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Bloom MW, Vo JB, Rodgers JE, Ferrari AM, Nohria A, Deswal A, Cheng RK, Kittleson MM, Upshaw JN, Palaskas N, Blaes A, Brown SA, Ky B, Lenihan D, Maurer MS, Fadol A, Skurka K, Cambareri C, Chauhan C, Barac A. Cardio-Oncology and Heart Failure: a Scientific Statement From the Heart Failure Society of America. J Card Fail 2024:S1071-9164(24)00363-4. [PMID: 39419165 DOI: 10.1016/j.cardfail.2024.08.045] [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: 04/16/2024] [Revised: 08/27/2024] [Accepted: 08/28/2024] [Indexed: 10/19/2024]
Abstract
Heart failure and cancer remain 2 of the leading causes of morbidity and mortality, and the 2 disease entities are linked in a complex manner. Patients with cancer are at increased risk of cardiovascular complications related to the cancer therapies. The presence of cardiomyopathy or heart failure in a patient with new cancer diagnosis portends a high risk for adverse oncology and cardiovascular outcomes. With the rapid growth of cancer therapies, many of which interfere with cardiovascular homeostasis, heart failure practitioners need to be familiar with prevention, risk stratification, diagnosis, and management strategies in cardio-oncology. This Heart Failure Society of America statement addresses the complexities of heart failure care among patients with active cancer diagnoses and cancer survivors. Risk stratification, monitoring and management of cardiotoxicity are presented across stages A through D heart failure, with focused discussion on heart failure with preserved ejection fraction and special populations, such as survivors of childhood and young-adulthood cancers. We provide an overview of the shared risk factors between cancer and heart failure, highlighting heart failure as a form of cardiotoxicity associated with many different cancer therapeutics. Finally, we discuss disparities in the care of patients with cancer and cardiac disease and present a framework for a multidisciplinary-team approach and critical collaboration among heart failure, oncology, palliative care, pharmacy, and nursing teams in the management of these complex patients.
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Affiliation(s)
| | - Jacqueline B Vo
- Radiation Epidemiology Branch, Division of Cancer Epidemiology & Genetics, National Cancer Institute, Bethesda, MD
| | - Jo E Rodgers
- Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, Chapel Hill, NC
| | - Alana M Ferrari
- Division of Hematology/ Oncology, University of Virginia Health, Charlottesville, VA
| | - Anju Nohria
- Cardio-Oncology Program, Cardiovascular Division, Brigham and Women's Hospital, Boston, MA
| | - Anita Deswal
- Department of Cardiology, University of Texas MD Anderson Cancer Center, Houston, TX
| | - Richard K Cheng
- Division of Cardiology, University of Washington, Seattle, WA
| | - Michelle M Kittleson
- Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA
| | | | - Nicolas Palaskas
- Department of Cardiology, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Anne Blaes
- Division of Hematology/Oncology/Transplantation, University of Minnesota, Minneapolis, MN
| | - Sherry-Ann Brown
- Department of Medicine, Medical College of Wisconsin, Milwaukee, WI; Research Collaborator, Mayo Clinic, Rochester, MN
| | - Bonnie Ky
- Division of Cardiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; Thalheimer Center for Cardio-Oncology, Abramson Cancer Center and Division of Cardiovascular Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Daniel Lenihan
- Saint Francis Healthcare, Cape Girardeau, MO and the International Cardio-Oncology Society, Tampa, FL
| | - Mathew S Maurer
- Division of Cardiology, Columbia University Irving Medical Center, New York, NY
| | | | | | - Christine Cambareri
- Clinical Oncology Pharmacist, Hospital of the University of Pennsylvania, Abramson Cancer Center, Philadelphia, PA
| | | | - Ana Barac
- Department of Cardiology, Inova Schar Heart and Vascular, Inova Schar Cancer, Falls Church, VA
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Veettil S, Khan O, Durocher DP. Takotsubo Cardiomyopathy After Oxaliplatin Chemotherapy Exposure: A Case Report. CJC Open 2024; 6:1174-1177. [PMID: 39525344 PMCID: PMC11544183 DOI: 10.1016/j.cjco.2024.07.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Accepted: 07/07/2024] [Indexed: 11/16/2024] Open
Affiliation(s)
- Shafaz Veettil
- Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada
| | - Omar Khan
- Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada
| | - Daniel P. Durocher
- Division of Cardiology, Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada
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3
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Jiang R, Lou L, Shi W, Chen Y, Fu Z, Liu S, Sok T, Li Z, Zhang X, Yang J. Statins in Mitigating Anticancer Treatment-Related Cardiovascular Disease. Int J Mol Sci 2024; 25:10177. [PMID: 39337662 PMCID: PMC11432657 DOI: 10.3390/ijms251810177] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Revised: 09/14/2024] [Accepted: 09/20/2024] [Indexed: 09/30/2024] Open
Abstract
Certain anticancer therapies inevitably increase the risk of cardiovascular events, now the second leading cause of death among cancer patients. This underscores the critical need for developing effective drugs or regimens for cardiovascular protection. Statins possess properties such as antioxidative stress, anti-inflammatory effects, antifibrotic activity, endothelial protection, and immune modulation. These pathological processes are central to the cardiotoxicity associated with anticancer treatment. There is prospective clinical evidence confirming the protective role of statins in chemotherapy-induced cardiotoxicity. Numerous preclinical studies have demonstrated that statins can ameliorate heart and endothelial damage caused by radiotherapy, although clinical studies are scarce. In the animal models of trastuzumab-induced cardiomyopathy, statins provide protection through anti-inflammatory, antioxidant, and antifibrotic mechanisms. In animal and cell models, statins can mitigate inflammation, endothelial damage, and cardiac injury induced by immune checkpoint inhibitors. Chimeric antigen receptor (CAR)-T cell therapy-induced cardiotoxicity and immune effector cell-associated neurotoxicity syndrome are associated with uncontrolled inflammation and immune activation. Due to their anti-inflammatory and immunomodulatory effects, statins have been used to manage CAR-T cell therapy-induced immune effector cell-associated neurotoxicity syndrome in a clinical trial. However, direct evidence proving that statins can mitigate CAR-T cell therapy-induced cardiotoxicity is still lacking. This review summarizes the possible mechanisms of anticancer therapy-induced cardiotoxicity and the potential mechanisms by which statins may reduce related cardiac damage. We also discuss the current status of research on the protective effect of statins in anticancer treatment-related cardiovascular disease and provide directions for future research. Additionally, we propose further studies on using statins for the prevention of cardiovascular disease in anticancer treatment.
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Affiliation(s)
- Rong Jiang
- Department of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Lian Lou
- Department of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Wen Shi
- Department of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Yuxiao Chen
- Department of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Zhaoming Fu
- Department of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Shuo Liu
- Department of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Thida Sok
- Department of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Zhihang Li
- Department of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Xuan Zhang
- Department of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Jian Yang
- Department of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
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4
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Tini G, Arcari L, Mistrulli R, Follesa F, Cianca A, Sclafani M, Tocci G, Spallarossa P, Battistoni A, Cacciotti L, Musumeci B, Barbato E. A contemporary update on cancer and takotsubo syndrome. Front Cardiovasc Med 2024; 10:1301383. [PMID: 38259302 PMCID: PMC10800806 DOI: 10.3389/fcvm.2023.1301383] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2023] [Accepted: 12/18/2023] [Indexed: 01/24/2024] Open
Abstract
Takotsubo syndrome (TTS) is characterized by a transient left ventricular systolic dysfunction, burdened by significant acute and long-term mortality and morbidity. The prognosis of TTS, especially in the long-term, is influenced by both non-cardiovascular (non-CV) and CV comorbidities, among which cancer is one of the most common. The presence of a malignancy is proven to be associated with higher mortality in TTS. Moreover, a number of anticancer treatments has been reported to possibly cause TTS as a form of cardiotoxicity, even though clearcut associations are lacking. The aim of this narrative review is to sum up contemporary knowledge on the association of cancer and TTS, addressing unmet needs and practical implications. The importance of a close collaboration between cardiologists and oncologists is herein highlighted, both to allow an adequate management of the acute TTS phase, and to actively and safely return to the oncologic management once the acute setting is resolved.
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Affiliation(s)
- Giacomo Tini
- Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy
| | - Luca Arcari
- Cardiology Unit, Madre Giuseppina Vannini Hospital, Rome, Italy
- Department of Clinical, Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Policlinico Umberto I, Rome, Italy
| | - Raffaella Mistrulli
- Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy
| | - Federico Follesa
- Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy
| | - Alessandro Cianca
- Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy
| | - Matteo Sclafani
- Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy
| | - Giuliano Tocci
- Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy
| | - Paolo Spallarossa
- Cardiovascular Disease Unit, IRCCS Ospedale Policlinico San Martino—IRCCS Italian Cardiology Network, Genova, Italy
| | - Allegra Battistoni
- Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy
| | - Luca Cacciotti
- Cardiology Unit, Madre Giuseppina Vannini Hospital, Rome, Italy
| | - Beatrice Musumeci
- Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy
| | - Emanuele Barbato
- Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy
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Osawa T, Tajiri K, Ieda M, Ishizu T. Clinical outcomes of takotsubo syndrome in patients with cancer: a systematic review and meta-analysis. Front Cardiovasc Med 2023; 10:1244808. [PMID: 37840966 PMCID: PMC10570743 DOI: 10.3389/fcvm.2023.1244808] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Accepted: 09/14/2023] [Indexed: 10/17/2023] Open
Abstract
Background Recent studies suggested a relationship between Takotsubo syndrome (TTS) and malignancy. However, clinical outcomes of TTS associated with cancer have not been assessed completely. This study was aimed to investigate the outcomes of patients with TTS and cancer. Methods We performed a systematic review and meta-analysis to evaluate the clinical outcomes of TTS in patients with and without malignancy. We systematically reviewed and analyzed 14 studies (189,210 patients) published in PubMed and Cochrane Library databases until December 2022. The primary outcome was all-cause mortality at the longest follow-up. Results The prevalence of current or previous malignancy in patients with TTS was 8.7% (16,461 patients). Patients with TTS and malignancy demonstrated a higher risk of mortality at the longest follow-up than those with TTS alone (odds ratio [OR], 2.41; 95% confidence interval [CI]; 1.95-2.98; P < 0.001). Moreover, cancer was significantly associated with an increased risk of in-hospital or 30-day mortality (OR 2.36; 95% CI, 1.67-3.33; P < 0.001), shock (OR 1.42; 95% CI, 1.30-1.55; P < 0.001), mechanical respiratory support (OR 1.68; 95% CI, 1.59-1.77; P < 0.001), arrhythmia (OR 1.27; 95% CI, 1.21-1.34; P < 0.001), and major adverse cardiac events (OR 1.69; 95% CI, 1.18-2.442; P < 0.001). Conclusions This study revealed significant associations between previous or active cancer and an increased risk of all-cause mortality and in-hospital adverse events in patients with TTS.
