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Luo Y, Liu J, Qu P, Han S, Li X, Wang Y, Su X, Zeng J, Li J, Deng S, Liang Q, Hou L, Cheng P. The crosstalk of breast cancer and ischemic heart disease. Cell Death Discov 2025; 11:185. [PMID: 40251177 PMCID: PMC12008236 DOI: 10.1038/s41420-025-02428-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2024] [Revised: 03/07/2025] [Accepted: 03/21/2025] [Indexed: 04/20/2025] Open
Abstract
In recent years, the continuous optimization of anti-tumor therapy has greatly improved the cancer-specific survival rate for patients with breast cancer (BC). The prevention and treatment of breast cancer-related heart diseases have become a new breakthrough in improving the long-term survival for BC patient. The cardiac damages caused by BC treatment are increasingly prominent among BC patients, of which ischemic heart disease (IHD) is the most prominent. Besides, the systemic inflammatory response activated by tumor microenvironment c an induce and exacerbate IHD and increase the risk of myocardial infarction (MI). Conversely, IHD can also exert detrimental effects on tumors. MI not only increases the risk of BC, but also induces specialized immune cell to BC and accelerates the progression of BC. Meanwhile, the treatment of IHD can also promote BC metastasis and transition to more aggressive phenotypes. Although BC and IHD are diseases of two independent systems, their crosstalk increases the difficulty of anti-cancer treatment and IHD management, which reduces the survival for both diseases. Therefore, this review mainly explores the mutual influence and underlying mechanisms between BC and IHD, aiming to provide insights for improving the long-term survival for patients with BC or IHD.
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Affiliation(s)
- Yunbo Luo
- Department of Breast Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, 610041, China
- Department of Academician (expert) Workstation, Biological Targeting Laboratory of Breast Cancer, Breast and Thyroid Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, 637000, P. R. China
| | - Jun Liu
- Institute of Cardiovascular Diseases & Department of Cardiology, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, P.R. China
| | - Peng Qu
- Department of Clinical Laboratory, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, People's Republic of China
- School of Laboratory Medicine, North Sichuan Medical College, Nanchong, 637007, People's Republic of China
- Translational Medicine Research Center, North Sichuan Medical College, Nanchong, 637007, People's Republic of China
| | - Shiqi Han
- Department of Academician (expert) Workstation, Biological Targeting Laboratory of Breast Cancer, Breast and Thyroid Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, 637000, P. R. China
| | - Xue Li
- Department of Clinical Laboratory, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, People's Republic of China
- School of Laboratory Medicine, North Sichuan Medical College, Nanchong, 637007, People's Republic of China
- Translational Medicine Research Center, North Sichuan Medical College, Nanchong, 637007, People's Republic of China
| | - Yali Wang
- Department of Academician (expert) Workstation, Biological Targeting Laboratory of Breast Cancer, Breast and Thyroid Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, 637000, P. R. China
| | - Xiaohan Su
- Department of Breast Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, 610041, China
| | - Jiao Zeng
- Department of Academician (expert) Workstation, Biological Targeting Laboratory of Breast Cancer, Breast and Thyroid Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, 637000, P. R. China
| | - Jinsui Li
- Department of Academician (expert) Workstation, Biological Targeting Laboratory of Breast Cancer, Breast and Thyroid Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, 637000, P. R. China
| | - Shishan Deng
- Department of Academician (expert) Workstation, Biological Targeting Laboratory of Breast Cancer, Breast and Thyroid Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, 637000, P. R. China
| | - Qi Liang
- Department of Clinical Laboratory, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, People's Republic of China.
- School of Laboratory Medicine, North Sichuan Medical College, Nanchong, 637007, People's Republic of China.
- Translational Medicine Research Center, North Sichuan Medical College, Nanchong, 637007, People's Republic of China.
| | - Lingmi Hou
- Department of Breast Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, 610041, China.
| | - Panke Cheng
- Institute of Cardiovascular Diseases & Department of Cardiology, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, P.R. China.
- Ultrasound in Cardiac Electrophysiology and Biomechanics Key Laboratory of Sichuan Province, Chengdu, 610072, P.R. China.
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Thompson JT, Wood DM, Dargan PI. Review of the fluoropyrimidine antidote uridine triacetate. Br J Clin Pharmacol 2025; 91:615-627. [PMID: 39468799 DOI: 10.1111/bcp.16319] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Revised: 09/24/2024] [Accepted: 09/26/2024] [Indexed: 10/30/2024] Open
Abstract
In 2015, the United States Food and Drug Administration (FDA) approved uridine triacetate to treat overdose and severe toxicity of the fluoropyrimidine chemotherapy agents 5-fluorouracil (5-FU) and its oral prodrug capecitabine. Uridine triacetate is as an oral prodrug of uridine that competes with cytotoxic fluoropyrimidine metabolites for incorporation into nucleotides. Two million people worldwide start fluoropyrimidine chemotherapy each year, with 20-30% developing severe or life-threatening adverse effects, often attributable to a genetic predisposition such as dihydropyrimidine dehydrogenase deficiency. Whilst genetic prescreening is recommended prior to starting fluoropyrimidine agents, this only prevents 20-30% of early-onset life-threatening toxicity and so does not obviate the need for an antidote. Initial in-human studies established that uridine triacetate more than doubles the maximum tolerated weekly 5-FU bolus dose. A lack of clinical equipoise meant a placebo-controlled phase III trial was not ethical and so the phase III trials used historical controls. These found that uridine triacetate improved survival in those with fluoropyrimidine overdose and severe toxicity from 16% to 94%, with 34% able to resume chemotherapy within 30 days. Five case reports of delayed fluoropyrimidine toxicity demonstrate improvement following uridine triacetate treatment 120-504 h after last fluoropyrimidine administration, suggesting efficacy beyond the FDA licencing indications. Mechanistically uridine triacetate would be expected to be effective for overdose and severe toxicity of tegafur (a 5-FU prodrug), but there are no published case reports describing this. Uridine triacetate is available internationally through an expanded access scheme and has been available in the UK since 2019 on a named patient basis.
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Affiliation(s)
- Jack T Thompson
- Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - David M Wood
- Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust, London, UK
- Faculty of Life Sciences and Medicine, King's College London, London, UK
| | - Paul I Dargan
- Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust, London, UK
- Faculty of Life Sciences and Medicine, King's College London, London, UK
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Meng C, Wang Y, Zheng T, Rong Z, Lv Z, Wu C, Zhou X, Mao W. A novel approach to the prevention and management of chemotherapy-induced cardiotoxicity: PANoptosis. Chem Biol Interact 2025; 407:111379. [PMID: 39788474 DOI: 10.1016/j.cbi.2025.111379] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2024] [Revised: 12/31/2024] [Accepted: 01/07/2025] [Indexed: 01/12/2025]
Abstract
As a fundamental component of antitumor therapy, chemotherapy-induced cardiotoxicity (CIC) has emerged as a leading cause of long-term mortality in patients with malignant tumors. Unfortunately, there are currently no effective therapeutic preventive or treatment strategies, and the underlying pathophysiological mechanisms of CIC remain inadequately understood. A growing number of studies have shown that different mechanisms of cell death, such as apoptosis, pyroptosis, and necroptosis, are essential for facilitating the cardiotoxic effects of chemotherapy. The PANoptosis mode represents a highly synchronized and dynamically balanced programmed cell death (PCD) process that integrates the principal molecular characteristics of necroptosis, apoptosis, and pyroptosis. Recent research has revealed a significant correlation between PANoptosis and the apoptosis of tumor cells. Chemotherapy drugs can activate PANoptosis, which is involved in the development of cardiovascular diseases. These findings suggest that PANoptosis marks the point where the effectiveness of chemotherapy against tumors overlaps with the onset and development of cardiovascular diseases. Furthermore, previous studies have demonstrated that CIC can simultaneously induce pyrodeath, apoptosis, and necrotic apoptosis. Therefore, PANoptosis may represent a potential mechanism and target for the prevention of CIC. This study explored the interactions among the three main mechanisms of PCD, pyroptosis, apoptosis, and necroptosis in CICs and analyzed the relevant literature on PANoptosis and CICs. The purpose of this work is to serve as a reference for future investigations on the role of PANoptosis in the development and mitigation of cardiotoxicity associated with chemotherapy.
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Affiliation(s)
- Chenchen Meng
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, 310053, Hangzhou, China
| | - Yali Wang
- Department of Cardiology, Zhejiang Hospital (Affiliated Zhejiang Hospital, Zhejiang University School of Medicine), Hangzhou, Zhejiang, 310007, China
| | - Tiantian Zheng
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, 310053, Hangzhou, China
| | - Zheng Rong
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, 310053, Hangzhou, China
| | - Zhengtian Lv
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, 310053, Hangzhou, China
| | - Chenxia Wu
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, 310053, Hangzhou, China; Department of Cardiology, Zhejiang Hospital (Affiliated Zhejiang Hospital, Zhejiang University School of Medicine), Hangzhou, Zhejiang, 310007, China
| | - Xinbin Zhou
- Department of Cardiology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), 310006, Hangzhou, Zhejiang, China.
| | - Wei Mao
- Department of Cardiology, Zhejiang Hospital (Affiliated Zhejiang Hospital, Zhejiang University School of Medicine), Hangzhou, Zhejiang, 310007, China; Zhejiang Key Laboratory of Integrative Chinese and Western Medicine for Diagnosis and Treatment of Circulatory Diseases, Zhejiang Hospital (Affiliated Zhejiang Hospital, Zhejiang University School of Medicine), Hangzhou, Zhejiang, 310007, China; Zhejiang Engineering Research Center for Precise Diagnosis and Innovative Traditional Chinese Medicine for Cardiovascular Diseases, Zhejiang Hospital (Affiliated Zhejiang Hospital, Zhejiang University School of Medicine), Hangzhou, Zhejiang, 310007, China.
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Hwang HJ, Han SA, Sohn IS. Breast Cancer and Therapy-Related Cardiovascular Toxicity. J Breast Cancer 2024; 27:147-162. [PMID: 38769686 PMCID: PMC11221208 DOI: 10.4048/jbc.2024.0085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Revised: 04/10/2024] [Accepted: 04/23/2024] [Indexed: 05/22/2024] Open
Abstract
The global incidence of breast cancer is on the rise, a trend also observed in South Korea. However, thanks to the rapid advancements in anticancer therapies, survival rates are improving. Consequently, post-treatment health and quality of life for breast cancer survivors are emerging as significant concerns, particularly regarding treatment-related cardiotoxicity. In this review, we delve into the cardiovascular complications associated with breast cancer treatment, explore surveillance protocols for early detection and diagnosis of late complications, and discuss protective strategies against cardiotoxicity in breast cancer patients undergoing anticancer therapy, drawing from multiple guidelines.
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Affiliation(s)
- Hui-Jeong Hwang
- Department of Cardiology, Kyung Hee University College of Medicine, Kyung Hee University Hospital at Gangdong, Seoul, Korea
| | - Sang-Ah Han
- Department of Surgery, Kyung Hee University College of Medicine, Kyung Hee University Hospital at Gangdong, Seoul, Korea
| | - Il Suk Sohn
- Department of Cardiology, Kyung Hee University College of Medicine, Kyung Hee University Hospital at Gangdong, Seoul, Korea.
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Kong MW, Sun FD, Pei ZY, Xu L, Wang ZB, Chen Y, Tang SQ, Yang TF, He GX. Cardiotoxicity induced by fluoropyrimidine drugs in the treatment of gastrointestinal tumors. World J Gastrointest Oncol 2024; 16:251-254. [PMID: 38425398 PMCID: PMC10900142 DOI: 10.4251/wjgo.v16.i2.251] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2023] [Revised: 12/28/2023] [Accepted: 01/19/2024] [Indexed: 02/02/2024] Open
Abstract
In this editorial, we review the article published in World J Gastrointest Oncol 2019, 11: 1031-1042. We specifically focus on the occurrence, clinical characteristics, and risk factors of fluoropyrimidine drug-related cardiotoxicity in patients with gastrointestinal tumors. Despite significant advancements in diagnostic and therapeutic techniques that have reduced mortality rates associated with digestive system tumors, the incidence and mortality rates of treatment-related cardiotoxicity have been increasing, severely impacting the survival and prognosis of cancer patients. Fluoropyrimidine drugs are widely used as antimetabolites in the treatment of malignant tumors, including gastrointestinal tumors, and they represent the second largest class of drugs associated with cardiotoxicity. However, there is often a lack of awareness or understanding regarding their cardiotoxic effects and associated risks.
