Risk Factors For Cardiotoxicity Research Articles

A Retrospective Analysis of the Association of Obesity with Anthracycline and Trastuzumab-Induced Cardiotoxicity in the Treatment of Breast Cancer and Lymphoma

IntroductionBackground: Trastuzumab and anthracyclines are mainstays of chemotherapy in breast cancer and lymphoma patients. We aimed to assess the relationship between obesity and the risk of developing chemotherapy-associated cardiotoxicity.Material and methodsA retrospective chart review was conducted of all patients who received trastuzumab or anthracyclines at our tertiary care center. Bivariate analyses were conducted to determine the association between demographic and clinical variables with cardiotoxicity status. Two multivariate logistic regression models were generated to assess whether BMI was independently associated with cardiotoxicity.ResultsOf the 368 patients receiving either trastuzumab or anthracyclines, 16 patients developed cardiotoxicity. Demographically, age, race, BMI, BSA, and weight did not differ between the patients who developed cardiotoxicity and those who did not. The mean dose of anthracycline and trastuzumab did not differ between the patients who developed cardiotoxicity and those who did not. Obesity was not found to increase the odds of developing cardiotoxicity and was slightly protective. A non-significant decrease in the odds of developing cardiotoxicity was found for every one-unit increase in BMI. In a multivariable model using BMI as a continuous predictor and controlling for BMI, age, hypertension, chemotherapy type and coronary artery disease, the only significant predictor of cardiotoxicity was a previous history of arrhythmia.ConclusionsObesity was not a significant risk factor for patients developing cardiotoxicity from trastuzumab or anthracycline based chemotherapy and may be a protective factor for cardiotoxicity. Additional studies with greater statistical power are needed to further evaluate this effect and independently evaluate obesity as a risk factor for cardiotoxicity.

Abstract Db1-01: Anthracyclines …to give or not to give? “For” argument

Abstract Anthracyclines have been one of the mainstays of early breast cancer treatment for decades. In a recent patient-level meta-analysis including data from over 18,000 patients, anthracycline-containing regimens were associated with improvements in disease-free survival and overall survival, regardless of estrogen receptor or nodal status. Importantly, trials specifically designed and powered to assess the safety of anthracyclines omission failed to demonstrate the non-inferiority of taxane-based anthracycline-free regimens and confirmed the benefit of these agents, particularly in patients with node-positive and hormone receptor-negative breast cancer. Several therapies incorporated into the management of early breast cancer were studied in populations largely treated with anthracycline-based chemotherapy backbones in both HER2-negative (i.e., perioperative pembrolizumab, post neoadjuvant olaparib and capecitabine) and HER2-positive disease (i.e., dual HER2 blockade, adjuvant T-DM1). It is uncertain whether the benefits demonstrated by these strategies would be maintained if anthracyclines were omitted. While anthracyclines are associated with some long-term toxicities, particularly with an increased risk of lymphoproliferative malignancies and dose-dependent cardiotoxicity, these adverse events are not associated with an increased risk of death (including deaths from cardiovascular causes) when compared to anthracycline-free regimens. The identification of risk factors for cardiotoxicity, combined with improvements in monitoring strategies, allows improvements in patient selection, early detection of myocardial damage and, possibly, implementation of cardioprotective interventions, leading to improved cardiovascular outcomes. Until high-quality evidence demonstrates the safety of omitting anthracyclines in high-risk populations, these agents should continue to be used in carefully selected patients after individual risk versus benefit assessment to be shared with the patient. Citation Format: Martine Piccart, Guilherme Nader-Marta. Anthracyclines …to give or not to give? “For” argument [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr Db1-01.

Risk factors of osimertinib-related cardiotoxicity in non-small cell lung cancer.

