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1
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Zhang Y, Zhang Z, Li H, Xiao Y, Ying H. Recent advancements in the application of multi-elemental profiling and ionomics in cardiovascular diseases. J Trace Elem Med Biol 2025; 88:127616. [PMID: 39933207 DOI: 10.1016/j.jtemb.2025.127616] [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: 12/10/2024] [Revised: 02/03/2025] [Accepted: 02/06/2025] [Indexed: 02/13/2025]
Abstract
BACKGROUND Trace elements and minerals are crucial for human growth and health, whose imbalance is associated with a variety of diseases. Recently, multi-elemental profiling and ionomics have been rapidly developed and widely used to study the distribution, variation, and interactions of various elements in diverse physiological and pathological conditions. By utilizing high-throughput elemental analytical techniques and bioinformatics approaches, researchers can uncover the relationship between the metabolism and balance of different elements and numerous human diseases. METHODS The presented work reviews recent advances in multi-elemental and ionomic profiling of human biological samples for several major types of cardiovascular diseases. RESULTS Research indicates distinct and dynamic patterns of ion contents in these diseases. Accumulation of copper and environmental toxic metals as well as deficiencies in zinc and selenium appear to be the most significant risk factors for the majority of cardiovascular diseases, suggesting that an imbalance in these elements may play a role in the development of these illnesses. Furthermore, each type of cardiovascular disease exhibits a relatively unique distribution of ions in biofluid and hair samples from patients, potentially serving as indicators for the specific disease. CONCLUSION Multi-elemental profiling and ionomics not only enhance our understanding of the association between elemental dyshomeostasis and the development of cardiovascular diseases but also facilitate the discovery of novel diagnostic and prognostic markers for these conditions.
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Affiliation(s)
- Yan Zhang
- Shenzhen Key Laboratory of Marine Bioresources and Ecology, Brain Disease and Big Data Research Institute, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, Guangdong Province 518055, PR China; Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, Guangdong Province 518055, PR China.
| | - Zaicheng Zhang
- Shenzhen Key Laboratory of Marine Bioresources and Ecology, Brain Disease and Big Data Research Institute, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, Guangdong Province 518055, PR China
| | - Hengtao Li
- Shenzhen Key Laboratory of Marine Bioresources and Ecology, Brain Disease and Big Data Research Institute, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, Guangdong Province 518055, PR China
| | - Yao Xiao
- Shenzhen Key Laboratory of Marine Bioresources and Ecology, Brain Disease and Big Data Research Institute, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, Guangdong Province 518055, PR China
| | - Huimin Ying
- Department of Endocrinology, Hangzhou Xixi Hospital, Hangzhou Sixth People's Hospital, Hangzhou Xixi Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province 310023, PR China.
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2
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Fu C, Yang X. Cardiac injury caused by iron overload in thalassemia. Front Pediatr 2025; 13:1514722. [PMID: 39931654 PMCID: PMC11808023 DOI: 10.3389/fped.2025.1514722] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Accepted: 01/03/2025] [Indexed: 02/13/2025] Open
Abstract
Cardiac iron overload affects approximately 25% of patients with β-thalassemia major, which is associated with increased morbidity and mortality. Two mechanisms are responsible for iron overload in β-thalassemia: increased iron absorption due to ineffective erythropoiesis and blood transfusions. This review examines the mechanisms of myocardial injury caused by cardiac iron overload and role of various clinical examination techniques in assessing cardiac iron burden and functional impairment. Early identification and intervention for cardiac injury and iron overload in β-thalassemia have the potential to prevent and reverse or delay its progression in the early stages, playing a crucial role in its prognosis.
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Affiliation(s)
- Chunxi Fu
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, China
| | - Xue Yang
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, China
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3
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Qin S, Zhu C, Chen C, Sheng Z, Cao Y. An emerging double‑edged sword role of ferroptosis in cardiovascular disease (Review). Int J Mol Med 2025; 55:16. [PMID: 39540363 PMCID: PMC11573318 DOI: 10.3892/ijmm.2024.5457] [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: 09/02/2024] [Accepted: 10/24/2024] [Indexed: 11/16/2024] Open
Abstract
The pathophysiology of cardiovascular disease (CVD) is complex and presents a serious threat to human health. Cardiomyocyte loss serves a pivotal role in both the onset and progression of CVD. Among various forms of programmed cell death, ferroptosis, along with apoptosis, autophagy and pyroptosis, is closely linked to the advancement of CVD. Ferroptosis, a mechanism of cell death, is driven by the buildup of oxidized lipids and excess iron. This pathway is modulated by lipid, amino acid and iron metabolism. Key characteristics of ferroptosis include disrupted iron homeostasis, increased peroxidation of polyunsaturated fatty acids due to reactive oxygen species, decreased glutathione levels and inactivation of glutathione peroxidase 4. Treatments targeting ferroptosis could potentially prevent or alleviate CVD by inhibiting the ferroptosis pathway. Ferroptosis is integral to the pathogenesis of several types of CVD and inhibiting its occurrence in cardiomyocytes could be a promising therapeutic strategy for the future treatment of CVD. The present review provided an in‑depth analysis of advancements in understanding the mechanisms underlying ferroptosis. The present manuscript summarized the interplay between ferroptosis and CVDs, highlighting its dual roles in these conditions. Additionally, potential therapeutic targets within the ferroptosis pathway were discussed, alongside the current limitations and future directions of these novel treatment strategies. The present review may offer novel insights into preventive and therapeutic approaches for CVDs.
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Affiliation(s)
- Sirun Qin
- Department of Cardiovascular Medicine, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China
| | - Can Zhu
- Department of Cardiovascular Medicine, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China
| | - Chenyang Chen
- Department of Cardiovascular Medicine, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China
| | - Zhe Sheng
- Department of Cardiovascular Medicine, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China
| | - Yu Cao
- Department of Cardiovascular Medicine, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China
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4
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Truby LK, Michelis K, Grodin JL. More Than Meets the Eye: Defining the Prevalence, Pathophysiology, and Approach to Myocardial Iron Overload. Am J Cardiol 2024; 219:38-43. [PMID: 38461925 DOI: 10.1016/j.amjcard.2024.01.033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2023] [Revised: 01/05/2024] [Accepted: 01/19/2024] [Indexed: 03/12/2024]
Affiliation(s)
- Lauren K Truby
- University of Texas Southwestern Medical Center, Dallas, Texas
| | - Katherine Michelis
- University of Texas Southwestern Medical Center, Dallas, Texas; Dallas VA Medical Center, Dallas, Texas
| | - Justin L Grodin
- University of Texas Southwestern Medical Center, Dallas, Texas.
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5
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Jin S, Wang H, Zhang X, Song M, Liu B, Sun W. Emerging regulatory mechanisms in cardiovascular disease: Ferroptosis. Biomed Pharmacother 2024; 174:116457. [PMID: 38518600 DOI: 10.1016/j.biopha.2024.116457] [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: 12/21/2023] [Revised: 03/03/2024] [Accepted: 03/15/2024] [Indexed: 03/24/2024] Open
Abstract
Ferroptosis, distinct from apoptosis, necrosis, autophagy, and other types of cell death, is a novel iron-dependent regulated cell death characterized by the accumulation of lipid peroxides and redox imbalance with distinct morphological, biochemical, and genetic features. Dysregulation of iron homeostasis, the disruption of antioxidative stress pathways and lipid peroxidation are crucial in ferroptosis. Ferroptosis is involved in the pathogenesis of several cardiovascular diseases, including atherosclerosis, cardiomyopathy, myocardial infarction, ischemia-reperfusion injury, abdominal aortic aneurysm, aortic dissection, and heart failure. Therefore, a comprehensive understanding of the mechanisms that regulate ferroptosis in cardiovascular diseases will enhance the prevention and treatment of these diseases. This review discusses the latest findings on the molecular mechanisms of ferroptosis and its regulation in cardiovascular diseases, the application of ferroptosis modulators in cardiovascular diseases, and the role of traditional Chinese medicines in ferroptosis regulation to provide a comprehensive understanding of the pathogenesis of cardiovascular diseases and identify new prevention and treatment options.
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Affiliation(s)
- Sijie Jin
- Department of Cardiology, The Second Hospital of Jilin University, 4026 YaTai Street, Changchun 130041, China
| | - He Wang
- Department of Cardiology, The Second Hospital of Jilin University, 4026 YaTai Street, Changchun 130041, China
| | - Xiaohao Zhang
- Department of Cardiology, The Second Hospital of Jilin University, 4026 YaTai Street, Changchun 130041, China
| | - Mengyang Song
- Department of Cardiology, The Second Hospital of Jilin University, 4026 YaTai Street, Changchun 130041, China
| | - Bin Liu
- Department of Cardiology, The Second Hospital of Jilin University, 4026 YaTai Street, Changchun 130041, China.
| | - Wei Sun
- Department of Cardiology, The Second Hospital of Jilin University, 4026 YaTai Street, Changchun 130041, China.
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6
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Xu X, Deng X, Li Y, Xia S, Baryshnikov G, Bondarchuk SV, Ågren H, Wang X, Liu P, Tan Y, Huang T, Zhang H, Wei Y. Applications of Boron Cluster Supramolecular Frameworks as Metal-Free Chemodynamic Therapy Agents for Melanoma. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2024; 20:e2307029. [PMID: 37712137 DOI: 10.1002/smll.202307029] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/15/2023] [Revised: 08/31/2023] [Indexed: 09/16/2023]
Abstract
Chemodynamic therapy (CDT) is a highly targeted approach to treat cancer since it converts hydrogen peroxide into harmful hydroxyl radicals (OH·) through Fenton or Fenton-like reactions. However, the systemic toxicity of metal-based CDT agents has limited their clinical applications. Herein, a metal-free CDT agent: 2,4,6-tri(4-pyridyl)-1,3,5-triazine (TPT)/ [closo-B12 H12 ]2- (TPT@ B12 H12 ) is reported. Compared to the traditional metal-based CDT agents, TPT@B12 H12 is free of metal avoiding cumulative toxicity during long-term therapy. Density functional theory (DFT) calculation revealed that TPT@B12 H12 decreased the activation barrier more than 3.5 times being a more effective catalyst than the Fe2+ ion (the Fenton reaction), which decreases the barrier about twice. Mechanismly, the theory calculation indicated that both [B12 H12 ]-· and [TPT-H]2+ have the capacity to decompose hydrogen into 1 O2 , OH·, and O2 -· . With electron paramagnetic resonance and fluorescent probes, it is confirmed that TPT@B12 H12 increases the levels of 1 O2 , OH·, and O2 -· . More importantly, TPT@B12 H12 effectively suppress the melanoma growth both in vitro and in vivo through 1 O2 , OH·, and O2 -· generation. This study specifically highlights the great clinical translational potential of TPT@B12 H12 as a CDT reagent.
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Affiliation(s)
- Xiaoran Xu
- Department of Radiation and Medical Oncology, Hubei Cancer Clinical Study Center & Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital of Wuhan University, Wuhan, 430072, China
| | - Xuefan Deng
- College of Chemistry and Molecular Sciences and National Demonstration Center for Experimental Chemistry, Wuhan University, Wuhan, 430072, China
| | - Yi Li
- Department of Radiation and Medical Oncology, Hubei Cancer Clinical Study Center & Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital of Wuhan University, Wuhan, 430072, China
| | - Shiying Xia
- College of Chemistry and Molecular Sciences and National Demonstration Center for Experimental Chemistry, Wuhan University, Wuhan, 430072, China
| | - Glib Baryshnikov
- Department of Science and Technology, Linköping University, Norrköping, 60174, Sweden
| | - Sergey V Bondarchuk
- Department of Chemistry and Nanomaterials Science, Bogdan Khmelnitsky Cherkasy National University, Shevchenko 81, Cherkasy, 18031, Ukraine
| | - Hans Ågren
- Department of Physics and Astronomy, Division of X-ray Photon Science, Uppsala University, Lägerhyddsvägen 1, Uppsala, SE-75121, Sweden
| | - Xinyu Wang
- Department of Radiation and Medical Oncology, Hubei Cancer Clinical Study Center & Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital of Wuhan University, Wuhan, 430072, China
| | - Pan Liu
- Department of Radiation and Medical Oncology, Hubei Cancer Clinical Study Center & Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital of Wuhan University, Wuhan, 430072, China
| | - Yujia Tan
- Department of Radiation and Medical Oncology, Hubei Cancer Clinical Study Center & Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital of Wuhan University, Wuhan, 430072, China
| | - Tianhe Huang
- Department of Radiation and Medical Oncology, Hubei Cancer Clinical Study Center & Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital of Wuhan University, Wuhan, 430072, China
| | - Haibo Zhang
- College of Chemistry and Molecular Sciences and National Demonstration Center for Experimental Chemistry, Wuhan University, Wuhan, 430072, China
| | - Yongchang Wei
- Department of Radiation and Medical Oncology, Hubei Cancer Clinical Study Center & Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital of Wuhan University, Wuhan, 430072, China
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7
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Ullah H, Salih N, Tavaratsyan A, Sandesara M, Syed S, Us Saher N, Fleihan T. Secondary Hemochromatosis Leading to Acute Coronary Syndrome in a Thalassemic Patient. Cureus 2023; 15:e48226. [PMID: 38050510 PMCID: PMC10693904 DOI: 10.7759/cureus.48226] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/03/2023] [Indexed: 12/06/2023] Open
Abstract
Thalassemia, a congenital hemoglobinopathy, is characterized by impaired erythropoiesis and peripheral hemolysis, leading to anemia. Thalassemia major, in particular, necessitates regular blood transfusions, resulting in iron accumulation in the body. Iron overload primarily affects the heart and can induce cardiac disorder, including defects in the pump and conduction system, which is one of the leading causes of mortality among thalassemics. The existing literature has revealed limited support for the occurrence of acute coronary syndrome (ACS) due to hemochromatosis. However, it does show that elevated troponin levels can be observed even in cases not associated with ACS. Here, we offer a rare case study of acute coronary syndrome in a patient with thalassemia major who also had elevated ferritin levels and abnormal troponin I values. The difficulty of cardiac problems in thalassemia major is highlighted by this case, as well as the necessity for more clinical attention and study to better comprehend and handle such instances.
