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Kinoshita T, Onda N, Ohno R, Ikeda T, Sugizaki Y, Ohara H, Nakagami T, Yuzawa H, Shimada H, Shimizu K, Ikeda T. Activation recovery interval as an electrocardiographic repolarization index to detect doxorubicin-induced cardiotoxicity. J Cardiol 2023; 82:473-480. [PMID: 37506822 DOI: 10.1016/j.jjcc.2023.07.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Revised: 05/12/2023] [Accepted: 07/21/2023] [Indexed: 07/30/2023]
Abstract
BACKGROUND It has been reported that early detection and treatment of cancer therapy- related cardiac dysfunction (CTRCD) improves its prognosis. The detailed relationships between electrocardiographic repolarization indices and decreased left ventricular function in CTRCD have not been elucidated. We closely assessed such relationships in patients with doxorubicin (DOX)-induced CTRCD. METHODS This retrospective, single-center, cohort study included 471 consecutive patients with malignant lymphoma who received chemotherapy including DOX. Of them, 17 patients with CTRCD and 68 patients without CTRCD who underwent 12‑lead electrocardiogram and an echocardiogram before and after chemotherapy were eventually analyzed. The fluctuations of the following electrocardiographic repolarization indices were evaluated in lead V5: QT, JT, T peak to T end interval (Tp-e), and activation recovery interval (ARI). These indices were corrected by heart rate with the Fridericia formula. RESULTS The median period from the end of chemotherapy to the diagnosis of the CTRCD group was 346 days (IQR 170-1283 days). After chemotherapy, the QT interval was significantly prolonged in both with and without CTRCD groups compared with that before chemotherapy (pre QTc vs. post QTc in CTRCD group, 386 ± 27 ms vs. 411 ± 37 ms, p = 0.03, pre QTc vs. post QTc in non-CTRCD group, 388 ± 24 ms vs. 395 ± 25 ms, p = 0.04, respectively). ARIc after chemotherapy was characteristically observed only in the CTRCD group (pre ARIc vs. post ARIc in CTRCD group, 258 ± 53 ms vs. 211 ± 28 ms, p = 0.03, pre ARIc vs. post ARIc in non-CTRCD group, 221 ± 19 ms vs. 225 ± 23 ms, NS, respectively) and had negative correlations with left ventricular ejection fraction (r = -0.56, p < 0.001). Using the receiver-operating characteristic curve, the relationship between ARIc and CTRCD morbidity was examined. The optimal cut-off point of ARIc prolongation between before and after chemotherapy was 18 ms (sensitivity 75 %, specificity 79 %, area under the curve 0.76). CONCLUSIONS ARIc prolongation may be useful in the early detection of developing late-onset chronic DOX-induced CTRCD and lead to early treatment for cardiac protection.
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Affiliation(s)
- Toshio Kinoshita
- Division of Cardiovascular Medicine, Department of Internal Medicine, Toho University Sakura Medical Center, Chiba, Japan.
| | - Naoki Onda
- Division of Hematology and Oncology, Department of Medicine, Toho University Omori Medical Center, Tokyo, Japan
| | - Ruiko Ohno
- Division of Cardiovascular Medicine, Department of Internal Medicine, Toho University Sakura Medical Center, Chiba, Japan
| | - Takushi Ikeda
- Division of Cardiovascular Medicine, Department of Internal Medicine, Toho University Sakura Medical Center, Chiba, Japan
| | - Yuta Sugizaki
- Division of Cardiovascular Medicine, Department of Internal Medicine, Toho University Sakura Medical Center, Chiba, Japan
| | - Hiroshi Ohara
- Department of Cardiovascular Medicine, Toho University Faculty of Medicine, Tokyo, Japan
| | - Takahiro Nakagami
- Division of Cardiovascular Medicine, Department of Internal Medicine, Toho University Sakura Medical Center, Chiba, Japan
| | - Hitomi Yuzawa
- Division of Cardiology, Mitsui Memorial Hospital, Tokyo, Japan
| | - Hideaki Shimada
- Department of Gastroenterological Surgery and Clinical Oncology, Toho University Graduate School of Medicine, Tokyo, Japan
| | - Kazuhiro Shimizu
- Division of Cardiovascular Medicine, Department of Internal Medicine, Toho University Sakura Medical Center, Chiba, Japan
| | - Takanori Ikeda
- Department of Cardiovascular Medicine, Toho University Faculty of Medicine, Tokyo, Japan
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Iodine-123 β-methyl-P-iodophenyl-pentadecanoic Acid (123I-BMIPP) Myocardial Scintigraphy for Breast Cancer Patients and Possible Early Signs of Cancer-Therapeutics-Related Cardiac Dysfunction (CTRCD). J Imaging 2022; 8:jimaging8110296. [DOI: 10.3390/jimaging8110296] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2022] [Revised: 10/23/2022] [Accepted: 10/27/2022] [Indexed: 11/16/2022] Open
Abstract
(1) Background: The mortality of breast cancer has decreased due to the advancement of cancer therapies. However, more patients are suffering from cancer-therapeutics-related cardiac dysfunction (CTRCD). Diagnostic and treatment guidelines for CTRCD have not been fully established yet. Ultrasound cardiogram (UCG) is the gold standard for diagnosis of CTRCD, but many breast cancer patients cannot undergo UCG due to the surgery wounds or anatomical reasons. The purpose of the study is to evaluate the usefulness of myocardial scintigraphy using Iodine-123 β-methyl-P-iodophenyl-pentadecanoic acid (123I-BMIPP) in comparison with UCG. (2) Methods: 100 breast cancer patients who received chemotherapy within 3 years underwent Thallium (201Tl) and 23I-BMIPP myocardial perfusion and metabolism scintigraphy. The images were visually evaluated by doctors and radiological technologists, and the grade of uptake reduction was scored by Heart Risk View-S software (Nihon Medi-Physics). The scores were deployed in a 17-segment model of the heart. The distribution of the scores were analyzed. (3) Results: Nine patients (9%) could not undergo UCG. No correlation was found between left ventricular ejection fraction (LVEF) and Heart Risk View-S scores of 201Tl myocardial perfusion scintigraphy nor those of BMIPP myocardial metabolism scintigraphy. In a 17-segment model of the heart, the scores of the middle rings were higher than for the basal ring. (4) Conclusions: Evaluation by UCG is not possible for some patients. Myocardial scintigraphy cannot serve as a perfect alternative to UCG. However, it will become the preferable second-choice screening test, as it could point out the early stage of CTRCD.
