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El-Shorbagy EA, El-Bassiouny NA, Kassem AB, Salahuddin A, Mohamed Kamel M, El Bastawisy A, Nabeel Abuelsoud N. The impact of CBR3 (rs1056892) and ABCC1 (rs45511401) genetic polymorphisms on doxorubicin-induced cardiotoxicity and the potential role of brain natriuretic peptide as an early cardiac biomarker in breast cancer patients. Expert Opin Drug Metab Toxicol 2025:1-13. [PMID: 40207889 DOI: 10.1080/17425255.2025.2490736] [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: 09/04/2024] [Revised: 03/21/2025] [Accepted: 03/28/2025] [Indexed: 04/11/2025]
Abstract
BACKGROUND Doxorubicin (DOX), a potent antineoplastic drug, can induce cardiotoxicity through its cardiotoxic metabolites catalyzed by CBR 3 and its accumulation in cardiac tissue via the ABCC1 transporter. Here, we investigated CBR3 and ABCC1 genetic polymorphisms affecting doxorubicin cardiotoxicity in breast cancer patients and explored the potential role of brain natriuretic peptide (BNP) as an early cardiac biomarker. METHODS One hundred Breast cancer patients are receiving DOX treatment. Blood samples were analyzed for CBR3 and ABCC1 gene polymorphisms and echocardiography and BNP biomarkers were used to assess cardiotoxicity at baseline and three months post-DOX treatment. RESULTS Following the DOX treatment, CBR3 genotypes showed significant differences in BNP levels and delta BNP (p = 0.001 and 0.014, respectively). There was a significant association between different CBR3 genotypes and BNP levels after DOX (p = 0.001) and delta BNP (p = 0.01), with AA genotypes associated with cardiotoxicity. ABCC1 was not associated significantly with cardiotoxicity (p = 0.67). There was a statistically significant difference between CBR3 genotypes and the occurrence of anemia (p = 0.023). CONCLUSION Detecting CBR3 genetic polymorphisms is crucial for assessing cardiotoxicity before administering DOX, and monitoring BNP levels helps early detection. CBR3 is also associated with DOX anemia.
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Affiliation(s)
- Enas A El-Shorbagy
- Clinical Pharmacy and Pharmacy Practice Department, Faculty of Pharmacy, Egyptian Russian University, Cairo, Egypt
- Clinical Pharmacy and Pharmacy Practice Department, Faculty of Pharmacy, Damanhour University, Damanhour, Egypt
| | - Noha A El-Bassiouny
- Clinical Pharmacy and Pharmacy Practice Department, Faculty of Pharmacy, Damanhour University, Damanhour, Egypt
| | - Amira B Kassem
- Clinical Pharmacy and Pharmacy Practice Department, Faculty of Pharmacy, Damanhour University, Damanhour, Egypt
| | - Ahmad Salahuddin
- Biochemistry Department, Faculty of Pharmacy, Damanhour University, Damanhur, Egypt
- Department of Biochemistry, College of Pharmacy, Al-Ayen Iraqi University, Nasiriyah, Iraq
| | - Mahmoud Mohamed Kamel
- Clinical Pathology Department, National Cancer Institute, Cairo University, Cairo, Egypt
- Baheya Center for Early Detection and Treatment of Breast Cancer, Cairo, Egypt
| | - Ahmed El Bastawisy
- Baheya Center for Early Detection and Treatment of Breast Cancer, Cairo, Egypt
- Medical Oncology Department, National Cancer Institute, Cairo University, Cairo, Egypt
| | - Nermeen Nabeel Abuelsoud
- Pharmacy Practice Department, Faculty of Pharmacy, Heliopolis University for Sustainable Development, Cairo, Egypt
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Ibrahim ESH, Chaudhary L, Cheng YC, Sosa A, An D, Charlson J. Cardiac MRI for differentiating chemotherapy-induced cardiotoxicity in sarcoma and breast cancer. Radiol Oncol 2025; 59:79-90. [PMID: 40014780 PMCID: PMC11867570 DOI: 10.2478/raon-2025-0012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Accepted: 11/21/2024] [Indexed: 03/01/2025] Open
Abstract
BACKGROUND Over the past few decades, many studies have focused on anthracyclines effect on the heart (cardiotoxicity), but only a few have focused on sarcoma. In this study, we harness the capabilities of advanced cardiac magnetic resonance imaging (MRI) for characterizing anthracyclines-induced cardiotoxicity in sarcoma and compare the results to those from breast cancer patients. PATIENTS AND METHODS The patients receive an MRI exam at three timepoints: baseline (pre-treatment), posttreatment, and at 6-months follow-up. RESULTS The results demonstrated a differential response in sarcoma, characterized by increasing left-ventricular (LV) mass and decreasing right ventricular ejection fraction (RVEF). In all patients, left ventricular ejection fraction (LVEF) remained > 50% at all timepoints. Myocardial strain was always lower than the normal threshold values and showed small changes between different timepoints. Myocardial T2 and extracellular volume (ECV) showed increasing and decreasing patterns, respectively, in sarcoma, which were the opposite patterns of those in breast cancer. While myocardium T1 showed increasing values in breast cancer, T1 in sarcoma increased post-treatment and then decreased at the 6-months follow-up. The results showed inverse correlation between dose and different strain components in sarcoma, which was not the case in breast cancer. Certain myocardial segments showed high correlation coefficients with dose, which may reflect their increased sensitivity to cardiotoxicity. CONCLUSIONS Cardiac MRI proved to be a valuable technique for determining anthracycline-induced changes in cardiac function and myocardial tissue composition in sarcoma and differentiating it against breast cancer. It also provides a comprehensive assessment of heart health at baseline, which is important for risk stratification.
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Chong A, Stanton T, Taylor A, Prior D, La Gerche A, Anderson B, Scalia G, Cooke J, Dahiya A, To A, Davis M, Mottram P, Moir S, Playford D, Mahadavan D, Thomas L, Wahi S. 2024 CSANZ Position Statement on Indications, Assessment and Monitoring of Structural and Valvular Heart Disease With Transthoracic Echocardiography in Adults. Heart Lung Circ 2024; 33:773-827. [PMID: 38749800 DOI: 10.1016/j.hlc.2023.11.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2022] [Revised: 08/22/2023] [Accepted: 11/01/2023] [Indexed: 06/25/2024]
Abstract
Transthoracic echocardiography (TTE) is the most widely available and utilised imaging modality for the screening, diagnosis, and serial monitoring of all abnormalities related to cardiac structure or function. The primary objectives of this document are to provide (1) a guiding framework for treating clinicians of the acceptable indications for the initial and serial TTE assessments of the commonly encountered cardiovascular conditions in adults, and (2) the minimum required standard for TTE examinations and reporting for imaging service providers. The main areas covered within this Position Statement pertain to the TTE assessment of the left and right ventricles, valvular heart diseases, pericardial diseases, aortic diseases, infective endocarditis, cardiac masses, pulmonary hypertension, and cardiovascular diseases associated with cancer treatments or cardio-oncology. Facilitating the optimal use and performance of high quality TTEs will prevent the over or under-utilisation of this resource and unnecessary downstream testing due to suboptimal or incomplete studies.
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Affiliation(s)
- Adrian Chong
- Department of Cardiology, Princess Alexandra Hospital, Mater Hospital Brisbane, University of Queensland, Brisbane, Qld, Australia
| | - Tony Stanton
- Sunshine Coast University Hospital, School of Health University of Sunshine Coast, School of Medicine and Dentistry Griffith University, Birtinya, Qld, Australia
| | - Andrew Taylor
- Department of Cardiology, Royal Melbourne Hospital, Alfred Hospital, Melbourne, Vic, Australia
| | - David Prior
- Albury Wodonga Health, Albury, NSW, Australia
| | - Andre La Gerche
- St Vincent's Hospital, Baker Heart and Diabetes Institute, University of Melbourne, Melbourne, Vic, Australia
| | - Bonita Anderson
- Cardiac Sciences Unit, The Prince Charles Hospital, Queensland University of Technology, Brisbane, Qld, Australia
| | - Gregory Scalia
- The Prince Charles Hospital, University of Queensland, Brisbane, Qld, Australia
| | - Jennifer Cooke
- Department of Cardiology, Eastern Health, Monash University, Melbourne, Vic, Australia
| | - Arun Dahiya
- Department of Cardiology, Princess Alexandra Hospital, Logan Hospital, Griffith University, Brisbane, Qld, Australia
| | - Andrew To
- Department of Cardiology, Health New Zealand Waitemata, Auckland, New Zealand
| | | | - Philip Mottram
- Victorian Heart Institute, Monash University, Melbourne, Vic, Australia
| | - Stuart Moir
- Victorian Heart Institute, Monash University, Melbourne, Vic, Australia
| | | | - Devan Mahadavan
- Department of Cardiology, Queen Elizabeth Hospital, Lyell McEwin Hospital, Adelaide, SA, Australia
| | - Liza Thomas
- Department of Cardiology, Westmead Hospital, Westmead Clinical School University of Sydney, South West Clinical School University of New South Wales, Sydney, NSW, Australia
| | - Sudhir Wahi
- Department of Cardiology, Princess Alexandra Hospital, University of Queensland, Brisbane, Qld, Australia.
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Sulaiman A, Chambers J, Chilumula SC, Vinod V, Kandunuri R, McGarry S, Kim S. At the Intersection of Cardiology and Oncology: TGFβ as a Clinically Translatable Therapy for TNBC Treatment and as a Major Regulator of Post-Chemotherapy Cardiomyopathy. Cancers (Basel) 2022; 14:1577. [PMID: 35326728 PMCID: PMC8946238 DOI: 10.3390/cancers14061577] [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: 02/03/2022] [Revised: 03/13/2022] [Accepted: 03/17/2022] [Indexed: 02/01/2023] Open
Abstract
Triple-negative breast cancer (TNBC) is a subtype of breast cancer that accounts for the majority of breast cancer-related deaths due to the lack of specific targets for effective treatments. While there is immense focus on the development of novel therapies for TNBC treatment, a persistent and critical issue is the rate of heart failure and cardiomyopathy, which is a leading cause of mortality and morbidity amongst cancer survivors. In this review, we highlight mechanisms of post-chemotherapeutic cardiotoxicity exposure, evaluate how this is assessed clinically and highlight the transforming growth factor-beta family (TGF-β) pathway and its significance as a mediator of cardiomyopathy. We also highlight recent findings demonstrating TGF-β inhibition as a potent method to prevent cardiac remodeling, fibrosis and cardiomyopathy. We describe how dysregulation of the TGF-β pathway is associated with negative patient outcomes across 32 types of cancer, including TNBC. We then highlight how TGF-β modulation may be a potent method to target mesenchymal (CD44+/CD24-) and epithelial (ALDHhigh) cancer stem cell (CSC) populations in TNBC models. CSCs are associated with tumorigenesis, metastasis, relapse, resistance and diminished patient prognosis; however, due to plasticity and differential regulation, these populations remain difficult to target and continue to present a major barrier to successful therapy. TGF-β inhibition represents an intersection of two fields: cardiology and oncology. Through the inhibition of cardiomyopathy, cardiac damage and heart failure may be prevented, and through CSC targeting, patient prognoses may be improved. Together, both approaches, if successfully implemented, would target the two greatest causes of cancer-related morbidity in patients and potentially lead to a breakthrough therapy.
