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Xu H, Yu Z, Zhu J, Liu H, Chen X, Jiang J, Zhu M, Li J. Types of cell death in diabetic cardiomyopathy: insights from animal models. Acta Biochim Biophys Sin (Shanghai) 2024. [PMID: 39719881 DOI: 10.3724/abbs.2024213] [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: 12/26/2024] Open
Abstract
Approximately one-tenth of the global population is affected by diabetes mellitus, and its incidence continues to rise each year. In China, 1.4 million patients die from diabetes-related complications every year. Additionally, approximately 26% of patients with diabetes develop diabetic cardiomyopathy, with heart failure being one of the main causes of death in these patients. However, early detection of diabetic cardiomyopathy has proven to be difficult in a clinical setting; furthermore, there are limited guidelines and targeted means of prevention and treatment for this disease. In recent years, several studies have provided evidence for the occurrence of various forms of regulated cell death in diabetic myocardial cells, including apoptosis, necroptosis, ferroptosis, and cuproptosis, which are closely linked to the pathological progression of diabetic cardiomyopathy. Although most research on diabetic cardiomyopathy is currently in the animal trial phase, the inhibition of these regulatory cell death processes can limit or slow down the progression of diabetic cardiomyopathy. Therefore, this review discusses the appropriate animal experimental models currently available for diabetic cardiomyopathy and evaluates the roles of apoptosis, necroptosis, ferroptosis, and cuproptosis in diabetic cardiomyopathy. We hope to provide new methods and ideas for future research in diabetic cardiomyopathy.
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Affiliation(s)
- Hongjiao Xu
- Department of Anesthesiology, Shanghai General Hospital of Nanjing Medical University, Shanghai 200080, China
| | - Zhuang Yu
- Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
| | - Jun Zhu
- Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
| | - Haoran Liu
- Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
| | - Xiangyuan Chen
- Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
| | - Jihong Jiang
- Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
| | - Minmin Zhu
- Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
| | - Jinbao Li
- Department of Anesthesiology, Shanghai General Hospital of Nanjing Medical University, Shanghai 200080, China
- Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
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Yeo JL, Dattani A, Bilak JM, Wood AL, Athithan L, Deshpande A, Singh A, Arnold JR, Brady EM, Adlam D, Biglands JD, Kellman P, Xue H, Yates T, Davies MJ, Gulsin GS, McCann GP. Sex differences and determinants of coronary microvascular function in asymptomatic adults with type 2 diabetes. J Cardiovasc Magn Reson 2024; 27:101132. [PMID: 39647765 PMCID: PMC11761338 DOI: 10.1016/j.jocmr.2024.101132] [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: 11/11/2023] [Revised: 11/24/2024] [Accepted: 12/03/2024] [Indexed: 12/10/2024] Open
Abstract
BACKGROUND Coronary microvascular dysfunction (CMD) is a significant complication in type 2 diabetes (T2D) and may be more common in women. We aimed to evaluate the sex differences and sex-specific clinical determinants of CMD in adults with T2D without prevalent cardiovascular disease. METHODS Single center pooled analysis of four prospective studies comparing asymptomatic people with T2D and controls. All subjects underwent comprehensive cardiovascular phenotyping with myocardial perfusion reserve (MPR) quantified with perfusion cardiovascular magnetic resonance (CMR). Participants with silent coronary disease were excluded. Multivariable linear regression was performed to identify determinants of MPR with an interaction term for sex. RESULTS Four hundred and seventy-nine T2D (age 57 ± 11 years, 42% [202/479] women) were compared with 116 controls (age 53 ± 11 years, 41% [48/116] women). Men with T2D, but not women, demonstrated worse systolic function and higher extracellular volume fraction than controls. MPR was significantly lower in T2D than controls (women, 2.6 ± 0.9 vs 3.3 ± 1.0, p < 0.001; men, 3.1 ± 0.9 vs 3.5 ± 1.0, p = 0.004), and lower in women than men with T2D (p < 0.001). More women than men with T2D had MPR <2.5 (46% [79/202] vs 26% [64/277], p < 0.001). There was a significant interaction between sex and body mass index (BMI) for MPR (p interaction <0.001). Following adjustment for clinical risk factors, inverse association with MPR were BMI in women (β = -0.17, p = 0.045) and systolic blood pressure in men (β = -0.14, p = 0.049). CONCLUSION Among asymptomatic adults with T2D, women had a greater prevalence of CMD than men. Risk factors modestly but significantly associated with CMD in asymptomatic people with T2D were BMI among women and systolic blood pressure among men.
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Affiliation(s)
- Jian L Yeo
- Department of Cardiovascular Sciences, University of Leicester and the National Institute for Health and Care Research (NIHR) Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, United Kingdom
| | - Abhishek Dattani
- Department of Cardiovascular Sciences, University of Leicester and the National Institute for Health and Care Research (NIHR) Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, United Kingdom
| | - Joanna M Bilak
- Department of Cardiovascular Sciences, University of Leicester and the National Institute for Health and Care Research (NIHR) Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, United Kingdom
| | - Alice L Wood
- Department of Cardiovascular Sciences, University of Leicester and the National Institute for Health and Care Research (NIHR) Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, United Kingdom
| | - Lavanya Athithan
- Department of Cardiovascular Sciences, University of Leicester and the National Institute for Health and Care Research (NIHR) Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, United Kingdom
| | - Aparna Deshpande
- Radiology, University Hospitals of Leicester NHS Trust, Leicester, United Kingdom
| | - Anvesha Singh
- Department of Cardiovascular Sciences, University of Leicester and the National Institute for Health and Care Research (NIHR) Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, United Kingdom
| | - J Ranjit Arnold
- Department of Cardiovascular Sciences, University of Leicester and the National Institute for Health and Care Research (NIHR) Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, United Kingdom
| | - Emer M Brady
- Department of Cardiovascular Sciences, University of Leicester and the National Institute for Health and Care Research (NIHR) Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, United Kingdom
| | - David Adlam
- Department of Cardiovascular Sciences, University of Leicester and the National Institute for Health and Care Research (NIHR) Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, United Kingdom
| | - John D Biglands
- NIHR Leeds Biomedical Research Centre and Medical Physics and Engineering, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom
| | - Peter Kellman
- National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
| | - Hui Xue
- National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
| | - Thomas Yates
- Diabetes Research Centre, University of Leicester and the NIHR Leicester Biomedical Research Centre, Leicester General Hospital, Leicester, United Kingdom
| | - Melanie J Davies
- Diabetes Research Centre, University of Leicester and the NIHR Leicester Biomedical Research Centre, Leicester General Hospital, Leicester, United Kingdom
| | - Gaurav S Gulsin
- Department of Cardiovascular Sciences, University of Leicester and the National Institute for Health and Care Research (NIHR) Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, United Kingdom
| | - Gerry P McCann
- Department of Cardiovascular Sciences, University of Leicester and the National Institute for Health and Care Research (NIHR) Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, United Kingdom.
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Jianghua H, Feier M, Dong Z, Qiuying L, Ya W, Yan W. Meta-analysis of the effects of different exercise modes on cardiac function and peak oxygen uptake in patients with type 2 diabetes mellitus. Front Physiol 2024; 15:1448385. [PMID: 39600919 PMCID: PMC11588746 DOI: 10.3389/fphys.2024.1448385] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Accepted: 10/25/2024] [Indexed: 11/29/2024] Open
Abstract
Background The benefits of exercise for primary and secondary prevention of cardiovascular events have been reported in patients with type 2 diabetes mellitus (T2DM). However, the effects of exercise on cardiac structure and function require clarification. Methods A literature search for clinical studies reporting on the effects of exercise on cardiac structure, cardiac function, and VO2peak in T2DM patients was conducted. PubMed, Embase, EBSCO, Web of Science, and China National Knowledge Infrastructure were systematically searched for original articles published from January 2000 to July 2023. The effect size was expressed as the mean difference (MD) or standardized mean difference (SMD) and its 95% confidence interval (CI). Subgroup analyses were performed by exercise mode (high-intensity interval training [HIIT] or moderate-intensity continuous training [MICT]) and intervention duration (>6 or ≤6 months). Results Compared to usual care, both HIIT and MICT significantly affected left ventricular end-diastolic volume (MD: 19.44, 95% CI: 13.72 to 25.17, p < 0.00001; I2 = 42%; MD: 13.90, 95% CI: 7.64 to 20.16, p < 0.0001; I2 = 0%), but only HIIT significantly affected left ventricular mass (MD: 17.04 g, 95% CI: 5.45 to 28.62, p = 0.004; I2 = 0%). HIIT significantly improved left ventricular ejection fraction (MD: 5.52, 95% CI: 2.31 to 8.73, p = 0.0008; I2 = 0%), as did MICT in the ≤6 months subgroup (MD: 1.36, 95% CI: 0.61 to 2.10, p = 0.0004; I2 = 0%). Neither significantly affected systolic tissue velocity. HIIT significantly improved VO2peak (MD: 8.04, 95% CI: 6.26 to 9.83, p < 0.00001; I2 = 0%), as did MICT in the ≤6 months subgroup (MD: 3.33, 95% CI: 2.39 to 4.27, p < 0.00001; I2 = 0%). Conclusion Exercise significantly improved cardiac structure, systolic function, and VO2peak, but did not significantly affect diastolic function in T2DM patients. HIIT seemed to be superior to MICT at improving VO2peak and left ventricular ejection fraction in T2DM patients. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, PROSPERO registration no.: CRD4242018087376.
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Affiliation(s)
- He Jianghua
- School of Sports Medicine and Rehabilitation, Beijing Sport University, Beijing, China
| | - Ma Feier
- School of Sports Medicine and Rehabilitation, Beijing Sport University, Beijing, China
| | - Zhu Dong
- College of Sports Medicine and Healthcare, Hunan University of Medicine, Huaihua, China
| | - Li Qiuying
- College of Sports Medicine and Healthcare, Hunan University of Medicine, Huaihua, China
| | - Wen Ya
- College of Sports Medicine and Healthcare, Hunan University of Medicine, Huaihua, China
| | - Wang Yan
- School of Sports Medicine and Rehabilitation, Beijing Sport University, Beijing, China
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Shu H, Xu H, Pan Z, Liu Y, Deng W, Zhao R, Sun Y, Wang Z, Yang J, Gao H, Yao K, Zheng J, Yu Y, Li X. Early detection of myocardial involvement by non-contrast T1ρ mapping of cardiac magnetic resonance in type 2 diabetes mellitus. Front Endocrinol (Lausanne) 2024; 15:1335899. [PMID: 38510696 PMCID: PMC10952821 DOI: 10.3389/fendo.2024.1335899] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Accepted: 02/07/2024] [Indexed: 03/22/2024] Open
Abstract
Objective This study aims to determine the effectiveness of T1ρ in detecting myocardial fibrosis in type 2 diabetes mellitus (T2DM) patients by comparing with native T1 and extracellular volume (ECV) fraction. Methods T2DM patients (n = 35) and healthy controls (n = 30) underwent cardiac magnetic resonance. ECV, T1ρ, native T1, and global longitudinal strain (GLS) values were assessed. Diagnostic performance was analyzed using receiver operating curves. Results The global ECV and T1ρ of T2DM group (ECV = 32.1 ± 3.2%, T1ρ = 51.6 ± 3.8 msec) were significantly higher than those of controls (ECV = 26.2 ± 1.6%, T1ρ = 46.8 ± 2.0 msec) (all P < 0.001), whether there was no significant difference in native T1 between T2DM and controls (P = 0.264). The GLS decreased significantly in T2DM patients compared with controls (-16.5 ± 2.4% vs. -18.3 ± 2.6%, P = 0.015). The T1ρ and native T1 were associated with ECV (Pearson's r = 0.50 and 0.25, respectively, both P < 0.001); the native T1, T1ρ, and ECV were associated with hemoglobin A1c (Pearson's r = 0.41, 0.52, and 0.61, respectively, all P < 0.05); and the ECV was associated with diabetes duration (Pearson's r = 0.41, P = 0.016). The AUC of ECV, T1ρ, GLS, and native T1 were 0.869, 0.810, 0.659, and 0.524, respectively. Conclusion In T2DM patients, T1ρ may be a new non-contrast cardiac magnetic resonance technique for identifying myocardial diffuse fibrosis, and T1ρ may be more sensitive than native T1 in the detection of myocardial diffuse fibrosis.
