Search

With an ever-expanding repertoire of cancer therapies, cardiologists increasingly encounter patients with cancer therapy-related cardiac dysfunction. This can range from asymptomatic mild left ventricular dysfunction to severe symptomatic congestive heart failure. A multidisciplinary approach involving oncologists and cardiologists is needed in the management of these patients. This case-based review provides a practical guide for clinicians regarding the diagnosis and management of cancer therapy-related cardiac dysfunction associated with commonly used cancer treatments: anthracyclines, human epidermal receptor 2-targeted therapies, and immune checkpoint inhibitors., Competing Interests: Declaration of competing interest The authors have no competing interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Cardio-oncology, a burgeoning subspecialty, addresses the complex interplay between cardiology and oncology, particularly in light of increased cardiovascular (CV) disease mortality in cancer patients. This review provides a comprehensive overview of cardio-oncology with a focus on the therapies used in hematological malignancies. We explore the bidirectional relationship between heart failure and cancer, emphasizing the need for collaborative care. The review discusses risk stratification, highlighting the importance of baseline CV risk assessment and personalized surveillance regimens. Primary and secondary prevention strategies, including pharmacological interventions, are outlined. The review also delves into the cardiotoxicity associated with hematological cancer therapies, focusing on anthracyclines, Bruton kinase inhibitors, BCR-ABL tyrosine kinase inhibitors, CAR-T cell therapy, immune checkpoint inhibitors, multiple myeloma treatments, and hematopoietic stem cell transplantation. We then highlight the high risk of venous and arterial thromboembolisms in cancer patients and the challenges of anticoagulation management in cardio-oncology. Finally, the review touches on the importance of long-term follow-up and appropriate screening in cancer survivors at high risk of CV morbidity and mortality, based on their CV risk profile and the type and dose of cardiotoxic therapies they received such as anthracyclines or high radiation doses., Competing Interests: Both authors received a grant from Boehringer Ingelheim for SGLT2i in cardio-oncology patients., (Thieme. All rights reserved.)

Carfilzomib (CFZ), a proteasome inhibitor commonly used in the treatment of multiple myeloma (MM), exhibits limited clinical application due to its cardiotoxicity. In our study, electroacupuncture (EA) at Neiguan acupoint (PC6) effectively reversed CFZ-induced reduction in ejection fraction (EF) and fractional shortening (FS), demonstrating great potential effect for heart protection. Through comparative analysis of the transcriptome profile from heart samples of mice treated with DMSO control, CFZ injection, and EA stimulation, we identified a total of 770 differentially expressed genes (DEGs) in CFZ (vs. Control) group and 329 DEGs in EA (vs. CFZ) group. Specifically, CFZ (vs. Control) group exhibited 65 up-regulated DEGs and 705 down-regulated DEGs, while EA (vs. CFZ) group displayed 251 up-regulated DEGs and 78 down-regulated DEGs. Metascape analysis revealed that among these treatment groups, there were 137 co-expressed DEGs remarkably enriched in skeletal system development, cellular response to growth factor stimulus, negative regulation of Wnt signaling pathway, and muscle contraction. The expression patterns of miR-8114, Myl4, Col1a1, Tmem163, Myl7, Sln, and Fxyd3, which belong to the top 30 DEGs, were verified by quantitative real-time PCR (RT-qPCR). In summary, this study firstly discloses novel insights into the regulatory mechanisms underlying PC6-based EA therapy against CFZ-induced cardiotoxicity, potentially serving as a theoretical foundation for further clinical applications., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Cardiovascular diseases and cancer are the most common causes of death in Germany. Cancer treatment can lead to significant cardiovascular side effects and thus form a link between the two disease groups. The focus of cardio-oncology is on the best possible prevention, diagnostics and treatment of cardiovascular complications caused by cancer treatment. It is crucial for cardio-oncology to adapt to the continuous development of new forms of oncological treatment with previously unknown cardiovascular side effects. One such new form of treatment is immune checkpoint inhibitor (ICI) therapy, which is regarded as the most important oncological milestone of the last decade due to its excellent oncological efficacy; however, the growing use has revealed a high risk of diverse cardiovascular side effects with high morbidity and mortality, so that cardio-oncological care of affected patients is of particular importance. This review summarizes the current scientific and clinical state of the pathophysiology, incidence, diagnosis and treatment of cardiovascular side effects of ICI therapy., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Introduction: Aluminum phosphide (AlP) is a chemical compound that can cause death in some countries. AlP inhibits the functioning of cytochrome C oxidase in the mitochondria of cardiomyocytes, leading to toxicity. Oxidative stress and ROS production, as well as inflammatory signaling, mediate the mechanisms of AlP-related toxicity in the poisoned patient. Unfortunately, there are no approved medicines available to treat AlP poisoning yet. To address this issue, researchers have explored various interventions to reduce the toxicity associated with AlP tablets., Methods: We systematically searched relevant databases for English articles published between 2013 and 2024., Results: The evaluated treatments included correcting oxidative stress parameters, enhancing exogenous antioxidant capacity, modifying electrocardiographic abnormalities, and improving heart contraction strength. Our evaluation indicated that compounds like Triiodothyronine, Vasopressin and milrinone, Iron sucrose, Acetyl-l-carnitine, Melatonin, Fresh red blood cell transfusion, Minocycline, Moringa oleifera extract, Dihydroxyacetone, Selegiline, Nanocurcumin, Levosimendan, Exenatide, Taurine, Cannabidiol and Edaravone are effective in lessening AlP-induced cardiotoxicity., Conclusion: Based on the present study's findings and the evaluation of clinical studies, dihydroxyacetone, fresh red blood cell infusion, Oil-based disinfection, and gastric lavage have the most potential to save patients' lives and treat acute aluminum phosphide. However, there is a need for more research in this regard., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Advances in cancer therapeutics have revolutionized survival outcomes in patients with cancer. However, cardiovascular toxicities associated with specific cancer therapeutics adversely affect the outcomes of patients with cancer. Recent studies have uncovered excess risks of these cardiotoxic events, especially in traditionally underrepresented populations. Despite advances in strategies to limit the risks of cardiovascular events among cancer survivors, relatively limited guidance is available to address the rapidly growing problem of disparate cardiotoxic risks among women and underrepresented patient populations. Previously decentralized and sporadic evaluations have led to a lack of consensus on the definitions, investigation, and potential optimal strategies to address disparate cardiotoxicity in contemporary cancer care (eg, with immunotherapy, biologic, or cytotoxic therapies) settings. This scientific statement aims to define the current state of evidence for disparate cardiotoxicity while proposing uniform and novel methodological approaches to inform the identification and mitigation of disparate cardio-oncology outcomes in future clinical trials, registries, and daily clinical care settings. We also propose an evidence-based integrated approach to identify and mitigate disparities in the routine clinical setting. This consensus scientific statement summarizes and clarifies available evidence while providing guidance on addressing inequities in the era of emerging anticancer therapies.

