Novel anti-psoriasis agent-associated cardiotoxicity, analysis of the FDA adverse event reporting system (FAERS).

INTRODUCTION: Psoriasis is a chronic skin condition characterized by hyperproliferation of epidermal keratinocytes, resulting in erythematous and scaling lesions. The US Food and Drug Administration (FDA) has approved nine biologic agents to address the burden of psoriasis, but their cardiovascular risks remain poorly studied. METHODS: This retrospective pharmacovigilance study utilized the FDA Adverse Event Reporting System (FAERS) database to analyze adverse events associated with newly approved therapeutic agents for psoriasis. We employed disproportionally signal analysis, calculating the reporting odds ratio (ROR) with a 95% confidence interval. RESULTS: Among the vast FAERS database, which contained >25 million adverse events, a total of 334,399 events were associated with newly approved therapeutic agents for psoriasis. Cardiac adverse events accounted for 3852 cases, including pericarditis, atrial fibrillation, and coronary artery disease. Secukinumab had the highest number of reported adverse events, followed by brodalumab, while tildrakizumab had the lowest. Coronary artery disease was the most reported adverse event (1438 cases), followed by pericarditis (572 cases) and atrial fibrillation (384 cases). Secukinumab had the highest incidence of coronary artery disease, pericarditis, and atrial fibrillation. Risankizumab was significantly associated with an increased risk of coronary artery disease and atrial fibrillation, while tildrakizumab and Ixekizumab were associated with atrial fibrillation. Secukinumab was associated with an elevated risk of pericarditis. CONCLUSIONS: The study uncovers the cardiovascular adverse effects related to biologic agents used in psoriasis treatment. These findings emphasize the importance of monitoring and evaluating the cardiovascular safety profiles of biological agents used in psoriasis treatment.

Late Cardiac Toxic Effects Associated With Treatment Protocols for Hodgkin Lymphoma in Children.

Importance: Contemporary North American trials for children with Hodgkin lymphoma (HL) have decreased radiation therapy (RT) use and increased pharmacologic cardioprotection but also increased the cumulative doxorubicin dose, making overall treatment consequences for late cardiac toxic effects uncertain. Objective: To estimate the risk of cardiac toxic effects associated with treatments used in modern pediatric HL clinical trials. Design, Setting, and Participants: For this cohort study, Fine and Gray models were fitted using survivors in the Childhood Cancer Survivor Study who were diagnosed with HL between January 1, 1970, and December 31, 1999, and were followed for a median of 23.5 (range, 5.0-46.3) years. These models were applied to the exposures in the study population to estimate the 30-year cumulative incidence of cardiac disease. The study population comprised patients with intermediate-risk or high-risk HL treated in 4 consecutive Children's Oncology Group clinical trials from September 2002 to October 2022: AHOD0031, AHOD0831, AHOD1331, and S1826. Data analysis was performed from April 2020 to February 2023. Exposures: All patients received chemotherapy including doxorubicin, and some patients received mediastinal RT, dexrazoxane, or mediastinal RT and dexrazoxane. Main Outcomes and Measures: Estimated 30-year cumulative incidence of grade 3 to 5 cardiac disease. Results: The study cohort comprised 2563 patients, with a median age at diagnosis of 15 (range, 1-22) years. More than half of the patients were male (1357 [52.9%]). All 2563 patients received doxorubicin, 1362 patients (53.1%) received mediastinal RT, and 307 patients (12.0%) received dexrazoxane. Radiation therapy use and the median mean heart dose among patients receiving RT decreased, whereas the planned cumulative dose of doxorubicin and use of dexrazoxane cardioprotection increased. For patients treated at age 15 years, the estimated 30-year cumulative incidence of severe or fatal cardiac disease was 9.6% (95% CI, 4.2%-16.4%) in the AHOD0031 standard treatment group (enrolled 2002-2009), 8.6% (95% CI, 3.8%-14.9%) in the AHOD0831 trial (enrolled 2009-2012), 8.2% (95% CI, 3.6%-14.3%) in the AHOD1331 trial (enrolled 2015-2019), and 6.2% (95% CI, 2.7%-10.9%) in the S1826 trial (enrolled 2019-2022), whereas the expected rate in an untreated population was 5.0% (95% CI, 2.1%-9.3%). Despite the estimated reduction in late cardiac morbidity, the frequency of recommended echocardiographic screening among survivors will increase based on current guidelines. Conclusions and Relevance: In this cohort study of sequential HL trials, reductions in the proportion of children receiving mediastinal RT and increases in dexrazoxane use were estimated to offset the increased doxorubicin dose and produce a net reduction in late cardiac disease. Further studies on dexrazoxane are warranted to confirm whether its role in reducing cardiac toxic effects is maintained long term. These findings suggest that survivorship follow-up guidelines should be refined to align with the risks associated with treatment.