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Affiliation(s)
- Takumi Osawa
- Department of Cardiology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
- Department of Cardiology, Tsukuba Medical Center Hospital, Tsukuba, Japan
- Department of Cardiology, National Cancer Center Hospital East, Kashiwa, Japan
| | - Kazuko Tajiri
- Department of Cardiology, National Cancer Center Hospital East, Kashiwa, Japan
- Tsukuba Life Science Innovation Program (T-LSI), School of Integrative and Global Majors (SIGMA), University of Tsukuba, Tsukuba, Japan
| | - Masaki Ieda
- Department of Cardiology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Tomoko Ishizu
- Department of Cardiology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
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Zagami P, Nicolò E, Corti C, Valenza C, Curigliano G. New Concepts in Cardio-Oncology. Cancer Treat Res 2023; 188:303-341. [PMID: 38175351 DOI: 10.1007/978-3-031-33602-7_12] [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] [Indexed: 01/05/2024]
Abstract
Cancer and cardiovascular disease are the two major causes of morbidity and mortality in worldwide. Discovering new therapeutic agents for the management of breast cancer (BC) has increased the numbers of cancer survivors but with the risk of cardiovascular adverse events (CV-AEs). All drugs can potentially damage the cardiovascular system, with different types of clinical manifestations from ischemic myocardial disease to vasculitis, thrombosis or pericarditis. An early detection of CV-AEs guarantees an earlier treatment, which is associated with better outcomes. Cardio-oncology field enlarged its studies to improve prevention, monitoring and treatment of all cardiotoxic manifestations related to old or modern oncological agents. A multidisciplinary approach with a close partnership between oncologists and cardiologists is essential for an optimal management and therapeutic decision-making. The aim of this chapter is to review all types of cardiotoxic manifestations related to novel and old agents approved for treatment of BC patients including chemotherapy, anti-HER2 agents, cyclin-dependent kinase 4/6 inhibitors, PolyADP-ribose polymerase (PARP) inhibitors, antiangiogenic drugs and immunotherapy. We also focused our discussion on prevention, monitoring, treatment, and management of CV-AEs.
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Affiliation(s)
- Paola Zagami
- Division of Early Drug Development for Innovative Therapies, IEO, European Institute of Oncology IRCCS, Milan, Italy.
- Department of Oncology and Hematology, University of Milano, Milan, Italy.
| | - Eleonora Nicolò
- Division of Early Drug Development for Innovative Therapies, IEO, European Institute of Oncology IRCCS, Milan, Italy
- Department of Oncology and Hematology, University of Milano, Milan, Italy
| | - Chiara Corti
- Division of Early Drug Development for Innovative Therapies, IEO, European Institute of Oncology IRCCS, Milan, Italy
- Department of Oncology and Hematology, University of Milano, Milan, Italy
| | - Carmine Valenza
- Division of Early Drug Development for Innovative Therapies, IEO, European Institute of Oncology IRCCS, Milan, Italy
- Department of Oncology and Hematology, University of Milano, Milan, Italy
| | - Giuseppe Curigliano
- Division of Early Drug Development for Innovative Therapies, IEO, European Institute of Oncology IRCCS, Milan, Italy
- Department of Oncology and Hematology, University of Milano, Milan, Italy
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Osorio-Toro LM, Bonilla-Bonilla DM, Escobar-Dávila SL, Quintana-Ospina JH, Melo-Burbano LÁ, Benitez-Escobar EN, Galindes-Casanova DA, Daza-Arana JE, Rivas-Tafurt GP. Oxaliplatin-Associated Takotsubo Cardiomyopathy in a Patient with Metastatic Gastric Cancer: A Case Report. Case Rep Oncol 2023; 16:613-620. [PMID: 37900810 PMCID: PMC10601726 DOI: 10.1159/000531389] [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: 10/26/2022] [Accepted: 05/26/2023] [Indexed: 10/31/2023] Open
Abstract
We present the case of a 64-year-old female with stage IV gastric adenocarcinoma, pulmonary, and abdominal wall metastases, and no history of cardiovascular disease. In palliative care, she received systemic cytotoxic treatment with fluorouracil, leucovorin, oxaliplatin, and docetaxel protocol, which was well tolerated over five cycles. During cycle 6, she presented with cardiovascular symptoms with hemodynamic consequences while receiving oxaliplatin injection without docetaxel or 5-fluorouracil. She was transferred to the emergency department and then to the intensive care unit. She developed no complications during the hospital stay and was discharged after 10 days with preserved systolic function and no structural changes at the myocardial level. The electrocardiogram, echocardiogram, cardiac catheterization, and magnetic resonance imaging findings indicated an oxaliplatin-associated Takotsubo syndrome. The immunochemistry analysis showed PD-L1 expression level TPS: 40% and the foundation one genomic profiling revealed high mutation load, microsatellite instability, and HER2 not found. The patient is currently asymptomatic and on pembrolizumab monotherapy with good tolerance and partial treatment response.
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Affiliation(s)
- Luis Miguel Osorio-Toro
- Specialization Program in Internal Medicine, School of Health, Universidad Santiago de Cali, Santiago de Cali, Colombia
- Research and Education Department, Clínica de Occidente S.A., Santiago de Cali, Colombia
- Genetics, Physiology and Metabolism Research Group (GEFIME), Universidad Santiago de Cali, Santiago de Cali, Colombia
| | - Diana Marcela Bonilla-Bonilla
- Specialization Program in Internal Medicine, School of Health, Universidad Santiago de Cali, Santiago de Cali, Colombia
- Research and Education Department, Clínica de Occidente S.A., Santiago de Cali, Colombia
- Genetics, Physiology and Metabolism Research Group (GEFIME), Universidad Santiago de Cali, Santiago de Cali, Colombia
| | - Santiago Leandro Escobar-Dávila
- Research and Education Department, Clínica de Occidente S.A., Santiago de Cali, Colombia
- Department of Medical Oncology, Comprehensive Cancer Center, Clínica de Occidente S.A., Santiago de Cali, Colombia
| | - Jhon Herney Quintana-Ospina
- Specialization Program in Internal Medicine, School of Health, Universidad Santiago de Cali, Santiago de Cali, Colombia
- Research and Education Department, Clínica de Occidente S.A., Santiago de Cali, Colombia
| | - Luis Álvaro Melo-Burbano
- Specialization Program in Internal Medicine, School of Health, Universidad Santiago de Cali, Santiago de Cali, Colombia
- Research and Education Department, Clínica de Occidente S.A., Santiago de Cali, Colombia
- Genetics, Physiology and Metabolism Research Group (GEFIME), Universidad Santiago de Cali, Santiago de Cali, Colombia
| | - Edith Norela Benitez-Escobar
- Specialization Program in Internal Medicine, School of Health, Universidad Santiago de Cali, Santiago de Cali, Colombia
- Research and Education Department, Clínica de Occidente S.A., Santiago de Cali, Colombia
- Genetics, Physiology and Metabolism Research Group (GEFIME), Universidad Santiago de Cali, Santiago de Cali, Colombia
| | - Duván Arley Galindes-Casanova
- Specialization Program in Internal Medicine, School of Health, Universidad Santiago de Cali, Santiago de Cali, Colombia
- Research and Education Department, Clínica de Occidente S.A., Santiago de Cali, Colombia
- Genetics, Physiology and Metabolism Research Group (GEFIME), Universidad Santiago de Cali, Santiago de Cali, Colombia
| | - Jorge Enrique Daza-Arana
- Specialization Program in Internal Medicine, School of Health, Universidad Santiago de Cali, Santiago de Cali, Colombia
- Health and Movement Research Group, Universidad Santiago de Cali, Santiago de Cali, Colombia
| | - Giovanna Patricia Rivas-Tafurt
- Specialization Program in Internal Medicine, School of Health, Universidad Santiago de Cali, Santiago de Cali, Colombia
- Department of Medical Oncology, Comprehensive Cancer Center, Clínica de Occidente S.A., Santiago de Cali, Colombia
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Bairashevskaia AV, Belogubova SY, Kondratiuk MR, Rudnova DS, Sologova SS, Tereshkina OI, Avakyan EI. Update of Takotsubo cardiomyopathy: Present experience and outlook for the future. IJC HEART & VASCULATURE 2022; 39:100990. [PMID: 35281752 PMCID: PMC8913320 DOI: 10.1016/j.ijcha.2022.100990] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Revised: 02/24/2022] [Accepted: 03/01/2022] [Indexed: 11/21/2022]
Abstract
Takotsubo cardiomyopathy (TTS) has become a recognised clinical entity since the Japanese scientist Sato first described it in 1990. Despite an increasing number of confirmed cases, especially during the COVID-19 pandemic, its pathophysiology remains incompletely understood, and decision-making differs in the diagnosis and treatment. In addition, it is not evident whether a significant increase in TTS is due to better understanding among practitioners and widespread access to coronary angiography, or if it is a reflection of an actual increase in incidence. We analysed a series of international research studies from 1990 to 2021. Beyond epidemiology and clinical presentation, we evaluated and summarised fundamental knowledge about various predisposing factors, with particular attention to the iatrogenic impact of certain drugs, namely antidepressants, chemotherapy, and antiarrhythmics. Furthermore, we highlighted the main pathophysiological theories to date. In addition, based on published studies and clinical cases, we investigated the role of numerous diagnostic approaches in the differential diagnosis of TTS and identified predictors of TTS complications, such as cardiogenic shock, ventricular fibrillation, and left ventricular thrombi. Accordingly, we sought to propose a diagnostic algorithm and further treatment management of TTS under the presence of possible complications to help practitioners make more informed decisions, as the initial presentation continues to pose a challenge due to its close similarity to acute coronary syndrome with ST-elevation. In conclusion, this article examines Takotsubo cardiomyopathy from different perspectives and, along with future systematic reviews and meta-analyses, can be of particular interest to practising cardiologists and researchers in developing clinical guidelines.
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Affiliation(s)
- Anastasiia V. Bairashevskaia
- Department of Paediatrics, Institute of Child’s Health, Sechenov First Moscow State Medical University (Sechenov University), 119435 Moscow, Russia
| | - Sofiya Y. Belogubova
- Department of Faculty Therapy, Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia
- AMEE International Networking Centre, Sechenov First Moscow State Medical University (Sechenov University), 123242 Moscow, Russia
| | - Mikhail R. Kondratiuk
- Department of Faculty Therapy, Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia
| | - Daria S. Rudnova
- International School “Medicine of the Future”, Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia
| | - Susanna S. Sologova
- Department of Pharmacology, Institute of Pharmacy, Sechenov First Moscow State Medical University (Sechenov University), 119571 Moscow, Russia
| | - Olga I. Tereshkina
- Department of Pharmacology, Institute of Pharmacy, Sechenov First Moscow State Medical University (Sechenov University), 119571 Moscow, Russia
| | - Esma I. Avakyan
- Department of Faculty Therapy, Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia
- AMEE International Networking Centre, Sechenov First Moscow State Medical University (Sechenov University), 123242 Moscow, Russia
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9
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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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10
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Fan X, Yang G, Kowitz J, Akin I, Zhou X, El-Battrawy I. Takotsubo Syndrome: Translational Implications and Pathomechanisms. Int J Mol Sci 2022; 23:ijms23041951. [PMID: 35216067 PMCID: PMC8875072 DOI: 10.3390/ijms23041951] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Revised: 02/04/2022] [Accepted: 02/05/2022] [Indexed: 02/07/2023] Open
Abstract
Takotsubo syndrome (TTS) is identified as an acute severe ventricular systolic dysfunction, which is usually characterized by reversible and transient akinesia of walls of the ventricle in the absence of a significant obstructive coronary artery disease (CAD). Patients present with chest pain, ST-segment elevation or ischemia signs on ECG and increased troponin, similar to myocardial infarction. Currently, the known mechanisms associated with the development of TTS include elevated levels of circulating plasma catecholamines and their metabolites, coronary microvascular dysfunction, sympathetic hyperexcitability, inflammation, estrogen deficiency, spasm of the epicardial coronary vessels, genetic predisposition and thyroidal dysfunction. However, the real etiologic link remains unclear and seems to be multifactorial. Currently, the elusive pathogenesis of TTS and the lack of optimal treatment leads to the necessity of the application of experimental models or platforms for studying TTS. Excessive catecholamines can cause weakened ventricular wall motion at the apex and increased basal motion due to the apicobasal adrenoceptor gradient. The use of beta-blockers does not seem to impact the outcome of TTS patients, suggesting that signaling other than the beta-adrenoceptor-associated pathway is also involved and that the pathogenesis may be more complex than it was expected. Herein, we review the pathophysiological mechanisms related to TTS; preclinical TTS models and platforms such as animal models, human-induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) models and their usefulness for TTS studies, including exploring and improving the understanding of the pathomechanism of the disease. This might be helpful to provide novel insights on the exact pathophysiological mechanisms and may offer more information for experimental and clinical research on TTS.