Survivorship issues and treatment related toxicities have considerably increased in breast cancer patients following improved therapeutic options. Cardiotoxicity has been a major treatment related side effects in these patients. Despite this being a well-known entity, the real magnitude of the problem remains an enigma. The amount of research in mitigation of cardiotoxicity or its management in breast cancer survivors is limited and there is an urgent need for finding solutions for the problem. In this article, we are reviewing the agents that cause cardiotoxicity and suggesting a proposal for follow up of breast cancer survivors in an attempt to reduce the magnitude of impact on their quality of life., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

The aberration of programmed cell death including cell death associated with autophagy/mitophagy, apoptosis, necroptosis, pyroptosis, and ferroptosis can be observed in the development and progression of doxorubicin-induced cardiotoxicity (DIC). Vagus nerve stimulation (VNS) has been shown to exert cardioprotection against cardiomyocyte death through the release of the neurotransmitter acetylcholine (ACh) under a variety of pathological conditions. However, the roles of VNS and its underlying mechanisms against DIC have never been investigated. Forty adults male Wistar rats were divided into 5 experimental groups: (i) control without VNS (CSham) group, (ii) doxorubicin (3 mg/kg/day, i.p.) without VNS (DSham) group, (iii) doxorubicin + VNS (DVNS) group, (iv) doxorubicin + VNS + mAChR antagonist (atropine; 1 mg/kg/day, ip, DVNS + Atro) group, and (v) doxorubicin + VNS + nAChR antagonist (mecamylamine; 7.5 mg/kg/day, ip, DVNS + Mec) group. Our results showed that doxorubicin insult led to left ventricular (LV) dysfunction through impaired cardiac autonomic balance, decreased mitochondrial function, imbalanced mitochondrial dynamics, and exacerbated cardiomyocyte death including autophagy/mitophagy, apoptosis, necroptosis, pyroptosis, and ferroptosis. However, VNS treatment improved cardiac mitochondrial and autonomic functions, and suppressed excessive autophagy, apoptosis, necroptosis, pyroptosis, and ferroptosis, leading to improved LV function. Consistent with this, ACh effectively improved cell viability and suppressed cell cytotoxicity in doxorubicin-treated H9c2 cells. In contrast, either inhibitors of muscarinic (mAChR) or nicotinic acetylcholine receptor (nAChR) completely abrogated the favorable effects mediated by VNS and acetylcholine. These findings suggest that VNS exerts cardioprotective effects against doxorubicin-induced cardiomyocyte death via activation of both mAChR and nAChR., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Myocardial injury influenced by cisplatin (Cis) is a compelling reason to hunt out a treatment modality to overcome such a threat in cisplatin-treated patients. Breast Milk mesenchymal stem cells (Br-MSCs) are a non-invasive, highly reproducible source of stem cells. Herein, we investigate Br-MSCs' role in cardiotoxicity induced by cisplatin. Rats were divided into; control, Cis-treated (received 12 mg/kg single intraperitoneal injection), BrMSCs-treated (received single intraperitoneal injection of 0.5 ml sterilized phosphate-buffered saline containing 2 × 10 7 cells of Br-MSCs); metformin-treated (received 250 mg/kg/day orally) and BrMSCs + metformin + Cis treated groups. At the experiment end, serum creatine kinase (CK-MB) and cardiac troponin T (cTnT) activates were estimated, cardiac malondialdehyde (MDA), superoxide dismutase (SOD), interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α) levels were measured, cardiac expression of Bax and Bcl-2 and AMP-activated protein kinase (AMPK), as well as heart histopathology, were evaluated. Study results showed that Cis explored acute cardiotoxicity evidenced by deteriorated cardiac indices, induction of oxidative stress, and inflammation with myocardium histological alterations. Treatment with Br-MSCs restored heart function and structure deteriorated by Cis injection. The antioxidant/anti-inflammatory/anti-apoptotic results of Br-MSCs were supported by AMPK activation denoting their protective role against cisplatin-induced cardiac injury. These results were superior when metformin was added to the treatment protocol., (© 2022. The Author(s).)

Background: Intravenous administration of mesenchymal stromal cells (MSCs) has an acknowledged competence of cardiac repair, despite a lack of systematic description of the underlying biological mechanisms. The lung, but not the heart, is the main trapped site for intravenously transplanted MSCs, which leaves a spatial gap between intravenously transplanted MSCs and the injured myocardium. How lung-trapped MSCs after intravenous transplantation rejuvenate the injured myocardium remains unknown., Methods: MSCs were isolated from human placenta tissue, and DF-MSCs or Gluc-MSCs were generated by transduced with firefly luciferase (Fluc)/enhanced green fluorescence protein (eGFP) or Gaussia luciferase (Gluc) lactadherin fusion protein. The therapeutic efficiency of intravenously transplanted MSCs was investigated in a murine model of doxorubicin (Dox)-induced cardiotoxicity. Trans-organ communication from the lung to the heart with the delivery of blood was investigated by testing the release of MSC-derived extracellular vesicles (MSC-EVs), and the potential miRNA inner MSC-EVs were screened out and verified. The potential therapeutic miRNA inner MSC-EVs were then upregulated or downregulated to assess the further therapeutic efficiency RESULTS: Dox-induced cardiotoxicity, characterized by cardiac atrophy, left ventricular dysfunction, and injured myocardium, was alleviated by consecutive doses of MSCs. These cardioprotective effects might be attributed to suppressing GRP78 triggering endoplasmic reticulum (ER) stress-induced apoptosis in cardiomyocytes. Our results confirmed that miR-181a-5p from MSCs-derived EVs (MSC-EVs) inhibited GRP78. Intravenous DF-MSCs were trapped in lung vasculature, secreted a certain number of EVs into serum, which could be confirmed by the detection of eGFP + EVs. GLuc activity was increased in serum EVs from mice administrated with GLuc-MSCs. MiR-181a-5p, inhibiting GRP78 with high efficacy, was highly expressed in serum EVs and myocardium after injecting consecutive doses of MSCs into mice treated with Dox. Finally, upregulation or downregulation of miR-181a-5p levels in MSC-EVs enhanced or weakened therapeutic effects on Dox-induced cardiotoxicity through modulating ER stress-induced apoptosis., Conclusions: This study identifies intravenously transplanted MSCs, as an endocrine reservoir, to secrete cardioprotective EVs into blood continuously and gradually to confer the trans-organ communication that relieves Dox-induced cardiotoxicity., (© 2022. The Author(s).)

Introduction: Lipid emulsion therapy (LET) has been most thoroughly studied to reverse local anesthetic systemic toxicity (LAST). Case reports suggest that LET can successfully rescue cardiovascular collapse from bupropion, amitriptyline, and propranolol. The efficacy of LET against refractory hypotension and dysrhythmias from diphenhydramine, a commonly ingested lipophilic cardiotoxic agent, is less well described., Objective: Summarize the evidence that LET rescues cardiac ion channel blockade (QRS, QTc widening) or hypotension attributable to diphenhydramine overdose., Methods: We searched MEDLINE, EMBASE, and Google Scholar for English-language full-length case reports of diphenhydramine (DPH) intoxication in patients 17 years of age or older. We extracted data with a PRISMA-compliant protocol, dividing the case reports into two groups, one that received LET and one that did not. We performed a pooled analysis to compare the change in mean arterial pressure (MAP), QRS duration, and QTc duration between the two groups., Results: We identified 23 reports (25 patients). Lipid emulsion therapy (LET) was used in 6 cases because the patient suffered from hypotension refractory to traditional resuscitation. Those who received LET and those who did not were comparable in age, gender, amount ingested, and frequency of seizures. The mean arterial pressure (MAP) decreased by 4.5 ± 11.5 mm Hg in those who did not receive LET compared to an increase in MAP 37 ± 17.5 mm Hg in those who did receive LET. The QRS narrowed by 29 ± 33.9 ms (no LET group) vs 68 ± 49.5 ms (LET group) and QTc by 168.5 ± 126.75 ms (no LET group) vs 134 ± 88 ms (LET group). All values are expressed as median ± interquartile range. One out of the 6 patients who received LET died after withdrawal of care. In the group that did not receive LET 4 out of 19 died and 3 had no outcome reported., Discussion: LET may improve MAP in patients with hypotension refractory to vasopressors due to diphenhydramine toxicity. We found no significant effect of LET on QRS or QTc duration. These results are limited by a small sample size, reporting bias of case reports, incomplete data, and heterogeneity., Conclusion: An analysis of pooled case reports suggests that LET may rescue hypotension when other methods have failed in patients with hypotension attributable to diphenhydramine overdose.