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Affiliation(s)
- Mo-Wei Kong
- Department of Cardiology, Guiqian International General Hospital, Guiyang 550018, Guizhou Province, China
| | - Feng-Di Sun
- Department of Cardiology, Guiqian International General Hospital, Guiyang 550018, Guizhou Province, China
| | - Zhen-Ying Pei
- Department of Cardiology, Guiqian International General Hospital, Guiyang 550018, Guizhou Province, China
| | - Li Xu
- Department of Cardiology, Guiqian International General Hospital, Guiyang 550018, Guizhou Province, China
| | - Ze-Bi Wang
- Department of Cardiology, Guiqian International General Hospital, Guiyang 550018, Guizhou Province, China
| | - Yan Chen
- Department of Cardiology, Guiqian International General Hospital, Guiyang 550018, Guizhou Province, China
| | - Shu-Qing Tang
- Department of Cardiology, Guiqian International General Hospital, Guiyang 550018, Guizhou Province, China
| | - Ting-Fang Yang
- Department of Oncology, Guiqian International General Hospital, Guiyang 550018, Guizhou Province, China
| | - Guo-Xiang He
- Department of Cardiology, Guiqian International General Hospital, Guiyang 550018, Guizhou Province, China
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Rajaeinejad M, Parhizkar-Roudsari P, Khoshfetrat M, Kazemi-Galougahi MH, Mosaed R, Arjmand R, Mohsenizadeh SA, Arjmand B. Management of Fluoropyrimidine-Induced Cardiac Adverse Outcomes Following Cancer Treatment. Cardiovasc Toxicol 2024; 24:184-198. [PMID: 38324115 DOI: 10.1007/s12012-024-09834-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2023] [Accepted: 01/20/2024] [Indexed: 02/08/2024]
Abstract
Advancements in cancer treatments have improved survival rates but have also led to increased cardiotoxicities, which can cause adverse cardiovascular events or worsen pre-existing conditions. Herein, cardiotoxicity is a severe adverse effect of 5-fluorouracil (5-FU) therapy in cancer patients, with reported incidence rates ranging from 1 to 20%. Some studies have also suggested subclinical effects and there are reports which have documented instances of cardiac arrest or sudden death during 5-FU treatment, highlighting the importance of timely management of cardiovascular symptoms. However, despite being treated with conventional medical approaches for this cardiotoxicity, a subset of patients has demonstrated suboptimal or insufficient responses. The frequent use of 5-FU in chemotherapy and its association with significant morbidity and mortality indicates the need for a greater understanding of 5-FU-associated cardiotoxicity. It is essential to reduce the adverse effects of anti-tumor medications while preserving their efficacy, which can be achieved through drugs that mitigate toxicity associated with these drugs. Underpinning cardiotoxicity associated with 5-FU therapy also has the potential to offer valuable guidance in pinpointing pharmacological approaches that can be employed to prevent or ameliorate these effects. The present study provides an overview of management strategies for cardiac events induced by fluoropyrimidine-based cancer treatments. The review encompasses the underlying molecular and cellular mechanisms of cardiotoxicity, associated risk factors, and diagnostic methods. Additionally, we provide information on several available treatments and drug choices for angina resulting from 5-FU exposure, including nicorandil, ranolazine, trimetazidine, ivabradine, and sacubitril-valsartan, which have demonstrated potential in mitigating or protecting against chemotherapy-induced adverse cardiac effects.
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Affiliation(s)
- Mohsen Rajaeinejad
- AJA Cancer Epidemiology Research and Treatment Center (AJA-CERTC), AJA University of Medical Sciences, Tehran, Iran
| | - Peyvand Parhizkar-Roudsari
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical sciences, Tehran, Iran
- Iranian Cancer Control Center, Tehran, Iran
| | - Mehran Khoshfetrat
- Department of Cardiology, School of Medicine, AJA University of Medical Sciences, Tehran, Iran
| | | | - Reza Mosaed
- Infection Diseases Research Center, AJA University of Medical Sciences, Tehran, Iran
- Student Research Committee, AJA University of Medical Sciences, Tehran, Iran
| | - Rasta Arjmand
- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Babak Arjmand
- Department of Internal Medicine, School of Medicine, AJA University of Medical Sciences, Tehran, Iran.
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Xia Y, Gu M, Wang J, Zhang X, Shen T, Shi X, Yuan WE. Tumor microenvironment-activated, immunomodulatory nanosheets loaded with copper(II) and 5-FU for synergistic chemodynamic therapy and chemotherapy. J Colloid Interface Sci 2024; 653:137-147. [PMID: 37713912 DOI: 10.1016/j.jcis.2023.09.042] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Revised: 08/18/2023] [Accepted: 09/08/2023] [Indexed: 09/17/2023]
Abstract
The tumor microenvironment (TME) has a redox state that differs greatly from normal tissues, as characterized by the overexpression of H2O2 and glutathione (GSH). To address the GSH-related restrictions on chemodynamic therapy (CDT) efficacy, we have developed a Cu(II)-based CDT strategy. In this study, a novel organic-inorganic hybrid drug delivery system (LDH/HA/5-FU) was conceived and prepared by the intercalation of 5-FU into the interlayer of copper-aluminum layered double hydroxide (CuAl-LDH) via ion exchange strategy and the adsorption of hyaluronic acid (HA) on the surface of CuAl-LDH. Taking advantage of the pH-degradable property of CuAl-LDH and the CD44-targeting property of HA, the formed LDH/HA/5-FU nanosheets could specifically target tumor cells' overexpressing CD44 receptor, rapidly release Cu(II) and 5-FU in tumor cells, inducing tumor cell apoptosis and cuproptosis, and long-term intracellular GSH depletion and toxic hydroxyl radicals (·OH) generation could be achieved through the cyclic catalytic reaction of Cu(I)/Cu(II). Meanwhile, peritumoral injection of LDH/HA/5-FU nanosheets might function as an adjuvant to increase the levels of antitumor tumor-associated macrophages (TAMs) and T cells. In vivo experiments further verified that the intelligently designed LDH/HA/5-FU nanosheets successfully promoted the immune systems, with an excellent inhibition efficacy towards tumors by combining Cu-based CDT and chemotherapy, showing promising potential for solid tumor treatments.
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Affiliation(s)
- Yi Xia
- Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, China; Shanghai Frontiers Science Center of Drug Target Identification and Delivery, School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai 200240, China; National Key Laboratory of Innovative Immunotherapy, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Muge Gu
- Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, China; Shanghai Frontiers Science Center of Drug Target Identification and Delivery, School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai 200240, China; National Key Laboratory of Innovative Immunotherapy, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Jiayu Wang
- Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, China; Shanghai Frontiers Science Center of Drug Target Identification and Delivery, School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai 200240, China; National Key Laboratory of Innovative Immunotherapy, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Xiangqi Zhang
- Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, China; Shanghai Frontiers Science Center of Drug Target Identification and Delivery, School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai 200240, China; National Key Laboratory of Innovative Immunotherapy, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Tianyi Shen
- Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, China; Shanghai Frontiers Science Center of Drug Target Identification and Delivery, School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai 200240, China; National Key Laboratory of Innovative Immunotherapy, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Xiaoying Shi
- Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, China; Shanghai Frontiers Science Center of Drug Target Identification and Delivery, School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai 200240, China; National Key Laboratory of Innovative Immunotherapy, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Wei-En Yuan
- Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, China; Shanghai Frontiers Science Center of Drug Target Identification and Delivery, School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai 200240, China; National Key Laboratory of Innovative Immunotherapy, Shanghai Jiao Tong University, Shanghai 200240, China.
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Liu S, Fang C, Zhong C, Li J, Xiao Q. Recent advances in pluripotent stem cell-derived cardiac organoids and heart-on-chip applications for studying anti-cancer drug-induced cardiotoxicity. Cell Biol Toxicol 2023; 39:2527-2549. [PMID: 37889357 DOI: 10.1007/s10565-023-09835-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2023] [Accepted: 10/11/2023] [Indexed: 10/28/2023]
Abstract
Cardiovascular disease (CVD) caused by anti-cancer drug-induced cardiotoxicity is now the second leading cause of mortality among cancer survivors. It is necessary to establish efficient in vitro models for early predicting the potential cardiotoxicity of anti-cancer drugs, as well as for screening drugs that would alleviate cardiotoxicity during and post treatment. Human induced pluripotent stem cells (hiPSCs) have opened up new avenues in cardio-oncology. With the breakthrough of tissue engineering technology, a variety of hiPSC-derived cardiac microtissues or organoids have been recently reported, which have shown enormous potential in studying cardiotoxicity. Moreover, using hiPSC-derived heart-on-chip for studying cardiotoxicity has provided novel insights into the underlying mechanisms. Herein, we summarize different types of anti-cancer drug-induced cardiotoxicities and present an extensive overview on the applications of hiPSC-derived cardiac microtissues, cardiac organoids, and heart-on-chips in cardiotoxicity. Finally, we highlight clinical and translational challenges around hiPSC-derived cardiac microtissues/organoids/heart-on chips and their applications in anti-cancer drug-induced cardiotoxicity. • Anti-cancer drug-induced cardiotoxicities represent pressing challenges for cancer treatments, and cardiovascular disease is the second leading cause of mortality among cancer survivors. • Newly reported in vitro models such as hiPSC-derived cardiac microtissues/organoids/chips show enormous potential for studying cardio-oncology. • Emerging evidence supports that hiPSC-derived cardiac organoids and heart-on-chip are promising in vitro platforms for predicting and minimizing anti-cancer drug-induced cardiotoxicity.
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Affiliation(s)
- Silin Liu
- The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China
- Centre for Clinical Pharmacology and Precision Medicine, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Heart Centre, Charterhouse Square, London, EC1M 6BQ, UK
- Guangdong Provincial Clinical Research Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China
| | - Chongkai Fang
- Centre for Clinical Pharmacology and Precision Medicine, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Heart Centre, Charterhouse Square, London, EC1M 6BQ, UK
- Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China
| | - Chong Zhong
- The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China
- Guangdong Provincial Clinical Research Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China
| | - Jing Li
- The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China.
- Guangdong Provincial Clinical Research Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China.
- Faculty of Biological Sciences, University of Leeds, Leeds, UK.
| | - Qingzhong Xiao
- Centre for Clinical Pharmacology and Precision Medicine, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Heart Centre, Charterhouse Square, London, EC1M 6BQ, UK.
- Key Laboratory of Cardiovascular Diseases, School of Basic Medical Sciences, Guangzhou Institute of Cardiovascular Disease, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 511436, China.
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Hammond ST, Baumfalk DR, Parr SK, Butenas AL, Scheuermann BC, Turpin VRG, Behnke BJ, Hashmi MH, Ade CJ. Impaired microvascular reactivity in patients treated with 5-fluorouracil chemotherapy regimens: Potential role of endothelial dysfunction. IJC HEART & VASCULATURE 2023; 49:101300. [PMID: 38173789 PMCID: PMC10761309 DOI: 10.1016/j.ijcha.2023.101300] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Revised: 10/27/2023] [Accepted: 11/06/2023] [Indexed: 01/05/2024]
Abstract
Background 5-fluorouracil (5-FU) is the second most common cancer chemotherapy associated with short- and long-term cardiotoxicity. Although the mechanisms mediating these toxicities are not well understood, patients often present with symptoms suggestive of microvascular dysfunction. We tested the hypotheses that patients undergoing cancer treatment with 5-FU based chemotherapy regimens would present with impaired microvascular reactivity and that these findings would be substantiated by decrements in endothelial nitric oxide synthase (eNOS) gene expression in 5-FU treated human coronary artery endothelial cells (HCAEC). Methods We first performed a cross-sectional analysis of 30 patients undergoing 5-FU based chemotherapy treatment for cancer (5-FU) and 32 controls (CON) matched for age, sex, body mass index, and prior health history (excluding cancer). Cutaneous microvascular reactivity was evaluated by laser Doppler flowmetry in response to endothelium-dependent (local skin heating; acetylcholine iontophoresis, ACh) and -independent (sodium nitroprusside iontophoresis, SNP) stimuli. In vitro experiments in HCAEC were completed to assess the effects of 5-FU on eNOS gene expression. Results 5-FU presented with diminished microvascular reactivity following eNOS-dependent local heating compared to CON (P = 0.001). Iontophoresis of the eNOS inhibitor L-NAME failed to alter the heating response in 5-FU (P = 0.95), despite significant reductions in CON (P = 0.03). These findings were corroborated by lower eNOS gene expression in 5-FU treated HCAEC (P < 0.01) compared to control. Peak vasodilation to ACh (P = 0.58) nor SNP (P = 0.39) were different between groups. Conclusions The present findings suggest diminished microvascular function along the eNOS-NO vasodilatory pathway in patients with cancer undergoing treatment with 5-FU-based chemotherapy regimens and thus, may provide insight into the underlying mechanisms of 5-FU cardiotoxicity.
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Affiliation(s)
- Stephen T. Hammond
- Department of Kinesiology, Kansas State University, Manhattan, KS, USA
- Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
- Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI, USA
| | | | - Shannon K. Parr
- Department of Kinesiology, Kansas State University, Manhattan, KS, USA
| | - Alec L.E. Butenas
- Department of Kinesiology, Kansas State University, Manhattan, KS, USA
| | | | | | - Bradley J. Behnke
- Department of Kinesiology, Kansas State University, Manhattan, KS, USA
- Johnson Cancer Research Center, Kansas State University, Manhattan, KS, USA
| | | | - Carl J. Ade
- Department of Kinesiology, Kansas State University, Manhattan, KS, USA
- Johnson Cancer Research Center, Kansas State University, Manhattan, KS, USA
- Physicians Associates Studies, Kansas State University, Manhattan, KS, USA
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10
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Kwok C, Nolan M. Cardiotoxicity of anti-cancer drugs: cellular mechanisms and clinical implications. Front Cardiovasc Med 2023; 10:1150569. [PMID: 37745115 PMCID: PMC10516301 DOI: 10.3389/fcvm.2023.1150569] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2023] [Accepted: 07/17/2023] [Indexed: 09/26/2023] Open
Abstract
Cardio-oncology is an emerging field that seeks to enhance quality of life and longevity of cancer survivors. It is pertinent for clinicians to understand the cellular mechanisms of prescribed therapies, as this contributes to robust understanding of complex treatments and off-target effects, improved communication with patients, and guides long term care with the goal to minimise or prevent cardiovascular complications. Our aim is to review the cellular mechanisms of cardiotoxicity involved in commonly used anti-cancer treatments and identify gaps in literature and strategies to mitigate cardiotoxicity effects and guide future research endeavours.