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Mohan UP, Tirupathi Pichiah PB, Kunjiappan S, Arunachalam S. A Hypothesis Concerning the role of PPAR family on Cardiac Energetics in Adriamycin-Induced Cardiomyopathy. J Appl Toxicol 2022; 42:1910-1920. [PMID: 35944906 DOI: 10.1002/jat.4374] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Revised: 08/06/2022] [Accepted: 08/06/2022] [Indexed: 11/10/2022]
Abstract
Adriamycin is an effective anti-neoplastic drug against a variety of cancer types. However, the drug causes adverse side-effects in a number of organ systems. Cardiomyopathy is one of the life-threatening side-effects of Adriamycin. In the current work, we have derived the possible involvement of PPAR family members in the development of Adriamycin-induced cardiomyopathy. Dysregulation of PPAR family by Adriamycin causes impairment in the transport and β-oxidation of fatty acids, the key substrate for ATP synthesis in heart. Evidences suggest that dysregulation of PPAR family results in alters the recruitment of glucose transporters. Furthermore, Hemeoxygenase-1 is a crucial enzyme regulating the iron homeostasis in the heart whose expression is regulated by PPAR family. Inverse relationship exists between the expression levels of PPARγ and hemeoxygenase-1. Adriamycin upregulates the expression of hemeoxygenase-1 which in turn disrupts the iron homeostasis in cardiomyocytes. Our molecular docking results show that Adriamycin has high affinity for iron binding sites of hemeoxygenase-1, thereby hindering formation of iron-sulfur complex. Lack of iron-sulfur complex impairs the electron transport chain. In addition, succinate dehydrogenase subunit A is downregulated by Adriamycin. The lack of this subunit uncouples Krebs cycle from ETC. Further lack of this subunit causes increases the concentration of succinate which further alters the mitochondrial membrane potential. Overall, in the present work we hypothesize that alteration in the expression of PPAR family members is one of the major causes of metabolic chaos and oxidative stress caused by Adriamycin during the development of cardiomyopathy.
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Affiliation(s)
- Uma Priya Mohan
- Centre for Cardiovascular and Adverse Drug Reactions, Department of Biotechnology, School of Bio and Chemical Engineering, Kalasalingam Academy of Research and Education, Krishnankoil, Tamilnadu, India
| | | | - Selvaraj Kunjiappan
- Department of Biotechnology, School of Bio and Chemical Engineering, Kalasalingam Academy of Research and Education, Krishnankoil, Tamilnadu, India
| | - Sankarganesh Arunachalam
- Centre for Cardiovascular and Adverse Drug Reactions, Department of Biotechnology, School of Bio and Chemical Engineering, Kalasalingam Academy of Research and Education, Krishnankoil, Tamilnadu, India
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Harada Y, Shimada K, Kubota Y, Yamashita M. Effectiveness of Iodine-123 β-methyl-P-iodophenyl-pentadecanoic acid (BMIPP) Myocardial Scintigraphy for Cancer Therapeutics-Related Cardiac Dysfunction (CTRCD) in Breast Cancer Patients. Cureus 2022; 14:e25524. [PMID: 35800804 PMCID: PMC9245443 DOI: 10.7759/cureus.25524] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/31/2022] [Indexed: 11/05/2022] Open
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Cadour F, Thuny F, Sourdon J. New Insights in Early Detection of Anticancer Drug-Related Cardiotoxicity Using Perfusion and Metabolic Imaging. Front Cardiovasc Med 2022; 9:813883. [PMID: 35198613 PMCID: PMC8858802 DOI: 10.3389/fcvm.2022.813883] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Accepted: 01/06/2022] [Indexed: 12/16/2022] Open
Abstract
Cardio-oncology requires a good knowledge of the cardiotoxicity of anticancer drugs, their mechanisms, and their diagnosis for better management. Anthracyclines, anti-vascular endothelial growth factor (VEGF), alkylating agents, antimetabolites, anti-human epidermal growth factor receptor (HER), and receptor tyrosine kinase inhibitors (RTKi) are therapeutics whose cardiotoxicity involves several mechanisms at the cellular and subcellular levels. Current guidelines for anticancer drugs cardiotoxicity are essentially based on monitoring left ventricle ejection fraction (LVEF). However, knowledge of microvascular and metabolic dysfunction allows for better imaging assessment before overt LVEF impairment. Early detection of anticancer drug-related cardiotoxicity would therefore advance the prevention and patient care. In this review, we provide a comprehensive overview of the cardiotoxic effects of anticancer drugs and describe myocardial perfusion, metabolic, and mitochondrial function imaging approaches to detect them before over LVEF impairment.