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Affiliation(s)
- Hongmin Shu
- Department of Radiology, the First Affiliated Hospital of Anhui Medical University, Research Center of Clinical Medical Imaging, Anhui Province Clinical Image Quality Control Center, Hefei, Anhui, China
| | - Huimin Xu
- Department of Radiology, the First Affiliated Hospital of Anhui Medical University, Research Center of Clinical Medical Imaging, Anhui Province Clinical Image Quality Control Center, Hefei, Anhui, China
| | - Zixiang Pan
- Department of Radiology, the First Affiliated Hospital of Anhui Medical University, Research Center of Clinical Medical Imaging, Anhui Province Clinical Image Quality Control Center, Hefei, Anhui, China
| | - Yan Liu
- Department of Radiology, the First Affiliated Hospital of Anhui Medical University, Research Center of Clinical Medical Imaging, Anhui Province Clinical Image Quality Control Center, Hefei, Anhui, China
| | - Wei Deng
- Department of Radiology, the First Affiliated Hospital of Anhui Medical University, Research Center of Clinical Medical Imaging, Anhui Province Clinical Image Quality Control Center, Hefei, Anhui, China
| | - Ren Zhao
- Department of Cardiology, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Yan Sun
- Department of Geriatric Endocrinology, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Zhen Wang
- Department of Radiology, the First Affiliated Hospital of Anhui Medical University, Research Center of Clinical Medical Imaging, Anhui Province Clinical Image Quality Control Center, Hefei, Anhui, China
| | - Jinxiu Yang
- Department of Radiology, the First Affiliated Hospital of Anhui Medical University, Research Center of Clinical Medical Imaging, Anhui Province Clinical Image Quality Control Center, Hefei, Anhui, China
| | - Hui Gao
- Department of Radiology, the First Affiliated Hospital of Anhui Medical University, Research Center of Clinical Medical Imaging, Anhui Province Clinical Image Quality Control Center, Hefei, Anhui, China
| | - Kaixuan Yao
- Department of Radiology, the First Affiliated Hospital of Anhui Medical University, Research Center of Clinical Medical Imaging, Anhui Province Clinical Image Quality Control Center, Hefei, Anhui, China
| | - Jie Zheng
- Mallinckrodt Institute of Radiology, Washington University School of Medicine in St. Louis, St. Louis, MO, United States
| | - Yongqiang Yu
- Department of Radiology, the First Affiliated Hospital of Anhui Medical University, Research Center of Clinical Medical Imaging, Anhui Province Clinical Image Quality Control Center, Hefei, Anhui, China
| | - Xiaohu Li
- Department of Radiology, the First Affiliated Hospital of Anhui Medical University, Research Center of Clinical Medical Imaging, Anhui Province Clinical Image Quality Control Center, Hefei, Anhui, China
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Dattani A, Singh A, McCann GP, Gulsin GS. Myocardial Calcium Handling in Type 2 Diabetes: A Novel Therapeutic Target. J Cardiovasc Dev Dis 2023; 11:12. [PMID: 38248882 PMCID: PMC10817027 DOI: 10.3390/jcdd11010012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Revised: 12/20/2023] [Accepted: 12/28/2023] [Indexed: 01/23/2024] Open
Abstract
Type 2 diabetes (T2D) is a multisystem disease with rapidly increasing global prevalence. Heart failure has emerged as a major complication of T2D. Dysregulated myocardial calcium handling is evident in the failing heart and this may be a key driver of cardiomyopathy in T2D, but until recently this has only been demonstrated in animal models. In this review, we describe the physiological concepts behind calcium handling within the cardiomyocyte and the application of novel imaging techniques for the quantification of myocardial calcium uptake. We take an in-depth look at the evidence for the impairment of calcium handling in T2D using pre-clinical models as well as in vivo studies, following which we discuss potential novel therapeutic approaches targeting dysregulated myocardial calcium handling in T2D.
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Affiliation(s)
- Abhishek Dattani
- Department of Cardiovascular Sciences, University of Leicester and NIHR Leicester Biomedical Research Centre, Leicester LE3 9QP, UK; (A.S.); (G.P.M.); (G.S.G.)
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Li N, Zhao M, Yuan L, Chen Y, Zhou H. Association between glycosylated hemoglobin levels, diabetes duration, and left ventricular diastolic dysfunction in patients with type 2 diabetes and preserved ejection fraction: a cross-sectional study. Front Endocrinol (Lausanne) 2023; 14:1326891. [PMID: 38174338 PMCID: PMC10761463 DOI: 10.3389/fendo.2023.1326891] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Accepted: 12/01/2023] [Indexed: 01/05/2024] Open
Abstract
Background We aimed to explore the intricate interplay between glycated hemoglobin (HbA1C) levels, disease duration, and left ventricular diastolic dysfunction in patients with type 2 diabetes mellitus (T2DM) characterized by preserved ejection fraction. Methods A cross-sectional study was conducted at the Second Affiliated Hospital of Hebei Medical University from January 2022 to December 2022. A total of 114 inpatients from the Department of Endocrinology were randomly selected based on the inclusion and exclusion criteria. Patients with T2DM were stratified into three subgroups, each comprising 38 patients, based on disease duration and HbA1C levels. A sub-analysis was conducted to explore variations among these three distinct groups. A control group comprised 38 age, gender, body mass index (BMI), and smoking habit-matched healthy volunteers form the Physical Examination Center of the same hospital. General demographic information, biochemical results, and echocardiographic data were collected, and correlation and linear regression analyses were performed. Results Diabetic patients exhibited lower E/A values (0.85 (0.72, 1.17) vs. 1.20 (0.97, 1.30)) and elevated E/e' values (9.50 (8.75, 11.00) vs. 9.00 (7.67, 9.85)) compared to their normal controls. In the subgroup analysis, patients with a disease duration exceeding 2 years displayed reduced E/A values (0.85 (0.75, 1.10) vs. 1.10 (0.80, 1.30)) and elevated E/e' values (9.80 (9.20, 10.80) vs. 8.95 (7.77, 9.50)) in comparison to those with a disease duration of ≤2 years, p<0.05. Among patients with a disease duration surpassing 2 years, those with higher HbA1C levels exhibited lower E/A values (0.80 (0.70, 0.90) vs. (0.85 (0.75, 1.10)) and higher E/e' values (11.00 (9.87, 12.15) vs. 9.80 (9.20, 10.80)) in contrast to patients with low HbA1C levels, p<0.05. Multiple linear regression analysis identified HbA1C (β=0.294, p<0.001) and disease duration (β=0.319, p<0.001) as independent risk factors for the E/A value in diabetes patients. Furthermore, HbA1C (β=0.178, p=0.015) and disease duration (β=0.529, p<0.001) emerged as independent risk factors for the E/e' value in diabetic patients. Conclusions In individuals with T2DM exhibiting preserved ejection fraction, the presence of left ventricular diastolic dysfunction is significantly associated with HbA1C levels and the duration of diabetes.
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Affiliation(s)
| | | | | | | | - Hong Zhou
- Department of Endocrinology, the Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
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Wei L, Dong JX, Jin LX, He J, Zhao CX, Kong LC, An DAL, Ding S, Yang F, Yang YN, Yan FH, Xiu JC, Wang HW, Ge H, Pu J. Peak early diastolic strain rate improves prediction of adverse cardiovascular outcomes in patients with ST-elevation myocardial infarction. LA RADIOLOGIA MEDICA 2023; 128:1372-1385. [PMID: 37640898 DOI: 10.1007/s11547-023-01700-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Accepted: 08/09/2023] [Indexed: 08/31/2023]
Abstract
BACKGROUND The prognostic role of diastolic dysfunction measured by the circumferential peak early diastolic strain rate (PEDSR) on ST-elevation myocardial infarction (STEMI) is not completely established. OBJECTIVES We aimed to investigate the prognostic value of diastolic function by measuring PEDSR within 1 week after STEMI. METHODS The cardiac magnetic resonance (CMR) pictures of 420 subjects from a clinical registry study (NCT03768453) were analyzed and the composite major adverse cardiac events (MACEs) were followed up. RESULTS The PEDSR of patients was significantly lower compared with that of control subjects (P < 0.001). Within the median follow-up period of 52 months, PEDSR of patients who experienced MACEs deceased more significantly than that of patients without MACEs (P < 0.001). After adjusting with clinical or CMR indexes, per 0.1/s reduction of PEDSR increased the risks of MACEs to 1.402 or 1.376 fold and the risk of left ventricular (LV) remodeling to 1.503 or 1.369 fold. When PEDSR divided by best cutoff point, significantly higher risk of MACEs (P < 0.001) and more remarkable LV remodeling (P < 0.001) occurred in patients with PEDSR ≤ 0.485/s. Moreover, when adding the PEDSR to the conventional prognostic factors such as LV ejection fraction and infarction size, better prognostic risk classification models were created. Finally, aging, tobacco use, remarkable LV remodeling, and a low LV ejection fraction were factors related with the reduction of PEDSR. CONCLUSIONS Diastolic dysfunction has an important prognostic effect on patients with STEMI. Measurement of the PEDSR in the acute phase could serve as an effective index to predict the long-term risk of MACEs and cardiac remodeling.
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Affiliation(s)
- Lai Wei
- Department of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Jian-Xun Dong
- Department of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Li-Xing Jin
- Department of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Jie He
- Department of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Chen-Xu Zhao
- Department of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Ling-Cong Kong
- Department of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Dong-Ao-Lei An
- Department of Radiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Song Ding
- Department of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Fan Yang
- Department of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yi-Ning Yang
- The First Affiliated Hospital, Xinjiang Medical University, Wulumuqi, China
| | - Fu-Hua Yan
- Department of Radiology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Jian-Cheng Xiu
- Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Hu-Wen Wang
- Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong, Hong Kong Special Administrative Region, China
| | - Heng Ge
- Department of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
| | - Jun Pu
- Department of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
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Li Z, Han D, Qi T, Deng J, Li L, Gao C, Gao W, Chen H, Zhang L, Chen W. Hemoglobin A1c in type 2 diabetes mellitus patients with preserved ejection fraction is an independent predictor of left ventricular myocardial deformation and tissue abnormalities. BMC Cardiovasc Disord 2023; 23:49. [PMID: 36698087 PMCID: PMC9878773 DOI: 10.1186/s12872-023-03082-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Accepted: 01/18/2023] [Indexed: 01/27/2023] Open
Abstract
BACKGROUND Early detection of subclinical myocardial dysfunction in patients with type 2 diabetes mellitus (T2DM) is essential for preventing heart failure. This study aims to search for predictors of left ventricular (LV) myocardial deformation and tissue abnormalities in T2DM patients with preserved ejection fraction by using CMR T1 mapping and feature tracking. METHODS 70 patients and 44 sex- and age-matched controls (Cs) were recruited and underwent CMR examination to obtain LV myocardial extracellular volume fraction (ECV) and global longitudinal strain (GLS). The patients were subdivided into three groups, including 19 normotensive T2DM patients (G1), 19 hypertensive T2DM patients (G2) and 32 hypertensive patients (HT). The baseline biochemical indices were collected before CMR examination. RESULTS LV ECV in T2DM patients was significantly higher than that in Cs (30.75 ± 3.65% vs. 26.33 ± 2.81%; p < 0.05). LV GLS in T2DM patients reduced compared with that in Cs (-16.51 ± 2.53% vs. -19.66 ± 3.21%, p < 0.001). In the subgroup analysis, ECV in G2 increased compared with that in G1 (31.92 ± 3.05% vs. 29.59 ± 3.90%, p = 0.032) and that in HT, too (31.92 ± 3.05% vs. 29.22 ± 6.58%, p = 0.042). GLS in G2 significantly reduced compared with that in G1 (-15.75 ± 2.29% vs. -17.27 ± 2.57%, p < 0.05) and in HT, too (-15.75 ± 2.29% vs. -17.54 ± 3.097%, p < 0.05). In T2DM group, including both G1 and G2, hemoglobin A1c (HbA1c) can independently forecast the increase in ECV (β = 0.274, p = 0.001) and decrease in GLS (β = 0.383, p = 0.018). CONCLUSIONS T2DM patients with preserved ejection fraction show increased ECV but deteriorated GLS, which may be exacerbated by hypertension of these patients. Hemoglobin A1c is an index that can independently predict T2DM patients' LV myocardial deformation and tissue abnormalities.
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Affiliation(s)
- Zhiming Li
- Department of Radiology, First Affiliated Hospital of Kunming Medical University, 295 Xichang Road, Kunming, 650032, China
| | - Dan Han
- Department of Radiology, First Affiliated Hospital of Kunming Medical University, 295 Xichang Road, Kunming, 650032, China
| | - Tianfu Qi
- Department of Radiology, First Affiliated Hospital of Kunming Medical University, 295 Xichang Road, Kunming, 650032, China
| | - Jie Deng
- Department of Radiology, First Affiliated Hospital of Kunming Medical University, 295 Xichang Road, Kunming, 650032, China
| | - Lili Li
- Department of Radiology, First Affiliated Hospital of Kunming Medical University, 295 Xichang Road, Kunming, 650032, China
| | - Chao Gao
- Department of Radiology, First Affiliated Hospital of Kunming Medical University, 295 Xichang Road, Kunming, 650032, China
| | - Wei Gao
- Department of Radiology, First Affiliated Hospital of Kunming Medical University, 295 Xichang Road, Kunming, 650032, China
- Department of Radiology, First People's Hospital of Honghe State, 1 Xiyuan Road, Honghe, 661100, China
| | - Haiyan Chen
- Department of Radiology, First Affiliated Hospital of Kunming Medical University, 295 Xichang Road, Kunming, 650032, China
| | - Lihua Zhang
- Department of General Medicine, First Affiliated Hospital of Kunming Medical University, 295 Xichang Road, Kunming, 650032, China.
| | - Wei Chen
- Department of Radiology, First Affiliated Hospital of Kunming Medical University, 295 Xichang Road, Kunming, 650032, China.