Cardiac dysfunction and their determinants in patients treated for breast cancer and lymphoma: A cardio-oncology center experience.

OBJECTIVE: Cancer and cardiovascular diseases both have adverse effects on each other. We aim in the current study to investigate cardiac dysfunction including its prevalence, and associated factors in patients treated for breast cancer and lymphoma in a unique cardiac oncology center. METHODS: A single-center retrospective study included 180 patients with cancer breast and lymphoma who presented and were treated at our oncology center from January 2019 to February 2022. RESULT: Out of 180 consecutive patients, 155 patients (86 %) were diagnosed with cancer breast and 25 patients (14 %) were diagnosed with lymphoma. Patients with lymphoma were older age, less obese, and showed more prevalence of diabetes mellitus (DM) (P = 0.026, 0.05, and 0.04 respectively). They also showed more post-therapy left ventricular (LV) dilatation and lower values of global longitudinal strain (GLS); however, they did not develop more LV dysfunction compared to cancer breast patients. Moreover, lymphoma patients showed poor in-hospital outcomes (P = 0.04, 0.001, and 0.015 for infection, pericardial effusion, and mortality respectively). Cancer therapy-related cardiac dysfunction (CTRCD) was observed in 41 patients (23 %) of our population. The independent predictors of CTRCD in the current study were DM, low body mass index (BMI), and the use of trastuzumab. CONCLUSIONS: Some patients treated for breast cancer and lymphoma develop LV dysfunction. Lymphoma patients showed more subclinical LV dysfunction and poor in-hospital outcomes compared to patients with cancer breast. DM, low body mass index (BMI), and the use of trastuzumab were the independent predictors of cardiac dysfunction among our patients.

Cancer and cardiotoxicity in the transgender population.

The relationship between cancer diagnosis and cardiovascular diseases is complex, with newly diagnosed patients facing a higher risk of coronary disease, heart failure, and atrial fibrillation. Compared to the general population, they have two to six times more risk of dying from cardiovascular causes. Cardiovascular complications arising from chemotherapy and radiotherapy, along with social and healthcare access disparities, complicate the collection of accurate data on the incidence of cancer and cardiotoxicity in marginalized populations. Among the LGBTQ community, certain types of cancer are more prevalent, and hormone administration for gender affirmation is also under study. The delay in cancer screening in the transgender population results in late detections and deaths from cancer. Research on cancer in the transgender population and cardiotoxicity is limited, but special attention is needed to develop detection and prevention strategies in specific situations, such as hormone-dependent tumors.

La relación entre el diagnóstico de cáncer y enfermedades cardiovasculares es compleja, con pacientes recién diagnosticados enfrentando un mayor riesgo de enfermedad coronaria, insuficiencia cardíaca y fibrilación auricular. Comparados con la población general, tienen de dos a seis veces más riesgo de morir por causas cardiovasculares. Las complicaciones cardiovasculares derivadas de la quimioterapia y la radioterapia, junto con disparidades sociales y de acceso a la salud, complican la recopilación de datos precisos sobre la incidencia de cáncer y cardiotoxicidad en poblaciones marginadas. Entre la comunidad LGTBQ, ciertos tipos de cáncer son más frecuentes, y la administración de hormonas para la reafirmación de género también está bajo estudio. El retraso en el cribado de cáncer en la población transgénero resulta en detecciones tardías y muertes por cáncer. La investigación sobre cáncer en la población transgénero y cardiotoxicidad es limitada, pero se requiere atención especial para desarrollar estrategias de detección y prevención en situaciones específicas, como tumores dependientes de hormonas.

Acute and early-onset cardiotoxicity in children and adolescents with cancer: a systematic review.