To investigate the risk factors associated with cardiotoxicity in patients with non-small cell lung cancer (NSCLC) treated with osimertinib. A total of 268 patients with NSCLC treated with osimertinib in our hospital from June 2019 to December 2023 were selected to observe the occurrence of cardiotoxicity and were divided into cardiotoxicity group and non-cardiotoxicity group. The differences in age, gender, body mass index (BMI), smoking, alcohol consumption, tumor stage, hypertension, diabetes, hyperlipidemia, chemotherapy, radiotherapy, antiangiogenic drugs, and osimertinib treatment time were recorded and analyzed. Logistic regression was used to analyze the risk factors for cardiotoxicity in patients with non-small cell lung cancer caused by osimertinib treatment. Among the 268 patients with NSCLC treated with osimertinib, 58 patients developed cardiotoxicity, and the incidence of cardiotoxicity was 21.64%. There were statistically significant differences between the cardiotoxicity group and the non-cardiotoxicity group in terms of smoking history, hyperlipidemia history, combined chemotherapy, and combined radiotherapy (P < 0.05). Further analysis showed that patients with a smoking history were at increased risk of cardiotoxicity compared with non-smoking patients (OR = 2.569, 95% CI = 1.398-6.523). Patients with hyperlipidemia were at increased risk of cardiotoxicity compared with those without hyperlipidemia (OR = 3.412, 95% CI = 2.539-7.628). Patients with chemotherapy were at increased risk of cardiotoxicity compared with those without combination chemotherapy (OR = 2.018, 95% CI = 1.426-4.517). Patients undergoing radiotherapy to the left chest were at increased risk of cardiotoxicity compared with those without combined radiotherapy (OR = 1.629, 95% CI = 1.273-4.206). The incidence of cardiotoxicity in patients with NSCLC is high due to osimertinib treatment. A history of smoking, hyperlipidemia, combination chemotherapy, and radiotherapy to the left chest are independent risk factors for cardiotoxicity in patients with NSCLC treated with osimertinib.

Prevalence and Risk Factors of Cardiotoxicity in Elderly Cancer Patients

Prevalence and Risk Factors of Cardiotoxicity in Elderly Cancer Patients

Racial Disparity in Anthracycline-induced Cardiotoxicity in Breast Cancer Patients.

Breast cancer has become the most common cancer in the US and worldwide. While advances in early detection and treatment have resulted in a 40% reduction in breast cancer mortality, this reduction has not been achieved uniformly among racial groups. A large percentage of non-metastatic breast cancer mortality is related to the cardiovascular effects of breast cancer therapies. These effects appear to be more prevalent among patients from historically marginalized racial/ethnic backgrounds, such as African American and Hispanic individuals. Anthracyclines, particularly doxorubicin and daunorubicin, are the first-line treatments for breast cancer patients. However, their use is limited by their dose-dependent and cumulative cardiotoxicity, manifested by cardiomyopathy, ischemic heart disease, arrhythmias, hypertension, thromboembolic disorders, and heart failure. Cardiotoxicity risk factors, such as genetic predisposition and preexisting obesity, diabetes, hypertension, and heart diseases, are more prevalent in racial/ethnic minorities and undoubtedly contribute to the risk. Yet, beyond these risk factors, racial/ethnic minorities also face unique challenges that contribute to disparities in the emerging field of cardio-oncology, including socioeconomic factors, food insecurity, and the inability to access healthcare providers, among others. The current review will address genetic, clinical, and social determinants that potentially contribute to this disparity.

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.

Cancer Treatment-Related Cardiovascular Toxicity in Gynecologic Malignancies

Improvements in early detection and treatment of gynecologic malignancies have led to an increasing number of survivors who are at risk of long-term cardiac complications from cancer treatment. Multimodality therapies for gynecologic malignancies, including conventional chemotherapy, targeted therapeutics, and hormonal agents, place patients at risk of cancer therapy-related cardiovascular toxicity during and following treatment. Although the cardiotoxicity associated with some female predominant cancers (eg, breast cancer) have been well recognized, there has been less recognition of the potential adverse cardiovascular effects of anticancer therapies used to treat gynecologic malignancies. In this review, the authors provide a comprehensive overview of the cancer therapeuticagents used in gynecologic malignancies, associated cardiovascular toxicities, risk factors for cardiotoxicity, cardiacimaging, and prevention strategies.