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Exploring the Role of Obesity in Dilated Cardiomyopathy Based on Bio-informatics Analysis. J Cardiovasc Dev Dis 2022; 9:jcdd9120462. [PMID: 36547458 PMCID: PMC9783214 DOI: 10.3390/jcdd9120462] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Revised: 12/08/2022] [Accepted: 12/13/2022] [Indexed: 12/23/2022] Open
Abstract
(1) Background: Obesity is a major risk factor for cardiovascular disease (CVD), contributing to increasing global disease burdens. Apart from heart failure, coronary artery disease, and arrhythmia, recent research has found that obesity also elevates the risk of dilated cardiomyopathy (DCM). The main purpose of this study was to investigate the underlying biological role of obesity in increasing the risk of DCM. (2) Methods: The datasets GSE120895, GSE19303, and GSE2508 were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were analyzed using GSE120895 for DCM and GSE2508 for obesity, and the findings were compiled to discover the common genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted for the common genes in RStudio. In addition, CIBERSORT was used to obtain the immune cellular composition from DEGs. The key genes were identified in the set of common genes by the least absolute shrinkage and selection operator (LASSO) algorithm, the prognostic risk models of which were verified by receiver operator characteristic (ROC) curves in GSE19303. Finally, Spearman's correlation was used to explore the connections between key genes and immune cells. (3) Results: GO and KEGG pathway enrichment analyses showed that the main enriched terms of the common genes were transforming growth factor-beta (TGF-β), fibrillar collagen, NADPH oxidase activity, and multiple hormone-related signaling pathways. Both obesity and DCM had a disordered immune environment, especially obesity. The key genes NOX4, CCDC80, COL1A2, HTRA1, and KLHL29 may be primarily responsible for the changes. Spearman's correlation analysis performed for key genes and immune cells indicated that KLHL29 closely correlated to T cells and M2 macrophages, and HTRA1 very tightly correlated to plasma cells. (4) Conclusions: Bio-informatics analyses performed for DCM and obesity in our study suggested that obesity disturbed the immune micro-environment, promoted oxidative stress, and increased myocardial fibrosis, resulting in ventricular remodeling and an increased risk of DCM. The key genes KLHL29 and HTRA1 may play critical roles in obesity-related DCM.
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10
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Myocardial tissue characterization by cardiovascular magnetic resonance T1 mapping and pericardial fat quantification in adolescents with morbid obesity. Cardiac dimorphism by gender. Int J Cardiovasc Imaging 2022; 39:781-792. [PMID: 36508057 DOI: 10.1007/s10554-022-02773-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Accepted: 11/30/2022] [Indexed: 12/14/2022]
Abstract
PURPOSE Changes in the myocardial extracellular matrix (ECM) identified using T1 mapping cardiovascular magnetic resonance (CMR) have been only reported in obese adults, but with opposite conclusions. The objectives are to assess the composition of the myocardial ECM in an obese pediatric population without type 2 diabetes by quantifying native T1 time, and to quantify the pericardial fat index (PFI) and their relationship with cardiovascular risk factors. METHODS Observational case-control research of 25 morbidly obese adolescents and 13 normal-weight adolescents. Native T1 and T2 times (ms), left ventricular (LV) geometry and function, PFI (g/ht3) and hepatic fat fraction (HFF, %) were calculated by 1.5-T CMR. RESULTS No differences were noticed in native T1 between obese and non-obese adolescents (1000.0 vs. 990.5 ms, p0.73), despite showing higher LV mass values (28.3 vs. 22.9 g/ht3, p0.01). However, the T1 mapping values were significantly higher in females (1012.7 vs. 980.7 ms, p < 0.01) while in males, native T1 was better correlated with obesity parameters, particularly with triponderal mass index (TMI) (r = 0.51), and inflammatory cells. Similarly, the PFI was correlated with insulin resistance (r = 0.56), highly sensitive C-reactive protein (r = 0.54) and TMI (r = 0.77). CONCLUSION Female adolescents possess myocardium peculiarities associated with higher mapping values. In males, who are commonly more exposed to future non-communicable diseases, TMI may serve as a useful predictor of native T1 and pericardial fat increases. Furthermore, HFF and PFI appear to be markers of adipose tissue infiltration closely related with hypertension, insulin resistance and inflammation.
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11
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Interpretation of pre-morbid cardiac 3T MRI findings in overweight and hypertensive young adults. PLoS One 2022; 17:e0278308. [PMID: 36454872 PMCID: PMC9714856 DOI: 10.1371/journal.pone.0278308] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Accepted: 11/15/2022] [Indexed: 12/02/2022] Open
Abstract
In young adults, overweight and hypertension possibly already trigger cardiac remodeling as seen in mature adults, potentially overlapping non-ischemic cardiomyopathy findings. To this end, in young overweight and hypertensive adults, we aimed to investigate changes in left ventricular mass (LVM) and cardiac volumes, and the impact of different body scales for indexation. We also aimed to explore the presence of myocardial fibrosis, fat and edema, and changes in cellular mass with extracellular volume (ECV), T1 and T2 tissue characteristics. We prospectively recruited 126 asymptomatic subjects (51% male) aged 27-41 years for 3T cardiac magnetic resonance imaging: 40 controls, 40 overweight, 17 hypertensive and 29 hypertensive overweight. Myocyte mass was calculated as (100%-ECV) * height2.7-indexed LVM. Absolute LVM was significantly increased in overweight, hypertensive and hypertensive overweight groups (104 ± 23, 109 ± 27, 112 ± 26 g) versus controls (87 ± 21 g), with similar volumes. Body surface area (BSA) indexation resulted in LVM normalization in overweights (48 ± 8 g/m2) versus controls (47 ± 9 g/m2), but not in hypertensives (55 ± 9 g/m2) and hypertensive overweights (52 ± 9 g/m2). BSA-indexation overly decreased volumes in overweight versus normal-weight (LV end-diastolic volume; 80 ± 14 versus 92 ± 13 ml/m2), where height2.7-indexation did not. All risk groups had lower ECV (23 ± 2%, 23 ± 2%, 23 ± 3%) than controls (25 ± 2%) (P = 0.006, P = 0.113, P = 0.039), indicating increased myocyte mass (16.9 ± 2.7, 16.5 ± 2.3, 18.1 ± 3.5 versus 14.0 ± 2.9 g/m2.7). Native T1 values were similar. Lower T2 values in the hypertensive overweight group related to heart rate. In conclusion, BSA-indexation masks hypertrophy and causes volume overcorrection in overweight subjects compared to controls, height2.7-indexation therefore seems advisable.
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12
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Wamil M, Goncalves M, Rutherford A, Borlotti A, Pellikka PA. Multi-modality cardiac imaging in the management of diabetic heart disease. Front Cardiovasc Med 2022; 9:1043711. [DOI: 10.3389/fcvm.2022.1043711] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Accepted: 10/17/2022] [Indexed: 11/06/2022] Open
Abstract
Diabetic heart disease is a major healthcare problem. Patients with diabetes show an excess of death from cardiovascular causes, twice as high as the general population and those with diabetes type 1 and longer duration of the disease present with more severe cardiovascular complications. Premature coronary artery disease and heart failure are leading causes of morbidity and reduced life expectancy. Multimodality cardiac imaging, including echocardiography, cardiac computed tomography, nuclear medicine, and cardiac magnetic resonance play crucial role in the diagnosis and management of different pathologies included in the definition of diabetic heart disease. In this review we summarise the utility of multi-modality cardiac imaging in characterising ischaemic and non-ischaemic causes of diabetic heart disease and give an overview of the current clinical practice. We also describe emerging imaging techniques enabling early detection of coronary artery inflammation and the non-invasive characterisation of the atherosclerotic plaque disease. Furthermore, we discuss the role of MRI-derived techniques in studying altered myocardial metabolism linking diabetes with the development of diabetic cardiomyopathy. Finally, we discuss recent data regarding the use of artificial intelligence applied to large imaging databases and how those efforts can be utilised in the future in screening of patients with diabetes for early signs of disease.
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13
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Dasgupta K, Boulé N, Henson J, Chevalier S, Redman E, Chan D, McCarthy M, Champagne J, Arsenyadis F, Rees J, Da Costa D, Gregg E, Yeung R, Hadjiconstantinou M, Dattani A, Friedrich MG, Khunti K, Rahme E, Fortier I, Prado CM, Sherman M, Thompson RB, Davies MJ, McCann GP, Yates T. Remission of type 2 diabetes and improved diastolic function by combining structured exercise with meal replacement and food reintroduction among young adults: the RESET for REMISSION randomised controlled trial protocol. BMJ Open 2022; 12:e063888. [PMID: 36130753 PMCID: PMC9494595 DOI: 10.1136/bmjopen-2022-063888] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
INTRODUCTION Type 2 diabetes mellitus (T2DM) onset before 40 years of age has a magnified lifetime risk of cardiovascular disease. Diastolic dysfunction is its earliest cardiac manifestation. Low energy diets incorporating meal replacement products can induce diabetes remission, but do not lead to improved diastolic function, unlike supervised exercise interventions. We are examining the impact of a combined low energy diet and supervised exercise intervention on T2DM remission, with peak early diastolic strain rate, a sensitive MRI-based measure, as a key secondary outcome. METHODS AND ANALYSIS This prospective, randomised, two-arm, open-label, blinded-endpoint efficacy trial is being conducted in Montreal, Edmonton and Leicester. We are enrolling 100 persons 18-45 years of age within 6 years' T2DM diagnosis, not on insulin therapy, and with obesity. During the intensive phase (12 weeks), active intervention participants adopt an 800-900 kcal/day low energy diet combining meal replacement products with some food, and receive supervised exercise training (aerobic and resistance), three times weekly. The maintenance phase (12 weeks) focuses on sustaining any weight loss and exercise practices achieved during the intensive phase; products and exercise supervision are tapered but reinstituted, as applicable, with weight regain and/or exercise reduction. The control arm receives standard care. The primary outcome is T2DM remission, (haemoglobin A1c of less than 6.5% at 24 weeks, without use of glucose-lowering medications during maintenance). Analysis of remission will be by intention to treat with stratified Fisher's exact test statistics. ETHICS AND DISSEMINATION The trial is approved in Leicester (East Midlands - Nottingham Research Ethics Committee (21/EM/0026)), Montreal (McGill University Health Centre Research Ethics Board (RESET for remission/2021-7148)) and Edmonton (University of Alberta Health Research Ethics Board (Pro00101088). Findings will be shared widely (publications, presentations, press releases, social media platforms) and will inform an effectiveness trial. TRIAL REGISTRATION NUMBER ISRCTN15487120.
