Cardiotoxicity Research Articles

A Comparative Study Of Intrathecal 0.5% Hyperbaric Bupivacaine And Intrathecal 0.75% Hyperbaric Ropivacaine In Lower Abdominal Surgeries.

Background: Spinal anaesthesia has been widely used since its introduction in 1898 due to its safety and advantages over general anaesthesia. However, traditional agents like bupivacaine have some disadvantages, including cardiovascular effects and longer duration of action. Ropivacaine has emerged as a potential alternative with reduced cardiovascular toxicity. The study was aimed to compare the efficacy and suitability of 0.75% hyperbaric ropivacaine with 0.5% hyperbaric bupivacaine in patients undergoing lower limb and endoscopic urological surgeries, evaluating onset, quality, duration of block, and incidence of complications. Materials and Methods: A prospective randomized trial was conducted with 130 patients (65 per group) aged 16-60 years, ASA grades 1 & 2. Group B received 3.0 ml of 0.5% hyperbaric bupivacaine, while Group R received 3.0 ml of 0.75% hyperbaric ropivacaine. Onset of anaesthesia, quality of block, duration, hemodynamic parameters, and complications were assessed. Results: Ropivacaine showed faster sensory and motor recovery, better hemodynamic stability, and fewer side effects compared to bupivacaine. The onset of sensory block was slightly faster with bupivacaine (2.17 vs 2.54 minutes), but ropivacaine had a shorter duration of sensory (114.7 vs 158 minutes) and motor block (112 vs 130 minutes). Ropivacaine group experienced less hypotension (4.6% vs 7.7%) and no bradycardia or vomiting compared to the bupivacaine group. Conclusion: Hyperbaric ropivacaine 0.75% was found to be a comparable and safer alternative to hyperbaric bupivacaine 0.5% for patients undergoing lower abdominal surgery, offering faster recovery and better hemodynamic stability

Double Duty: SGLT2 Inhibitors as Cardioprotective and Anticancer Allies

Sodium glucose cotransporter-2 inhibitors (SGLT2i), originally developed for type II diabetes mellitus, have recently been approved for the treatment of heart failure in both diabetic and non-diabetic patients due to their significant cardiovascular benefits. Beyond their established role in diabetes and heart failure management, current research is exploring the potential applications of SGLT2 inhibitors in the field of cardio-oncology. This interest is driven by dual possible benefits: cardioprotection against the adverse effects of antitumor therapies and inherent antitumor properties. Patients affected by cancer often face the challenge of managing cardiovascular toxicity induced by antineoplastic treatments. SGLT2 inhibitors have shown promise in mitigating toxicities, thereby enhancing the cardiovascular health of these patients. Additionally, emerging evidence suggests that SGLT2 inhibitors may possess direct antitumor effects, further contributing to their therapeutic potential in oncology. This review aims to provide a comprehensive overview of the molecular mechanisms through which SGLT2 inhibitors exert their cardioprotective and antitumor effects. Furthermore, we will examine the current body of evidence supporting the use of these inhibitors in a cardio-oncology setting.

Multi-Modality Imaging to Detect Ischemic and Valvular Heart Disease in Adult Cancer Patients.

Thanks to impressive advances in the field of oncology over the last 30years, there has been a significant rise in cancer survivors. Nowadays, cardiovascular disease is one of the leading causes of death in this patient population. Coronary artery disease (CAD) is a major problem due to shared risk factors, an aging population and in many cases induced and/or accelerated atherosclerosis by antitumoral treatment during and even decades after the end of cancer therapy. Furthermore, the presence of CAD or valvular heart disease (VHD) at the time point of cancer diagnosis largely increases the risk of any cancer therapy-related cardiovascular toxicity (CTR-CVT). It is therefore of utmost importance to detect CAD and VHD before, during, and after certain types of chemotherapy, target therapies, and radiotherapy. Multimodality cardiovascular imaging plays a central role in this vulnerable population where individual risk stratification and multidisciplinary decision-making are critical.

Induction Chemotherapy-Related Covert Cardiac Remodeling in Pre-Autologous Hematopoietic Stem Cell Transplantation for Multiple Myeloma: A Retrospective Observational Study.

Autologous hematopoietic stem cell transplantation (ASCT) has emerged as a cornerstone in multiple myeloma (MM) management, offering the prospect of prolonged disease control. However, the induction chemotherapy drugs required prior to ASCT carry cardiovascular toxicity (CVT), potentially leading to a range of cardiovascular complications. This retrospective observational study, conducted at Guangdong Provincial People's Hospital from January 2020 to December 2023, analyzed 47 of the initial 173 patients who met the criteria. The cohort, comprising 22 males (46.81%) and 25 females (53.19%), had a mean age of 55.68 ± 11.38 years. They underwent various induction chemotherapy regimens, receiving a median of 5 (4-6) cycles of the course over an average duration of 7.10 ± 2.46 months. Before ASCT treatment following induction chemotherapy, echocardiographic findings indicated reductions in left ventricular end-systolic dimension, right atrial diameter, E-wave velocity, E/e' ratio, and the E/A ratio. The latter altered from a pretreatment value greater than 1 to posttreatment less than 1, marking diastolic dysfunction emergence or aggravation in 51.06% of patients. The electrocardiographic data indicate a reduced heart rate and prolonged P-wave duration and P-R duration, with an increase in arrhythmia incidence to 19.15% following induction chemotherapy. Induction chemotherapy, administered prior to ASCT in patients with MM, can lead to the emergence or aggravation of cardiac diastolic dysfunction and increase the incidence of arrhythmic events. Therefore, it is crucial to emphasize the importance of balancing the benefits and risks of induction chemotherapy to maximize its efficacy while minimizing CVT.