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Affiliation(s)
- Hidayat Ullah
- General Practice, Hayatabad Medical Complex Peshawar, Peshawar, PAK
| | - Noman Salih
- Internal Medicine, Hayatabad Medical Complex Peshawar, Peshawar, PAK
| | - Ani Tavaratsyan
- Cardiology, Yerevan State Medical University (YSMU), Yerevan, ARM
| | | | - Sarah Syed
- Medicine, Combined Military Hospital (CMH) Lahore Medical College and Institute of Dentistry, Lahore, PAK
| | - Najam Us Saher
- Internal Medicine, Hayatabad Medical Complex Peshawar, Peshawar, PAK
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8
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Habib A, Shaaban A, Thompson J, Chinnakotla S, Martin CM, Vercellotti GM. Sudden Onset Iron Overload Cardiomyopathy After Liver Transplantation. J Investig Med High Impact Case Rep 2023; 11:23247096231159812. [PMID: 36914978 PMCID: PMC10017927 DOI: 10.1177/23247096231159812] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/15/2023] Open
Abstract
Iron overload cardiomyopathy has been described in patients who develop acute heart failure after liver transplantation but few reports of this are available. We present a case of a patient with end-stage liver disease who underwent a deceased donor liver transplantation and developed acute onset systolic heart failure with reduced left ventricular ejection fraction. A cardiac magnetic resonance image demonstrated late gadolinium enhancement with diffuse enhancement globally and T1 mapping with severely decreased pre-contrast T1 values suggesting iron overload cardiomyopathy. The patient was treated with iron chelating therapy as well as heart failure guideline-directed medical therapy with subsequent improvement in cardiac function on follow-up magnetic resonance images. Despite our patient's diagnosis of iron overload cardiomyopathy, her iron studies showed normal serum iron and ferritin levels and no evidence of hepatic iron deposition in the transplanted liver.
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Affiliation(s)
- Alma Habib
- University of Minnesota, Minneapolis, MN, USA.,The Ohio State University Wexner Medical Center, Columbus, OH, USA
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9
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Zhang C, Fang Z, Wang K, Wang J, Wan X. Role of iron in the treatment of sepsis. Biointerphases 2022; 19:060801. [PMID: 39540794 DOI: 10.1116/6.0003879] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Accepted: 10/18/2024] [Indexed: 11/16/2024] Open
Abstract
Iron is an important microelement in human and microbial life activities. During the pathophysiological process of sepsis, iron metabolism changes and the body undergoes a series of changes to fight microbial infection. Meanwhile, alterations in iron metabolism during sepsis lead to the development of some diseases, such as transfusion-induced siderosis and anemia. In recent years, several studies have demonstrated the use of iron-chelating agents to fight microbial infections, and new antimicrobial agents have been developed using "Trojan horse" and siderophores immunity. In addition, the use of iron-based nanomaterials as drug delivery systems for gene delivery may be applied to the treatment of sepsis in the future. In this review, we describe the pathophysiological changes in the development and course of sepsis, focusing on the potential of iron in the treatment of sepsis.
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Affiliation(s)
- Chenyang Zhang
- Department of Critical Care Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116021, China
| | - Zhiyao Fang
- Department of Critical Care Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116021, China
| | - Kaixuan Wang
- Department of Critical Care Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116021, China
| | - Jia Wang
- Department of Critical Care Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116021, China
| | - Xianyao Wan
- Department of Critical Care Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116021, China
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10
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Rapezzi C, Aimo A, Barison A, Emdin M, Porcari A, Linhart A, Keren A, Merlo M, Sinagra G. Restrictive cardiomyopathy: definition and diagnosis. Eur Heart J 2022; 43:4679-4693. [PMID: 36269634 PMCID: PMC9712030 DOI: 10.1093/eurheartj/ehac543] [Citation(s) in RCA: 82] [Impact Index Per Article: 27.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Revised: 08/23/2022] [Accepted: 09/16/2022] [Indexed: 01/05/2023] Open
Abstract
Restrictive cardiomyopathy (RCM) is a heterogeneous group of diseases characterized by restrictive left ventricular pathophysiology, i.e. a rapid rise in ventricular pressure with only small increases in filling volume due to increased myocardial stiffness. More precisely, the defining feature of RCM is the coexistence of persistent restrictive pathophysiology, diastolic dysfunction, non-dilated ventricles, and atrial dilatation, regardless of ventricular wall thickness and systolic function. Beyond this shared haemodynamic hallmark, the phenotypic spectrum of RCM is wide. The disorders manifesting as RCM may be classified according to four main disease mechanisms: (i) interstitial fibrosis and intrinsic myocardial dysfunction, (ii) infiltration of extracellular spaces, (iii) accumulation of storage material within cardiomyocytes, or (iv) endomyocardial fibrosis. Many disorders do not show restrictive pathophysiology throughout their natural history, but only at an initial stage (with an evolution towards a hypokinetic and dilated phenotype) or at a terminal stage (often progressing from a hypertrophic phenotype). Furthermore, elements of both hypertrophic and restrictive phenotypes may coexist in some patients, making the classification challenge. Restrictive pathophysiology can be demonstrated by cardiac catheterization or Doppler echocardiography. The specific conditions may usually be diagnosed based on clinical data, 12-lead electrocardiogram, echocardiography, nuclear medicine, or cardiovascular magnetic resonance, but further investigations may be needed, up to endomyocardial biopsy and genetic evaluation. The spectrum of therapies is also wide and heterogeneous, but disease-modifying treatments are available only for cardiac amyloidosis and, partially, for iron overload cardiomyopathy.
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Affiliation(s)
- Claudio Rapezzi
- Corresponding author. Tel: +39 0532239882, Fax: +39 0532 293031,
| | - Alberto Aimo
- Health Science Interdisciplinary Center, Scuola Superiore Sant'Anna, piazza Martiri della Libertà 33, 56127 Pisa, Italy,Cardiology Division, Fondazione Toscana Gabriele Monasterio, via Moruzzi 1, 56124 Pisa, Italy
| | - Andrea Barison
- Health Science Interdisciplinary Center, Scuola Superiore Sant'Anna, piazza Martiri della Libertà 33, 56127 Pisa, Italy,Cardiology Division, Fondazione Toscana Gabriele Monasterio, via Moruzzi 1, 56124 Pisa, Italy
| | - Michele Emdin
- Health Science Interdisciplinary Center, Scuola Superiore Sant'Anna, piazza Martiri della Libertà 33, 56127 Pisa, Italy,Cardiology Division, Fondazione Toscana Gabriele Monasterio, via Moruzzi 1, 56124 Pisa, Italy
| | - Aldostefano Porcari
- Center for Diagnosis and Treatment of Cardiomyopathies, Cardiovascular Department, Azienda Sanitaria Universitaria Giuliano-Isontina (ASUGI), University of Trieste, European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart-ERN GUARD-Heart, Via Giacomo Puccini, 50, 34148 Trieste, Italy
| | - Ales Linhart
- General University Hospital and Charles University, Opletalova 38, 110 00 Staré Město, Czech Republic
| | - Andre Keren
- Cardiology Division, Hadassah Hebrew University Hospital, Sderot Churchill 8, Jerusalem, Israel,Heart Failure Center, Clalit Health Services, Bnei Brit St 22, Jerusalem, Israel
| | - Marco Merlo
- Center for Diagnosis and Treatment of Cardiomyopathies, Cardiovascular Department, Azienda Sanitaria Universitaria Giuliano-Isontina (ASUGI), University of Trieste, European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart-ERN GUARD-Heart, Via Giacomo Puccini, 50, 34148 Trieste, Italy
| | - Gianfranco Sinagra
- Center for Diagnosis and Treatment of Cardiomyopathies, Cardiovascular Department, Azienda Sanitaria Universitaria Giuliano-Isontina (ASUGI), University of Trieste, European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart-ERN GUARD-Heart, Via Giacomo Puccini, 50, 34148 Trieste, Italy
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11
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Cardiac Magnetic Resonance at 3.0 T in Patients With C282Y Homozygous Hereditary Hemochromatosis: Superiority of Radial and Circumferential Strain Over Cardiac T2* Measurements at Baseline and at Post Venesection Follow-up. J Thorac Imaging 2022; 37:300-306. [PMID: 35426858 DOI: 10.1097/rti.0000000000000645] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Iron-overload cardiomyopathy initially manifests with diastolic dysfunction and can progress to dilated cardiomyopathy if untreated. Previous studies have shown that patients with primary and secondary hemochromatosis can have subclinical left ventricle dysfunction with abnormalities on strain imaging. This study aimed to evaluate the relationship between cardiac T2* values and myocardial-wall strain in patients with hereditary hemochromatosis (HH) at the time of diagnosis and after a course of venesection treatment. MATERIALS AND METHODS Baseline cardiac magnetic resonance (CMR) at 3 T was performed in 19 patients with newly diagnosed HH with elevated serum ferritin levels and repeated after a course of treatment with venesection. Quantitative T2* mapping and strain analysis were performed offline using dedicated relaxometry fitting and feature-tracking software. RESULTS The majority (84%) of patients had normal baseline myocardial T2* values (mean 19.3 ms, range 8.9 to 31.2 ms), which improved significantly after venesection (mean 24.1 ms, range 11 to 38.1 ms) ( P =0.021). Mean global radial strain significantly improved from 25.0 (range: 15.6 to 32.9) to 28.3 (range: 19.8 to 35.8) ( P =0.001) and mean global circumferential strain improved, decreasing from -15.7 (range: -11.1 to -19.2) to -17.1 (range: -13.0 to -20.1) ( P =0.001). CONCLUSION Patients with HH may have normal T2* values in the presence of subclinical left ventricle dysfunction, which can be detected by abnormal radial and circumferential strain. As strain imaging improves following venesection in HH, it may serve as a useful biomarker to guide treatment.
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12
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Limongelli G, Adorisio R, Baggio C, Bauce B, Biagini E, Castelletti S, Favilli S, Imazio M, Lioncino M, Merlo M, Monda E, Olivotto I, Parisi V, Pelliccia F, Basso C, Sinagra G, Indolfi C, Autore C. Diagnosis and Management of Rare Cardiomyopathies in Adult and Paediatric Patients. A Position Paper of the Italian Society of Cardiology (SIC) and Italian Society of Paediatric Cardiology (SICP). Int J Cardiol 2022; 357:55-71. [PMID: 35364138 DOI: 10.1016/j.ijcard.2022.03.050] [Citation(s) in RCA: 42] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Revised: 03/21/2022] [Accepted: 03/24/2022] [Indexed: 12/20/2022]
Abstract
Cardiomyopathies (CMPs) are myocardial diseases in which the heart muscle is structurally and functionally abnormal in the absence of coronary artery disease, hypertension, valvular disease and congenital heart disease sufficient to cause the observed myocardial abnormality. Thought for a long time to be rare diseases, it is now clear that most of the CMPs can be easily observed in clinical practice. However, there is a group of specific heart muscle diseases that are rare in nature whose clinical/echocardiographic phenotypes resemble those of the four classical morphological subgroups of hypertrophic, dilated, restrictive, arrhythmogenic CMPs. These rare CMPs, often but not solely diagnosed in infants and paediatric patients, should be more properly labelled as specific CMPs. Emerging consensus exists that these conditions require tailored investigation and management. Indeed, an appropriate understanding of these conditions is mandatory for early treatment and counselling. At present, however, the multisystemic and heterogeneous presentation of these entities is a challenge for clinicians, and time delay in diagnosis is a significant concern. The aim of this paper is to define practical recommendations for diagnosis and management of the rare CMPs in paediatric or adult age. A modified Delphi method was adopted to grade the recommendations proposed by each member of the writing committee.
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Affiliation(s)
- Giuseppe Limongelli
- Inherited and Rare Cardiovascular Disease Unit, University of Campania "Luigi Vanvitelli", AORN dei Colli, Monaldi Hospital, Naples, Italy; Member of ERN GUARD-HEART (European Reference Network for Rare and Complex Diseases of the Heart; http://guardheart.ern-net.eu).