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Affiliation(s)
- Kaberi Dasgupta
- Department of Medicine, McGill University and Centre for Outcomes Research and Evaluation, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada
| | - Normand Boulé
- Faculty of Kinesiology, Sport, and Recreation, University of Alberta, Edmonton, Alberta, Canada
| | - Joseph Henson
- Diabetes Research Centre, University of Leicester and NIHR Leicester Biomedical Research Centre, University of Leicester and University Hospitals of Leicester NHS Trust, Leicester, UK
| | | | - Emma Redman
- Leicester Diabetes Centre, University Hospitals of Leicester NHS Trust and NIHR Leicester Biomedical Research Centre, University of Leicester and University Hospitals of Leicester NHS Trust, Leicester, UK
| | - Deborah Chan
- Centre for Outcomes Research and Evaluation, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada
| | - Matthew McCarthy
- Diabetes Research Centre, University of Leicester and NIHR Leicester Biomedical Research Centre, University of Leicester and University Hospitals of Leicester NHS Trust, Leicester, UK
| | - Julia Champagne
- Centre for Outcomes Research and Evaluation, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada
| | - Frank Arsenyadis
- Diabetes Research Centre, University of Leicester and NIHR Leicester Biomedical Research Centre, University of Leicester and University Hospitals of Leicester NHS Trust, Leicester, UK
| | - Jordan Rees
- Faculty of Kinesiology, Sport, and Recreation, University of Alberta, Edmonton, Alberta, Canada
| | - Deborah Da Costa
- Department of Medicine, McGill University and Centre for Outcomes Research and Evaluation, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada
| | - Edward Gregg
- School of Public Health, Imperial College London, London, UK
| | - Roseanne Yeung
- Division of Endocrinology & Metabolism, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
| | - Michelle Hadjiconstantinou
- Diabetes Research Centre, University of Leicester and NIHR Leicester Biomedical Research Centre, University of Leicester and University Hospitals of Leicester NHS Trust, Leicester, UK
| | - Abhishek Dattani
- Department of Cardiovascular Sciences, University of Leicester and NIHR Leicester Biomedical Research Centre, University of Leicester and University Hospitals of Leicester NHS Trust, Leicester, UK
| | - Matthias G Friedrich
- Courtois Cardiovascular Signature Centre, McGill University Health Centre and Departments of Medicine and Diagnostic Radiology, McGill University, Montreal, Quebec, Canada
| | - Kamlesh Khunti
- Diabetes Research Centre, University of Leicester and NIHR Applied Research Collaboration - East Midlands (ARC-EM), University of Leicester and University Hospitals of Leicester NHS Trust, Leicester, UK
| | - Elham Rahme
- Department of Medicine, McGill University and Centre for Outcomes Research and Evaluation, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada
| | - Isabel Fortier
- Department of Medicine, McGill University and Centre for Outcomes Research and Evaluation, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada
| | - Carla M Prado
- Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada
| | - Mark Sherman
- Department of Medicine, McGill University, Montreal, Quebec, Canada
| | - Richard B Thompson
- Department of Biomedical Engineering, University of Alberta, Edmonton, Alberta, Canada
| | - Melanie J Davies
- Diabetes Research Centre, University of Leicester and NIHR Leicester Biomedical Research Centre, University of Leicester and University Hospitals of Leicester NHS Trust, Leicester, UK
| | - Gerry P McCann
- Department of Cardiovascular Sciences, University of Leicester and NIHR Leicester Biomedical Research Centre, University of Leicester and University Hospitals of Leicester NHS Trust, Leicester, UK
| | - Thomas Yates
- Diabetes Research Centre, University of Leicester and NIHR Leicester Biomedical Research Centre, University of Leicester and University Hospitals of Leicester NHS Trust, Leicester, UK
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14
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Fukamachi D, Yamada A, Ohgaku A, Koyama Y, Fujito H, Arai R, Ebuchi Y, Migita S, Morikawa T, Monden M, Takei N, Tamaki T, Kojima K, Akutsu N, Murata N, Saito Y, Kitano D, Sudo M, Okumura Y. Protective effect of the Impella on the left ventricular function after acute broad anterior wall ST elevation myocardial infarctions with cardiogenic shock: cardiovascular magnetic resonance imaging strain analysis. BMC Cardiovasc Disord 2022; 22:201. [PMID: 35484492 PMCID: PMC9052554 DOI: 10.1186/s12872-022-02632-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Accepted: 04/13/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The clinical efficacy of the Impella for high-risk percutaneous coronary intervention (PCI) and cardiogenic shock remains under debate. We thus sought to investigate the protective effects on the heart with the Impella's early use pre-PCI using cardiac magnetic resonance imaging (CMRI). METHODS We retrospectively evaluated the difference in the subacute phase CMR imaging results (19 ± 9 days after admission) between patients undergoing an Impella (n = 7) or not (non-Impella group: n = 18 [12 intra-aortic balloon pumps (1 plus veno-arterial extracorporeal membrane oxygenation) and 6 no mechanical circulation systems]) in broad anterior ST-elevation myocardial infarction (STEMI) cases. A mechanical circulation system was implanted pre-PCI. RESULTS No differences were found in the door-to-balloon time, peak creatine kinase, and hospital admission days between the Impella and non-Impella groups; however, the CMRI-derived left ventricular ejection fraction was significantly greater (45 ± 13% vs. 34 ± 7.6%, P = 0.034) and end-diastolic and systolic volumes smaller in the Impella group (149 ± 29 vs. 187 ± 41 mL, P = 0.006: 80 ± 29 vs. 121 ± 40 mL, P = 0.012). Although the global longitudinal peak strain did not differ, the global radial (GRS) and circumferential peak strain (GCS) were significantly higher in the IMPELLA than non-IMPELLA group. Greater systolic and diastolic strain rates (SRs) in the Impella than non-Impella group were observed in non-infarcted rather than infarcted areas. CONCLUSIONS Early implantation of an Impella before PCIs for STEMIs sub-acutely prevented cardiac dysfunction through preserving the GRS, GCS, and systolic and diastolic SRs in the remote myocardium. This study provided mechanistic insight into understanding the usefulness of the Impella to prevent future heart failure.
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Affiliation(s)
- Daisuke Fukamachi
- Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Ohyaguchi-kamicho, Itabashi-ku, Tokyo, 173-8610, Japan.
| | - Akimasa Yamada
- Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Ohyaguchi-kamicho, Itabashi-ku, Tokyo, 173-8610, Japan
| | - Akihito Ohgaku
- Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Ohyaguchi-kamicho, Itabashi-ku, Tokyo, 173-8610, Japan
| | - Yutaka Koyama
- Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Ohyaguchi-kamicho, Itabashi-ku, Tokyo, 173-8610, Japan
| | - Hidesato Fujito
- Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Ohyaguchi-kamicho, Itabashi-ku, Tokyo, 173-8610, Japan
| | - Riku Arai
- Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Ohyaguchi-kamicho, Itabashi-ku, Tokyo, 173-8610, Japan
| | - Yasunari Ebuchi
- Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Ohyaguchi-kamicho, Itabashi-ku, Tokyo, 173-8610, Japan
| | - Suguru Migita
- Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Ohyaguchi-kamicho, Itabashi-ku, Tokyo, 173-8610, Japan
| | - Tomoyuki Morikawa
- Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Ohyaguchi-kamicho, Itabashi-ku, Tokyo, 173-8610, Japan
| | - Masaki Monden
- Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Ohyaguchi-kamicho, Itabashi-ku, Tokyo, 173-8610, Japan
| | - Norio Takei
- Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Ohyaguchi-kamicho, Itabashi-ku, Tokyo, 173-8610, Japan
| | - Takehiro Tamaki
- Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Ohyaguchi-kamicho, Itabashi-ku, Tokyo, 173-8610, Japan
| | - Keisuke Kojima
- Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Ohyaguchi-kamicho, Itabashi-ku, Tokyo, 173-8610, Japan
| | - Naotaka Akutsu
- Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Ohyaguchi-kamicho, Itabashi-ku, Tokyo, 173-8610, Japan
| | - Nobuhiro Murata
- Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Ohyaguchi-kamicho, Itabashi-ku, Tokyo, 173-8610, Japan
| | - Yuki Saito
- Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Ohyaguchi-kamicho, Itabashi-ku, Tokyo, 173-8610, Japan
| | - Daisuke Kitano
- Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Ohyaguchi-kamicho, Itabashi-ku, Tokyo, 173-8610, Japan
| | - Mitsumasa Sudo
- Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Ohyaguchi-kamicho, Itabashi-ku, Tokyo, 173-8610, Japan
| | - Yasuo Okumura
- Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Ohyaguchi-kamicho, Itabashi-ku, Tokyo, 173-8610, Japan
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15
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Morales MA, Snel GJH, van den Boomen M, Borra RJH, van Deursen VM, Slart RHJA, Izquierdo-Garcia D, Prakken NHJ, Catana C. DeepStrain Evidence of Asymptomatic Left Ventricular Diastolic and Systolic Dysfunction in Young Adults With Cardiac Risk Factors. Front Cardiovasc Med 2022; 9:831080. [PMID: 35479280 PMCID: PMC9035693 DOI: 10.3389/fcvm.2022.831080] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Accepted: 03/11/2022] [Indexed: 11/17/2022] Open
Abstract
Purpose To evaluate if a fully-automatic deep learning method for myocardial strain analysis based on magnetic resonance imaging (MRI) cine images can detect asymptomatic dysfunction in young adults with cardiac risk factors. Methods An automated workflow termed DeepStrain was implemented using two U-Net models for segmentation and motion tracking. DeepStrain was trained and tested using short-axis cine-MRI images from healthy subjects and patients with cardiac disease. Subsequently, subjects aged 18–45 years were prospectively recruited and classified among age- and gender-matched groups: risk factor group (RFG) 1 including overweight without hypertension or type 2 diabetes; RFG2 including hypertension without type 2 diabetes, regardless of overweight; RFG3 including type 2 diabetes, regardless of overweight or hypertension. Subjects underwent cardiac short-axis cine-MRI image acquisition. Differences in DeepStrain-based left ventricular global circumferential and radial strain and strain rate among groups were evaluated. Results The cohort consisted of 119 participants: 30 controls, 39 in RFG1, 30 in RFG2, and 20 in RFG3. Despite comparable (>0.05) left-ventricular mass, volumes, and ejection fraction, all groups (RFG1, RFG2, RFG3) showed signs of asymptomatic left ventricular diastolic and systolic dysfunction, evidenced by lower circumferential early-diastolic strain rate (<0.05, <0.001, <0.01), and lower septal circumferential end-systolic strain (<0.001, <0.05, <0.001) compared with controls. Multivariate linear regression showed that body surface area correlated negatively with all strain measures (<0.01), and mean arterial pressure correlated negatively with early-diastolic strain rate (<0.01). Conclusion DeepStrain fully-automatically provided evidence of asymptomatic left ventricular diastolic and systolic dysfunction in asymptomatic young adults with overweight, hypertension, and type 2 diabetes risk factors.
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Affiliation(s)
- Manuel A. Morales
- Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States
- Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA, United States
- *Correspondence: Manuel A. Morales
| | - Gert J. H. Snel
- Department of Radiology, Medical Imaging Center, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
| | - Maaike van den Boomen
- Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States
- Department of Radiology, Medical Imaging Center, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
- Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States
| | - Ronald J. H. Borra
- Department of Radiology, Medical Imaging Center, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
- Department of Nuclear Medicine and Molecular Imaging, Medical Imaging Center, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
| | - Vincent M. van Deursen
- Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
| | - Riemer H. J. A. Slart
- Department of Nuclear Medicine and Molecular Imaging, Medical Imaging Center, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
- Department of Biomedical Photonic Imaging, Faculty of Science and Technology, University of Twente, Enschede, Netherlands
| | - David Izquierdo-Garcia
- Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States
- Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA, United States
| | - Niek H. J. Prakken
- Department of Radiology, Medical Imaging Center, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
| | - Ciprian Catana
- Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States
- Ciprian Catana
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16
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Multiparametric CMR imaging of myocardial structure and function changes in diabetic mini-pigs with preserved LV function: a preliminary study. BMC Cardiovasc Disord 2022; 22:143. [PMID: 35366800 PMCID: PMC8976391 DOI: 10.1186/s12872-022-02597-7] [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] [Received: 06/12/2021] [Accepted: 03/29/2022] [Indexed: 11/10/2022] Open
Abstract
Background The purpose of this study is to dynamically monitor the myocardial structure and function changes in diabetic mini-pigs by 1.5 T cardiac magnetic resonance. Methods Three male mini-pigs underwent cardiac magnet resonance (CMR) imaging, and histologic examination. T1-mapping was acquired at basal, mid and apical segments. CMR feature-tracking (CMR-FT) is used to quantify left ventricle global longitudinal (LVGLS), circumferential (LVGCS) and radial strain (LVGRS). Epicardial adipose tissue (EAT) was evaluated using a commercially available software. Results Left ventricular mass (LVM), myocardial native T1 value, extracellular volume (ECV) value and EAT were increased gradually after 6 months of modeling, while LVGLS decreased gradually after 6 months of modeling (LVM: 24.5 (23.4, 26.7) vs. 42.7 (41.4, 44.6) g/m2, p < 0.001; Native T1: 1005.5 (992.6, 1010.7) vs. 1028.7 (1015.5, 1035.6) ms, p = 0.041; EAT: 16.1 (14.5, 18.2) vs. 24.6 (20.8, 26.9) mL, p = 0.020; ECV: 21.4 (20.2, 23.9) vs. 28.9 (26.7, 30.3) %, p = 0.011; LVGLS: − 22.8 (− 21.4, − 23.9) vs. − 17.4 (− 17.2, − 19.2)%, p = 0.008). The diffuse myocardial interstitial fibrosis was found in histology samples. Conclusion The progressive impairments in LV structure and myocardial deformation occurs in diabetic mini-pigs. T1 mapping and CMR-FT technology are promising to monitor abnormal changes of diabetic myocardium in the early stage of diabetic cardiomyopathy.
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17
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Snel GJH, van den Boomen M, Hurtado-Ortiz K, Slart RHJA, van Deursen VM, Nguyen CT, Sosnovik DE, Dierckx RAJO, Velthuis BK, Borra RJH, Prakken NHJ. Cardiac Alterations on 3T MRI in Young Adults With Sedentary Lifestyle-Related Risk Factors. Front Cardiovasc Med 2022; 9:840790. [PMID: 35274012 PMCID: PMC8902075 DOI: 10.3389/fcvm.2022.840790] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Accepted: 01/18/2022] [Indexed: 12/04/2022] Open
Abstract
Background Young adult populations with the sedentary lifestyle-related risk factors overweight, hypertension, and type 2 diabetes (T2D) are growing, and associated cardiac alterations could overlap early findings in non-ischemic cardiomyopathy on cardiovascular MRI. We aimed to investigate cardiac morphology, function, and tissue characteristics for these cardiovascular risk factors. Methods Non-athletic non-smoking asymptomatic adults aged 18-45 years were prospectively recruited and underwent 3Tesla cardiac MRI. Multivariate linear regression was performed to investigate independent associations of risk factor-related parameters with cardiac MRI values. Results We included 311 adults (age, 32 ± 7 years; men, 49%). Of them, 220 subjects had one or multiple risk factors, while 91 subjects were free of risk factors. For overweight, increased body mass index (per SD = 5.3 kg/m2) was associated with increased left ventricular (LV) mass (+7.3 g), biventricular higher end-diastolic (LV, +8.6 ml), and stroke volumes (SV; +5.0 ml), higher native T1 (+7.3 ms), and lower extracellular volume (ECV, -0.38%), whereas the higher waist-hip ratio was associated with lower biventricular volumes. Regarding hypertension, increased systolic blood pressure (per SD = 14 mmHg) was associated with increased LV mass (+6.9 g), higher LV ejection fraction (EF; +1.0%), and lower ECV (-0.48%), whereas increased diastolic blood pressure was associated with lower LV EF. In T2D, increased HbA1c (per SD = 9.0 mmol/mol) was associated with increased LV mass (+2.2 g), higher right ventricular end-diastolic volume (+3.2 ml), and higher ECV (+0.27%). Increased heart rate was linked with decreased LV mass, lower biventricular volumes, and lower T2 values. Conclusions Young asymptomatic adults with overweight, hypertension, and T2D show subclinical alterations in cardiac morphology, function, and tissue characteristics. These alterations should be considered in cardiac MRI-based clinical decision making.