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Affiliation(s)
- Xuehui Fan
- First Department of Medicine, Medical Faculty Mannheim, University Medical Centre Mannheim (UMM), University of Heidelberg, 68167 Mannheim, Germany; (X.F.); (J.K.); (I.A.)
- Key Laboratory of Medical Electrophysiology, Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Collaborative Innovation Center for Prevention of Cardiovascular Diseases, Institute of Cardiovascular Research, Southwest Medical University, Luzhou 646000, China
- DZHK (German Center for Cardiovascular Research), Partner Site, Heidelberg-Mannheim, 68167 Mannheim, Germany
| | - Guoqiang Yang
- Department of Acupuncture and Rehabilitation, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou 646000, China;
- Research Unit of Molecular Imaging Probes, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Jacqueline Kowitz
- First Department of Medicine, Medical Faculty Mannheim, University Medical Centre Mannheim (UMM), University of Heidelberg, 68167 Mannheim, Germany; (X.F.); (J.K.); (I.A.)
| | - Ibrahim Akin
- First Department of Medicine, Medical Faculty Mannheim, University Medical Centre Mannheim (UMM), University of Heidelberg, 68167 Mannheim, Germany; (X.F.); (J.K.); (I.A.)
- DZHK (German Center for Cardiovascular Research), Partner Site, Heidelberg-Mannheim, 68167 Mannheim, Germany
| | - Xiaobo Zhou
- First Department of Medicine, Medical Faculty Mannheim, University Medical Centre Mannheim (UMM), University of Heidelberg, 68167 Mannheim, Germany; (X.F.); (J.K.); (I.A.)
- Key Laboratory of Medical Electrophysiology, Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Collaborative Innovation Center for Prevention of Cardiovascular Diseases, Institute of Cardiovascular Research, Southwest Medical University, Luzhou 646000, China
- DZHK (German Center for Cardiovascular Research), Partner Site, Heidelberg-Mannheim, 68167 Mannheim, Germany
- Correspondence: (X.Z.); (I.E.-B.)
| | - Ibrahim El-Battrawy
- First Department of Medicine, Medical Faculty Mannheim, University Medical Centre Mannheim (UMM), University of Heidelberg, 68167 Mannheim, Germany; (X.F.); (J.K.); (I.A.)
- DZHK (German Center for Cardiovascular Research), Partner Site, Heidelberg-Mannheim, 68167 Mannheim, Germany
- Correspondence: (X.Z.); (I.E.-B.)
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11
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Carbone A, Bottino R, Russo V, D'Andrea A, Liccardo B, Maurea N, Quagliariello V, Cimmino G, Golino P. Takotsubo Cardiomyopathy as Epiphenomenon of Cardiotoxicity in Patients With Cancer: A Meta-summary of Case Reports. J Cardiovasc Pharmacol 2021; 78:e20-e29. [PMID: 34001727 DOI: 10.1097/fjc.0000000000001026] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Accepted: 03/06/2021] [Indexed: 12/16/2022]
Abstract
ABSTRACT Many antitumoral drugs have been linked to takotsubo cardiomyopathy, with no clear pathogenetic mechanisms. Data about this condition are lacking in literature. The aim of this meta-summary is to summarize the characteristics of patients with antitumoral drug-induced takotsubo cardiomyopathy, described in case reports available in literature. We searched for published case reports in PubMed, Google Scholar, EMBASE, and Scopus from 2009 about stress cardiomyopathy and antiblastic drugs. We selected 41 case reports. All cases underwent chemotherapy/immunotherapy for different types of cancer. The median age was 58 years, and 61% of them were women. The most common comorbidities were hypertension (12.2%) and dyslipidemia (4.9%), but most of the population had no cardiological clinical history. Takotsubo cardiomyopathy is associated to the 5-fluorouracil (36.5%), capecitabine (9.7%), trastuzumab (9.7%), and immune check point inhibitor (9.7%) treatment. The median time of onset was 2 days (1-150). Cardiogenic shock was the first manifestation in 11 patients (26.8%). Left ventricle ejection fraction recovery was showed in 33 patients (89%) with mean ejection fraction 57.7 ± 7%, after a median of 30-day (4-300) follow-up. Patients with cancer experienced takotsubo cardiomyopathy within few days from the beginning of therapy, and the most of them normalized the heart function in few weeks. Cardiogenic shock showed high prevalence in this setting of patients. Larger studies are needed to better understand the pathological mechanisms of antiblastic drug-induced stress cardiomyopathy, to find risk factors associated and preventive strategies for limit this type of cardiotoxicities.
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Affiliation(s)
- Andreina Carbone
- Department of Cardiology, University of Campania "Luigi Vanvitelli," Naples, Italy
| | - Roberta Bottino
- Department of Cardiology, University of Campania "Luigi Vanvitelli," Naples, Italy
| | - Vincenzo Russo
- Department of Cardiology, University of Campania "Luigi Vanvitelli," Naples, Italy
| | - Antonello D'Andrea
- Department of Cardiology and Intensive Coronary Unit, "Umberto I" Hospital, Nocera Inferiore (SA), Italy; and
| | - Biagio Liccardo
- Department of Cardiology, University of Campania "Luigi Vanvitelli," Naples, Italy
| | - Nicola Maurea
- Department of Cardiology, National Cancer Institute, IRCCS Pascale, Cardiology Unit, Naples, Italy
| | - Vincenzo Quagliariello
- Department of Cardiology, National Cancer Institute, IRCCS Pascale, Cardiology Unit, Naples, Italy
| | - Giovanni Cimmino
- Department of Cardiology, University of Campania "Luigi Vanvitelli," Naples, Italy
| | - Paolo Golino
- Department of Cardiology, University of Campania "Luigi Vanvitelli," Naples, Italy
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12
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Kumar D, Warsha F, Mehta A, Deepak V, Jawad W. 5-Fluorouracil Induced Takotsubo Cardiomyopathy Complicated by Left Ventricular Thrombosis. Cureus 2021; 13:e14049. [PMID: 33898135 PMCID: PMC8060147 DOI: 10.7759/cureus.14049] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
A 42-year-old woman with a remote history of smoking and recently diagnosed anorectal cancer presented with typical anginal chest pain, dyspnea, palpitations, and hallucinations. She was started on continuous 5-flurouracil (5-FU) infusion five days before presentation. Her physical examination was significant for bilateral bibasilar crackles and tachycardia. Her bloodwork was significant for an increased troponin and brain natriuretic peptide (BNP). Electrocardiogram (EKG) showed sinus tachycardia with ST elevation in multiple contiguous leads, whereas transthoracic echocardiogram (TTE) showed estimated ejection fraction of 17% with severe global hypokinesis with apical akinesis and matted thrombus at the apex. Coronary angiogram showed 20% occlusion of the left anterior descending artery. She was diagnosed with 5-FU induced Takotsubo cardiomyopathy complicated by left ventricular (LV) thrombosis. 5-FU was discontinued, uridine triacetate was given as reversal agent. Aspirin and apixaban were started for three months for LV thrombosis. Her six-week TTE showed return of normal heart function with resolution of LV thrombosis.
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Affiliation(s)
- Dilpat Kumar
- Internal Medicine, Western Michigan University, Kalamazoo, USA
| | - Fnu Warsha
- Internal Medicine, Interfaith Medical Center, Brooklyn, USA
| | - Aditya Mehta
- Internal Medicine, Western Michigan University Homer Stryker M.D. School of Medicine, Kalamazoo, USA
| | - Vishal Deepak
- Critical Care Medicine, West Virginia University School of Medicine, Kalamazoo, USA
| | - Wassim Jawad
- Electrophysiology, Spectrum Health Medical Group, Grand Rapids, USA
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13
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Romitan DM, Rădulescu D, Berindan-Neagoe I, Stoicescu L, Grosu A, Rădulescu L, Gulei D, Ciuleanu TE. Cardiomyopathies and Arrhythmias Induced by Cancer Therapies. Biomedicines 2020; 8:biomedicines8110496. [PMID: 33198152 PMCID: PMC7696637 DOI: 10.3390/biomedicines8110496] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Revised: 11/09/2020] [Accepted: 11/10/2020] [Indexed: 12/17/2022] Open
Abstract
Cardiology and oncology are two fields dedicated to the study of various types of oncological and cardiac diseases, but when they collide, a new specialty is born, i.e., cardio-oncology. Continuous research on cancer therapy has brought into the clinic novel therapeutics that have significantly improved patient survival. However, these therapies have also been associated with adverse effects that can impede the proper management of oncological patients through the necessity of drug discontinuation due to life-threatening or long-term morbidity risks. Cardiovascular toxicity from oncological therapies is the main issue that needs to be solved. Proper knowledge, interpretation, and management of new drugs are key elements for developing the best therapeutic strategies for oncological patients. Upon continuous investigations, the profile of cardiotoxicity events has been enlarged with the inclusion of myocarditis upon administration of immune checkpoint inhibitors and cardiac dysfunction in the context of cytokine release syndrome with chimeric antigen receptor T cell therapy. Affinity enhanced and chimeric antigen receptor T cells have both been associated with hypotension, arrhythmia, and left ventricular dysfunction, typically in the setting of cytokine release syndrome. Therefore, the cardiologist must adhere to the progressing field of cancer therapy and become familiar with the adverse effects of novel drugs, and not only the ones of standard care, such as anthracycline, trastuzumab, and radiation therapy. The present review provides essential information summarized from the latest studies from cardiology, oncology, and hematology to bring together the three specialties and offers proper management options for oncological patients.
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Affiliation(s)
- Dragoș-Mihai Romitan
- Department of Cardiology, Municipal Clinical Hospital of Cluj-Napoca, 400139 Cluj-Napoca, Romania; (D.R.); (L.S.); (A.G.); (L.R.)
- Correspondence:
| | - Dan Rădulescu
- Department of Cardiology, Municipal Clinical Hospital of Cluj-Napoca, 400139 Cluj-Napoca, Romania; (D.R.); (L.S.); (A.G.); (L.R.)
| | - Ioana Berindan-Neagoe
- Research Center for Functional Genomic, Biomedicine and Translational Medicine, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400139 Cluj-Napoca, Romania;
| | - Laurențiu Stoicescu
- Department of Cardiology, Municipal Clinical Hospital of Cluj-Napoca, 400139 Cluj-Napoca, Romania; (D.R.); (L.S.); (A.G.); (L.R.)
| | - Alin Grosu
- Department of Cardiology, Municipal Clinical Hospital of Cluj-Napoca, 400139 Cluj-Napoca, Romania; (D.R.); (L.S.); (A.G.); (L.R.)
| | - Liliana Rădulescu
- Department of Cardiology, Municipal Clinical Hospital of Cluj-Napoca, 400139 Cluj-Napoca, Romania; (D.R.); (L.S.); (A.G.); (L.R.)
| | - Diana Gulei
- Research Center for Advanced Medicine-Medfuture, “Iuliu Hațieganu” University of Medicine and Pharmacy Cluj-Napoca, 400139 Cluj-Napoca, Romania;
| | - Tudor-Eliade Ciuleanu
- Department of Chemotherapy, Ion Chiricuta Clinical Cancer Center, 400139 Cluj Napoca, Romania;
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14
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Takotsubo Cardiomyopathy Secondary to Rituximab. Am J Ther 2020; 29:451-454. [PMID: 33021535 DOI: 10.1097/mjt.0000000000001239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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15
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Abstract
Remarkable progress has been made in the development of new therapies for cancer, dramatically changing the landscape of treatment approaches for several malignancies and continuing to increase patient survival. Accordingly, adverse effects of cancer therapies that interfere with the continuation of best-possible care, induce life-threatening risks or lead to long-term morbidity are gaining increasing importance. Cardiovascular toxic effects of cancer therapeutics and radiation therapy are the epitome of such concerns, and proper knowledge, interpretation and management are needed and have to be placed within the context of the overall care of individual patients with cancer. Furthermore, the cardiotoxicity spectrum has broadened to include myocarditis with immune checkpoint inhibitors and cardiac dysfunction in the setting of cytokine release syndrome with chimeric antigen receptor T cell therapy. An increase in the incidence of arrhythmias related to inflammation such as atrial fibrillation can also be expected, in addition to the broadening set of cancer therapeutics that can induce prolongation of the corrected QT interval. Therefore, cardiologists of today have to be familiar not only with the cardiotoxicity associated with traditional cancer therapies, such as anthracycline, trastuzumab or radiation therapy, but even more so with an ever-increasing repertoire of therapeutics. This Review provides this information, summarizing the latest developments at the juncture of cardiology, oncology and haematology.