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.

Abstract 15699: High-Dose Anthracycline Administration and Development of Cardiotoxicity in Women With Breast Cancer: An Analysis of Real-World Data From a Nationwide Claims Database in Japan

Introduction: Breast cancer is the most common malignancy affecting women, and the number of survivors is increasing with the advent of new therapies. However, Anthracyclines (ACs) retain an essential role in the drug treatment of breast cancer, despite their known cardiotoxicity. Although dexrazoxane, a cardioprotective agent for high-dose AC administration, has been approved in the US and Europe, it remains one of the drug-lag issues in Japan. Objective: To evaluate real-world data on the proportion of high-dose anthracycline administration and the incidence of cardiotoxicity in Japanese patients with breast cancer using a nationwide claims database. Methods. This study is a retrospective observational analysis using the Japan Medical Data Centre (JMDC, Tokyo, Japan) database, an anonymized patient-level claims database younger than 75 years old. We first identified women diagnosed with breast cancer and treatment with AC. Patients with a history of heart failure and a treatment start record of fewer than six months were excluded. After adjusting for patient background factors by propensity score matching (PSM), cardiotoxicity risk factors and outcomes were compared between the high-dose group (AC-H) and the low-dose group (AC-L). Results: Among women with breast cancer who underwent AC treatment between January 2015 and September 2020, 5.3% (255/4,831) were classified to the high-dose group. After PSM, the number of cases, age (years) and follow-up (months) in each group were as follows: AC-H group (n=254, median 51.0 [IQR: 46.0-55.0], 26.0 [14.0-52.0]), AC-L group (n=254, 51.0 [46.0-57.0], 32.5 [15.0-59.0]). The 5-year rates of mortality and heart failure in AC-H and AC-L groups were 33.1% vs 4.5% (Log-rank p &amp;lt; .0001) and 11.0% vs 4.3% (Log-rank p=0.003), respectively. Conclusion: The proportion of women with breast cancer who received AC in the high dose group was approximately 5%. However, compared with the low-dose group, the high-dose group had a lower survival rate and a higher incidence of heart failure. Therefore, in Japan, clinical development of cardioprotective agents for patients with metastatic or recurrent breast cancer who require high doses of AC is warranted.

Cardiotoxicity in patients with early breast cancer treated with adjuvant trastuzumab

Introduction. Breast cancer is the most common cancer among women in Poland. The aim of this study was to evalu­ate the incidence of cardiotoxicity in patients treated with adjunctive trastuzumab, as well as to determine risk factors for cardiotoxicity. Material and methods. The study covered 100 patients who completed one year of trastuzumab therapy or discon­tinued treatment due to acute cardiac complications. They underwent an oncological, cardiological, questionnaire and laboratory follow-up. Results. Acute cardiac complications (CC(+)) occurred in 11 (11%) patients. Patients in the CC(+) group were more likely to have hypertension, ischemic heart disease, hypothyroidism, and were more likely to smoke compared to the gro­up without cardiac complications (CC(–)). They had a lower left ventricular ejection fraction before, during and after trastuzumab therapy, and larger left ventricular dimensions in systole and diastole after treatment. The CC(+) received a higher dose of anthracyclines compared to CC(–). The NT-proBNP value remained elevated in the CC(+) group after treatment, despite normal LVEF values, and was higher than in the CC(–) group. Conclusions. Based on the study, type II cardiotoxicity, diagnosed early and treated appropriately, was found to be reversible.