BACKGROUND: Cardiotoxicity is among the most important adverse effects of childhood cancer treatment. Anthracyclines, mitoxantrone and radiotherapy involving the heart are its main causes. Subclinical cardiac dysfunction may over time progress to clinical heart failure. The majority of previous studies have focused on late-onset cardiotoxicity. In this systematic review, we discuss the prevalence and risk factors for acute and early-onset cardiotoxicity in children and adolescents with cancer treated with anthracyclines, mitoxantrone or radiotherapy involving the heart. METHODS: A literature search was performed within PubMed and reference lists of relevant studies. Studies were eligible if they reported on cardiotoxicity measured by clinical, echocardiographic and biochemical parameters routinely used in clinical practice during or within one year after the start of cancer treatment in ≥ 25 children and adolescents with cancer. Information about study population, treatment, outcomes of diagnostic tests used for cardiotoxicity assessment and risk factors was extracted and risk of bias was assessed. RESULTS: Our PubMed search yielded 3649 unique publications, 44 of which fulfilled the inclusion criteria. One additional study was identified by scanning the reference lists of relevant studies. In these 45 studies, acute and early-onset cardiotoxicity was studied in 7797 children and adolescents. Definitions of acute and early-onset cardiotoxicity prove to be highly heterogeneous. Prevalence rates varied for different cardiotoxicity definitions: systolic dysfunction (0.0-56.4%), diastolic dysfunction (30.0-100%), combinations of echocardiography and/or clinical parameters (0.0-38.1%), clinical symptoms (0.0-25.5%) and biomarker levels (0.0-37.5%). Shortening fraction and ejection fraction significantly decreased during treatment. Cumulative anthracycline dose proves to be an important risk factor. CONCLUSIONS: Various definitions have been used to describe acute and early-onset cardiotoxicity due to childhood cancer treatment, complicating the establishment of its exact prevalence. Our findings underscore the importance of uniform international guidelines for the monitoring of cardiac function during and shortly after childhood cancer treatment.

Incidence of interstitial lung disease and cardiotoxicity with trastuzumab deruxtecan in breast cancer patients: a systematic review and single-arm meta-analysis.

BACKGROUND: Trastuzumab deruxtecan (T-DXd) has been shown to benefit progression-free survival and overall survival in patients with metastatic breast cancer (mBC) after progression on ≥1 human epidermal growth factor receptor 2 (HER2)-targeted therapies. However, interstitial lung disease (ILD) and cardiotoxicity are the most significant toxicities associated with T-DXd. Therefore, we conducted a systematic review and meta-analysis to assess the incidence and severity of these toxicities in mBC patients treated with T-DXd. MATERIALS AND METHODS: We searched PubMed, Cochrane, and Scopus databases, and conferences websites for randomized clinical trials and nonrandomized studies of intervention including HER2-low or HER2-positive mBC patients who received at least one dose of T-DXd. Statistical analysis was carried out using R software. RESULTS: We included 15 studies comprising 1970 patients with a mean follow-up of 13.3 months. Median age ranged from 53 to 59 years, 61.9% were non-Asian, and 67.4% had hormone receptor-positive mBC. In a pooled analysis, the incidence of ILD was 11.7% [222 patients; 95% confidence interval (CI) 9.1% to 15.0%]. Patients receiving T-DXd dose of 6.4 mg/kg developed a significantly higher rate of ILD (22.7%) compared to those receiving a dose of 5.4 mg/kg (9.3%) (P < 0.01). Most cases of ILD (80.2%; 174/217 patients) were mild (grade 1 or 2). Grade 3 or 4 ILD was reported in 29 patients (13.4%), and grade 5 in 14 patients (6.4%). The incidence of decreased left ventricular ejection fraction (LVEF) was 1.95% (95% CI 0.65% to 3.73%), and the QT interval (QTi) prolongation was 7.77% (95% CI 2.74% to 20.11%). Most patients were asymptomatic, but four had LV dysfunction and heart failure (0.26%). CONCLUSIONS: In this meta-analysis of 1970 patients with mBC, treatment with T-DXd was associated with a 11.7% incidence of ILD, 7.7% incidence of prolonged QTi, and 1.9% incidence of reduced LVEF. Early detection and management of T-DXd-related toxicity by a multidisciplinary team may ultimately improve patient outcomes.

Cardio-Oncology for the Primary Care Provider.

Cardiovascular disease is a major cause of mortality among oncologic patients. As cancer therapies continue to evolve and advance, cancer survival rates have been increasing and so has the burden of cardiovascular disease within this population. For this reason, cardio-oncology plays an important role in promoting multidisciplinary care with the primary care provider, oncology, and cardiology. In this review, we discuss the roles of different providers, strategies to monitor patients receiving cardiotoxic therapies, and summarize cancer therapy class-specific toxicities. Continued collaboration among providers and ongoing research related to cardiotoxic cancer therapies will enable patients to receive maximal, evidence-based, comprehensive care.