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Affiliation(s)
- Joerg Herrmann
- Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA.
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16
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Valero M, Courand PY, Gilbert T, Bonnin N, Bonnefoy M, Lantelme P, Falandry C. Geriatric oncologists should be aware of cardio-oncology: Impact of age and gender on 5-FU-mediated TakoTsubo cardiomyopathy. J Geriatr Oncol 2020; 11:1337-1339. [PMID: 32280034 DOI: 10.1016/j.jgo.2020.03.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2020] [Accepted: 03/26/2020] [Indexed: 10/24/2022]
Affiliation(s)
- Marie Valero
- Geriatric Unit, Lyon-Sud Hospital, Hospices Civils de Lyon, Lyon, France
| | - Pierre-Yves Courand
- Cardiology Department, European Society of Hypertension Excellence Center, Croix-Rousse Hospital and Lyon-Sud Hospital, Hospices Civils de Lyon, Lyon, France; Lyon University, CREATIS, CNRS UMR5220, INSERM U1044, INSA-Lyon, Université Claude Bernard Lyon 1, Lyon, France
| | - Thomas Gilbert
- Geriatric Unit, Lyon-Sud Hospital, Hospices Civils de Lyon, Lyon, France; Health Services and Performance Research (HESPER EA7425), Lyon, France
| | - Nathalie Bonnin
- Oncology Unit, Lyon-Sud Hospital, Hospices Civils de Lyon, Lyon, France
| | - Marc Bonnefoy
- Geriatric Unit, Lyon-Sud Hospital, Hospices Civils de Lyon, Lyon, France; Lyon University, CarMeN Laboratory, Inserm U1060, INRA U1397, Université Claude Bernard Lyon 1, INSA Lyon, Charles Mérieux Medical School, Oullins, France
| | - Pierre Lantelme
- Cardiology Department, European Society of Hypertension Excellence Center, Croix-Rousse Hospital and Lyon-Sud Hospital, Hospices Civils de Lyon, Lyon, France; Lyon University, CREATIS, CNRS UMR5220, INSERM U1044, INSA-Lyon, Université Claude Bernard Lyon 1, Lyon, France
| | - Claire Falandry
- Geriatric Unit, Lyon-Sud Hospital, Hospices Civils de Lyon, Lyon, France; Lyon University, CarMeN Laboratory, Inserm U1060, INRA U1397, Université Claude Bernard Lyon 1, INSA Lyon, Charles Mérieux Medical School, Oullins, France.
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17
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Storey K, Sharkey SW. Clinical Features and Outcomes of Patients with Chemotherapy-induced Takotsubo Syndrome. US CARDIOLOGY REVIEW 2020. [DOI: 10.15420/usc.2019.10.1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
Chemotherapy treatment of malignancy accounts for 1–2% of takotsubo syndrome (TS) triggers. Women comprise 60–70% of patients with chemotherapy-associated TS, a distinctly lower prevalence than the 90% female prevalence in TS overall. Fluorouracil is the most commonly reported TS-triggering chemotherapeutic agent, although this must be interpreted in the context of the frequency of worldwide use of this agent. The onset of TS relative to chemotherapy initiation is quite variable, ranging from the initial administration to subsequent chemotherapy cycles several weeks beyond initiation. Limited information suggests chemotherapy can be safely reinitiated once the patient has recovered from the initial TS event. Having a TS event in the setting of chemotherapy treatment for malignancy is associated with substantial mortality.
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Affiliation(s)
- Katelyn Storey
- Minneapolis Heart Institute and Foundation, Minneapolis, MN
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18
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The Current and Future Role of Echocardiography for the Detection of Cardiotoxicity Related to Cancer Therapy. CURRENT CARDIOVASCULAR IMAGING REPORTS 2020. [DOI: 10.1007/s12410-019-9523-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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19
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Raber I, Warack S, Kanduri J, Pribish A, Godishala A, Abovich A, Orbite A, Dommaraju S, Frazer M, Peters ML, Asnani A. Fluoropyrimidine-Associated Cardiotoxicity: A Retrospective Case-Control Study. Oncologist 2019; 25:e606-e609. [PMID: 32162823 DOI: 10.1634/theoncologist.2019-0762] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2019] [Accepted: 11/18/2019] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND The fluoropyrimidines, 5-fluorouracil (5-FU) and capecitabine, are commonly used chemotherapeutic agents that have been associated with coronary vasospasm. METHODS In this retrospective case-control study, we identified patients at our institution who received 5-FU or capecitabine in 2018. We compared characteristics of patients who experienced cardiotoxicity with controls. We described phenotypes and outcomes of cardiotoxic cases. RESULTS We identified 177 patients who received fluoropyrimidines. After adjudication, 4.5% of the cohort met the criteria for cardiovascular toxicity. Coronary artery disease was more common among cases than controls (38% vs. 7%, p < .05). There was also a trend toward increased prevalence of cardiovascular risk factors in cases compared with controls. Most cardiotoxic cases had chest pain, although a minority of cases presented with nonischemic cardiomyopathy. CONCLUSION Cardiotoxicity phenotypes associated with fluoropyrimidine use are not limited to coronary vasospasm. Cardiac risk factors and ischemic heart disease were highly prevalent among patients with cardiotoxicity.
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Affiliation(s)
- Inbar Raber
- Department of Internal Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Sarah Warack
- Department of Pharmacy, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Jaya Kanduri
- Department of Internal Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Abby Pribish
- Department of Internal Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Anuradha Godishala
- Department of Cardiovascular Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Arielle Abovich
- Department of Cardiovascular Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Anna Orbite
- Department of Pharmacy, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Sujithraj Dommaraju
- Department of Cardiovascular Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Morgan Frazer
- Department of Pharmacy, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Mary Linton Peters
- Division of Medical Oncology, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
| | - Aarti Asnani
- Department of Cardiovascular Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
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20
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Matsumoto T, Oda T, Yoshida Y, Kimura S, Himei H, Tsuduki T, Takagi S, Takatani M, Morishita H. Takotsubo cardiomyopathy caused by infusion reaction to trastuzumab. Int Cancer Conf J 2019; 9:28-31. [PMID: 31950014 DOI: 10.1007/s13691-019-00396-0] [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] [Received: 08/06/2019] [Accepted: 11/26/2019] [Indexed: 12/25/2022] Open
Abstract
Takotsubo cardiomyopathy (TCM) is also known as stress-induced cardiomyopathy. The occurrence of TCM due to infusion reaction is extremely rare. A 65-year-old man began receiving trastuzumab monotherapy for gastric cancer. However, he developed an infusion reaction after administration. Electrocardiography revealed negative T waves, ST segment elevation, and apical akinesis and hypokinesis of the left ventricle with apical ballooning in the systole and diastole. Furthermore, troponin I and creatinine kinase (CK) levels and CK-myocardial band were elevated. Based on these findings, he was diagnosed with TCM. This is the first report of TCM due to an infusion reaction.
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Affiliation(s)
- Toshihiko Matsumoto
- 1Department of Internal Medicine, Himeji Red Cross Hospital, 1-12-1, Shimoteno, Himeji, Hyogo 6708540 Japan
| | - Takashi Oda
- 1Department of Internal Medicine, Himeji Red Cross Hospital, 1-12-1, Shimoteno, Himeji, Hyogo 6708540 Japan
| | - Yu Yoshida
- 2Department of Cardiology, Himeji Red Cross Hospital, 1-12-1, Shimoteno, Himeji, Hyogo 6708540 Japan
| | - Shogo Kimura
- 1Department of Internal Medicine, Himeji Red Cross Hospital, 1-12-1, Shimoteno, Himeji, Hyogo 6708540 Japan
| | - Hitomi Himei
- 1Department of Internal Medicine, Himeji Red Cross Hospital, 1-12-1, Shimoteno, Himeji, Hyogo 6708540 Japan
| | - Takao Tsuduki
- 1Department of Internal Medicine, Himeji Red Cross Hospital, 1-12-1, Shimoteno, Himeji, Hyogo 6708540 Japan
| | - Shinjiro Takagi
- 1Department of Internal Medicine, Himeji Red Cross Hospital, 1-12-1, Shimoteno, Himeji, Hyogo 6708540 Japan
| | - Masahiro Takatani
- 1Department of Internal Medicine, Himeji Red Cross Hospital, 1-12-1, Shimoteno, Himeji, Hyogo 6708540 Japan
| | - Hirofumi Morishita
- 1Department of Internal Medicine, Himeji Red Cross Hospital, 1-12-1, Shimoteno, Himeji, Hyogo 6708540 Japan
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21
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Mubarak G, Haddadin M, Samra B, Luhrs C, Taiwo E. Doxorubicin-associated takotsubo cardiomyopathy in a patient with adult T-cell leukemia/lymphoma. Clin Case Rep 2019; 7:2466-2471. [PMID: 31893081 PMCID: PMC6935604 DOI: 10.1002/ccr3.2504] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2019] [Revised: 08/15/2019] [Accepted: 10/02/2019] [Indexed: 12/26/2022] Open
Abstract
This case highlights the first reported association of doxorubicin with takotsubo cardiomyopathy (TC) presenting as cardiogenic shock during the first continuous infusion in a patient with adult T-cell leukemia/lymphoma. We aim to raise awareness to recognize and distinguish between irreversible doxorubicin-associated cardiomyopathy and reversible doxorubicin-associated TC in patients with cancer.