| | - Rachele Adorisio
- Heart Failure, Transplant and Mechanical Cardiocirculatory Support Unit, Department of Pediatric Cardiology and Cardiac Surgery, Heart Lung Transplantation, Bambino Gesù Hospital and Research Institute, Rome, Italy
| | - Chiara Baggio
- Cardiothoracovascular and Medical Surgical and Health Science Department, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), University of Trieste, 34149 Trieste, Italy
| | - Barbara Bauce
- Member of ERN GUARD-HEART (European Reference Network for Rare and Complex Diseases of the Heart; http://guardheart.ern-net.eu); Department of Cardio-Thoraco-Vascular Sciences and Public Health, University of Padua, Padua, Italy
| | - Elena Biagini
- Member of ERN GUARD-HEART (European Reference Network for Rare and Complex Diseases of the Heart; http://guardheart.ern-net.eu); Cardiology Unit, St. Orsola Hospital, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Silvia Castelletti
- Cardiomyopathy Unit and Center for Cardiac Arrhythmias of Genetic Origin, Department of Cardiovascular, Neural and Metabolic Science, Istituto Auxologico Italiano IRCCS, Milan, Italy
| | - Silvia Favilli
- Department of Pediatric Cardiology, Meyer Children's Hospital, Viale Gaetano Pieraccini, 24, 50139 Florence, Italy
| | - Massimo Imazio
- Head of Cardiology, Cardiothoracic Department, University Hospital "Santa Maria della Misericordia", ASUFC, Piazzale Santa Maria della Misericordia 15, Udine 33100, Italy
| | - Michele Lioncino
- Inherited and Rare Cardiovascular Disease Unit, University of Campania "Luigi Vanvitelli", AORN dei Colli, Monaldi Hospital, Naples, Italy
| | - Marco Merlo
- Member of ERN GUARD-HEART (European Reference Network for Rare and Complex Diseases of the Heart; http://guardheart.ern-net.eu); Cardiothoracovascular and Medical Surgical and Health Science Department, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), University of Trieste, 34149 Trieste, Italy
| | - Emanuele Monda
- Inherited and Rare Cardiovascular Disease Unit, University of Campania "Luigi Vanvitelli", AORN dei Colli, Monaldi Hospital, Naples, Italy
| | - Iacopo Olivotto
- Cardiomyopathy Unit, Azienda Ospedaliera Universitaria Careggi and the University of Florence, Florence, Italy
| | - Vanda Parisi
- Cardiology Unit, St. Orsola Hospital, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | | | - Cristina Basso
- Member of ERN GUARD-HEART (European Reference Network for Rare and Complex Diseases of the Heart; http://guardheart.ern-net.eu); Cardiovascular Pathology Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health Azienda Ospedaliera, University of Padua Padova, Italy
| | - Gianfranco Sinagra
- Member of ERN GUARD-HEART (European Reference Network for Rare and Complex Diseases of the Heart; http://guardheart.ern-net.eu); Cardiothoracovascular and Medical Surgical and Health Science Department, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), University of Trieste, 34149 Trieste, Italy
| | - Ciro Indolfi
- Department of Medical and Surgical Sciences, Magna Grecia University, Catanzaro, Italy
| | - Camillo Autore
- Department of Clinical and Molecular Medicine, Sapienza University of Rome, Division of Cardiology, Sant'Andrea Hospital, Via di Grottarossa 1035-1039, 00189 Rome, Italy
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13
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Li S, Lei Z, Yang X, Zhao M, Hou Y, Wang D, Tang S, Li J, Yu J. Propofol Protects Myocardium From Ischemia/Reperfusion Injury by Inhibiting Ferroptosis Through the AKT/p53 Signaling Pathway. Front Pharmacol 2022; 13:841410. [PMID: 35370724 PMCID: PMC8966655 DOI: 10.3389/fphar.2022.841410] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Accepted: 02/21/2022] [Indexed: 12/19/2022] Open
Abstract
The molecular mechanism underlying the protective role of propofol against myocardial ischemia/reperfusion (I/R) injury remains poorly understood. Previous studies have shown that ferroptosis is an imperative pathological process in myocardial I/R injury. We hypothesized that propofol prevents myocardial I/R injury by inhibiting ferroptosis via the AKT/p53 signaling pathway. The ferroptosis-inducing agent erastin (E) and AKT inhibitor MK2206 (MK) were used to investigate the role of propofol in myocardial I/R injury. H9C2 cells treated without any reagents, erastin for 24 h, propofol for 1 h before adding erastin were assigned as the control (C), E, and E + P group, respectively. Cell viability, reactive oxygen species (ROS), and the expression of antioxidant enzymes, including ferritin heavy chain 1 (FTH1), cysteine/glutamate transporter (XCT), and glutathione peroxidase 4 (GPX4) in H9C2 cells. Rat hearts from the I/R + P or I/R groups were treated with or without propofol for 20 min before stopping perfusion for 30 min and reperfusion for 60 min. Rat hearts from the I/R + P + MK or I/R + MK groups were treated with or without propofol for 20 min, with a 10-min treatment of MK2206 before stopping perfusion. Myocardial histopathology, mitochondrial structure, iron levels, and antioxidant enzymes expression were assessed. Our results demonstrated that erastin increased H9C2 cell mortality and reduced the expression of antioxidant enzymes. I/R, which reduced the expression of antioxidant enzymes and increased iron or p53 (p < 0.05), boosted myocardium pathological and mitochondrion damage. Propofol inhibited these changes; however, the effects of propofol on I/R injury were antagonized by MK (p < 0.05). In addition, AKT siRNA inhibited the propofol-induced expression of antioxidant enzymes (p < 0.05). Our findings confirm that propofol protects myocardium from I/R injury by inhibiting ferroptosis via the AKT/p53 signal pathway.
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Affiliation(s)
- Shengqiang Li
- Department of Anesthesiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Zhen Lei
- Department of Anesthesiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Xiaomei Yang
- Department of Anesthesiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Meng Zhao
- Department of Anesthesiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Yonghao Hou
- Department of Anesthesiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Di Wang
- Department of Anesthesiology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Shuhai Tang
- Department of Anesthesiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Jingxin Li
- Department of Physiology, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
- *Correspondence: Jingxin Li, ; Jingui Yu,
| | - Jingui Yu
- Department of Anesthesiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- *Correspondence: Jingxin Li, ; Jingui Yu,
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14
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Gowda SN, Ali HJ, Hussain I. Overview of Restrictive Cardiomyopathies. Methodist Debakey Cardiovasc J 2022; 18:4-16. [PMID: 35414858 PMCID: PMC8932380 DOI: 10.14797/mdcvj.1078] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2022] [Accepted: 02/10/2022] [Indexed: 11/18/2022] Open
Abstract
Restrictive cardiomyopathy (RCM) includes a heterogeneous group of diseases that cause increased myocardial stiffness, leading to impaired ventricular relaxation and severe diastolic dysfunction. Given that it is the least common type of cardiomyopathy, it can be a diagnostic challenge due to its varied pathogenesis, clinical presentation, and diagnostic evaluation. In this review, we provide an overview of different etiologies of RCM and examine the diagnostic and treatment approaches for various types.
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Affiliation(s)
- Smitha Narayana Gowda
- Department of Cardiovascular Medicine, Houston Methodist Hospital, Houston, Texas, US
| | - Hyeon-Ju Ali
- Department of Cardiovascular Medicine, Houston Methodist Hospital, Houston, Texas, US
| | - Imad Hussain
- Department of Cardiovascular Medicine, Houston Methodist Hospital, Houston, Texas, US
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15
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Joshi PK, Patel SC, Shreya D, Zamora DI, Patel GS, Grossmann I, Rodriguez K, Soni M, Sange I. Hereditary Hemochromatosis: A Cardiac Perspective. Cureus 2021; 13:e20009. [PMID: 34987900 PMCID: PMC8716004 DOI: 10.7759/cureus.20009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/29/2021] [Indexed: 11/21/2022] Open
Abstract
Hereditary hemochromatosis (HH) is a common genetic metabolic disorder characterized by excessive iron absorption and elevated serum iron levels, which accumulate in various organs, such as the heart, pancreas, gonads, and damage these organs. There are only a few articles and clinical studies describing the characteristics of cardiac involvement in HH along with the significance of early diagnosis and management in preventing complications. In this review article, we have reviewed multiple pieces of literature and gathered available information regarding the subject. We compiled the data to investigate the importance of early detection of symptoms, regular monitoring, and prompt management with strict adherence to reverse or prevent complications. This article has reviewed different aspects of cardiac hemochromatosis, such as pathogenesis, clinical presentation, diagnosis, and management. Recognition of early symptoms, diagnosis of cardiac involvement with various modalities, and implementation of early treatment are essentially the foundation of better outcomes in HH.
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16
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Moinipour N, Barati M, Sahebkar A, Iranshahy M, Shakeri A. Protective effects of curcumin against iron-induced toxicity. Curr Pharm Biotechnol 2021; 23:1020-1027. [PMID: 34521323 DOI: 10.2174/1389201022666210914122846] [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: 03/04/2021] [Revised: 08/02/2021] [Accepted: 08/05/2021] [Indexed: 11/22/2022]
Abstract
Iron is an essential element in cellular metabolism that participates in many biochemical reactions. Nevertheless, iron overload in the body is the cause of damage in some organs including liver, glands, brain, heart, gastrointestinal tract and lung. Iron chelation therapy could be considered as an effective approach for removing excess iron. Deferoxamine, deferiprone and deferasirox are three common iron chelators in clinical practice but cause several side effects. In this context, the use of curcumin, a dietary phytochemical derived from turmeric, as a natural and safe antioxidant with iron-chelating activity may be a useful strategy for the management of iron overload. This review focuses on the deleterious effect of iron accumulation in different organs of the body as well as the therapeutic potential of curcumin against iron-induced toxicity.
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Affiliation(s)
- Nastaran Moinipour
- Department of Pharmacognosy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad. Iran
| | - Mahdi Barati
- Department of Immunology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad. Iran
| | - Amirhosein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad. Iran
| | - Milad Iranshahy
- Department of Pharmacognosy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad. Iran
| | - Abolfazl Shakeri
- Department of Pharmacognosy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad. Iran
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17
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Moore AB, Wing JR, Goiffon RJ, Leaf RK, Tsao L, Misdraji J. Case 25-2021: A 48-Year-Old Man with Fatigue and Leg Swelling. N Engl J Med 2021; 385:745-754. [PMID: 34407347 DOI: 10.1056/nejmcpc2100282] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Affiliation(s)
- Amber B Moore
- From the Departments of Medicine (A.B.M., J.R.W., R.K.L., L.T.), Radiology (R.J.G.), and Pathology (J.M.), Massachusetts General Hospital, and the Departments of Medicine (A.B.M., J.R.W., R.K.L., L.T.), Radiology (R.J.G.), and Pathology (J.M.), Harvard Medical School - both in Boston
| | - Jonathan R Wing
- From the Departments of Medicine (A.B.M., J.R.W., R.K.L., L.T.), Radiology (R.J.G.), and Pathology (J.M.), Massachusetts General Hospital, and the Departments of Medicine (A.B.M., J.R.W., R.K.L., L.T.), Radiology (R.J.G.), and Pathology (J.M.), Harvard Medical School - both in Boston
| | - Reece J Goiffon
- From the Departments of Medicine (A.B.M., J.R.W., R.K.L., L.T.), Radiology (R.J.G.), and Pathology (J.M.), Massachusetts General Hospital, and the Departments of Medicine (A.B.M., J.R.W., R.K.L., L.T.), Radiology (R.J.G.), and Pathology (J.M.), Harvard Medical School - both in Boston
| | - Rebecca K Leaf
- From the Departments of Medicine (A.B.M., J.R.W., R.K.L., L.T.), Radiology (R.J.G.), and Pathology (J.M.), Massachusetts General Hospital, and the Departments of Medicine (A.B.M., J.R.W., R.K.L., L.T.), Radiology (R.J.G.), and Pathology (J.M.), Harvard Medical School - both in Boston
| | - Lana Tsao
- From the Departments of Medicine (A.B.M., J.R.W., R.K.L., L.T.), Radiology (R.J.G.), and Pathology (J.M.), Massachusetts General Hospital, and the Departments of Medicine (A.B.M., J.R.W., R.K.L., L.T.), Radiology (R.J.G.), and Pathology (J.M.), Harvard Medical School - both in Boston
| | - Joseph Misdraji
- From the Departments of Medicine (A.B.M., J.R.W., R.K.L., L.T.), Radiology (R.J.G.), and Pathology (J.M.), Massachusetts General Hospital, and the Departments of Medicine (A.B.M., J.R.W., R.K.L., L.T.), Radiology (R.J.G.), and Pathology (J.M.), Harvard Medical School - both in Boston
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18
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Advancement of echocardiography for surveillance of iron overload cardiomyopathy: comparison to cardiac magnetic resonance imaging. J Echocardiogr 2021; 19:141-149. [PMID: 33772457 DOI: 10.1007/s12574-021-00524-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Revised: 02/03/2021] [Accepted: 03/13/2021] [Indexed: 10/21/2022]
Abstract
The prevalence of iron overload cardiomyopathy (IOC) is increasing. Patients with transfusion-dependent anemias or conditions associated with increased iron absorption over time are at a significant risk for the development of iron-overloaded states such as IOC. Current guidelines regarding the diagnostic evaluation and follow-up of patients at risk for IOC exist, and are composed of multiple components, including such as echocardiography, genetic testing, magnetic resonance imaging of liver, and cardiac magnetic resonance imaging (CMR). While these are considered reliable for the evaluation of patients at risk for an iron-overloaded state, there is an access challenge associated with initial and serial CMR scanning in this patient population. Furthermore, there are other limiting factors, such as patient characteristics that may preclude the use of CMR as a viable diagnostic imaging modality for these patients. On the other hand, recent evidence in the literature suggests that transthoracic echocardiography, which has had significant technological advances, can equal or even outperform CMR to identify cardiac functional abnormalities such as subclinical left ventricular strain and left atrial functional abnormalities in iron overload conditions. Therefore, there is a potential role of more frequent use of echocardiography for surveillance of the development of IOC. Our purpose with this narrative review is to describe recent advances in echocardiography and propose a potential increased use of echocardiography in the surveillance of the development of IOC.
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19
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Blood donation and heavy metal poisoning in developing nations: Any link? Transfus Apher Sci 2021; 60:103067. [PMID: 33541762 DOI: 10.1016/j.transci.2021.103067] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Revised: 01/04/2021] [Accepted: 01/09/2021] [Indexed: 11/24/2022]
Abstract
Long term health effects of heavy metal exposure from both occupational and environmental settings involve multi-organ toxicities including but not limited to disturbances of neurological, cognitive, and metabolic processes, immune system dysregulation, carcinogenesis and sometimes permanent disabilities. Humans are exposed to toxic metals through various sources and routes of entry. The risk of heavy metal poisoning from donor blood has been the subject of many scientific investigations. In this review we highlight how the access to a safe and adequate blood transfusion with minimal risk of toxic metals to recipients is a public health challenge, especially in developing nations. For quality assurance purposes, blood donors are screened for various blood-borne pathogens, but screening for toxic metal levels is not routine. Evidence from scientific studies used in this review lends credence to the risk of heavy metal poisoning from donors with high blood concentrations of these heavy metals. The risk of toxicity is exceptionally high in vulnerable populations such as neonates and preterm infants, as well as in pregnant women and other individuals with conditions requiring multiple blood transfusions. This is worse in developing countries where some members of the population engage in illegal refining and artisanal mining activities. In order to reduce toxic metal exposure in vulnerable populations, blood meant for transfusion in vulnerable subjects, e.g. children, should be routinely screened for heavy metal concentrations. Patients receiving multiple blood transfusions should also be monitored for iron overload and its attendant toxicities.