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Affiliation(s)
- Farah Cadour
- Aix-Marseille Université, CNRS, CRMBM, Marseille, France
- APHM, Hôpital Universitaire Timone, CEMEREM, Marseille, France
| | - Franck Thuny
- Aix-Marseille University, University Mediterranean Center of Cardio-Oncology, Unit of Heart Failure and Valvular Heart Diseases, Department of Cardiology, North Hospital, Assistance Publique - Hôpitaux de Marseille, Centre for CardioVascular and Nutrition Research (C2VN), Inserm 1263, Inrae 1260, Marseille, France
| | - Joevin Sourdon
- Aix-Marseille Université, CNRS, CRMBM, Marseille, France
- APHM, Hôpital Universitaire Timone, CEMEREM, Marseille, France
- *Correspondence: Joevin Sourdon
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Feher A, Boutagy NE, Stendahl JC, Hawley C, Guerrera N, Booth CJ, Romito E, Wilson S, Liu C, Sinusas AJ. Computed Tomographic Angiography Assessment of Epicardial Coronary Vasoreactivity for Early Detection of Doxorubicin-Induced Cardiotoxicity. JACC: CARDIOONCOLOGY 2020; 2:207-219. [PMID: 34396230 PMCID: PMC8352292 DOI: 10.1016/j.jaccao.2020.05.007] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/15/2020] [Revised: 05/08/2020] [Accepted: 05/11/2020] [Indexed: 11/27/2022]
Abstract
Background The vascular endothelium is a novel target for the detection, management, and prevention of doxorubicin (DOX)-induced cardiotoxicity. Objectives The study aimed to: 1) develop a methodology by computed tomography angiography (CTA) to evaluate stress-induced changes in epicardial coronary diameter; and 2) apply this to a chronic canine model of DOX-induced cardiotoxicity to assess vascular toxicity. Methods To develop and validate quantitative methods, sequential retrospectively gated coronary CTAs were performed in 16 canines. Coronary diameters were measured at prespecified distances during rest, adenosine (ADE) (280 μg/kg/min), rest 30 min post-ADE, and dobutamine (DOB) (5 μg/kg/min). A subgroup of 8 canines received weekly intravenous DOX (1 mg/kg) for 12 to 15 weeks, followed by rest-stress CTA at cumulative doses of ∼4-mg/kg (3 to 5 mg/kg), ∼8-mg/kg (7 to 9 mg/kg), and ∼12-mg/kg (12 to 15 mg/kg) of DOX. Echocardiograms were performed at these timepoints to assess left ventricular ejection fraction and global longitudinal strain. Results Under normal conditions, epicardial coronary arteries reproducibly dilated in response to ADE (left anterior descending coronary artery [LAD]: 12 ± 2%, left circumflex coronary artery [LCx]: 13 ± 2%, right coronary artery [RCA]: 14 ± 2%) and DOB (LAD: 17 ± 3%, LCx: 18 ± 2%, RCA: 15 ± 3%). With DOX, ADE vasodilator responses were impaired after ∼4-mg/kg (LAD: –3 ± 1%, LCx: 0 ± 2%, RCA: –5 ± 2%) and ∼8-mg/kg (LAD: –3 ± 1%, LCx: 0 ± 1%, RCA: –2 ± 2%). The DOB dilation response was preserved at ∼4-mg/kg of DOX (LAD: 18 ± 4%, LCx: 11 ± 3%, RCA: 11 ± 2%) but tended to decrease at ∼8-mg/kg of DOX (LAD: 4 ± 2%, LCx: 8 ± 3%, RCA: 3 ± 2%). A significant left ventricular ejection fraction reduction was observed only at 12 to 15 mg/kg DOX (baseline: 63 ± 2%, 12-mg/kg: 45 ± 3%). Global longitudinal strain was abnormal at ∼4-mg/kg of DOX (p = 0.011). Conclusions CTA can reliably assess epicardial coronary diameter in response to pharmacological stressors, providing a noninvasive functional index of coronary vasoreactivity. Impaired epicardial vasodilation occurs early in DOX-induced cardiotoxicity.
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Key Words
- ADE, adenosine
- CAD, coronary artery disease
- CT angiography
- CTA, computed tomography angiography
- DOB, dobutamine
- DOX, doxorubicin
- GLS, global longitudinal strain
- HR, heart rate
- LAD, left anterior descending coronary artery
- LCx, left circumflex coronary artery
- LV, left ventricular
- LVEF, left ventricular ejection fraction
- MAP, mean arterial pressure
- RCA, right coronary artery
- TTE, transthoracic echocardiography
- anthracycline
- cardiomyopathy
- diagnosis
- imaging
- preclinical study
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Affiliation(s)
- Attila Feher
- Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA
- Yale Translational Research Imaging Center, Yale University, New Haven, Connecticut, USA
| | - Nabil E. Boutagy
- Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA
- Yale Translational Research Imaging Center, Yale University, New Haven, Connecticut, USA
| | - John C. Stendahl
- Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA
- Yale Translational Research Imaging Center, Yale University, New Haven, Connecticut, USA
| | - Christi Hawley
- Yale Translational Research Imaging Center, Yale University, New Haven, Connecticut, USA
| | - Nicole Guerrera
- Yale Translational Research Imaging Center, Yale University, New Haven, Connecticut, USA
| | - Carmen J. Booth
- Department of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut, USA
| | - Eva Romito
- Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA
- Yale Translational Research Imaging Center, Yale University, New Haven, Connecticut, USA
| | - Steven Wilson
- Department of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut, USA
| | - Chi Liu
- Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, Connecticut, USA
| | - Albert J. Sinusas
- Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA
- Yale Translational Research Imaging Center, Yale University, New Haven, Connecticut, USA
- Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, Connecticut, USA
- Department of Biomedical Engineering, Yale University School of Medicine, New Haven, Connecticut, USA
- Address for correspondence: Dr. Albert J. Sinusas, Section of Cardiovascular Medicine, Yale University School of Medicine, P.O. Box 208017, Dana 3, New Haven, Connecticut 06520-8017. @attilafehermd
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Tong D, Zaha VG. Metabolic Imaging in Cardio-oncology. J Cardiovasc Transl Res 2019; 13:357-366. [PMID: 31696405 DOI: 10.1007/s12265-019-09927-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2019] [Accepted: 10/14/2019] [Indexed: 12/13/2022]
Abstract
Tremendous progress in cancer detection and therapy has improved survival. However, cardiovascular complications are a major source of morbidity in cancer survivors. Cardiotoxicity is currently defined by structural myocardial changes and cardiac injury biomarkers. In many instances, such changes are late and irreversible. Therefore, diagnostic modalities that can identify early alterations in potentially reversible biochemical and molecular signaling processes are of interest. This review is focused on emerging translational metabolic imaging modalities. We present in context relevant mitochondrial biology aspects that ground the development and application of these technologies for detection of cancer therapy-related cardiac dysfunction (CTRCD). The application of these modalities may improve the assessment of cardiovascular risk when anticancer treatments with a defined cardiometabolic toxic mechanism are to be used. Also, they may serve as screening tools for cardiotoxicity when novel lines of cancer therapies are applied.