Opinion Statement: It is a fact that the field of Cardio-Oncology is growing rapidly throughout the USA and abroad. Cancer and heart disease continue to be the leading causes of death in the USA, and oncologic therapies are evolving to the point that cancer survivors are increasing yearly, some living long enough to develop cardiovascular disease, and others living with sequelae from their cancer therapy. The financial burdens to the healthcare system continue to present barriers for the delivery of healthcare, especially for patients with heart disease and cancer as chronic diseases. Collaboration between cardiologists and oncologists is paramount to ensure timely cancer care while minimizing cardiotoxicity. The field of Cardio-Oncology is the perfect model for the current management of these patients, positioned to break down silos, avoid delays in cancer care, and treating potential short- and long-term sequela of cancer therapy in a cost-efficient manner. While cardio-oncology programs initially sprang from the academic and defined cancer centers, it is rapidly growing in the nonacademic settings. This paper explores reasons that occurred and explores some of the unique aspects to cancer care and cardio-oncology delivery in the nonacademic setting. The ultimate goal is to achieve the best cancer care with the least degree of disruption to therapy that also minimizes cardiotoxicity, lowering costs, and improving outcomes for patients., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The therapeutic landscape for the treatment of cancer has evolved significantly in recent decades, aided by the development of effective oncology drugs. However, many cancer drugs are often poorly tolerated by the body and in particular the cardiovascular system, causing adverse and sometimes fatal side effects that negate the chemotherapeutic benefits. The prevalence and severity of chemotherapy-induced cardiotoxicity warrants a deeper investigation of the mechanisms and implicating factors in this phenomenon, and a consolidation of scientific efforts to develop mitigating strategies. Aiding these efforts is the emergence of induced pluripotent stem cells (iPSCs) in recent years, which has allowed for the generation of iPSC-derived cardiomyocytes (iPSC-CMs): a human-based, patient-derived, and genetically variable platform that can be applied to the study of chemotherapy-induced cardiotoxicity and beyond. After surveying chemotherapy-induced cardiotoxicity and the associated chemotherapeutic agents, we discuss the use of iPSC-CMs in cardiotoxicity modeling, drug screening, and other potential applications. Improvements to the iPSC-CM platform, such as the development of more adult-like cardiomyocytes and ongoing advances in biotechnology, will only enhance the utility of iPSC-CMs in both basic science and clinical applications.

With the advent of novel cancer therapeutics and improved screening, more patients are surviving a cancer diagnosis or living longer with advanced disease. Many of these treatments have associated cardiovascular toxicities that can manifest in both an acute and a delayed fashion. Arrhythmias are an increasingly identified complication with unique management challenges in the cancer population. The purpose of this scientific statement is to summarize the current state of knowledge regarding arrhythmia identification and treatment in patients with cancer. Atrial tachyarrhythmias, particularly atrial fibrillation, are most common, but ventricular arrhythmias, including those related to treatment-induced QT prolongation, and bradyarrhythmias can also occur. Despite increased recognition, dedicated prospective studies evaluating true incidence are lacking. Moreover, few studies have addressed appropriate prevention and treatment strategies. As such, this scientific statement serves to mobilize the cardio-oncology, electrophysiology, and oncology communities to develop clinical and scientific collaborations that will improve the care of patients with cancer who have arrhythmias.

Opinion Statement: Immunotherapies have transformed the current landscape for cancer treatment and demonstrated unparalleled improvements in survival rates. Now, a third of cancer patients are eligible for treatment with the most widely used class of immunotherapy, immune checkpoint inhibitors (ICIs). As more patients are treated with these novel agents, it is critical for both oncologists and subspecialists to establish a better understanding of the adverse events which can occur. The incidence of myocarditis associated with ICI therapy has been reported to be between 0.27 and 1.14%, 5 times that of myocarditis from other cancer therapies, and, of those patients, 20-50% develop a fulminant form. However, because of unclear risk factors, a broad clinical spectrum, and lack of specific noninvasive studies for diagnosis, the care of patients with ICI-associated cardiotoxicity can be challenging. Here, we have provided a brief overview of the current immunotherapy agents with a focus on the emerging evidence regarding diagnosis and management of cardiac adverse events.

Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that activate the immune system, aiming at enhancing antitumor immunity. ICIs have shown great promise in the treatment of several advanced malignancies. However, therapy with these immunomodulatory antibodies may lead to a wide spectrum of immune-related adverse events in any organ and any tissue. Cardiologic immune-related events include pericarditis, pericardial effusion, various types of arrhythmias including the occurrence of complete atrioventricular block, myocardial infarction, heart failure, and myocarditis. Although relatively rare, myocarditis is associated with a very high reported mortality in comparison to other adverse events. Myocarditis often presents significant diagnostic complexity and may be under-recognized. When confronted with an unexpected change in the clinical picture, the physician must differentiate between immune-related adverse events, cancer worsening, or other causes unrelated to the cancer or its therapy. However, this is not always easy. Therefore, with the increasing use of checkpoint inhibitors in cancer, all providers who care for patients with cancer should be made aware of this rare, but potentially fatal, cardiologic immune-related adverse event, and able to recognize when prompt consultation with a cardiologist specialist is indicated. In this review, we evaluate currently available scientific evidence and discuss clinical manifestations and new potential approaches to the diagnosis and therapy of acute myocarditis induced by ICIs. Temporary or permanent discontinuation of the ICIs and high-dose steroids have been administered to treat myocarditis, but symptoms may worsen in some patients despite therapy.

In response to the coronavirus disease 2019 (COVID-19) pandemic, the Cardio-Oncology and Imaging Councils of the American College of Cardiology offers recommendations to clinicians regarding the cardiovascular care of cardio-oncology patients in this expert consensus statement. Cardio-oncology patients-individuals with an active or prior cancer history and with or at risk of cardiovascular disease-are a rapidly growing population who are at increased risk of infection, and experiencing severe and/or lethal complications by COVID-19. Recommendations for optimizing screening and monitoring visits to detect cardiac dysfunction are discussed. In addition, judicious use of multimodality imaging and biomarkers are proposed to identify myocardial, valvular, vascular, and pericardial involvement in cancer patients. The difficulties of diagnosing the etiology of cardiovascular complications in patients with cancer and COVID-19 are outlined, along with weighing the advantages against risks of exposure, with the modification of existing cardiovascular treatments and cardiotoxicity surveillance in patients with cancer during the COVID-19 pandemic., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Doxorubicin is one of the most potent chemotherapeutic agents. However, its clinical use is restricted due to the severe risk of cardiotoxicity, partially attributed to elevated production of reactive oxygen species (ROS). Telomerase canonically maintains telomeres during cell division but is silenced in adult hearts. In non-dividing cells such as cardiomyocytes, telomerase confers pro-survival traits, likely owing to the detoxification of ROS. Therefore, we hypothesized that pharmacological overexpression of telomerase may be used as a therapeutic strategy for the prevention of doxorubicin-induced cardiotoxicity. We used adeno-associated virus (AAV)-mediated gene therapy for long-term expression of telomerase in in vitro and in vivo models of doxorubicin-induced cardiotoxicity. Overexpression of telomerase protected the heart from doxorubicin-mediated apoptosis and rescued cardiac function, which was accompanied by preserved cardiomyocyte size. At the mechanistic level, we observed altered mitochondrial morphology and dynamics in response to telomerase expression. Complementary in vitro experiments confirmed the anti-apoptotic effects of telomerase overexpression in human induced pluripotent stem cell-derived cardiomyocytes after doxorubicin treatment. Strikingly, elevated levels of telomerase translocated to the mitochondria upon doxorubicin treatment, which helped to maintain mitochondrial function. Thus, telomerase gene therapy could be a novel preventive strategy for cardiotoxicity by chemotherapy agents such as the anthracyclines., Competing Interests: Declaration of interests S.B. and T.T. are co-founders and hold shares of Cardior Pharmaceuticals GmbH. T.T. filed and licensed patents on noncoding RNAs (outside of this paper). C. Bär. has filed and licensed patents on the therapeutic use of AAV9-mediated delivery of telomerase. The other authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Doxorubicin (DOX)-induced cardiotoxicity in chemotherapy is a major treatment drawback. Clinical trials on the cardioprotective effects of exercise in cancer patients have not yet been published. Thus, we conducted a systematic review and meta-analysis of preclinical studies for to assess the efficacy of exercise training on DOX-induced cardiomyopathy. We included studies with animal models of DOX-induced cardiomyopathy and exercise training from PubMed, Web of Sciences and Scopus databases. The outcome was the mean difference (MD) in fractional shortening (FS, %) assessed by echocardiography between sedentary and trained DOX-treated animals. Trained DOX-treated animals improved 7.40% (95% CI 5.75-9.05, p < 0.001) in FS vs. sedentary animals. Subgroup analyses revealed a superior effect of exercise training execution prior to DOX exposure (MD = 8.20, 95% CI 6.27-10.13, p = 0.010). The assessment of cardiac function up to 10 days after DOX exposure and completion of exercise protocol was also associated with superior effect size in FS (MD = 7.89, 95% CI 6.11-9.67, p = 0.020) vs. an echocardiography after over 4 weeks. Modality and duration of exercise, gender and cumulative DOX dose did were not individually associated with changes on FS. Exercise training is a cardioprotective approach in rodent models of DOX-induced cardiomyopathy. Exercise prior to DOX exposure exerts greater effect sizes on FS preservation.