Early and late onset cardiotoxicity following anthracycline-based chemotherapy in breast cancer patients: Incidence and predictors.

INTRODUCTION: Cardiotoxicity represents a major limitation for the use of anthracyclines or trastuzumab in breast cancer patients. Data on longitudinal studies about early and late onset cardiotoxicity in this group of patients is scarce. The objective of the present study was to assess predictors of early and late onset cardiotoxicity in patients with breast cancer treated with A. METHODS: 100 consecutive patients receiving anthracycline-based chemotherapy (CHT) to treat breast cancer were included in this prospective study. All patients underwent evaluation at baseline, at the end of CHT, 3 months after the end of CHT and 1 and 4 years after the beginning of CHT. Clinical data, systolic and diastolic echo parameters and cardiac biomarkers including high sensitivity Troponin T (TnT), N-terminal pro-brain natriuretic peptide (NT-proBNP) and Heart-type fatty acid binding protein (H-FABP) were assessed. RESULTS: Mean doxorubicin dose was 243 mg/m2. Mean follow-up was 51.8 ± 8.2 months. At one-year incidence of anthracycline related-cardiotoxicity (AR-CT) was 4% and at the end of follow-up was 18% (15 patients asymptomatic left ventricular systolic dysfunction, 1 patients heart failure and 2 patients a sudden cardiac death). Forty-nine patients developed diastolic dysfunction (DD) during first year. In the univariate analysis DD during first year was the only parameter associated with AR-CT (Table 1). In the logistic regression model DD was independently related with the development of AR-CT, with an odds ratio value of 7.5 (95% CI 1.59-35.3). CONCLUSIONS: Incidence of late-onset cardiotoxicity is high but mostly subclinical. Diastolic dysfunction early after chemotherapy is a strong predictor of anthracycline cardiotoxicity.

Prevalence of cancer therapy cardiotoxicity as assessed by imaging procedures: A scoping review.

BACKGROUND: Advances in treatment and optimization of chemotherapy protocols have greatly improved survival in cancer patients. Unfortunately, treatment can cause a reduction in left ventricular (LV) ejection fraction (EF) leading to cancer therapy-related cardiac dysfunction (CTRCD). We conducted a scoping review of published literature in order to identify and summarize the reported prevalence of cardiotoxicity evaluated by noninvasive imaging procedures in a wide-ranging of patients referred to cancer treatment as chemotherapy and/or radiation therapy. METHODS: Different databases were checked (PubMed, Embase, and Web of Science) to identify studies published from January 2000 to June 2021. Articles were included if they reported data on LVEF evaluation in oncological patients treated with chemotherapeutic agents and/or radiotherapy, measured by echocardiography and/or nuclear or cardiac magnetic resonance imaging test, providing criteria of CTRCD evaluation such as the specific threshold for LVEF decrease. RESULTS: From 963 citations identified, 46 articles, comprising 6841 patients, met the criteria for the inclusion in the scoping review. The summary prevalence of CTRCD as assessed by imaging procedures in the studies reviewed was 17% (95% confidence interval, 14-20). CONCLUSIONS: The results of our scoping review endorse the recommendations regarding imaging modalities to ensure identification of cardiotoxicity in patients undergoing cancer therapies. However, to improve patient management, more homogeneous CTRCD evaluation studies are required, reporting a detailed clinical assessment of the patient before, during and after treatment.

Low incidence of cardiotoxicity in patients with non-Hodgkin lymphoma receiving EPOCH after prior anthracycline exposure.

OBJECTIVE: To describe the incidence of cardiotoxicity in patients with anthracycline exposure who subsequently receive EPOCH for non-Hodgkin lymphoma (NHL). METHODS: We conducted a retrospective cohort study of adults with anthracycline exposure who subsequently received EPOCH for NHL at Memorial Sloan Kettering Cancer Center. The primary outcome was cumulative incidence of arrhythmia, heart failure (HF), left ventricular (LV) dysfunction, or cardiac death. RESULTS: Among 140 patients, most had diffuse large B-cell lymphoma. Inclusive of EPOCH, median cumulative doxorubicin-equivalent dose was 364 mg/m2 ; exposure was 400 mg/m2 or higher in 41%. With median 36-month follow-up, 23 cardiac events were noted in 20 patients. Cumulative incidence of cardiac events at 60 months was 15% (95% confidence interval [CI]: 9%-21%). When limited to LV dysfunction/HF, cumulative incidence at 60 months was 7% (95% CI: 3%-13%), with most events occurring after the first year. Univariate analysis indicated only history of cardiac disease and dyslipidemia to be associated with cardiotoxicity; no other risk factors, including cumulative anthracycline dose, were identified. CONCLUSIONS: In this retrospective cohort, representing the largest experience in this setting with extended follow-up, cumulative incidence of cardiac events was low. Rates of LV dysfunction or HF were particularly low, suggesting infusional administration may mitigate risk despite prior exposure.