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20
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Wang Q, Xiao H, Yu X, Lin H, Yang B, Zhang Y, Feng D, Yan F, Wang H. R1ρ at high spin-lock frequency could be a complementary imaging biomarker for liver iron overload quantification. Magn Reson Imaging 2021; 75:141-148. [PMID: 33129937 DOI: 10.1016/j.mri.2020.10.014] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2020] [Revised: 10/25/2020] [Accepted: 10/26/2020] [Indexed: 01/16/2023]
Abstract
PURPOSE To compare the correlations among the R1ρ, R2, and R2* relaxation rates with liver iron concentration (LIC) in the assessment of rat liver iron content and explore the application potential of R1ρ in assessing liver iron content. METHODS Iron dextran (dosage of 0, 25, 50, 100, and 200 mg/kg body weight) was injected into 35 male rats to increase the amount of iron storage in the liver. After one week, all rats were euthanized with isoflurane. A portion of the largest hepatic lobe was extracted to quantify the LIC by inductively coupled plasma, and the remaining liver tissue was stored in 4% buffered paraformaldehyde for 24 h before MRI. Spin-lock preparation with a RARE (rapid acquisition with relaxation enhancement) readout (9 different spin-lock times and 7 different spin-lock frequencies (FSLs)) and multi-echo UTE (ultrashort TE) pulses were developed to quantify R1ρ and R2 * on a Bruker 11.7 T MR system. For comparisons with R1ρ and R2*, R2 was acquired using the CPMG sequence. RESULTS Mean R1ρ values displayed dispersion, with decrease in R1ρ at higher FSLs. Spearman's correlation analysis (two-tailed) indicated that the R1ρ values were significantly associated with LIC at FSL = 2000, 2500, and 3000 Hz (r = 0.365 and P = 0.031, r = 0.608 and P < 0.001, and r = 0.764 and P < 0.001, respectively), and were not significantly associated with LIC at FSL = 500, 1000, 1250, and 1500 Hz (all P > 0.05). R2 and R2* showed significant linear correlations with LIC (r = 0.787 and P < 0.001, and r = 0.859 and P < 0.001, respectively). Correlation analysis across R1ρ, R2, and R* also suggested that the correlation strength between R1ρ and R2 and between R1ρ and R* showed an increasing trend with increase in FSL. CONCLUSION In this study, a strong association was observed between R1ρ and LIC at high FSLs further confirming previous findings. The results demonstrated that R1ρ at high FSL might serve as a complementary imaging biomarker for liver iron overload quantification.
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Affiliation(s)
- Qianfeng Wang
- Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China
| | - Hong Xiao
- Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xuchen Yu
- Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China
| | - Huimin Lin
- Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Baofeng Yang
- Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China
| | - Yuwen Zhang
- Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China
| | - Danyang Feng
- Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China
| | - Fuhua Yan
- Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
| | - He Wang
- Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China; Human Phenome Institute, Fudan University, Shanghai, China; Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence (Fudan University), Ministry of Education, China.
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21
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Naghavi B, Fattahi H, Parsaee M, Rezaeian N, Azarkeivan A, Meimand S, Mohammadi K. Comparison between two and three-dimensional speckle-tracking echocardiography and cardiac T2* magnetic resonance imaging in ß-thalassemia. Res Cardiovasc Med 2021. [DOI: 10.4103/rcm.rcm_15_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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22
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Pieske B, Tschöpe C, de Boer RA, Fraser AG, Anker SD, Donal E, Edelmann F, Fu M, Guazzi M, Lam CSP, Lancellotti P, Melenovsky V, Morris DA, Nagel E, Pieske-Kraigher E, Ponikowski P, Solomon SD, Vasan RS, Rutten FH, Voors AA, Ruschitzka F, Paulus WJ, Seferovic P, Filippatos G. How to diagnose heart failure with preserved ejection fraction: the HFA-PEFF diagnostic algorithm: a consensus recommendation from the Heart Failure Association (HFA) of the European Society of Cardiology (ESC). Eur Heart J 2020; 40:3297-3317. [PMID: 31504452 DOI: 10.1093/eurheartj/ehz641] [Citation(s) in RCA: 962] [Impact Index Per Article: 192.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2018] [Revised: 10/30/2018] [Accepted: 08/26/2019] [Indexed: 02/07/2023] Open
Abstract
Making a firm diagnosis of chronic heart failure with preserved ejection fraction (HFpEF) remains a challenge. We recommend a new stepwise diagnostic process, the 'HFA-PEFF diagnostic algorithm'. Step 1 (P=Pre-test assessment) is typically performed in the ambulatory setting and includes assessment for HF symptoms and signs, typical clinical demographics (obesity, hypertension, diabetes mellitus, elderly, atrial fibrillation), and diagnostic laboratory tests, electrocardiogram, and echocardiography. In the absence of overt non-cardiac causes of breathlessness, HFpEF can be suspected if there is a normal left ventricular ejection fraction, no significant heart valve disease or cardiac ischaemia, and at least one typical risk factor. Elevated natriuretic peptides support, but normal levels do not exclude a diagnosis of HFpEF. The second step (E: Echocardiography and Natriuretic Peptide Score) requires comprehensive echocardiography and is typically performed by a cardiologist. Measures include mitral annular early diastolic velocity (e'), left ventricular (LV) filling pressure estimated using E/e', left atrial volume index, LV mass index, LV relative wall thickness, tricuspid regurgitation velocity, LV global longitudinal systolic strain, and serum natriuretic peptide levels. Major (2 points) and Minor (1 point) criteria were defined from these measures. A score ≥5 points implies definite HFpEF; ≤1 point makes HFpEF unlikely. An intermediate score (2-4 points) implies diagnostic uncertainty, in which case Step 3 (F1: Functional testing) is recommended with echocardiographic or invasive haemodynamic exercise stress tests. Step 4 (F2: Final aetiology) is recommended to establish a possible specific cause of HFpEF or alternative explanations. Further research is needed for a better classification of HFpEF.
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Affiliation(s)
- Burkert Pieske
- Department of Internal Medicine and Cardiology, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum.,German Center for Cardiovascular Research (DZHK), Berlin, Partner Site, Germany.,Department of Internal Medicine and Cardiology, German Heart Institute, Berlin, Germany.,Berlin Institute of Health (BIH), Germany
| | - Carsten Tschöpe
- Department of Internal Medicine and Cardiology, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum.,German Center for Cardiovascular Research (DZHK), Berlin, Partner Site, Germany.,Berlin Institute of Health (BIH) Center for Regenerative Therapies (BCRT), Charite, Berlin, Germany
| | - Rudolf A de Boer
- University Medical Centre Groningen, University of Groningen, Department of Cardiology, Groningen, the Netherlands
| | | | - Stefan D Anker
- Department of Internal Medicine and Cardiology, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum.,German Center for Cardiovascular Research (DZHK), Berlin, Partner Site, Germany.,Berlin Institute of Health (BIH) Center for Regenerative Therapies (BCRT), Charite, Berlin, Germany.,Department of Cardiology and Pneumology, University Medicine Göttingen (UMG), Germany
| | - Erwan Donal
- Cardiology and CIC, IT1414, CHU de Rennes LTSI, Université Rennes-1, INSERM 1099, Rennes, France
| | - Frank Edelmann
- Department of Internal Medicine and Cardiology, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum.,German Center for Cardiovascular Research (DZHK), Berlin, Partner Site, Germany
| | - Michael Fu
- Section of Cardiology, Department of Medicine, Sahlgrenska University Hosptal/Ostra, Göteborg, Sweden
| | - Marco Guazzi
- Department of Biomedical Sciences for Health, University of Milan, IRCCS, Milan, Italy.,Department of Cardiology, IRCCS Policlinico, San Donato Milanese, Milan, Italy
| | - Carolyn S P Lam
- National Heart Centre, Singapore & Duke-National University of Singapore.,University Medical Centre Groningen, The Netherlands
| | - Patrizio Lancellotti
- Department of Cardiology, Heart Valve Clinic, University of Liège Hospital, GIGA Cardiovascular Sciences, CHU Sart Tilman, Liège, Belgium
| | - Vojtech Melenovsky
- Institute for Clinical and Experimental Medicine - IKEM, Prague, Czech Republic
| | - Daniel A Morris
- Department of Internal Medicine and Cardiology, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum
| | - Eike Nagel
- Institute for Experimental and Translational Cardiovascular Imaging, University Hospital Frankfurt.,German Centre for Cardiovascular Research (DZHK), Partner Site Frankfurt, Germany
| | - Elisabeth Pieske-Kraigher
- Department of Internal Medicine and Cardiology, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum
| | | | - Scott D Solomon
- Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Ramachandran S Vasan
- Section of Preventive Medicine and Epidemiology and Cardiovascular Medicine, Department of Medicine, Boston University School of Medicine, Boston, MA, USA
| | - Frans H Rutten
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Adriaan A Voors
- University Medical Centre Groningen, University of Groningen, Department of Cardiology, Groningen, the Netherlands
| | - Frank Ruschitzka
- University Heart Centre, University Hospital Zurich, Switzerland
| | - Walter J Paulus
- Department of Physiology and Amsterdam Cardiovascular Sciences, Amsterdam University Medical Center, The Netherlands
| | - Petar Seferovic
- University of Belgrade School of Medicine, Belgrade University Medical Center, Serbia
| | - Gerasimos Filippatos
- Department of Cardiology, National and Kapodistrian University of Athens Medical School; University Hospital "Attikon", Athens, Greece.,University of Cyprus, School of Medicine, Nicosia, Cyprus
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Meloni A, Righi R, Missere M, Renne S, Schicchi N, Gamberini MR, Cuccia L, Lisi R, Spasiano A, Roberti MG, Zuccarelli A, Ait-Ali L, Festa P, Aquaro GD, Mangione M, Barra V, Positano V, Pepe A. Biventricular Reference Values by Body Surface Area, Age, and Gender in a Large Cohort of Well-Treated Thalassemia Major Patients Without Heart Damage Using a Multiparametric CMR Approach. J Magn Reson Imaging 2020; 53:61-70. [PMID: 32311193 DOI: 10.1002/jmri.27169] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Revised: 03/30/2020] [Accepted: 03/30/2020] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND Cardiac MRI plays a critical role in the management of thalassemic patients. No accurate biventricular reference values are available. PURPOSE To establish the ranges for normal left ventricular (LV) and right ventricular (RV) volumes and ejection fraction (EF) and LV mass normalized to body surface area (BSA), age, and gender in a large cohort of well-treated beta-thalassemia major (β-TM) patients without heart damage using a multiparametric MRI. STUDY TYPE Retrospective/cohort study. POPULATION In all, 251 β-TM patients with no known risk factors or cardiac disease, normal electrocardiogram, no macroscopic myocardial fibrosis, and all cardiac segments with T2 * ≥20 msec, and 246 healthy subjects. FIELD STRENGTH/SEQUENCE 1.5T/cine steady-state free precession (SSFP), gradient-echo T2 *, late gadolinium enhancement (LGE) images. ASSESSMENT Biventricular end-diastolic volume, end-systolic volume, stroke volume, and LV mass were normalized to BSA (EDVI, ESVI, SVI). STATISTICAL TESTS Comparisons between the two groups was performed with two-samples t-test or Wilcoxon's signed rank test. For more than two groups, one-way analysis of variance (ANOVA) or a Kruskal-Wallis test were applied. RESULTS Compared to controls, males with β-TM showed significantlt higher LVEDVI in all the age groups, while for the other volumes the difference was significant only within one or more age groups. In females the volumes were comparable between β-TM patients and healthy subjects in all the age groups. In the male β-TM population we found a significant effect of age on LVEDVI (P = 0.017), LVESVI (P = 0.001), RVESVI (P = 0.029), and RVEF (P = 0.031), while for females none of the biventricular parameters were significantly different among the age groups (LVEDVI: P = 0.614; LVESVI: P = 0.449; LVSVI: P = 0.186; LV mass index: P = 0.071; LVEF: P = 0.059; RVEDVI: P = 0.374; RVESVI: P = 0.180; RVSVI: P = 0.206; RVEF: P = 0.057). In β-TM patients all biventricular volume indexes as well as the LV mass index were significantly larger in males than in females (P < 0.0001 in all cases). The LV and the RV EF were comparable between the sexes (P = 0.568 and P = 0.268, respectively). DATA CONCLUSION Appropriate "normal" reference ranges normalized to BSA, sex, and age are recommended to avoid misdiagnosis of cardiomyopathy in β-TM patients. LEVEL OF EVIDENCE 4 TECHNICAL EFFICACY STAGE: 2.