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Affiliation(s)
- Cecilia Kwok
- Department of Medicine, Western Health, Melbourne, VIC, Australia
| | - Mark Nolan
- Department of Medicine, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
- Cardiovascular Imaging, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia
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11
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Uruski P, Matuszewska J, Leśniewska A, Rychlewski D, Niklas A, Mikuła-Pietrasik J, Tykarski A, Książek K. An integrative review of nonobvious puzzles of cellular and molecular cardiooncology. Cell Mol Biol Lett 2023; 28:44. [PMID: 37221467 DOI: 10.1186/s11658-023-00451-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Accepted: 04/17/2023] [Indexed: 05/25/2023] Open
Abstract
Oncologic patients are subjected to four major treatment types: surgery, radiotherapy, chemotherapy, and immunotherapy. All nonsurgical forms of cancer management are known to potentially violate the structural and functional integrity of the cardiovascular system. The prevalence and severity of cardiotoxicity and vascular abnormalities led to the emergence of a clinical subdiscipline, called cardiooncology. This relatively new, but rapidly expanding area of knowledge, primarily focuses on clinical observations linking the adverse effects of cancer therapy with deteriorated quality of life of cancer survivors and their increased morbidity and mortality. Cellular and molecular determinants of these relations are far less understood, mainly because of several unsolved paths and contradicting findings in the literature. In this article, we provide a comprehensive view of the cellular and molecular etiology of cardiooncology. We pay particular attention to various intracellular processes that arise in cardiomyocytes, vascular endothelial cells, and smooth muscle cells treated in experimentally-controlled conditions in vitro and in vivo with ionizing radiation and drugs representing diverse modes of anti-cancer activity.
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Affiliation(s)
- Paweł Uruski
- Department of Hypertensiology, Poznań University of Medical Sciences, Długa ½ Str., 61-848, Poznan, Poland
| | - Julia Matuszewska
- Department of Pathophysiology of Ageing and Civilization Diseases, Poznań University of Medical Sciences, Długa ½ Str., 61-848, Poznan, Poland
| | - Aleksandra Leśniewska
- Department of Pathophysiology of Ageing and Civilization Diseases, Poznań University of Medical Sciences, Długa ½ Str., 61-848, Poznan, Poland
| | - Daniel Rychlewski
- Department of Pathophysiology of Ageing and Civilization Diseases, Poznań University of Medical Sciences, Długa ½ Str., 61-848, Poznan, Poland
| | - Arkadiusz Niklas
- Department of Hypertensiology, Poznań University of Medical Sciences, Długa ½ Str., 61-848, Poznan, Poland
| | - Justyna Mikuła-Pietrasik
- Department of Pathophysiology of Ageing and Civilization Diseases, Poznań University of Medical Sciences, Długa ½ Str., 61-848, Poznan, Poland
| | - Andrzej Tykarski
- Department of Hypertensiology, Poznań University of Medical Sciences, Długa ½ Str., 61-848, Poznan, Poland
| | - Krzysztof Książek
- Department of Pathophysiology of Ageing and Civilization Diseases, Poznań University of Medical Sciences, Długa ½ Str., 61-848, Poznan, Poland.
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12
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da Silva MC, Fabiano LC, da Costa Salomão KC, de Freitas PLZ, Neves CQ, Borges SC, de Souza Carvalho MDG, Breithaupt-Faloppa AC, de Thomaz AA, Dos Santos AM, Buttow NC. A Rodent Model of Human-Dose-Equivalent 5-Fluorouracil: Toxicity in the Liver, Kidneys, and Lungs. Antioxidants (Basel) 2023; 12:antiox12051005. [PMID: 37237871 DOI: 10.3390/antiox12051005] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Accepted: 04/24/2023] [Indexed: 05/28/2023] Open
Abstract
5-Fluorouracil (5-FU) is a chemotherapy drug widely used to treat a range of cancer types, despite the recurrence of adverse reactions. Therefore, information on its side effects when administered at a clinically recommended dose is relevant. On this basis, we examined the effects of the 5-FU clinical treatment on the integrity of the liver, kidneys, and lungs of rats. For this purpose, 14 male Wistar rats were divided into treated and control groups and 5-FU was administered at 15 mg/kg (4 consecutive days), 6 mg/kg (4 alternate days), and 15 mg/kg on the 14th day. On the 15th day, blood, liver, kidney, and lung samples were collected for histological, oxidative stress, and inflammatory evaluations. We observed a reduction in the antioxidant markers and an increase in lipid hydroperoxides (LOOH) in the liver of treated animals. We also detected elevated levels of inflammatory markers, histological lesions, apoptotic cells, and aspartate aminotransferase. Clinical treatment with 5-FU did not promote inflammatory or oxidative alterations in the kidney samples; however, histological and biochemical changes were observed, including increased serum urea and uric acid. 5-FU reduces endogenous antioxidant defenses and increases LOOH levels in the lungs, suggesting oxidative stress. Inflammation and histopathological alterations were also detected. The clinical protocol of 5-FU promotes toxicity in the liver, kidneys, and lungs of healthy rats, resulting in different levels of histological and biochemical alterations. These results will be useful in the search for new adjuvants to attenuate the adverse effects of 5-FU in such organs.
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Affiliation(s)
- Mariana Conceição da Silva
- Biological Physics and Cell Signaling Laboratory, Institute of Biology, Department of Structural and Functional Biology, State University of Campinas, Campinas 13083-970, SP, Brazil
| | - Lilian Catarim Fabiano
- Department of Morphological Science, State University of Maringá, Maringá 87020-900, PR, Brazil
| | | | | | - Camila Quaglio Neves
- Department of Morphological Science, State University of Maringá, Maringá 87020-900, PR, Brazil
| | | | - Maria das Graças de Souza Carvalho
- Biological Physics and Cell Signaling Laboratory, Institute of Biology, Department of Structural and Functional Biology, State University of Campinas, Campinas 13083-970, SP, Brazil
| | - Ana Cristina Breithaupt-Faloppa
- Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação (LIM-11), Instituto do Coração (InCor), Faculdade de Medicina da Universidade de São Paulo, São Paulo 01246-904, SP, Brasil
| | - André Alexandre de Thomaz
- Quantum Electronic Department, Institute of Physics Gleb Wataghin, State University of Campinas, Campinas 13083-872, SP, Brazil
| | - Aline Mara Dos Santos
- Biological Physics and Cell Signaling Laboratory, Institute of Biology, Department of Structural and Functional Biology, State University of Campinas, Campinas 13083-970, SP, Brazil
| | - Nilza Cristina Buttow
- Department of Morphological Science, State University of Maringá, Maringá 87020-900, PR, Brazil
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13
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Lombardi P, Aimar G, Peraldo-Neia C, Bonzano A, Depetris I, Fenocchio E, Filippi R, Quarà V, Milanesio M, Cavalloni G, Gammaitoni L, Basiricò M, Cagnazzo C, Ostano P, Chiorino G, Aglietta M, Leone F. Fluoropyrimidine‑induced cardiotoxicity in colorectal cancer patients: a prospective observational trial (CHECKPOINT). Oncol Rep 2022; 49:31. [PMID: 36562382 PMCID: PMC9827273 DOI: 10.3892/or.2022.8468] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2022] [Accepted: 11/22/2022] [Indexed: 12/24/2022] Open
Abstract
Fluoropyrimidines (FP) are the backbone chemotherapy in colorectal cancer (CRC) treatment; however, their use is associated with cardiotoxicity, which is underreported. In the present study, it was aimed to prospectively determine the incidence rates and related risk factors of FP‑induced cardiotoxicity (FIC) in CRC patients and at identifying predictive biomarkers. A total of 129 consecutive previously untreated CRC patients underwent active cardiological monitoring, including 5‑items simplified questionnaire on symptoms, electrocardiogram (ECG) and plasma sample collection during FP chemotherapy. FIC was defined as the presence of ECG alterations and/or the arising of at least one symptom of chest pain, dyspnoea, palpitations or syncope. The primary objective was the evaluation of FIC incidence. Secondary objectives were the correlation of FIC with well‑known cardiological risk factors and the identification of circulating biomarkers (serum levels of troponin I, pro hormone BNP; miRNA analysis) as predictors of FIC. A total of 20 out of 129 (15.5%) patients experienced FIC. The most common symptoms were dyspnoea (60%) and chest pain (40%), while only 15% of patients presented ECG alterations, including one acute myocardial infarction. Retreatment with FP was attempted in 90% of patients with a favourable outcome. Despite 48% of patients having cardiological comorbidities, an increased FIC was not observed in this subgroup. Only the subgroup of females with the habit of alcohol consumption showed an increased risk of FIC. None of the circulating biomarkers evaluated demonstrated a clinical utility as FIC predictors. FIC can be an unexpected, life‑threatening adverse event that can limit the subsequent treatment choices in patients with CRC. In this prospective study, well‑known cardiological comorbidities were not related to higher FIC risk and circulating biomarkers predictive of toxicity could not be found. With careful monitoring, mainly based on symptoms, almost all patients completed the FP treatment.
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Affiliation(s)
- Pasquale Lombardi
- Department of Oncology, University of Turin, I-10124 Torino, Italy,Phase 1 Unit, Agostino Gemelli Foundation University Hospital IRCCS, I-00168 Roma, Italy
| | - Giacomo Aimar
- Department of Oncology, University of Turin, I-10124 Torino, Italy,Department of Oncology, S. Croce and Carle Hospital, I-12100 Cuneo, Italy
| | | | | | - Ilaria Depetris
- Division of Medical Oncology 1, AOU City of Health and Science of Turin, I-12126 Turin, Italy
| | - Elisabetta Fenocchio
- Department of Medical Oncology, Candiolo Cancer Institute, FPO-IRCCS, I-10060 Candiolo, Italy
| | - Roberto Filippi
- Department of Oncology, University of Turin, I-10124 Torino, Italy,Division of Medical Oncology 1, AOU City of Health and Science of Turin, I-12126 Turin, Italy
| | - Virginia Quarà
- Department of Oncology, University of Turin, I-10124 Torino, Italy,Department of Medical Oncology, Candiolo Cancer Institute, FPO-IRCCS, I-10060 Candiolo, Italy
| | | | - Giuliana Cavalloni
- Department of Medical Oncology, Candiolo Cancer Institute, FPO-IRCCS, I-10060 Candiolo, Italy
| | | | - Marco Basiricò
- Department of Public Health and Pediatric Sciences, AOU City of Health and Science of Turin, Regina Margherita Hospital, I-10126 Torino, Italy
| | - Celeste Cagnazzo
- Department of Public Health and Pediatric Sciences, AOU City of Health and Science of Turin, Regina Margherita Hospital, I-10126 Torino, Italy
| | - Paola Ostano
- Laboratory of Cancer Genomics, Fondazione Edo ed Elvo Tempia, I-13900 Biella, Italy
| | - Giovanna Chiorino
- Laboratory of Cancer Genomics, Fondazione Edo ed Elvo Tempia, I-13900 Biella, Italy
| | - Massimo Aglietta
- Department of Medical Oncology, Candiolo Cancer Institute, FPO-IRCCS, I-10060 Candiolo, Italy
| | - Francesco Leone
- Department of Medical Oncology, Infermi Hospital of Biella, Ponderano, I-13875 Biella, Italy,Correspondence to: Dr Francesco Leone, Department of Medical Oncology, Infermi Hospital of Biella, 2 Via dei Ponderanesi, Ponderano, I-13875 Biella, Italy, E-mail:
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14
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Design, synthesis and preclinical evaluations of (s)-2-((s)-1-benzyl-2,5-dioxopyrrolidin-3-yl)-3-(4-isopropylphenyl)-2-methylpropanal (succ-5) as cardioprotective, hepatoprotective and lipid lowering molecule. in-vivo and in-silico approaches. ARAB J CHEM 2022. [DOI: 10.1016/j.arabjc.2022.104504] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
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15
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Safdar A, Ahmed T, Liu VY, Addoumieh A, Agha AM, Giza DE, Balanescu DV, Donisan T, Dayah T, Lopez-Mattei JC, Kim PY, Hassan S, Karimzad K, Palaskas N, Tsai JY, Iliescu GD, Yang EH, Herrmann J, Marmagkiolis K, Angelini P, Iliescu CA. Trigger related outcomes of takotsubo syndrome in a cancer population. Front Cardiovasc Med 2022; 9:1019284. [PMID: 36386379 PMCID: PMC9651211 DOI: 10.3389/fcvm.2022.1019284] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2022] [Accepted: 09/28/2022] [Indexed: 01/21/2023] Open
Abstract
Background Takotsubo syndrome (TTS) occurs more frequently in cancer patients than in the general population, but the effect of specific TTS triggers on outcomes in cancer patients is not well studied. Objectives The study sought to determine whether triggering event (chemotherapy, immune-modulators vs. procedural or emotional stress) modifies outcomes in a cancer patient population with TTS. Methods All cancer patients presenting with acute coronary syndrome (ACS) between December 2008 and December 2020 at our institution were enrolled in the catheterization laboratory registry. Demographic and clinical data of the identified patients with TTS were retrospective collected and further classified according to the TTS trigger. The groups were compared with regards to major adverse cardiac events, overall survival and recovery of left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) after TTS presentation. Results Eighty one of the 373 cancer patients who presented with ACS met the Mayo criteria for TTS. The triggering event was determined to be "cancer specific triggers" (use of chemotherapy in 23, immunomodulators use in 7, and radiation in 4), and "traditional triggers" (medical triggers 22, and procedural 18 and emotional stress in 7). Of the 81 patients, 47 died, all from cancer-related causes (no cardiovascular mortality). Median survival was 11.9 months. Immunomodulator (IM) related TTS and radiation related TTS were associated with higher mortality during the follow-up. Patients with medical triggers showed the least recovery in LVEF and GLS while patients with emotional and chemotherapy triggers, showed the most improvement in LVEF and GLS, respectively. Conclusion Cancer patients presenting with ACS picture have a high prevalence of TTS due to presence of traditional and cancer specific triggers. Survival and improvement in left ventricular systolic function seem to be related to the initial trigger for TTS.