Neurotoxicity and Cardiovascular Toxicity of Zinc Oxide Nanoparticles to Oryzias melastigma.

Zinc oxide nanoparticles (ZnO NPs) are widely used in manufacturing cosmetic and pharmaceutical products. Although previous studies have reported their toxic effects on fish, the underlying mechanisms behind their toxic effects are yet to be identified. This study evaluated the impact of ZnO NPs on marine medaka's survival, heart rates (Oryzias melastigma), and the expression of genes linked to neurotoxicity and cardiovascular toxicity. Marine medaka samples were exposed to ZnO NPs at varying concentrations: 0.01, 0.1, 1, and 10 mg/L. Survival rates and heart rates were monitored on the 12th day postfertilization. Gene expression related to neurotoxicity (α-tubulin, elavl3, gap43, gfap) and cardiovascular toxicity (cdh2, atp2a1, cacna1da, crhr1, ahrra, arnt2) was assessed by performing real-time polymerase chain reaction. The survival rate of marine medaka samples was not significantly impacted by exposure to up to 1 mg/L of ZnO NPs; however, exposure to 10 mg/L of ZnO NPs resulted in a 60% reduction in survival rate. The heart rate of the samples did not significantly change across all concentrations. High ZnO NP concentrations (10 mg/L) significantly suppressed the expression of neurotoxic and cardiotoxic genes, including elavl3 and gfap. ZnO NPs exhibited dose-dependent toxic effects on the marine medaka samples by affecting the expression of genes related to neurological and cardiovascular functions. These findings underscore the potential risks of ZnO NPs to aquatic organisms. The distinct toxic actions of ZnO NPs and dissolved ions complicate the interpretation of results, as this study did not measure ion release, a critical factor in understanding NP toxicity. Moreover, ZnO NPs may cause oxidative stress and disrupt cellular pathways. Furthermore, without distinguishing between NP and ion effects, it is challenging to determine the exact cause of toxicity. These findings highlight the need for future studies to measure dissolved ions and particles separately to clarify their contributions to toxicity, where the mechanisms of action are still debated.

4‑Year Experience of the Cardio-Oncology Center of Sechenov University: Single-Center Epidemiological Study

To present the four-year experience and the accomplishments of the Scientific and Practical Cardio-Oncology Center of the Sechenov University. The records of patients referred for cardio-oncology consultation from January 2020 through March 2024 were retrospectively analyzed. The patients' cardiovascular (CV) status was assessed at baseline and after optimizing the cardiac therapy during the antitumor treatment. The endpoints were the completion of all antitumor therapy courses and the level of overall and CV mortality. Among 233 enrolled patients (66% women), a considerable part belonged to the group of high/very high cardio-oncological risk (n=134, 57%). Various cardiovascular toxicities were observed in 22% of patients. At baseline, these patients significantly more frequently had heart failure and ischemic heart disease as well as previous radiation and chemotherapy. After the optimization of cardiac therapy, 88% of patients successfully completed all scheduled treatments. The overall mortality, including the CV mortality, was 14% (n=7). Creation of cardio-oncological services allows considerably reducing the probability of adverse CV events during the antitumor therapy and successfully completing all scheduled treatments in most patients..

Artificial intelligence: Applications in cardio-oncology and potential impact on racial disparities

Numerous cancer therapies have detrimental cardiovascular effects on cancer survivors. Cardiovascular toxicity can span the course of cancer treatment and is influenced by several factors. To mitigate these risks, cardio-oncology has evolved, with an emphasis on prevention and treatment of cardiovascular complications resulting from the presence of cancer and cancer therapy. Artificial intelligence (AI) holds multifaceted potential to enhance cardio-oncologic outcomes. AI algorithms are currently utilizing clinical data input to identify patients at risk for cardiac complications. Additional application opportunities for AI in cardio-oncology involve multimodal cardiovascular imaging, where algorithms can also utilize imaging input to generate predictive risk profiles for cancer patients. The impact of AI extends to digital health tools, playing a pivotal role in the development of digital platforms and wearable technologies. Multidisciplinary teams have been formed to implement and evaluate the efficacy of these technologies, assessing AI-driven clinical decision support tools. Other avenues similarly support practical application of AI in clinical practice, such as incorporation into electronic health records (EHRs) to detect patients at risk for cardiovascular diseases. While these AI applications may help improve preventive measures and facilitate tailored treatment to patients, they are also capable of perpetuating and exacerbating healthcare disparities, if trained on limited, homogenous datasets. However, if trained and operated appropriately, AI holds substantial promise in positively influencing clinical practice in cardio-oncology. In this review, we explore the impact of AI on cardio-oncology care, particularly regarding predicting cardiotoxicity from cancer treatments, while addressing racial and ethnic biases in algorithmic implementation.