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Affiliation(s)
- Antonella Meloni
- Magnetic Resonance Imaging Unit, Fondazione G. Monasterio CNR-Regione Toscana, Pisa, Italy
| | - Riccardo Righi
- Diagnostica per Immagini e Radiologia Interventistica, Ospedale del Delta, Lagosanto, Italy
| | - Massimiliano Missere
- Dipartimento di Immagini, Fondazione di Ricerca e Cura "Giovanni Paolo II", Campobasso, Italy
| | - Stefania Renne
- Struttura Complessa di Cardioradiologia-UTIC, Presidio Ospedaliero "Giovanni Paolo II", Lamezia Terme, Italy
| | - Nicolò Schicchi
- Dipartimento di Radiologia, Azienda Ospedaliero-Universitaria Ospedali Riuniti "Umberto I-Lancisi-Salesi", Ancona, Italy
| | - Maria Rita Gamberini
- Dipartimento della Riproduzione e dell'Accrescimento Day Hospital della Talassemia e delle Emoglobinopatie, Azienda Ospedaliero-Universitaria Arcispedale "S. Anna", Ferrara, Italy
| | - Liana Cuccia
- Unità Operativa Complessa Ematologia con Talassemia, ARNAS Civico "Benfratelli-Di Cristina", Palermo, Italy
| | - Roberto Lisi
- Unità Operativa Dipartimentale Talassemia, Presidio Ospedaliero Garibaldi-Centro-ARNAS Garibaldi, Catania, Italy
| | - Anna Spasiano
- Unità Operativa Semplice Dipartimentale Malattie Rare del Globulo Rosso, Azienda Ospedaliera di Rilievo Nazionale "A. Cardarelli", Naples, Italy
| | - Maria Grazia Roberti
- Servizio Trasfusionale, Azienda Ospedaliero-Universitaria OO.RR. Foggia, Foggia, Italy
| | - Angelo Zuccarelli
- U.O. Medicina trasfusionale, Presidio Ospedaliero Sirai, Carbonia, Italy
| | - Lamia Ait-Ali
- Institute of Clinical Physiology, National Research Council, Massa, Italy
| | - Pierluigi Festa
- Magnetic Resonance Imaging Unit, Fondazione G. Monasterio CNR-Regione Toscana, Pisa, Italy.,Pediatric Cardiology and GUCH Unit, Fondazione G. Monasterio CNR-Regione Toscana, Massa, Italy
| | - Giovanni Donato Aquaro
- Magnetic Resonance Imaging Unit, Fondazione G. Monasterio CNR-Regione Toscana, Pisa, Italy
| | - Maurizio Mangione
- U.O.S. Sistemi informativi (UOSI), Fondazione G. Monasterio CNR-Regione Toscana, Pisa, Italy
| | - Valerio Barra
- Magnetic Resonance Imaging Unit, Fondazione G. Monasterio CNR-Regione Toscana, Pisa, Italy
| | - Vincenzo Positano
- Magnetic Resonance Imaging Unit, Fondazione G. Monasterio CNR-Regione Toscana, Pisa, Italy
| | - Alessia Pepe
- Magnetic Resonance Imaging Unit, Fondazione G. Monasterio CNR-Regione Toscana, Pisa, Italy
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Pieske B, Tschöpe C, de Boer RA, Fraser AG, Anker SD, Donal E, Edelmann F, Fu M, Guazzi M, Lam CSP, Lancellotti P, Melenovsky V, Morris DA, Nagel E, Pieske-Kraigher E, Ponikowski P, Solomon SD, Vasan RS, Rutten FH, Voors AA, Ruschitzka F, Paulus WJ, Seferovic P, Filippatos G. How to diagnose heart failure with preserved ejection fraction: the HFA-PEFF diagnostic algorithm: a consensus recommendation from the Heart Failure Association (HFA) of the European Society of Cardiology (ESC). Eur J Heart Fail 2020; 22:391-412. [PMID: 32133741 DOI: 10.1002/ejhf.1741] [Citation(s) in RCA: 202] [Impact Index Per Article: 40.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2018] [Revised: 10/30/2018] [Accepted: 08/26/2019] [Indexed: 12/11/2022] Open
Abstract
Making a firm diagnosis of chronic heart failure with preserved ejection fraction (HFpEF) remains a challenge. We recommend a new stepwise diagnostic process, the 'HFA-PEFF diagnostic algorithm'. Step 1 (P=Pre-test assessment) is typically performed in the ambulatory setting and includes assessment for heart failure symptoms and signs, typical clinical demographics (obesity, hypertension, diabetes mellitus, elderly, atrial fibrillation), and diagnostic laboratory tests, electrocardiogram, and echocardiography. In the absence of overt non-cardiac causes of breathlessness, HFpEF can be suspected if there is a normal left ventricular (LV) ejection fraction, no significant heart valve disease or cardiac ischaemia, and at least one typical risk factor. Elevated natriuretic peptides support, but normal levels do not exclude a diagnosis of HFpEF. The second step (E: Echocardiography and Natriuretic Peptide Score) requires comprehensive echocardiography and is typically performed by a cardiologist. Measures include mitral annular early diastolic velocity (e'), LV filling pressure estimated using E/e', left atrial volume index, LV mass index, LV relative wall thickness, tricuspid regurgitation velocity, LV global longitudinal systolic strain, and serum natriuretic peptide levels. Major (2 points) and Minor (1 point) criteria were defined from these measures. A score ≥5 points implies definite HFpEF; ≤1 point makes HFpEF unlikely. An intermediate score (2-4 points) implies diagnostic uncertainty, in which case Step 3 (F1 : Functional testing) is recommended with echocardiographic or invasive haemodynamic exercise stress tests. Step 4 (F2 : Final aetiology) is recommended to establish a possible specific cause of HFpEF or alternative explanations. Further research is needed for a better classification of HFpEF.
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Affiliation(s)
- Burkert Pieske
- Department of Internal Medicine and Cardiology, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum.,German Center for Cardiovascular Research (DZHK), Berlin, Partner Site, Germany.,Department of Internal Medicine and Cardiology, German Heart Institute, Berlin, Germany.,Berlin Institute of Health (BIH), Germany
| | - Carsten Tschöpe
- Department of Internal Medicine and Cardiology, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum.,German Center for Cardiovascular Research (DZHK), Berlin, Partner Site, Germany.,Berlin Institute of Health (BIH) Center for Regenerative Therapies (BCRT), Charite, Berlin, Germany
| | - Rudolf A de Boer
- University Medical Centre Groningen, University of Groningen, Department of Cardiology, Groningen, the Netherlands
| | | | - Stefan D Anker
- Department of Internal Medicine and Cardiology, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum.,German Center for Cardiovascular Research (DZHK), Berlin, Partner Site, Germany.,Berlin Institute of Health (BIH) Center for Regenerative Therapies (BCRT), Charite, Berlin, Germany.,Department of Cardiology and Pneumology, University Medicine Göttingen (UMG), Germany
| | - Erwan Donal
- Cardiology and CIC, IT1414, CHU de Rennes LTSI, Université Rennes-1, INSERM 1099, Rennes, France
| | - Frank Edelmann
- Department of Internal Medicine and Cardiology, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum.,German Center for Cardiovascular Research (DZHK), Berlin, Partner Site, Germany
| | - Michael Fu
- Section of Cardiology, Department of Medicine, Sahlgrenska University Hosptal/Ostra, Göteborg, Sweden
| | - Marco Guazzi
- Department of Biomedical Sciences for Health, University of Milan, IRCCS, Milan, Italy.,Department of Cardiology, IRCCS Policlinico, San Donato Milanese, Milan, Italy
| | - Carolyn S P Lam
- National Heart Centre, Singapore & Duke-National University of Singapore.,University Medical Centre Groningen, The Netherlands
| | - Patrizio Lancellotti
- Department of Cardiology, Heart Valve Clinic, University of Liège Hospital, GIGA Cardiovascular Sciences, CHU Sart Tilman, Liège, Belgium
| | - Vojtech Melenovsky
- Institute for Clinical and Experimental Medicine - IKEM, Prague, Czech Republic
| | - Daniel A Morris
- Department of Internal Medicine and Cardiology, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum
| | - Eike Nagel
- Institute for Experimental and Translational Cardiovascular Imaging, University Hospital Frankfurt.,German Centre for Cardiovascular Research (DZHK), Partner Site Frankfurt, Germany
| | - Elisabeth Pieske-Kraigher
- Department of Internal Medicine and Cardiology, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum
| | | | - Scott D Solomon
- Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Ramachandran S Vasan
- Section of Preventive Medicine and Epidemiology and Cardiovascular Medicine, Department of Medicine, Boston University School of Medicine, Boston, MA, USA
| | - Frans H Rutten
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Adriaan A Voors
- University Medical Centre Groningen, University of Groningen, Department of Cardiology, Groningen, the Netherlands
| | - Frank Ruschitzka
- University Heart Centre, University Hospital Zurich, Switzerland
| | - Walter J Paulus
- Department of Physiology and Amsterdam Cardiovascular Sciences, Amsterdam University Medical Center, The Netherlands
| | - Petar Seferovic
- University of Belgrade School of Medicine, Belgrade University Medical Center, Serbia
| | - Gerasimos Filippatos
- Department of Cardiology, National and Kapodistrian University of Athens Medical School; University Hospital "Attikon", Athens, Greece.,University of Cyprus, School of Medicine, Nicosia, Cyprus
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The value of magnetic resonance imaging in evaluation of myocardial and liver iron overload in a thalassaemia endemic population: a report from Northeastern Thailand. Pol J Radiol 2019; 84:e262-e268. [PMID: 31481999 PMCID: PMC6717950 DOI: 10.5114/pjr.2019.86094] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2018] [Accepted: 04/25/2019] [Indexed: 12/29/2022] Open
Abstract
Purpose Patients with chronic haemolytic anaemia, such as in thalassaemia, require repeated blood transfusions, which leads to iron overload and cellular damage, especially in the heart and liver. Classically, serum ferritin and liver biopsy have been used to monitor patient response to chelation therapy. Magnetic resonance imaging (MRI) has proven to be effective in detecting and quantifying iron in the heart and liver. The aim of the paper is to evaluate the accuracy of the MRI T2* procedure in the assessment of liver iron concentration and myocardial iron overload. Material and methods In 210 cases of monthly transfused patients, hepatic and myocardial iron overload was measured by multi-breath-hold MRI T2* and compared to serum ferritin (a traditional marker of iron overload). Results No significant correlation was observed between serum ferritin level and cardiac T2* MRI (p = 0.68, r = 0.06). However, a significant correlation was observed between serum ferritin and liver iron concentration evaluated by MRI (p = 0.04, r = 0.68). Conclusion Routine evaluation of liver and heart iron content using MRI T2* is suggested to better evaluate the haemosiderosis status in thalassaemic patients.
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Byrne D, Walsh JP, Daly C, McKiernan S, Norris S, Murphy RT, King G. Improvements in cardiac function detected using echocardiography in patients with hereditary haemochromatosis. Ir J Med Sci 2019; 189:109-117. [DOI: 10.1007/s11845-019-02032-5] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2018] [Accepted: 05/02/2019] [Indexed: 12/12/2022]
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27
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Seferović PM, Polovina M, Bauersachs J, Arad M, Gal TB, Lund LH, Felix SB, Arbustini E, Caforio AL, Farmakis D, Filippatos GS, Gialafos E, Kanjuh V, Krljanac G, Limongelli G, Linhart A, Lyon AR, Maksimović R, Miličić D, Milinković I, Noutsias M, Oto A, Oto Ö, Pavlović SU, Piepoli MF, Ristić AD, Rosano GM, Seggewiss H, Ašanin M, Seferović JP, Ruschitzka F, Čelutkiene J, Jaarsma T, Mueller C, Moura B, Hill L, Volterrani M, Lopatin Y, Metra M, Backs J, Mullens W, Chioncel O, Boer RA, Anker S, Rapezzi C, Coats AJ, Tschöpe C. Heart failure in cardiomyopathies: a position paper from the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail 2019; 21:553-576. [DOI: 10.1002/ejhf.1461] [Citation(s) in RCA: 133] [Impact Index Per Article: 22.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2019] [Revised: 02/20/2019] [Accepted: 02/28/2019] [Indexed: 12/20/2022] Open
Affiliation(s)
- Petar M. Seferović
- University of Belgrade Faculty of Medicine Belgrade Serbia
- Serbian Academy of Sciences and Arts Belgrade Serbia
| | - Marija Polovina
- University of Belgrade Faculty of Medicine Belgrade Serbia
- Department of CardiologyClinical Center of Serbia Belgrade Serbia
| | - Johann Bauersachs
- Department of Cardiology and AngiologyMedical School Hannover Hannover Germany
| | - Michael Arad
- Cardiomyopathy Clinic and Heart Failure Institute, Leviev Heart Center, Sheba Medical Center and Sackler School of Medicine, Tel Aviv University Tel Aviv Israel
| | - Tuvia Ben Gal
- Department of CardiologyRabin Medical Center, Sackler Faculty of Medicine, Tel Aviv University Tel Aviv Israel
| | - Lars H. Lund
- Department of MedicineKarolinska Institutet, and Heart and Vascular Theme, Karolinska University Hospital Stockholm Sweden
| | - Stephan B. Felix
- Department of Internal Medicine BUniversity Medicine Greifswald Greifswald Germany
| | - Eloisa Arbustini
- Centre for Inherited Cardiovascular Diseases, IRCCS Foundation, University Hospital Policlinico San Matteo Pavia Italy
| | - Alida L.P. Caforio
- Division of Cardiology, Department of Cardiological, Thoracic and Vascular SciencesUniversity of Padua Padua Italy
| | - Dimitrios Farmakis
- University of Cyprus Medical School, Nicosia, Cyprus; Heart Failure Unit, Department of CardiologyAthens University Hospital Attikon, National and Kapodistrian University of Athens Athens Greece
| | - Gerasimos S. Filippatos
- University of Cyprus Medical School, Nicosia, Cyprus; Heart Failure Unit, Department of CardiologyAthens University Hospital Attikon, National and Kapodistrian University of Athens Athens Greece
| | - Elias Gialafos
- Second Department of CardiologyHeart Failure and Preventive Cardiology Section, Henry Dunant Hospital Athens Greece
| | | | - Gordana Krljanac
- University of Belgrade Faculty of Medicine Belgrade Serbia
- Department of CardiologyClinical Center of Serbia Belgrade Serbia
| | - Giuseppe Limongelli
- Department of Cardiothoracic Sciences, Università della Campania ‘Luigi VanvitellI’Monaldi Hospital, AORN Colli, Centro di Ricerca Cardiovascolare, Ospedale Monaldi, AORN Colli, Naples, Italy, and UCL Institute of Cardiovascular Science London UK
| | - Aleš Linhart
- Second Department of Medicine, Department of Cardiovascular MedicineGeneral University Hospital, Charles University in Prague Prague Czech Republic
| | - Alexander R. Lyon
- National Heart and Lung Institute, Imperial College London and Royal Brompton Hospital London UK
| | - Ružica Maksimović
- University of Belgrade Faculty of Medicine Belgrade Serbia
- Centre for Radiology and Magnetic Resonance Imaging, Clinical Centre of Serbia Belgrade Serbia