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Affiliation(s)
- Andrew Sulaiman
- Department of Basic Science, Kansas City University, 1750 Independence Ave, Kansas City, MO 64106, USA; (S.C.C.); (V.V.); (R.K.); (S.K.)
| | - Jason Chambers
- Schulich School of Medicine, Western University, London, ON N6A5C1, Canada;
| | - Sai Charan Chilumula
- Department of Basic Science, Kansas City University, 1750 Independence Ave, Kansas City, MO 64106, USA; (S.C.C.); (V.V.); (R.K.); (S.K.)
| | - Vishak Vinod
- Department of Basic Science, Kansas City University, 1750 Independence Ave, Kansas City, MO 64106, USA; (S.C.C.); (V.V.); (R.K.); (S.K.)
| | - Rohith Kandunuri
- Department of Basic Science, Kansas City University, 1750 Independence Ave, Kansas City, MO 64106, USA; (S.C.C.); (V.V.); (R.K.); (S.K.)
| | - Sarah McGarry
- Children’s Mercy Hospital Kansas City, 2401 Gillham Rd, Kansas City, MO 64108, USA;
| | - Sung Kim
- Department of Basic Science, Kansas City University, 1750 Independence Ave, Kansas City, MO 64106, USA; (S.C.C.); (V.V.); (R.K.); (S.K.)
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Hyafil F, Mirabel M, Tavitian B. Molecular imaging of free radicals for anthracycline-induced cardiotoxicity: See the burn? J Nucl Cardiol 2022; 29:226-229. [PMID: 32627135 DOI: 10.1007/s12350-020-02254-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Accepted: 06/17/2020] [Indexed: 10/23/2022]
Affiliation(s)
- Fabien Hyafil
- Department of Nuclear Medicine and DMU IMAGINA, Hôpital Européen Georges-Pompidou, Assistance Publique - Hôpitaux de Paris, 75015, Paris, France.
- Paris Cardiovascular Research Center (PARCC), INSERM, UMR970, Université de Paris, 75015, Paris, France.
| | - Mariana Mirabel
- Paris Cardiovascular Research Center (PARCC), INSERM, UMR970, Université de Paris, 75015, Paris, France
- Cardio-oncology and DMU CARTE, Hôpital Européen Georges-Pompidou, Assistance Publique - Hôpitaux de Paris, 75015, Paris, France
| | - Bertrand Tavitian
- Paris Cardiovascular Research Center (PARCC), INSERM, UMR970, Université de Paris, 75015, Paris, France
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Li Z, Ye Z, Ma J, Gu Q, Teng J, Gong X. MicroRNA‑133b alleviates doxorubicin‑induced cardiomyocyte apoptosis and cardiac fibrosis by targeting PTBP1 and TAGLN2. Int J Mol Med 2021; 48:125. [PMID: 33982775 PMCID: PMC8128419 DOI: 10.3892/ijmm.2021.4958] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Accepted: 03/04/2021] [Indexed: 12/16/2022] Open
Abstract
Doxorubicin is one of the most important chemotherapeutic drugs for the treatment of malignant tumors, but the cardiotoxicity of doxorubicin severely limits its clinical application. Increasing numbers of microRNAs (miRNAs/miRs) have been found to be dysregulated in doxorubicin-treated cardiomyocytes or animal hearts. The current study aimed to investigate the role of miR-133b in doxorubicin-induced cardiomyocyte injury. Doxorubicin was used to treat HL-1 cardiomyocytes to mimic cardiomyocyte injury in vitro. A mouse model of cardiac injury was generated by chronic intraperitoneal injections of doxorubicin. Masson's trichrome staining was performed on cardiac tissues to reveal cardiac fibrosis. Bioinformatics analysis and luciferase reporter assays were applied to explore the downstream targets of miR-133b. Flow cytometry and western blotting were conducted to detect cardiomyocyte apoptosis. Protein expression levels of collagen I, III and IV, and fibronectin were detected to reveal extracellular matrix deposition. The results revealed that doxorubicin decreased miR-133b expression in the treated HL-1 cardiomyocytes and mouse hearts. Overexpression of miR-133b restrained cardiomyocyte apoptosis, inhibited collagen accumulation and alleviated cardiac fibrosis in vivo. Mechanistically, polypyrimidine tract binding protein 1 (PTBP1) and transgelin 2 (TAGLN2) were confirmed to bind to miR-133b after prediction and screening. Moreover, miR-133b negatively regulated the protein expression levels of PTBP1 and TAGLN2. Finally, overexpression of PTBP1 or TAGLN2 reversed the effects of miR-133b on apoptosis and collagen accumulation. Thus, the current results indicated that miR-133b alleviated doxorubicin-induced cardiomyocyte apoptosis and cardiac fibrosis by targeting PTBP1 and TAGLN2, implying that miR-133b may be a potential biomarker for doxorubicin-induced cardiac injury.
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Affiliation(s)
- Zhen Li
- Department of Emergency, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
| | - Zekang Ye
- Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
| | - Jiazheng Ma
- Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
| | - Qian Gu
- Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
| | - Jianzhen Teng
- Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
| | - Xiaoxuan Gong
- Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
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7
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Ansheles AA, Sergienko IV, Prus YA, Sergienko VB. Nuclear imaging of chemotherapy-induced cardiotoxicity. КАРДИОВАСКУЛЯРНАЯ ТЕРАПИЯ И ПРОФИЛАКТИКА 2021. [DOI: 10.15829/1728-8800-2021-2537] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
The high efficiency of modern chemotherapy has made it possible to achieve great success in the treatment of cancer. Cardiovascular adverse effects are a major disadvantage of anticancer therapy, often requiring low and less effective doses or even drug withdrawal. Nuclear imaging techniques are the most sensitive in early detection of left ventricular damage and dysfunction during chemotherapy. This review presents modern data on the potential of nuclear imaging of cardiotoxicity.
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Affiliation(s)
| | | | - Yu. A. Prus
- National Medical Research Center of Cardiology
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8
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Wang B, Yu Y, Zhang Y, Hao X, Yang S, Zhao H, Sun Q, Wang Y. Right ventricular dysfunction in patients with diffuse large B-cell lymphoma undergoing anthracycline-based chemotherapy: a 2D strain and 3D echocardiography study. Int J Cardiovasc Imaging 2021; 37:1311-1319. [PMID: 33392873 DOI: 10.1007/s10554-020-02120-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2020] [Accepted: 11/24/2020] [Indexed: 10/22/2022]
Abstract
To investigate whether 2D strain and 3D echocardiography could early identify the impaired right ventricular (RV) function after anthracycline exposure. Sixty-one patients with diffuse large B-cell lymphoma treated with anthracycline were studied. Echocardiography was conducted at baseline, after the third cycle of the chemotherapy, after the completion of the chemotherapy, and follow-up at 10 months after the initiation of chemotherapy. RV global longitudinal strain (RV GLS) and RV free wall longitudinal strain (RV FWLS) were calculated using speckle tracking echocardiography. RV ejection fraction (RVEF) was analyzed by 3D echocardiography. RV systolic dysfunction was defined by ≥ 2 RV parameters below the threshold value, and cardiotoxicity was defined as a reduction in left ventricular EF > 10 to < 53%. After the third cycle of chemotherapy, only RV GLS was significantly decreased, while after the completion of the chemotherapy, RV GLS, RV FWLS, and RVEF were all significantly decreased compared with baseline measurements. At the end of follow-up, 9 patients (14.8%) were diagnosed with RV systolic dysfunction, and 16 patients (26.2%) had at least 1 abnormal RV function parameter. The proportion of RV systolic dysfunction was significantly higher in patients with cardiotoxicity than in patients without cardiotoxicity, yielding an odds ratio of 5.143. A percentage decrease in RV FWLS and RVEF were independent predictors of RV systolic dysfunction. Two-dimensional strain and 3D echocardiography are valuable methods for evaluating anthracycline-related impairment of RV function in DLBCL patients receiving chemotherapy. RV FWLS and RVEF are reliable predictors of RV systolic dysfunction.
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Affiliation(s)
- Baozhen Wang
- Department of Ultrasound, Cangzhou People's Hospital, Cangzhou, China
| | - Yang Yu
- Medical Imaging Center, Cangzhou People's Hospital, Cangzhou, China
| | - Yue Zhang
- Department of Ultrasound, Cangzhou People's Hospital, Cangzhou, China
| | - Xiaoyi Hao
- Department of Ultrasound, Cangzhou People's Hospital, Cangzhou, China.
| | - Shan Yang
- Department of Ultrasound, Cangzhou People's Hospital, Cangzhou, China
| | - Hong Zhao
- Department of Ultrasound, Cangzhou People's Hospital, Cangzhou, China
| | - Qianqian Sun
- Department of Ultrasound, Cangzhou People's Hospital, Cangzhou, China
| | - Yue Wang
- Medical Imaging Center, Cangzhou People's Hospital, Cangzhou, China
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Galderisi M, Santoro C, Bossone E, Mancusi C. Rationale and proposal for cardio-oncology services in Italy. J Cardiovasc Med (Hagerstown) 2020; 23:207-215. [PMID: 32858628 DOI: 10.2459/jcm.0000000000001087] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
: In the last 20 years, a substantial improvement in the efficacy of cancer treatment has induced a progressive increase in cancer survival, with an obvious parallel increase in morbidity and mortality related to the adverse effects of anticancer therapy, in particular, cardiovascular complications. In relation to the peculiar aspects related to cardiac and vascular toxicity, clinical management of patients should be ideally reserved for experts in the field of this novel medical discipline, which has been defined as cardio-oncology. The rationale for this choice corresponds to the aim of identifying patients more prone to developing cardiovascular damage, prevent overt cardiotoxicity and conduct active surveillance of treated patients for early identification of cardiac and vascular involvement during short- and long-term follow-up. Due to the burden of treated cancer patients, the development of dedicated cardio-oncology services has become one of the main goals of contemporary medicine, needed to accomplish the peculiar mission of guiding the patients through the narrow path of cancer survival without the expense of cardiovascular damage. The main purpose of cardio-oncology services is to provide dedicated cardiologic care to cancer patients affected by concomitant (subclinical or overt) cardiovascular diseases, either preexisting the cancer onset or acquired during and after the time course of anticancer therapy. In this article, we describe a possible spoke-hub model of cardio-oncology services, which could be appropriately applied in Italy. Rationale, organization, definition of referral criteria, strategies, interventional programs, long-term surveillance and home assistance of this model are described and discussed.