Propanil impairs organ development in zebrafish by inducing apoptosis and inhibiting mitochondrial respiration

Propanil, an anilide herbicide, has frequently been detected in surface waters in Europe and the United States, largely due to its use in paddy cultivation areas. Particularly in specific regions like Sri Lanka, propanil is considered a potential cause of certain diseases and toxicities due to its high environmental runoff; however, there has been little research on its developmental toxicity. In the present study, we confirmed the developmental toxicity of propanil in zebrafish embryos exposed to 0, 2, 5, and 6 mg/L based on the LC50 value. Propanil exposure in embryos induced morphological changes, including decreased body length and eye size, and increased the heart and yolk sac edema. It increased the number of apoptotic cells in the brains and eyes of zebrafish larvae by 214 % and 184 %, respectively. Propanil-treated embryos exhibited altered mitochondrial metabolism, reducing basal respiration by 28 %, maximal respiration by 24 %, and ATP production by 38 %. These alterations induced organ defects in transgenic zebrafish models (cmlc2:DsRed, flk1:EGFP, olig2:DsRed, lfabp:DsRed;elastase:EGFP, and insulin:EGFP). It induced cardiovascular toxicity, as confirmed by the reduced atrial area, cerebrovascular intensity, and intersegmental vessels. Additionally, propanil decreased the fluorescence intensity of neurons, liver, and pancreas. Collectively, this study indicates that propanil causes early developmental toxicity through apoptosis and mitochondrial dysfunction. It presents a new perspective on how mitochondrial dysfunction, previously unreported in toxicity studies of other anilide herbicides, may affect developmental toxicity.

Fine particulate matter‑induced cardiac developmental toxicity (Review).

Fine particulate matter (PM2.5) has become an important risk factor threatening human health. Epidemiological and toxicological investigations have revealed that PM2.5 not only leads to cardiovascular dysfunction, but it also gives rise to various adverse health effects on the human body, such as cardiovascular and cerebrovascular diseases, cancers, neurodevelopmental disorders, depression and autism. PM2.5 is able to penetrate both respiratory and placental barriers, thereby resulting in negative effects on fetal development. A large body of epidemiological evidences has suggested that gestational exposure to PM2.5 increases the incidence of congenital diseases in offspring, including congenital heart defects. In addition, animal model studies have revealed that gestational exposure to PM2.5 can disrupt normal heart development in offspring, although the potential molecular mechanisms have yet to be fully elucidated. The aim of the present review was to provide a brief overview of what is currently known regarding the molecular mechanisms underlying cardiac developmental toxicity in offspring induced by gestational exposure to PM2.5.

Acute Myocardial Infarction in a Amphetamine Abuser with Low ASCVD Risk: A Case Report

Wide availability of recreational drugs, like amphetamine, cocaine, cannabis etc has spread out these drugs to all classes and age groups in the society of Bangladesh. Among them association cocaine and cannabis with acute myocardial infarction has been well established. But the popular drug, amphetamine, which is available in tablet form containing the active ingredient named 3,4 methylenedioxymethamphetamine (MDMA), has been reported to have significant cardiac and CNS toxicity. Repeated angina, even myocardial infarction due to active coronary vasospasm and accelerated atherothrombosis in amphetamine abusers has been reported in several case studies worldwide. But, only a few cases has been reported in Bangladesh. Here we present a case of acute myocardial infarction in a amphetamine abuser with low 10 years ASCVD risk. J Inv Clin Cardiol 2023; 5(2): 53-55

Vaping/e-cigarette-induced pulmonary extracellular vesicles contribute to exacerbated cardiomyocyte impairment through the translocation of ERK5

AimsThe impact of e-cigarettes/vaping on cardiac function remains contradictory owing to insufficient direct evidence of interorgan communication. Extracellular vesicles (EVs) have protective or detrimental effects depending on pathological conditions, making it crucial to understand their role in lung-cardiac cell interactions mediated by vaping inhalation. Methods and key findingsPulmonary EVs were characterized from animals that underwent 12 weeks of nicotine inhalation (vaping component) (EVsNicotine) or vehicle control (EVsVehicle). EVsNicotine significantly increased in size and abundance compared with EVsVehicle. The direct effect of EVs Nicotine and EVs Vehicle on cardiomyocytes was then assessed in vitro and in vivo. EVs Nicotine led to a decrease in cardiac function as manifested by reduced cardiac contractility and impaired relaxation. EVs Nicotine induced increased levels of cleaved caspase-1 and cleaved caspase-11 in cardiomyocytes, indicating the promotion of pyroptosis. Meanwhile, EVsNicotine stimulated the secretion of fibrotic factors. Further analysis revealed that nicotine inhalation stimulated EVs Nicotine enriched with high levels of ERK5 (EVs Nicotine-ERK5). It was discovered that these EVs derived from pulmonary epithelial cells. Furthermore, inhibiting cardiac ERK5 blunted the EVs Nicotine-induced pyroptosis and fibrotic factor secretion. We further identified GATA4, a pro-pyroptosis transcription factor, as being activated through ERK5-dependent phosphorylation. SignificanceOur research demonstrates that nicotine inhalation exacerbates cardiac injury through the activation of EVs derived from the lungs during e-cigarettes/vaping. Specifically, the EVs containing ERK5 play a crucial role in mediating the detrimental effects on cardiac function. This research provides new insights into the cardiac toxicity of vaping and highlights the role of EVs Nicotine-ERK5 in this process.