| | - Davor Miličić
- Department of Cardiovascular DiseasesUniversity Hospital Center Zagreb, University of Zagreb Zagreb Croatia
| | - Ivan Milinković
- Department of CardiologyClinical Center of Serbia Belgrade Serbia
| | - Michel Noutsias
- Mid‐German Heart Center, Department of Internal Medicine III, Division of CardiologyAngiology and Intensive Medical Care, University Hospital Halle, Martin‐Luther‐University Halle Halle Germany
| | - Ali Oto
- Department of CardiologyHacettepe University Faculty of Medicine Ankara Turkey
| | - Öztekin Oto
- Department of Cardiovascular SurgeryDokuz Eylül University Faculty of Medicine İzmir Turkey
| | - Siniša U. Pavlović
- University of Belgrade Faculty of Medicine Belgrade Serbia
- Pacemaker Center, Clinical Center of Serbia Belgrade Serbia
| | | | - Arsen D. Ristić
- University of Belgrade Faculty of Medicine Belgrade Serbia
- Department of CardiologyClinical Center of Serbia Belgrade Serbia
| | - Giuseppe M.C. Rosano
- Centre for Clinical and Basic Research, Department of Medical SciencesIRCCS San Raffaele Pisana Rome Italy
| | - Hubert Seggewiss
- Medizinische Klinik, Kardiologie & Internistische Intensivmedizin, Klinikum Würzburg‐Mitte Würzburg Germany
| | - Milika Ašanin
- University of Belgrade Faculty of Medicine Belgrade Serbia
- Department of CardiologyClinical Center of Serbia Belgrade Serbia
| | - Jelena P. Seferović
- Cardiovascular DivisionBrigham and Women's Hospital, Harvard Medical School Boston MA USA
- Clinic for Endocrinology, Diabetes and Metabolic Disorders, Clinical Center Serbia and Faculty of MedicineUniversity of Belgrade Belgrade Serbia
| | - Frank Ruschitzka
- Department of CardiologyUniversity Heart Center Zürich Switzerland
| | - Jelena Čelutkiene
- Clinic of Cardiac and Vascular Diseases, Institute of Clinical Medicine, Faculty of MedicineVilnius University Vilnius Lithuania
- State Research Institute Centre for Innovative Medicine Vilnius Lithuania
| | - Tiny Jaarsma
- Department of Social and Welfare Studies, Faculty of Health ScienceLinköping University Linköping Sweden
| | - Christian Mueller
- Cardiovascular Research Institute Basel (CRIB) and Department of CardiologyUniversity Hospital Basel, University of Basel Basel Switzerland
| | - Brenda Moura
- Cardiology DepartmentCentro Hospitalar São João Porto Portugal
| | - Loreena Hill
- School of Nursing and Midwifery, Queen's University Belfast Belfast UK
| | | | - Yuri Lopatin
- Volgograd State Medical University, Regional Cardiology Centre Volgograd Volgograd Russia
| | - Marco Metra
- Cardiology, Department of Medical and Surgical SpecialtiesRadiological Sciences, and Public Health, University of Brescia Brescia Italy
| | - Johannes Backs
- Department of Molecular Cardiology and EpigeneticsUniversity of Heidelberg Heidelberg Germany
- DZHK (German Centre for Cardiovascular Research) partner site Heidelberg/Mannheim Heidelberg Germany
| | - Wilfried Mullens
- BIOMED ‐ Biomedical Research Institute, Faculty of Medicine and Life SciencesHasselt University Diepenbeek Belgium
- Department of CardiologyZiekenhuis Oost‐Limburg Genk Belgium
| | - Ovidiu Chioncel
- University of Medicine Carol Davila Bucharest Romania
- Emergency Institute for Cardiovascular Diseases, ‘Prof. C. C. Iliescu’ Bucharest Romania
| | - Rudolf A. Boer
- Department of CardiologyUniversity Medical Center Groningen, University of Groningen Groningen The Netherlands
| | - Stefan Anker
- Division of Cardiology and Metabolism, Department of Cardiology (CVK)Charité Berlin Germany
- Berlin‐Brandenburg Center for Regenerative Therapies (BCRT) Berlin Germany
- DZHK (German Centre for Cardiovascular Research) partner site Berlin, Charité Berlin Germany
| | - Claudio Rapezzi
- Cardiology, Department of ExperimentalDiagnostic and Specialty Medicine, Alma Mater Studiorum University of Bologna Bologna Italy
| | - Andrew J.S. Coats
- Monash University, Australia, and University of Warwick Coventry UK
- Pharmacology, Centre of Clinical and Experimental Medicine, IRCCS San Raffaele Pisana, Rome, Italy, and St George's University of London London UK
| | - Carsten Tschöpe
- Berlin‐Brandenburg Center for Regenerative Therapies, Deutsches Zentrum für Herz‐Kreislauf‐Forschung (DZHK) Berlin, Department of CardiologyCampus Virchow Klinikum, Charite ‐ Universitaetsmedizin Berlin Berlin Germany
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Duncan CN, Talano JAM, McArthur JA. Care of the Critically Ill Pediatric Sickle Cell Patient. CRITICAL CARE OF THE PEDIATRIC IMMUNOCOMPROMISED HEMATOLOGY/ONCOLOGY PATIENT 2019. [PMCID: PMC7122989 DOI: 10.1007/978-3-030-01322-6_6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Sickle cell disease is the most common inherited disease in the United States. Through the effects of hemolysis and vaso-occlusion, it has the potential to incite critical illness involving multiple organ systems. Children with sickle cell disease are at risk of multiple types of shock resulting in a need for ICU care. Our youngest patients with sickle cell disease are at highest risk of infection due to lack of splenic function, and this can present with septic shock. Hypovolemic shock can occur secondary to severe acute anemia as seen with splenic sequestration or a delayed transfusion reaction. As one ages, the risk of cardiac dysfunction – diastolic and systolic dysfunction as well as pulmonary hypertension – can result in cardiogenic shock. In addition to shock, patients with sickle cell disease are at risk for respiratory failure from acute chest syndrome as well as acute neurologic deterioration from stroke. For these reasons, critical care physicians must be familiar with the unique management of sickle cell complications in order to provide the best possible care for this vulnerable population.
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Affiliation(s)
| | - Julie-An M. Talano
- Children’s Hospital of Wisconsin-Milwaukee, Medical College of Wisconsin, Milwaukee, WI USA
| | - Jennifer A. McArthur
- Department of Pediatric Medicine, St. Jude Children’s Research Hospital, Memphis, TN USA
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29
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Pauwels R, Vandecasteele E, Devos D, Pauwels W, De Pauw M. An unexpected cause of liver cirrhosis and cardiomyopathy in a young man. Acta Clin Belg 2018; 73:393-397. [PMID: 29199911 DOI: 10.1080/17843286.2017.1409474] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
Introduction Juvenile hemochromatosis is a rare but severe form of hereditary hemochromatosis that typically presents early in life and can be fatal if left untreated. Case presentation We present the case of a 30-year-old man with a clear symptomatology of juvenile hemochromatosis, but in whom the diagnosis was initially mistaken for alcoholic liver disease because of known excessive use of alcohol, with the consequence that an adequate treatment was postponed. Discussion In this report, we discuss the diagnosis and treatment of juvenile hemochromatosis, focusing on the interaction between hemochromatosis and alcohol induced liver disease and how to differentiate both. We conclude that every young patient with suspected alcoholic liver disease and signs of iron overload should have a testing to rule out other iron overloading pathology, since early recognition and treatment with phlebotomy may prevent organ damage and improve life expectancy.
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Affiliation(s)
- Ruben Pauwels
- Department of Cardiology, University Hospital, Ghent, Belgium
| | | | - Daniel Devos
- Department of Cardiovascular Radiology, University Hospital, Ghent, Belgium
| | - Walter Pauwels
- Department of Gastroenterology and Hepatology, Sint-Lucas Hospital, Ghent, Belgium
| | - Michel De Pauw
- Department of Cardiology, University Hospital, Ghent, Belgium
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30
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Khamseekaew J, Kumfu S, Palee S, Wongjaikam S, Srichairatanakool S, Fucharoen S, Chattipakorn SC, Chattipakorn N. Effects of the iron chelator deferiprone and the T-type calcium channel blocker efonidipine on cardiac function and Ca 2+ regulation in iron-overloaded thalassemic mice. Cell Calcium 2018; 72:18-25. [DOI: 10.1016/j.ceca.2018.01.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2017] [Revised: 01/29/2018] [Accepted: 01/29/2018] [Indexed: 01/07/2023]
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Ambachew S, Biadgo B. Hepcidin in Iron Homeostasis: Diagnostic and Therapeutic Implications in Type 2 Diabetes Mellitus Patients. Acta Haematol 2017; 138:183-193. [PMID: 29136618 DOI: 10.1159/000481391] [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: 02/22/2017] [Accepted: 09/08/2017] [Indexed: 12/21/2022]
Abstract
The prevalence of type 2 diabetes is increasing in epidemic proportions worldwide. Evidence suggests body iron overload is frequently linked and observed in patients with type 2 diabetes. Body iron metabolism is based on iron conservation and recycling by which only a part of the daily need is replaced by duodenal absorption. The principal liver-produced peptide called hepcidin plays a fundamental role in iron metabolism. It directly binds to ferroportin, the sole iron exporter, resulting in the internalization and degradation of ferroportin. However, inappropriate production of hepcidin has been shown to play a role in the pathogenesis of type 2 diabetes mellitus and its complications, based on the regulation and expression in iron-abundant cells. Underexpression of hepcidin results in body iron overload, which triggers the production of reactive oxygen species simultaneously thought to play a major role in diabetes pathogenesis mediated both by β-cell failure and insulin resistance. Increased hepcidin expression results in increased intracellular sequestration of iron, and is associated with the complications of type 2 diabetes. Besides, hepcidin concentrations have been linked to inflammatory cytokines, matriptase 2, and chronic hepatitis C infection, which have in turn been reported to be associated with diabetes by several approaches. Either hepcidin-targeted therapy alone or as adjunctive therapy with phlebotomy, iron chelators, or dietary iron restriction may be able to alter iron parameters in diabetic patients. Therefore, measuring hepcidin may improve differential diagnosis and the monitoring of disorders of iron metabolism.
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Affiliation(s)
- Sintayehu Ambachew
- Department of Clinical Chemistry, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
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Rai P, Niss O, Malik P. A reappraisal of the mechanisms underlying the cardiac complications of sickle cell anemia. Pediatr Blood Cancer 2017; 64. [PMID: 28453224 DOI: 10.1002/pbc.26607] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2016] [Revised: 03/07/2017] [Accepted: 03/24/2017] [Indexed: 12/28/2022]
Abstract
Anemia, hemolysis-driven vasculopathy, and intrinsic myocardial injury have been proposed as predisposing factors to cardiac disease in sickle cell anemia (SCA). The individual impact of these mechanisms on the cardiac features of SCA and the way they influence complications such as sudden death and dysrhythmias have been unclear. Recent findings of an acquired restrictive SCA-related cardiomyopathy, driven by myocardial fibrosis, may explain some of these cardiac features. Given the complexity of cardiac pathology in SCA, using additional parameters to tricuspid regurgitant jet velocity (left atrial volume, diastolic parameters, NT-proBNP) may improve the accuracy of noninvasive screening for cardiopulmonary complications in SCA.
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Affiliation(s)
- Parul Rai
- Division of Experimental Hematology & Cancer Biology and Division of Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Omar Niss
- Division of Experimental Hematology & Cancer Biology and Division of Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.,Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio
| | - Punam Malik
- Division of Experimental Hematology & Cancer Biology and Division of Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.,Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio
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Karimi M, Amirmoezi F, Haghpanah S, Ostad S, Lotfi M, Sefidbakht S, Rezaian S. Correlation of serum ferritin levels with hepatic MRI T2 and liver iron concentration in nontransfusion beta-thalassemia intermediate patients: A contemporary issue. Pediatr Hematol Oncol 2017; 34:292-297. [PMID: 29190176 DOI: 10.1080/08880018.2017.1400135] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
BACKGROUND Beta-thalassemia intermediate is a genetic disease that is milder than beta-thalassemia major. The T2* magnetic resonance imaging (MRI) technique is currently the gold standard for iron load detection. However, it is expensive and needs an expert radiologist to report findings. Therefore, we conducted this study to determine an optimal cut-off value of ferritin in proportion to T2 MRI of liver and measurement of liver iron concentration for early detection of hepatic iron overload in Beta-thalassemia intermediate patients. METHODS This cross-sectional study was conducted on 108 patients with Beta-thalassemia intermediate who referred to tertiary hospital, Shiraz, Iran. Serum ferritin, hepatic T2 MRI, and liver iron concentration were assessed. Receiver operator characteristic was used to determine the sensitivity and specificity of cut-off value. RESULTS Serum ferritin levels showed a statistically significant negative correlation with T2 hepatic MRI (r = -0.290, p value =.003) and positive correlation with liver iron concentration (r = 0.426, p value <.001) in the patients with Beta-thalassemia intermediate. According to the receiver operator characteristic, the best cut-off value for ferritin to show early diagnosis of liver iron overload was 412 ng/mL. Calculated sensitivities and specificities were 0.78 and 0.82 for T2 MRI and 0.76 and 0.86 for liver iron concentration, respectively. CONCLUSION Serum ferritin levels of around 450 ng/mL might be considered as a cut-off point to evaluate hepatic iron overload before using expensive, not readily available T2 MRI. This level of serum ferritin could be considered for starting iron chelation therapy in patients with Beta-thalassemia intermediate in areas where T2 MRI is not available.