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Affiliation(s)
- Ayesha Safdar
- Department of Medicine, Army Medical College, Rawalpindi, Pakistan
| | - Talha Ahmed
- Department of Cardiology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States,Department of Cardiovascular Medicine, The University of Texas Health Science Center at Houston, Houston, TX, United States
| | - Victor Y. Liu
- Department of Cardiology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States,Department of Cardiovascular Medicine, The University of Texas Health Science Center at Houston, Houston, TX, United States
| | - Antoine Addoumieh
- Department of Cardiology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States,Department of Cardiovascular Medicine, The University of Texas Health Science Center at Houston, Houston, TX, United States
| | - Ali M. Agha
- Department of Cardiovascular Medicine, The University of Texas Health Science Center at Houston, Houston, TX, United States
| | - Dana E. Giza
- Department of Family and Community Medicine, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, TX, United States
| | - Dinu V. Balanescu
- Department of Family and Community Medicine, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, TX, United States
| | - Teodora Donisan
- Department of Cardiology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Tariq Dayah
- Department of Cardiovascular Medicine, The University of Texas Health Science Center at Houston, Houston, TX, United States
| | - Juan C. Lopez-Mattei
- Department of Cardiology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Peter Y. Kim
- Department of Cardiology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Saamir Hassan
- Department of Cardiology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Kaveh Karimzad
- Department of Cardiology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Nicolas Palaskas
- Department of Cardiology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - January Y. Tsai
- Department of Anesthesiology and Perioperative Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Gloria D. Iliescu
- Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Eric H. Yang
- Department of Medicine, University of California, Los Angeles, Los Angeles, CA, United States
| | - Joerg Herrmann
- Division of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, United States
| | - Konstantinos Marmagkiolis
- Department of Cardiovascular Medicine, Florida Hospital Pepin Heart Institute, Tampa, FL, United States
| | - Paolo Angelini
- Department of Cardiology, Texas Heart Institute, Houston, TX, United States
| | - Cezar A. Iliescu
- Department of Cardiology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States,*Correspondence: Cezar A. Iliescu,
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16
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Cucciniello L, Bidoli E, Viel E, Canale ML, Gerratana L, Lestuzzi C. The puzzling clinical presentation of fluoropyrimidines cardiotoxicity. Front Cardiovasc Med 2022; 9:960240. [PMID: 36186986 PMCID: PMC9515374 DOI: 10.3389/fcvm.2022.960240] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Accepted: 08/16/2022] [Indexed: 11/24/2022] Open
Abstract
The cardiotoxicity of fluoropyrimidines (FP) [5-Fluorouracil and Capecitabine] is often reported as acute cardiac ischemia with rest typical angina, signs of ischemia at electrocardiogram (ECG), and ventricular kinetics abnormalities. However, silent ischemia, effort-related toxicity, and ventricular arrhythmias (VA) have been also described. The aim of this study is to report a consecutive series of 115 patients with FP cardiotoxicity observed in a single center both within clinical prospective studies and during the clinical routine. The clinical presentation widely varied as regards symptoms, ECG abnormalities, and clinical outcomes. We report also the strategies used to prevent cardiotoxicity in a subgroup of 35 patients who continued o rechallenged FP therapy after cardiotoxicity. In nearly half of the patients, the cardiotoxicity was triggered by physical effort. Typical angina was rare: the symptoms were absent in 51% of cases and were atypical in half of the other cases. ST-segment elevation and VA were the most frequent ECG abnormality; however, ST segment depression or negative T waves were the only abnormalities in 1/3 of the cases. Troponins essays were often within the normal limits, even in presence of extensive signs of ischemia. The most effective strategy to prevent cardiotoxicity at rechallenge was reducing FP dosage and avoiding physical effort. Anti-ischemic therapies were not always effective. Raltitrexed was a safe alternative to FP. Fluoropyrimidine cardiotoxicity shows a wide variety of clinical presentations in real life, from silent ischemia to atypical symptoms, acute coronary syndrome, left ventricular dysfunction (LVD), VA, or complete atrio-ventricular block. Physical effort is the trigger of cardiotoxicity in nearly half of the cases. The recognition of cardiotoxicity cannot rely on symptoms only but requires an active screening with ECG and stress test in selected cases.
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Affiliation(s)
- Linda Cucciniello
- Department of Oncology, Centro di Riferimento Oncologico, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), National Cancer Institute, Aviano, Italy
| | - Ettore Bidoli
- Unit of Cancer Epidemiology, Centro di Riferimento Oncologico, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), National Cancer Institute, Aviano, Italy
| | - Elda Viel
- Department of Cardiology, Azienda Sanitaria Friuli Occidentale, ASFO, Pordenone, Italy
| | - Maria Laura Canale
- Ospedale Versilia, Azienda Usl Toscana nord ovest, Lido di Camaiore, Italy
| | - Lorenzo Gerratana
- Department of Medical Oncology, Aviano Oncology Reference Center (IRCCS), Aviano, Italy
| | - Chiara Lestuzzi
- Department of Cardiology, Azienda Sanitaria Friuli Occidentale, ASFO, Pordenone, Italy
- *Correspondence: Chiara Lestuzzi,
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17
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Chen Y, Li T, Qiu X, Shang X. Eu3+-doped MgAl LDH with fluorescence as carrier for 5-fluorouracil: intercalation and release. RESEARCH ON CHEMICAL INTERMEDIATES 2022. [DOI: 10.1007/s11164-022-04828-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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18
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Terwoord JD, Beyer AM, Gutterman DD. Endothelial dysfunction as a complication of anti-cancer therapy. Pharmacol Ther 2022; 237:108116. [PMID: 35063569 PMCID: PMC9294076 DOI: 10.1016/j.pharmthera.2022.108116] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Revised: 12/16/2021] [Accepted: 01/12/2022] [Indexed: 12/14/2022]
Abstract
Recent strides in anti-cancer therapeutics have improved longevity and led to a growing population of cancer survivors, who are increasingly likely to die of other causes. Treatment-induced cardiotoxicity is a complication of several therapeutic agents with acute and long-term consequences for cancer patients. Vascular endothelial dysfunction is a precursor and hallmark of ischemic coronary disease and may play a role in anti-cancer therapy-induced cardiotoxicity. This review summarizes clinical evidence for endothelial dysfunction following anti-cancer therapy and extends the discussion to include the impact of therapeutic agents on conduit arteries and the microcirculation. We highlight the role of innate immune system activation and cross-talk between inflammation and oxidative stress as pathogenic mechanisms underlying anti-cancer therapy-induced vascular toxicity. Understanding the impact of anti-cancer agents on the vascular endothelium will inform therapeutic approaches to prevent or reverse treatment-induced cardiotoxicity and may serve as an important tool to predict, monitor, and prevent adverse cardiovascular outcomes in patients undergoing treatment.
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Affiliation(s)
- Janée D Terwoord
- Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, United States of America; Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI, United States of America.
| | - Andreas M Beyer
- Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, United States of America; Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI, United States of America; Cancer Center, Medical College of Wisconsin, Milwaukee, WI, United States of America
| | - David D Gutterman
- Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, United States of America; Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI, United States of America
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19
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Analysis of Epidemiological Characteristics of New Cardiovascular Diseases in Cancer Patients with Cardiovascular Disease. JOURNAL OF ONCOLOGY 2022; 2022:5157398. [PMID: 36090898 PMCID: PMC9452938 DOI: 10.1155/2022/5157398] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Accepted: 06/27/2022] [Indexed: 11/25/2022]
Abstract
In cancer patients, a cardiovascular disease (CVD) is a prevalent occurrence. When a patient has both heart disease and cancer, the treatment can be complicated because treatment for one condition can have an adverse effect on the outcome of the other. A cardiovascular disease that involves heart failures, coronary artery disease (CAD), stroke, pericardial diseases, arrhythmias, and valve and vascular dysfunction is a serious worry for long-term cancer patients. Because preclinical research is limited, it is critical to comprehend the pathophysiology of CVD as a consequence of anticancerous therapies while taking into account the developing and expanding heart. As a result, in this research, we look at the epidemiological characteristics of cancer patients who also have cardiovascular illness. Low-dose chest computed tomography, cardiac CT, and cardiac magnetic resonance imaging (MRI) are used to acquire the data and perform the screening. Chemotherapeutic drugs such as anthracyclines and trastuzumab are used to treat the condition. Univariate analysis is used to examine risk factors and predict cardiovascular damage. Sensitivity, specificity, positive predictive value, negative predictive value, life expectancy, left ventricular ejection fraction (LVEF), and longitudinal strain are among the metrics examined.
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20
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Cherukuri SP, Chikatimalla R, Dasaradhan T, Koneti J, Gadde S, Kalluru R. Breast Cancer and the Cardiovascular Disease: A Narrative Review. Cureus 2022; 14:e27917. [PMID: 36110451 PMCID: PMC9464354 DOI: 10.7759/cureus.27917] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/12/2022] [Indexed: 11/05/2022] Open
Abstract
Breast cancer is the most common malignancy affecting females worldwide and is also among the top causes of all cancer-related deaths. Cardiovascular disease (CVD) is known to have the highest rate of mortality in women. There are several risk factors for both CVD and breast cancer that overlap, such as diet, smoking, and obesity, and also the current breast cancer treatment has a significant detrimental effect on cardiovascular health in general. Patients with exposure to potentially cardiotoxic treatments, including anthracyclines, trastuzumab, and radiation therapy, are more likely to develop CVD than non-cancer controls. Early detection and treatment may reduce the risk of the development of cardiac morbidity and mortality and would increase the number of breast cancer survivors. This article provides a comprehensive overview of breast cancer, identifies shared risk factors among breast cancer and CVD, and the cardiotoxic effects of therapy. It also reviews possible prevention and treatment of CVD in breast cancer patients and reviews literature about chemoprevention of cardiac disease in the setting of breast cancer treatment.
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21
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Safarpour S, Safarpour S, Moghadamnia AA, Kazemi S, Ebrahimpour A, Shirafkan F, Golchoobian R. Cardioprotective effect of silymarin nanoemulsion on 5-fluorouracil-induced cardiotoxicity in rats. Arch Pharm (Weinheim) 2022; 355:e2200060. [PMID: 35411625 DOI: 10.1002/ardp.202200060] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Revised: 03/12/2022] [Accepted: 03/15/2022] [Indexed: 11/10/2022]
Abstract
5-Fluorouracil (5-FU)-associated cardiotoxicity has been ranked as the second most common cause of cardiotoxicity induced by chemotherapeutic drugs after anthracyclines. In the present study, we investigated the protective impacts of silymarin (SIL) and silymarin nanoemulsion (SLN) against cardiotoxicity caused by 5-FU in rats. Thirty male Wistar rats were divided into six groups as follows: control, SLN (5 mg/kg), SIL (5 mg/kg), 5-FU + SLN, 5-FU + SIL, and 5-FU. Cardiotoxicity was induced by a single intraperitoneal injection of 5-FU (100 mg/kg). The control group received an intraperitoneal injection (ip) of normal saline and the treatment groups received ips of SIL and SLN for 14 days. 5-FU resulted in significant cardiotoxicity, represented by an increase in the serum levels of cardiac enzymes and malondialdehyde, as well as cyclooxygenase-2 (COX-2) and tumor necrosis factor-α (TNF-α) expression, and histopathological degeneration. 5-FU treatment also induced a decrease in body weight, total antioxidant capacity (TAC), and catalase values. Evaluation of electrocardiographic parameters in 5-FU-treated rats showed increases in the ST segment, QRS duration, and RR interval. Treatment with SIL and SLN reduced oxidative stress, cardiac enzymes, histopathological degeneration, and the expression of TNF-α and COX-2 in cardiac tissue. Our results demonstrated that treatment with SIL and SLN significantly improved cardiotoxicity induced by 5-FU in rats.