Cardiac and obstetric outcomes of pregnancies for women after cardiotoxic therapy in childhood: a single center observational study.

BACKGROUND: Childhood cancer survivors (CCS) are at increased risk of cardiomyopathy during pregnancy if they have prior cardiotoxic exposure. Currently, there is no consensus on the necessity, timing and modality of cardiac monitoring during and after pregnancy. Therefore, we examined cardiac function using contemporary echocardiographic parameters during pregnancy in CCS with cardiotoxic treatment exposure, and we observed obstetric outcomes in CCS, including in women without previous cardiotoxic treatment exposure. METHOD: A single-center retrospective cohort study was conducted among 39 women enrolled in our institution's cancer survivorship outpatient clinic. Information on potential cardiotoxic exposure in childhood, cancer diagnosis and outcomes of all pregnancies were collected through interviews and review of health records. Echocardiographic exams before and during pregnancy were retrospectively analyzed for left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) if available. The primary outcomes were (i) left ventricular dysfunction (LVD) during pregnancy, defined as LVEF < 50% or a decline of ≥ 10% in LVEF below normal (< 54%), and (ii) symptomatic heart failure (HF). Rate of obstetric and fetal complications was compared to the general population through the national perinatal registry (PERINED). RESULTS: All pregnancies (91) of 39 women were included in this study. The most common malignancy was leukemia (N = 17, 43.6%). In 22 patients, echocardiograms were retrospectively analyzed. LVEFbaseline was 55.4 ± 1.2% and pre-existing subnormal LVEF was common (7/22, 31.8/%). The minimum value of LVEF during pregnancy was 3.8% lower than baseline (p = 0.002). LVD occurred in 9/22 (40.9%) patients and HF was not observed. When GLS was normal at baseline (< -18.0%; N = 12), none of the women developed LVD. Nine of out ten women with abnormal GLS at baseline developed LVD later in pregnancy. In our cohort, the obstetric outcomes seemed comparable with the general population unless patients underwent abdominal irradiation (N = 5), where high rates of preterm birth (only 5/18 born at term) and miscarriage (6/18 pregnancies) were observed. CONCLUSION: Our study suggests that women with prior cardiotoxic treatment have a low risk of LVD during pregnancy if GLS at baseline was normal. Pregnancy outcomes are similar to the healthy population except when patients underwent abdominal irradiation.

Risk Prediction Models for Cardiotoxicity of Chemotherapy Among Patients With Breast Cancer: A Systematic Review.

Importance: Cardiotoxicity is a serious adverse effect that can occur in women undergoing treatment for breast cancer. Identifying patients who will develop cardiotoxicity remains challenging. Objective: To identify, describe, and evaluate all prognostic models developed to predict cardiotoxicity following treatment in women with breast cancer. Evidence Review: This systematic review searched the Medline, Embase, and Cochrane databases up to September 22, 2021, to include studies developing or validating a prediction model for cardiotoxicity in women with breast cancer. The Prediction Model Risk of Bias Assessment Tool (PROBAST) was used to assess both the risk of bias and the applicability of the prediction modeling studies. Transparency reporting was assessed with the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) tool. Findings: After screening 590 publications, we identified 7 prognostic model studies for this review. Six were model development studies and 1 was an external validation study. Outcomes included occurrence of cardiac dysfunction (echocardiographic parameters), heart failure, and composite clinical outcomes. Model discrimination, measured by the area under receiver operating curves or C statistic, ranged from 0.70 (95% IC, 0.62-0.77) to 0.87 (95% IC, 0.77-0.96). The most common predictors identified in final prediction models included age, baseline left ventricular ejection fraction, hypertension, and diabetes. Four of the developed models were deemed to be at high risk of bias due to analysis concerns, particularly for sample size, handling of missing data, and not presenting appropriate performance statistics. None of the included studies examined the clinical utility of the developed model. All studies met more than 80% of the items in TRIPOD checklist. Conclusions and Relevance: In this systematic review of the 6 predictive models identified, only 1 had undergone external validation. Most of the studies were assessed as being at high overall risk of bias. Application of the reporting guidelines may help future research and improve the reproducibility and applicability of prediction models for cardiotoxicity following breast cancer treatment.