Extracorporeal life support is the utilisation of advanced techniques to sustain circulatory and/or ventilatory functions in critically ill patients when standard therapies fail. It is well established in developed countries. There is increasing literature supporting its application in refractory cardiac arrest with a potential reversible cause, a procedure also known as extracorporeal cardiopulmonary resuscitation (eCPR). Two cases where eCPR was successfully utilised in a busy (&gt;30 000 visits per year) private South African emergency department are described here, the first such cases to be reported on the African continent. The first patient had a life-threatening cardiac arrhythmia due to toxin ingestion, and the second a refractory ventricular fibrillation due to acute myocardial infarction. In both these cases the cardiac arrest was witnessed, occurred in the emergency department, and failed to respond to standard advanced resuscitative measures. Both the patients were discharged neurologically intact. Although it is effective, the benefit of this advanced method of resuscitation in a low- to middle-income country is debated.

Background: The ASPIRE and ENDEAVOUR trials have shown cardiovascular adverse effects in patients treated with carfilzomib-based regimens. Therefore, we conducted this meta- analysis of published clinical trials to identify the cumulative incidence and risk of cardiovascular adverse effects due to carfilzomib., Methods: A systematic search of PubMed, Embase, Web of Science, and Cochrane library was performed, and we identified 45 prospective trials of carfilzomib with data on 5583 patients. Among all patients being treated with carfilzomib (N=5,583), 8.9% sustained all grade cardiotoxicity, while 4.4% sustained high-grade cardiotoxicity. All-grade hypertension was present in 13.2%, while the incidence of high-grade hypertension was 5.3%., Results: The observed incidences of all-grade heart failure, edema, and ischemia were 5.1%, 20.7%, and 4.6%, respectively. Likewise, for high-grade heart failure and edema observed incidence was 3.2%, and 2.7%, respectively. There was no difference in the event rate of all and highgrade cardiotoxicity between newly diagnosed multiple myeloma and relapsed/refractory (p-value 0.42 and 0.86, respectively). Likewise, we did not observe any difference in the event rate of all and high-grade cardiotoxicity when carfilzomib was used as a single agent versus when used in combination therapy with other agents (p-value 0.43 and 0.73, respectively)., Conclusion: Carfilzomib is associated with a significant risk of cardiovascular toxicity and hypertension. With the increasing utilization of carfilzomib, it is critical for primary care physicians, oncologists and cardiologists to be aware of the risk of cardiotoxicity associated with the use of carfilzomib to recognize and treat baseline cardiovascular risk factors in such patients., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

In recent years, major advances in oncology especially the advent of targeted agents and immunotherapies (immune checkpoint inhibitors [ICIs] and chimeric antigen receptor [CAR] T-cell therapy) have led to improved quality of life and survival rates in patients with cancer. This article focuses on the clinical features, and grading and management of toxicities associated with ICIs and CAR T-cell therapy. In addition, because cardiotoxicity is one of the most harmful effects of anticancer therapeutics, we describe the risk factors and mechanisms of cardiovascular injury associated with newer agents, screening technologies for at-risk patients, and preventive and treatment strategies., Competing Interests: Disclosure The authors have no commercial or financial conflicts of interest related to this article., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Advances in cancer treatments have improved clinical outcomes, leading to an increasing population of cancer survivors. However, this success is associated with high rates of short- and long-term cardiovascular (CV) toxicities. The number and variety of cancer drugs and CV toxicity types make long-term care a complex undertaking. This requires a multidisciplinary approach that includes expertise in oncology, cardiology and other related specialties, and has led to the development of the cardio-oncology subspecialty. This paper aims to provide an overview of the main adverse events, risk assessment and risk mitigation strategies, early diagnosis, medical and complementary strategies for prevention and management, and long-term follow-up strategies for patients at risk of cancer therapy-related cardiotoxicities. Research to better define strategies for early identification, follow-up and management is highly necessary. Although the academic cardio-oncology community may be the best vehicle to foster awareness and research in this field, additional stakeholders (industry, government agencies and patient organizations) must be involved to facilitate cross-discipline interactions and help in the design and funding of cardio-oncology trials. The overarching goals of cardio-oncology are to assist clinicians in providing optimal care for patients with cancer and cancer survivors, to provide insight into future areas of research and to search for collaborations with industry, funding bodies and patient advocates. However, many unmet needs remain. This document is the product of brainstorming presentations and active discussions held at the Cardiovascular Round Table workshop organized in January 2020 by the European Society of Cardiology., (© 2020 European Society of Cardiology.)

Chemotherapy-associated cardiotoxicity may delay or impair the ability to administer fully myeloablative chemotherapy for stem cell transplant in those with reduced left ventricular ejection fraction. Studies in adults have been inconsistent regarding the value of ejection fraction in predicting cardiotoxicity in the posttransplant period. Recent publications, however, have demonstrated successful stem cell transplantation in adults despite low ejection fractions. This case series highlights 2 pediatric patients who were successfully treated with stem cell transplantation without posttransplant cardiac complications, despite pretransplant ejection fractions of 38% and 29%.

Background: The US Food and Drug Administration (FDA) has approved several immunotherapeutic drugs for cancer since 2010, and many more are still being evaluated in other clinical studies. These inhibitors significantly increase response rates and result in the treatment of patients with advanced cancer. However, cancer immunotherapy leads to essential cardiac toxicity properties that have become distinct from other cancer patients' care and are mostly related to their etiology., Aim of Review: As potential implications, the occurrence of cardiovascular adverse events is particularly challenging and needs a comprehensive understanding of overall cancer-related etiology, clinical outcomes with different variable severity, and management., Key Scientific Concepts of Review: In terms of improving the overall survival of patients with cancer, clinicians should be careful in selecting either programmed cell death-1 (PD-1) or its programmed cell death ligand (PDL-1) inhibitors by evaluating their risk and clinical benefit for early intervention and decrease the level of morbidity and mortality of their patients. This review focuses on the effectiveness of PD-1/PL-1 antibodies and associated cardiotoxicity adverse events, including etiological mechanisms, diagnosis, and treatment., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 Cairo University.)