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Affiliation(s)
- Soheila Safarpour
- Student Research Committee, School of Medicine, Babol University of Medical Sciences, Babol, Iran.,Department of Pharmacology and Toxicology, School of Medicine, Babol University of Medical Sciences, Babol, Iran
| | - Samaneh Safarpour
- Department of Biochemistry, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Ali A Moghadamnia
- Department of Pharmacology and Toxicology, School of Medicine, Babol University of Medical Sciences, Babol, Iran.,Cellular and Molecular Biology Research Center, Health Research Institute, School of Medicine, Babol University of Medical Sciences, Babol, Iran
| | - Sohrab Kazemi
- Cellular and Molecular Biology Research Center, Health Research Institute, School of Medicine, Babol University of Medical Sciences, Babol, Iran
| | - Anahita Ebrahimpour
- Cellular and Molecular Biology Research Center, Health Research Institute, School of Medicine, Babol University of Medical Sciences, Babol, Iran
| | - Fatemeh Shirafkan
- Cellular and Molecular Biology Research Center, Health Research Institute, School of Medicine, Babol University of Medical Sciences, Babol, Iran
| | - Ravieh Golchoobian
- Cellular and Molecular Biology Research Center, Health Research Institute, School of Medicine, Babol University of Medical Sciences, Babol, Iran
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22
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Fu Z, Lin Z, Yang M, Li C. Cardiac Toxicity From Adjuvant Targeting Treatment for Breast Cancer Post-Surgery. Front Oncol 2022; 12:706861. [PMID: 35402243 PMCID: PMC8988147 DOI: 10.3389/fonc.2022.706861] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2021] [Accepted: 02/24/2022] [Indexed: 12/14/2022] Open
Abstract
Breast cancer is one of the most prevalent types of cancers worldwide, especially for females. Surgery is the preferred treatment for breast cancer, and various postoperative adjuvant therapies can be reasonably used according to different pathological characteristics, especially traditional radiotherapy, chemotherapy, and endocrine therapy. In recent years, targeting agent therapy has also become one of the selective breast cancer treatment strategies, including anti-HER-2 drugs, CDK4/6 inhibitor, poly ADP-ribose polymerase inhibitor, PI3K/AKT/mTOR pathway inhibitor, ER targeting drugs, and aromatase inhibitor. Because of the different pathologic mechanisms of these adjuvant therapies, each of the strategies may cause cardiotoxicity in clinic. The cardiac adverse events of traditional endocrine therapy, radiotherapy, and chemotherapy for breast cancer have been widely detected in clinic; however, the targeting therapy agents have been paid more attention with the extension of application. This review will summarize the cardiac toxicity of various adjuvant therapies for breast cancer, especially for targeting drug therapy.
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Affiliation(s)
- Zhenkun Fu
- Department of Immunology & Wu Lien-Teh Institute & Heilongjiang Provincial Key Laboratory for Infection and Immunity, Harbin Medical University & Heilongjiang Academy of Medical Science, Harbin, China
- State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, China
- Basic Medical College, Harbin Medical University, Harbin, China
| | - Zhoujun Lin
- State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, China
| | - Mao Yang
- Basic Medical College, Harbin Medical University, Harbin, China
- Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Chenggang Li
- State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, China
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23
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Fabin N, Bergami M, Cenko E, Bugiardini R, Manfrini O. The Role of Vasospasm and Microcirculatory Dysfunction in Fluoropyrimidine-Induced Ischemic Heart Disease. J Clin Med 2022; 11:jcm11051244. [PMID: 35268333 PMCID: PMC8910913 DOI: 10.3390/jcm11051244] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Revised: 02/13/2022] [Accepted: 02/23/2022] [Indexed: 12/10/2022] Open
Abstract
Cardiovascular diseases and cancer are the leading cause of morbidity and mortality globally. Cardiotoxicity from chemotherapeutic agents results in substantial morbidity and mortality in cancer survivors and patients with active cancer. Cardiotoxicity induced by 5-fluorouracil (5-FU) has been well established, yet its incidence, mechanisms, and manifestation remain poorly defined. Ischemia secondary to coronary artery vasospasm is thought to be the most frequent cardiotoxic effect of 5-FU. The available evidence of 5-FU-induced epicardial coronary artery spasm and coronary microvascular dysfunction suggests that endothelial dysfunction or primary vascular smooth muscle dysfunction (an endothelial-independent mechanism) are the possible contributing factors to this form of cardiotoxicity. In patients with 5-FU-related coronary artery vasospasm, termination of chemotherapy and administration of nitrates or calcium channel blockers may improve ischemic symptoms. However, there are variable results after administration of nitrates or calcium channel blockers in patients treated with 5-FU presumed to have myocardial ischemia, suggesting mechanisms other than impaired vasodilatory response. Clinicians should investigate whether chest pain and ECG changes can reasonably be attributed to 5-FU-induced cardiotoxicity. More prospective data and clinical randomized trials are required to understand and mitigate potentially adverse outcomes from 5-FU-induced cardiotoxicity.
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24
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A drug delivery system with red fluorescence for the delivery and release of 5-fluorouracil in vitro. CHEMICAL PAPERS 2022. [DOI: 10.1007/s11696-021-02028-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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25
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26
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Anaka M, Abdel-Rahman O. Managing 5FU Cardiotoxicity in Colorectal Cancer Treatment. Cancer Manag Res 2022; 14:273-285. [PMID: 35115827 PMCID: PMC8799936 DOI: 10.2147/cmar.s273544] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2021] [Accepted: 01/11/2022] [Indexed: 11/28/2022] Open
Abstract
Fluorouracil (5FU) is the backbone chemotherapy agent in the treatment of colorectal cancer (CRC). Cardiotoxicity represents an uncommon but serious side effect of treatment with 5FU. Here, we review the current literature on 5FU-cardiotoxicity in the setting of CRC specifically, with a focus on data from the modern era of combination chemotherapy. Despite decades of study, there is little consensus on risk factors and biomarkers for 5FU-cardiotoxicity, nor how patients with CRC should be managed following a cardiotoxicity event. Given the elevated risk of recurrent cardiotoxicity on rechallenge, the use of alternative regimens that do not contain 5FU is a critical aspect of management. Data on the cardiotoxicity risk and efficacy of non-5FU regimens in CRC are therefore reviewed in detail.
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Affiliation(s)
- Matthew Anaka
- Department of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, AB, Canada
| | - Omar Abdel-Rahman
- Department of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, AB, Canada
- Correspondence: Omar Abdel-Rahman, Department of Oncology, Cross Cancer Institute, University of Alberta, 11560 University Avenue, Edmonton, AB, T6G 1Z2, Canada, Tel +1 780-432-8290, Fax +1 780-432-8888, Email
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27
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Chintamani, Tandon M, Ghosh J. Breast Cancer with Associated Problems. Breast Cancer 2022. [DOI: 10.1007/978-981-16-4546-4_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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28
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Montisci A, Palmieri V, Liu JE, Vietri MT, Cirri S, Donatelli F, Napoli C. Severe Cardiac Toxicity Induced by Cancer Therapies Requiring Intensive Care Unit Admission. Front Cardiovasc Med 2021; 8:713694. [PMID: 34540917 PMCID: PMC8446380 DOI: 10.3389/fcvm.2021.713694] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2021] [Accepted: 07/27/2021] [Indexed: 12/28/2022] Open
Abstract
A steadying increase of cancer survivors has been observed as a consequence of more effective therapies. However, chemotherapy regimens are often associated with significant toxicity, and cardiac damage emerges as a prominent clinical issue. Many mechanisms sustain chemotherapy-induced cardiac toxicity: direct myocyte damage, arrhythmia induction, coronary vasospasm, and accelerated atherosclerosis. Anthracyclines are the most studied cardiotoxic drugs and represent a clinical model for cardiac damage induced by chemotherapy. In patients suffering from advanced heart failure (HF) because of chemotherapy-related cardiomyopathy, when refractory to optimal medical therapy, mechanical circulatory support or heart transplantation represents an effective treatment. Here, the main mechanisms of cardiac toxicity induced by cancer therapies are analyzed, with a focus on patients requiring intensive care unit (ICU) admission during the course of the disease because of acute cardiac toxicity, takotsubo syndrome, and acute-on-chronic HF in patients suffering from chemotherapy-induced cardiomyopathy. In a subset of patients, cardiac toxicity can be acute and life-threatening, leading to overt cardiogenic shock. The management of critically ill cancer patients poses a unique challenge and requires a multidisciplinary approach. Moreover, no etiologic therapy is available, and only supportive measures can be implemented.
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Affiliation(s)
- Andrea Montisci
- Division of Cardiothoracic Intensive Care, Azienda Socio-Sanitaria Territoriale (ASST) Spedali Civili, Brescia, Italy
| | - Vittorio Palmieri
- Department of Cardiac Surgery and Transplantation, Ospedali dei Colli Monaldi-Cotugno-CTO, Naples, Italy
| | - Jennifer E Liu
- Department of Medicine/Cardiology Service, Memorial Sloan Kettering Cancer Center, New York, NY, United States
| | - Maria T Vietri
- Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Silvia Cirri
- Department of Anesthesia and Intensive Care, Istituto Clinico Sant'Ambrogio, Milan, Italy
| | | | - Claudio Napoli
- Clinical Department of Internal Medicine and Specialistics, University Department of Advanced Clinical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy.,Istituto di Ricovero e Cura a Carattere Scientifico - Synlab Diagnostica Nucleare (IRCCS SDN), Naples, Italy
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29
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Hsu PY, Mammadova A, Benkirane-Jessel N, Désaubry L, Nebigil CG. Updates on Anticancer Therapy-Mediated Vascular Toxicity and New Horizons in Therapeutic Strategies. Front Cardiovasc Med 2021; 8:694711. [PMID: 34386529 PMCID: PMC8353082 DOI: 10.3389/fcvm.2021.694711] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Accepted: 06/18/2021] [Indexed: 12/11/2022] Open
Abstract
Vascular toxicity is a frequent adverse effect of current anticancer chemotherapies and often results from endothelial dysfunction. Vascular endothelial growth factor inhibitors (VEGFi), anthracyclines, plant alkaloids, alkylating agents, antimetabolites, and radiation therapy evoke vascular toxicity. These anticancer treatments not only affect tumor vascularization in a beneficial manner, they also damage ECs in the heart. Cardiac ECs have a vital role in cardiovascular functions including hemostasis, inflammatory and coagulation responses, vasculogenesis, and angiogenesis. EC damage can be resulted from capturing angiogenic factors, inhibiting EC proliferation, survival and signal transduction, or altering vascular tone. EC dysfunction accounts for the pathogenesis of myocardial infarction, atherothrombosis, microangiopathies, and hypertension. In this review, we provide a comprehensive overview of the effects of chemotherapeutic agents on vascular toxicity leading to hypertension, microvascular rarefaction thrombosis and atherosclerosis, and affecting drug delivery. We also describe the potential therapeutic approaches such as vascular endothelial growth factor (VEGF)-B and prokineticin receptor-1 agonists to maintain endothelial function during or following treatments with chemotherapeutic agents, without affecting anti-tumor effectiveness.
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Affiliation(s)
| | | | | | | | - Canan G. Nebigil
- INSERM UMR 1260, Regenerative Nanomedicine, University of Strasbourg, FMTS (Fédération de Médecine Translationnelle de l'Université de Strasbourg), Strasbourg, France
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30
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Heat/pH-boosted release of 5-fluorouracil and albumin-bound paclitaxel from Cu-doped layered double hydroxide nanomedicine for synergistical chemo-photo-therapy of breast cancer. J Control Release 2021; 335:49-58. [PMID: 33989692 DOI: 10.1016/j.jconrel.2021.05.011] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2021] [Revised: 05/05/2021] [Accepted: 05/09/2021] [Indexed: 12/24/2022]
Abstract
Considerable attention has been devoted to nanomedicine development for breast cancer therapy, while the therapeutic efficiency is far from satisfactory owing to non-specific biodistribution-caused side effects and limitation of single modal treatment. In this study, we have developed a novel nanomedicine for efficient combination breast cancer therapy. This nanomedicine was based on copper-doped layered double hydroxide (Cu-LDH) nanoparticles loaded with two FDA-approved anticancer drugs, i.e. 5-fluorouracil (5-FU) and albumin-bound paclitaxel (nAb-PTX) with complementary chemotherapeutic actions. The 5-FU/Cu-LDH@nAb-PTX nanomedicine showed pH-sensitive heat-facilitated therapeutic on-demand release and demonstrated the moderate-to-strong synergy of photothermal therapy and chemotherapy in inducing apoptosis of breast cancer cells (4 T1). This nanomedicine had a high colloidal stability in saline and serum, and efficiently accumulated in the tumor tissue. Remarkably, this nanomedicine nearly eliminated 4 T1 tumors in vivo after a two-course treatment under mild 808 nm laser irradiation (0.75 W/cm2, 3 min) at very low doses of 5-FU and nAb-PTX (0.25 and 0.50 mg/kg, 8-50 times less than that used in other nanoformulations), without observable side effects. Therefore, this research provides a novel approach to designing multifunctional nanomedicines for on-demand release of chemotherapeutics to cost-effectively treat breast cancer with minimal side effects in future clinic applications.
