, Single-Blind, Placebo-Controlled Trial.

Chemotherapy-induced cardiotoxicity is a major and leading cause of death in breast cancer survivors. It can present decades after chemotherapy and can manifest in different ways; some chemotherapeutic agents have a powerful dose-dependent relationship with cardiotoxicity. The aim of this study was to investigate the effect of rosuvastatin on preventing chemotherapy-induced cardiotoxicity in patients with breast cancer. Our study was a randomized, single-blind, placebo-controlled trial that involved 89 women with newly diagnosed breast cancer who were scheduled to receive chemotherapy. Patients were randomly assigned to receive rosuvastatin or a placebo in a 1:1 ratio for 6 months. Echocardiography, using 2-dimensional (2D) Doppler, tissue Doppler, and speckle-tracking methods, was used to determine the absolute changes in the left ventricular systolic ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left atrial (LA) diameter, transmitral Doppler early diastolic velocity (E wave), tissue Doppler early diastolic (e') and peak systolic (s') mitral annular velocities, E/e' ratio, and global longitudinal systolic strain. The LVEF was significantly reduced in the placebo group at the end of the study when compared with the baseline value. However, there was no significant difference in the LVEF in the intervention group (intergroup P = .012). Furthermore, compared with the intervention group at the end of the study, there was a significant increase in the 4- and 2-chamber LVESV, LA diameter, and E/e' ratio in the placebo group (intergroup P = .019, P = .024, P < .001, and P = .021, respectively) and a significant decrease in the e' and s' velocities in the placebo group (intergroup P < .001 and P < .006, respectively). The present study showed that the prophylactic use of rosuvastatin may prevent the development of chemotherapy-induced cardiotoxicity.

Mechanisms and Genetic Susceptibility of Chemotherapy-Induced Cardiotoxicity in Patients With Breast Cancer.

Cardiotoxicity remains an important adverse reaction of chemotherapy used in the treatment of breast cancer, leading to increased morbidity and mortality. Anthracyclines, taxanes, and trastuzumab are the most commonly used cytotoxic drugs for the treatment of breast cancer. Cardiotoxicity may vary from asymptomatic forms to irreducible heart failure and death. Susceptibility for the occurrence of chemotherapy-induced cardiotoxicity and treatment resistance is multifactorial, with interindividual variability, determined by the interaction between genetic and phenotypic factors. Implementation of pharmacogenomic findings into clinical practice might be useful, to predict cardiotoxicity and to allow appropriate therapeutic measures. This review will summarize the cellular mechanisms of chemotherapy-induced cardiotoxicity in breast cancer patients and will discuss the role of the genetic susceptibility for cardiac dysfunction.

CARDIO-PROTECTIVE EFFECT OF BETA-BLOCKADE DURING CHEMOTHERAPY FOR BREAST CANCER

Myocardial deformation parameters are early markers of chemotherapy-induced cardiotoxicity in patients treated with trastuzumab. Based on the cardio-protective effect of beta-blockade (BB) in LV dysfunction, we sought whether BB provided effective cardio-protection in pts treated with trastuzumab.

Chemotherapy-Induced Cardiotoxicity in Women

Chemotherapy-induced cardiotoxicity (CIC) is a major complication found with some life-saving medications used to treat breast and other cancers. Cardiotoxicity may present immediately during treatment or years later. These patients need education, screening, preventive measures, prompt interventions, and proper follow-up. This article focuses on CIC in patients who have breast cancer, but the process of evaluation and treatment design applies to all types of cancer and organ toxicities. Comprehensive pretreatment history, examination, and testing are needed for proper diagnosis and staging. CIC and other toxicities need to be considered in drug selection, treatment sequencing, testing, and appropriate follow-up.