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Affiliation(s)
- Ghassan Mubarak
- Department of MedicineSUNY Downstate Medical CenterBrooklynNYUSA
| | - Michael Haddadin
- Department of MedicineSUNY Downstate Medical CenterBrooklynNYUSA
| | - Bachar Samra
- Department of Hematology/OncologySUNY Downstate Medical CenterBrooklynNYUSA
- Department of LeukemiaThe University of Texas MD Anderson Cancer CenterHoustonTXUSA
| | - Carol Luhrs
- Department of Hematology/OncologySUNY Downstate Medical CenterBrooklynNYUSA
| | - Evelyn Taiwo
- Department of Hematology/OncologySUNY Downstate Medical CenterBrooklynNYUSA
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22
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Mishra T, Shokr M, Ahmed A, Afonso L. Acute reversible left ventricular systolic dysfunction associated with 5-fluorouracil therapy: a rare and increasingly recognised cardiotoxicity of a commonly used drug. BMJ Case Rep 2019; 12:12/9/e230499. [PMID: 31519717 DOI: 10.1136/bcr-2019-230499] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
5-Fluorouracil (5-FU) is the third most common chemotherapeutic agent for treating solid cancers and the second most common to cause cardiotoxicity. We present a rare case of acute reversible severe left ventricular systolic dysfunction associated with 5-FU. A 54-year-old woman with a history of stage IV gastric cancer presented with features of transient ischaemic attack after receiving the first dose of FLOT (5-FU, leucovorin, oxaliplatin and docetaxel). During the diagnostic workup, it was found that her ejection fraction was severely reduced to 15% with features of global hypokinesis, which later improved back to 65% within 13 days. These cases challenge our current understanding of the underlying mechanisms of this cardiotoxicity. Additionally, even though the patient did not experience any cardiac symptoms, it is important to monitor these patients closely as they are at high risk for fatal complications like arrhythmia and thrombus formation.
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Affiliation(s)
- Tushar Mishra
- Department of Internal Medicine, Wayne State University, Detroit, Michigan, USA
| | - Mohamed Shokr
- Division of Cardiology, Wayne State University, Detroit, Michigan, USA
| | - Abdelrahman Ahmed
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Luis Afonso
- Division of Cardiology, Wayne State University, Detroit, Michigan, USA
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23
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Abstract
Fluoropyrimidines are chemotherapeutic agents that confer great benefit to many patients with solid tumors, but their use is often limited by cardiotoxicity. The incidence and precise mechanisms of cardiotoxicity remain uncertain. Clinical presentations of fluoropyrimidine toxicity are varied and include chest pain, myocardial infarction, acute cardiomyopathy, arrhythmia, cardiogenic shock, and sudden cardiac death. Proposed mechanisms include coronary vasospasm, coronary endothelial dysfunction, direct myocardial toxicity, myocarditis, and Takotsubo cardiomyopathy. Therapeutic and prophylactic interventions primarily target coronary vasospasm as the underlying cause. Prospective studies are needed to develop evidence-based approaches to cardioprotection in patients receiving fluoropyrimidines.
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Affiliation(s)
- Jaya Kanduri
- Department of Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA
| | - Luis Alberto More
- CardioVascular Institute, Beth Israel Deaconess Medical Center, 3 Blackfan Circle, Center for Life Sciences 9th Floor, Boston, MA 02215, USA
| | - Anuradha Godishala
- Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA
| | - Aarti Asnani
- Cardio-Oncology Program, Division of Cardiovascular Medicine, CardioVascular Institute, Beth Israel Deaconess Medical Center, 3 Blackfan Circle, Center for Life Sciences Room 911, Boston, MA 02215, USA.
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24
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Desai A, Noor A, Joshi S, Kim AS. Takotsubo cardiomyopathy in cancer patients. CARDIO-ONCOLOGY 2019; 5:7. [PMID: 32154014 PMCID: PMC7048040 DOI: 10.1186/s40959-019-0042-9] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/01/2019] [Accepted: 05/21/2019] [Indexed: 01/09/2023]
Abstract
Background Cancer is a chronic condition that induces significant emotional and physical stress, which may increase the risk for developing Takotsubo cardiomyopathy (TCM). Main body Takotsubo cardiomyopathy, also known as stress cardiomyopathy, is a clinical syndrome that generally presents as chest pain mimicking acute coronary syndrome or as an acute heart failure characterized by severe left ventricular systolic dysfunction in response to emotional, physical, or medical stress. The potential triggers for Takotsubo syndrome in cancer patients include the emotional turmoil of a cancer diagnosis, the inflammatory state of the cancer itself, and the physical stress of cancer surgery, systemic anti-neoplastic therapy, and radiation treatment. TCM is becoming increasingly recognized among patients with cancer and has been associated with adverse outcomes in this patient population. In this study, we searched the Pubmed database using keywords “Takotsubo cardiomyopathy”, “cancer”, and “anti-neoplastic therapy” to review case reports of Takotsubo syndrome occurring in oncologic patients after systemic anti-neoplastic therapy. Clinical presentation, electrocardiogram, laboratory data, transthoracic echocardiogram and coronary angiogram results, and patient outcomes were collected and analyzed. Conclusion Patients with cancer are at an elevated risk for developing stress cardiomyopathy, and it is important to know which cancer drugs have been associated with the development of the Takotsubo syndrome.
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Affiliation(s)
- Aakash Desai
- Department of Medicine, University of Connecticut School of Medicine, Farmington, CT, USA
| | - Arish Noor
- Department of Medicine, University of Connecticut School of Medicine, Farmington, CT, USA
| | - Saurabh Joshi
- Department of Medicine, University of Connecticut School of Medicine, Farmington, CT, USA.,2Department of Medicine, Division of Cardiology, University of Connecticut School of Medicine, 263 Farmington Avenue, Farmington, CT 06030-2202 USA
| | - Agnes S Kim
- Department of Medicine, University of Connecticut School of Medicine, Farmington, CT, USA.,2Department of Medicine, Division of Cardiology, University of Connecticut School of Medicine, 263 Farmington Avenue, Farmington, CT 06030-2202 USA
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Takotsubo syndrome: an overview of pathophysiology, diagnosis and treatment with emphasis on cancer patients. Heart Fail Rev 2019; 24:833-846. [PMID: 31197563 DOI: 10.1007/s10741-019-09813-1] [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: 02/07/2023]
Abstract
Takotsubo syndrome is a disease of great clinical importance that remains underdiagnosed. It is a form of acute heart failure characterized by a transient wall motion abnormality of the left ventricular apex typically triggered by emotional or physical stress. Takotsubo syndrome is commonly associated with cancer and results in poor outcomes. Therefore, early recognition and prompt therapy are essential to improve prognosis. The aim of this manuscript is to review the consequences of the association between cancer and Takotsubo to summarize the available evidence to guide physicians to improve the management of these patients.
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Babak S, Brezden-Masley C. Cardiovascular sequelae of breast cancer treatments: A review. Curr Probl Cancer 2018; 42:409-421. [PMID: 30195806 DOI: 10.1016/j.currproblcancer.2018.06.009] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2018] [Accepted: 06/30/2018] [Indexed: 12/17/2022]
Affiliation(s)
- Sam Babak
- St. Michael's Hospital, Division of Medical Oncology and Hematology, University of Toronto, Toronto, Canada
| | - Christine Brezden-Masley
- St. Michael's Hospital, Division of Medical Oncology and Hematology, University of Toronto, Toronto, Canada.
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Sara JD, Kaur J, Khodadadi R, Rehman M, Lobo R, Chakrabarti S, Herrmann J, Lerman A, Grothey A. 5-fluorouracil and cardiotoxicity: a review. Ther Adv Med Oncol 2018; 10:1758835918780140. [PMID: 29977352 PMCID: PMC6024329 DOI: 10.1177/1758835918780140] [Citation(s) in RCA: 254] [Impact Index Per Article: 36.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2018] [Accepted: 04/25/2018] [Indexed: 12/15/2022] Open
Abstract
Fluoropyrimidines such as 5-fluorouracil (5-FU) form the foundation of a wide variety of chemotherapy regimens. 5-FU is in fact the third most commonly used chemotherapeutic agent in the treatment of solid malignancies across the world. As with all chemotherapy, balancing the potential benefits of therapy against the risks of drug-related toxicity is crucial when clinicians and patients make shared decisions about treatment. 5-FU is the second most common chemotherapeutic drug associated with cardiotoxicity after anthracyclines, which can manifest as chest pain, acute coronary syndrome/myocardial infarction or death. Nevertheless a widespread appreciation of 5-FU-related cardiotoxicity and its implications is lacking amongst clinicians. In this review, we outline the incidence, possible risk factors, and likely pathophysiological mechanisms that may account for 5-FU-related cardiotoxicity and also highlight potential management strategies for this poorly understood clinical entity.
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Affiliation(s)
- Jaskanwal D Sara
- Department of Cardiovascular Diseases, Mayo College of Medicine, 200 First Street SW, Rochester, MN 55905-0001, USA
| | - Jasvinder Kaur
- Kent Oncology Centre, Maidstone and Tunbridge Wells NHS Trust, Maidstone, Kent, UK
| | - Ryan Khodadadi
- Department of Internal Medicine, Mayo College of Medicine, Rochester, MN, USA
| | - Muneeb Rehman
- Department of Internal Medicine, Mayo College of Medicine, Rochester, MN, USA
| | - Ronstan Lobo
- Department of Internal Medicine, Mayo College of Medicine, Rochester, MN, USA
| | - Sakti Chakrabarti
- Department of Medical Oncology, Mayo College of Medicine, Rochester, MN, USA
| | - Joerg Herrmann
- Department of Cardiovascular Diseases, Mayo College of Medicine, Rochester, MN, USA
| | - Amir Lerman
- Department of Cardiovascular Diseases, Mayo College of Medicine, Rochester, MN, USA
| | - Axel Grothey
- Department of Medical Oncology, Mayo College of Medicine, Rochester, MN, USA
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Budnik M, Kucharz J, Wiechno P, Demkow T, Kochanowski J, Górska E, Opolski G. Chemotherapy-Induced Takotsubo Syndrome. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2018; 1114:19-29. [DOI: 10.1007/5584_2018_222] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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Giza DE, Lopez-Mattei J, Vejpongsa P, Munoz E, Iliescu G, Kitkungvan D, Hassan SA, Kim P, Ewer MS, Iliescu C. Stress-Induced Cardiomyopathy in Cancer Patients. Am J Cardiol 2017; 120:2284-2288. [PMID: 29096885 DOI: 10.1016/j.amjcard.2017.09.009] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2017] [Revised: 08/28/2017] [Accepted: 09/01/2017] [Indexed: 11/24/2022]
Abstract
Takotsubo syndrome, also known as stress-induced cardiomyopathy (SC), is underrecognized in cancer patients. This study aims to investigate the incidence, natural history, and triggers of SC in cancer patients and its impact on cancer therapy and overall survival. A total of 30 subjects fulfilled the diagnostic criteria for SC at MD Anderson Cancer Center over a 6-year period. Clinical presentation, electrocardiogram, laboratory data, and transthoracic echocardiogram results registered during the acute phase and follow-up were collected. All patients underwent coronary angiography. The most frequent presenting symptoms were chest pain in 63.3% of the patients and shortness of breath/dyspnea on exertion in 27% of the patients. T-wave inversion was a more common electrocardiographic presentation (60%) than ST elevation (13.3%). The median and interquartile range of peak creatine kinase MB fraction, troponin I, and brain natriuretic peptide were creatine kinase MB fraction 8.9, 4.6 to 21.1; troponin I 1.31, 0.7 to 3.3; and brain natriuretic peptide 1,124, 453.5 to 2,369.5. The most common complication of SC was cardiogenic shock requiring inotropic agents (20%). Of the 21 patients who required ongoing cancer treatment, 16 were able to resume chemotherapy, 5 underwent surgery, and 4 received radiation treatment. Median time to resume cancer treatment was 20 days after SC. None of the patients experienced recurrence of SC and other cardiac events. In conclusion, SC should be considered in the differential diagnosis of cancer patients who present with chest pain and ECG findings characteristic of acute coronary syndrome. Most of these patients normalize ejection fraction and may resume cancer therapy early.