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31
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Whelton SP, Berning P, Blumenthal RS, Marshall CH, Martin SS, Mortensen MB, Blaha MJ, Dzaye O. Multidisciplinary prevention and management strategies for colorectal cancer and cardiovascular disease. Eur J Intern Med 2021; 87:3-12. [PMID: 33610416 DOI: 10.1016/j.ejim.2021.02.003] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Revised: 01/09/2021] [Accepted: 02/06/2021] [Indexed: 02/06/2023]
Abstract
Colorectal cancer (CRC) and cardiovascular disease (CVD) are leading causes of morbidity and mortality worldwide. Their numerous shared and modifiable risk factors underscore the importance of effective prevention strategies for these largely preventable diseases. Conventionally regarded as separate disease entities, clear pathophysiological links and overlapping risk factors represent an opportunity for synergistic collaborative efforts of oncologists and cardiologists. In addition, current CRC treatment approaches can exert cardiotoxicity and thus increase CVD risk. Given the complex interplay of both diseases and increasing numbers of CRC survivors who are at increased risk for CVD, multidisciplinary cardio-oncological approaches are warranted for optimal patient care from primary prevention to acute disease treatment and long-term surveillance.
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Affiliation(s)
- Seamus P Whelton
- Johns Hopkins Ciccarone Center for Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Philipp Berning
- Department of Hematology and Oncology, University Hospital Muenster, Muenster, Germany
| | - Roger S Blumenthal
- Johns Hopkins Ciccarone Center for Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Catherine Handy Marshall
- Johns Hopkins Ciccarone Center for Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Seth S Martin
- Johns Hopkins Ciccarone Center for Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Martin Bødtker Mortensen
- Johns Hopkins Ciccarone Center for Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark
| | - Michael J Blaha
- Johns Hopkins Ciccarone Center for Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Omar Dzaye
- Johns Hopkins Ciccarone Center for Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD, United States; Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
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32
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McAndrew EN, Jassal DS, Goldenberg BA, Kim CA. Capecitabine-mediated heart failure in colorectal cancer: a case series. Eur Heart J Case Rep 2021; 5:ytab079. [PMID: 33709051 PMCID: PMC7936921 DOI: 10.1093/ehjcr/ytab079] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Revised: 10/28/2020] [Accepted: 02/04/2021] [Indexed: 11/20/2022]
Abstract
BACKGROUND Capecitabine is a pyrimidine antimetabolite that inhibits thymidylate synthase and is commonly used in the treatment of colorectal cancer. Adverse cardiac side effects are reported in 1-18% of patients receiving Capecitabine. The most commonly proposed mechanism of cardiotoxicity in the setting of Capecitabine use is vasospasm of the coronary arteries. However, cardiotoxicity can also present as an acute coronary syndrome, arrhythmia, hypertension, and/or sudden cardiac death. Profound non-vasospastic cardiotoxicity is rare. CASE SUMMARY We describe two cases of acute heart failure leading to cardiogenic shock in patients shortly after exposure to Capecitabine. Both patients did not demonstrate the characteristic transient ST elevation seen in patients with coronary artery vasospasms secondary to Capecitabine. Both patients required admission to the Acute Cardiac Care Unit requiring vasopressor and inotropic support. Thorough diagnostic investigations including echocardiography, cardiac magnetic resonance imaging, and cardiac computed tomography did not identify infarction, myocarditis, or any infiltrative process to explain their symptoms. Both patients had complete resolution of cardiac function, with no long-term sequalae. DISCUSSION In patients receiving Capecitabine, reversible heart failure leading to cardiogenic shock should be considered as a potential cardiotoxic side effect.
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Affiliation(s)
- Erin N McAndrew
- Department of Internal Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Davinder S Jassal
- Department of Internal Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
- Institute of Cardiovascular Sciences, St. Boniface Hospital, University of Manitoba, Winnipeg, Manitoba, Canada
- Section of Cardiology, Department of Internal Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
- Department of Radiology, St. Boniface Hospital, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Benjamin A Goldenberg
- Department of Internal Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
- Section of Medical Oncology and Haematology, Department of Internal Medicine, Rady Faculty of Health Sciences, University of Manitoba, 409 Tache Ave, Winnipeg, Manitoba R2H 2A6, Canada
| | - Christina A Kim
- Department of Internal Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
- Section of Medical Oncology and Haematology, Department of Internal Medicine, Rady Faculty of Health Sciences, University of Manitoba, 409 Tache Ave, Winnipeg, Manitoba R2H 2A6, Canada
- Research Institute in Oncology and Hematology, Cancer Care Manitoba, Winnipeg, Manitoba, Canada
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Dyhl‐Polk A, Schou M, Vistisen KK, Sillesen A, Serup‐Hansen E, Faber J, Klausen TW, Bojesen SE, Vaage‐Nilsen M, Nielsen DL. Myocardial Ischemia Induced by 5-Fluorouracil: A Prospective Electrocardiographic and Cardiac Biomarker Study. Oncologist 2021; 26:e403-e413. [PMID: 32959474 PMCID: PMC7930422 DOI: 10.1002/onco.13536] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Accepted: 09/04/2020] [Indexed: 11/09/2022] Open
Abstract
BACKGROUND Cardiotoxicity induced by 5-fluorouracil (5-FU) is well known but poorly understood. In this study, we undertook ECG recording (Holter) and analyses of the biomarkers troponin and copeptin in patients receiving 5-FU to increase our understanding of the cardiotoxicity. SUBJECTS, MATERIALS, AND METHODS Patients with colorectal or anal cancer that received first-time treatment with 5-FU-based chemotherapy were prospectively included. Holter recording, clinical evaluation, 12-lead electrocardiogram, and assessment of plasma concentrations of troponin I and copeptin were performed before (control) and during 5-FU treatment (intervention). RESULTS A total of 108 patients were included, 82 with colorectal and 26 with anal cancer. The proportion of patients with myocardial ischemia on Holter recording was significantly higher during the first 5-FU infusion (14.1%) than before (3.7%; p = .001). The ischemic burden per day (p = .001), the number of ST depression episodes per day (p = .003), and the total duration of ischemic episodes per day (p = .003) were higher during the first 5-FU infusion than before, as was plasma copeptin (p < .001), whereas plasma troponin I was similar (p > 0.999). Six patients (5.6%) developed acute coronary syndromes and two (1.8%) developed symptomatic arrhythmias during 5-FU treatment. CONCLUSION 5-FU infusion is associated with an increase in the number of patients with myocardial ischemia on Holter recording. According to biomarker analyses, 5-FU is associated with an increase in copeptin, but rarely with increases in cardiac troponin I. However, 5%-6% of the patients developed acute coronary syndromes during treatment with 5-FU. IMPLICATIONS FOR PRACTICE Symptomatic 5-fluorouracil (5-FU) cardiotoxicity occurs in 0.6%-19% of patients treated with this drug, but a small electrocardiographic (Holter) study has revealed silent myocardial ischemia in asymptomatic patients, suggesting a more prevalent subclinical cardiac influence. This study demonstrated a significant increase in the number of patients with myocardial ischemia on Holter recording during 5-FU treatment and an increase in ischemic burden. Cardiac biomarker analyses suggested that 5-FU infusion results in endogenous stress (increased copeptin) but rarely induces myocyte injury (no change in troponin). These findings suggest a more prevalent cardiac influence from 5-FU and that Holter recording is an important tool in the evaluation of patients with suspected cardiotoxicity from 5-FU.
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Affiliation(s)
- Anne Dyhl‐Polk
- Departments of Oncology, Herlev‐Gentofte Hospital, University of CopenhagenHerlevDenmark
- Faculty of Health and Medical Sciences, University of CopenhagenCopenhagenDenmark
| | - Morten Schou
- Departments of Cardiology, Herlev‐Gentofte Hospital, University of CopenhagenHerlevDenmark
- Faculty of Health and Medical Sciences, University of CopenhagenCopenhagenDenmark
| | - Kirsten K. Vistisen
- Departments of Oncology, Herlev‐Gentofte Hospital, University of CopenhagenHerlevDenmark
| | - Anne‐Sophie Sillesen
- Departments of Cardiology, Herlev‐Gentofte Hospital, University of CopenhagenHerlevDenmark
| | - Eva Serup‐Hansen
- Departments of Oncology, Herlev‐Gentofte Hospital, University of CopenhagenHerlevDenmark
| | - Jens Faber
- Departments of Medicine, Herlev‐Gentofte Hospital, University of CopenhagenHerlevDenmark
- Faculty of Health and Medical Sciences, University of CopenhagenCopenhagenDenmark
| | - Tobias W. Klausen
- Departments of Hematology, Herlev‐Gentofte Hospital, University of CopenhagenHerlevDenmark
| | - Stig E. Bojesen
- Departments of Clinical Biochemistry, Herlev‐Gentofte Hospital, University of CopenhagenHerlevDenmark
- Faculty of Health and Medical Sciences, University of CopenhagenCopenhagenDenmark
| | - Merete Vaage‐Nilsen
- Departments of Cardiology, Herlev‐Gentofte Hospital, University of CopenhagenHerlevDenmark
| | - Dorte L. Nielsen
- Departments of Oncology, Herlev‐Gentofte Hospital, University of CopenhagenHerlevDenmark
- Faculty of Health and Medical Sciences, University of CopenhagenCopenhagenDenmark
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34
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Hu Q, Chang CP, Rowe K, Snyder J, Deshmukh V, Newman M, Fraser A, Smith K, Gren LH, Porucznik C, Stanford JB, Gaffney D, Henry NL, Lopez I, Hashibe M. Disparities in Cardiovascular Disease Risk Among Hispanic Breast Cancer Survivors in a Population-Based Cohort. JNCI Cancer Spectr 2021; 5:pkab016. [PMID: 33889806 PMCID: PMC8052955 DOI: 10.1093/jncics/pkab016] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Revised: 12/18/2020] [Accepted: 01/20/2021] [Indexed: 12/22/2022] Open
Abstract
Background Breast cancer is the leading cause of cancer death among Hispanic women. The aim of our study was to estimate cardiovascular disease (CVD) risk among Hispanic and non-Hispanic White (NHW) breast cancer survivors compared with their respective general population cohorts. Methods Cohorts of 17 469 breast cancer survivors (1774 Hispanic and 15 695 NHW) in the Utah Cancer Registry diagnosed between 1997 and 2016, and 65 866 women (6209 Hispanic and 59 657 NHW) from the general population in the Utah Population Database were identified. Cox proportional hazards models were used to estimate hazard ratios (HRs) for CVD. Results The risk of diseases of the circulatory system was higher in Hispanic than NHW breast cancer survivors 1-5 years after cancer diagnosis, in comparison with their respective general population cohorts (HRHispanic = 1.94, 99% confidence interval [CI] = 1.49 to 2.53; HNHW = 1.38, 99% CI = 1.33 to 1.43; 2-sided Pheterogeneity = .01, respectively). Increased risks were observed for both Hispanic and NHW breast cancer survivors for diseases of the heart and the veins and lymphatics, compared with the general population cohorts. More than 5 years after cancer diagnosis, elevated risk of diseases of the veins and lymphatics persisted in both ethnicities. The CVD risk due to chemotherapy and hormone therapy was higher in Hispanic than NHW breast cancer survivors but did not differ for distant stage, higher baseline comorbidities, or baseline smoking. Conclusions We observed a risk difference for diseases of the circulatory system between Hispanic and NHW breast cancer survivors compared with their respective general population cohorts but only within the first 5 years of cancer diagnosis.