Rationale: Doxorubicin is one of the most potent antitumor agents available; however, its clinical use is restricted because it poses a risk of severe cardiotoxicity. Previous work has established that CircITCH (circular RNA ITCH [E3 ubiquitin-protein ligase]) is a broad-spectrum tumor-suppressive circular RNA and that its host gene, ITCH (E3 ubiquitin protein ligase), is involved in doxorubicin-induced cardiotoxicity (DOXIC). Whether CircITCH plays a role in DOXIC remains unknown., Objective: We aimed to dissect the role of CircITCH in DOXIC and further decipher its potential mechanisms., Methods and Results: Circular RNA sequencing was performed to screen the potentially involved circRNAs in DOXI pathogenesis. Quantitative polymerase chain reaction and RNA in situ hybridization revealed that CircITCH was downregulated in doxorubicin-treated human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) as well as in the autopsy specimens from cancer patients who suffered from doxorubicin-induced cardiomyopathy. Cell death/viability assays, detection of cardiomyocyte necrosis markers, microelectrode array, and cardiomyocyte functional assays revealed that CircITCH ameliorated doxorubicin-induced cardiomyocyte injury and dysfunction. Detection of cellular/mitochondrial oxidative stress and DNA damage markers verified that CircITCH alleviated cellular/mitochondrial oxidative stress and DNA damage induced by doxorubicin. RNA pull-down assays, Ago2 immunoprecipitation and double fluorescent in situ hybridization identified miR-330-5p as a direct target of CircITCH. Moreover, CircITCH was found to function by acting as an endogenous sponge that sequestered miR-330-5p. Bioinformatic analysis, luciferase reporter assays, and quantitative polymerase chain reaction showed that SIRT6 (sirtuin 6), BIRC5 (baculoviral IAP repeat containing 5, Survivin), and ATP2A2 (ATPase sarcoplasmic/endoplasmic reticulum Ca 2+ transporting 2, SERCA2a [SR Ca 2+ -ATPase 2]) were direct targets of miR-330-5p and that they were regulated by the CircITCH/miR-330-5p axis in DOXIC. Further experiments demonstrated that CircITCH-mediated alleviation of DOXIC was dependent on the interactions between miR-330-5p and the 3'-UTRs of SIRT6, BIRC5, and ATP2A2 mRNA. Finally, AAV9 (adeno-associated virus serotype 9) vector-based overexpression of the well-conserved CircITCH partly prevented DOXIC in mice., Conclusions: CircITCH represents a novel therapeutic target for DOXIC because it acts as a natural sponge of miR-330-5p, thereby upregulating SIRT6, Survivin and SERCA2a to alleviate doxorubicin-induced cardiomyocyte injury and dysfunction.

Background: Anthracycline chemotherapy (AC) is an efficacious (neo) adjuvant treatment for early-stage breast cancer (BCa), but is associated with an increased risk of cardiac dysfunction and functional disability. Observations suggest that regular exercise may be a useful therapy for the prevention of cardiovascular morbidity but it is yet to be interrogated in a large randomised trial. The primary aims of this study are to: 1) determine if 12-months of ET commenced at the onset of AC can reduce the proportion of BCa patients with functional disability (peak VO 2 , < 18 ml/kg/min), and 2) compare current standard-of-care for detecting cardiac dysfunction (resting left-ventricular ejection fraction assessed from 3-dimensional echocardiography) to measures of cardiac reserve (peak exercise cardiac output assessed from exercise cardiac magnetic resonance imaging) for predicting the development of functional disability 12-months following AC. Secondary aims are to assess the effects of ET on VO2peak, left ventricular morphology, vascular stiffness, cardiac biomarkers, body composition, bone mineral density, muscle strength, physical function, habitual physical activity, cognitive function, and multidimensional quality of life., Methods: One hundred women with early-stage BCa (40-75 years) scheduled for AC will be randomized to 12-months of structured exercise training (n = 50) or a usual care control group (n = 50). Participants will be assessed at baseline, 4-weeks following completion of AC (4-months) and at 12-months for all measures., Discussion: Women diagnosed with early-stage BCa have increased cardiac mortality. More sensitive strategies for diagnosing and preventing AC-induced cardiovascular impairment are critical for reducing cardiovascular morbidity and improving long-term health outcomes in BCa survivors., Trial Registration: Australia & New Zealand Clinical Trials Registry (ANZCTR), ID: 12617001408370 . Registered on 5th of October 2017.

Cyclophosphamide (CP) is a nitrogen mustard alkylating agent with effective antineoplastic, immunomodulatory and immunosuppressive properties. Despite its vast therapeutic uses, it is known to trigger strict cardiac toxicity. The objective of the current study was to examine the protective role of metformin (MET) and/or low dose radiation (LDR) on cardiotoxicity and apoptosis induced by CP in rats. CP (200 mg/kg i.p) induces cardiotoxicity and apoptosis as indicated by elevation of troponin, cardiac caspase-3 and Endothelin-I (ET-1). While, treatment with MET (150 mg/kg, orally for 14 days) and/or LDR (0.5 Gy) before CP hindered CP-induced toxicity. By estimating the apoptotic index (BAX/Bcl-2 ratio) CP showed significantly the highest BAX/Bcl-2 ratio. Administration of MET and/or LDR showed a significant improvement in oxidative stress indices and reverse the inhibitory effect of CP on SIRT-1. Also, Histological examination of cardiac tissues showed a sign of necrosis of myocardium after CP treatment. Conclusions: The results revealed that MET and/or LDR attenuate CP-induced cardiotoxicity by inhibiting oxidative stress and preserving the activity of antioxidant enzymes through SIRT-1/SOD and BAX/Bcl-2 pathways.

Purpose of Review: Multiple myeloma is the second most common hematologic malignancy in the USA, with over 32,000 new cases and nearly 13,000 deaths expected in 2019. The past few decades in myeloma research have yielded significant advances, leading to the expansion of novel anti-myeloma agents. This review describes the incidence and mechanisms of cardiotoxicity for the FDA-approved proteasome inhibitors in myeloma and proposes strategies to assess and manage resultant cardiovascular adverse events., Recent Findings: Proteasome inhibition precipitates protein aggregation and alters transcriptional activation of NF-κB targets which contributes to a pro-apoptotic signaling cascade in myeloma cells. Similar effects in cardiomyocytes and vascular smooth muscle endothelium, along with off-target downregulation of autophagy and signaling alterations of nitric oxide homeostasis, may be linked to observed cardiotoxic effects. There is preliminary evidence for cardioprotective potential for rutin, dexrazoxane, and apremilast that could have clinical applicability in the future. Of the proteasome inhibitors used in clinical practice, carfilzomib is the most strongly associated with cardiotoxicity. Patients with anticipated carfilzomib treatment should undergo assessment and optimization of baseline cardiovascular risk, with close monitoring during treatment. Previous clinical trials were not specifically designed to assess proteasome inhibitor-related cardiotoxicity, creating a need for future studies to identify and risk stratify vulnerable individuals and to develop potential cardioprotective strategies in attenuating cardiac injury.

Who: This position statement is a collaborative effort by the American Academy of Clinical Toxicology (AACT) and the American Association of Poison Control Centers (AAPCC) and has been endorsed by the American College of Medical Toxicology (ACMT). The position statement describes loperamide misuse, proposed mechanisms of toxicity, adverse clinical effects, and recommendations for the acute monitoring and management of patients with loperamide toxicity. Why: Use of high-dose loperamide for its euphoric effects and to self-treat opioid use disorder (in place of evidence-based therapies, like buprenorphine or methadone), is increasing. Despite reports in the medical literature and lay press, many remain unaware of high-dose loperamide use and how to manage patients with loperamide-associated toxicities. Target audience: Providers in Emergency Medicine; Prehospital; Intensive Care; Internal Medicine; Primary Care; Gastroenterology; Addiction Medicine; Pharmacy.