Essentials of cardio-oncology.

Cardio-oncology is a subspecialty that provides cardiac care for patients with cancer. Newer oncological agents have not only increased survivorship, but also sprouted novel cardiovascular toxicity (CVT) involving any component of the cardiovascular system, albeit with some preferential targets. Patients with cancer should undergo a baseline cardiovascular risk assessment and have individualised surveillance planned during cancer therapy and post treatment. The early diagnosis of CVT, by clinical history and examination along with imaging and laboratory analysis, is paramount. Management includes cardioprotective strategies and multidisciplinary decision-making regarding the risk-benefit ratio of oncological treatment based on CVT.

Cardiotoxicity with human epidermal growth factor receptor-2 inhibitors in breast cancer: Disproportionality analysis of the FDA adverse event reporting system.

BACKGROUND: The cardiotoxicity induced by human epidermal growth factor receptor-2 (HER-2) inhibitors in patients with breast cancer has been reported widely. However, these data sources were largely limited to fewer patients in clinical trials and case reports, lacking more comprehensive analysis from real-world data. METHODS: The cases diagnosed with breast cancer from January 2004 to December 2021 were extracted from the FDA adverse event database and further divided into 3 groups (the HER-2 inhibitor group, the positive control group, and the control group). The association between HER-2 inhibitors and cardiovascular adverse events was evaluated using the reporting odds ratio (ROR), a disproportionality method. RESULTS: A total of 167,639 breast cancer patients were included, including 18,615 cases in the HER-2 inhibitor drug group, 2568 cases in the positive control group, and 146,456 cases in the control group. A total of 2529 cases (13.5%) treated with HER-2 inhibitors experienced cardiovascular adverse events, mainly reported by health professionals (81.5%). The disproportionality analysis showed that cardiomyopathy was observed in all HER-2 inhibitors except trastuzumab deruxtecan. Trastuzumab-related CVAEs were most frequently reported (N =2075), and the median time was 80.50 days (IQR: 8.00 to 206.75 days). CONCLUSION: Based on real-world data analysis, our study demonstrated a significant association between HER-2 inhibitors and cardiovascular toxicity. Cardiac function in patients with breast cancer should be monitored early during anti-HER therapy, especially within six months.

Prevalence and risk factors of trastuzumab induced cardiotoxicity in Tunisian HER2-positive breast cancer patients.

INTRODUCTION: Cardiotoxicity is the most important side effect of Trastuzumab treatment. The purpose of this study is to evaluate the prevalence of Trastuzumab induced cardiotoxicity and to analyze risk factors associated with this side effect. MATERIALS AND METHODS: A retrospective institutional study was carried out from June 2018 to December 2018 at the department of Medical Oncology of Salah Azaiz institute, Tunis, Tunisia. Demographic, clinical characteristics (menopausal status, breast cancer stage, anthracyclines exposure, comorbidities presence…) and left ventricular ejection function (LVEF) measurements, were collected from patient records. RESULTS: Twenty-three women (20%) had Trastuzumab induced cardiotoxicity.65.2% (N = 15) experienced a decrease in LVEF more than 10% with a decrease below normal value and 34.8% (N = 8) experienced a decrease in LVEF more than 20%. Obesity is a risk factor for the occurrence of Trastuzumab induced cardiotoxicity (adjusted odds ratio (OR) = 2.919 (95% confidence interval (CI) [1.0411-8.186]; p = 0.042). CONCLUSION: Our study highlighted that obesity is associated with a high risk of cardiotoxicity in women treated with Trastuzumab. Therefore, close monitoring of cardiac function is recommended especially for obese women during Trastuzumab administering.

Cardiovascular complications of modern multiple myeloma therapy: A pharmacovigilance study.