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Giza DE, Moudgil R, Lopez-Mattei J, Kim P, Iliescu C. Association between ibrutinib and mid-cavitary Takotsubo cardiomyopathy: a case report and a review of chemotherapy-induced Takostubo's cardiomyopathy. EUROPEAN HEART JOURNAL-CASE REPORTS 2017; 1:ytx006. [PMID: 31020065 PMCID: PMC6177044 DOI: 10.1093/ehjcr/ytx006] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/28/2017] [Accepted: 10/11/2017] [Indexed: 11/22/2022]
Abstract
Takotsubo cardiomyopathy (TC) is a rare but increasingly recognized phenomenon, which can occur as a side effect of cancer treatment. We report an interesting case of a 53-year-old woman with non-small-cell lung cancer, who developed TC after chemotherapy with ibrutinib. Echocardiography revealed marked left ventricular dysfunction with apical hyperkinesis and mid-ventricular hypokinesia. Coronary angiogram was normal but did show mid-cavitary akinesis. To our knowledge, this is the first case of TC with ibrutinib. Therefore, TC remains a rare entity, and we present an elegant case of ibrutinib-mediated mid-cavitary Takotsubo cardiomyopathy with a literature review.
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Affiliation(s)
- Dana Elena Giza
- Department of Cardiology, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Houston, 77030 TX, USA
| | - Rohit Moudgil
- Department of Cardiology, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Houston, 77030 TX, USA
| | - Juan Lopez-Mattei
- Department of Cardiology, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Houston, 77030 TX, USA
| | - Peter Kim
- Department of Cardiology, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Houston, 77030 TX, USA
| | - Cezar Iliescu
- Department of Cardiology, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Houston, 77030 TX, USA
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Coen M, Rigamonti F, Roth A, Koessler T. Chemotherapy-induced Takotsubo cardiomyopathy, a case report and review of the literature. BMC Cancer 2017; 17:394. [PMID: 28578653 PMCID: PMC5457651 DOI: 10.1186/s12885-017-3384-4] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2016] [Accepted: 05/24/2017] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Several chemotherapy molecules, monoclonal antibodies and tyrosine kinase inhibitors, have been linked to Takotsubo cardiomyopathy (TC). CASE PRESENTATION In this article, we describe the case of a 45-year-old woman who developed TC after receiving an intra-arterial and intra-venous polychemotherapy for locally advanced epidermoid carcinoma of the anal canal. This is the first described case of TC associated with intra-arterial chemotherapy. CONCLUSIONS A review of the literature points to 5-fluorouracil as the most common molecule associated with TC and highlights the potential risk associated with rechallenging patient with the same drug.
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Affiliation(s)
- Matteo Coen
- Department of Internal Medicine, Geneva University Hospitals, Geneva, Switzerland
| | - Fabio Rigamonti
- Department of Internal Medical Specialties, Division of Cardiology, Geneva University Hospitals, Geneva, Switzerland
| | - Arnaud Roth
- Department of Internal Medical Specialties, Division of Oncology, Geneva University Hospitals, rue Gabrielle Perret-Gentil 4, 1211 Geneva 14, Switzerland
| | - Thibaud Koessler
- Department of Internal Medical Specialties, Division of Oncology, Geneva University Hospitals, rue Gabrielle Perret-Gentil 4, 1211 Geneva 14, Switzerland
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Abstract
BACKGROUND The most plausible hypothesis for takotsubo cardiomyopathy (TCM) is a catecholamine surge. Direct administration of catecholamines or medications causing catecholamine surge is frequently used in clinical practice. METHODS A Medline/PubMed database search was conducted for case reports or series of drug-induced TCM. All reported cases of drug-induced TCM were systemically identified and analyzed. RESULTS We identified 157 cases of drug-induced TCM. Fifty-seven (36.3%) cases were related to the administration of exogenous catecholamines. In 50 (31.9%) other cases, there was potential adrenergic effect. This included drugs with adrenergic vasoconstriction properties (3.2%), hyperadrenergic state due to alcohol or opioid withdrawal (7.7%), inhibitors of catecholamine reuptake (14.7%), anaphylactic reaction that is accompanied by catecholamine release (3.2%), and psychological or somatic stress coinciding with the administration of a drug that was thought to be the culprit (3.2%). Overall, 68.2% of these drug-induced TCM cases were catecholamine related. In 14 (8.9%) cases, the likely etiology of cardiomyopathy was chemotherapy-induced coronary vasospasm. CONCLUSION Our systematic review showed that over two-thirds of drug-induced TCM cases were due to direct or indirect catecholamine stimulation. The lowest effective dose and shortest duration of catecholamines should be utilized, and alternative therapies should be considered if feasible.
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Affiliation(s)
- Kazuhiko Kido
- 1 Department of Pharmacy Practice, South Dakota State University, Sioux Falls, SD, USA.,2 Department of Pharmacy, Avera McKennan Hospital, Sioux Falls, SD, USA
| | - Maya Guglin
- 3 Gill Heart Institute, University of Kentucky HealthCare, Lexington, KY, USA
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Giza DE, Iliescu G, Hassan S, Marmagkiolis K, Iliescu C. Cancer as a Risk Factor for Cardiovascular Disease. Curr Oncol Rep 2017; 19:39. [DOI: 10.1007/s11912-017-0601-x] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Herrmann J, Yang EH, Iliescu CA, Cilingiroglu M, Charitakis K, Hakeem A, Toutouzas K, Leesar MA, Grines CL, Marmagkiolis K. Vascular Toxicities of Cancer Therapies: The Old and the New--An Evolving Avenue. Circulation 2016; 133:1272-89. [PMID: 27022039 DOI: 10.1161/circulationaha.115.018347] [Citation(s) in RCA: 212] [Impact Index Per Article: 23.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
Since the late 1990s, there has been a steady decline in cancer-related mortality, in part related to the introduction of so-called targeted therapies. Intended to interfere with a specific molecular pathway, these therapies have, paradoxically, led to a number of effects off their intended cancer tissue or molecular targets. The latest examples are tyrosine kinase inhibitors targeting the Philadelphia Chromosome mutation product, which have been associated with progressive atherosclerosis and acute vascular events. In addition, agents designed to interfere with the vascular growth factor signaling pathway have vascular side effects ranging from hypertension to arterial events and cardiomyocyte toxicity. Interestingly, the risk of cardiotoxicity with drugs such as trastuzumab is predicted by preexisting cardiovascular risk factors and disease, posing the question of a vascular component to the pathophysiology. The effect on the coronary circulation has been the leading explanation for the cardiotoxicity of 5-fluorouracil and may be the underlying the mechanism of presentation of apical ballooning syndrome with various chemotherapeutic agents. Classical chemotherapeutic agents such as cisplatin, often used in combination with bleomycin and vinca alkaloids, can lead to vascular events including acute coronary thrombosis and may be associated with an increased long-term cardiovascular risk. This review is intended to provide an update on the evolving spectrum of vascular toxicities with cancer therapeutics, particularly as they pertain to clinical practice, and to the conceptualization of cardiovascular diseases, as well. Vascular toxicity with cancer therapy: the old and the new, an evolving avenue.
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Affiliation(s)
- Joerg Herrmann
- From Mayo Clinic, Division of Cardiovascular Diseases, Rochester, MN (J.H.); University of California at Los Angeles, Division of Cardiology, Los Angeles (E.-H.Y.); University of Texas, MD Anderson Cancer Center, Houston (C.A.I.); Arkansas Heart Hospital, Little Rock, AR and Koc University School of Medicine, Istanbul, Turkey (M.C.); University of Texas Health Science Center, Houston (K.C.); University of Arkansas for Medical Sciences, Little Rock (A.H.); Athens Medical School, Hippokration General Hospital, Greece (K.T.); University of Alabama at Birmingham (M.A.L.); Detroit Medical Center, Cardiovascular Institute, MI (C.L.G.); and Citizens Memorial Hospital, Bolivar, MO and University of Missouri, Columbia (K.M.).
| | - Eric H Yang
- From Mayo Clinic, Division of Cardiovascular Diseases, Rochester, MN (J.H.); University of California at Los Angeles, Division of Cardiology, Los Angeles (E.-H.Y.); University of Texas, MD Anderson Cancer Center, Houston (C.A.I.); Arkansas Heart Hospital, Little Rock, AR and Koc University School of Medicine, Istanbul, Turkey (M.C.); University of Texas Health Science Center, Houston (K.C.); University of Arkansas for Medical Sciences, Little Rock (A.H.); Athens Medical School, Hippokration General Hospital, Greece (K.T.); University of Alabama at Birmingham (M.A.L.); Detroit Medical Center, Cardiovascular Institute, MI (C.L.G.); and Citizens Memorial Hospital, Bolivar, MO and University of Missouri, Columbia (K.M.)
| | - Cezar A Iliescu
- From Mayo Clinic, Division of Cardiovascular Diseases, Rochester, MN (J.H.); University of California at Los Angeles, Division of Cardiology, Los Angeles (E.-H.Y.); University of Texas, MD Anderson Cancer Center, Houston (C.A.I.); Arkansas Heart Hospital, Little Rock, AR and Koc University School of Medicine, Istanbul, Turkey (M.C.); University of Texas Health Science Center, Houston (K.C.); University of Arkansas for Medical Sciences, Little Rock (A.H.); Athens Medical School, Hippokration General Hospital, Greece (K.T.); University of Alabama at Birmingham (M.A.L.); Detroit Medical Center, Cardiovascular Institute, MI (C.L.G.); and Citizens Memorial Hospital, Bolivar, MO and University of Missouri, Columbia (K.M.)
| | - Mehmet Cilingiroglu
- From Mayo Clinic, Division of Cardiovascular Diseases, Rochester, MN (J.H.); University of California at Los Angeles, Division of Cardiology, Los Angeles (E.-H.Y.); University of Texas, MD Anderson Cancer Center, Houston (C.A.I.); Arkansas Heart Hospital, Little Rock, AR and Koc University School of Medicine, Istanbul, Turkey (M.C.); University of Texas Health Science Center, Houston (K.C.); University of Arkansas for Medical Sciences, Little Rock (A.H.); Athens Medical School, Hippokration General Hospital, Greece (K.T.); University of Alabama at Birmingham (M.A.L.); Detroit Medical Center, Cardiovascular Institute, MI (C.L.G.); and Citizens Memorial Hospital, Bolivar, MO and University of Missouri, Columbia (K.M.)
| | - Konstantinos Charitakis
- From Mayo Clinic, Division of Cardiovascular Diseases, Rochester, MN (J.H.); University of California at Los Angeles, Division of Cardiology, Los Angeles (E.-H.Y.); University of Texas, MD Anderson Cancer Center, Houston (C.A.I.); Arkansas Heart Hospital, Little Rock, AR and Koc University School of Medicine, Istanbul, Turkey (M.C.); University of Texas Health Science Center, Houston (K.C.); University of Arkansas for Medical Sciences, Little Rock (A.H.); Athens Medical School, Hippokration General Hospital, Greece (K.T.); University of Alabama at Birmingham (M.A.L.); Detroit Medical Center, Cardiovascular Institute, MI (C.L.G.); and Citizens Memorial Hospital, Bolivar, MO and University of Missouri, Columbia (K.M.)
| | - Abdul Hakeem
- From Mayo Clinic, Division of Cardiovascular Diseases, Rochester, MN (J.H.); University of California at Los Angeles, Division of Cardiology, Los Angeles (E.-H.Y.); University of Texas, MD Anderson Cancer Center, Houston (C.A.I.); Arkansas Heart Hospital, Little Rock, AR and Koc University School of Medicine, Istanbul, Turkey (M.C.); University of Texas Health Science Center, Houston (K.C.); University of Arkansas for Medical Sciences, Little Rock (A.H.); Athens Medical School, Hippokration General Hospital, Greece (K.T.); University of Alabama at Birmingham (M.A.L.); Detroit Medical Center, Cardiovascular Institute, MI (C.L.G.); and Citizens Memorial Hospital, Bolivar, MO and University of Missouri, Columbia (K.M.)