Baseline blood pressure and development of cardiotoxicity in patients treated with anthracyclines: A systematic review

AimsAnthracyclines, a mainstay of cancer treatment, are associated with significant life-threatening cardiotoxicity. As cancer survivorship improves, there is a growing need to identify patients most at risk and strategies to mitigate anthracycline-associated cardiotoxicity. Elevated baseline blood pressure (bBP) is a possible risk factor for cardiotoxicity. The aim of this systematic review was to summarise the literature and evaluate relationships between bBP and anthracycline-associated cardiotoxicity. Methods and resultsSystematic searches were conducted, limited to English language but without restrictions on study type or country of origin. All studies fulfilled the PRISMA statement and relevant studies reviewed and narratively synthesised. A total of 1330 papers were screened, with 12 included in the qualitative synthesis. Eight papers indicated elevated bBP was associated with significantly higher risk of developing cardiotoxicity. Four papers noted significant relationships between left ventricular ejection fraction (LVEF) decline and elevated bBP. Of the four papers that failed to show an association, one noted increased risk of developing chronic heart failure. A relationship between baseline diastolic and systolic BP and anthracycline-associated cardiotoxicity is also noted. ConclusionsThis study indicates adult patients with elevated bBP have increased vulnerability to anthracycline-associated cardiotoxicity, with those with pre-hypertension or raised systolic versus diastolic pressure potentially an overlooked population. Recommendations for inclusion of bBP, incorporating individual systolic versus diastolic pressures, in cardio-oncology risk prediction models to guide clinical decision-making are thus warranted.

Cardio-Oncology in Childhood: State of the Art.

Cardio-oncology is an increasingly important field of cardiology that focuses on the detection, monitoring, and treatment of cardiovascular disease (CVD) occurring during and after oncological treatments. The survival rate for childhood cancer patients has dramatically increased thanks to new treatment protocols and cardiovascular (CV) sequelae represent the third most frequent cause of mortality in surviving patients. This study aims to provide a complete and updated review of all the main aspects of cardio-oncology in childhood and to highlight the critical issues. The problem of CV complications in childhood cancer survivors raises the need to make an early diagnosis of cardiotoxicity by the new imaging and laboratory techniques in order to intervene promptly and to implement pharmacological strategies and lifestyle changes to reduce or even to prevent cardiac injury. Furthermore, a stratification of CV risk, also including new predisposing factors such as the presence of some genetic mutations, is of paramount importance before undertaking oncological treatments. Besides, a systematic and personalized planning of long-term follow-up is fundamental to ensure a transition from pediatric to adult hospital and to avoid missed or late diagnosis of cardiomyopathy. We reviewed the main risk factors for cardiotoxicity in children, both traditional and emerging ones: the mechanisms of toxicity of both old and new antineoplastic therapies, the techniques for detecting cardiac damage, and the current evidence regarding pharmacological cardioprotection. At the end, we focused our attention on the existing guidelines and strategies about the long-term follow-up of childhood cancer survivors.

Effect of cumulative daunorubicin dose on cardiotoxicity after allogeneic stem cell transplantation

Cardiotoxicity after allogeneic stem cell transplantation (SCT) is associated with a high rate of mortality and worsening quality of life. The relation between daunorubicin dose and post- allogeneic stem cell transplantation (SCT) cardiotoxicity remains unclear. We retrospectively evaluated 171 patients with acute myeloid leukemia (AML) who underwent their first allogeneic SCT at our institution between 2005 and 2021. High-dose daunorubicin (50 mg/m2/day for 5 days) and cytarabine were usually used as induction therapy for AML. The median cumulative daunorubicin dose was 310 mg/m2 (range, 0–950 mg/m2), and 43 patients received two courses of induction therapy with high-dose daunorubicin (daunorubicin doses of ≥500 mg/m2). Cardiotoxicity developed in 12 patients, and the cumulative incidence at 2 years after SCT was 7.1%. Univariable analysis revealed that female sex, left ventricular ejection fraction (LVEF) of < 60% before SCT, and daunorubicin doses of ≥ 500 mg/m2 were associated with cardiotoxicity. Multivariable analysis showed that a daunorubicin dose of ≥ 500 mg/m2 was an independent risk factor for cardiotoxicity. LVEF decline during the study was observed with an increase in the daunorubicin dose, and only a daunorubicin dose of ≥ 500 mg/m2 was associated with a pre-SCT decreased LVEF. Second induction therapy with high-dose daunorubicin is a risk factor for cardiotoxicity after SCT. This should be taken into consideration when determining reinduction therapies for SCT-eligible patients with relapsed or refractory AML.