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Affiliation(s)
- Maurizio Galderisi
- Interdepartmental Program of Cardiovascular Emergencies and Onco-Hematologic Complications, Department of advanced Biomedical Sciences, Federico II University Hospital
| | - Ciro Santoro
- Interdepartmental Program of Cardiovascular Emergencies and Onco-Hematologic Complications, Department of advanced Biomedical Sciences, Federico II University Hospital
| | - Eduardo Bossone
- Unit of Cardiac Rehabilitation, Antonio Cardarelli Hospital, Naples, Italy
| | - Costantino Mancusi
- Department of Advanced Biomedical Science, Federico II, University Hospital
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10
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Andrikopoulou E. Diastolic assessment by CZT-SPECT: Could it be the next best thing for the detection of subclinical chemotherapy-induced cardiotoxicity? J Nucl Cardiol 2020; 27:1202-1206. [PMID: 31309461 DOI: 10.1007/s12350-019-01792-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2019] [Accepted: 06/13/2019] [Indexed: 11/29/2022]
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Barac A, Isaacs C, M Shara N, Lynce F, Desale S, Haynes K, Potosky AL. Trends in the Use of Cardiac Imaging for Women with Newly Diagnosed Breast Cancer. J Cardiovasc Transl Res 2020; 13:478-489. [PMID: 32458402 DOI: 10.1007/s12265-020-10023-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2020] [Accepted: 05/05/2020] [Indexed: 10/24/2022]
Abstract
We investigated time trends and factors associated with the use of cardiac imaging among women with early-stage breast cancer prior to the initiation of treatment. Of 11,732 women ages 24-64, diagnosed with stage I-III breast cancer in 2006-2011, 2550 (22%) received anthracycline-based chemotherapy. Baseline cardiac imaging was used in 79% of patients receiving anthracyclines and increased over time. Of 2277 (20%) women who received non-anthracycline therapy, 16% received cardiac imaging. Women receiving cardiac imaging in non-anthracycline therapy group were more likely to have higher cardiovascular risk, as well as higher cancer stage and worse histological tumor grade suggesting that results of imaging might have influenced the choice of cancer therapy. Our findings indicate the need for cardio-oncology collaboration in identification and treatment of women at high risk for adverse oncology and cardiovascular outcomes.
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Affiliation(s)
- Ana Barac
- MedStar Heart and Vascular Institute, Georgetown University, 110 Irving Street, NW, Ste. 1218, Washington, DC, 20010, USA.
| | - Claudine Isaacs
- Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA
| | - Nawar M Shara
- Department of Biostatistics and Biomedical Informatics, MedStar Health Research Institute, Hyattsville, MD, USA
| | - Filipa Lynce
- Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA
| | - Sameer Desale
- Department of Biostatistics and Biomedical Informatics, MedStar Health Research Institute, Hyattsville, MD, USA
| | | | - Arnold L Potosky
- Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA
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12
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Curigliano G, Lenihan D, Fradley M, Ganatra S, Barac A, Blaes A, Herrmann J, Porter C, Lyon AR, Lancellotti P, Patel A, DeCara J, Mitchell J, Harrison E, Moslehi J, Witteles R, Calabro MG, Orecchia R, de Azambuja E, Zamorano JL, Krone R, Iakobishvili Z, Carver J, Armenian S, Ky B, Cardinale D, Cipolla CM, Dent S, Jordan K. Management of cardiac disease in cancer patients throughout oncological treatment: ESMO consensus recommendations. Ann Oncol 2020; 31:171-190. [PMID: 31959335 PMCID: PMC8019325 DOI: 10.1016/j.annonc.2019.10.023] [Citation(s) in RCA: 610] [Impact Index Per Article: 122.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2019] [Revised: 10/18/2019] [Accepted: 10/21/2019] [Indexed: 12/13/2022] Open
Abstract
Cancer and cardiovascular (CV) disease are the most prevalent diseases in the developed world. Evidence increasingly shows that these conditions are interlinked through common risk factors, coincident in an ageing population, and are connected biologically through some deleterious effects of anticancer treatment on CV health. Anticancer therapies can cause a wide spectrum of short- and long-term cardiotoxic effects. An explosion of novel cancer therapies has revolutionised this field and dramatically altered cancer prognosis. Nevertheless, these new therapies have introduced unexpected CV complications beyond heart failure. Common CV toxicities related to cancer therapy are defined, along with suggested strategies for prevention, detection and treatment. This ESMO consensus article proposes to define CV toxicities related to cancer or its therapies and provide guidance regarding prevention, screening, monitoring and treatment of CV toxicity. The majority of anticancer therapies are associated with some CV toxicity, ranging from asymptomatic and transient to more clinically significant and long-lasting cardiac events. It is critical however, that concerns about potential CV damage resulting from anticancer therapies should be weighed against the potential benefits of cancer therapy, including benefits in overall survival. CV disease in patients with cancer is complex and treatment needs to be individualised. The scope of cardio-oncology is wide and includes prevention, detection, monitoring and treatment of CV toxicity related to cancer therapy, and also ensuring the safe development of future novel cancer treatments that minimise the impact on CV health. It is anticipated that the management strategies discussed herein will be suitable for the majority of patients. Nonetheless, the clinical judgment of physicians remains extremely important; hence, when using these best clinical practices to inform treatment options and decisions, practitioners should also consider the individual circumstances of their patients on a case-by-case basis.
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Affiliation(s)
- G. Curigliano
- European Institute of Oncology IRCCS, Milan
- Department of Oncology and Haematology (DIPO), University of Milan, Milan, Italy
| | - D. Lenihan
- Cardiovascular Division, Cardio-Oncology Center of Excellence, Washington University Medical Center, St. Louis
| | - M. Fradley
- Cardio-oncology Program, Division of Cardiovascular Medicine, Morsani College of Medicine and H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, Tampa
| | - S. Ganatra
- Cardio-Oncology Program, Lahey Medical Center, Burlington
| | - A. Barac
- Cardio-Oncology Program, Medstar Heart and Vascular Institute and MedStar Georgetown Cancer Institute, Georgetown University Hospital, Washington DC
| | - A. Blaes
- Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis
| | | | - C. Porter
- University of Kansas Medical Center, Lawrence, USA
| | - A. R. Lyon
- Royal Brompton Hospital and Imperial College, London, UK
| | - P. Lancellotti
- GIGA Cardiovascular Sciences, Acute Care Unit, Heart Failure Clinic, CHU Sart Tilman, University Hospital of Liège, Liège, Belgium
| | - A. Patel
- Morsani College of Medicine, University of South Florida, Tampa
| | - J. DeCara
- Medicine Section of Cardiology, University of Chicago, Chicago
| | - J. Mitchell
- Washington University Medical Center, St. Louis
| | - E. Harrison
- HCA Memorial Hospital and University of South Florida, Tampa
| | - J. Moslehi
- Vanderbilt University School of Medicine, Nashville
| | - R. Witteles
- Division of Cardiovascular Medicine, Falk CVRC, Stanford University School of Medicine, Stanford, USA
| | - M. G. Calabro
- Department of Anesthesia and Intensive Care, IRCCS, San Raffaele Scientific Institute, Milan, Italy
| | | | - E. de Azambuja
- Institut Jules Bordet and L’Université Libre de Bruxelles, Brussels, Belgium
| | | | - R. Krone
- Division of Cardiology, Washington University, St. Louis, USA
| | - Z. Iakobishvili
- Clalit Health Services, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - J. Carver
- Division of Cardiology, Abramson Cancer Center, Hospital of the University of Pennsylvania, Philadelphia
| | - S. Armenian
- Department of Population Sciences, City of Hope Comprehensive Cancer Center, Duarte
| | - B. Ky
- University of Pennsylvania School of Medicine, Philadelphia, USA
| | - D. Cardinale
- Cardioncology Unit, European Institute of Oncology, IRCCS, Milan
| | - C. M. Cipolla
- Cardiology Department, European Institute of Oncology, IRCCS, Milan, Italy
| | - S. Dent
- Duke Cancer Institute, Duke University, Durham, USA
| | - K. Jordan
- Department of Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, Heidelberg, Germany
| | - ESMO Guidelines Committee
- Correspondence to: ESMO Guidelines Committee, ESMO Head Office, Via Ginevra 4, CH-6900 Lugano, Switzerland, (ESMO Guidelines Committee)
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Abstract
Cardiotoxicity is a known complication of many cancer therapies. While the cardiotoxicity of established agents such as anthracyclines, antimetabolites, and alkylating agents is well known, it is important to realize that newer anticancer therapies such as tyrosine kinase inhibitors, angiogenesis inhibitors, and checkpoint inhibitors are also associated with significant adverse cardiovascular effects. Echocardiography, magnetic resonance imaging, and radionuclide imaging have been used to identify these complications early and prevent further consequences. We will discuss the different classes of cancer therapeutic agents that cause cardiotoxicity, the mechanisms that lead to these effects, and strategies that can be used to prevent the cardiac morbidity and mortality associated with their use.
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Cai F, Luis MAF, Lin X, Wang M, Cai L, Cen C, Biskup E. Anthracycline-induced cardiotoxicity in the chemotherapy treatment of breast cancer: Preventive strategies and treatment. Mol Clin Oncol 2019; 11:15-23. [PMID: 31289672 PMCID: PMC6535635 DOI: 10.3892/mco.2019.1854] [Citation(s) in RCA: 84] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2018] [Accepted: 04/30/2019] [Indexed: 12/13/2022] Open
Abstract
Anthracyclines are highly effective chemotherapeutic agents, used for a wide variety of malignancies. Cardiotoxicity is a well-recognized side effect of anthracycline therapy that limits the total amount of drug administered and can cause heart failure in some patients. Most experimental data support oxidative stress as the etiology of anthracycline-induced cardiotoxicity. The objective of this paper was to provide a review of the clinical classification, risk factors, monitoring and prevention of anthracycline-induced cardiotoxicity in patients with breast cancer.
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Affiliation(s)
- Fengfeng Cai
- Department of Breast Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai 200090, P.R. China
| | - Manuel Antonio Falar Luis
- Department of Breast Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai 200090, P.R. China
| | - Xiaoyan Lin
- Department of Breast Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai 200090, P.R. China
| | - Minghong Wang
- Department of General Practice, Yangpu Hospital, Tongji University School of Medicine, Shanghai 200090, P.R. China
- Department of Cardiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, P.R. China
| | - Lu Cai
- Department of Breast Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai 200090, P.R. China
| | - Chunmei Cen
- Department of Breast Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai 200090, P.R. China
| | - Ewelina Biskup
- Department of Basic Medical Sciences, Shanghai University of Medicine and Health Sciences, Shanghai 201318, P.R. China
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15
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Abstract
Doxorubicin-induced cardiotoxicity in childhood cancer survivors is a growing problem. The population of patients at risk for cardiovascular disease is steadily increasing, as five-year survival rates for all types of childhood cancers continue to improve. Doxorubicin affects the developing heart differently from the adult heart and in a subset of exposed patients, childhood exposure leads to late, irreversible cardiomyopathy. Notably, the prevalence of late-onset toxicity is increasing in parallel with improved survival. By the year 2020, it is estimated that there will be 500,000 childhood cancer survivors and over 50,000 of them will suffer from doxorubicin-induced cardiotoxicity. The majority of the research to-date, concentrated on childhood cancer survivors, has focused mostly on clinical outcomes through well-designed epidemiological and retrospective cohort studies. Preclinical studies have elucidated many of the cellular mechanisms that elicit acute toxicity in cardiomyocytes. However, more research is needed in the areas of early- and late-onset cardiotoxicity and more importantly improving the scientific understanding of how other cells present in the cardiac milieu are impacted by doxorubicin exposure. The overall goal of this review is to succinctly summarize the major clinical and preclinical studies focused on doxorubicin-induced cardiotoxicity. As the prevalence of patients affected by doxorubicin exposure continues to increase, it is imperative that the major gaps in existing research are identified and subsequently utilized to develop appropriate research priorities for the coming years. Well-designed preclinical research models will enhance our understanding of the pathophysiology of doxorubicin-induced cardiotoxicity and directly lead to better diagnosis, treatment, and prevention. © 2019 American Physiological Society. Compr Physiol 9:905-931, 2019.