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Affiliation(s)
- Mehran Karimi
- a Hematology Research Center, Shiraz University of Medical Sciences , Shiraz , Iran
| | - Fatemeh Amirmoezi
- a Hematology Research Center, Shiraz University of Medical Sciences , Shiraz , Iran
| | - Sezaneh Haghpanah
- a Hematology Research Center, Shiraz University of Medical Sciences , Shiraz , Iran
| | - Seyedpouria Ostad
- b Radiology Research Center, Shiraz University of Medical Sciences , Shiraz , Iran
| | - Mehrzad Lotfi
- c Department of Radiology , Medical imaging research center, Shiraz University of Medical Sciences , Shiraz , Iran
| | - Sepideh Sefidbakht
- c Department of Radiology , Medical imaging research center, Shiraz University of Medical Sciences , Shiraz , Iran
| | - Shahed Rezaian
- b Radiology Research Center, Shiraz University of Medical Sciences , Shiraz , Iran
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Kucukseymen S, Oner Yuksel I, Cagirci G, Koklu E, Karakus V, Cay S, Kus G, Kurtoglu E, Arslan S. Heart Rate Recovery as a Novel Test for Predicting Cardiac Involvement in Beta-Thalassemia Major. ACTA CARDIOLOGICA SINICA 2017; 33:410-419. [PMID: 29033512 PMCID: PMC5534421 DOI: 10.6515/acs20161104a] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 05/01/2016] [Accepted: 11/04/2016] [Indexed: 11/23/2022]
Abstract
BACKGROUND Abnormal heart rate recovery (HRR) is predictive of cardiac mortality. Autonomic abnormalities in beta-thalassemia major (TM) patients have been reported in previous studies. However, the importance of low HRR in exercise stress test in TM patients has not yet been ascertained. Therefore, this study will be the first of its kind in the literature. METHODS Exercise stress test was performed on 56 TM patients who were being treated at the Thalassemia Center of our hospital, along with 46 non-TM iron deficiency anemia (IDA) patients as a control group. Values for HHR were recorded at 1, 2, 3, 4 and 5 min, and HRR was calculated by the difference of heart rate at peak exercise and at a specific time interval following the onset of recovery. RESULTS All HRR values were found to be lower in TM patients compared to those in the IDA group. Exercise capacity [metabolic equivalents (METs)] was also found to be low in these patients (p < 0.001) as well. Total exercise time was significantly lower in the TM group compared to the IDA group (8.40 ± 1.7 min vs. 11.17 ± 1.51 min, p < 0.001). Exercise capacity (METs) was also lower in the TM group compared to the IDA group. Mean T2* value was 28.3 ± 13.7 ms in TM patients on magnetic resonance imaging (MRI). In addition, there are 18 TM patients with T2* value was < 20 ms. CONCLUSIONS This study found that TM was independently associated with low HRR. Such a condition is an indicator of autonomic dysfunction in TM patients, since abnormal HRR is related to impaired autonomic response. In addition, impaired HRR may be a marker of early cardiac involvement in patients, whose T2* value is high on MRI. Modifying HRR with a cardiac rehabilitation program in TM patients with impaired HRR is a field open for further investigation.
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Affiliation(s)
- Selcuk Kucukseymen
- Department of Cardiology, Antalya Education and Research Hospital, Antalya
| | - Isa Oner Yuksel
- Department of Cardiology, Antalya Education and Research Hospital, Antalya
| | - Goksel Cagirci
- Department of Cardiology, Antalya Education and Research Hospital, Antalya
| | - Erkan Koklu
- Department of Cardiology, Antalya Education and Research Hospital, Antalya
| | - Volkan Karakus
- Department of Hematology, Muğla Sıtkı Koçman University, School of Medicine, Muğla
| | - Serkan Cay
- Department of Cardiology, Türkiye Yüksek İhtisas Training and Research Hospital, Ankara
| | - Gorkem Kus
- Department of Cardiology, Antalya Education and Research Hospital, Antalya
| | - Erdal Kurtoglu
- Department of Hematology, Antalya Education and Research Hospital, Antalya, Turkey
| | - Sakir Arslan
- Department of Cardiology, Antalya Education and Research Hospital, Antalya
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De Sanctis V, Soliman AT, Elsedfy H, Yaarubi SAL, Skordis N, Khater D, El Kholy M, Stoeva I, Fiscina B, Angastiniotis M, Daar S, Kattamis C. The ICET-A Recommendations for the Diagnosis and Management of Disturbances of Glucose Homeostasis in Thalassemia Major Patients. Mediterr J Hematol Infect Dis 2016; 8:e2016058. [PMID: 27872738 PMCID: PMC5111521 DOI: 10.4084/mjhid.2016.058] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2016] [Accepted: 09/20/2016] [Indexed: 01/19/2023] Open
Abstract
Iron overload in patients with thalassemia major (TM) affects glucose regulation and is mediated by several mechanisms. The pathogenesis of glycaemic abnormalities in TM is complex and multifactorial. It has been predominantly attributed to a combination of reduced insulin secretory capacity and insulin resistance. The exact mechanisms responsible for progression from norm glycaemia to overt diabetes in these patients are still poorly understood but are attributed mainly to insulin deficiency resulting from the toxic effects of iron deposited in the pancreas and insulin resistance. A group of endocrinologists, haematologists and paediatricians, members of the International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescence Medicine (ICET-A) convened to formulate recommendations for the diagnosis and management of abnormalities of glucose homeostasis in thalassemia major patients on the basis of available evidence from clinical and laboratory data and consensus practice. The results of their work and discussions are described in this article.
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Affiliation(s)
| | - Ashraf T. Soliman
- Department of Pediatrics, Division of Endocrinology, Alexandria University Children’s Hospital, Alexandria, Egypt
| | - Heba Elsedfy
- Department of Pediatrics, Ain Shams University, Cairo, Egypt
| | - Saif AL Yaarubi
- Pediatric Endocrine Unit, Department of Child Health, Sultan Qaboos University Hospital, Al-Khoud, Sultanate of Oman
| | - Nicos Skordis
- Division of Pediatric and Adolescent Endocrinology, Paedi Center for Specialized Pediatrics, St. George’s University Medical School at the University of Nicosia, Cyprus
| | - Doaa Khater
- Department of Pediatrics, Endocrinology Unit, Alexandria University Children’s Hospital, Egypt, and Child Health Department, Sultan Qaboos University Hospital, Muscat, Oman
| | | | - Iva Stoeva
- Paediatric Endocrinologist,”Screening and Functional Endocrine Diagnostics” SBALDB. Professor Ivan Mitev, Medical University Sofia, Bulgaria
| | | | | | - Shahina Daar
- Department of Hematology, College of Medicine and Health Sciences Sultan Qaboos University Oman, Sultanate of Oman & Visiting Scholar, Stellenbosch Institute for Advanced Study (STIAS), Wallenberg Research Centre at Stellenbosch University, Stellenbosch 7600, South Africa
| | - Christos Kattamis
- First Department of Paediatrics, University of Athens, Athens, Greece
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Khamseekaew J, Kumfu S, Chattipakorn SC, Chattipakorn N. Effects of Iron Overload on Cardiac Calcium Regulation: Translational Insights Into Mechanisms and Management of a Global Epidemic. Can J Cardiol 2016; 32:1009-16. [DOI: 10.1016/j.cjca.2015.10.012] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2015] [Revised: 09/26/2015] [Accepted: 10/15/2015] [Indexed: 11/16/2022] Open
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Oudit GY, Backx PH. Amlodipine Therapy for Iron-Overload Cardiomyopathy: The Enduring Value of Translational Research. Can J Cardiol 2016; 32:938-40. [DOI: 10.1016/j.cjca.2015.11.017] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2015] [Revised: 11/20/2015] [Accepted: 11/21/2015] [Indexed: 10/22/2022] Open
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McCullough KD, Bartfay WJ. The Dose-Dependent Effects of Chronic Iron Overload on the Production of Oxygen Free Radicals and Vitamin E Concentrations in the Liver of a Murine Model. Biol Res Nurs 2016; 8:300-4. [PMID: 17456591 DOI: 10.1177/109980040629873] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Genetic disorders of iron metabolism such as primary and secondary hemochromatosis affect thousands of individuals worldwide and are major causes of liver dysfunction, morbidity, and mortality. Although the exact mechanism of hepatic injury associated with these genetic disorders is not fully understood, the propagation of excess concentrations of iron-catalyzed oxygen free radicals (OFRs) may play a role. The authors hypothesized that chronic iron burden would result in dose-dependent (a) increases in hepatic iron stores, (b) increases in hepatic OFR-mediated hepatic cellular injury as quantified by the cytotoxic aldehydes malondialdehyde (MDA) and hexanal, and (c) decreases in protective antioxidant reserve status as quantified by plasma vitamin E (alpha-tocopherol) levels in a murine model. Twenty B6D2F1 male mice were randomized to the (a) saline control (0.05 mL intraperiotoneal [i.p.]/mouse/day, n = 5), (b) 100 mg total iron burden (n = 5), (c) 200 mg total iron burden (n = 5), or (d) 400 mg total iron burden (n = 5) group. Iron burden was achieved by daily injections of iron dextran (Imferon, 0.05 mL i.p./mouse/day). In comparison to control mice and in support of the hypothesis, the authors observed significant dose-dependent increases in total hepatic iron burden (p < .001) with corresponding increases in MDA and hexanal concentrations (p < .001) and decreases in the protective plasma antioxidant vitamin E (p < .001). These findings suggest that iron-catalyzed OFR-mediated damage may play a role in damaging the liver in chronic states of iron burden.
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Tissue Doppler Imaging-derived Diastolic Function Assessment in Children With Sickle Cell Disease and Its Relation With Ferritin. J Pediatr Hematol Oncol 2016; 38:17-21. [PMID: 26491854 DOI: 10.1097/mph.0000000000000430] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Diastolic dysfunction has been shown to occur earlier than systolic dysfunction in iron overload states in adult patients with sickle cell disease (SCD). Tissue Doppler imaging (TDI)-derived E/E' has emerged as a noninvasive marker of diastolic function. We sought to determine diastolic function in children with SCD and study its relation with iron overload. A retrospective review of medical records of 225 pediatric patients with SCD who received an echocardiogram between January 2008 and December 2012 was performed. Echocardiographic measures including M-mode, spectral Doppler, and TDI-derived E/E' were compared with previously published data in healthy children. The left ventricular end-diastolic and end-systolic dimensions were significantly higher in SCD (P<0.0001) and the shortening fraction was similar (P=0.66). E/E' ratio was significantly higher in SCD at the mitral annulus, septum, and tricuspid annulus. In 54% of subjects, the septal E/E' was >8, indicating elevated left ventricular filling pressure. However, there was no significant correlation between ferritin level and E/E' ratios. Pediatric patients with SCD have a high prevalence of elevated estimated left ventricular filling pressure, but this does not correlate with ferritin levels.
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Fahmy HS, Khater NH, El Shahat HM, Madani AA, El Hadidy SS. Reassessing the value of MRI T2∗ in evaluation of hepatic and myocardial iron concentration: An institutional study. THE EGYPTIAN JOURNAL OF RADIOLOGY AND NUCLEAR MEDICINE 2015. [DOI: 10.1016/j.ejrnm.2015.06.008] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022] Open
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Iron metabolism and regulation by neutrophil gelatinase-associated lipocalin in cardiomyopathy. Clin Sci (Lond) 2015; 129:851-62. [PMID: 26318828 DOI: 10.1042/cs20150075] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Neutrophil gelatinase-associated lipocalin (NGAL) has recently become established as an important contributor to the pathophysiology of cardiovascular disease. Accordingly, it is now viewed as an attractive candidate as a biomarker for various disease states, and in particular has recently become regarded as one of the best diagnostic biomarkers available for acute kidney injury. Nevertheless, the precise physiological effects of NGAL on the heart and the significance of their alterations during the development of heart failure are only now beginning to be characterized. Furthermore, the mechanisms via which NGAL mediates its effects are unclear because there is no conventional receptor signalling pathway. Instead, previous work suggests that regulation of iron metabolism could represent an important mechanism of NGAL action, with wide-ranging consequences spanning metabolic and cardiovascular diseases to host defence against bacterial infection. In the present review, we summarize rapidly emerging evidence for the role of NGAL in regulating heart failure. In particular, we focus on iron transport as a mechanism of NGAL action and discuss this in the context of the existing strong associations between iron overload and iron deficiency with cardiomyopathy.
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Puukila S, Bryan S, Laakso A, Abdel-Malak J, Gurney C, Agostino A, Belló-Klein A, Prasad K, Khaper N. Secoisolariciresinol diglucoside abrogates oxidative stress-induced damage in cardiac iron overload condition. PLoS One 2015; 10:e0122852. [PMID: 25822525 PMCID: PMC4379144 DOI: 10.1371/journal.pone.0122852] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2014] [Accepted: 02/23/2015] [Indexed: 02/07/2023] Open
Abstract
Cardiac iron overload is directly associated with cardiac dysfunction and can ultimately lead to heart failure. This study examined the effect of secoisolariciresinol diglucoside (SDG), a component of flaxseed, on iron overload induced cardiac damage by evaluating oxidative stress, inflammation and apoptosis in H9c2 cardiomyocytes. Cells were incubated with 50 μ5M iron for 24 hours and/or a 24 hour pre-treatment of 500 μ M SDG. Cardiac iron overload resulted in increased oxidative stress and gene expression of the inflammatory mediators tumor necrosis factor-α, interleukin-10 and interferon γ, as well as matrix metalloproteinases-2 and -9. Increased apoptosis was evident by increased active caspase 3/7 activity and increased protein expression of Forkhead box O3a, caspase 3 and Bax. Cardiac iron overload also resulted in increased protein expression of p70S6 Kinase 1 and decreased expression of AMP-activated protein kinase. Pre-treatment with SDG abrogated the iron-induced increases in oxidative stress, inflammation and apoptosis, as well as the increased p70S6 Kinase 1 and decreased AMP-activated protein kinase expression. The decrease in superoxide dismutase activity by iron treatment was prevented by pre-treatment with SDG in the presence of iron. Based on these findings we conclude that SDG was cytoprotective in an in vitro model of iron overload induced redox-inflammatory damage, suggesting a novel potential role for SDG in cardiac iron overload.