Cardiac safety analysis of anti-HER2-targeted therapy in early breast cancer

To evaluate the cardiac safety of anti-HER2-targeted therapy for early breast cancer; to investigate whether trastuzumab combined with pertuzumab increases cardiac toxicity compared with trastuzumab; to evaluate the predictive value of high-sensitivity Troponin (hs-TnI) and QTc for the cardiotoxicity associated with anti-HER2 targeted therapy in early breast cancer. A total of 420 patients with early-stage HER2-positive breast cancer who received trastuzumab or trastuzumab combined with pertuzumab for more than half a year in Tianjin Medical University Cancer Hospital from January 2018 to February 2021 were included. Left ventricle ejection fraction (LVEF), hs-TnI values, and QTc were measured at baseline and 3, 6, 9, 12 months. Cardiotoxicity was defined as a decrease in LVEF of at least 10 percentage points from baseline on follow-up echocardiography. Cardiotoxicity developed in 67 of the 420 patients (15.9%) and all patients had LVEF above 50% before and after treatment. The incidence of cardiotoxicity in trastuzumab and trastuzumab combined with pertuzumab was 14.3% and 17.9%, respectively (P > 0.05). Logistic regression analysis showed that age, coronary heart disease, left chest wall radiotherapy, and anthracyclines sequential therapy were independent risk factors for cardiotoxicity (P < 0.05). The value of hs-TnI and QTc at the end of treatment (12th month) were selected for ROC curve prediction analysis and the area under the ROC curve was 0.724 and 0.713, respectively, which was significantly different from the area of 0.5 (P < 0.05). The decrease of LVEF in the study was mostly asymptomatic, from the heart safety point of view, the anti-HER2 targeted therapy for early breast cancer was well tolerated. Trastuzumab combined with pertuzumab did not significantly increase cardiotoxicity. However, subgroup analysis suggests that in the presence of coronary artery disease (CAD) and sequential treatment with anthracene, trastuzumab and pertuzumab may increase the cardiac burden compared with trastuzumab. Hs-TnI and QTc may be useful in monitoring and predicting cardiotoxicity associated with anti-HER2 targeted therapy for early breast cancer.

The Value of Left Atrial Volume Changes in Predicting Cardiotoxicity in Patients Undergoing Anthracycline Chemotherapy.

In order to study the value of left atrial volume three-dimensional echocardiography in predicting cardiotoxicity in patients with multiple myeloma undergoing anthracycline chemotherapy, a total of 53 patients with multiple myeloma who are treated in the Department of Hematology of our hospital from January 2018 to December 2020 are selected as the research object, and all patients underwent three cycles (T1–T3) of chemotherapy. Before and after each cycle of chemotherapy, the patients are examined with 3D ultrasound and serology detection. These patients are divided into the cardiotoxicity group and noncardiotoxicity group. The serological indexes and three-dimensional echocardiographic parameters between two groups are compared. Multivariate logistic regression is used to determine the independent risk factors of cardiotoxicity in patients undergoing chemotherapy. And ROC curves are performed to evaluate the diagnostic value of related indicators in predicting cardiotoxicity. A total of 53 patients with multiple myeloma are included in this study. Serological indexes (T3 cTnI and T3 Pro-BNP), T2 LAVmin, T3 LAVmin, T2 LAVprep, and T3 LAVprep in the cardiotoxicity group are significantly higher than those in the noncardiotoxicity group. Multivariate logistic regression further found that T3 cTnI, T3 Pro-BNP, T2 LAVmin, T3 LAVmin, T2 LAVprep, T3 LAVprep could be used to predict the occurrence of cardiotoxicity (P < 0.05). The results of ROC curves showed that T3 LAVmin had the most diagnostic efficiency of cardiotoxicity (AUC = 0.938; sensitivity 75.72%; specificity 93.82%). Detection of changes in left atrial volume using three-dimensional ultrasound could be used as strong predictors of cardiotoxicity caused by anthracycline chemotherapy drugs in patients with multiple myeloma.