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Affiliation(s)
- Trevi R. Mancilla
- University of Texas Health Science Center San Antonio, San Antonio, Texas, USA
| | - Brian Iskra
- University of Texas Health Science Center San Antonio, San Antonio, Texas, USA
| | - Gregory J. Aune
- University of Texas Health Science Center San Antonio, San Antonio, Texas, USA
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16
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Diastolic dysfunction can precede systolic dysfunction on MUGA in cancer patients receiving trastuzumab-based therapy. Nucl Med Commun 2018; 40:22-29. [PMID: 30418380 PMCID: PMC6282666 DOI: 10.1097/mnm.0000000000000941] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/03/2022]
Abstract
Background Trastuzumab (T) and anthracycline (A)-based chemotherapy is considered the standard of care in human epidermal growth factor receptor-2+ overexpressing breast cancer, but requires monitoring for known cardiotoxicity using left ventricular (LV) ejection fraction (EF) every 3–4 months during treatment. It is not conclusively established whether diastolic dysfunction (DD) precedes LVEF decrease in patients developing trastuzumab-induced cardiotoxicity (TIC). Objective The aim was to elucidate whether DD precedes LVEF decrease in trastuzumab-treated patients being monitored with radionuclide multigated acquisition for TIC. Patients and methods Patients treated with T±A-based chemotherapy who had undergone multigated acquisition were selected by date range (January 2006–September 2015). Up to four scans were analyzed per patient: (a) pre-A therapy, (b) pre-T therapy, (c) 4 months into T therapy, and (d) at end of T therapy. Baseline referred to the first scan of each patient (i.e. pre-A or pre-T). LV systolic and DD were defined as follows: EF less than 50% or a 10-point decrease from baseline and LV peak filling rate (PFR) less than 2.5 end-diastolic volume/s and time to peak LV filling rates (TPFR) greater than 180 ms, respectively. Results A total of 202 patients were screened for this study, of whom 153 had received A therapy (5.1±4.1 months duration) before T, 192 had 4 months of follow-up data, and 146 had 4 months of follow-up data and beyond (10.5±5.0 months). LVEF decreased with A and T therapy (P<0.005), but remained stable between 4 months and the final exam (P=0.26). In patients with normal diastolic function at baseline (45.5%), PFR decreased with A and T, and DD preceded SD by 73 days on average. In the remaining patients, with abnormal diastolic function at baseline (54.5%), PFR did not change over the course of treatment (P>0.1), nor did TPFR (P>0.3). Conclusion Patients with normal diastolic function at baseline receiving trastuzumab±anthracycline adjuvant therapy may develop DD before SD, therefore offering an opportunity for early referral to cardiologists to optimize cardiovascular risk factors and manage cardiotoxicity.
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Abstract
Several anticancer agents are associated with significant cardiotoxicity. The list of cardiotoxic cancer therapeutic agents includes anthracyclines, trastuzumab, alkylating agents, antimetabolites, which have been in use for decades; and recently introduced anticancer therapies such as tyrosine kinase inhibitors, angiogenesis inhibitors, checkpoint inhibitors and proteasome inhibitors. Cardiac imaging using echocardiography, nuclear imaging techniques, and magnetic resonance (MR) imaging can help in the early detection of chemotherapy-related cardiotoxicity. This can prevent the morbidity and mortality resulting from the cardiotoxicity of these agents. Further research is needed to improve our understanding of the underlying mechanism of their cardiotoxicity and to develop newer preventive and therapeutic strategies for chemotherapy related cardiotoxicity.
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Affiliation(s)
- Diwakar Jain
- a Section of Cardiovascular Medicine, Department of Medicine , Westchester Medical Center, New York Medical College , Valhalla , NY , USA
| | - Wilbert Aronow
- a Section of Cardiovascular Medicine, Department of Medicine , Westchester Medical Center, New York Medical College , Valhalla , NY , USA
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18
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Awadalla M, Hassan MZO, Alvi RM, Neilan TG. Advanced imaging modalities to detect cardiotoxicity. Curr Probl Cancer 2018; 42:386-396. [PMID: 30297038 PMCID: PMC6628686 DOI: 10.1016/j.currproblcancer.2018.05.005] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2018] [Accepted: 05/18/2018] [Indexed: 12/31/2022]
Abstract
Recent advances in cancer treatments have significantly improved survival rates, reemphasizing the focus on reducing the potential complications associated with some therapies. Cardiovascular disease associated with chemotherapies is a major cause of morbidity and mortality in cancer survivors. Early detection of cardiotoxicity improves cardiac outcomes among cancer patients. The review will focus on imaging modalities used to assess cardiotoxicity - the cardiovascular consequences of chemotherapies. The review will discuss the benefits and limitations associated with each technique, as well as the guidelines available to help identify at risk patients. We will discuss novel techniques that may help detect earlier signs of cardiotoxicity, directing management that may improve clinical outcomes.
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Affiliation(s)
- Magid Awadalla
- Cardiac MR PET CT Program, Massachusetts General Hospital, Boston, MA
| | - Malek Z O Hassan
- Cardiac MR PET CT Program, Massachusetts General Hospital, Boston, MA
| | - Raza M Alvi
- Cardiac MR PET CT Program, Massachusetts General Hospital, Boston, MA
| | - Tomas G Neilan
- Cardiac MR PET CT Program, Massachusetts General Hospital, Boston, MA; Cardio-oncology Program, Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Boston, MA.
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19
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Asnani A, Zheng B, Liu Y, Wang Y, Chen HH, Vohra A, Chi A, Cornella-Taracido I, Wang H, Johns DG, Sosnovik DE, Peterson RT. Highly potent visnagin derivatives inhibit Cyp1 and prevent doxorubicin cardiotoxicity. JCI Insight 2018; 3:96753. [PMID: 29321375 PMCID: PMC5821184 DOI: 10.1172/jci.insight.96753] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2017] [Accepted: 11/28/2017] [Indexed: 11/17/2022] Open
Abstract
Anthracyclines such as doxorubicin are highly effective chemotherapy agents used to treat many common malignancies. However, their use is limited by cardiotoxicity. We previously identified visnagin as protecting against doxorubicin toxicity in cardiac but not tumor cells. In this study, we sought to develop more potent visnagin analogs in order to use these analogs as tools to clarify the mechanisms of visnagin-mediated cardioprotection. Structure-activity relationship studies were performed in a zebrafish model of doxorubicin cardiomyopathy. Movement of the 5-carbonyl to the 7 position and addition of short ester side chains led to development of visnagin analogs with 1,000-fold increased potency in zebrafish and 250-fold increased potency in mice. Using proteomics, we discovered that doxorubicin caused robust induction of Cytochrome P450 family 1 (CYP1) that was mitigated by visnagin and its potent analog 23. Treatment with structurally divergent CYP1 inhibitors, as well as knockdown of CYP1A, prevented doxorubicin cardiomyopathy in zebrafish. The identification of potent cardioprotective agents may facilitate the development of new therapeutic strategies for patients receiving cardiotoxic chemotherapy. Moreover, these studies support the idea that CYP1 is an important contributor to doxorubicin cardiotoxicity and suggest that modulation of this pathway could be beneficial in the clinical setting.
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Affiliation(s)
- Aarti Asnani
- Cardiovascular Research Center, Cardiology Division, Massachusetts General Hospital
- CardioVascular Institute, Beth Israel Deaconess Medical Center
| | - Bahoui Zheng
- Cardiovascular Research Center, Cardiology Division, Massachusetts General Hospital
| | - Yan Liu
- Cardiovascular Research Center, Cardiology Division, Massachusetts General Hospital
| | - You Wang
- Cardiovascular Research Center, Cardiology Division, Massachusetts General Hospital
| | - Howard H. Chen
- Cardiovascular Research Center, Cardiology Division, Massachusetts General Hospital
- Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Anita Vohra
- CardioVascular Institute, Beth Israel Deaconess Medical Center
| | - An Chi
- Merck & Co., Inc., Boston, Massachusetts, USA
| | | | - Huijun Wang
- Merck & Co., Inc., Boston, Massachusetts, USA
| | | | - David E. Sosnovik
- Cardiovascular Research Center, Cardiology Division, Massachusetts General Hospital
- Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Randall T. Peterson
- Cardiovascular Research Center, Cardiology Division, Massachusetts General Hospital
- College of Pharmacy, University of Utah, Salt Lake City, Utah, USA
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20
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Jain D, Russell RR, Schwartz RG, Panjrath GS, Aronow W. Cardiac Complications of Cancer Therapy: Pathophysiology, Identification, Prevention, Treatment, and Future Directions. Curr Cardiol Rep 2018; 19:36. [PMID: 28374177 DOI: 10.1007/s11886-017-0846-x] [Citation(s) in RCA: 60] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
PURPOSE OF REVIEW Cardiotoxicity is an important complication of cancer therapy. With a significant improvement in the overall survival and prognosis of patients undergoing cancer therapy, cardiovascular toxicity of cancer therapy has become an important public health issue. Several well-established as well as newer anticancer therapies such as anthracyclines, trastuzumab, and other HER2 receptor blockers, antimetabolites, alkylating agents, tyrosine kinase inhibitors, angiogenesis inhibitors, checkpoint inhibitors, and thoracic irradiation are associated with significant cardiotoxicity. RECENT FINDINGS Cardiovascular imaging employing radionuclide imaging, echocardiography, and magnetic resonance imaging is helpful in early detection of the cardiotoxicity and prevention of overt heart failure. These techniques also provide important tools for understanding the mechanism of cardiotoxicity of these modalities, which would help develop strategies for the prevention of cardiac morbidity and mortality related to the use of these agents. An understanding of the mechanism of the cardiotoxicity of cancer therapies can help prevent and treat their adverse cardiovascular consequences. Clinical implementation of algorithms based upon cardiac imaging and several non-imaging biomarkers can prevent cardiac morbidity and mortality associated with the use of cardiotoxic cancer therapies.