Opinion Statement: Cardiovascular disease is a leading cause of death among cancer survivors. While the field of cardiology as a whole is driven by evidence generated through robust clinical trials, data in cardio-oncology is limited to a relatively small number of prospective clinical trials with heterogeneous groups of cancer patients. In addition, many pharmaceutical trials in oncology are flawed from a cardiovascular perspective because they exclude patients with significant cardiovascular (CV) history and have wide variation in the definitions of CV events and cardiotoxicity. Ultimately, oncology trials often underrepresent the possibility of cardiovascular events in a "real world" population. Thus, the signal for CV toxicity from a cancer treatment is often not manifested until phase IV studies; where we are often caught trying to mitigate the CV effects rather than preventing them. Most of the data about cardiotoxicity from cancer therapy and cardioprotective strategies has been developed from our experience in using anthracyclines for over 50 years with dramatic improvement in cancer survivorship. However, as we are in an era where cancer drug discovery is moving at lightning pace with increasing survival rates, it is imperative to move beyond anthracyclines and commit to research on the cardiovascular side effects of all aspects of cancer therapy with a focus on prevention. We emphasize the role of pre-cancer treatment CV assessment to anticipate cardiac issues and ultimately optimizing CV risk prior to cancer therapy as an opportunity to mitigate cardiovascular risk from cancer therapy.

Objective: To review the published literature on clozapine associated cardiotoxicity (CACT), summarize diagnostic features, and evaluate monitoring procedures for safe clozapine re-challenge., Results: Clozapine-associated Myocarditis (CAM) - Incidence of early myocarditis (≤2 months) is infrequent but serious. Clinical diagnosis is confounded by variability in presentation and non-specificity of symptoms. Re-challenge considerations include clozapine impact on symptomatic severity and associated disability and risk of suicidality. Re-challenging is recommended only after full clinical resolution of myocarditis and cardiac function impairment, under closely controlled conditions, starting at very low dosage, extremely slow titration and frequent assays of lab and cardio biomarkers. Clozapine associated cardiomyopathy (CAC) -develops later but mortality has been reported at 12.5-24.0%. Re-challenge is generally not recommended due to paucity of outcome data. Monitoring Cardiac Toxicity: Plausible steps include closer clinical monitoring, repeated assays of biomarkers, and echocardiographic studies, and cardiac MRI changes with unremarkable findings of cardiac dysfunction with echocardiography. Subclinical clozapine associated cardiotoxicity is more prevalent than CAM and CAC. Diagnosis is often challenging due to non specific presentation. Active monitoring is recommended. Rechallenging is feasible but should be done under close monitoring conditions. A protocol is proposed based on literature review and clinical experience in order to reduce the risk of CACT., Conclusion: Clozapine-associated myocarditis and cardiomyopathy may have been underreported worldwide. Identification of subclinical cardiotoxic effects can improve outcomes by earlier recognition before clinical manifestations of cardiac impairments. A pragmatic close clinical monitoring protocol including cardiac biomarkers aimed at timely detection of cardiac toxicity, in the initial phase of treatment is proposed., Competing Interests: Declaration of Competing Interest We declare we have no conflict of interest in preparing this manuscript, (Copyright © 2020 Elsevier B.V. All rights reserved.)

Advances in cancer screening and improved treatment approaches have led to an increase in survivorship and, consequently, recognition of an association between cancer treatments and the development of cardiovascular complications. In addition, as the population becomes proportionally older, comorbid cardiovascular risk factors are more prevalent in the population and compound the risk of developing cancer treatment-related cardiovascular toxicity. Cardio-oncology has emerged as a new subspecialty of medicine that provides a multidisciplinary approach, bringing together oncologists, cardiologists, and allied health care providers who are tasked with optimizing the cardiovascular health of patients exposed to potentially cardiotoxic cancer therapy. Using a case-based approach, practical advice on how to identify, monitor, and treat patients with cancer who are at risk for developing cancer treatment-related cardiovascular dysfunction is discussed. Cardiovascular risk factors (e.g., age, hypertension, diabetes) and cancer therapies (chemotherapy, targeted therapy, radiation) associated with cardiovascular toxicity are presented. Current cardiac monitoring strategies such as two- and three-dimensional echocardiography, cardiac MRI, and biomarkers (troponin and brain natriuretic peptide [BNP]) are discussed. Last, the current literature on pharmacologic (e.g., angiotensin-converting enzyme inhibitors, β-blockers, statins) and lifestyle (diet and exercise) strategies to mitigate cardiovascular toxicity during and following completion of cancer therapy are reviewed.

Background: The use of immune checkpoint inhibitors has dramatically improved the prognosis of many cancer patients. However, their increasing use has also revealed several unexpected side effects - including cardiovascular complications. Increased attention was paid to them in recent years only, especially due to their potentially fatal character. Checkpoint inhibitors cardiotoxicity includes myocarditis, rhythm disorders (atrioventricular blocks, atrial and ventricular arrhythmias), pericarditis, myocardial infarction, left ventricular dysfunction/heart failure, dilated cardiomyopathy, cardiogenic shock and sudden cardiac death. The risk of ICI-associated cardiotoxicity is increased in patients treated with dual immune therapy, in combination with other cardiotoxic drugs, with preexisting cardiac damage, diabetes mellitus, underlying autoimmune disease and some other factors. Currently, there are no guidelines for prediction and management of ICI-associated cardiotoxicity., Purpose: Herein, we briefly summarize the findings regarding checkpoint inhibitor-induced cardiotoxicity and provide a new definition of anti-tumor-induced myocarditis together with a suitable design for immune- induced myocarditis management prepared by experts from the field of cardiooncology.

Objectives: To examine and summarize current international guidelines regarding cardiovascular risk reduction before and during cancer therapy, and to discuss the emerging role of cardio-oncology as a subspecialty in cancer care and the role of cardio-oncology rehabilitation., Data Sources: Published articles and guidelines., Conclusion: With improvements in cancer detection and the use of novel adjuvant therapies, an increasing number of individuals now survive a cancer diagnosis. However, for some the cost is high - many survivors are now at higher risk of death from cardiovascular disease than from recurrent cancer. Cardiovascular morbidity and mortality are common and associated with common cancer therapies serially administered in adult oncology care., Implications for Nursing Practice: Timely risk-reduction interventions hold promise in reducing cardiovascular morbidity and mortality. Oncology nurses are the key providers to identify baseline risks, perform necessary referrals, provide individualized teaching, and support the patient within the family and community., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Cardiac arrest (CA) is a public health problem, with various etiologies and a fatal issue in 90-95% of cases. Toxin-induced cardiac arrests (TICA) are poorly described. Scarcity of national data prompted us to carry-out this study., Aim: To determine TICA frequency in a Tunisian reference center in toxicology and its hospital prognosis, and to describe its clinical and therapeutic aspects Methods : Data were collected retrospectively over an 8-years period. We included patients admitted for post-CA care with highly suspected or confirmed TICA. Clinical and toxicological data were recorded., Results: We recorded 21 cases of TICA, which represented 48.8% of CA. A single toxic agent was incriminated in 90% of cases. Main causative agents identified in our series were pesticides and betablockers: chloralosed (n = 6), carbamate inhibitor of cholinesterase (n = 5), acebutolol (n = 4) and organophosphate (n = 2). One case of opiates and cocaine poisoning was reported. Median duration of "no flow" was 0 minutes. Mean duration of "low flow" was 13.74±9.15 minutes. An initial shockable rhythm was noted only in three patients. Mortality rate was 76% (16/21). Four of the five survivors had a Cerebral Performance Category Scale (CPC) 1, only one patient survived with a CPC 3. Factors associated with mortality were : the duration of "low flow" (p=0.02) and APACHE II score (p=0.014). APACHE II≥29 was the only independent factor (OR=2.0, 95%CI [1.07;3.71])., Conclusion: TICA were most frequently provoked by pesticides, mortality was high and was independently predicted by APACHE II score.