Cardiotoxicity risk factors with immune checkpoint inhibitors

BackgroundCheckpoint-inhibitor immunotherapies have had a profound effect in the treatment of cancer by inhibiting down-regulation of T-cell response to malignancy. The cardiotoxic potential of these agents was first described in murine models and, more recently, in numerous clinical case reports of pericarditis, myocarditis, pericardial effusion, cardiomyopathy, and new arrhythmias. The objective of our study was to determine the frequency of and associated risk factors for cardiotoxic events in patients treated with immune checkpoint inhibitors.MethodsMedical records of patients who underwent immunotherapy with durvalumab, ipilimumab, nivolumab, and pembrolizumab at Wake Forest Baptist Health were reviewed. We collected retrospective data regarding sex, cancer type, age, and cardiovascular disease risk factors and medications. We aimed to identify new diagnoses of heart failure, atrial fibrillation, ventricular fibrillation/tachycardia, myocarditis, and pericarditis after therapy onset. To assess the relationship between CVD risk factors and the number of cardiac events, a multivariate model was applied using generalized linear regression. Incidence rate ratios were calculated for every covariate along with the adjusted P-value. We applied a multivariate model using logistic regression to assess the relationship between CVD risk factors and mortality. Odds ratios were calculated for every covariate along with the adjusted P-value. Adjusted P-values were calculated using multivariable regression adjusting for other covariates.ResultsReview of 538 medical records revealed the following events: 3 ventricular fibrillation/tachycardia, 12 pericarditis, 11 atrial fibrillation with rapid ventricular rate, 0 myocarditis, 8 heart failure. Significant risk factors included female gender, African American race, and tobacco use with IRR 3.34 (95% CI 1.421, 7.849; P = 0.006), IRR 3.39 (95% CI 1.141, 10.055; P = 0.028), and IRR 4.21 (95% CI 1.289, 13.763; P = 0.017) respectively.ConclusionsOur study revealed 34 significant events, most frequent being pericarditis (2.2%) and atrial fibrillation (2.0%) with strongest risk factors being female gender, African American race, and tobacco use. Patients who meet this demographic, particularly those with planned pembrolizumab treatment, may benefit from early referral to a cardio-oncologist. Further investigation is warranted on the relationship between CTLA-4 and PD-L1 expression and cardiac adverse events with ICIs, particularly for these subpopulations.

Incidence of trastuzumab-induced cardiotoxicity and impact of body mass index in patients with breast cancer: Results from a Saudi tertiary cancer center.

