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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.)