AIMS: Multiple myeloma accounts for over 10-15% of haematological malignancies. Continued molecular advances have resulted in the development of new drugs for treatment of multiple myeloma. Four drugs were approved by the Food and Drug Administration (FDA) in 2015, but their safety is not well defined. The aim of this study is to delineate the cardiovascular adverse events of these drugs. METHODS: We reviewed the adverse cardiac events of newly approved FDA drugs since 2015 using the US FDA Adverse Events Reporting System (FAERS) database. We calculated the reporting odds ratio (ROR) with 95% confidence interval (CIs) for the drugs that have the highest incidence of cardiovascular adverse events. RESULTS: Among the medications that have approved for multiple myeloma between 2015 and 2020, 4 novel drugs showed the highest incidence of cardiotoxicity. ROR (95% CI) for atrial fibrillation due to elotuzumab, ixazomib, daratumumab and panobinostat compared to other FAERS drugs was 5.8 (4.4-7.7), 1.9 (1.5-2.3), 4.8 (4.2-5.6) and 5.7 (4.1-8.1), respectively. The ROR (95% CI) for cardiac failure was 8.2 (6.4-10.5), 4.7 (4.1-5.4), 5.8 (4.9-6.7) and 5.6 (3.8-8.1) and ROR (95% CI) for coronary disease was 2.7 (1.9-3.9), 2.7 (2.3-3.2), 2.3 (1.9-2.8) and 4.6 (3.2-6.6) due to elotuzumab, ixazomib, daratumumab and panobinostat compared to all other drugs in FAERS. CONCLUSION: Our results demonstrated that certain newly approved antimyeloma therapies are significantly associated with previously unknown cardiotoxicity. These results warrant further studies and highlight the importance of considering the cardiac history of patients with multiple myeloma when utilizing these novel agents.

Association of Neurohormonal Antagonists on Incident Cardiotoxicity in Patients With Breast Cancer.

Cardiovascular disease is the leading cause of mortality among breast cancer survivors. Anthracyclines and trastuzumab have been associated with an increased risk of cardiotoxicity, requiring close follow-up for signs of clinical heart failure or asymptomatic left ventricular systolic dysfunction. Whether neurohormonal antagonism with angiotensin-converting enzyme inhibitor (ACE-I), angiotensin receptor blockers (ARBs), or ß-blockers can prevent the development of chemotherapy-induced cardiomyopathy in this population remains unknown. We studied 459 women who were diagnosed with breast cancer at our medical center from January 2014 to December 2021 and evaluated baseline characteristics, oncologic treatment, and outcomes. The primary end point was the development of cardiotoxicity, defined as symptomatic decline in ejection fraction of ≥5% below 55% or an asymptomatic decline of ≥10% after treatment with chemotherapy. Patients who were exposed to neurohormonal antagonists were more likely to have hypertension, hyperlipidemia, and diabetes. There was an increased risk of cardiotoxicity noted for patients who were older (hazard ratio [HR] 1.04, 95% confidence interval [CI] 1.01 to 1.1), smokers within the past 10 years (HR 2.54, 95% CI 1.41 to 4.6), or who received a combination of both trastuzumab and anthracycline therapy (HR 2.52, 95% CI 1.01 to 6.3). Over a median follow-up of 12 months, there were no significant protective benefits noted for patients who were taking ACE-I/ARBs (HR 0.49, 95% CI 0.17 to 1.4), ß-blockers (HR 0.50, 95% CI 0.16 to 1.6), or both (HR 1.30, 95% CI 0.44 to 3.9). In conclusion, previous use of ACE-I/ARBs and ß-blockers, separately or in combination, was not associated with a reduction in the development of cardiotoxicity in patients receiving anthracycline or trastuzumab therapies. Older age, smoking, and combination chemotherapy were found to be associated with an increased risk.

Comparison of Patients' Phenotypes, Guideline-Directed Recommendations Compliance and Rates of Cardiotoxicity between Caribbean and United States Cardio-oncology Programs.