The effect of BMI as a risk factor in trastuzumab-induced cardiotoxicity in Saudi patients with HER2-neu positive breast cancer treated with trastuzumab and anthracyclines is not fully understood. The present study retrospectively evaluated the overall incidence of cardiotoxicity and the effect of BMI as a risk factor for cardiotoxicity. A retrospective study performed between 2011 and 2015 of patients with Her2-neu positive early breast cancer who were treated with either a combination of trastuzumab and anthracycline or a combination of trastuzumab with non-anthracycline or hormonal treatment in the adjuvant settings was carried out. The incidence of cardiotoxicity and the effect of BMI, hypertension and diabetes mellitus as risk factors for cardiotoxicity were assessed. Cardiotoxicity was measured using a drop in the ejection fraction of >10 percentage points to a left ventricular ejection fraction of <50%. The present cohort included 105 patients diagnosed with stage I and II breast cancer. The mean age of the present cohort was 47.5±1.0 years (range, 25-76 years), the mean height was 153.9±14.1 cm (range, 126-170 cm), the mean body weight was 75.7±15.6 kg (range, 40-143 kg) and the mean BMI was 31.3±5.8 (range, 18-49). Cardiotoxicity was detected in 21.9% of the cohort. The BMI was calculated for 81 patients who were treated with a combination of trastuzumab and anthracycline. Cardiotoxicity was detected in 3 out of 9 patients with a BMI <25, in 9 out of 23 patients with a BMI between 25 and 29, and in 6 patients with a BMI >30. There was a significant association between cardiotoxicity and BMI (P=0.03). No significant association between age, hypertension and diabetes and cardiotoxicity was identified. In conclusion, compared with global cohorts, the present results revealed a higher incidence of cardiotoxicity among Saudi patients with HER2-neu positive early breast cancer treated with trastuzumab combinations in adjuvant settings. Increased BMI was significantly associated with cardiotoxicity.

Telehealth consultations in cardio-oncology

Aim. To evaluate the role of a cardiologist in telehealth counseling of cancer patients at the federal oncology center.Material and methods. This retrospective study was conducted based on the materials of 215 telehealth consultations on cardiooncology, performed in the period from January 2019 to September 2021. Data on referrals to a cardiologist (cardio-oncologist) from various Russian regions and consultants’ answers were analyzed, taking into account the following data: region, sex, age of a patient, cancer type, stage, participation of other consultants, type of cardiovascular disease, the need for additional information and features of treatment — surgery, chemotherapy, radiation therapy. Risk was stratified based on a checklist including the main risk factors for cardiotoxicity. The recommendations of consultants for monitoring patients, as well as drug therapy prescriptions, were analyzed.Results. The most common cancer sites in patients referred for telehealth consultations on cardio-oncology were lungs, larynx and trachea, colon and rectum, kidneys and bladder, ovaries and uterus, and stomach. Cardiologists consulted together with oncologists — surgeons, medical oncologists, as well as anesthesiologists and radiation oncologists. The most common cardiovascular diseases were hypertension — 80,9% of patients, heart failure — 60%, arrhythmias — 41,6% and coronary heart disease — 37,7%. From 71 to 80,3%, 15,6-21% and 3,9-7,8% of patients had preserved, mid-range and reduced left ventricular ejection fraction. In 47,6-66,7% of cases, consultants required additional information. Based on risk stratification of cardiotoxicity of anticancer treatment, 118 (81,9%) patients out of 144 were classified as high and very high risk. Most patients were recommended cardioprotective therapy, which most often included angiotensin-converting enzyme inhibitors/angiotensin receptor blockers — 43,1-53,1%, beta-blockers — 44,8-58,6%, and statins — 22,4-38,3%. An algorithm for creating a request for a cardio-oncology telehealth consultation has been developed.Conclusion. The important role of cardio-oncology telehealth consultations in the work of the federal oncology center is demonstrated. Consulting cardiologists are part of a single multidisciplinary team of specialists and must act taking into account the characteristics of cancer and antitumor therapy prescribed by oncologists.