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Affiliation(s)
- Dan Tong
- Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, USA
| | - Vlad G Zaha
- Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, USA. .,Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, USA. .,Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, USA.
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Boutagy NE, Wu J, Cai Z, Zhang W, Booth CJ, Kyriakides TC, Pfau D, Mulnix T, Liu Z, Miller EJ, Young LH, Carson RE, Huang Y, Liu C, Sinusas AJ. In Vivo Reactive Oxygen Species Detection With a Novel Positron Emission Tomography Tracer, 18F-DHMT, Allows for Early Detection of Anthracycline-Induced Cardiotoxicity in Rodents. JACC Basic Transl Sci 2018; 3:378-390. [PMID: 30062224 PMCID: PMC6058999 DOI: 10.1016/j.jacbts.2018.02.003] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2017] [Revised: 02/06/2018] [Accepted: 02/09/2018] [Indexed: 02/05/2023]
Abstract
LVEF is used to detect doxorubicin-induced cardiotoxicity in patients, but this index is variable and has limited ability to detect early cardiotoxicity. Doxorubicin induces cardiotoxicity largely through the excessive production of ROS. We hypothesized that 18F-DHMT, a PET tracer that detects superoxide production, would provide an early index of cardiotoxicity in rodents. 18F-DHMT PET imaging was able to detect an elevation in cardiac superoxide production before a fall in LVEF. The early elevation in myocardial superoxide production was associated with only mild myocardial toxicity and occurred before cellular apoptosis or significant activation of MMPs; enzymes associated with myocardial remodeling. A drop in LVEF was associated with a significant increase in MMP activation, cellular apoptosis, and significant myocardial toxicity. Reactive oxygen species (ROS) are involved in doxorubicin-induced cardiotoxicity. The authors investigated the efficacy of 18F-DHMT, a marker of ROS, for early detection of doxorubicin-induced cardiotoxicity in rats. Echocardiography was performed at baseline and 4, 6, and 8 weeks post-doxorubicin initiation, whereas in vivo superoxide production was measured at 4 and 6 weeks with 18F-DHMT positron emission tomography. Left ventricular ejection fraction (LVEF) was not significantly decreased until 6 weeks post-doxorubicin treatment, whereas myocardial superoxide production was significantly elevated at 4 weeks. 18F-DHMT imaging detected an elevation in cardiac superoxide production before a fall in LVEF in rodents and may allow for early cardiotoxicity detection in cancer patients.
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Key Words
- 2D, 2-dimensional
- CT, computed tomography
- DOX, doxorubicin HCl
- H&E, hematoxylin and eosin
- LV, left ventricle/ventricular
- LVEF, left ventricular ejection fraction
- MMP, matrix metalloproteinase
- MT, Masson’s trichrome
- PET, positron emission tomography
- ROS, reactive oxygen species
- SUV, standardized uptake value
- TUNEL, terminal deoxynucleotidyl transferase-mediated nick-end labeling
- VOI, volume of interest
- cardiotoxicity
- doxorubicin
- positron emission tomography
- reactive oxygen species
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Affiliation(s)
- Nabil E. Boutagy
- Section of Cardiovascular Medicine, Department of Medicine, Yale Translational Research Imaging Center, Yale School of Medicine, New Haven, Connecticut
| | - Jing Wu
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut
| | - Zhengxi Cai
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut
| | - Wenjie Zhang
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut
- Department of Nuclear Medicine, West China Hospital of Sichuan University, Chengdu, China
| | - Carmen J. Booth
- Section of Comparative Medicine, Yale School of Medicine, New Haven, Connecticut
| | - Tassos C. Kyriakides
- Yale School of Public Health (Biostatistics), Yale School of Medicine, New Haven, Connecticut
| | - Daniel Pfau
- Section of Cardiovascular Medicine, Department of Medicine, Yale Translational Research Imaging Center, Yale School of Medicine, New Haven, Connecticut
| | - Tim Mulnix
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut
| | - Zhao Liu
- Section of Cardiovascular Medicine, Department of Medicine, Yale Translational Research Imaging Center, Yale School of Medicine, New Haven, Connecticut
| | - Edward J. Miller
- Section of Cardiovascular Medicine, Department of Medicine, Yale Translational Research Imaging Center, Yale School of Medicine, New Haven, Connecticut
| | - Lawrence H. Young
- Section of Cardiovascular Medicine, Department of Medicine, Yale Translational Research Imaging Center, Yale School of Medicine, New Haven, Connecticut
| | - Richard E. Carson
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut
| | - Yiyun Huang
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut
| | - Chi Liu
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut
| | - Albert J. Sinusas
- Section of Cardiovascular Medicine, Department of Medicine, Yale Translational Research Imaging Center, Yale School of Medicine, New Haven, Connecticut
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut
- Address for correspondence: Dr. Albert J. Sinusas, Section of Cardiovascular Medicine, Yale University School of Medicine, P.O. Box 208017, Dana 3, New Haven, Connecticut 06520-8017.
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Clinical Application of 2D Speckle Tracking Strain for Assessing Cardio-Toxicity in Oncology. J Funct Morphol Kinesiol 2016. [DOI: 10.3390/jfmk1040343] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
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Pepe A, Pizzino F, Gargiulo P, Perrone-Filardi P, Cadeddu C, Mele D, Monte I, Novo G, Zito C, Di Bella G. Cardiovascular imaging in the diagnosis and monitoring of cardiotoxicity: cardiovascular magnetic resonance and nuclear cardiology. J Cardiovasc Med (Hagerstown) 2016; 17 Suppl 1:e45-e54. [PMID: 27183525 DOI: 10.2459/jcm.0000000000000380] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
Chemotherapy-induced cardiotoxicity (CTX) is a determining factor for the quality of life and mortality of patients administered potentially cardiotoxic drugs and in long-term cancer survivors. Therefore, prevention and early detection of CTX are highly desirable, as is the exploration of alternative therapeutic strategies and/or the proposal of potentially cardioprotective treatments. In recent years, cardiovascular imaging has acquired a pivotal role in this setting. Although echocardiography remains the diagnostic method most used to monitor cancer patients, the need for more reliable, reproducible and accurate detection of early chemotherapy-induced CTX has encouraged the introduction of second-line advanced imaging modalities, such as cardiac magnetic resonance (CMR) and nuclear techniques, into the clinical setting. This review of the Working Group on Drug Cardiotoxicity and Cardioprotection of the Italian Society of Cardiology aims to afford an overview of the most important findings from the literature about the role of CMR and nuclear techniques in the management of chemotherapy-treated patients, describe conventional and new parameters for detecting CTX from both diagnostic and prognostic perspectives and provide integrated insight into the role of CMR and nuclear techniques compared with other imaging tools and versus the positions of the most important international societies.