The CTOX-Score, a clinical risk prediction tool for cardiovascular toxicity secondary to cancer therapies

Abstract Introduction Cardiovascular toxicity (cardiotoxicity) is recognized as a major side-effect of cancer therapies. As early diagnosis and management is crucial in clinical practice1,2, knowledge about risk factors and risk scores is scarce3,4. Purpose The aim of this study is to develop a clinical prediction score to identify patients at high/very high risk of cardiotoxicity. Methods The CARDIOTOX registry5,6 included patients receiving cancer therapies related to moderate/high risk for cardiotoxicity (2012-2017). Clinical, laboratory and echo parameters were collected at baseline and at 3 weeks, 3 and 6 months, 1, 1.5 and 2 years after initiation of cancer therapy. Patients were classified according to current cardioncology guidelines2 and divided in two groups: no or mild cardiotoxicity vs moderate or high cardiotoxicity. Difference between groups were tested with t-student or U Mann-Withney for continuous variables and Fisher’s exact test for categorical data. Variables with p<0.05 were included in a multivariate binary logistic regression model to find independent predictors of cardiotoxicity and construct a clinical risk score, CTOX-Score. The calibration was evaluated by Hosmer-Lemeshow goodness-of-fit test and discrimination using ROC curves. Results From the 1324 individuals included in the registry we discarded all those with pre-existing symptomatic heart failure or LVEF<40% at baseline and those with incomplete baseline data. We considered 998 patients, aged 54.62±14.15 years, 176 men (17.6%), of which 53 (5.3%) developed moderate or severe cardiotoxicity. These patients had lower baseline LVEF (59.91±7.50% vs 64.20±5.88%), higher creatinine levels (0.90 (0.76, 1.10) mg/dl vs 0.74 (0.62, 0.90) mg/dl) and higher NT-ProBNP (177 (58, 476) pg/ml vs 66 (38, 133) pg/ml) compared with patients with no or mild cardiotoxicity (p<0.001). We found previous radiotherapy (OR=4.66, CI:1.24-17.52), acute myeloid leukemia (OR=6.85; CI:1.16-40.50), monoclonal antibodies (OR=3.27; CI:1.35-7.89), LVEF (OR=0.96; CI:0.84-0.98) and serum creatinine (OR=5.43; CI:1.63-18.14) as independent predictors of cardiotoxicity (p<0.05). A clinical risk score was developed based in beta coefficient of variables (Table 1). The model has good calibration according to Hosmer-Lemeshow goodness-of-fit (χ2=2.800, p=0.424) and good discrimination power (AUC:0.780, CI:0.69-0.87; p<0.001). The best cut-off value of CTOX-Score is ≥3 points (Sensitivity:70.00%, Specificity:72.25%, NPV:98.11%). Patients were classified in four risk categories: low (0-1 points); moderate (2); high (3-4); very high (≥5) (Figure 1). The model has good accuracy to identify very high-risk patients (Specificity 98.80%). Conclusion The CTOX-Score is a clinical risk prediction model to identify patients at high/very high-risk of cardiotoxicity and could allow for more personalized monitoring of patients. Additional studies are needed to externally validate the model prior to implementation in clinical practice.Multivariate binary logistic regressionCTOX-Score values among population

Prognostic value of neutrophil-to-lymphocyte ratio and cardiac troponin I in patients with immune checkpoint inhibitors-related myocarditis