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Affiliation(s)
- Diwakar Jain
- Section of Cardiovascular Medicine, New York Medical College and Westchester Medical Center, 100 Woods Road, Valhalla, NY, USA.
| | - Raymond R Russell
- Rhode Island Cardiovascular Institute, Rhode Island Hospital, The Warren Alpert Medical School of Brown University, Providence, RI, 02903, USA
| | - Ronald G Schwartz
- Cardiology Division, Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA
- Nuclear Medicine Division, Department of Imaging Sciences, University of Rochester Medical Center, Rochester, NY, USA
| | - Gurusher S Panjrath
- Heart and Vascular Institute, George Washington University School of Medicine and Health Sciences, Washington, DC, USA
| | - Wilbert Aronow
- Section of Cardiovascular Medicine, New York Medical College and Westchester Medical Center, 100 Woods Road, Valhalla, NY, USA
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21
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Abstract
PURPOSE OF REVIEW Cardio-oncology focuses increased effort to decrease cancer treatment-related cardiotoxicity while continuing to improve outcomes. We sought to synthesize the latest in nuclear cardiology as it pertains to the assessment of left ventricular function in preventative guidelines and comparison to other modalities, novel molecular markers of pre-clinical cardiotoxicity, and its role in cardiac amyloid diagnosis. RECENT FINDINGS Planar ERNA (equilibrium radionuclide angiocardiography) provides a reliable and proven means of monitoring and preventing anthracycline cardiotoxicity, and SPECT ERNA using solid-state gamma cameras may provide reproducible assessments of left ventricular function with reduced radiation exposure. While certain chemotherapeutics have vascular side effects, the use of stress perfusion imaging has still not been adequately studied for routine use. Similarly, markers of apoptosis, inflammation, and sympathetic nerve dysfunction are promising, but are still not ready for uniform usage. SPECT tracers can assist in nonbiopsy diagnosis of cardiac amyloid. Nuclear cardiology is a significant contributor to the multimodality approach to cardio-oncology.
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Affiliation(s)
- Jorge A Alvarez
- Warren Alpert Medical School, Brown University, Providence, RI, USA
| | - Raymond R Russell
- Warren Alpert Medical School, Brown University, Providence, RI, USA.
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22
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Early Evidence of Cardiotoxicity and Tumor Response in Patients with Sarcomas after High Cumulative Dose Doxorubicin Given as a Continuous Infusion. Sarcoma 2017; 2017:7495914. [PMID: 29081684 PMCID: PMC5634608 DOI: 10.1155/2017/7495914] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2017] [Accepted: 08/20/2017] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND Despite the dose-dependent response rate of sarcomas to doxorubicin, clinicians limit its cumulative dose due to cardiotoxicity. This study evaluates early evidence of cardiotoxicity in patients treated with high-dose doxorubicin given as a continuous infusion. METHODS Data was collected on patients who received 90 mg/m2 doxorubicin as a continuous infusion and 10 gm/m2 ifosfamide for up to 6 cycles as part of a phase II study. Cardiotoxicity was assessed with serial echocardiograms or multigated acquisition scans and serum brain natriuretic peptide and troponin levels. Tumor responses were determined by serial radiographic imaging per RECIST. RESULT Out of the 48 patients enrolled, no patient developed heart failure symptoms; however, 4 out of the 38 (10%) patients with serial left ventricular ejection fraction assessments developed subclinical cardiotoxicity (asymptomatic drop in LVEF ≥ 10%). Twenty-three patients received all six 72-hour cycles of doxorubicin with a mean cumulative dose of 540 mg/m2. Among these patients, 4% (n = 1) developed subclinical cardiotoxicity. In the advanced disease group (n = 39), patients with a complete or partial response received a higher mean cumulative dose than those with stable disease (p < 0.033). CONCLUSIONS Doxorubicin cardiotoxicity can be limited by administering doxorubicin as a continuous infusion, allowing higher cumulative dosing to maximize efficacy.
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23
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Jain D, Ahmad T, Cairo M, Aronow W. Cardiotoxicity of cancer chemotherapy: identification, prevention and treatment. ANNALS OF TRANSLATIONAL MEDICINE 2017; 5:348. [PMID: 28936442 DOI: 10.21037/atm.2017.06.35] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Cardiotoxicity is an important complication of several cancer therapeutic agents. Several well established and newer anticancer therapies such as anthracyclines, trastuzumab and other HER2 receptor blockers, antimetabolites, alkylating agents, tyrosine kinase inhibitors (TKIs), angiogenesis inhibitors, and checkpoint inhibitors are associated with significant cardiotoxicity. Cardiovascular imaging employing radionuclide imaging, echocardiography and magnetic resonance imaging are helpful in early detection and prevention of overt heart failure secondary to cardiotoxicity of cancer therapy. An understanding of the mechanism of the cardiotoxicity of cancer therapies can help prevent and treat their adverse cardiovascular consequences. Clinical implementation of algorithms based upon cardiac imaging and several non-imaging biomarkers can prevent cardiac morbidity and mortality associated with the use of cardiotoxic cancer therapies.
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Affiliation(s)
- Diwakar Jain
- Section of Cardiovascular Medicine, Department of Pediatrics, New York Medical College and Westchester Medical Center, Valhalla, NY, USA
| | - Tauseef Ahmad
- Section of Oncology and Hematology, Department of Pediatrics, New York Medical College and Westchester Medical Center, Valhalla, NY, USA
| | - Mitchel Cairo
- Section of Pediatric Hematology and Oncology, Department of Pediatrics, New York Medical College and Westchester Medical Center, Valhalla, NY, USA
| | - Wilbert Aronow
- Section of Cardiovascular Medicine, Department of Pediatrics, New York Medical College and Westchester Medical Center, Valhalla, NY, USA
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24
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Cutaneous Lymphoma—Inpatient Considerations. CURRENT DERMATOLOGY REPORTS 2017. [DOI: 10.1007/s13671-017-0173-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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25
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Chen-Scarabelli C, McRee C, Leesar MA, Hage FG, Scarabelli TM. Comprehensive review on cardio-oncology: Role of multimodality imaging. J Nucl Cardiol 2017; 24:906-935. [PMID: 27225513 DOI: 10.1007/s12350-016-0535-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2016] [Accepted: 04/19/2016] [Indexed: 10/21/2022]
Abstract
Cancer and cardiovascular disease are the two leading causes of mortality worldwide. Evolving oncologic therapy, including the use of newer targeted agents, has led to an improvement in survival from childhood- and adult-onset cancers. Consequently, there has been a growing realization of cardiotoxic complications related to cancer therapy, with some complications manifesting over months to decades after completion of cancer treatment. This paper reviews cancer therapeutics-related cardiovascular toxicity and its manifestations, multimodality imaging techniques for surveillance and detection of this complication, and the current state of knowledge in this emerging field.
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Affiliation(s)
- Carol Chen-Scarabelli
- Birmingham Veterans Affairs Medical Center, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Chad McRee
- Division of Cardiovascular Disease, University of Alabama at Birmingham, 1530 3rd Avenue, South Tinsley Harrison Tower, Birmingham, Alabama, 35294-0006, USA
| | - Massoud A Leesar
- Birmingham Veterans Affairs Medical Center, University of Alabama at Birmingham, Birmingham, Alabama, USA
- Division of Cardiovascular Disease, University of Alabama at Birmingham, 1530 3rd Avenue, South Tinsley Harrison Tower, Birmingham, Alabama, 35294-0006, USA
| | - Fadi G Hage
- Birmingham Veterans Affairs Medical Center, University of Alabama at Birmingham, Birmingham, Alabama, USA
- Division of Cardiovascular Disease, University of Alabama at Birmingham, 1530 3rd Avenue, South Tinsley Harrison Tower, Birmingham, Alabama, 35294-0006, USA
| | - Tiziano M Scarabelli
- Birmingham Veterans Affairs Medical Center, University of Alabama at Birmingham, Birmingham, Alabama, USA.
- Division of Cardiovascular Disease, University of Alabama at Birmingham, 1530 3rd Avenue, South Tinsley Harrison Tower, Birmingham, Alabama, 35294-0006, USA.
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26
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Srikanthan K, Klug R, Tirona M, Thompson E, Visweshwar H, Puri N, Shapiro J, Sodhi K. Creating a Biomarker Panel for Early Detection of Chemotherapy Related Cardiac Dysfunction in Breast Cancer Patients. ACTA ACUST UNITED AC 2017. [PMID: 28642833 DOI: 10.4172/2155-9880.1000507] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Cardiotoxicity is an important issue for breast cancer patients receiving anthracycline-trastuzumab therapy in the adjuvant setting. Studies show that 3-36% of patients receiving anthracyclines and/or trastuzumab experience chemotherapy related cardiac dysfunction (CRCD) and approximately 17% of patients must stop chemotherapy due to the consequences of CRCD. There is currently no standardized, clinically verified way to detect CRCD early, but common practices include serial echocardiography and troponin measurements, which can be timely, costly, and not always available in areas where health care resources are scarce. Furthermore, detection of CRCD, before there is any echocardiographic evidence of dysfunction or clinical symptoms present, would allow maximal benefit of chemotherapy and minimize cardiac complications. Creating a panel of serum biomarkers would allow for more specificity and sensitivity in the early detection of CRCD, which would be easy to implement and cost effective in places with limited health care. Based on a review of the literature, we propose creating a biomarker panel consisting of topoisomerase 2β, serum troponin T/I, myeloperoxidase, NT-proBNP, miR-208b, miR-34a, and miR-150 in breast cancer patients receiving anthracyclines and/or trastuzumab to detect CRCD before any signs of overt cardiotoxicity are apparent.
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Affiliation(s)
- Krithika Srikanthan
- Department of Internal Medicine, Marshall University Joan C Edwards School of Medicine, Huntington, WV, USA
| | - Rebecca Klug
- Department of Surgery, Marshall University Joan C Edwards School of Medicine, Huntington, WV, USA
| | - Maria Tirona
- Division of Hematology and Oncology, Department of Internal Medicine, Marshall University Joan C Edwards School of Medicine, Huntington, WV, USA
| | - Ellen Thompson
- Department of Cardiology, Marshall University Joan C Edwards School of Medicine, Huntington, WV, USA
| | - Haresh Visweshwar
- Department of Internal Medicine, Marshall University Joan C Edwards School of Medicine, Huntington, WV, USA
| | - Nitin Puri
- Department of Physiology and Pharmacology, University of Toledo College of Medicine, Toledo, OH, 43614, USA
| | - Joseph Shapiro
- Department of Internal Medicine, Marshall University Joan C Edwards School of Medicine, Huntington, WV, USA
| | - Komal Sodhi
- Department of Surgery, Marshall University Joan C Edwards School of Medicine, Huntington, WV, USA
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27
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Laursen AH, Thune JJ, Hutchings M, Hasbak P, Kjaer A, Elming MB, Ripa RS. 123
I-MIBG imaging for detection of anthracycline-induced cardiomyopathy. Clin Physiol Funct Imaging 2017; 38:176-185. [DOI: 10.1111/cpf.12419] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2016] [Accepted: 01/19/2017] [Indexed: 01/08/2023]
Affiliation(s)
- Adam H. Laursen
- Department of Haematology; Rigshospitalet; Copenhagen Denmark
| | | | | | - Philip Hasbak
- Department of Clinical Physiology; Nuclear Medicine & PET and Cluster for Molecular Imaging; Rigshospitalet and University of Copenhagen; Copenhagen Denmark
| | - Andreas Kjaer
- Department of Clinical Physiology; Nuclear Medicine & PET and Cluster for Molecular Imaging; Rigshospitalet and University of Copenhagen; Copenhagen Denmark
| | - Marie B. Elming
- Department of Cardiology; Rigshospitalet; Copenhagen Denmark
| | - Rasmus S. Ripa
- Department of Clinical Physiology; Nuclear Medicine & PET and Cluster for Molecular Imaging; Rigshospitalet and University of Copenhagen; Copenhagen Denmark
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28
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Thavendiranathan P, Amir E. Left Ventricular Dysfunction With Trastuzumab Therapy: Is Primary Prevention the Best Option? J Clin Oncol 2016; 35:820-825. [PMID: 28029315 DOI: 10.1200/jco.2016.71.0038] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 51-year-old women with left-sided, T2N1, grade 3, estrogen receptor- and progesterone receptor-negative, human epidermal growth factor receptor 2 (HER2)-positive breast cancer was referred to a cardio-oncology clinic for pre-cancer treatment cardiovascular risk assessment. The planned cancer treatment was 3 cycles of FEC (fluorouracil, epirubicin [100 mg/m2 per dose], and cyclophosphamide), followed by 3 cycles of concurrent docetaxel and trastuzumab, followed by maintenance trastuzumab to complete a 1-year course. Other than a prior history of hysterectomy, there was no relevant medical history. Her cardiac history was notable for the absence of prior cardiovascular disease, hypertension, diabetes, or hypercholesterolemia. She was a nonsmoker. At initial clinic visit, her blood pressure was 138/84 with an unremarkable cardiovascular examination. Her echocardiography demonstrated normal sinus rhythm at 73 beats per minute. During cancer treatment, she was observed with echocardiography (baseline left ventricular ejection fraction [LVEF], 61%; global longitudinal strain, -21.5%), cardiac magnetic resonance imaging (CMR, as part of an ongoing study), high-sensitivity troponin I, and B-type natriuretic peptide ( Table 1 ). Given that her baseline evaluations were negative at her initial visit, we discussed whether there were agents to prevent the rare, but serious, complication of congestive heart failure (HF) associated with anthracycline- and trastuzumab-based therapy.