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Affiliation(s)
- Gert J. H. Snel
- Department of Radiology, Medical Imaging Center, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
| | - Maaike van den Boomen
- Department of Radiology, Medical Imaging Center, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
- Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States
- Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States
| | - Katia Hurtado-Ortiz
- Faculty of Medicine, National Autonomous University of Mexico (UNAM), Ciudad Universitaria, Mexico City, Mexico
| | - Riemer H. J. A. Slart
- Department of Nuclear Medicine and Molecular Imaging, Medical Imaging Center, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
- Department of Biomedical Photonic Imaging, Faculty of Science and Technology, University of Twente, Enschede, Netherlands
| | - Vincent M. van Deursen
- Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
| | - Christopher T. Nguyen
- Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States
- Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States
| | - David E. Sosnovik
- Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States
- Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States
- Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA, United States
| | - Rudi A. J. O. Dierckx
- Department of Nuclear Medicine and Molecular Imaging, Medical Imaging Center, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
| | - Birgitta K. Velthuis
- Department of Radiology, University Medical Center Utrecht, University of Utrecht, Utrecht, Netherlands
| | - Ronald J. H. Borra
- Department of Radiology, Medical Imaging Center, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
- Department of Nuclear Medicine and Molecular Imaging, Medical Imaging Center, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
| | - Niek H. J. Prakken
- Department of Radiology, Medical Imaging Center, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
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Phipps K, van de Boomen M, Eder R, Michelhaugh SA, Spahillari A, Kim J, Parajuli S, Reese TG, Mekkaoui C, Das S, Gee D, Shah R, Sosnovik DE, Nguyen C. Accelerated in Vivo Cardiac Diffusion-Tensor MRI Using Residual Deep Learning-based Denoising in Participants with Obesity. Radiol Cardiothorac Imaging 2021; 3:e200580. [PMID: 34250491 DOI: 10.1148/ryct.2021200580] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2020] [Revised: 05/07/2021] [Accepted: 05/11/2021] [Indexed: 12/21/2022]
Abstract
Purpose To develop and assess a residual deep learning algorithm to accelerate in vivo cardiac diffusion-tensor MRI (DT-MRI) by reducing the number of averages while preserving image quality and DT-MRI parameters. Materials and Methods In this prospective study, a denoising convolutional neural network (DnCNN) for DT-MRI was developed; a total of 26 participants, including 20 without obesity (body mass index [BMI] < 30 kg/m2; mean age, 28 years ± 3 [standard deviation]; 11 women) and six with obesity (BMI ≥ 30 kg/m2; mean age, 48 years ± 11; five women), were recruited from June 19, 2019, to July 29, 2020. DT-MRI data were constructed at four averages (4Av), two averages (2Av), and one average (1Av) without and with the application of the DnCNN (4AvDnCNN, 2AvDnCNN, 1AvDnCNN). All data were compared against the reference DT-MRI data constructed at eight averages (8Av). Image quality, characterized by using the signal-to-noise ratio (SNR) and structural similarity index (SSIM), and the DT-MRI parameters of mean diffusivity (MD), fractional anisotropy (FA), and helix angle transmurality (HAT) were quantified. Results No differences were found in image quality or DT-MRI parameters between the accelerated 4AvDnCNN DT-MRI and the reference 8Av DT-MRI data for the SNR (29.1 ± 2.7 vs 30.5 ± 2.9), SSIM (0.97 ± 0.01), MD (1.3 µm2/msec ± 0.1 vs 1.31 µm2/msec ± 0.11), FA (0.32 ± 0.05 vs 0.30 ± 0.04), or HAT (1.10°/% ± 0.13 vs 1.11°/% ± 0.09). The relationship of a higher MD and lower FA and HAT in individuals with obesity compared with individuals without obesity in reference 8Av DT-MRI measurements was retained in 4AvDnCNN and 2AvDnCNN DT-MRI measurements but was not retained in 4Av or 2Av DT-MRI measurements. Conclusion Cardiac DT-MRI can be performed at an at least twofold-accelerated rate by using DnCNN to preserve image quality and DT-MRI parameter quantification.Keywords: Adults, Cardiac, Obesity, Technology Assessment, MR-Diffusion Tensor Imaging, Heart, Tissue CharacterizationSupplemental material is available for this article.© RSNA, 2021.
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Affiliation(s)
- Kellie Phipps
- Cardiovascular Research Center, Massachusetts General Hospital, 149 13th St, 4.213, Charlestown, MA 02129 (K.P., M.v.d.B., R.E., J.K., S.P., S.D., R.S., D.E.S., C.N.); Department of Radiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (M.v.d.B.); A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Charlestown, Mass (M.v.d.B., T.G.R., C.M., D.E.S., C.N.); Cardiology Division (S.A.M., A.S., S.D., R.S., D.E.S.) and Weight Center (D.G.), Massachusetts General Hospital, Boston, Mass; and Departments of Radiology (T.G.R., C.M.), Medicine (S.D., R.S., D.E.S., C.N.), and Surgery (D.G.), Harvard Medical School, Boston, Mass
| | - Maaike van de Boomen
- Cardiovascular Research Center, Massachusetts General Hospital, 149 13th St, 4.213, Charlestown, MA 02129 (K.P., M.v.d.B., R.E., J.K., S.P., S.D., R.S., D.E.S., C.N.); Department of Radiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (M.v.d.B.); A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Charlestown, Mass (M.v.d.B., T.G.R., C.M., D.E.S., C.N.); Cardiology Division (S.A.M., A.S., S.D., R.S., D.E.S.) and Weight Center (D.G.), Massachusetts General Hospital, Boston, Mass; and Departments of Radiology (T.G.R., C.M.), Medicine (S.D., R.S., D.E.S., C.N.), and Surgery (D.G.), Harvard Medical School, Boston, Mass
| | - Robert Eder
- Cardiovascular Research Center, Massachusetts General Hospital, 149 13th St, 4.213, Charlestown, MA 02129 (K.P., M.v.d.B., R.E., J.K., S.P., S.D., R.S., D.E.S., C.N.); Department of Radiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (M.v.d.B.); A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Charlestown, Mass (M.v.d.B., T.G.R., C.M., D.E.S., C.N.); Cardiology Division (S.A.M., A.S., S.D., R.S., D.E.S.) and Weight Center (D.G.), Massachusetts General Hospital, Boston, Mass; and Departments of Radiology (T.G.R., C.M.), Medicine (S.D., R.S., D.E.S., C.N.), and Surgery (D.G.), Harvard Medical School, Boston, Mass
| | - Sam Allen Michelhaugh
- Cardiovascular Research Center, Massachusetts General Hospital, 149 13th St, 4.213, Charlestown, MA 02129 (K.P., M.v.d.B., R.E., J.K., S.P., S.D., R.S., D.E.S., C.N.); Department of Radiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (M.v.d.B.); A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Charlestown, Mass (M.v.d.B., T.G.R., C.M., D.E.S., C.N.); Cardiology Division (S.A.M., A.S., S.D., R.S., D.E.S.) and Weight Center (D.G.), Massachusetts General Hospital, Boston, Mass; and Departments of Radiology (T.G.R., C.M.), Medicine (S.D., R.S., D.E.S., C.N.), and Surgery (D.G.), Harvard Medical School, Boston, Mass
| | - Aferdita Spahillari
- Cardiovascular Research Center, Massachusetts General Hospital, 149 13th St, 4.213, Charlestown, MA 02129 (K.P., M.v.d.B., R.E., J.K., S.P., S.D., R.S., D.E.S., C.N.); Department of Radiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (M.v.d.B.); A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Charlestown, Mass (M.v.d.B., T.G.R., C.M., D.E.S., C.N.); Cardiology Division (S.A.M., A.S., S.D., R.S., D.E.S.) and Weight Center (D.G.), Massachusetts General Hospital, Boston, Mass; and Departments of Radiology (T.G.R., C.M.), Medicine (S.D., R.S., D.E.S., C.N.), and Surgery (D.G.), Harvard Medical School, Boston, Mass
| | - Joan Kim
- Cardiovascular Research Center, Massachusetts General Hospital, 149 13th St, 4.213, Charlestown, MA 02129 (K.P., M.v.d.B., R.E., J.K., S.P., S.D., R.S., D.E.S., C.N.); Department of Radiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (M.v.d.B.); A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Charlestown, Mass (M.v.d.B., T.G.R., C.M., D.E.S., C.N.); Cardiology Division (S.A.M., A.S., S.D., R.S., D.E.S.) and Weight Center (D.G.), Massachusetts General Hospital, Boston, Mass; and Departments of Radiology (T.G.R., C.M.), Medicine (S.D., R.S., D.E.S., C.N.), and Surgery (D.G.), Harvard Medical School, Boston, Mass
| | - Shestruma Parajuli
- Cardiovascular Research Center, Massachusetts General Hospital, 149 13th St, 4.213, Charlestown, MA 02129 (K.P., M.v.d.B., R.E., J.K., S.P., S.D., R.S., D.E.S., C.N.); Department of Radiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (M.v.d.B.); A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Charlestown, Mass (M.v.d.B., T.G.R., C.M., D.E.S., C.N.); Cardiology Division (S.A.M., A.S., S.D., R.S., D.E.S.) and Weight Center (D.G.), Massachusetts General Hospital, Boston, Mass; and Departments of Radiology (T.G.R., C.M.), Medicine (S.D., R.S., D.E.S., C.N.), and Surgery (D.G.), Harvard Medical School, Boston, Mass
| | - Timothy G Reese
- Cardiovascular Research Center, Massachusetts General Hospital, 149 13th St, 4.213, Charlestown, MA 02129 (K.P., M.v.d.B., R.E., J.K., S.P., S.D., R.S., D.E.S., C.N.); Department of Radiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (M.v.d.B.); A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Charlestown, Mass (M.v.d.B., T.G.R., C.M., D.E.S., C.N.); Cardiology Division (S.A.M., A.S., S.D., R.S., D.E.S.) and Weight Center (D.G.), Massachusetts General Hospital, Boston, Mass; and Departments of Radiology (T.G.R., C.M.), Medicine (S.D., R.S., D.E.S., C.N.), and Surgery (D.G.), Harvard Medical School, Boston, Mass
| | - Choukri Mekkaoui
- Cardiovascular Research Center, Massachusetts General Hospital, 149 13th St, 4.213, Charlestown, MA 02129 (K.P., M.v.d.B., R.E., J.K., S.P., S.D., R.S., D.E.S., C.N.); Department of Radiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (M.v.d.B.); A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Charlestown, Mass (M.v.d.B., T.G.R., C.M., D.E.S., C.N.); Cardiology Division (S.A.M., A.S., S.D., R.S., D.E.S.) and Weight Center (D.G.), Massachusetts General Hospital, Boston, Mass; and Departments of Radiology (T.G.R., C.M.), Medicine (S.D., R.S., D.E.S., C.N.), and Surgery (D.G.), Harvard Medical School, Boston, Mass
| | - Saumya Das
- Cardiovascular Research Center, Massachusetts General Hospital, 149 13th St, 4.213, Charlestown, MA 02129 (K.P., M.v.d.B., R.E., J.K., S.P., S.D., R.S., D.E.S., C.N.); Department of Radiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (M.v.d.B.); A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Charlestown, Mass (M.v.d.B., T.G.R., C.M., D.E.S., C.N.); Cardiology Division (S.A.M., A.S., S.D., R.S., D.E.S.) and Weight Center (D.G.), Massachusetts General Hospital, Boston, Mass; and Departments of Radiology (T.G.R., C.M.), Medicine (S.D., R.S., D.E.S., C.N.), and Surgery (D.G.), Harvard Medical School, Boston, Mass
| | - Denise Gee
- Cardiovascular Research Center, Massachusetts General Hospital, 149 13th St, 4.213, Charlestown, MA 02129 (K.P., M.v.d.B., R.E., J.K., S.P., S.D., R.S., D.E.S., C.N.); Department of Radiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (M.v.d.B.); A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Charlestown, Mass (M.v.d.B., T.G.R., C.M., D.E.S., C.N.); Cardiology Division (S.A.M., A.S., S.D., R.S., D.E.S.) and Weight Center (D.G.), Massachusetts General Hospital, Boston, Mass; and Departments of Radiology (T.G.R., C.M.), Medicine (S.D., R.S., D.E.S., C.N.), and Surgery (D.G.), Harvard Medical School, Boston, Mass
| | - Ravi Shah
- Cardiovascular Research Center, Massachusetts General Hospital, 149 13th St, 4.213, Charlestown, MA 02129 (K.P., M.v.d.B., R.E., J.K., S.P., S.D., R.S., D.E.S., C.N.); Department of Radiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (M.v.d.B.); A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Charlestown, Mass (M.v.d.B., T.G.R., C.M., D.E.S., C.N.); Cardiology Division (S.A.M., A.S., S.D., R.S., D.E.S.) and Weight Center (D.G.), Massachusetts General Hospital, Boston, Mass; and Departments of Radiology (T.G.R., C.M.), Medicine (S.D., R.S., D.E.S., C.N.), and Surgery (D.G.), Harvard Medical School, Boston, Mass
| | - David E Sosnovik
- Cardiovascular Research Center, Massachusetts General Hospital, 149 13th St, 4.213, Charlestown, MA 02129 (K.P., M.v.d.B., R.E., J.K., S.P., S.D., R.S., D.E.S., C.N.); Department of Radiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (M.v.d.B.); A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Charlestown, Mass (M.v.d.B., T.G.R., C.M., D.E.S., C.N.); Cardiology Division (S.A.M., A.S., S.D., R.S., D.E.S.) and Weight Center (D.G.), Massachusetts General Hospital, Boston, Mass; and Departments of Radiology (T.G.R., C.M.), Medicine (S.D., R.S., D.E.S., C.N.), and Surgery (D.G.), Harvard Medical School, Boston, Mass