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Affiliation(s)
- Qingqing Hu
- Division of Public Health, Department of Family & Preventive Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA.,Huntsman Cancer Institute, Salt Lake City, UT, USA
| | - Chun-Pin Chang
- Division of Public Health, Department of Family & Preventive Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA.,Huntsman Cancer Institute, Salt Lake City, UT, USA
| | - Kerry Rowe
- Intermountain Healthcare, Salt Lake City, UT, USA
| | - John Snyder
- Intermountain Healthcare, Salt Lake City, UT, USA
| | - Vikrant Deshmukh
- University of Utah Health Sciences Center, Salt Lake City, UT, USA
| | - Michael Newman
- University of Utah Health Sciences Center, Salt Lake City, UT, USA
| | - Alison Fraser
- Pedigree and Population Resource, Population Sciences, Huntsman Cancer Institute, Salt Lake City, UT, USA
| | - Ken Smith
- Pedigree and Population Resource, Population Sciences, Huntsman Cancer Institute, Salt Lake City, UT, USA
| | - Lisa H Gren
- Division of Public Health, Department of Family & Preventive Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA
| | - Christina Porucznik
- Division of Public Health, Department of Family & Preventive Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA
| | - Joseph B Stanford
- Division of Public Health, Department of Family & Preventive Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA
| | - David Gaffney
- Huntsman Cancer Institute, Salt Lake City, UT, USA.,Department of Radiation Oncology, University of Utah, Salt Lake City, UT, USA
| | - N Lynn Henry
- Division of Hematology/Oncology, University of Michigan Rogel Cancer Center, Ann Arbor, MI, USA
| | - Ivette Lopez
- Division of Public Health, Department of Family & Preventive Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA
| | - Mia Hashibe
- Division of Public Health, Department of Family & Preventive Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA.,Huntsman Cancer Institute, Salt Lake City, UT, USA.,Utah Cancer Registry, Salt Lake City, UT, USA
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35
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ECG Markers of Cardiovascular Toxicity in Adult and Pediatric Cancer Treatment. DISEASE MARKERS 2021; 2021:6653971. [PMID: 33532005 PMCID: PMC7837776 DOI: 10.1155/2021/6653971] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Revised: 12/20/2020] [Accepted: 01/07/2021] [Indexed: 12/22/2022]
Abstract
When a cardiologist is asked to evaluate the cardiac toxic effects of chemotherapy, he/she can use several tools: ECG, echocardiography, coronary angiography, ventriculography, and cardiac MRI. Of all these, the fastest and easiest to use is the ECG, which can provide information on the occurrence of cardiac toxic effects and can show early signs of subclinical cardiac damage. These warning signs are the most desired to be recognized by the cardiologist, because the dose of chemotherapeutics can be adjusted so that the clinical side effects do not occur, or the therapy can be stopped in time, before irreversible side effects. This review addresses the problem of early detection of cardiotoxicity in adult and pediatric cancer treatment, by using simple ECG recordings.
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36
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Wang Z, Qin W, Zhai Z, Huang L, Feng J, Guo X, Liu K, Zhang C, Wang Z, Lu G, Dong S. Use of spectral tracking technique to evaluate the changes in left ventricular function in patients undergoing chemotherapy for colorectal cancer. Int J Cardiovasc Imaging 2020; 37:1203-1213. [PMID: 33247369 DOI: 10.1007/s10554-020-02103-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Accepted: 11/08/2020] [Indexed: 12/21/2022]
Abstract
To evaluate the changes in left ventricular myocardial function in patients with colorectal cancer undergoing chemotherapy with mFOLFOX6 (oxaliplatin + 5-fluorouracil + calcium folinate) using three-dimensional speckle-tracking echocardiography (3D-STE). Data were collected from 30 patients diagnosed with colorectal cancer in our hospital treated with mFOLFOX6. We used 3D-STE to measure the following parameters of left ventricle function: global longitudinal strain (GLS), global area strain (GAS), global circumferential strain (GCS), global radial strain (GRS), and left ventricular twist (LVtw). Myocardial composite index (MCI) was calculated from measured values (MCI = GLS × LVtw). The above listed parameters were compared before and after chemotherapy. Receiver operating curves (ROC) were prepared for each parameter and analyzed to identify correlations among MCI, LVEF, GLS, and cTnT. Compared with the pre-chemotherapy state, the absolute values of MCI, LVtw, GLS, GAS, GCS, and GRS decreased with increasing cumulative doses of chemotherapeutic drugs. The absolute values of GAS, GLS, MCI, and LVtw decreased after the first cycle of chemotherapy (P < 0.05). The areas under the ROC curves for MCI and GLS were 0.903 and 0.838, respectively. The correlation observed between MCI and cTnT (r = - 0.7228) was found to be stronger than that between GLS and cTnT (r = - 0.6008). In conclusion, 3D-STE may help detect early changes in left ventricular myocardial function caused by mFOLFOX6 treatment in patients with colorectal cancer. MCI is a relatively sensitive index among the various measurable parameters.
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Affiliation(s)
- Zhen Wang
- Department of Ultrasonography, First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, 832008, China
| | - Wenjuan Qin
- Department of Ultrasonography, First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, 832008, China
| | - Zijing Zhai
- Department of Ultrasonography, First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, 832008, China
| | - Lei Huang
- Department of Ultrasonography, First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, 832008, China
| | - Jia Feng
- Department of Ultrasonography, First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, 832008, China
| | - Xueting Guo
- Department of Ultrasonography, First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, 832008, China
| | - Kuican Liu
- Department of Ultrasonography, First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, 832008, China
| | - Caiyun Zhang
- Department of Ultrasonography, First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, 832008, China
| | - Zhong Wang
- Department of Cardiology, First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, 832008, China
| | - Guilin Lu
- Department of Ultrasonography, First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, 832008, China.
| | - Shanshan Dong
- Department of Ultrasonography, First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, 832008, China.
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37
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Dimitrova IN. A Case of 5-Fluorouracil-Induced Coronary Artery Vasospasm in a Patient With Salivary Gland Cancer. Cureus 2020; 12:e10887. [PMID: 33178539 PMCID: PMC7652361 DOI: 10.7759/cureus.10887] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
5-Fluorouracil (5-FU), a pyrimidine analogue, is widely used in different chemotherapy regimens with established indications for the treatment of gastrointestinal, breast, head, and neck tumors. Various prospective studies including randomized controlled trials and retrospective reviews have shown a wide range of reported incidence of cardiotoxicity related to 5-FU use. This incidence is dependent on drug regimen, doses, concomitant therapy, patients’ clinical characteristics, and risk factors. Herein, we present a clinical case of coronary vasospasm mimicking ST-elevation myocardial infarction during a 5-FU infusion for salivary gland cancer. Cardiologists and oncologists must keep in mind the potential life-threatening side effects of 5-FU on the heart and they must be familiar with the risk factors for their occurrence and their management strategies.
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38
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39
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Batra A, Rigo R, Hannouf MB, Cheung WY. Real-world Safety and Efficacy of Raltitrexed in Patients With Metastatic Colorectal Cancer. Clin Colorectal Cancer 2020; 20:e75-e81. [PMID: 33268287 DOI: 10.1016/j.clcc.2020.09.006] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2020] [Revised: 09/01/2020] [Accepted: 09/14/2020] [Indexed: 12/28/2022]
Abstract
BACKGROUND Use of fluoropyrimidine-based therapy in patients with metastatic colorectal cancer is associated with significant toxicities. This study aimed to assess the safety and efficacy of raltitrexed use in patients with metastatic colorectal cancer who developed significant toxicities after fluoropyrimidine-based treatment. PATIENTS AND METHODS We identified patients with metastatic colorectal cancer who were treated with raltitrexed-based systemic therapy after developing serious adverse events with fluoropyrimidine-based treatment in a large Canadian province from 2004 to 2018. Demographic, tumor, and treatment characteristics were retrieved from the electronic medical records. Progression-free and overall survival were assessed from the start of raltitrexed-based therapy. RESULTS A total of 86 patients were identified for the study. The median age was 66.5 years, and 58.1% of patients were men. The primary cancer site was right, left, and transverse colon in 38.4%, 27.9%, and 9.3%, respectively. The remaining 24.4% had rectal cancer. Among all patients, 43.0% had received more than 2 prior systemic therapies, and 37.6% had developed previous cardiotoxicity to fluoropyrimidine-based treatment. The median progression-free and overall survival were 8.5 and 10.2 months, respectively. On multivariable Cox regression model, patients with left-sided colon cancer (hazard ratio [HR], 0.33; 95% confidence interval [CI], 0.12-0.97; P = .044) and the Eastern Cooperative Oncology Group performance status of 0/1 (HR, 0.10; 95% CI, 0.01-0.82; P = .032) had a longer progression-free survival, whereas left-sidedness of colon cancer was the only factor that predicted overall survival (HR, 0.30; 95% CI, 0.10-0.88; P = .029). Raltitrexed was well-tolerated with common adverse events that included anemia in 41.7% of patients and chemotherapy-induced nausea and vomiting in 27.4%. Most toxicities were grade 1/2, but 16.7% of patients experienced grade 3. There were no cardiac events and treatment-related deaths. CONCLUSIONS Raltitrexed in patients with colorectal cancer who were previously treated with fluoropyrimidine-based systemic therapy is effective and well-tolerated.
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Affiliation(s)
- Atul Batra
- Department of Medical Oncology, Tom Baker Cancer Center, Calgary, Alberta, Canada; University of Calgary, Calgary, Alberta, Canada
| | - Rodrigo Rigo
- Department of Medical Oncology, Tom Baker Cancer Center, Calgary, Alberta, Canada; University of Calgary, Calgary, Alberta, Canada
| | | | - Winson Y Cheung
- Department of Medical Oncology, Tom Baker Cancer Center, Calgary, Alberta, Canada; University of Calgary, Calgary, Alberta, Canada.
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40
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Abstract
Chemotherapy, alone or in association with radiation therapy, has represented the cornerstone of cancer treatment for decades. However, in the last several years, an unprecedented progress in the understanding of cancer biology and the discovery of novel therapeutic targets have led to a paradigm shift in the management of patients with neoplastic diseases. The introduction of tyrosine kinase inhibitors, vascular endothelial growth factor pathway inhibitors, immunomodulatory agents, proteasome inhibitors, immune checkpoint inhibitors, and chimeric antigen receptor T cells, among others, has been associated with prolonged survival in many forms of cancer. A common feature of both chemotherapy and novel cancer treatments is the frequent occurrence of vascular toxicity, mainly mediated by injury to the endothelium. While the mechanisms may vary between agents, the clinical manifestations may overlap and range from hypertension, vasospastic and thrombotic arterial events (myocardial ischemia and infarction, peripheral ischemia, and limb gangrene), venous thromboembolism (deep vein thrombosis and pulmonary embolism) to capillary leak syndrome. Therefore, the effective management of patients with cancer requires a multidisciplinary team approach in which oncologist and cardiovascular medicine specialists work together to prevent, detect, and minimize acute vascular toxicity and long-term consequences of cancer therapy.
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Affiliation(s)
- Umberto Campia
- Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
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41
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Muhammad RN, Sallam N, El-Abhar HS. Activated ROCK/Akt/eNOS and ET-1/ERK pathways in 5-fluorouracil-induced cardiotoxicity: modulation by simvastatin. Sci Rep 2020; 10:14693. [PMID: 32895407 PMCID: PMC7477553 DOI: 10.1038/s41598-020-71531-8] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2019] [Accepted: 08/18/2020] [Indexed: 12/11/2022] Open
Abstract
5-Fluorouracil (5-FU) is used in the treatment of different solid tumors; however, its use is associated with rare, but serious cardiotoxicity. Nevertheless, the involvement of ROCK/NF-κB, Akt/eNOS and ET-1/ERK1/2 trajectories in the cardiotoxic effect and in the potential cardioprotective upshot of simvastatin has been elusive. Male Wistar rats were allocated into 5-FU (50 mg/kg/week; i.p, 6 weeks), simvastatin (15 mg/kg/day; p.o, 8 weeks) treated groups and simvastatin + 5-FU, besides the normal control group. 5-FU-induced cardiotoxicity boosted the serum level of N-terminal pro-brain (B-type) natriuretic peptide (NT-proBNP), aortic contents of endothelin (ET)-1 and thromboxane (TX) A2, as well as cardiac contents of NADPH oxidases (Nox), cyclooxygenase (COX)-2, malondialdehyde (MDA), phosphorylated Akt (p-Akt), phosphorylated extracellular signal-regulated kinase (p-ERK)1/2 and the protein expressions of rho-kinase (ROCK) and caspase-3. On the other hand, it suppressed cardiac reduced glutathione (GSH) and phosphorylated endothelial nitric oxide synthase (p-eNOS). Contrariwise, co-administration with simvastatin overcame these disturbed events and modulated the ROCK/NF-κB, Akt/eNOS and ET-1/ERK1/2 signaling pathways. This study highlights other mechanisms than coronary artery spasm in the 5-FU cardiotoxicity and reveals that NT-proBNP is a potential early marker in this case. Moreover, the cross-talk between ROCK/ NF-κB, ROS/COX-2/TXA2, Akt/eNOS and ET-1/ERK1/2 pathways contributes via different means to upsetting the vasoconstriction/vasodilatation equilibrium as well as endothelial cell function and finally leads to cardiomyocyte stress and death-the modulation of these trajectories offers simvastatin its potential cardio-protection against 5-FU.