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Affiliation(s)
- Paaladinesh Thavendiranathan
- Paaladinesh Thavendiranathan, Ted Rogers Program in Cardiotoxicity Prevention, University Health Network, Toronto, Ontario, Canada; and Eitan Amir, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
| | - Eitan Amir
- Paaladinesh Thavendiranathan, Ted Rogers Program in Cardiotoxicity Prevention, University Health Network, Toronto, Ontario, Canada; and Eitan Amir, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
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29
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Cao L, Zhu W, Wagar EA, Meng QH. Biomarkers for monitoring chemotherapy-induced cardiotoxicity. Crit Rev Clin Lab Sci 2016; 54:87-101. [PMID: 28013560 DOI: 10.1080/10408363.2016.1261270] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Cardiotoxicity, including acute and late-onset cardiotoxicity, is a well-known adverse effect of many types of antitumor agents. Early identification of patients with cardiotoxicity is important to ensure prompt treatment and minimize toxic effects. The etiology of chemotherapy-induced cardiotoxicity is multifactorial. Traditional methods for assessment of chemotherapy-induced cardiotoxicity typically involve serial measurements of cardiac function via multi-modality imaging techniques. Typically, however, significant left ventricular dysfunction has already occurred when cardiotoxicity is detected by imaging techniques. Biomarkers, most importantly cardiac natriuretic peptides and troponins, are promising markers for identifying patients potentially at risk for clinical heart failure symptoms. This review summarizes the recent progress in clinical utilization of biomarkers for early diagnosis of acute cardiotoxicity and for prediction of late-onset cardiotoxicity. We also discuss the conflicting results of different studies and the association of results with study design.
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Affiliation(s)
- Liyun Cao
- a Department of Laboratory Medicine , Unit 37, The University of Texas MD Anderson Cancer Center , Houston , TX , USA and
| | - Wuqiang Zhu
- b Department of Biomedical Engineering , University of Alabama at Birmingham , Birmingham , AL , USA
| | - Elizabeth A Wagar
- a Department of Laboratory Medicine , Unit 37, The University of Texas MD Anderson Cancer Center , Houston , TX , USA and
| | - Qing H Meng
- a Department of Laboratory Medicine , Unit 37, The University of Texas MD Anderson Cancer Center , Houston , TX , USA and
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30
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An emerging epidemic: cancer and heart failure. Clin Sci (Lond) 2016; 131:113-121. [DOI: 10.1042/cs20160412] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2016] [Revised: 10/17/2016] [Accepted: 11/03/2016] [Indexed: 02/07/2023]
Abstract
Heart disease and cancer are the two leading causes of mortality globally. Cardiovascular complications of cancer therapy significantly contribute to the global burden of cardiovascular disease. Heart failure (HF) in particular is a relatively common and life-threatening complication. The increased risk is driven by the shared risk factors for cancer and HF, the direct impact of cancer therapy on the heart, an existing care gap in the cardiac care of patients with cancer and the increasing population of adult cancer survivors. The clear relationship between cancer treatment initiation and the potential for myocardial injury makes this population attractive for prevention strategies, targeted cardiovascular monitoring and treatment. However, there is currently no consensus on the optimal strategy for managing this at-risk population. Uniform treatment using cardioprotective medications may reduce the incidence of HF, but would impose frequently unnecessary and burdensome side effects. Ideally we could use validated risk-prediction models to target HF-preventive strategies, but currently no such models exist. In the present review, we focus on evidence and rationales for contemporary clinical decision-making in this novel field and discuss issues, including the burden of HF in patients with cancer, the reasons for the elevated risk and potential prevention strategies.
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Bozkurt B, Colvin M, Cook J, Cooper LT, Deswal A, Fonarow GC, Francis GS, Lenihan D, Lewis EF, McNamara DM, Pahl E, Vasan RS, Ramasubbu K, Rasmusson K, Towbin JA, Yancy C. Current Diagnostic and Treatment Strategies for Specific Dilated Cardiomyopathies: A Scientific Statement From the American Heart Association. Circulation 2016; 134:e579-e646. [PMID: 27832612 DOI: 10.1161/cir.0000000000000455] [Citation(s) in RCA: 492] [Impact Index Per Article: 54.7] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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Giubbini R, Milan E. The time for radionuclide ventriculography resurrection is coming. J Nucl Cardiol 2016; 23:1139-1141. [PMID: 26253328 DOI: 10.1007/s12350-015-0245-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2015] [Revised: 07/10/2015] [Indexed: 11/30/2022]
Affiliation(s)
| | - Elisa Milan
- San Giacomo Apostolo Hospital, Castelfranco Veneto, TV, Italy
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33
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Zamorano JL, Lancellotti P, Rodriguez Muñoz D, Aboyans V, Asteggiano R, Galderisi M, Habib G, Lenihan DJ, Lip GYH, Lyon AR, Lopez Fernandez T, Mohty D, Piepoli MF, Tamargo J, Torbicki A, Suter TM, Zamorano JL, Aboyans V, Achenbach S, Agewall S, Badimon L, Barón‐Esquivias G, Baumgartner H, Bax JJ, Bueno H, Carerj S, Dean V, Erol Ç, Fitzsimons D, Gaemperli O, Kirchhof P, Kolh P, Lancellotti P, Lip GYH, Nihoyannopoulos P, Piepoli MF, Ponikowski P, Roffi M, Torbicki A, Vaz Carneiro A, Windecker S, Achenbach S, Minotti G, Agewall S, Badimon L, Bueno H, Cardinale D, Carerj S, Curigliano G, de Azambuja E, Dent S, Erol C, Ewer MS, Farmakis D, Fietkau R, Fitzsimons D, Gaemperli O, Kirchhof P, Kohl P, McGale P, Ponikowski P, Ringwald J, Roffi M, Schulz‐Menger J, Stebbing J, Steiner RK, Szmit S, Vaz Carneiro A, Windecker S. 2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines. Eur J Heart Fail 2016; 19:9-42. [DOI: 10.1002/ejhf.654] [Citation(s) in RCA: 227] [Impact Index Per Article: 25.2] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
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Zamorano JL, Lancellotti P, Rodriguez Muñoz D, Aboyans V, Asteggiano R, Galderisi M, Habib G, Lenihan DJ, Lip GYH, Lyon AR, Lopez Fernandez T, Mohty D, Piepoli MF, Tamargo J, Torbicki A, Suter TM. 2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines. Eur Heart J 2016; 37:2768-2801. [DOI: 10.1093/eurheartj/ehw211] [Citation(s) in RCA: 1498] [Impact Index Per Article: 166.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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Russell RR, Alexander J, Jain D, Poornima IG, Srivastava AV, Storozynsky E, Schwartz RG. The role and clinical effectiveness of multimodality imaging in the management of cardiac complications of cancer and cancer therapy. J Nucl Cardiol 2016; 23:856-84. [PMID: 27251147 DOI: 10.1007/s12350-016-0538-8] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2016] [Accepted: 04/13/2016] [Indexed: 12/24/2022]
Abstract
With the increasing number of individuals living with a current or prior diagnosis of cancer, it is important for the cardiovascular specialist to recognize the various complications of cancer and its therapy on the cardiovascular system. This is true not only for established cancer therapies, such as anthracyclines, that have well established cardiovascular toxicities, but also for the new targeted therapies that can have "off target" effects in the heart and vessels. The purpose of this informational statement is to provide cardiologists, cardiac imaging specialists, cardio-oncologists, and oncologists an understanding of how multimodality imaging may be used in the diagnosis and management of the cardiovascular complications of cancer therapy. In addition, this document is meant to provide useful general information concerning the cardiovascular complications of cancer and cancer therapy as well as established recommendations for the monitoring of specific cardiotoxic therapies.
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Affiliation(s)
- Raymond R Russell
- Rhode Island Cardiovascular Institute, Rhode Island Hospital, The Warren Alpert Medical School of Brown University, 593 Eddy Street, APC 737, Providence, RI, 02903, USA.
| | - Jonathan Alexander
- Cardiology Division, Western Connecticut Medical Center at Danbury Hospital, Danbury, CT, USA
| | - Diwakar Jain
- Section of Cardiovascular Medicine, New York Medical College and Westchester Medical Center, Valhalla, NY, USA
| | - Indu G Poornima
- Division of Cardiology, Allegheny Health Network, Pittsburgh, PA, USA
| | - Ajay V Srivastava
- Division of Cardiovascular Medicine, Scripps Clinic, La Jolla, CA, USA
| | - Eugene Storozynsky
- Cardiology Division, Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA
| | - Ronald G Schwartz
- Cardiology Division, Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA
- Nuclear Medicine Division, Department of Imaging Sciences, University of Rochester Medical Center, Rochester, NY, USA
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Reuvekamp EJ, Bulten BF, Nieuwenhuis AA, Meekes MRA, de Haan AFJ, Tol J, Maas AHEM, Elias-Smale SE, de Geus-Oei LF. Does diastolic dysfunction precede systolic dysfunction in trastuzumab-induced cardiotoxicity? Assessment with multigated radionuclide angiography (MUGA). J Nucl Cardiol 2016; 23:824-32. [PMID: 26048264 PMCID: PMC4956716 DOI: 10.1007/s12350-015-0164-x] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2015] [Accepted: 04/10/2015] [Indexed: 01/09/2023]
Abstract
BACKGROUND Trastuzumab is successfully used for the treatment of HER2-positive breast cancer. Because of its association with cardiotoxicity, LVEF is monitored by MUGA, though this is a relatively late measure of cardiac function. Diastolic dysfunction (DD) is believed to be an early predictor of cardiac impairment. We evaluate the merit of MUGA-derived diastolic function parameters in the early detection of trastuzumab-induced cardiotoxicity (TIC). METHODS AND RESULTS 77 trastuzumab-treated patients with normal baseline systolic and diastolic function were retrospectively selected (n = 77). All serial MUGA examinations were re-analyzed for systolic and diastolic function parameters. 36 patients (47%) developed SD and 45 patients (58%) DD during treatment. Both systolic and diastolic parameters significantly decreased. Of the patients with SD, 24 (67%) also developed DD. DD developed prior to systolic impairment in 54% of cases, in 42% vice versa, while time to occurrence did not differ significantly (P = .52). This also applied to the subgroup of advanced stage breast cancer patients (P = .1). CONCLUSIONS Trastzumab-induced SD and DD can be detected by MUGA. An impairment of MUGA-derived diastolic parameters does not occur prior to SD and therefore cannot be used as earlier predictors of TIC.