| | - Christopher Nguyen
- Cardiovascular Research Center, Massachusetts General Hospital, 149 13th St, 4.213, Charlestown, MA 02129 (K.P., M.v.d.B., R.E., J.K., S.P., S.D., R.S., D.E.S., C.N.); Department of Radiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (M.v.d.B.); A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Charlestown, Mass (M.v.d.B., T.G.R., C.M., D.E.S., C.N.); Cardiology Division (S.A.M., A.S., S.D., R.S., D.E.S.) and Weight Center (D.G.), Massachusetts General Hospital, Boston, Mass; and Departments of Radiology (T.G.R., C.M.), Medicine (S.D., R.S., D.E.S., C.N.), and Surgery (D.G.), Harvard Medical School, Boston, Mass
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Thirunavukarasu S, Brown LAE, Chowdhary A, Jex N, Swoboda P, Greenwood JP, Plein S, Levelt E. Rationale and design of the randomised controlled cross-over trial: Cardiovascular effects of empaglifozin in diabetes mellitus. Diab Vasc Dis Res 2021; 18:14791641211021585. [PMID: 34182806 PMCID: PMC8481726 DOI: 10.1177/14791641211021585] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND Type 2 diabetes (T2D) is associated with an increased risk of cardiovascular (CV) disease. In patients with T2D and established CV disease, selective inhibitors of sodium-glucose cotransporter 2 (SGLT2) have been shown to decrease CV and all-cause mortality, and heart failure (HF) admissions. Utilising CV magnetic resonance imaging (CMR) and continuous glucose monitoring (CGM) by FreeStyle Libre Pro Sensor, we aim to explore the mechanisms of action which give Empagliflozin, an SGLT2 inhibitor, its beneficial CV effects and compare these to the effects of dipeptidyl peptidase-4 inhibitor Sitagliptin. METHODS This is a single centre, open-label, cross-over trial conducted at the Leeds Teaching Hospitals NHS Trust. Participants are randomised for the order of treatment and receive 3 months therapy with Empagliflozin, and 3 months therapy with Sitagliptin sequentially. Twenty-eight eligible T2D patients with established ischaemic heart disease will be recruited. Patients undergo serial CMR scans on three visits. DISCUSSION The primary outcome measure is the myocardial perfusion reserve in remote myocardium. We hypothesise that Empaglifozin treatment is associated with improvements in myocardial blood flow and reductions in myocardial interstitial fibrosis, independent of CGM measured glycemic control in patients with T2D and established CV disease. TRIAL REGISTRATION This study has full research ethics committee approval (REC: 18/YH/0190) and data collection is anticipated to finish in December 2021. This study was retrospectively registered at https://doi.org/10.1186/ISRCTN82391603 and monitored by the University of Leeds. The study results will be submitted for publication within 6 months of completion.
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Affiliation(s)
- Sharmaine Thirunavukarasu
- Multidisciplinary Cardiovascular Research Centre and Biomedical Imaging Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK
| | - Louise AE Brown
- Multidisciplinary Cardiovascular Research Centre and Biomedical Imaging Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK
| | - Amrit Chowdhary
- Multidisciplinary Cardiovascular Research Centre and Biomedical Imaging Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK
| | - Nicholas Jex
- Multidisciplinary Cardiovascular Research Centre and Biomedical Imaging Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK
| | - Peter Swoboda
- Multidisciplinary Cardiovascular Research Centre and Biomedical Imaging Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK
| | - John P Greenwood
- Multidisciplinary Cardiovascular Research Centre and Biomedical Imaging Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK
| | - Sven Plein
- Multidisciplinary Cardiovascular Research Centre and Biomedical Imaging Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK
| | - Eylem Levelt
- Multidisciplinary Cardiovascular Research Centre and Biomedical Imaging Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK
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Gulsin GS, Brady E, Marsh AM, Squire G, Htike ZZ, Wilmot EG, Biglands JD, Kellman P, Xue H, Webb DR, Khunti K, Yates T, Davies MJ, McCann GP. Clinical associations with stage B heart failure in adults with type 2 diabetes. Ther Adv Endocrinol Metab 2021; 12:20420188211030144. [PMID: 34349975 PMCID: PMC8287269 DOI: 10.1177/20420188211030144] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Accepted: 06/16/2021] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND There is a high prevalence of asymptomatic (American Heart Association Stage B) heart failure (SBHF) in people with type 2 diabetes (T2D). We aimed to identify associations between clinical characteristics and markers of SBHF in adults with T2D, which may allow therapeutic interventions prior to symptom onset. METHODS Adults with T2D from a multi-ethnic population with no prevalent cardiovascular disease [n = 247, age 52 ± 12 years, glycated haemoglobin A1c (HbA1c) 7.4 ± 1.1% (57 ± 12 mmol/mol), duration of diabetes 61 (32, 120) months] underwent echocardiography and adenosine stress perfusion cardiovascular magnetic resonance imaging. Multivariable linear regression analyses were performed to identify independent associations between clinical characteristics and markers of SBHF. RESULTS In a series of multivariable linear regression models containing age, sex, ethnicity, smoking history, number of glucose-lowering agents, systolic blood pressure (BP) duration of diabetes, body mass index (BMI), HbA1c, serum creatinine, and low-density lipoprotein (LDL)-cholesterol, independent associations with: left ventricular mass:volume were age (β = 0.024), number of glucose-lowering agents (β = 0.022) and systolic BP (β = 0.027); global longitudinal strain were never smoking (β = -1.196), systolic BP (β = 0.328), and BMI (β = -0.348); myocardial perfusion reserve were age (β = -0.364) and male sex (β = 0.458); and aortic distensibility were age (β = -0.629) and systolic BP (β = -0.348). HbA1c was not independently associated with any marker of SBHF. CONCLUSIONS In asymptomatic adults with T2D, age, systolic BP, BMI, and smoking history, but not glycaemic control, are the major determinants of SBHF. Given BP and BMI are modifiable, these may be important targets to reduce the development of symptomatic heart failure.
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Affiliation(s)
| | - Emer Brady
- Department of Cardiovascular Sciences, University of Leicester and the National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, Leicester, UK
| | - Anna-Marie Marsh
- Department of Cardiovascular Sciences, University of Leicester and the National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, Leicester, UK
| | - Gareth Squire
- Department of Cardiovascular Sciences, University of Leicester and the National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, Leicester, UK
| | - Zin Z. Htike
- Diabetes Research Centre, University of Leicester and the NIHR Leicester Biomedical Research Centre, UK
| | - Emma G. Wilmot
- Diabetes Department, Royal Derby Hospital, University Hospitals of Derby and Burton NHS Foundation Trust, Derby, UK
| | | | - Peter Kellman
- National Heart, Lung and Blood Institute, Bethesda, MD, USA
| | - Hui Xue
- National Heart, Lung and Blood Institute, Bethesda, MD, USA
| | - David R. Webb
- Diabetes Research Centre, University of Leicester and the NIHR Leicester Biomedical Research Centre, UK
| | - Kamlesh Khunti
- Diabetes Research Centre, University of Leicester and the NIHR Leicester Biomedical Research Centre, UK
| | - Tom Yates
- Diabetes Research Centre, University of Leicester and the NIHR Leicester Biomedical Research Centre, UK
| | - Melanie J. Davies
- Diabetes Research Centre, University of Leicester and the NIHR Leicester Biomedical Research Centre, UK
| | - Gerry P. McCann
- Department of Cardiovascular Sciences, University of Leicester and the National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, Leicester, UK
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Tadic M, Cuspidi C, Calicchio F, Grassi G, Mancia G. Diabetic cardiomyopathy: How can cardiac magnetic resonance help? Acta Diabetol 2020; 57:1027-1034. [PMID: 32285200 DOI: 10.1007/s00592-020-01528-2] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2020] [Accepted: 03/26/2020] [Indexed: 12/17/2022]
Abstract
Diabetes cardiomyopathy is a specific form of cardiac disease characteristic for diabetic patients. Development of echocardiography enabled diagnosis of diabetic cardiomyopathy significantly before the occurrence of heart failure. Previously was believed that left ventricular (LV) diastolic dysfunction represents the first detectable stage of diabetic cardiomyopathy. However, speckle tracking imaging and strain evaluation showed that mechanical changes occur before LV diastolic dysfunction. Nevertheless, it seems that the first detectable stage of diabetic cardiomyopathy is myocardial interstitial fibrosis, which currently could be diagnosed predominantly by cardiac magnetic resonance. T1 mapping evaluation before and after contrast injection enables assessment of extracellular volume (ECV) and provides qualitative and quantitative assessment of interstitial myocardial fibrosis in diabetic patients. Studies showed a strong correlation between ECV-parameter of interstitial fibrosis and level of glycated hemoglobin-main parameter of glucose control in diabetes. This stage of fibrosis is still not LV hypertrophy and it is reversible, which is of a great importance because of timely initiation of treatment. The necessity for early diagnose is significantly increasing due to the fact that diabetes and arterial hypertension are concomitant disorders in the large number of diabetic patients and it has been known that the risk of interstitial myocardial fibrosis is multiplied in patients with both conditions. Future follow-up investigations are essential to determine the causal relationship between interstitial fibrosis and outcome in these patients. The aim of this review was to summarize the current knowledge and clinical usefulness of CMR in diabetic patients.
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Affiliation(s)
- Marijana Tadic
- Department of Cardiology, University Hospital "Dr. Dragisa Misovic - Dedinje", Heroja Milana Tepica 1, 11000, Belgrade, Serbia.
| | - Cesare Cuspidi
- University of Milan-Bicocca, Milan, Italy
- Clinical Research Unit, Istituto Auxologico Italiano, Viale della Resistenza 23, 20036, Meda, Italy
| | | | | | - Giuseppe Mancia
- University of Milan-Bicocca, Milan, Italy
- Policlinico di Monza, Monza, Italy
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22
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Gulsin GS, Henson J, Brady EM, Sargeant JA, Wilmot EG, Athithan L, Htike ZZ, Marsh AM, Biglands JD, Kellman P, Khunti K, Webb D, Davies MJ, Yates T, McCann GP. Cardiovascular Determinants of Aerobic Exercise Capacity in Adults With Type 2 Diabetes. Diabetes Care 2020; 43:2248-2256. [PMID: 32680830 PMCID: PMC7440912 DOI: 10.2337/dc20-0706] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Accepted: 06/09/2020] [Indexed: 02/03/2023]
Abstract
OBJECTIVE To assess the relationship between subclinical cardiac dysfunction and aerobic exercise capacity (peak VO2) in adults with type 2 diabetes (T2D), a group at high risk of developing heart failure. RESEARCH DESIGN AND METHODS Cross-sectional study. We prospectively enrolled a multiethnic cohort of asymptomatic adults with T2D and no history, signs, or symptoms of cardiovascular disease. Age-, sex-, and ethnicity-matched control subjects were recruited for comparison. Participants underwent bioanthropometric profiling, cardiopulmonary exercise testing, and cardiovascular magnetic resonance with adenosine stress perfusion imaging. Multivariable linear regression analysis was undertaken to identify independent associations between measures of cardiovascular structure and function and peak VO2. RESULTS A total of 247 adults with T2D (aged 51.8 ± 11.9 years, 55% males, 37% black or south Asian ethnicity, HbA1c 7.4 ± 1.1% [57 ± 12 mmol/mol], and duration of diabetes 61 [32-120] months) and 78 control subjects were included. Subjects with T2D had increased concentric left ventricular remodeling, reduced myocardial perfusion reserve (MPR), and markedly lower aerobic exercise capacity (peak VO2 18.0 ± 6.6 vs. 27.8 ± 9.0 mL/kg/min; P < 0.001) compared with control subjects. In a multivariable linear regression model containing age, sex, ethnicity, smoking status, and systolic blood pressure, only MPR (β = 0.822; P = 0.006) and left ventricular diastolic filling pressure (E/e') (β = -0.388; P = 0.001) were independently associated with peak VO2 in subjects with T2D. CONCLUSIONS In a multiethnic cohort of asymptomatic people with T2D, MPR and diastolic function are key determinants of aerobic exercise capacity, independent of age, sex, ethnicity, smoking status, or blood pressure.