| | - Konstantinos Toutouzas
- From Mayo Clinic, Division of Cardiovascular Diseases, Rochester, MN (J.H.); University of California at Los Angeles, Division of Cardiology, Los Angeles (E.-H.Y.); University of Texas, MD Anderson Cancer Center, Houston (C.A.I.); Arkansas Heart Hospital, Little Rock, AR and Koc University School of Medicine, Istanbul, Turkey (M.C.); University of Texas Health Science Center, Houston (K.C.); University of Arkansas for Medical Sciences, Little Rock (A.H.); Athens Medical School, Hippokration General Hospital, Greece (K.T.); University of Alabama at Birmingham (M.A.L.); Detroit Medical Center, Cardiovascular Institute, MI (C.L.G.); and Citizens Memorial Hospital, Bolivar, MO and University of Missouri, Columbia (K.M.)
| | - Massoud A Leesar
- From Mayo Clinic, Division of Cardiovascular Diseases, Rochester, MN (J.H.); University of California at Los Angeles, Division of Cardiology, Los Angeles (E.-H.Y.); University of Texas, MD Anderson Cancer Center, Houston (C.A.I.); Arkansas Heart Hospital, Little Rock, AR and Koc University School of Medicine, Istanbul, Turkey (M.C.); University of Texas Health Science Center, Houston (K.C.); University of Arkansas for Medical Sciences, Little Rock (A.H.); Athens Medical School, Hippokration General Hospital, Greece (K.T.); University of Alabama at Birmingham (M.A.L.); Detroit Medical Center, Cardiovascular Institute, MI (C.L.G.); and Citizens Memorial Hospital, Bolivar, MO and University of Missouri, Columbia (K.M.)
| | - Cindy L Grines
- From Mayo Clinic, Division of Cardiovascular Diseases, Rochester, MN (J.H.); University of California at Los Angeles, Division of Cardiology, Los Angeles (E.-H.Y.); University of Texas, MD Anderson Cancer Center, Houston (C.A.I.); Arkansas Heart Hospital, Little Rock, AR and Koc University School of Medicine, Istanbul, Turkey (M.C.); University of Texas Health Science Center, Houston (K.C.); University of Arkansas for Medical Sciences, Little Rock (A.H.); Athens Medical School, Hippokration General Hospital, Greece (K.T.); University of Alabama at Birmingham (M.A.L.); Detroit Medical Center, Cardiovascular Institute, MI (C.L.G.); and Citizens Memorial Hospital, Bolivar, MO and University of Missouri, Columbia (K.M.)
| | - Konstantinos Marmagkiolis
- From Mayo Clinic, Division of Cardiovascular Diseases, Rochester, MN (J.H.); University of California at Los Angeles, Division of Cardiology, Los Angeles (E.-H.Y.); University of Texas, MD Anderson Cancer Center, Houston (C.A.I.); Arkansas Heart Hospital, Little Rock, AR and Koc University School of Medicine, Istanbul, Turkey (M.C.); University of Texas Health Science Center, Houston (K.C.); University of Arkansas for Medical Sciences, Little Rock (A.H.); Athens Medical School, Hippokration General Hospital, Greece (K.T.); University of Alabama at Birmingham (M.A.L.); Detroit Medical Center, Cardiovascular Institute, MI (C.L.G.); and Citizens Memorial Hospital, Bolivar, MO and University of Missouri, Columbia (K.M.)
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Page RL, O'Bryant CL, Cheng D, Dow TJ, Ky B, Stein CM, Spencer AP, Trupp RJ, Lindenfeld J. Drugs That May Cause or Exacerbate Heart Failure: A Scientific Statement From the American Heart Association. Circulation 2016; 134:e32-69. [PMID: 27400984 DOI: 10.1161/cir.0000000000000426] [Citation(s) in RCA: 279] [Impact Index Per Article: 31.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Heart failure is a common, costly, and debilitating syndrome that is associated with a highly complex drug regimen, a large number of comorbidities, and a large and often disparate number of healthcare providers. All of these factors conspire to increase the risk of heart failure exacerbation by direct myocardial toxicity, drug-drug interactions, or both. This scientific statement is designed to serve as a comprehensive and accessible source of drugs that may cause or exacerbate heart failure to assist healthcare providers in improving the quality of care for these patients.
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Fakhri Y, Dalsgaard M, Nielsen D, Lav Madsen P. 5-Fluorouracil-induced acute reversible heart failure not explained by coronary spasms, myocarditis or takotsubo: lessons from MRI. BMJ Case Rep 2016; 2016:bcr-2015-213783. [PMID: 27251602 DOI: 10.1136/bcr-2015-213783] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
A 69-year-old woman presented with arterial hypotension, pulmonary oedema and a severely depressed left ventricular ejection fraction (LVEF) of 25% only 3 days after having received her first treatment for colorectal cancer with 5-fluorouracil (5-FU)-based therapy. The ECG demonstrated widespread ST-segment depression and echocardiography showed uniform hypokinesia of all left ventricular (LV) myocardial segments without signs of regional LV ballooning. Coronary angiography was normal and the patient gained full recovery after receiving treatment with heart failure medication. Interestingly, cardiac MRI scan 9 days later showed a normal LVEF with signs of neither myocardial oedema nor necrosis. Despite the high therapeutic efficacy of 5-FU in treatment of colorectal cancer, it is associated with undesired cardiac toxicities including coronary spasms, toxic inflammation and takotsubo cardiomyopathy. However, our patient did not fulfil the diagnostic criteria for the aforementioned complications. Based on this case report, we discuss alternative mechanisms including myocardial adenosine triphosphate depletion suggested from animal experiments.
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Affiliation(s)
- Yama Fakhri
- Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark Department of Medicine, Division of Cardiology, Nykøbing F Hospital, Copenhagen University Hospital, Nykøbing F, Denmark
| | - Morten Dalsgaard
- Department of Cardiology, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
| | - Dorte Nielsen
- Department of Oncology, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
| | - Per Lav Madsen
- Department of Cardiology, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
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Coli S, Pigazzani F, Gaibazzi N. Midventricular Takotsubo cardiomyopathy after oxaliplatin infusion: an unreported side effect. J Cardiovasc Med (Hagerstown) 2016; 16:646-9. [PMID: 25333375 DOI: 10.2459/jcm.0000000000000204] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
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Abdelrahman M, McCarthy MT, Yusof H, Osman N. Successful capecitabine rechallenge following 5-fluorouracil-induced Takotsubo syndrome. Oxf Med Case Reports 2016; 2016:47-50. [PMID: 26989494 PMCID: PMC4794555 DOI: 10.1093/omcr/omv072] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2015] [Revised: 12/01/2015] [Accepted: 12/03/2015] [Indexed: 01/10/2023] Open
Abstract
Cardiac toxicity is a widely reported complication of fluoropyrimidine chemotherapies (5-fluorouracil and capecitabine); however, Takotsubo syndrome (TS) is less widely reported. There is little data available describing the viability of fluoropyrimidine rechallenge after fluoropyrimidine-induced TS. We report the case of Ms X, a 41-year-old woman with metastatic oesophageal cancer, who developed acute onset left ventricular dysfunction, with a measured left ventricular ejection fraction of 15% on cycle 1 day 3 of FOLFOX chemotherapy, after disconnection of the fluorouracil infusion pump. Her symptoms resolved over 2 days, and an echocardiogram returned to normal within 2 weeks. 5-Fluorouracil was discontinued, and replaced with capecitabine, without recurrence of symptoms. The remainder of her treatment was uneventful. This is the second case to describe successful capecitabine retreatment following 5-fluorouracil-induced TS.
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Affiliation(s)
- Mohamed Abdelrahman
- Department of Medical Oncology , University Hospital Limerick , Limerick , Ireland
| | - Michael T McCarthy
- Department of Medical Oncology , University Hospital Limerick , Limerick , Ireland
| | - Haliana Yusof
- Department of Medical Oncology , University Hospital Limerick , Limerick , Ireland
| | - Nemer Osman
- Department of Medical Oncology , University Hospital Limerick , Limerick , Ireland
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Iliescu CA, Grines CL, Herrmann J, Yang EH, Cilingiroglu M, Charitakis K, Hakeem A, Toutouzas KP, Leesar MA, Marmagkiolis K. SCAI Expert consensus statement: Evaluation, management, and special considerations of cardio-oncology patients in the cardiac catheterization laboratory (endorsed by the cardiological society of india, and sociedad Latino Americana de Cardiologıa intervencionista). Catheter Cardiovasc Interv 2016; 87:E202-23. [PMID: 26756277 DOI: 10.1002/ccd.26379] [Citation(s) in RCA: 130] [Impact Index Per Article: 14.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2015] [Accepted: 11/28/2015] [Indexed: 12/24/2022]
Abstract
In the United States alone, there are currently approximately 14.5 million cancer survivors, and this number is expected to increase to 20 million by 2020. Cancer therapies can cause significant injury to the vasculature, resulting in angina, acute coronary syndromes (ACS), stroke, critical limb ischemia, arrhythmias, and heart failure, independently from the direct myocardial or pericardial damage from the malignancy itself. Consequently, the need for invasive evaluation and management in the cardiac catheterization laboratory (CCL) for such patients has been increasing. In recognition of the need for a document on special considerations for cancer patients in the CCL, the Society for Cardiovascular Angiography and Interventions (SCAI) commissioned a consensus group to provide recommendations based on the published medical literature and on the expertise of operators with accumulated experience in the cardiac catheterization of cancer patients.
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Affiliation(s)
- Cezar A Iliescu
- MD Anderson Cancer Center, University of Texas, Houston, Texas
| | - Cindy L Grines
- Detroit Medical Center, Cardiovascular Institute, Detroit, Michigan
| | - Joerg Herrmann
- Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota
| | - Eric H Yang
- Division of Cardiology, University of California at Los Angeles, Los Angeles, California
| | - Mehmet Cilingiroglu
- School of Medicine, Arkansas Heart Hospital, Little Rock, Arkansas.,Department of Cardiology, Koc University, Istanbul, Turkey
| | | | - Abdul Hakeem
- Department of Cardiology, University of Arkansas for Medical Sciences, Little Rock, Arkansas
| | | | - Massoud A Leesar
- Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, Alabama
| | - Konstantinos Marmagkiolis
- Department of Cardiology, Citizens Memorial Hospital, Bolivar, Missouri.,Department of Medicine, University of Missouri, Columbia, Missouri
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Ng KH, Dearden C, Gruber P. Rituximab-induced Takotsubo syndrome: more cardiotoxic than it appears? BMJ Case Rep 2015; 2015:bcr-2014-208203. [PMID: 25733089 DOI: 10.1136/bcr-2014-208203] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Rituximab is used for treatment of multiple haematological cancers. Caution for use is advised in patients with significant cardiorespiratory disease due to known cases of exacerbations of angina and arrhythmias. However, its cardiotoxicity profile is not as well recognised as other monoclonal antibodies such as transtuzumab. We report a case of a 66-year-old man who developed Takotsubo's cardiomyopathy (TC) after an elective infusion of rituximab. This case is exceptional in that rituximab has not been linked to TC, and the vast majority of chemotherapy-linked and immunotherapy-linked TC reactions have occurred during initial infusions. We also discuss the different mechanisms which link TC to immunotherapy and chemotherapy, and propose that there may be a potential for risk-stratifying recipients of this frequently used immunotherapy prior to administering treatment.