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Affiliation(s)
- Alessia Pepe
- aU.O.C. Magnetic Resonance Imaging, Fondazione Toscana G. Monasterio C.N.R., Pisa bDepartment of Clinical and Experimental Medicine. Section of Cardiology A.O.U. Policlinico 'G. Martino' University of Messina, Messina cSDN, Institute of Diagnostic and Nuclear Development dDepartment of Advanced Biomedical Sciences, 'Federico II' University, Naples eDepartment of Medical Sciences 'Mario Aresu', University of Cagliari, Cagliari fCardiology Unit, University Hospital of Ferrara, Ferrara gDepartment of General Surgery and Medical-Surgery Specialities, University of Catania, Catania hChair and Division of Cardiology, University of Palermo, Palermo, Italy
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Govender J, Loos B, Marais E, Engelbrecht AM. Mitochondrial catastrophe during doxorubicin-induced cardiotoxicity: a review of the protective role of melatonin. J Pineal Res 2014; 57:367-80. [PMID: 25230823 DOI: 10.1111/jpi.12176] [Citation(s) in RCA: 141] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2014] [Accepted: 09/12/2014] [Indexed: 12/18/2022]
Abstract
Anthracyclines, such as doxorubicin, are among the most valuable treatments for various cancers, but their clinical use is limited due to detrimental side effects such as cardiotoxicity. Doxorubicin-induced cardiotoxicity is emerging as a critical issue among cancer survivors and is an area of much significance to the field of cardio-oncology. Abnormalities in mitochondrial functions such as defects in the respiratory chain, decreased adenosine triphosphate production, mitochondrial DNA damage, modulation of mitochondrial sirtuin activity and free radical formation have all been suggested as the primary causative factors in the pathogenesis of doxorubicin-induced cardiotoxicity. Melatonin is a potent antioxidant, is nontoxic, and has been shown to influence mitochondrial homeostasis and function. Although a number of studies support the mitochondrial protective role of melatonin, the exact mechanisms by which melatonin confers mitochondrial protection in the context of doxorubicin-induced cardiotoxicity remain to be elucidated. This review focuses on the role of melatonin on doxorubicin-induced bioenergetic failure, free radical generation, and cell death. A further aim is to highlight other mitochondrial parameters such as mitophagy, autophagy, mitochondrial fission and fusion, and mitochondrial sirtuin activity, which lack evidence to support the role of melatonin in the context of cardiotoxicity.
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Affiliation(s)
- Jenelle Govender
- Department of Physiological Sciences, Stellenbosch University, Stellenbosch, South Africa
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Kongbundansuk S, Hundley WG. Noninvasive imaging of cardiovascular injury related to the treatment of cancer. JACC Cardiovasc Imaging 2014; 7:824-38. [PMID: 25124015 PMCID: PMC4183055 DOI: 10.1016/j.jcmg.2014.06.007] [Citation(s) in RCA: 51] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2014] [Revised: 06/20/2014] [Accepted: 06/26/2014] [Indexed: 01/03/2023]
Abstract
The introduction of multiple treatments for cancer, including chemotherapeutic agents and radiation therapy, has significantly reduced cancer-related morbidity and mortality. However, these therapies can promote a variety of toxicities, among the most severe being the ones involving the cardiovascular system. Currently, for many surviving cancer patients, cardiovascular (CV) events represent the primary cause of morbidity and mortality. Recent data suggest that CV injury occurs early during cancer treatment, creating a substrate for subsequent cardiovascular events. Researchers have investigated the utility of noninvasive imaging strategies to detect the presence of CV injury during and after completion of cancer treatment because it starts early during cancer therapy, often preceding the development of chemotherapy or cancer therapeutics related cardiac dysfunction. In this State-of-the-Art Paper, we review the utility of current clinical and investigative CV noninvasive modalities for the identification and characterization of cancer treatment-related CV toxicity.
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Affiliation(s)
- Suwat Kongbundansuk
- Department of Internal Medicine (Section on Cardiology), Wake Forest School of Medicine, Winston-Salem, North Carolina
| | - W Gregory Hundley
- Department of Internal Medicine (Section on Cardiology), Wake Forest School of Medicine, Winston-Salem, North Carolina; Department of Radiology, Wake Forest School of Medicine, Winston-Salem, North Carolina.
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D’Amore C, Gargiulo P, Paolillo S, Pellegrino AM, Formisano T, Mariniello A, Della Ratta G, Iardino E, D’Amato M, La Mura L, Fabiani I, Fusco F, Perrone Filardi P. Nuclear imaging in detection and monitoring of cardiotoxicity. World J Radiol 2014; 6:486-492. [PMID: 25071889 PMCID: PMC4109100 DOI: 10.4329/wjr.v6.i7.486] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2014] [Revised: 04/21/2014] [Accepted: 05/29/2014] [Indexed: 02/06/2023] Open
Abstract
Cardiotoxicity as a result of cancer treatment is a novel and serious public health issue that has a significant impact on a cancer patient’s management and outcome. The coexistence of cancer and cardiac disease in the same patient is more common because of aging population and improvements in the efficacy of antitumor agents. Left ventricular dysfunction is the most typical manifestation and can lead to heart failure. Left ventricular ejection fraction measurement by echocardiography and multigated radionuclide angiography is the most common diagnostic approach to detect cardiac damage, but it identifies a late manifestation of myocardial injury. Early non-invasive imaging techniques are needed for the diagnosis and monitoring of cardiotoxic effects. Although echocardiography and cardiac magnetic resonance are the most commonly used imaging techniques for cardiotoxicity assessment, greater attention is focused on new nuclear cardiologic techniques, which can identify high-risk patients in the early stage and visualize the pathophysiologic process at the tissue level before clinical manifestation. The aim of this review is to summarize the role of nuclear imaging techniques in the non-invasive detection of myocardial damage related to antineoplastic therapy at the reversible stage, focusing on the current role and future perspectives of nuclear imaging techniques and molecular radiotracers in detection and monitoring of cardiotoxicity.