Heart failure in cancer patients

The purpose of the study was to conduct a systematic review of data on the role of heart failure (HF) in the development of cancer, as well as to discuss problems dealing with diagnosis and treatment of heart failure in cancer patients. Material and methods. A literature search was conducted using the Cochrane library, elibrary, medline, and embase databases over the past 7 years. The general mechanisms of heart failure and cancer, cardiotoxicity risk factors, and some aspects of the diagnosis and treatment of HF in cancer patients were analyzed. Results. The literature analysis indicates that cardiovascular disease and cancer have common risk factors. Several common pathophysiological mechanisms that associate HF with cancer have been identified. They include inflammation, oxidative stress, and neurohomonal activation. HF is known to be a common complication of aggressive cardiotoxic cancer therapy that can aggravate or trigger existing HF. Recent epidemiological studies have shown that the development of cancer is more common among patients with pre-existing HF. Although the reason for this relationship has not yet been identified, it is assumed that HF may be a pro-oncogenic condition. There are several strategies to prevent and treat toxicity of various chemotherapeutic drugs. They are all based on accurate patient selection, short- and longterm follow-up, and therapies that can prevent and delay cardiac dysfunction. Conclusion. The main goal of cardio-oncology is to prevent and treat of cardiotoxic effects of chemotherapy drugs. In this context, elucidation of the underlying mechanisms plays an important role in the development of strategies for the prevention of chemotherapy-associated cardiomyopathy. It is necessary to pay attention to the fact that there is more and more evidence that patients with HF have high risks of developing cancer, thereby requiring more attention. In general, understanding the direct and indirect mechanisms of the relationship between HF and cancer can help in the prevention and early diagnosis of these diseases.

Aortic hemodynamic parameters as predictors of incident or deteriorating hypertension during carfilzomib therapy in patients with relapsed multiple myeloma

Abstract Background Carfilzomib (CFZ) improves survival in relapsed/refractory multiple myeloma but is associated with cardiovascular adverse events, among which hypertension is commonly reported. Purpose To evaluate aortic hemodynamics as possible predictors for CFZ-associated hypertension. Methods In a prospective study of 48 patients treated with Kd (CFZ 20/56 mg/m2 and dexamethasone) followed until disease progression or cycle 6 for a median of 10 months, patients underwent peripheral hemodynamic assessment, including applanation tonometry, which allows estimation of aortic blood pressure and arterial wave reflections and assessment of pulse wave velocity, which allows estimation of aortic stiffness. Hemodynamic parameters were examined at baseline and at pre-specified time points before and 24 hours after drug infusion. Results Thirteen patients (27.1%) developed hypertension or merited more intensive anti-hypertensive treatment (grade I or II: 6.25%, grade III: 20.8%). Patients with new onset or worsening hypertension had increased aortic [130±12.9 mmHg versus 115±16.7 mmHg, p=0.004] and peripheral systolic blood pressure (SBP) [145±15.7 mmHg versus 130±19.5 mmHg, p=0.001] at baseline. Patients distributed at highest tertile of baseline aortic SBP (log-rank test p=0.0001, Figure) or baseline peripheral SBP (log-rank test p=0.002) had significantly higher risk for CFZ associated hypertension as compared to those distributed at lower tertiles. After adjustment for age, gender and baseline hypertension, increased aortic [HR=8.0, 95% CIs 2.4–26.6, p=0.001] and peripheral SBP [HR=4.85, 95% CIs 1.53–15.4, p=0.007] remained significantly associated with hypertension. After adjustment for both baseline peripheral and aortic SBP in the same multivariable core model, aortic SBP was the only independent predictor of the study outcome (p=0.041). Accordingly, baseline aortic SBP was associated with higher discriminative value as compared to peripheral SBP [AUC: 0.819, 95% CIs 0.722–0.916 versus 0.724, 95% CIs 0.570–0.878, respectively]. Further adjustment for all cardiotoxicity risk factors using forced inclusion in non-parsimonious multivariable Cox regression models, revealed that increased aortic and peripheral SBP remained independent predictors of hypertensive events (p&amp;lt;0.05 for both). Conclusion Baseline aortic hemodynamics are associated with hypertension during CFZ treatment. Aortic SBP at baseline was the strongest predictor of CFZ-associated hypertensive adverse events, suggesting that an initial assessment of aortic blood pressure may facilitate discrimination of patients in need of close monitoring during treatment. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Funding from the Hellenic Foundation for Research and Innovation (HFRI) and the General Secretariat for Research and Technology (GSRT), under grant agreement No [1285].