Immune checkpoint inhibitors (ICIs) targeting programmed death-1 (PD-1), its ligand (PD-L1), and cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) have revolutionized cancer treatment by recovering the attack of T lymphocytes on the malignant cells. They have improved clinical outcomes dramatically in multiple types of advanced-stage malignancies. Even though the tolerance and safety profiles are generally good, it has been widely reported that ICIs can cause severe or fatal immune-related adverse events (irAEs), since the activated T lymphocytes are not specific for tumor cells. Cardiac irAEs appear to occur less frequently than irAEs in other organ systems but are notorious for high mortality. Here, we aim to identify and characterize the ICI-associated cardiotoxicity and summarize the optional diagnosis and treatment strategies., (© 2019 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

The growing success of immune checkpoint inhibitors (ICIs) has led to effectively treating several types of cancers. Even though their use has been associated with the development of cardiac adverse effects, which may decrease the overall survival in cancer patients. These cardiac toxicities are thought to be the result of targeting specific checkpoint proteins on normal myocardial cells leading to over stimulation of the immune system as well as secondary downstream off-target effects on normal tissue.Although cardiotoxicities related to immunotherapy are reportedly rare, they can be severe and associated with life-threatening conditions such as fulminant myocarditis, hemodynamic instability, and cardiac arrest.We will review the most commonly reported cardiovascular toxicities associated with ICIs and their management.

Cardiovascular (CV) disease is a common comorbidity in acute leukemia (AL) patients and can be worsened by the use of anthracyclines. Interruptions and underutilization of CV medications during AL treatments may negatively impact the CV health of these patients. A 30-question electronic survey was distributed to Canadian hematologists who treat adults with AL to determine the frequency, timing and rationale for interruptions in statins, antiplatelets and angiotensin antagonists in patients undergoing intensive chemotherapy. Strategies for mitigating anthracycline cardiotoxicity, methods of establishing baseline CV risk and utilization of clinical pharmacists were also assessed. Results indicate that it is common for AL patients undergoing intensive chemotherapy to require CV medication interruptions. This highlights the need for collaboration between hematology and cardiology healthcare teams and utilization of multidisciplinary healthcare professionals to improve CV care during AL.

Doxorubicin (Dox) is an effective antineoplastic agent used to treat cancers, but its use is limited as Dox induces adverse cardiotoxic effects. Dox-induced cardiotoxicity (DIC) can lead to heart failure and death. There is no study that investigates whether embryonic stem cell-derived exosomes (ES-Exos) in DIC can attenuate inflammation-induced pyroptosis, pro-inflammatory M1 macrophages, inflammatory cell signaling, and adverse cardiac remodeling. For this purpose, we transplanted ES-Exos and compared with ES-cells (ESCs) to examine pyroptosis, inflammation, cell signaling, adverse cardiac remodeling, and their influence on DIC induced cardiac dysfunction. Therefore, we used C57BL/6J mice ages 10 ± 2 weeks and divided them into four groups ( n = 6-8/group): Control, Dox, Dox + ESCs, and Dox + ES-Exos. Our data shows that the Dox treatment significantly increased expression of inflammasome markers (TLR4 and NLRP3), pyroptotic markers (caspase-1, IL1-β, and IL-18), cell signaling proteins (MyD88, p-P38, and p-JNK), pro-inflammatory M1 macrophages, and TNF-α cytokine. This increased pyroptosis, inflammation, and cell signaling proteins were inhibited with ES-Exos or ESCs. Moreover, ES-Exos or ESCs increased M2 macrophages and anti-inflammatory cytokine, IL-10. Additionally, ES-Exos or ESCs treatment inhibited significantly cytoplasmic vacuolization, myofibril loss, hypertrophy, and improved heart function. In conclusion, for the first time we demonstrated that Dox-induced pyroptosis and cardiac remodeling are ameliorated by ES-Exos or ESCs.

Purpose of Review: This review highlights the literature related to pericardial injury following radiation for oncologic diseases., Recent Findings: Radiation-associated pericardial disease can have devastating consequences. Unfortunately, there is considerably less evidence regarding pericardial syndromes following thoracic radiation as compared to other cardiovascular outcomes. Pericardial complications of radiation may arise acutely or have an insidious onset several decades after treatment. Transthoracic echocardiography is the screening imaging modality of choice, while cardiac magnetic resonance imaging further characterizes the pericardium and guides treatment decision-making. Cardiac CT can be useful for assessing pericardial calcification. Ongoing efforts to lessen inadvertent cardiac injury are directed towards the revision of radiation techniques and protocols. As survival of mediastinal and thoracic malignancies continues to improve, radiation-associated pericardial disease is increasingly relevant. Though advances in radiation oncology demonstrate promise in curtailing cardiotoxicity, the long-term effects pertaining to pericardial complications remain to be seen.

Introduction : Intravenous lipid emulsion (ILE) administration is capable of reversing the acute cardiac and neurological toxicity caused by local anesthetic agents. In recent years, ILE has also been explored as a potential antidote for cardiotoxicity caused by non-anesthetic agents too. Areas covered : The potential mechanisms, safety, and efficacy of this approach are considered. Data were sought from published reports listed in PubMed and EMBASE, and abstracts of meetings of the North American Congress of Clinical Toxicology and European Association of Poisons Centres and Clinical Toxicologists. There were reports involving 298 patients where ILE has been administered for severe drug toxicity. Clinical improvement was observed in 57 of 59 patients with local anesthetic toxicity (96.6%); there were 239 patients where toxicity was due to non-anesthetic agents, and ILE apparently improved clinical outcome in 215 (72.1%). Expert opinion : Response rates were similar between ILE treated toxicity caused by lipid soluble and non-lipid soluble drugs. Potential adverse effects of ILE include interference with laboratory assays, acute pancreatitis, and adult respiratory distress syndrome, although the rate of occurrence is difficult to ascertain.

The cardiotoxic adverse effect of doxorubicin (DOX) is the major factor limiting its use. Recently, mesenchymal stem cells (MSCs) have been implicated in the preclinical studies of treatment of DOX-induced cardiotoxicity. The question is MSCs pretreated with platelet-rich plasma (PRP) have a better influence on DOX-induced cardiotoxicity compared to the influence of MSCs alone. Twenty-four Wistar rats were categorized into control, DOX-treated, MSC-treated, and PRP/MSC-treated groups. DOX was injected for two consecutive weeks. Light microscopic, biochemical markers (interleukin 10 (IL-10), tumor necrosis factor alpha (TNF-α), and creatine kinase-MB (CK-MB)), immunohistochemical (Bax, Bcl2, vascular endothelial growth factor (VEGF), and cardiac troponin-I (CT-I)), and oxidative/antioxidative markers (malondialdehyde (MDA)/superoxide dismutase (SOD)) were measured. Degenerative cardiac changes were detected in the DOX-treated group with complete loss of the architecture and coagulative necrosis. These changes were accompanied with the elevation of the serum level of CK-MB and loss of CT-I immunoreactivity. The major factors in the DOX-induced cardiotoxicity were the oxidative stress (elevated MDA/decreased SOD), inflammation (elevated TNF-α/decreased IL-10), and cardiac apoptosis (lower Bcl2, higher Bax, and lower Bcl2/Bax ratio). MSCs and PRP/MSCs attenuate DOX-induced cardiotoxicity. Better attenuation was observed in the PRP/MSC-treated group. PRP/MSC combination reduced greatly the MDA and TNF-α and increased IL-10, Bcl2/Bax ratio, and VEGF. PRP had no significant influence over the Bcl2, Bax, and SOD. In conclusion, DOX in its toxic dose induced myocardial injury. This destructive effect is related to oxidative stress, inflammation, and cardiac apoptosis. PRP/MSC possesses a better attenuation over the DOX-induced toxicity compared to MSC alone.