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Affiliation(s)
- Radwa Nasser Muhammad
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt.
| | - Nada Sallam
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt
| | - Hanan Salah El-Abhar
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt
- Department of Pharmacology & Toxicology, Faculty of Pharmaceutical Sciences and Pharmaceutical Industries, Future University in Egypt, Cairo, 11835, Egypt
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42
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Desai A, Mohammed T, Patel KN, Almnajam M, Kim AS. 5-Fluorouracil Rechallenge After Cardiotoxicity. AMERICAN JOURNAL OF CASE REPORTS 2020; 21:e924446. [PMID: 32860674 PMCID: PMC7483515 DOI: 10.12659/ajcr.924446] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Patient: Male, 66-year-old Final Diagnosis: Colon adenocarcinoma • ventricular arrhythmia Symptoms: Cardiac arrest • syncope Medication: — Clinical Procedure: Cardiac catheterization • Cardiac Electronic Implantable Device (CEID) Specialty: Cardiology • General and Internal Medicine • Oncology
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Affiliation(s)
- Aakash Desai
- Department of Medicine, University of Connecticut Health, Farmington, CT, USA
| | - Turab Mohammed
- Department of Medicine, University of Connecticut Health, Farmington, CT, USA
| | - Kunal N Patel
- Department of Epidemiology and Biostatistics, School of Public Health, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA
| | - Mansour Almnajam
- Division of Cardiology, Department of Medicine, University of Connecticut Health, Farmington, CT, USA
| | - Agnes S Kim
- Division of Cardiology, Department of Medicine, University of Connecticut Health, Farmington, CT, USA
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Abstract
OPINION STATEMENT Fluoropyrimidine (FP) is used to treat a wide range of cancers; however, it is associated with drug-induced vascular toxicity, as well as angina pectoris and coronary spasm. FP has been administered for many years, although the incidence, mechanisms, and appropriate methods for managing its associated cardiovascular toxicities have not been clarified, and the management of these complications has not been standardized. This lack of evidence is not limited to FP. Many trials of anticancer agents have been conducted, excluding patients with heart diseases. Hence, there is a paucity of epidemiological data on cardiovascular adverse events caused by anticancer agents. There have been remarkable improvements in cancer treatment in recent years, with consequent improvements in prognosis. In this context, new cardiovascular toxicities related to new drugs have emerged. We are now compelled to respond to cardiovascular adverse events despite the lack of evidence regarding optimal management. The result has been establishment and rapid maturation of the new academic field of cardio-oncology. Despite the relative lack of evidence, we must review small pieces of evidence that have accumulated to date and make the utmost efforts to provide patients with effective evidence-based medical care. Simultaneously, we urgently need randomized clinical trials to build strong evidence.
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Affiliation(s)
- Taro Shiga
- Department of Onco-Cardiology/Cardiovascular Medicine, The Cancer Institute Hospital Of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.
| | - Makoto Hiraide
- Department of Pharmacy, The Cancer Institute Hospital Of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan
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44
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Campia U, Moslehi JJ, Amiri-Kordestani L, Barac A, Beckman JA, Chism DD, Cohen P, Groarke JD, Herrmann J, Reilly CM, Weintraub NL. Cardio-Oncology: Vascular and Metabolic Perspectives: A Scientific Statement From the American Heart Association. Circulation 2019; 139:e579-e602. [PMID: 30786722 DOI: 10.1161/cir.0000000000000641] [Citation(s) in RCA: 134] [Impact Index Per Article: 22.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Cardio-oncology has organically developed as a new discipline within cardiovascular medicine as a result of the cardiac and vascular adverse sequelae of the major advances in cancer treatment. Patients with cancer and cancer survivors are at increased risk of vascular disease for a number of reasons. First, many new cancer therapies, including several targeted therapies, are associated with vascular and metabolic complications. Second, cancer itself serves as a risk factor for vascular disease, especially by increasing the risk for thromboembolic events. Finally, recent data suggest that common modifiable and genetic risk factors predispose to both malignancies and cardiovascular disease. Vascular complications in patients with cancer represent a new challenge for the clinician and a new frontier for research and investigation. Indeed, vascular sequelae of novel targeted therapies may provide insights into vascular signaling in humans. Clinically, emerging challenges are best addressed by a multidisciplinary approach in which cardiovascular medicine specialists and vascular biologists work closely with oncologists in the care of patients with cancer and cancer survivors. This novel approach realizes the goal of providing superior care through the creation of cardio-oncology consultative services and the training of a new generation of cardiovascular specialists with a broad understanding of cancer treatments.
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45
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Nohria A. The clinical conundrum of managing 5-fluorouracil-induced vasospasm in colorectal carcinoma. Cancer 2019; 125:4346-4349. [PMID: 31544232 DOI: 10.1002/cncr.32486] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2019] [Accepted: 08/01/2019] [Indexed: 11/07/2022]
Affiliation(s)
- Anju Nohria
- Cardio-Oncology Program, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts
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46
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Raina AJ, Gilbar PJ, Grewal GD, Holcombe DJ. Optic neuritis induced by 5-fluorouracil chemotherapy: Case report and review of the literature. J Oncol Pharm Pract 2019; 26:511-516. [PMID: 31735134 DOI: 10.1177/1078155219886640] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Introduction For over 50 years, 5-Fluorouracil has played a critical role in the treatment of numerous malignancies, including colorectal cancer. Ocular side effects are uncommon and include blurred vision, conjunctivitis, excessive lacrimation and keratitis. Case report We report a 57-year-old male with metastatic colorectal cancer who had received extensive chemotherapy with 5-Fluorouracil-based regimens for over 12 months. Following his seventh cycle of cetuximab/FOLFIRI, he developed acute onset global headache, nausea and loss of vision in the right eye. After detailed investigations, including ophthalmologic and neurologic consultations, a diagnosis of optic neuritis was made. Management and outcome Chemotherapy was ceased immediately, and intravenous methylprednisolone (1 g) daily for five days was commenced. His headache resolved and vision started to improve within 24 h. Three weeks after completion of corticosteroids, constriction of the right visual field had fully resolved. Discussion Atypical optic neuritis is an inflammatory optic neuropathy that can be caused by ischaemia, mechanical compression, nutritional deficiency, toxins and drugs. Drug-induced optic neuritis, while rare, is associated with cytotoxic medications including methotrexate, cisplatin, carboplatin, vincristine and paclitaxel. There have only been five previous case reports implicating 5-Fluorouracil in the development of optic neuropathy. The likelihood of the adverse drug reaction due to 5-Fluorouracil was assessed using the Naranjo algorithm. A score of +7 indicates probable causality. Clinicians should be alert to this potential ocular toxicity in order to initiate prompt cessation of treatment and early ophthalmology referral to prevent visual loss and damage to ocular structures.
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Affiliation(s)
- Anant J Raina
- Cancer Care Services, Toowoomba Hospital, Toowoomba, Australia.,Rural Clinical School, Faculty of Medicine, The University of Queensland, Toowoomba, Australia
| | - Peter J Gilbar
- Cancer Care Services, Toowoomba Hospital, Toowoomba, Australia.,Rural Clinical School, Faculty of Medicine, The University of Queensland, Toowoomba, Australia
| | - Guranjan D Grewal
- Cancer Care Services, Toowoomba Hospital, Toowoomba, Australia.,Rural Clinical School, Faculty of Medicine, The University of Queensland, Toowoomba, Australia
| | - David J Holcombe
- Rural Clinical School, Faculty of Medicine, The University of Queensland, Toowoomba, Australia.,Toowoomba Ophthalmic Consultants, Toowoomba, Australia
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47
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Alomar M, Fradley MG. Electrophysiology Translational Considerations in Cardio-Oncology: QT and Beyond. J Cardiovasc Transl Res 2019; 13:390-401. [DOI: 10.1007/s12265-019-09924-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2019] [Accepted: 10/04/2019] [Indexed: 12/14/2022]
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48
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Redman JM, Rhea LP, Brofferio A, Whelpley M, Gulley JL, Gatti-Mays ME, McMahon S, Cordes LM, Strauss J. Successful 5-fluorouracil (5-FU) infusion re-challenge in a metastatic colorectal cancer patient with coronary artery disease who experienced symptoms consistent with coronary vasospasm during first 5-FU infusion. J Gastrointest Oncol 2019; 10:1010-1014. [PMID: 31602339 DOI: 10.21037/jgo.2019.07.04] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
5-fluorouracil (5-FU) is an important component of chemotherapy for metastatic colon cancer and can be administered as an intravenous infusion or bolus. Coronary vasospasm is a known complication of infusional and bolus 5-FU administration. In patients who experience coronary vasospasm, 5-FU is often discontinued. Several cases of successful re-challenge with bolus 5-FU, utilizing calcium channel blockers (CCBs) and nitrates to prophylaxis against coronary vasospasm recurrence, have been reported in the literature. However, since there is increased variability of time to symptom onset with infusional 5-FU, re-challenge with infusional 5-FU has not been widely studied. Given potential differences in the toxicity profile and exposure time, infusional may be more appropriate than bolus for some patients. Here we report successful re-challenge with infusional 5-FU, following coronary vasospasm during the first cycle of 5-FU plus leucovorin plus oxaliplatin chemotherapy, in a patient with metastatic colon cancer and coronary artery disease (CAD). The 5-FU re-challenge plan included dose reduction, CCB and nitrate prophylaxis, and telemetry monitoring.
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Affiliation(s)
- Jason M Redman
- Genitourinary Malignancy Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.,Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Logan P Rhea
- Department of Medicine, Inova Fairfax Medical Campus, Falls Church, VA, USA
| | - Alessandra Brofferio
- Cardiology Consult Service, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA
| | - Margaret Whelpley
- Cardiology Consult Service, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA
| | - James L Gulley
- Genitourinary Malignancy Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.,Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Margaret E Gatti-Mays
- Genitourinary Malignancy Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.,Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Sheri McMahon
- Genitourinary Malignancy Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Lisa M Cordes
- Genitourinary Malignancy Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Julius Strauss
- Genitourinary Malignancy Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.,Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
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49
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Joy G, Eissa H, Al Karoudi R, White SK. Fluorouracil-induced Takotsubo cardiomyopathy causing cardiogenic shock: a case report of clinical and acute cardiac magnetic resonance imaging features. EUROPEAN HEART JOURNAL-CASE REPORTS 2019; 3:1-6. [PMID: 31911978 PMCID: PMC6939794 DOI: 10.1093/ehjcr/ytz146] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/28/2019] [Revised: 03/26/2019] [Accepted: 09/06/2019] [Indexed: 01/13/2023]
Abstract
Background Takotsubo cardiomyopathy (TTS) is an extremely rare complication of fluorouracil containing chemotherapy regimes such as FOLFOX used for colorectal cancer, occurring in only five previous case reports. Due to its potentially fatal outcomes, yet infrequent presence in the literature, it is worthwhile reviewing the clinical features and outcomes of this phenomenon. Case summary A 54-year-old lady was admitted with cardiogenic shock. A cardiac magnetic resonance imaging (CMR) showed mid-ventricle to apical hypokinesis and confirmed TTS. She was managed with inotropes and non-invasive ventilation after which she recovered fully both clinically and in her CMR features 6 weeks following discharge. Discussion This is the first case showing the acute CMR features of this complication and highlights the need for awareness of this rarely occurring cardiotoxicity. It also shows the potentially fatal phenomenon can be fully reversible when diagnosed and managed promptly even in patients with metastatic cancer and critical illness.
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Affiliation(s)
- George Joy
- Cardiology Department, Conquest Hospital, The Ridge, Hastings, Saint Leonards-on-Sea, TN37 7RD, UK
| | - Hany Eissa
- Cardiology Department, Queen Elizabeth Queen Mother Hospital, St Peter's Rd, Margate CT9 4AN, UK
| | - Riyad Al Karoudi
- Cardiology Department, Queen Elizabeth Queen Mother Hospital, St Peter's Rd, Margate CT9 4AN, UK
| | - Steven K White
- Cardiology Department, Queen Elizabeth Queen Mother Hospital, St Peter's Rd, Margate CT9 4AN, UK
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50
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Moriyama S, Yokoyama T, Irie K, Ito M, Tsuchihashi K, Fukata M, Kusaba H, Maruyama T, Akashi K. Atrial fibrillation observed in a patient with esophageal cancer treated with fluorouracil. J Cardiol Cases 2019; 20:183-186. [PMID: 31719941 PMCID: PMC6834961 DOI: 10.1016/j.jccase.2019.08.005] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Revised: 07/18/2019] [Accepted: 07/30/2019] [Indexed: 11/20/2022] Open
Abstract
Fluorouracil (5-FU), a commonly used anticancer agent, has potent cardiotoxicity that is mediated by vascular endothelial injury and vasospasm. Here, we report a patient demonstrating atrial fibrillation (AF), which was most likely induced by vasospasm mediated by 5-FU. A 69-year-old man presented with dysphagia and was diagnosed with advanced esophageal cancer. Frequent paroxysms of atrial fibrillation (AF) were observed during combination chemotherapy including 5-FU. AF was refractory to disopyramide, but was sensitive to antianginal agents (nicorandil and nitroglycerin transdermal patch). Coronary angiography performed within the chemotherapeutic period demonstrated moderate stenosis in the right coronary artery (RCA). Severe spasm at the proximal portion of the atrial branch in RCA was induced by provocation test using acetylcholine. Our case indicated that 5-FU predisposed vasospasm in RCA and the subsequent atrial ischemia may lead to AF. <Learning objective: Fluorouracil (5-FU), a commonly used anticancer agent, induces cardiac ischemic events and sometimes leads to the paroxysms of atrial fibrillation (AF). Coronary-dilating agents should be considered for the treatment of AF which occurs after the administration of 5-FU and is refractory to antiarrhythmic agents.>
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Affiliation(s)
- Shohei Moriyama
- Corresponding author at: Department of Hematology/Oncology/Cardiovascular Medicine, Kyushu University Hospital, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8586, Japan.
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