Background: Little is known about the characteristics of oncological patients, cancer therapy-induced cardiotoxicity, and guidelines-directed interventions in the Caribbean; analysis of cardio-oncology services may shed light on this and clarify links between ethnicity, cultural, and local socioeconomic factors. Objectives: This study compared patients' phenotypes, adherence to guidelines recommendations, and patterns of cardiotoxicity between two cardio-oncology programs: one in the Dominican Republic (DR) and the other in Chicago IL, United States (US). Methods: Patients being considered for or treated with potentially cardiotoxic drugs were followed before, during, and after chemotherapy through both cardio-oncology clinics, where we recorded and compared clinical, demographic, and echocardiographic data. Results: We studied 597 consecutive patients, 330 (55%) from the DR and 267 (45%) from the US. DR vs. US mean age 55± 13/52 ± 13 years; female 77/87% (p < 0.001); breast cancer 57/73% (p < 0.001); treated with anthracyclines + taxanes 47/40% (p = 0.151); monoclonal antibodies + taxanes or platins 37/45% (p < 0.001). Cardiotoxicity DR vs. US occurred in 15/7% (p = 0.001); multivariate logistic regression (OR 2.29; 95% CI, 1.31-3.99; p < 0.005) did not identify age >60, HTN, DM, BMI, tobacco or chemotherapy as predictors. Compliance with ASCO guidelines was similar among both cohorts. Conclusion: Compared to the US cohort, the Caribbean cohort of cancer patients has similar rates of CV risk factors but a higher likelihood of developing drug-induced LV dysfunction. Programs' compliance with ASCO guidelines was equivalent. While further research is needed to ascertain regional variations of cardiotoxicity, these findings underline the relevance of cardio-oncology services in nations with limited resources and high CV risk.

Grading Evaluation of Cardiotoxicity in Patients with Breast Cancer Treated with Adjuvant Paclitaxel Anthracycline/Cyclophosphamide Chemotherapy: A Meta-Analysis.

Objective: The cardiac safety of concurrent treatment with anthracycline (A), cyclophosphamide (C), and paclitaxel (T) in an adjuvant BC treatment regimen is still under debate. In this study, we aimed to determine cardiotoxicity events following ACT chemotherapy among operable breast cancer patients without HER2-positive. Methods: We searched PubMed and the Cochrane Library for RCTs prior to July 2019 evaluating the cardiac impairment of ACT chemotherapy regimens in BC patients. The search terms were "BC," "chemotherapy," "docetaxel or "doxorubicin," "paclitaxel," and "cyclophosphamide." Cardiotoxic events included LVEF decline ≥ 10 points, congestive heart failure (CHF), and cardiac death. Results: In total, 12 studies with 4032 subjects were included in this meta-analysis, and all patients received ACT regimen. The analysis results indicated that LVEF decrease ≥ 10 points was the most common cardiotoxic event (16%; (95% CI (8%-24%)) with χ 2 = 95.75, P < 0.001, I 2 = 95.8%). CHF showed the lowest rate (1%; (95% CI (0%-1%)) with χ 2 = 8.00, P = 0.433, I 2 = 0.0%). Subgroup analysis demonstrated that the incidence of CHF due to A → C → T chemotherapy regimen was lower than that of other events, however, without significance. No significant difference was observed in the occurrence of cardiac death. Conclusion: The ACT regimen in patients with HER2-negative BC was associated with an increased risk of adverse cardiactoxic events.

Cardiotoxicity among socioeconomically marginalized breast cancer patients.

PURPOSE: Evidence of cardiotoxicity risk related to anthracycline or trastuzumab exposure is largely derived from breast cancer cohorts that under-represent socioeconomically marginalized women, who may be at increased risk of cardiotoxicity because of high prevalence of cardiovascular disease risk factors. Therefore, we aimed to estimate cardiotoxicity risk among socioeconomically marginalized breast cancer patients treated with anthracyclines or trastuzumab and describe clinical consequences of cardiotoxicity. METHODS: We linked electronic health records with institutional registry data from a Comprehensive Community Cancer Program within a safety-net health system. Eligible patients were adult females, diagnosed with first primary invasive breast cancer between 2013 and 2017, and initiated anthracyclines or trastuzumab as part of first-line therapy. We estimated cumulative incidence (risk) of cardiotoxicity with corresponding 95% confidence limits (CL) using the Aalen-Johansen estimator with death as competing risk. RESULTS: Our study population comprised 169 women with breast cancer (103 initiated anthracyclines and 66 initiated trastuzumab). Cumulative incidence of cardiotoxicity was 21% (95% CL: 12%, 32%) at one year and 25% (95% CL: 15%, 35%) at three years among women who initiated trastuzumab, whereas cumulative incidence was 3.9% (95% CL: 1.3%, 8.9%) at one year and 5.9% (95% CL: 2.4%, 12%) at three years among women who initiated anthracyclines. More than half of patients with cardiotoxicity experienced interruption of cancer treatment. CONCLUSION: Our findings suggest high risk of cardiotoxicity among socioeconomically marginalized breast cancer patients after initiation of anthracyclines or trastuzumab. Strategies are needed for optimizing cancer treatment effectiveness while minimizing cardiotoxicity in this population.