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Affiliation(s)
- E J Reuvekamp
- Department of Radiology and Nuclear Medicine, Radboudumc, Nijmegen, The Netherlands
| | - B F Bulten
- Biomedical Photonic Imaging Group, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, PO Box 217, 7500 AE, Enschede, The Netherlands.
| | - A A Nieuwenhuis
- Department of Radiology and Nuclear Medicine, Radboudumc, Nijmegen, The Netherlands
| | - M R A Meekes
- Department of Radiology and Nuclear Medicine, Radboudumc, Nijmegen, The Netherlands
| | - A F J de Haan
- Department for Health Evidence, Radboudumc, Nijmegen, The Netherlands
| | - J Tol
- Department of Medical Oncology, Radboudumc, Nijmegen, The Netherlands
| | - A H E M Maas
- Department of Cardiology, Radboudumc, Nijmegen, The Netherlands
| | - S E Elias-Smale
- Department of Cardiology, Radboudumc, Nijmegen, The Netherlands
| | - L F de Geus-Oei
- Biomedical Photonic Imaging Group, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, PO Box 217, 7500 AE, Enschede, The Netherlands
- Department of Radiology, Leiden University Medical Centre, Leiden, The Netherlands
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Echocardiography and Alternative Cardiac Imaging Strategies for Long-Term Cardiotoxicity Surveillance of Cancer Survivors Treated with Chemotherapy and/or Radiation Exposure. Curr Oncol Rep 2016; 18:52. [PMID: 27461436 DOI: 10.1007/s11912-016-0532-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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Murbraech K, Holte E, Broch K, Smeland KB, Holte H, Rösner A, Lund MB, Dalen H, Kiserud C, Aakhus S. Impaired Right Ventricular Function in Long-Term Lymphoma Survivors. J Am Soc Echocardiogr 2016; 29:528-36. [DOI: 10.1016/j.echo.2016.02.014] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2015] [Indexed: 01/08/2023]
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Zito C, Longobardo L, Cadeddu C, Monte I, Novo G, Dell'Oglio S, Pepe A, Madonna R, Tocchetti CG, Mele D. Cardiovascular imaging in the diagnosis and monitoring of cardiotoxicity: role of echocardiography. J Cardiovasc Med (Hagerstown) 2016; 17 Suppl 1:e35-e44. [PMID: 27183524 DOI: 10.2459/jcm.0000000000000374] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
The evaluation by cardiovascular imaging of chemotherapy patients became a central topic in the last several years. The use of drugs for the treatment of cancers increased, and new molecules and protocols were developed to improve outcomes in these patients. Although, these novel approaches also produced a progressive increase in side effects, particularly myocardial dysfunction. Imaging of the heart was highly accurate in the early diagnosis of cancer therapeutics related-cardiac dysfunction. Echocardiography is the first-line method to assess ventricular function alterations, and it is required to satisfy the need for an early, easy and accurate diagnosis to stratify the risk of heart failure and manage treatments. A careful monitoring of cardiac function during the course of therapy should prevent the onset of severe heart impairment. This review provides an overview of the most important findings of the role of echocardiography in the management of chemotherapy-treated patients to create a clear and complete description of the efficacy of conventional measurements, the importance of comprehensive heart evaluations, the additional role of new echocardiographic techniques, the utility of integrated studies using other imaging tools and the positions of the most important international societies on this topic.
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Affiliation(s)
- Concetta Zito
- aDepartment of Clinical and Experimental Medicine, Section of Cardiology, University of Messina, Messina bDepartment of Medical Sciences 'Mario Aresu', University of Cagliari, Cagliari cDepartment of General Surgery and Medical-Surgery Specialties, Section of Cardiology, University of Catania, Catania dChair and Division of Cardiology, University of Palermo, Palermo eU.O.C. Magnetic Resonance Imaging, Fondazione G. Monasterio C.N.R., Pisa fInstitute of Cardiology, Center of Excellence on Aging, 'G. d'Annunzio' University, Chieti gDipartimento di Scienze Mediche Traslazionali, Universita' degli Studi di Napoli Federico II hCardiology Unit, University Hospital of Ferrara, Ferrara, Italy
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40
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Subclinical Cardiovascular Disease in Lymphoma Survivors by Sex. J Obstet Gynecol Neonatal Nurs 2016; 45:438-53. [DOI: 10.1016/j.jogn.2015.12.014] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/01/2015] [Indexed: 12/29/2022] Open
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41
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Oliveira GH, Al-Kindi SG, Caimi PF, Lazarus HM. Maximizing anthracycline tolerability in hematologic malignancies: Treat to each heart's content. Blood Rev 2016; 30:169-78. [DOI: 10.1016/j.blre.2015.11.001] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2015] [Revised: 10/20/2015] [Accepted: 11/02/2015] [Indexed: 01/01/2023]
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Gavila J, Seguí MÁ, Calvo L, López T, Alonso JJ, Farto M, Sánchez-de la Rosa R. Evaluation and management of chemotherapy-induced cardiotoxicity in breast cancer: a Delphi study. Clin Transl Oncol 2016; 19:91-104. [PMID: 27101413 PMCID: PMC5215075 DOI: 10.1007/s12094-016-1508-y] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2016] [Accepted: 03/25/2016] [Indexed: 12/03/2022]
Abstract
Purpose While much progress has been made in the treatment of breast cancer, cardiac complications resulting from therapy remain a significant concern. Both anthracyclines and novel targeted agents can inflict cardiac damage. The present study aimed to evaluate the difference between what it is currently done and what standards of care should be used to minimizing and managing cardiac toxicity in breast cancer survivors. Methods A two-round multicenter Delphi study was carried out. The panel consisted of 100 oncologists who were asked to define the elected therapies for breast cancer patients, the clinical definition and patterns of cancer drug-derived cardiac toxicity, and those protocols focused on early detection and monitoring of cardiovascular outcomes. Results Experts agreed a more recent definition of cardiotoxicity. Around 38 % of patients with early-stage disease, and 51.3 % cases with advanced metastatic breast cancer had preexisting risk factors for cardiotoxicity. Among risk factors, cumulative dose of anthracycline ≥450 mg/m2 and its combination with other anticancer drugs, and a preexisting cardiovascular disease were considered the best predictors of cardiotoxicity. Echocardiography and radionuclide ventriculography have been the proposed methods for monitoring changes in cardiac structure and function. Breast cancer is generally treated with anthracyclines (80 %), so that the panel strongly stated about the need to plan a strategy to managing cardiotoxicity. A decline of left ventricular ejection fraction (LVEF) >10 %, to an LVEF value <53 % was suggested as a criterion for changing the dose schedule of anthracyclines, or suspending the treatment of chemotherapy plus trastuzumab until the normalization of the left ventricular function. The use of liposomal anthracyclines was strongly suggested as a treatment option for breast cancer patients. Conclusions The present report is the first to produce a set of statements on the prevention, evaluation and monitoring of chemotherapy-induced cardiac toxicity in breast cancer patients.
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Affiliation(s)
- J Gavila
- Servicio de Oncología Médica, Fundación Instituto Valenciano de Oncología, Calle del Profesor Beltrán Bàguena, 8, 46009, Valencia, Spain.
| | - M Á Seguí
- Servicio de Oncología Médica, Corporació Sanitaria ParcTaulí, Barcelona, Spain
| | - L Calvo
- Servicio de Oncología Médica, Complejo Hospitalario Universitario A Coruña, A Coruña, Spain
| | - T López
- Servicio de Cardiología, Hospital Universitario La Paz, Madrid, Spain
| | - J J Alonso
- Servicio de Cardiología, Hospital Universitario de Getafe, Madrid, Spain
| | - M Farto
- Medical Department, TEVA Pharma, Madrid, Spain
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Haarmark C, Haase C, Jensen MM, Zerahn B. Pre-chemotherapy values for left and right ventricular volumes and ejection fraction by gated tomographic radionuclide angiography using a cadmium-zinc-telluride detector gamma camera. J Nucl Cardiol 2016; 23:87-97. [PMID: 26338424 DOI: 10.1007/s12350-015-0177-5] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2015] [Accepted: 05/06/2015] [Indexed: 11/27/2022]
Abstract
BACKGROUND Estimation of left ventricular ejection fraction (LVEF) using equilibrium radionuclide angiography is an established method for assessment of left ventricular function. The purpose of this study was to establish normative data on left and right ventricular volumes and ejection fraction, using cadmium-zinc-telluride SPECT camera. METHODS AND RESULTS From routine assessments of left ventricular function in 1172 patients, we included 463 subjects (194 men and 269 women) without diabetes, previous potentially cardiotoxic chemotherapy, known cardiovascular or pulmonary disease. The lower limits defined as mean value minus two standard deviations for ventricular ejection fraction and end diastolic volume were LVEF (men: 50%, women: 50%), LEDV (men: 45 mL, women: 40 mL), RVEF (men: 29%, women: 28%), and REDV (men: 73 mL, women: 57 mL).There was a significant negative correlation between age and both left and right ventricular volumes in women (r = -0.4, P < .001) but only for right end systolic ventricular volume in men (r = -0.3, P = .001). CONCLUSION A set of reference values for cardiac evaluation prior to chemotherapy in cancer patients without other known cardiopulmonary disease is presented. There are age-related changes in cardiac dimensions with age depending on gender, although with only limited influence on LVEF or RVEF.
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Affiliation(s)
- Christian Haarmark
- Department of Clinical Physiology and Nuclear Medicine, Herlev Hospital, Herlev, Denmark.