Abstract Background Over the past decade, immune checkpoint inhibitors (ICIs) have significantly transformed cancer treatment. However, ICIs inevitably may cause a spectrum of immune-related adverse events, among which cardiovascular toxicity, particularly myocarditis, while infrequent, has garnered increasing attention due to its high fatality rate. Purpose We executed a multicenter study aimed at characterizing ICI-related myocarditis and risk factors influencing its prognosis. Methods The study included patients with ICIs-associated myocarditis at four medical centers in China from January 28, 2019 to June 15, 2023. Logistic regression was performed to explore the risk factors for the development of severe myocarditis. Receiver operating characteristic curves were conducted to assess the diagnostic abilities of biomarkers to distinguish severe myocarditis, and the performance and calibration were evaluated using Hosmer-Lemeshow test. Cox regression analysis was employed to investigate the influential risk factors affecting the prognosis of ICI-related myocarditis. Kaplan-Meier survival curve analyses were conducted to assess the differences in survival times among different myocarditis groups. Results 35 ICIs-associated myocarditis patients were identified. 21 patients (60%) were classified as severe myocarditis, and they presented higher cardiac troponin I (cTnI) levels (P=0.013), higher N-terminal pro-B-type natriuretic peptide levels (P=0.031), higher creatine kinase (CK) levels (P=0.018), higher CK-MB levels (P=0.026), and higher neutrophil to lymphocyte ratio (NLR) levels (P=0.016) compared to non-severe myocarditis patients. Multivariate logistic regression showed that cTnI (adjusted odds ratio: 1.021, 95% confidence interval (CI): 1.002-1.039, P=0.03) and NLR (adjusted odds ratio: 1.890, 95% CI: 1.026-3.483, P=0.041) were the independent risk factors of ICI-associated severe myocarditis. The receiver operating characteristic curve showed an area under curve of 0.765 (95% CI: 0.601 to 0.929, P=0.013) for cTnI, and 0.773 for NLR (95% CI: 0.597 to 0.948, P=0.016). Multivariate COX regression showed that NLR (adjusted hazard ratio: 1.189, 95% CI: 1.028-1.376, P=0.020) and pneumonitis (adjusted hazard ratio: 8.142, 95% CI: 1.191-55.651, P=0.032) were the independent prognostic risk factor associated ICI- related myocarditis. Further Kaplan-Meier survival curve analysis showed that the survival rate among patients without pneumonitis and with low level of NLR significantly outstripped that of patients with pneumonitis (P=0.015) and high level of NLR (P=0.024). Conclusions As independent risk factors for the development of ICI-associated severe myocarditis, cTnI and NLR demonstrated a promising predictive utility for the identification of ICI-associated severe myocarditis. NLR and the presence of pneumonitis were identified as independent risk factors that significantly impacted the prognosis of ICI-related myocarditis.

Development of a cardiotoxicity evaluation system using a Heart-on-a-Chip Microdevice with aligned fiber device

Abstract Background and Purpose Cardiovascular cells differentiated from human induced pluripotent stem (iPS) cells, such as cardiomyocytes, are expected to be useful for evaluating cardiac pharmacology and toxicity in humans. In recent years, myocardial damage caused by anticancer drugs has begun to attract attention. Being able to evaluate human cardiotoxicity early in the development of novel drugs like anticancer agents confers advantages in terms of cost and development speed. The aim of this study was to develop a highly sensitive bioassay system that can evaluate the physiological function of the human heart, and to validate the efficacy of the system toward detection of cardiotoxicity of drugs. Methods We differentiated human iPS cells into cardiovascular cells (cardiomyocytes, endothelial cells and mural cells) and applied dynamic culture training to generate vascularized microtissues (VCM) with vascular network structures. By integrating this VCM with a microfluidic chip containing microchannels, we developed a heart-on-a-chip microdevice (HMD) specialized for evaluating cardiac function (Figure 1). Furthermore, through a collaborative study with the Stem Cell & Device Laboratory (SCAD), application of their aligned fiber device improved throughput and stability, allowing development of a SCAD-HMD capable of evaluating longer-term cardiotoxicity. Results SCAD-HMD can quantify physiological parameters of VCM such as ejection volume and force based on displacement of particles within the microchannels. Our results showed that SCAD-HMD not only exhibited pharmacological responses to representative circulatory stimulants, but also reproduced clinical events occurring in actual practice, demonstrating that the anticancer drug trastuzumab, commonly used for breast cancer treatment, causes myocardial disfunction when combined with doxorubicin. Conclusions This study demonstrated that SCAD-HMD can stably evaluate the toxicity of drugs on the human heart. In the future, establishing SCAD-HMD using iPS cells derived from individual patients and assessing responses to specific drugs may enable "individualized cardiotoxicity assessment systems" that can preemptively avoid cardiac complications associated with anticancer drugs and other pharmacological agents.

Cardiovascular events in CML patients treated with nilotinib: validation of the HFA-ICOS baseline risk score