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Ong DS, Scherrer-Crosbie M, Coelho-Filho O, Francis SA, Neilan TG. Imaging methods for detection of chemotherapy-associated cardiotoxicity and dysfunction. Expert Rev Cardiovasc Ther 2014; 12:487-97. [DOI: 10.1586/14779072.2014.893824] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
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Abstract
Despite continuous improvements in management of patients with cancer, cardiac side-effects still account for a substantial limitation of chemotherapy. Evaluation of cardiac toxicity in patients includes consideration of biomarkers such as cardiac troponins and B-type natriuretic peptides, together with non-invasive imaging in the form of 2D-, 3D-, or strain-echocardiography, multiple gated radionuclide angiography, quantitative gated blood-pool SPECT, (123)I-metaiodobenzylguanidine scintigraphy, or cardiac magnetic resonance imaging. These approaches differ from each other with regards to availability, accuracy, sensitivity to detect early stages of cardiac injury, individual reliability, ease of use in a longitudinal follow-up perspective, and to related cost-effectiveness. Improving prevention of these cardiac side-effects depends on several, currently unresolved issues. Early detection and quantification of cardiac damage is required to adapt chemotherapy in progress for optimal management of patients. Whether increased availability of myocardial strain imaging and repeat blood biomarkers determinations will reliably and consistently achieve these goals remain to be confirmed. Also, protective approaches to reduce cardiac toxicity of anticancer drugs should be reconsidered according to the recently restricted approval for use of dexrazoxane. Anthracycline-based regimens, encapsulated anthracyclines and non-anthracycline regimens should be revisited with regards to antitumour efficacy and cardiac toxicity. Cardiovascular drugs that proved effective in prevention of anthracycline-induced cardiac toxicity in experimental models should be investigated in clinical trials. Finally, the efficacy of cardiovascular drugs that have already been tested in clinical settings should be confirmed and compared with each other in patients in increased numbers.
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Affiliation(s)
- Jean-Jacques Monsuez
- Cardiologie, Hôpital René-Muret, Hôpitaux Universitaires Paris-Seine-Saint-Denis, France.
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de Geus-Oei LF, Mavinkurve-Groothuis AMC, Bellersen L, Gotthardt M, Oyen WJG, Kapusta L, van Laarhoven HWM. Scintigraphic techniques for early detection of cancer treatment-induced cardiotoxicity. J Nucl Med 2011; 41:170-81. [PMID: 21421717 DOI: 10.2967/jnumed.110.082784] [Citation(s) in RCA: 79] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Abstract
New antitumor agents have resulted in significant survival benefits for cancer patients. However, several agents may have serious cardiovascular side effects. Left ventricular ejection fraction measurement by (99m)Tc multigated radionuclide angiography is regarded as the gold standard to measure cardiotoxicity in adult patients. It identifies left ventricular dysfunction with high reproducibility and low interobserver variability. A decrease in left ventricular ejection fraction, however, is a relatively late manifestation of myocardial damage. Nuclear cardiologic techniques that visualize pathophysiologic processes at the tissue level could detect myocardial injury at an earlier stage. These techniques may give the opportunity for timely intervention to prevent further damage and could provide insights into the mechanisms and pathophysiology of cardiotoxicity caused by anticancer agents. This review provides an overview of past, current, and promising newly developed radiopharmaceuticals and describes the role and recent advances of scintigraphic techniques to measure cardiotoxicity. Both first-order functional imaging techniques (visualizing mechanical [pump] function), such as (99m)Tc multigated radionuclide angiography and (99m)Tc gated blood-pool SPECT, and third-order functional imaging techniques (visualizing pathophysiologic and neurophysiologic processes at the tissue level) are discussed. Third-order functional imaging techniques comprise (123)I-metaiodobenzylguanidine scintigraphy, which images the efferent sympathetic nervous innervations; sympathetic neuronal PET, with its wide range of tracers; (111)In-antimyosin, which is a specific marker for myocardial cell injury and necrosis; (99m)Tc-annexin V scintigraphy, which visualizes apoptosis and cell death; fatty-acid-use scintigraphy, which visualizes the storage of free fatty acids in the lipid pool of the cytosol (which can be impaired by cardiotoxic agents); and (111)In-trastuzumab imaging, to study trastuzumab targeting to the myocardium. To define the prognostic importance and clinical value of each of these functional imaging techniques, prospective clinical trials are warranted.
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Affiliation(s)
- Lioe-Fee de Geus-Oei
- Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
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Okizaki A, Shuke N, Sato J, Sasaki T, Hasebe N, Kikuchi K, Aburano T. A compartment model analysis for investigation of myocardial fatty acid metabolism in patients with hypertrophic cardiomyopathy. Nucl Med Commun 2007; 28:726-35. [PMID: 17667752 DOI: 10.1097/mnm.0b013e32828da1c7] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE The purpose of this study was to investigate the myocardial fatty acid metabolism in patients with hypertrophic cardiomyopathy (HCM) from dynamic SPECT through a compartment model analysis. METHODS Twenty-four normal controls, seven patients with left ventricular hypertrophy (LVH) due to essential hypertension (eHT), and 30 patients with HCM were studied. 123I-BMIPP and 99mTc-tetrofosmin SPECT were performed. All the myocardium was divided into 13 segments, and a total of 390 segments of HCM were categorized into early, moderately and severely advanced HCM segments, based on these SPECT imaging. By using the myocardial and blood pool time-activity curves, BMIPP pharmacokinetics were analysed through a two-compartment model. We defined k1 and k2 as influx and outflux rate constants between blood and myocardial reversible component, and k3 as the specific uptake rate constant between myocardial reversible and irreversible compartments. RESULTS The averages of k3 in HCM were higher than in normal. In contrast, the averages of k1/k2 in HCM were lower than in normal, and gradually decreased with progression of HCM. There are no significant differences in these indexes between normal controls and patients with LVH due to eHT. CONCLUSION k3 might be a sensitive predictor for early detection of HCM, and k1/k2 could be a useful index to evaluate its progression. A mathematical compartment model analysis with a BMIPP SPECT study might be useful not only for identification of HCM in very early stage, but also for evaluation of the progression of HCM.