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Affiliation(s)
- Gaurav S Gulsin
- Department of Cardiovascular Sciences, University of Leicester and the NIHR Leicester Biomedical Research Centre, Leicester, U.K.
| | - Joseph Henson
- Diabetes Research Centre, University of Leicester and the NIHR Leicester Biomedical Research Centre, Leicester, U.K
| | - Emer M Brady
- Department of Cardiovascular Sciences, University of Leicester and the NIHR Leicester Biomedical Research Centre, Leicester, U.K
| | - Jack A Sargeant
- Diabetes Research Centre, University of Leicester and the NIHR Leicester Biomedical Research Centre, Leicester, U.K
| | - Emma G Wilmot
- Diabetes Department, Royal Derby Hospital, University Hospitals of Derby and Burton NHS Foundation Trust, Derby, U.K
| | - Lavanya Athithan
- Department of Cardiovascular Sciences, University of Leicester and the NIHR Leicester Biomedical Research Centre, Leicester, U.K
| | - Zin Z Htike
- Diabetes Department, Royal Derby Hospital, University Hospitals of Derby and Burton NHS Foundation Trust, Derby, U.K
| | - Anna-Marie Marsh
- Department of Cardiovascular Sciences, University of Leicester and the NIHR Leicester Biomedical Research Centre, Leicester, U.K
| | | | - Peter Kellman
- National Heart, Lung, and Blood Institute, Bethesda, MD
| | - Kamlesh Khunti
- Diabetes Research Centre, University of Leicester and the NIHR Leicester Biomedical Research Centre, Leicester, U.K
| | - David Webb
- Diabetes Research Centre, University of Leicester and the NIHR Leicester Biomedical Research Centre, Leicester, U.K
| | - Melanie J Davies
- Diabetes Research Centre, University of Leicester and the NIHR Leicester Biomedical Research Centre, Leicester, U.K
| | - Thomas Yates
- Diabetes Research Centre, University of Leicester and the NIHR Leicester Biomedical Research Centre, Leicester, U.K
| | - Gerry P McCann
- Department of Cardiovascular Sciences, University of Leicester and the NIHR Leicester Biomedical Research Centre, Leicester, U.K.
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23
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Webb DR, Htike ZZ, Swarbrick DJ, Brady EM, Gray LJ, Biglands J, Gulsin GS, Henson J, Khunti K, McCann GP, Waller HL, Webb MA, Sargeant JA, Yates T, Zaccardi F, Davies MJ. A randomized, open-label, active comparator trial assessing the effects of 26 weeks of liraglutide or sitagliptin on cardiovascular function in young obese adults with type 2 diabetes. Diabetes Obes Metab 2020; 22:1187-1196. [PMID: 32157772 DOI: 10.1111/dom.14023] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2020] [Revised: 02/27/2020] [Accepted: 03/05/2020] [Indexed: 02/06/2023]
Abstract
AIM To compare the effects of a glucagon-like peptide-1 receptor agonist and a dipeptidyl peptidase-4 inhibitor on magnetic resonance imaging-derived measures of cardiovascular function. MATERIALS AND METHODS In a prospective, randomized, open-label, blinded endpoint trial liraglutide (1.8 mg) and sitagliptin (100 mg) were compared in asymptomatic, non-insulin treated young (aged 18-50 years) adults with obesity and type 2 diabetes. The primary outcome was difference in circumferential peak early diastolic strain rate change (PEDSR), a biomarker of cardiac diastolic dysfunction 26 weeks after randomization. Secondary outcomes included other indices of cardiac structure and function, HbA1c and body weight. RESULTS Seventy-six participants were randomized (54% female, mean ± SD age 44 ± 6 years, diabetes duration 4.4 years, body mass index 35.3 ± 6.1 kg m-2 ), of whom 65% had ≥1 cardiovascular risk factor. Sixty-one participants had primary outcome data available. There were no statistically significant between-group differences (intention-to-treat; mean [95% confidence interval]) in PEDSR change (-0.01 [-0.07, +0.06] s-1 ), left ventricular ejection fraction (-1.98 [-4.90, +0.94]%), left ventricular mass (+1.14 [-5.23, +7.50] g) or aortic distensibility (-0.35 [-0.98, +0.28] mmHg-1 × 10-3 ) after 26 weeks. Reductions in HbA1c (-4.57 [-9.10, -0.37] mmol mol-1 ) and body weight (-3.88 [-5.74, -2.01] kg) were greater with liraglutide. CONCLUSION There were no differences in cardiovascular structure or function after short-term use of liraglutide and sitagliptin in younger adults with obesity and type 2 diabetes. Longer studies in patients with more severe cardiac dysfunction may be necessary before definitive conclusions can be made about putative pleiotropic properties of incretin-based therapies.
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Affiliation(s)
- David R Webb
- Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester, UK
- NIHR Leicester Biomedical Research Centre, Leicester General Hospital, Leicester, UK
| | - Zin Zin Htike
- Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester, UK
| | - Daniel J Swarbrick
- Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, UK
| | - Emer M Brady
- Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, UK
| | - Laura J Gray
- Department of Health Sciences, University of Leicester, Leicester, UK
| | - John Biglands
- NIHR Leeds Biomedical Research Centre, Chapel Allerton Hospital, Leeds, UK
| | - Gaurav S Gulsin
- Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, UK
| | - Joseph Henson
- Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester, UK
- NIHR Leicester Biomedical Research Centre, Leicester General Hospital, Leicester, UK
| | - Kamlesh Khunti
- Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester, UK
- NIHR Leicester Biomedical Research Centre, Leicester General Hospital, Leicester, UK
| | - Gerry P McCann
- NIHR Leicester Biomedical Research Centre, Leicester General Hospital, Leicester, UK
- Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, UK
| | - Helen L Waller
- Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester, UK
- NIHR Leicester Biomedical Research Centre, Leicester General Hospital, Leicester, UK
| | - M'Balu A Webb
- Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester, UK
- NIHR Leicester Biomedical Research Centre, Leicester General Hospital, Leicester, UK
| | - Jack A Sargeant
- Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester, UK
- NIHR Leicester Biomedical Research Centre, Leicester General Hospital, Leicester, UK
| | - Thomas Yates
- Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester, UK
- NIHR Leicester Biomedical Research Centre, Leicester General Hospital, Leicester, UK
| | - Francesco Zaccardi
- Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester, UK
| | - Melanie J Davies
- Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester, UK
- NIHR Leicester Biomedical Research Centre, Leicester General Hospital, Leicester, UK
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24
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Nazir SA, Shetye AM, Khan JN, Singh A, Arnold JR, Squire I, McCann GP. Inter-study repeatability of circumferential strain and diastolic strain rate by CMR tagging, feature tracking and tissue tracking in ST-segment elevation myocardial infarction. Int J Cardiovasc Imaging 2020; 36:1133-1146. [PMID: 32152811 PMCID: PMC7228913 DOI: 10.1007/s10554-020-01806-8] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2019] [Accepted: 02/24/2020] [Indexed: 02/07/2023]
Abstract
Strain assessment allows accurate evaluation of myocardial function and mechanics in ST-segment elevation myocardial infarction (STEMI). Strain using cardiovascular magnetic resonance (CMR) has traditionally been assessed with tagging but limitations of this technique have led to more widespread use of alternative methods, which may be more robust. We compared the inter-study repeatability of circumferential global peak-systolic strain (Ecc) and peak-early diastolic strain rate (PEDSR) derived by tagging with values obtained using novel cine-based software: Feature Tracking (FT) (TomTec, Germany) and Tissue Tracking (TT) (Circle cvi42, Canada) in patients following STEMI. Twenty male patients (mean age 56 ± 10 years, mean infarct size 13.7 ± 7.1% of left ventricular mass) were randomised to undergo CMR 1-5 days post-STEMI at 1.5 T or 3.0 T, repeated after ten minutes at the same field strength. Ecc and PEDSR were assessed using tagging, FT and TT. Inter-study repeatability was evaluated using Bland-Altman analyses, coefficients of variation (CoV) and intra-class correlation coefficient (ICC). Ecc (%) was significantly lower with tagging than with FT or TT at 1.5 T (- 9.5 ± 3.3 vs. - 17.5 ± 3.8 vs. -15.5 ± 5.2, respectively, p < 0.001) and 3.0 T (- 13.1 ± 1.8 vs. - 19.4 ± 2.9 vs. - 17.3 ± 2.1, respectively, p = 0.001). This was similar for PEDSR (.s-1): 1.5 T (0.6 ± 0.2 vs. 1.5 ± 0.4 vs. 1.0 ± 0.4, for tagging, FT and TT respectively, p < 0.001) and 3.0 T (0.6 ± 0.2 vs. 1.5 ± 0.3 vs. 0.9 ± 0.3, respectively, p < 0.001). Inter-study repeatability for Ecc at 1.5 T was good for tagging and excellent for FT and TT: CoV 16.7%, 6.38%, and 8.65%, respectively. Repeatability for Ecc at 3.0 T was good for all three techniques: CoV 14.4%, 11.2%, and 13.0%, respectively. However, repeatability of PEDSR was generally lower than that for Ecc at 1.5 T (CoV 15.1%, 13.1%, and 34.0% for tagging, FT and TT, respectively) and 3.0 T (CoV 23.0%, 18.6%, and 26.2%, respectively). Following STEMI, Ecc and PEDSR are higher when measured with FT and TT than with tagging. Inter-study repeatability of Ecc is good for tagging, excellent for FT and TT at 1.5 T, and good for all three methods at 3.0 T. The repeatability of PEDSR is good to moderate at 1.5 T and moderate at 3.0 T. Cine-based methods to assess Ecc following STEMI may be preferable to tagging.
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Affiliation(s)
- Sheraz A. Nazir
- Department of Cardiovascular Sciences, University of Leicester and the National Institute for Health for Research (NIHR) Leicester Cardiovascular Biomedical Research Centre, Glenfield Hospital, Leicester, LE3 9QF UK
| | - Abhishek M. Shetye
- Department of Cardiovascular Sciences, University of Leicester and the National Institute for Health for Research (NIHR) Leicester Cardiovascular Biomedical Research Centre, Glenfield Hospital, Leicester, LE3 9QF UK
| | - Jamal N. Khan
- Department of Cardiovascular Sciences, University of Leicester and the National Institute for Health for Research (NIHR) Leicester Cardiovascular Biomedical Research Centre, Glenfield Hospital, Leicester, LE3 9QF UK
| | - Anvesha Singh
- Department of Cardiovascular Sciences, University of Leicester and the National Institute for Health for Research (NIHR) Leicester Cardiovascular Biomedical Research Centre, Glenfield Hospital, Leicester, LE3 9QF UK
| | - Jayanth R. Arnold
- Department of Cardiovascular Sciences, University of Leicester and the National Institute for Health for Research (NIHR) Leicester Cardiovascular Biomedical Research Centre, Glenfield Hospital, Leicester, LE3 9QF UK
| | - Iain Squire
- Department of Cardiovascular Sciences, University of Leicester and the National Institute for Health for Research (NIHR) Leicester Cardiovascular Biomedical Research Centre, Glenfield Hospital, Leicester, LE3 9QF UK
| | - Gerry P. McCann
- Department of Cardiovascular Sciences, University of Leicester and the National Institute for Health for Research (NIHR) Leicester Cardiovascular Biomedical Research Centre, Glenfield Hospital, Leicester, LE3 9QF UK
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25
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Gulsin GS, Swarbrick DJ, Athithan L, Brady EM, Henson J, Baldry E, Argyridou S, Jaicim NB, Squire G, Walters Y, Marsh AM, McAdam J, Parke KS, Biglands JD, Yates T, Khunti K, Davies MJ, McCann GP. Effects of Low-Energy Diet or Exercise on Cardiovascular Function in Working-Age Adults With Type 2 Diabetes: A Prospective, Randomized, Open-Label, Blinded End Point Trial. Diabetes Care 2020; 43:1300-1310. [PMID: 32220917 DOI: 10.2337/dc20-0129] [Citation(s) in RCA: 49] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2020] [Accepted: 03/02/2020] [Indexed: 02/03/2023]
Abstract
OBJECTIVE To confirm the presence of subclinical cardiovascular dysfunction in working-age adults with type 2 diabetes (T2D) and determine whether this is improved by a low-energy meal replacement diet (MRP) or exercise training. RESEARCH DESIGN AND METHODS This article reports on a prospective, randomized, open-label, blinded end point trial with nested case-control study. Asymptomatic younger adults with T2D were randomized 1:1:1 to a 12-week intervention of 1) routine care, 2) supervised aerobic exercise training, or 3) a low-energy (∼810 kcal/day) MRP. Participants underwent echocardiography, cardiopulmonary exercise testing, and cardiac magnetic resonance (CMR) at baseline and 12 weeks. The primary outcome was change in left ventricular (LV) peak early diastolic strain rate (PEDSR) as measured by CMR. Healthy volunteers were enrolled for baseline case-control comparison. RESULTS Eighty-seven participants with T2D (age 51 ± 7 years, HbA1c 7.3 ± 1.1%) and 36 matched control participants were included. At baseline, those with T2D had evidence of diastolic dysfunction (PEDSR 1.01 ± 0.19 vs. 1.10 ± 0.16 s-1, P = 0.02) compared with control participants. Seventy-six participants with T2D completed the trial (30 routine care, 22 exercise, and 24 MRP). The MRP arm lost 13 kg in weight and had improved blood pressure, glycemia, LV mass/volume, and aortic stiffness. The exercise arm had negligible weight loss but increased exercise capacity. PEDSR increased in the exercise arm versus routine care (β = 0.132, P = 0.002) but did not improve with the MRP (β = 0.016, P = 0.731). CONCLUSIONS In asymptomatic working-age adults with T2D, exercise training improved diastolic function. Despite beneficial effects of weight loss on glycemic control, concentric LV remodeling, and aortic stiffness, a low-energy MRP did not improve diastolic function.