- Department of Clinical Physiology and Nuclear Medicine, Bispebjerg Hospital, Bispebjerg Bakke 23, Building 60, Floor A, 2400, Copenhagen, Denmark.
| | - Christine Haase
- Department of Clinical Physiology and Nuclear Medicine, Herlev Hospital, Herlev, Denmark
| | - Maria Maj Jensen
- Department of Clinical Physiology and Nuclear Medicine, Herlev Hospital, Herlev, Denmark
| | - Bo Zerahn
- Department of Clinical Physiology and Nuclear Medicine, Herlev Hospital, Herlev, Denmark
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Abstract
The identification of patients at risk of cardiac toxicity (cardiotoxicity) from cancer therapy is challenging. There is an increasing focus on early detection of cardiotoxicity such that interventions can be instituted to prevent advanced heart failure. Clinical risk prediction tools are limited and clinical symptoms are not specific. Direct assessment of myocardial function before and during cancer treatment using cardiac imaging appears to be an objective method to identify patients at risk. Although, multiple imaging modalities and measures of cardiac function are available, the best modality or the optimal measure of function is unknown. Measurement of left ventricular ejection fraction is most commonly used; however, growing literature suggests that it is inadequate for the detection of early cardiac injury. Other measures include left ventricular diastolic function, myocardial deformation, and myocardial tissue characterization. This review will provide an overview of the clinically available measures for the assessment of cardiotoxicity.
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46
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Mouli S, Nanayakkara G, AlAlasmari A, Eldoumani H, Fu X, Berlin A, Lohani M, Nie B, Arnold RD, Kavazis A, Smith F, Beyers R, Denney T, Dhanasekaran M, Zhong J, Quindry J, Amin R. The role of frataxin in doxorubicin-mediated cardiac hypertrophy. Am J Physiol Heart Circ Physiol 2015; 309:H844-59. [PMID: 26209053 DOI: 10.1152/ajpheart.00182.2015] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2015] [Accepted: 07/14/2015] [Indexed: 12/22/2022]
Abstract
Doxorubicin (DOX) is a highly effective anti-neoplastic agent; however, its cumulative dosing schedules are clinically limited by the development of cardiotoxicity. Previous studies have attributed the cause of DOX-mediated cardiotoxicity to mitochondrial iron accumulation and the ensuing reactive oxygen species (ROS) formation. The present study investigates the role of frataxin (FXN), a mitochondrial iron-sulfur biogenesis protein, and its role in development of DOX-mediated mitochondrial dysfunction. Athymic mice treated with DOX (5 mg/kg, 1 dose/wk with treatments, followed by 2-wk recovery) displayed left ventricular hypertrophy, as observed by impaired cardiac hemodynamic performance parameters. Furthermore, we also observed significant reduction in FXN expression in DOX-treated animals and H9C2 cardiomyoblast cell lines, resulting in increased mitochondrial iron accumulation and the ensuing ROS formation. This observation was paralleled in DOX-treated H9C2 cells by a significant reduction in the mitochondrial bioenergetics, as observed by the reduction of myocardial energy regulation. Surprisingly, similar results were observed in our FXN knockdown stable cell lines constructed by lentiviral technology using short hairpin RNA. To better understand the cardioprotective role of FXN against DOX, we constructed FXN overexpressing cardiomyoblasts, which displayed cardioprotection against mitochondrial iron accumulation, ROS formation, and reduction of mitochondrial bioenergetics. Lastly, our FXN overexpressing cardiomyoblasts were protected from DOX-mediated cardiac hypertrophy. Together, our findings reveal novel insights into the development of DOX-mediated cardiomyopathy.
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Affiliation(s)
- Shravanthi Mouli
- Department of Drug, Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, Alabama
| | - Gayani Nanayakkara
- Department of Drug, Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, Alabama
| | - Abdullah AlAlasmari
- Department of Drug, Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, Alabama
| | - Haitham Eldoumani
- Department of Drug, Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, Alabama
| | - Xiaoyu Fu
- Department of Drug, Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, Alabama
| | - Avery Berlin
- Department of Drug, Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, Alabama
| | - Madhukar Lohani
- Department of Drug, Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, Alabama
| | - Ben Nie
- Department of Drug, Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, Alabama
| | - Robert D Arnold
- Department of Drug, Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, Alabama
| | | | - Forrest Smith
- Department of Drug, Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, Alabama
| | - Ronald Beyers
- Auburn University MRI Research Center, Auburn, Alabama; and
| | - Thomas Denney
- Department of Electrical and Computer Engineering, Auburn University, Auburn, Alabama; Auburn University MRI Research Center, Auburn, Alabama; and
| | - Muralikrishnan Dhanasekaran
- Department of Drug, Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, Alabama
| | - Juming Zhong
- Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, Alabama
| | - John Quindry
- School of Kinesiology, Auburn University, Auburn, Alabama
| | - Rajesh Amin
- Department of Drug, Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, Alabama;
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Chang SA, Lim BK, Lee YJ, Hong MK, Choi JO, Jeon ES. A Novel Angiotensin Type I Receptor Antagonist, Fimasartan, Prevents Doxorubicin-induced Cardiotoxicity in Rats. J Korean Med Sci 2015; 30:559-68. [PMID: 25931786 PMCID: PMC4414639 DOI: 10.3346/jkms.2015.30.5.559] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2014] [Accepted: 02/13/2015] [Indexed: 11/20/2022] Open
Abstract
Angiotensin receptor blockers (ARBs) have organ-protective effects in heart failure and may be also effective in doxorubicin-induced cardiomyopathy (DOX-CMP); however, the efficacy of ARBs on the prevention of DOX-CMP have not been investigated. We performed a preclinical experiment to evaluate the preventive effect of a novel ARB, fimasartan, in DOX-CMP. All animals underwent echocardiography and were randomly assigned into three groups: treated daily with vehicle (DOX-only group, n=22), 5 mg/kg of fimasartan (Low-fima group, n=22), and 10 mg/kg of fimasartan (High-fima group, n=19). DOX was injected once a week for six weeks. Echocardiography and hemodynamic assessment was performed at the 8th week using a miniaturized conductance catheter. Survival rate of the High-fima group was greater (100%) than that of the Low-fima (75%) and DOX-only groups (50%). Echocardiography showed preserved left ventricular (LV) ejection fraction in the High-fima group, but not in the DOX-only group (P=0.002). LV dimensions increased in the DOX-only group; however, remodeling was attenuated in the Low-fima and High-fima groups. Hemodynamic assessment showed higher dP/dt in the High-fima group compared with the DOX-only group. A novel ARB, fimasartan, may prevent DOX-CMP and improve survival rate in a dose-dependent manner in a rat model of DOX-CMP and could be a treatment option for the prevention of DOX-CMP.
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Affiliation(s)
- Sung-A Chang
- Division of Cardiology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
- Cardiovascular Imaging Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Byung-Kwan Lim
- Department of Biomedical Science, Jungwon University, Goesan-gun, Korea
| | - You Jung Lee
- Division of Cardiology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Mi-Kyung Hong
- Cardiovascular Imaging Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jin-Oh Choi
- Division of Cardiology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
- Cardiovascular Imaging Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Eun-Seok Jeon
- Division of Cardiology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
- Cardiovascular Imaging Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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48
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Evaluation, prevention and management of cancer therapy-induced cardiotoxicity: a contemporary approach for clinicians. Curr Opin Cardiol 2015; 30:197-204. [PMID: 25574894 DOI: 10.1097/hco.0000000000000145] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
PURPOSE OF REVIEW While targeted therapies have improved cancer outcomes, unique cardiovascular toxicities are increasingly recognized, particularly when administered sequentially after anthracyclines or radiation. Patients with cancer therapy-induced cardiotoxicity benefit from collaborative care involving cardiology and oncology, leading to a new interdisciplinary field called cardio-oncology. The present review will highlight contemporary clinical issues in cardio-oncology. RECENT FINDINGS Recently, risk factors for cancer therapy-induced cardiotoxicity have been evaluated in real-world rather than in clinical trial patients. Biomarkers and advanced echocardiography are emerging as sensitive tools for preclinical identification of cancer therapy-induced cardiotoxicity. Single-center studies suggest that cancer therapy-induced cardiotoxicity responds to prompt heart failure medical treatment, and such therapy may even prevent cardiotoxicity. SUMMARY Modern cancer therapy has short-term cardiac risk that may require collaborative management by clinicians with expertise in cardiology and oncology. The increased effectiveness of modern cancer therapy is resulting in a growing population of cancer survivors who are at long-term risk for cardiovascular disease. The present review of contemporary clinical issues in cardio-oncology will be of interest to healthcare providers who manage cardiotoxicity during cancer therapy, and who follow patients who survive cancer but face increased long-term cardiovascular risk.
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Markman TM, Markman M. Cardiotoxicity of antineoplastic agents: what is the present and future role for imaging? Curr Oncol Rep 2015; 16:396. [PMID: 24992733 DOI: 10.1007/s11912-014-0396-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
As antineoplastic treatment options expand at an increasing rate, both traditional and novel agents continue to be limited by their cardiotoxic effects. While functional decline becomes clinically apparent at late states of toxicity, little is known about early stages during which treatment or prevention may still be an option. Several imaging modalities,including echocardiography, multiple gated acquisition, and cardiac magnetic resonance imaging have the ability to identify cardiac effects before they produce clinical symptoms.Here we discuss the current and future role of cardiac imaging in the assessment of cardiotoxicity of antineoplastic agents. effects on cardiac tissue, resulting in myocardial cellular damage,and ultimately lead to a wide range of effects including electrophysiological abnormalities, symptomatic heart failure(HF), and even death. This represents a limiting factor in the therapy of several otherwise treatable neoplasms [2].The cardiotoxicity of antineoplastic agents raises several important questions regarding the actual prevalence of cardiac toxicity, the ability to effectively treat or prevent such effects with pharmaceutical interventions, and the availability of a means for early diagnosis. Here, we focus on the latter, specifically examining current and potential future imaging strategies to detect the cardiac effects of chemotherapeutic agents.
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Sadurska E. Current Views on Anthracycline Cardiotoxicity in Childhood Cancer Survivors. Pediatr Cardiol 2015; 36:1112-9. [PMID: 25939787 PMCID: PMC4495714 DOI: 10.1007/s00246-015-1176-7] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2015] [Accepted: 04/18/2015] [Indexed: 12/28/2022]
Abstract
Owing to their high efficacy, anthracycline antibiotics are included in numerous chemotherapeutic regimens used-often in combination with radiation therapy and/or surgery-in treatment of solid tumours and blood malignancies, both in children and adults. However, the efficacy of modern cancer treatments, owing to which the population of cancer survivors has been on the rise in recent years, may be limited by the risk of serious complications involving multiple organs and systems, including the cardiovascular system. Being an important side effect of anthracyclines, cardiotoxicity may limit the efficacy of cancer therapies in the acute phase (i.e. during the treatment) and induce the long-term sequelae, observed years after treatment completion in childhood cancer survivors. It is very important to understand the cardiotoxicity-associated mechanisms and to determine its risk factors in order to develop and/or improve the effective countermeasures. Based on published data, the paper provides an outline of current views on anthracycline cardiotoxicity and discusses such aspects as molecular mechanisms of cardiotoxicity and its clinical manifestations as well as the new preventive strategies and diagnostic techniques used for the assessment of cardiovascular abnormalities. The widespread awareness of cancer treatment-related cardiotoxicity among the healthcare professionals may significantly improve the quality of life of the childhood cancer survivors.
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Affiliation(s)
- Elżbieta Sadurska
- Department of Pediatric Cardiology, Medical University of Lublin, Chodźki 2, 20-093, Lublin, Poland,
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