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Affiliation(s)
- Stephanie Puukila
- Department of Biology, Lakehead University, Thunder Bay, Ontario, Canada
| | - Sean Bryan
- Northern Ontario School of Medicine, Lakehead University, Thunder Bay, Ontario, Canada
| | - Anna Laakso
- Northern Ontario School of Medicine, Lakehead University, Thunder Bay, Ontario, Canada
| | | | - Carli Gurney
- Department of Biology, Lakehead University, Thunder Bay, Ontario, Canada
| | - Adrian Agostino
- Department of Biology, Lakehead University, Thunder Bay, Ontario, Canada
| | - Adriane Belló-Klein
- Department of Physiology, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | - Kailash Prasad
- Department of Physiology, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
| | - Neelam Khaper
- Northern Ontario School of Medicine, Lakehead University, Thunder Bay, Ontario, Canada
- * E-mail:
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Cheong BYC, Angelini P. Magnetic Resonance Imaging of the Myocardium, Coronary Arteries, and Anomalous Origin of Coronary Arteries. Coron Artery Dis 2015. [DOI: 10.1007/978-1-4471-2828-1_13] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
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El Sayed SM, Abou-Taleb A, Mahmoud HS, Baghdadi H, Maria RA, Ahmed NS, Nabo MMH. Percutaneous excretion of iron and ferritin (through Al-hijamah) as a novel treatment for iron overload in beta-thalassemia major, hemochromatosis and sideroblastic anemia. Med Hypotheses 2014; 83:238-46. [PMID: 24857772 DOI: 10.1016/j.mehy.2014.04.001] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2013] [Revised: 09/25/2013] [Accepted: 04/01/2014] [Indexed: 11/24/2022]
Abstract
Iron overload is a big challenge when treating thalassemia (TM), hemochromatosis and sideroblastic anemia. It persists even after cure of TM with bone marrow transplantation. Iron overload results from increased iron absorption and repeated blood transfusions causing increased iron in plasma and interstitial fluids. Iron deposition in tissues e.g. heart, liver, endocrine glands and others leads to tissue damage and organ dysfunction. Iron chelation therapy and phlebotomy for iron overload have treatment difficulties, side effects and contraindications. As mean iron level in skin of TM patients increases by more than 200%, percutaneous iron excretion may be beneficial. Wet cupping therapy (WCT) is a simple, safe and economic treatment. WCT is a familiar treatment modality in some European countries and in Chinese hospitals in treating different diseases. WCT was reported to clear both blood plasma and interstitial spaces from causative pathological substances (CPS). Standard WCT method is Al-hijamah (cupping, puncturing and cupping, CPC) method of WCT that was reported to clear blood and interstitial fluids better than the traditional WCT (puncturing and cupping method, PC method of WCT). In other word, traditional WCT may be described as scarification and suction method (double S technique), while Al-hijamah may be described as suction, scarification and suction method (triple S technique). Al-hijamah is a more comprehensive treatment modality that includes all steps and therapeutic benefits of traditional dry cupping therapy and WCT altogether according to the evidence-based Taibah mechanism (Taibah theory). During the first cupping step of Al-hijamah, a fluid mixture is collected inside skin uplifting due to the effect of negative pressure inside sucking cups. This fluid mixture contains collected interstitial fluids with CPS (iron, ferritin and hemolyzed RBCs in thalassemia), filtered fluids (from blood capillaries) with iron and hemolyzed blood cells (hemolyzed RBCs, WBCs and platelets). That fluid mixture does not contain intact blood cells (having diameters in microns) that are too big to pass through pores of skin capillaries (6-12nm in diameter) and cannot be filtered. Puncturing skin upliftings and applying second cupping step excrete collected fluids. Skin scarifications (shartat mihjam in Arabic) should be small, superficial (0.1mm in depth), short (1-2mm in length), multiple, evenly distributed and confined to skin upliftings. Sucking pressure inside cups (-150 to -420mmHg) applied to skin is transmitted to around skin capillaries to be added to capillary hydrostatic pressure (-33mmHg at arterial end of capillaries and -13mmHg at venous end of capillaries) against capillary osmotic pressure (+20mmHg). This creates a pressure gradient and a traction force across skin and capillaries and increases filtration at arterial end of capillaries at net pressure of -163 to -433mmHg and at venous end of capillaries at net pressure of -143 to -413mmHg resulting in clearance of blood from CPS (iron, ferritin and hemolyzed blood cells). Net filtration pressure at renal glomeruli is 10mmHg i.e. Al-hijamah exerts a more pressure-dependent filtration than renal glomeruli. Al-hijamah may benefit patients through inducing negative iron balance. Interestingly, Al-hijamah was reported to decrease serum ferritin significantly (by about 22%) in healthy subjects while excessive traditional WCT was reported to cause iron deficiency anemia. Al-hijamah is a highly recommended treatment in prophetic medicine. In conclusion, Al-hijamah may be a promising adjuvant treatment for iron overload in TM, hemochromatosis and sideroblastic anemia.
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Affiliation(s)
- Salah Mohamed El Sayed
- Department of Clinical Biochemistry and Molecular Medicine, Taibah Faculty of Medicine, Taibah University, Al-Madinah Al-Munawwarah, Saudi Arabia. Department of Medical Biochemistry, Sohag Faculty of Medicine, Sohag University, Egypt
| | - Ashraf Abou-Taleb
- Department of Pediatrics, Sohag Faculty of Medicine, Sohag University, Egypt
| | - Hany Salah Mahmoud
- World Federation of Alternative and Complementary Medicine, Cairo Regional Headquarter, Cairo, Egypt
| | - Hussam Baghdadi
- Department of Clinical Biochemistry and Molecular Medicine, Taibah Faculty of Medicine, Taibah University, Al-Madinah Al-Munawwarah, Kingdom of Saudi Arabia
| | - Reham A Maria
- Department of Clinical Biochemistry and Molecular Medicine, Taibah Faculty of Medicine, Taibah University, Al-Madinah Al-Munawwarah, Kingdom of Saudi Arabia; Department of Medical Biochemistry, Tanta Faulty of Medicine, Tanta University, Egypt
| | - Nagwa Sayed Ahmed
- Department of Medical Biochemistry, Sohag Faculty of Medicine, Sohag University, Egypt
| | - Manal Mohamed Helmy Nabo
- Department of Pediatrics, Sohag Teaching Hospital, Sohag, Egypt; Division of Pediatric Cardiology, Department of Pediatrics, Maternity and Children Hospital, King Abdullah Medical City, Al-Madinah Al-Munawwarah, Kingdom of Saudi Arabia
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Abstract
Cardiac hemochromatosis or primary iron-overload cardiomyopathy is an important and potentially preventable cause of heart failure. This is initially characterized by diastolic dysfunction and arrhythmias and in later stages by dilated cardiomyopathy. Diagnosis of iron overload is established by elevated transferrin saturation (>55%) and elevated serum ferritin (>300 ng/mL). Genetic testing for mutations in the HFE (high iron) gene and other proteins, such as hemojuvelin, transferrin receptor, and ferroportin, should be performed if secondary causes of iron overload are ruled out. Patients should undergo comprehensive 2D and Doppler echocardiography to evaluate their systolic and diastolic function. Newer modalities like strain imaging and speckle-tracking echocardiography hold promise for earlier detection of cardiac involvement. Cardiac magnetic resonance imaging with measurement of T2* relaxation times can help quantify myocardial iron overload. In addition to its value in diagnosis of cardiac iron overload, response to iron reduction therapy can be assessed by serial imaging. Therapeutic phlebotomy and iron chelation are the cornerstones of therapy. The average survival is less than a year in untreated patients with severe cardiac impairment. However, if treated early and aggressively, the survival rate approaches that of the regular heart failure population.
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Affiliation(s)
- Vinay Gulati
- From the *Department of Medicine, University of Connecticut Health Center, Farmington, CT; and †Division of Cardiology, Department of Medicine, New York Medical College/Westchester Medical Center, Valhalla, NY
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Sripetchwandee J, KenKnight SB, Sanit J, Chattipakorn S, Chattipakorn N. Blockade of mitochondrial calcium uniporter prevents cardiac mitochondrial dysfunction caused by iron overload. Acta Physiol (Oxf) 2014; 210:330-41. [PMID: 24034353 DOI: 10.1111/apha.12162] [Citation(s) in RCA: 66] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2013] [Revised: 07/15/2013] [Accepted: 08/29/2013] [Indexed: 12/24/2022]
Abstract
AIM Iron overload in the heart can lead to iron-overload cardiomyopathy and cardiac arrhythmia. In the past decades, growing evidence has suggested that cardiac mitochondrial dysfunction is associated with the development of cardiac dysfunction and lethal arrhythmias. Despite these facts, the effect of iron overload on cardiac mitochondrial function is still unclear. In this study, we determined the effects of iron overload on the cardiac mitochondrial function and the routes of cardiac mitochondrial iron uptake. We tested the hypothesis that iron overload can lead to cardiac mitochondrial dysfunction and that mitochondrial calcium uniporter (MCU) plays a major role for cardiac mitochondrial iron uptake under iron-overload condition. Cardiac mitochondrial function was assessed via the determination of mitochondrial swelling, mitochondrial reactive oxygen species (ROS) production and mitochondrial membrane potential changes. METHODS Isolated cardiac mitochondria from male Wistar rats were used in this study. To determine the routes for cardiac mitochondrial iron uptake, isolated mitochondria were exposed to MCU blocker (Ru360), mitochondrial permeability transition pore (mPTP) blocker (cyclosporin A) and an iron chelator (deferoxamine). RESULTS We found that (i) iron overload caused cardiac mitochondrial dysfunction, indicated by increased ROS production, mitochondrial membrane depolarization and mitochondrial swelling; and (ii) only MCU blocker completely protected cardiac mitochondrial dysfunction caused by iron overload. CONCLUSIONS These findings strongly suggest that MCU could be the major route for iron uptake into cardiac mitochondria. The inhibition of MCU could be the novel pharmacological intervention for preventing iron-overload cardiomyopathy.
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Affiliation(s)
- J. Sripetchwandee
- Cardiac Electrophysiology Research and Training Center; Faculty of Medicine; Chiang Mai University; Chiang Mai Thailand
- Cardiac Electrophysiology Unit; Department of Physiology; Faculty of Medicine; Chiang Mai University; Chiang Mai Thailand
| | - S. B. KenKnight
- Cardiac Electrophysiology Research and Training Center; Faculty of Medicine; Chiang Mai University; Chiang Mai Thailand
- Cardiac Electrophysiology Unit; Department of Physiology; Faculty of Medicine; Chiang Mai University; Chiang Mai Thailand
| | - J. Sanit
- Cardiac Electrophysiology Research and Training Center; Faculty of Medicine; Chiang Mai University; Chiang Mai Thailand
- Cardiac Electrophysiology Unit; Department of Physiology; Faculty of Medicine; Chiang Mai University; Chiang Mai Thailand
| | - S. Chattipakorn
- Cardiac Electrophysiology Research and Training Center; Faculty of Medicine; Chiang Mai University; Chiang Mai Thailand
- Faculty of Dentistry; Chiang Mai University; Chiang Mai Thailand
| | - N. Chattipakorn
- Cardiac Electrophysiology Research and Training Center; Faculty of Medicine; Chiang Mai University; Chiang Mai Thailand
- Cardiac Electrophysiology Unit; Department of Physiology; Faculty of Medicine; Chiang Mai University; Chiang Mai Thailand
- Biomedical Engineering Center; Chiang Mai University; Chiang Mai Thailand
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Min J, Kim M, Kim M, Lee MS, Song E. Phosphorylation ofβsubunit in F1F0ATP synthase is associated with increased iron uptake in iron-overloaded heart mitochondria. Anim Cells Syst (Seoul) 2013. [DOI: 10.1080/19768354.2013.867901] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
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Ghahramanlu E, Banihashem A, Mirhossini NZ, Hosseini G, Mostafavi-Toroghi H, Tavallaie S, Meshkat M, Ghayour-Mobarhan M, Ferns G. Effect of zinc supplementation on serum antibody titers to heat shock protein 27 in patients with thalassemia major. Hematology 2013; 19:113-9. [DOI: 10.1179/1607845413y.0000000099] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Affiliation(s)
- Elham Ghahramanlu
- Blood Transfusion Research CenterHigh Institute for Research and Education in Transfusion Medicine, North Khorasan, Iran
| | - Abdollah Banihashem
- Hematology DepartmentSheikh Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Naghme-Zahra Mirhossini
- Biochemistry of Nutrition Research Center and Cardiovascular Research Center Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Golkoo Hosseini
- Biochemistry of Nutrition Research Center and Cardiovascular Research Center Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hesam Mostafavi-Toroghi
- Biochemistry of Nutrition Research Center and Cardiovascular Research Center Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Shima Tavallaie
- Biochemistry of Nutrition Research Center and Cardiovascular Research Center Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mojtaba Meshkat
- Department of BiostatisticsIslamic Azad University, Mashhad Branch, Mashhad, Iran
| | - Majid Ghayour-Mobarhan
- Biochemistry of Nutrition Research Center and Cardiovascular Research Center Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Gordon Ferns
- Institute for Science & Technology in Medicine, Faculty of Health, University of Keele, Staffordshire ST4 7QB, UK
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Cheng CF, Lian WS. Prooxidant mechanisms in iron overload cardiomyopathy. BIOMED RESEARCH INTERNATIONAL 2013; 2013:740573. [PMID: 24350287 PMCID: PMC3852805 DOI: 10.1155/2013/740573] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/05/2013] [Accepted: 10/28/2013] [Indexed: 12/22/2022]
Abstract
Iron overload cardiomyopathy (IOC), defined as the presence of systolic or diastolic cardiac dysfunction secondary to increased deposition of iron, is emerging as an important cause of heart failure due to the increased incidence of this disorder seen in thalassemic patients and in patients of primary hemochromatosis. At present, although palliative treatment by regular iron chelation was recommended; whereas IOC is still the major cause for mortality in patient with chronic heart failure induced by iron-overloading. Because iron is a prooxidant and the associated mechanism seen in iron-overload heart is still unclear; therefore, we intend to delineate the multiple signaling pathways involved in IOC. These pathways may include organelles such as calcium channels, mitochondria; paracrine effects from both macrophages and fibroblast, and novel mediators such as thromboxane A2 and adiponectin; with increased oxidative stress and inflammation found commonly in these signaling pathways. With further understanding on these complex and inter-related molecular mechanisms, we can propose potential therapeutic strategies to ameliorate the cardiac toxicity induced by iron-overloading.
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Affiliation(s)
- Ching-Feng Cheng
- Department of Medical Research, Tzu Chi General Hospital and Department of Pediatrics, Tzu Chi University, Hualien, Taiwan
- Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
| | - Wei-Shiung Lian
- Department of Medical Research, Tzu Chi General Hospital and Department of Pediatrics, Tzu Chi University, Hualien, Taiwan
- Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
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