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Tokarska-Schlattner M, Zaugg M, Zuppinger C, Wallimann T, Schlattner U. New insights into doxorubicin-induced cardiotoxicity: the critical role of cellular energetics. J Mol Cell Cardiol 2006; 41:389-405. [PMID: 16879835 DOI: 10.1016/j.yjmcc.2006.06.009] [Citation(s) in RCA: 241] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2006] [Revised: 06/08/2006] [Accepted: 06/14/2006] [Indexed: 12/21/2022]
Abstract
Cardiotoxic side-effects represent a serious complication of anticancer therapy with anthracyclines, in particular with doxorubicin (DXR) being the leading drug of the group. Different hypotheses, accentuating various mechanisms and/or targets, have been proposed to explain DXR-induced cardiotoxicity. This review focuses on the myocardial energetic network as a target of DXR toxic action in heart and highlights the recent advances in understanding its role in development of the DXR related cardiac dysfunction. We present a survey of DXR-induced defects in different steps of cardiac energy metabolism, including reduction of oxidative capacity of mitochondria, changes in the profile of energy substrate utilization, disturbance of energy transfer between sites of energy production and consumption, as well as defects in energy signaling. Considering the wide spectrum and diversity of the changes reported, we attempt to integrate these facts into a common framework and to discuss important functional and temporal relationships between DXR-induced events and the possible underlying molecular mechanisms.
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Verberne HJ, Feenstra C, de Jong WM, Somsen GA, van Eck-Smit BLF, Busemann Sokole E. Influence of collimator choice and simulated clinical conditions on 123I-MIBG heart/mediastinum ratios: a phantom study. Eur J Nucl Med Mol Imaging 2005; 32:1100-7. [PMID: 15902438 DOI: 10.1007/s00259-005-1810-3] [Citation(s) in RCA: 73] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2004] [Accepted: 03/03/2005] [Indexed: 11/26/2022]
Abstract
PURPOSE (123)I presents imaging problems owing to high-energy photon emission. We investigated the influence of collimators on (123)I-MIBG heart/mediastinum ratios (H/M ratios). Secondly, we assessed the influence on H/M ratios of different activity concentrations, simulating clinical conditions. Thirdly, the value of scatter correction was assessed. METHODS The AGATE cardiac phantom was filled with (123)I in three sequential conditions: A, heart and mediastinal activity; B, adding lung activity; and C, adding liver activity (protocol I). In protocol II, myocardium and liver were filled with different activities ranging from low to high. For each condition, static anterior planar and single-photon emission computed tomography studies were acquired on a Siemens e.cam (SI) and a General Electric Millennium VG (GE) system, using low-energy high-resolution and medium-energy (ME) collimators for protocol I and only ME collimators for protocol II . For the SI camera, a triple energy window (TEW) scatter correction was applied. RESULTS Planar H/M ratios were influenced by scatter and septal penetration from increasing amounts of liver activity. These effects were less pronounced for ME collimators. Although the TEW scatter correction increased ratios overall, TEW correction did not improve the relative differences between the ratios. TEW correction therefore does not add any benefit to obtain an accurate reflection of myocardial activity concentrations. CONCLUSION For straightforward implementation of semi-quantitative (123)I-MIBG myocardial studies, we recommend the use of ME collimators without scatter correction.
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Affiliation(s)
- Hein J Verberne
- Department of Nuclear Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
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Inoue Y, Shirouzu I, Machida T, Yoshizawa Y, Akita F, Minami M, Ohtomo K. Collimator choice in cardiac SPECT with I-123-labeled tracers. J Nucl Cardiol 2004; 11:433-9. [PMID: 15295412 DOI: 10.1016/j.nuclcard.2004.04.009] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
BACKGROUND Septal penetration of high-energy photons may degrade the quality of single photon emission computed tomography (SPECT) of the heart with iodine 123-labeled tracers. We investigated the impact of collimator choice on cardiac SPECT with I-123. METHODS AND RESULTS SPECT of a thoracic phantom containing I-123 solution was performed with a low-energy high-resolution (LEHR) collimator, special LEHR (SLEHR) collimator, and medium-energy (ME) collimator, and the cavity-to-myocardium contrast, wall thickness, and defect contrast were compared among the collimators. For all indices, use of the SLEHR collimator yielded the best results. Comparison between the LEHR and ME collimators revealed that the cavity-to-myocardium contrast and contrast for large defects were better with the ME collimator, whereas wall thickness and contrast for small defects were similar. Scatter correction by the triple-energy window method improved the indices examined; however, the superiority of the SLEHR collimator was still observed after correction. CONCLUSIONS Collimator choice substantially influences the quality of cardiac SPECT with I-123-labeled agents, and an appropriate collimator needs to be selected in consideration of septal penetration and spatial resolution.
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Affiliation(s)
- Yusuke Inoue
- Department of Radiology, Institute of Medical Science, University of Tokyo, Japan.