Abstract Background The therapeutic landscape of chronic myeloid leukaemia (CML) has been transformed by tyrosine kinase inhibitors (TKI). Nilotinib, a potent 2nd generation TKI, showed higher rates of major molecular response than imatinib, however was associated with higher rates of cardiovascular (CV) toxicity. Objectives To describe the CV events associated with nilotinib in a real-world CML population and assess the predictive value of the HFA-ICOS baseline risk score in clinical practice. Methods The HFA-ICOS baseline risk was calculated (low, medium, high /very high) for patients with CML treated with nilotinib between 2006 and 2021. The incidence of all CV events, ischaemic events and Major CV Adverse Events (MACE) were reviewed and compared among the different risk groups. Results A total of two hundred and twenty-nine eligible patients were included in the analysis. The incidence of CV events, ischaemic events, and MACE, while on nilotinib, were 20.9% (95% CI: 15.7% to 26.2%), 12.7% (95% CI: 8.4% to 16.9%), and 12.2% (95% CI: 7.9% to 16.5%) respectively, following a median duration of treatment with nilotinib of 34.4 months for the entire cohort. Patients with a higher HFA-ICOS baseline risk score had higher rates of all CV events (low: 11.2%, medium: 28.2% [HR: 2.8, 95% CI: 1.2 to 6.2], high/very high: 32.4% [HR: 3.5, 95% CI: 1.8 to 6.8]), ischaemic events (low: 5.2%, medium: 17.9% [HR: 3.7, 95% CI: 1.2 to 10.9] , high/very high: 21.6% [HR: 3.7, 95% CI: 1.4 to 9.7]) and MACE (low: 7.8% , medium: 10.3% [HR:1.2, 95% CI: 0.38 to 4.1], high/very high: 20.2% [HR: 2.2, 95% CI: 0.9 to 5.3]). The predictive tool presented an 89% NPV, and an area under the ROC curve: 0.65 for all CV events, an NPV of 95% and AUC 0.68 for ischaemic events and NPV 92% and AUC 0.62 for MACE. Conclusions The HFA-ICOS risk stratification tool has been shown to be an efficient discriminator at low, medium and high/very high risk of developing cardiovascular events, with an overall positive trend towards increasing cardiotoxicity rates with rising risk categories. This study provides evidence to support the use of this predictive tool in nilotinib treated patients, as it also underscores the potential for further improvement in the overall discriminatory ability of the model.

Validation of the HFA-ICOS risk assessment tool with real-world data from a prospective cohort of breast cancer patients in treatment with anthracyclines and trastuzumab

Abstract Background The increasing prevalence of cancer therapy-related cardiovascular toxicity (CTRCD) poses a significant challenge to patient management, necessitating accurate risk assessments. Previous methodologies have struggled with precise risk stratification, partly due to varying definitions of CTRCD and the specificity of cancer treatments. Purpose This study aimed to evaluate the assessment tool proposed by the Heart Failure Association and the International Cardio-Oncology Society (HFA-ICOS) in predicting the risk of CTRCD in patients undergoing anthracycline and trastuzumab treatment for breast cancer at a national reference center. Methods A prospective cohort study was conducted, encompassing 172 patients treated from January 2022 to July 2023. Patients were assessed at baseline, three months, and six months post-treatment initiation, with exclusion criteria including baseline left ventricular ejection fraction (LVEF) <50%, history of heart failure, and stage IV breast cancer. The study utilized the HFA-ICOS tool for risk stratification and CTRCD was defined with the current criteria of the European Society of Cardiology guideline. Descriptive statistics were calculated, and incidence rates and Cox proportional-hazards models were developed according to the risk category. Results In our study, 138 (80.2%) patients were classified as low risk, 23 (13.4%) as moderate risk and 11 (6.4%) as high risk. We identified 81 (47.1%) patients that developed CTRCD in follow-up. Descriptive characteristics can be found in Table 1. The global incidence rate for CTRCD in our cohort was of 2.4 new cases per 1000 person-days, however no differences in incidence rates were found when stratifying by risk category (Figure 1A). Moreover, patients with moderate to high risk according to the HFA-ICOS tool did not show a significantly increased hazard ratio for cardiotoxicity (HR 0.41, 95%CI 0.15-1.12, p=0.082 and HR 1.39, 95%CI 0.50-3.86, p=0.5, respectively) as shown in Figure 1B. Conclusion While the HFA-ICOS tool provides a structured framework for assessing cardiotoxicity risk, its predictive value in this cohort was limited. The findings underscore the complexity of cancer therapy-related cardiotoxicity and the need for enhanced, individualized risk assessment tools. Future research should focus on refining risk prediction models, incorporating broader clinical and genetic factors to improve patient outcomes in cardio-oncology.Table 1.Clinical CharacteristicsFigure 1.Incidence rates and Cox models

Does HFpEF represent a risk factor and a marker of cardiotoxicity in patients undergoing cancer treatment?