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Affiliation(s)
- Kien Hoe Ng
- Department of Medicine, Royal Free London NHS Foundation Trust, London, UK
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Goel S, Sharma A, Garg A, Chandra A, Shetty V. Chemotherapy induced Takotsubo cardiomyopathy. World J Clin Cases 2014; 2:565-568. [PMID: 25325068 PMCID: PMC4198410 DOI: 10.12998/wjcc.v2.i10.565] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2014] [Revised: 06/23/2014] [Accepted: 07/18/2014] [Indexed: 02/05/2023] Open
Abstract
Chemotherapy has been linked with Takotsubo cardiomyopathy. Most of the literature on chemotherapy associated Takotsubo cardiomyopathy is on the drug 5-fluorouracil. In this report, we describe the case of a 55-year-old Asian male who developed Takotsubo cardiomyopathy while receiving dual chemotherapy with cytarabine and daunorubicin for acute myeloid leukemia. To our knowledge, it is the first case of Takotsubo cardiomyopathy associated with daunorubicin and/or cytarabine.
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Dermitzakis EV, Kimiskidis VK, Eleftheraki A, Lazaridis G, Konstantis A, Basdanis G, Tsiptsios I, Georgiadis G, Fountzilas G. The impact of oxaliplatin-based chemotherapy for colorectal cancer on the autonomous nervous system. Eur J Neurol 2014; 21:1471-7. [PMID: 25041285 DOI: 10.1111/ene.12514] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2013] [Accepted: 05/26/2014] [Indexed: 12/16/2022]
Abstract
BACKGROUND The oxaliplatin (ΟΧΑ)-based regimens FOLFOX and XELOX can cause peripheral neuropathy. It is unknown if ΟΧΑ, alone or in combination regimens, affects the Autonomous Nervous System (ANS). Accordingly, we evaluated the impact of ΟΧΑ-based chemotherapy on the ANS. METHODS We enrolled 36 patients with colorectal cancer, treated with adjuvant mFOLFOX6 or XELOX chemotherapy, and 22 healthy volunteers. For the assessment of ANS function, participants completed a questionnaire and underwent neurophysiological examination at three time points (baseline, 3-4 months and 6-8 months after the first chemotherapy cycle). ANS testing included assessment of the adrenergic cardiovascular function (orthostatic hypotension-OH), parasympathetic heart innervation (ratio 30/15) and Sympathetic Skin Response (SSR). RESULTS The values of the 30/15 ratio were significantly reduced at the two time point assessments compared to baseline (Wilcoxon signed ranks test, both P < 0.001), while patients had more often diastolic OH at the 6-8 month evaluation compared to baseline (P = 0.039). In contrast, SSR was not affected. The incidence of positive responses in the questionnaire assessing the subjective impact of symptoms attributable to ANS dysfunction was higher at the two time points compared to baseline (P = 0.036 and P = 0.020). CONCLUSIONS Oxaliplatin-based chemotherapy is associated with significant effects on the adrenergic cardiovascular reaction and the parasympathetic heart innervation, whereas SSR remains untouched.
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Affiliation(s)
- E V Dermitzakis
- Laboratory of Clinical Neurophysiology, Department of Neurology, "Papageorgiou" Hospital, Thessaloniki, Greece
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Baumann S, Huseynov A, Goranova D, Faust M, Behnes M, Nolte F, Heidenreich D, Hofmann WK, Borggrefe M, Akin I, Klein S. Takotsubo Cardiomyopathy after Systemic Consolidation Therapy with High-Dose Intravenous Cytarabine in a Patient with Acute Myeloid Leukemia. Oncol Res Treat 2014; 37:487-90. [DOI: 10.1159/000365536] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2014] [Accepted: 05/27/2014] [Indexed: 11/19/2022]
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Endo A, Yoshida Y, Nakashima R, Takahashi N, Tanabe K. Capecitabine induces both cardiomyopathy and multifocal cerebral leukoencephalopathy. Int Heart J 2014; 54:417-20. [PMID: 24309454 DOI: 10.1536/ihj.54.417] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Chemotherapy for malignant tumors has diversified, and recognizing its side effects has become more important than ever. Both cardiotoxicity and neurotoxicity are rare, but they are among the most serious side effects caused by 5-fluorouracil (5-FU). Capecitabine is an orally administered prodrug that converts preferentially to 5-FU within tumors, resulting in enhanced concentrations of 5-FU in tumor tissue. Given that it targets tumor tissue, capecitabine was expected to reduce the risk of side effects associated with fluoropyrimidine. Here, we present the case of a 62-year-old man with colorectal adenocarcinoma who simultaneously experienced cardiomyopathy with cardiogenic shock and cerebral leukoencephalopathy during treatment with capecitabine. During emergency coronary angiography, ST-segment elevation and severely reduced left ventricular wall motion were observed; however, no severe coronary stenosis or spasm was revealed. Furthermore, we present a review of the literature on capecitabine-induced cardiotoxicity. As of April 2013, 39 case reports on capecitabine-induced cardiotoxicity have been published; however, cardiomyopathy was very rare, with only 3 cases reported. It is important for physicians to be aware of the various rare, but potentially serious, adverse effects associated with capecitabine chemotherapy and to inform patients about the possibility of these side effects, including cardiotoxicity and neurotoxicity.
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Affiliation(s)
- Akihiro Endo
- Division of Cardiology, Shimane University Faculty of Medicine
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Ovadia D, Esquenazi Y, Bucay M, Bachier CR. Association between takotsubo cardiomyopathy and axitinib: case report and review of the literature. J Clin Oncol 2014; 33:e1-3. [PMID: 24567431 DOI: 10.1200/jco.2013.48.7280] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Affiliation(s)
- Daniela Ovadia
- Cardiology Clinic of San Antonio, Methodist Hospital, San Antonio, TX
| | | | - Moises Bucay
- Cardiology Clinic of San Antonio, Methodist Hospital, San Antonio, TX
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46
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Takotsubo cardiomyopathy and 5-Fluorouracil: getting to the heart of the matter. Case Rep Oncol Med 2013; 2013:206765. [PMID: 24368954 PMCID: PMC3866884 DOI: 10.1155/2013/206765] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2013] [Accepted: 10/29/2013] [Indexed: 11/17/2022] Open
Abstract
Takotsubo cardiomyopathy is a rare but increasingly recognized phenomenon, which can occur as a side-effect of chemotherapeutic agents, in particular, the antimetabolite 5-fluorouracil. We describe a case of delayed Takotsubo cardiomyopathy after 3 weeks of adjuvant 5-fluorouracil for resected rectal adenocarcinoma in a 66-year-old female, supported by angiographic, electrocardiographic, and echocardiographic features. As a complication, she developed an apical mural thrombus with subsequent cerebral thromboembolic events and was successfully anticoagulated to make a full recovery. We present a review of the literature on Takotsubo cardiomyopathy secondary to 5-fluorouracil and the rare occurrence of thromboembolic complications. As this is a significant clinical phenomenon which involves a multispeciality approach to management, oncologists and cardiologists need to recognize it as a potential toxicity of a widely administered chemotherapeutic drug.
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Sharma V, Srinivasan M, Sheehan DM, Ionescu A. Stress cardiomyopathy: case series and the review of literature. J Emerg Med 2013; 45:e95-8. [PMID: 23910162 DOI: 10.1016/j.jemermed.2012.11.017] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2012] [Revised: 07/25/2012] [Accepted: 11/04/2012] [Indexed: 11/27/2022]
Abstract
BACKGROUND Apical ballooning syndrome (ABS) or stress cardiomyopathy is increasingly recognized as a cause of acute coronary syndrome with unobstructed coronaries, but remains underdiagnosed. OBJECTIVES Retrospective review of the angiographic database (between January 2006 and December 2010) to obtain incidence and clinical presentation of ABS at our center. ABS was defined according to the modified Mayo Clinic criteria. CASE RESULTS Normal or unobstructed coronaries on angiography were observed in 1780 (25.4%) of a total of 6983 patients who underwent urgent or emergency coronary angiography. Twelve patients (0.17%) fulfilled the modified Mayo Clinic criteria for ABS. Eleven patients (92%) were aged ≥ 50 years (median 68 years, range 27-86 years), and 10 were female (83%). Four patients (31%) presented with ST-elevation myocardial infarction, and 1 patient presented with cardiogenic shock and acute coronary syndrome. Emotional stress was the precipitant in 4 patients (33%). Unusual precipitants like cold-water immersion and intravenous chemotherapy were observed. All 12 patients had the typical appearance of ABS on left ventriculogram (75%) or echocardiography (25%). Follow-up imaging with either echocardiography or magnetic resonance imaging (done in all 12 patients) up to 16 weeks after discharge showed that left ventricular function had normalized. CONCLUSIONS The incidence and clinical features of ABS in our tertiary center are similar to those reported in other settings. Unusual precipitants were observed, but left ventriculograms were performed less frequently and could be contributory to the under-diagnosis of ABS.
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Affiliation(s)
- Vinoda Sharma
- Morriston Hospital Cardiac Centre, Swansea, Wales, United Kingdom
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48
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Takotsubo syndrome: an underdiagnosed complication of 5-fluorouracil mimicking acute myocardial infarction. Blood Coagul Fibrinolysis 2013; 24:90-4. [PMID: 23249567 DOI: 10.1097/mbc.0b013e3283597605] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Takotsubo syndrome (TTS)/cardiomyopathy is a syndrome that mimics acute myocardial infarction in the absence of coronary artery disease and is characterized by acute onset of chest pain, electrocardiographic abnormalities, and reversible left ventricular dysfunction. It is usually induced by emotional and physical stress. Fluorouracil is one of the most frequently used chemotherapy agents and a relatively common adverse reaction of fluorouracil is cardiotoxicity. Herein we describe a patient without a history of cardiovascular disorder who developed severe heart failure during infusion of fluorouracil for metastatic gastric cancer. Remarkably, the patient did not develop TTS during prior chemotherapy regimen, which also included fluorouracil. The patient's findings were consistent with the proposed TTS diagnostic criteria and coronary angiography was normal, without obstructive coronary artery disease. With supportive care, the patient's cardiac functions returned to normal. TTS is not a well known syndrome to clinicians and this condition appears to occur more frequently than previously thought. In addition to the presented case, a review of the clinical features and outcome of 10 reported cases of fluorouracil-induced TTS is presented.
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Abstract
Takotsubo cardiomyopathy (TTC), also known as stress cardiomyopathy, is an increasingly recognized clinical syndrome of acute reversible left ventricular dysfunction precipitated by intense emotional or physical stress. Excessive sympathetic stimulation is believed to be central to the pathogenesis of this condition; thus, drugs with sympathetic effect could precipitate TTC. This review outlines previous reports regarding drugs that may induce TTC. Some reports link the use of the drug-primarily associated with sympathetic overstimulation-with the development of TTC Consequently, drug-induced TTC should be considered in patients diagnosed with TTC.
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Affiliation(s)
- Yasukatsu Izumi
- Department of Pharmacology, Osaka City University Medical School, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan.
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50
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Abstract
Stress cardiomyopathy, also known as takotsubo cardiomyopathy, is a rapidly reversible form of acute heart failure classically triggered by stressful events. It is associated with a distinctive left ventricular contraction pattern described as apical akinesis/ballooning with hyperdynamic contraction of the basal segments in the absence of obstructive coronary artery disease. The traditional paradigm has expanded to include other causes, in particular chemotherapeutic drugs. The literature increasingly suggests an association between cancer, chemotherapeutic drugs, and stress cardiomyopathy. Chemotherapy-induced takotsubo cardiomyopathy is a relatively new phenomenon, but one that merits detailed attention to the elucidation of possible mechanistic links.
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Affiliation(s)
- Sakima A Smith
- Division of Cardiovascular Medicine, Davis Heart & Lung Research Institute, The Ohio State University Medical Center, Suite 200, 473 West 12th Avenue, Columbus, OH 43210-1252, USA.
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