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Saito K, Takeda K, Imanaka-Yoshida K, Imai H, Sekine T, Kamikura Y. Assessment of fatty acid metabolism in taxan-induced myocardial damage with iodine-123 BMIPP SPECT: comparative study with myocardial perfusion, left ventricular function, and histopathological findings. Ann Nucl Med 2004; 17:481-8. [PMID: 14575384 DOI: 10.1007/bf03006439] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
UNLABELLED We investigated myocardial fatty acid metabolism in taxan-induced myocardial damage in patients with advanced lung cancer. PATIENTS AND METHODS Twenty-five patients with non-small-cell lung cancer were treated with taxan combined with carboplatin intravenously for three cycles. Myocardial SPECT imaging using 99mTc-methoxyisobutyl isonitrile (MIBI) and 123I-15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) was performed successively before and after chemotherapy. Regional uptake scores of BMIPP and MIBI were visually assessed and total uptake scores and the number of abnormal segments were calculated. Left ventricular ejection fraction (LVEF) was obtained by first-pass radionuclide angiocardiography using MIBI. Postmortem pathological examination was performed in 5 patients. RESULTS Total BMIPP uptake scores after chemotherapy were significantly lower than those before chemotherapy (23.4 +/- 3.4 vs. 26.6 +/- 0.8; p < 0.001). Mean LVEF showed a significant decrease after chemotherapy. Of the 25 patients, 4 exhibited a decrease in LVEF of more than 10%, 1 had a decrease in LVEF to below 50%, and 1 developed congestive heart failure. These 6 patients had significant decreases in total BMIPP uptake scores and increases in the number of abnormal segments as compared with the other 19 patients. Histopathological examination of myocardial tissue showed interstitial edema and disarrayed myocardial cells. CONCLUSION Taxan impairs myocardial fatty acid metabolism. 123I-BMIPP myocardial SPECT is useful for evaluating the cardiotoxicity induced by taxan.
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Affiliation(s)
- Kimimasa Saito
- Department of Pulmonology, Yamada Red Cross Hospital, Mie, Japan.
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Inoue Y, Suzuki A, Shirouzu I, Machida T, Yoshizawa Y, Akita F, Ohnishi S, Yoshikawa K, Ohtomo K. Effect of collimator choice on quantitative assessment of cardiac iodine 123 MIBG uptake. J Nucl Cardiol 2004; 10:623-32. [PMID: 14668774 DOI: 10.1016/s1071-3581(03)00652-4] [Citation(s) in RCA: 51] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
BACKGROUND Quantitative accuracy in iodine 123 studies may be impaired by septal penetration. We evaluated the effect of collimator choice on estimation of the heart-to-mediastinum (H/M) ratio in cardiac I-123 metaiodobenzylguanidine (MIBG) imaging. METHODS AND RESULTS A low-energy high-resolution (LEHR) collimator, special LEHR (SLEHR) collimator, and medium-energy (ME) collimator were used. In experiments in which a phantom of simple geometry was used, the use of the LEHR collimator provided the lowest contrast accuracy, suggesting the effect of septal penetration. Thoracic phantom studies demonstrated contamination of heart and mediastinum counts by lung and liver activities, which was greatest with the LEHR collimator and least with the ME collimator. In 8 patients anterior chest views were acquired successively with the three collimators after I-123 MIBG injection. H/M ratios were significantly higher with the SLEHR collimator than with the LEHR collimator and were still higher with the ME collimator. The difference in H/M ratios between the LEHR and ME collimators showed a high positive correlation with the lung-to-mediastinum ratio. CONCLUSIONS Collimator choice substantially influences estimation of the H/M ratios in cardiac I-123 MIBG imaging. The use of an ME collimator provides high quantitative accuracy and may enhance reliability in the evaluation of cardiac sympathetic nerve function.
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Affiliation(s)
- Yusuke Inoue
- Department of Radiology, Institute of Medical Sciences, University of Tokyo, Japan.
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Ohkura K, Lee JD, Shimizu H, Nakano A, Uzui H, Horikoshi M, Fujibayashi Y, Yonekura Y, Ueda T. Mitochondrials complex I activity is reduced in latent adriamycin-induced cardiomyopathy of rat. Mol Cell Biochem 2003; 248:203-8. [PMID: 12870675 DOI: 10.1023/a:1024161024231] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
We previously reported on the use of enzymatic analysis to impair fatty acid metabolism followed by reduced myocardial energy content, leading to severe heart failure in adriamycin (ADR)-treated rats. The aim of this study is to investigate whether impaired myocardial energy metabolism can also be detected by other methods; i.e. measuring mitochondrial complex I activity and myocardial 125I-15-(p-iodophenyl)-3-(R,S)- methylpentadecanoic acid (BMIPP) accumulation in ADR-treated rats. Eight-week-old male Sprague-Dawley rats received 6 intraperitoneal injections of ADR (total 15 mg/kg: group ADR) or saline (control group) over 2 weeks. Left ventricular (LV) ejection fraction was assessed using echocardiography at 3- and 6-weeks after ADR injection (3 weeks and 6 weeks, respectively). Myocardial fatty acid utilization was assessed at 3 weeks and 6 weeks. The myocardial counts of BMIPP were measured after intravenous BMIPP (370 kBq) injection, and 125I counts were measured to calculate the uptake ratio. The enzymatic activity of complex I was assessed by monitoring the oxidation of nicotinamide-adenine-dinucleotide-disodium-salt (NADH). In rats treated with ADR, significant decrease in LV ejection fraction was observed only at 6 weeks compared to control (72.5 vs. 84.5%, p < 0.01). LV ejection fraction at 3 weeks was identical between group ADR and control (81.8 vs. 84.4%). However, at 3 weeks, complex I activity was already reduced significantly in group ADR as compared to control group (p = 0.03), but the reduction in BMIPP accumulation was not (p = 0.15). Our data indicated that reduced complex I activity in a phenomenon occurred in early phase of ADR-induced cardiomyopathy, and it might play an important role in the progression of ADR-induced heart failure.
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Affiliation(s)
- Kiyotaka Ohkura
- First Department of Internal Medicine, Fukui Medical University, Shimoaizuki, Matsuoka-cho, Fukui, Japan
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Pharmacoepidemiology and drug safety. Pharmacoepidemiol Drug Saf 2001; 10:263-78. [PMID: 11505947 DOI: 10.1002/pds.548] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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