Abstract Background The prevalence of heart failure with preserved ejection fraction (HFpEF) increases with the aging of our population and shares risk factors with cancer. Furthermore, HFpEF conveys a worse prognosis if it remains unrecognized and untreated. However, it is not considered as a surrogate marker in the baseline risk stratificatoin of patients that will undergo potentially cardiotoxic cancer treatments. Moreover, the definition of cardiotoxicity focuses mainly on systolic dysfunction, based on left ventricular ejection fraction and global longitudinal strain changes. Data on the prevalence of new-onset HFpEF during cancer treatment are limited. Purpose We evaluated the prevalence of HFpEF in cancer patients followed in our cardio-oncology clinic, with new cancer therapy-related cardiovascular toxicity (CTR-CVT) events in patients with known HFpEF prior to cancer therapy. We also assessed the prevalence of patients diagnosed with HFpEF while undergoing cancer therapy. Methods A total of 630 cancer patients referred for either baseline evaluation, on-treatment surveillance, long-term follow-up or new complaints suspect for cardiovascular disease were included in this real-world observational study, with a mean follow-up duration of 507 days. They underwent comprehensive workup in accordance with the ESC guidelines, including clinical assessment, electrocardiogram, echocardiography and biomarker testing. Results From the total population, 36 (5.7%) were diagnosed with HFpEF prior to cancer treatment initiation. Among these, 18 (50%) developed CTR-CVT during follow-up, mainly heart failure events (cancer-therapy related cardiac dysfunction or HFpEF decompensation). Independent of baseline characteristics, 233 patients (37.0%) developed a heart failure event during or after cancer treatment. Of these, 92 patients (14.6% of the total population, 39.5% of all HF events on treatment) developed a HFpEF event during or after cancer treatment. Of these HFpEF events, 42 patients (45.7%) were known with pre-existing cardiovascular disease, of whom only 14 (15.2%) with pre-existing HFpEF. In 50 patients (54.3%) the HFpEF diagnosis was made de novo during (or after) cancer treatment. Patients developing HFpEF were mostly female (n=54, 58.7%) and relatively young (mean age 62.0 years). Most HFpEF events occurred in breast cancer patients (n=32, 34.7%), prostate cancer patients (n=13, 14.1%) and multiple myeloma patients (n=9, 9.8%). Conclusions HFpEF is frequently overlooked, but conveys a high risk of developing CTR-CVT and should therefore be taken into account in the baseline risk stratification. Furthermore, HFpEF is responsible for an important morbidity burden during or after cancer cardiotoxic treatments, even in patients without prior diagnosis of HFpEF at baseline evaluation. Further studies are needed to evaluate if this population may benefit from specific management and treatment strategies in order to improve prognosis.Prevalence of HFpEF in cancer patients

Multidisciplinary strategies for cardiotoxicity management in ambulatory care: exploring practices, insights, and prospects for advancement

Abstract Background The management of cardiotoxicity, a significant concern in chemotherapy patients, necessitates a multidisciplinary approach. This study investigates the variability in cardiotoxicity management in outpatient settings across different medical specialties, which may lead to inconsistencies in patient care. Methods An extensive questionnaire-based study was conducted to assess the current practices and viewpoints of cardiologists, oncologists, and gynecologists in the management of cardiotoxicity among patients receiving outpatient chemotherapy in Germany. The survey engaged 1,329 medical professionals through an online platform, with a participation rate of 9.9%, amounting to 132 respondents. Results Respondents reported managing a combined total of 1,905 chemotherapy patients monthly, with individual patient loads ranging from 1 to 200. Notably, only a fraction of these patients – 37% under oncologist care and 48% under gynecologist care – underwent routine cardiological examinations. As shown in Figure 1, the three most common causes of cardiological presentations in patients undergoing chemotherapy were due to acute patient complaints (65.2%), before the start of chemotherapy (91.3%), and after the end of chemotherapy (78.3%). Furthermore, 37% of healthcare providers reported incorporating chemotherapy-induced cardiovascular toxicity risk assessments in their clinical routines. Medical history, ECG, and echocardiography were the most frequent examinations. Notably, 91.3% did not include cardiac biomarker measurements in their follow-up procedures (Figure 2). More than half of the participants (56%) expressed a need for simplified cardio-oncology guidelines. The majority of participants (84% and 83%, respectively) requested tools to assist in cardiovascular toxicity risk assessment and the implementation of appropriate therapeutic measures for patients undergoing chemotherapy. Conclusions The study draws attention to significant interdisciplinary care gaps in managing cardiotoxicity, which may contribute to an increased risk of undiagnosed cardiovascular complications in chemotherapy patients. The evident variability in cardiotoxicity management practices among different medical specialties underscores the critical need for heightened awareness and enhanced collaborative efforts. The implementation of comprehensive interdisciplinary clinical pathways and the establishment of a dedicated cardio-oncology network could potentially address these challenges, particularly in supporting primary care physicians.Figure 1Figure 2

Causes and predictors of long-term mortality in patients referred to a cardiac rehabilitation program