Opinion Statement: The past 5 decades have seen significant improvements in outcomes for pediatric patients with cancer. Unfortunately, children and adolescents who have been treated for cancer are five to six times more likely to develop cardiovascular disease as a result of their therapies. Cardiovascular disease may manifest in a plethora of ways, from asymptomatic ventricular dysfunction to end-stage heart failure, hypertension, arrhythmia, valvular disease, early coronary artery disease, or peripheral vascular disease. A number of treatment modalities are implicated in pediatric and adult populations, including anthracyclines, radiation therapy, alkylating agents, targeted cancer therapies (small molecules and antibody therapies), antimetabolites, antimicrotubule agents, immunotherapy, interleukins, and chimeric antigen receptor T cells. For some therapies, such as anthracyclines, the mechanism of injury is elucidated, but for many others it is not. While a few protective strategies exist, in many cases, observation and close monitoring is the only defense against developing end-stage cardiovascular disease. Because of the variety of potential outcomes after cancer therapy, a one-size-fits-all approach is not appropriate. Rather, a good working relationship between oncology and cardiology to assess the risks and benefits of various therapies and planning for appropriate surveillance is the best model. When disease is identified, any of a number of therapies may be appropriate; however, in the pediatric and adolescent population supportive data are limited.

Opinion Statement: Treatment-related cardiotoxicity remains a significant concern for breast cancer patients undergoing cancer treatment and extends into the survivorship period, with adverse cardiovascular (CV) outcomes further compounded by the presence of pre-existing CV disease or traditional CV risk factors. Awareness of the cardiotoxicity profiles of contemporary breast cancer treatments and optimization of CV risk factors are crucial in mitigating cardiotoxicity risk. Assessment of patient- and treatment-specific risk with appropriate CV surveillance is another key component of care. Mismatch between baseline cardiotoxicity risk and intensity of cardiotoxicity surveillance can lead to unnecessary downstream testing, increased healthcare expenditure, and interruption or discontinuation of potentially life-saving treatment. Efforts to identify early imaging and/or circulating biomarkers of cardiotoxicity and develop effective management strategies are needed to optimize the CV and cancer outcomes of breast cancer survivors.

Purpose of Review: The number of cancer survivors is increasing, and cardiovascular events are a significant cause of morbidity and mortality in these patients. Preexisting cardiovascular conditions as well as the development of cancer therapeutics-related cardiac dysfunction (CTRCD), in particular left ventricular dysfunction and heart failure, limit the options for cancer therapies for these patients and contribute to reduced cancer survival., Recent Findings: Recent guidelines and position statements from various cardiology and oncology societies provide an outline for the practicing physician for the management of CTRCD. However, this is largely based on data extrapolated from the general heart failure population (including patients without cancers) and is not based on strong evidence. There is now emerging evidence for the prevention and treatment of heart failure related to certain established chemotherapeutic drugs, whereas there is lack of trials for specific cardioprotective strategies to reduce cardiotoxicity of newer targeted cancer therapies., Summary: In this article, we discuss the most recent literature for the management of asymptomatic left ventricular dysfunction and heart failure related to chemotherapy, from prevention to the use of goal-directed medical therapies as well as discuss the role for advanced heart failure treatment in this population.

Background: Carfilzomib, a proteasome inhibitor, known as a therapeutical option for people who have already received one or more previous treatments for multiple myeloma, has well known cardiac and systemic adverse effects., Objective: There is evidence supporting that adverse effects are dose dependent, yet there is no known patient phenotype characterized by worse associated consequences, nor are there widely accepted monitoring protocols., Results: In this article we describe two patients with cardiovascular adverse events related to carfilzomib treatment and their clinical course. Our goal was to present two cases of daily practice, which highlighted the complexity of their management and led to underline how baseline evaluation and close follow-up with echocardiography and cardiac biomarkers, including natriuretic peptides, remain an important tool for the cardiotoxicity surveillance., Conclusion: These reflections should lead to further studies in order to identify high risk patients for cardiovascular adverse event and clarify the real incidence of cardiotoxicity of this drug and adequate follow-up timing. Finally further research is needed to evaluate strategies for prevention and attenuation of cardiovascular complications of cancer therapy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The NCCN Guidelines for Survivorship provide screening, evaluation, and treatment recommendations for common physical and psychosocial consequences of cancer and cancer treatment to help healthcare professionals who work with survivors of adult-onset cancer in the posttreatment period. This portion of the guidelines describes recommendations regarding the management of anthracycline-induced cardiotoxicity and lymphedema. In addition, recommendations regarding immunizations and the prevention of infections in cancer survivors are included., (Copyright © 2018 by the National Comprehensive Cancer Network.)

Background: Anthracycline chemotherapy agents are commonly used to treat breast cancer, but also result in cardiac injury, and potentially detrimental effects to vascular and skeletal muscle. Preclinical evidence demonstrates that exercise and caloric restriction can independently reduce anthracycline-related injury to the heart as well as cancer progression, and may be promising short-term strategies prior to treatment administration. For women with breast cancer, a short-term strategy may be more feasible and appealing, as maintaining regular exercise training or a diet throughout chemotherapy can be challenging due to treatment symptoms and psychosocial distress., Methods: The Caloric Restriction and Exercise protection from Anthracycline Toxic Effects (CREATE) study will determine whether acute application of these interventions shortly prior to receipt of each treatment can reduce anthracycline-related toxicity to the heart, aorta, and skeletal muscle. Fifty-six women with early stage breast cancer scheduled to receive anthracycline treatment will be randomly assigned to one of three groups who will: 1) perform a single, 30-min, vigorous-intensity, aerobic exercise session 24 h prior to each anthracycline treatment; 2) consume a prepared diet reduced to 50% of caloric needs for 48 h prior to each anthracycline treatment; or 3) receive usual cancer care. The primary outcome is magnetic resonance imaging (MRI) derived left ventricular ejection fraction reserve (peak exercise LVEF - resting LVEF) at the end of anthracycline treatment. Secondary outcomes include MRI-derived measures of cardiac, aortic and skeletal muscle structure and function, circulating NT-proBNP, cardiorespiratory fitness and treatment symptoms. Exploratory outcomes include quality of life, fatigue, tumor size (only in neoadjuvant patients), oxidative stress and antioxidants, as well as clinical cardiac or cancer outcomes. MRI, exercise tests, and questionnaires will be administered before, 2-3 weeks after the last anthracycline treatment, and one-year follow-up., Discussion: The proposed lifestyle interventions are accessible, low cost, drug-free potential methods for mitigating anthracycline-related toxicity. Reduced toxic effects on the heart, aorta and muscle are very likely to translate to short and long-term cardiovascular health benefits, including enhanced resilience to the effects of subsequent cancer treatment (e.g., radiation, trastuzumab) aging, and infection., Trial Registration: ClinicalTrials.gov NCT03131024; 4/21/18.

Cardiovascular diseases are among the most significant causes of mortality in humans. Pesticides toxicity and risk for human health are controlled at a European level through a well-developed regulatory network, but cardiotoxicity is not described as a separate hazard class. Specific classification criteria should be developed within the frame of Regulation (EC) No 1272/2008 in order to classify chemicals as cardiotoxic, if applicable to avoid long-term cardiovascular complications. The aim of this study was to review the cardiac pathology and function impairment due to exposure to pesticides (i.e. organophosphates, organothiophisphates, organochlorines, carbamates, pyrethroids, dipyridyl herbicides, triazoles, triazines) based on both animal and human data. The majority of human data on cardiotoxicity of pesticides come from poisoning cases and epidemiological data. Several cardiovascular complications have been reported in animal models including electrocardiogram abnormalities, myocardial infarction, impaired systolic and diastolic performance, functional remodeling and histopathological findings, such as haemorrhage, vacuolisation, signs of apoptosis and degeneration., (Copyright © 2018. Published by Elsevier Inc.)