Abstract Introduction Cardiac rehabilitation (CR) programs have proven to reduce short-term mortality in patients with ischemic heart disease (IHD) and hospitalization rates in patients with heart failure (HF) (1-3). However, there is insufficient evidence about long-term mortality (>24-36 months) for patients receiving treatments based on recent clinical practice recommendations. Purpose To assess the long-term prognosis and predictors of mortality in a heterogenous group of patients referred to cardiac rehabilitation, and to obtain a detailed overview of death causes. Methods An inferential analysis of consecutive patients referred for exercise-based CR at a single site between January 2016 and January 2021 was performed. Included subjects were classified attending to four indications for referral: IHD, HF, valvular heart disease (VHD) and cancer therapy-related cardiovascular toxicity (CTR-CVT). Patients who did not initiate the CR program or were referred for other indications were excluded. The primary endpoint was all cause death. The secondary endpoint was cardiovascular (CV) death. A survival analysis was performed using Kaplan Meier estimates for each referral indication and a Cox proportional hazards model was fitted to investigate mortality predictors. The initiation of the exercise program was considered the inclusion date, and patients were followed until they met the primary endpoint or censored by January 2024. Results A total of 1180 patients were included in the analysis (81% male, mean age 61 ± 11 years), with a median follow-up of 5.3 years. Most of the patients had been referred due to IHD (87%), while the proportion for HF, VHD, and CTR-CVT was 9.9%, 1.8% and 1.4%, respectively. Seventy-eight patients (6.6%) died during follow-up, with a Kaplan-Meier estimated survival of 94.5% at 5 years (95% CI 93.2%-95.9%). Nineteen patients (24.4%) died due to a cardiovascular event, mostly sudden cardiac death (47%). The predominant non-CV causes of death were infectious disease (36%) and cancer (34%). A multivariate Cox model analysis (Table 1) showed an increased risk of all cause death for patients referred due to HF (HR 2.95, 95% CI 1.33 - 6.55), VHD (HR 5.55, 95% CI 1.19 - 25.9) and CTR-CVT (22.47, 95% IC 7.32 - 68.95) when compared to IHD (Figure 1). Other significant predictors of mortality were LVEF <40%, male sex, age, diabetes, peripheral vascular disease, and multivessel coronary disease. Only LVEF <40%, VHD, CTR-CVT and peripheral vascular disease were independent predictors of CV death. Conclusion Patients who initiated an exercise-based CR program had a low risk of all cause death at 5 years. Indications for CR other than IHD were associated with higher mortality rates after adjusting for confounder variables, likely due to a selection bias of patients in advanced stages of the disease.Table 1.Cox models for all-cause deathFigure 1.KM plot for all-cause death

Comparison of two anthracycline regimens for treatment of breast cancer and the incidence of cardiac injury

Abstract Background Anthracycline based breast cancer treatment regimens have evolved over time. Whether the risk of myocardial injury is different between regimens is unclear. Purpose To compare the incidence and significance of high sensitivity troponin-I (TpI) levels immediately post anthracycline therapy in women with breast cancer treated with two different anthracycline regimens. Methods We prospectively recruited women with early-stage breast cancer who received either dose-dense doxorubicin and cyclophosphamide (ddAC) or 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) with or without subsequent HER2 therapy. The ddAC regimen comprises 4 cycles of doxorubicin given every 2 weeks (240mg/m2), whereas FEC consists of 3 cycles of epirubicin given every 3 weeks (total epirubicin dose of 300mg/m2, which is doxorubicin equivalent dose of 240mg/m2 using a cardiovascular toxicity dose ratio of 0.80 as per the 2022 ESC Cardio-oncology guidelines). Clinical characteristics were collected and TpI levels were measured before anthracyclines and 4-6 weeks post last dose. Comprehensive echocardiograms were conducted at baseline and post-therapy. Results 236 female participants were enrolled; 103 (43.6%) received ddAC and 133 (56.4%) received FEC. Compared to FEC, patients receiving ddAC were older (mean age 58.1±10.2 vs 51.0±9.3 years; p < 0.001) received similar cumulative doxorubicin equivalent dose (237.4±23.4 vs 239.9 ± 11.9 mg/m2; p=0.30), had similar baseline LVEF (62.1 ± 4.8 vs 61.3 ± 3.6%, p=0.14), and TpI levels (median (IQR) 2.0 (2.0-2.0) vs 2 (2.0-3.0) ng/L, p=0.12) respectively. Baseline risk factors were similar (hypertension 21% vs 17%, p=0.34; diabetes 7% vs 5%, p=0.44; dyslipidemia 15% vs. 8%, p=0.12). Post-anthracycline, the ddAC group had higher TpI level compared to patients in the FEC group (median (IQR) 12 (7-29) vs 6 (4-11) ng/L; p<0.001). The proportion of patients with abnormal TpI levels (>99th percentile, >16.0 ng/L) was higher in the ddAC group (43.7% vs 15.0%; p < 0.001). In a multivariable linear regression model that included age, treatment regimen, baseline TpI, hypertension, diabetes mellitus and dyslipidemia, ddAC remained significantly associated with higher post anthracycline TpI levels (β=15.5, 95%CI: 8.7-22.3; p<0.001). There was no significant difference in the mean LVEF post-anthracycline (59.9 ± 5.1 vs 60.0 ± 3.8; p=0.91). No patients developed clinical heart failure. Conclusion Despite similar doxorubicin equivalent doses, the incidence of abnormal TpI levels was ~3 fold higher with DD-AC than FEC. Given that DD-AC is now more commonly used especially with immunotherapy this knowledge is clinically relevant. The difference in proportion with troponin elevation could be due to differences in the number of cycles (3 vs 4) and the frequency of chemotherapy administration (every 2 vs 3 weeks) between the regimens. However, this did not translate into a larger reduction in LVEF. But longer-term follow-up is needed.