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Affiliation(s)
- Gaurav S Gulsin
- Department of Cardiovascular Sciences, University of Leicester and the National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, Leicester, U.K
| | - Daniel J Swarbrick
- Department of Cardiovascular Sciences, University of Leicester and the National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, Leicester, U.K
| | - Lavanya Athithan
- Department of Cardiovascular Sciences, University of Leicester and the National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, Leicester, U.K
| | - Emer M Brady
- Department of Cardiovascular Sciences, University of Leicester and the National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, Leicester, U.K
| | - Joseph Henson
- Diabetes Research Centre, University of Leicester and the NIHR Leicester Biomedical Research Centre, Leicester, U.K
| | - Emma Baldry
- Diabetes Research Centre, University of Leicester and the NIHR Leicester Biomedical Research Centre, Leicester, U.K
| | - Stavroula Argyridou
- Diabetes Research Centre, University of Leicester and the NIHR Leicester Biomedical Research Centre, Leicester, U.K
| | - Nishal B Jaicim
- Leicester Clinical Trials Unit, University of Leicester, Leicester, U.K
| | - Gareth Squire
- Department of Cardiovascular Sciences, University of Leicester and the National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, Leicester, U.K
| | - Yvette Walters
- Leicester Clinical Trials Unit, University of Leicester, Leicester, U.K
| | - Anna-Marie Marsh
- Department of Cardiovascular Sciences, University of Leicester and the National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, Leicester, U.K
| | - John McAdam
- Department of Cardiovascular Sciences, University of Leicester and the National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, Leicester, U.K
| | - Kelly S Parke
- Department of Cardiovascular Sciences, University of Leicester and the National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, Leicester, U.K
| | | | - Thomas Yates
- Diabetes Research Centre, University of Leicester and the NIHR Leicester Biomedical Research Centre, Leicester, U.K
| | - Kamlesh Khunti
- Diabetes Research Centre, University of Leicester and the NIHR Leicester Biomedical Research Centre, Leicester, U.K
| | - Melanie J Davies
- Diabetes Research Centre, University of Leicester and the NIHR Leicester Biomedical Research Centre, Leicester, U.K
| | - Gerry P McCann
- Department of Cardiovascular Sciences, University of Leicester and the National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, Leicester, U.K.
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26
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Diabetic cardiomyopathy: molecular mechanisms, detrimental effects of conventional treatment, and beneficial effects of natural therapy. Heart Fail Rev 2020; 24:279-299. [PMID: 30349977 DOI: 10.1007/s10741-018-9749-1] [Citation(s) in RCA: 114] [Impact Index Per Article: 22.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
ABSTARCT Diabetic complications are among the largely exigent health problems currently. Cardiovascular complications, including diabetic cardiomyopathy (DCM), account for more than 80% of diabetic deaths. Investigators are exploring new therapeutic targets to slow or abate diabetes because of the growing occurrence and augmented risk of deaths due to its complications. Research on rodent models of type 1 and type 2 diabetes mellitus, and the use of genetic engineering techniques in mice and rats have significantly sophisticated for our understanding of the molecular mechanisms in human DCM. DCM is featured by pathophysiological mechanisms that are hyperglycemia, insulin resistance, oxidative stress, left ventricular hypertrophy, damaged left ventricular systolic and diastolic functions, myocardial fibrosis, endothelial dysfunction, myocyte cell death, autophagy, and endoplasmic reticulum stress. A number of molecular and cellular pathways, such as cardiac ubiquitin proteasome system, FoxO transcription factors, hexosamine biosynthetic pathway, polyol pathway, protein kinase C signaling, NF-κB signaling, peroxisome proliferator-activated receptor signaling, Nrf2 pathway, mitogen-activated protein kinase pathway, and micro RNAs, play a major role in DCM. Currently, there are a few drugs for the management of DCM and some of them have considerable adverse effects. So, researchers are focusing on the natural products to ameliorate it. Hence, in this review, we discuss the pathogical, molecular, and cellular mechanisms of DCM; the current diagnostic methods and treatments; adverse effects of conventional treatment; and beneficial effects of natural product-based therapeutics, which may pave the way to new treatment strategies. Graphical Abstract.
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27
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Athithan L, Chowdhary A, Swarbrick D, Gulsin GS, Singh A, Jex N, Jain M, Khan JN, Graham-Brown MPM, Wormleighton JV, Parke KS, Davies MJ, Karamitsos T, Clarke K, Neubauer S, Levelt E, McCann GP. Male sex adversely affects the phenotypic expression of diabetic heart disease. Ther Adv Endocrinol Metab 2020; 11:2042018820927179. [PMID: 32523675 PMCID: PMC7257847 DOI: 10.1177/2042018820927179] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2019] [Accepted: 04/21/2020] [Indexed: 01/09/2023] Open
Abstract
BACKGROUND Type 2 diabetes (T2D) is associated with an increased risk of heart failure (HF) and cardiovascular mortality. A large-scale meta-analysis on HF found that diabetes was more frequent in women than men, and diabetes appeared to have attenuated the otherwise protective effect of female sex on progression of cardiomyopathy. The exact underlying mechanisms for this remain unclear. Here, we aimed to determine the effect of sex on the phenotypic expression of diabetic heart disease in patients with T2D. METHODS A total of 62 male [mean age 44 ± 8 years, body mass index (BMI) 33 ± 5 kg/m2, mean HBA1c of 7.8 ± 1.8%] and 67 female (44 ± 10 years, BMI 35 ± 6 kg/m2, HBA1c 7.6 ± 1.2%) T2D patients on oral glucose-lowering treatment, and 16 male (48 ± 17 years, BMI 25 ± 3 kg/m2) and 14 female (50 ± 10 years, BMI 25 ± 4 kg/m2) controls were recruited. Left ventricular (LV) volumes, mass, function and deformation, and left atrial (LA) volumes and function were assessed using cardiac magnetic resonance imaging (CMR). RESULTS Participants in all groups were of similar age, and there were no significant differences in blood pressure (BP), diabetes duration or metabolic profile between the two diabetes groups. Concentric remodeling was present in both sexes (p < 0.0001), with greater degree of concentric hypertrophy in males (12%, p = 0.0015). Biplane LA ejection fraction (LAEF) (p = 0.038), peak systolic circumferential strain (p < 0.0001) and diastolic strain rates (p = 0.001) were significantly reduced in men compared with women with T2D. There were no significant differences in biplane LAEF, peak systolic circumferential strain and diastolic strain rates in women with T2D compared with female controls. Whereas in women with T2D, glycaemic control was linked to LV contractile function, there was no such relationship in men with T2D. CONCLUSION Male sex adversely affects the phenotypic expression of diabetic heart disease. The striking differences in the cardiac phenotype between male and female patients with T2D promote awareness of gender-specific risk factors in search of treatment and prevention of diabetes-associated HF. CONDENSED ABSTRACT We aimed to determine the effect of sex on the phenotypic expression of diabetic heart disease in patients with T2D. While our findings support the notion that in T2D, male sex adversely affects the phenotypic expression of diabetic heart disease, this is in apparent conflict with the previous large-scale study showing diabetes attenuates the otherwise protective effect of female sex on progression of cardiomyopathy. Further longitudinal studies looking at gender differences in clinical outcomes in T2D patients are needed. These sex-related differences promote awareness of sex-specific risk factors in search of treatment and prevention of diabetes-associated HF.
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Affiliation(s)
- Lavanya Athithan
- Department of Cardiovascular Sciences, University of Leicester and the Leicester NIHR Biomedical Research Centre, Leicester, UK
| | - Amrit Chowdhary
- Multidisciplinary Cardiovascular Research Centre and Biomedical Imaging Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, West Yorkshire, UK
| | - Daniel Swarbrick
- Department of Cardiovascular Sciences, University of Leicester and the Leicester NIHR Biomedical Research Centre, Leicester, UK
| | - Gaurav S. Gulsin
- Department of Cardiovascular Sciences, University of Leicester and the Leicester NIHR Biomedical Research Centre, Leicester, UK
| | - Anvesha Singh
- Department of Cardiovascular Sciences, University of Leicester and the Leicester NIHR Biomedical Research Centre, Leicester, UK
| | - Nicholas Jex
- Multidisciplinary Cardiovascular Research Centre and Biomedical Imaging Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, West Yorkshire, UK
| | - Manali Jain
- Multidisciplinary Cardiovascular Research Centre and Biomedical Imaging Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, West Yorkshire, UK
| | - Jamal N. Khan
- Department of Cardiovascular Sciences, University of Leicester and the Leicester NIHR Biomedical Research Centre, Leicester, UK
| | - Matthew P. M. Graham-Brown
- Department of Cardiovascular Sciences, University of Leicester and the Leicester NIHR Biomedical Research Centre, Leicester, UK
| | - Joanne V. Wormleighton
- Department of Cardiovascular Sciences, University of Leicester and the Leicester NIHR Biomedical Research Centre, Leicester, UK
| | - Kelly S. Parke
- Department of Cardiovascular Sciences, University of Leicester and the Leicester NIHR Biomedical Research Centre, Leicester, UK
| | | | - Theodoros Karamitsos
- Radcliffe Department of Medicine, University of Oxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, University of Oxford, Oxford, Oxfordshire, UK
| | - Kieran Clarke
- Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, Oxfordshire, UK
| | - Stefan Neubauer
- Radcliffe Department of Medicine, University of Oxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, University of Oxford, Oxford, Oxfordshire, UK
| | | | - Gerry P. McCann
- Department of Cardiovascular Sciences, University of Leicester and the Leicester NIHR Biomedical Research Centre, Leicester, UK
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28
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Athithan L, Gulsin GS, McCann GP, Levelt E. Diabetic cardiomyopathy: Pathophysiology, theories and evidence to date. World J Diabetes 2019; 10:490-510. [PMID: 31641426 PMCID: PMC6801309 DOI: 10.4239/wjd.v10.i10.490] [Citation(s) in RCA: 61] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Revised: 09/25/2019] [Accepted: 09/25/2019] [Indexed: 02/05/2023] Open
Abstract
The prevalence of type 2 diabetes (T2D) has increased worldwide and doubled over the last two decades. It features among the top 10 causes of mortality and morbidity in the world. Cardiovascular disease is the leading cause of complications in diabetes and within this, heart failure has been shown to be the leading cause of emergency admissions in the United Kingdom. There are many hypotheses and well-evidenced mechanisms by which diabetic cardiomyopathy as an entity develops. This review aims to give an overview of these mechanisms, with particular emphasis on metabolic inflexibility. T2D is associated with inefficient substrate utilisation, an inability to increase glucose metabolism and dependence on fatty acid oxidation within the diabetic heart resulting in mitochondrial uncoupling, glucotoxicity, lipotoxicity and initially subclinical cardiac dysfunction and finally in overt heart failure. The review also gives a concise update on developments within clinical imaging, specifically cardiac magnetic resonance studies to characterise and phenotype early cardiac dysfunction in T2D. A better understanding of the pathophysiology involved provides a platform for targeted therapy in diabetes to prevent the development of early heart failure with preserved ejection fraction.
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Affiliation(s)
- Lavanya Athithan
- Department of Cardiovascular Sciences, University of Leicester and NIHR Leicester Cardiovascular Biomedical Research Centre, Glenfield Hospital, Leicester LE3 9QP, United Kingdom
| | - Gaurav S Gulsin
- Department of Cardiovascular Sciences, University of Leicester and NIHR Leicester Cardiovascular Biomedical Research Centre, Glenfield Hospital, Leicester LE3 9QP, United Kingdom
| | - Gerald P McCann
- Department of Cardiovascular Sciences, University of Leicester and NIHR Leicester Cardiovascular Biomedical Research Centre, Glenfield Hospital, Leicester LE3 9QP, United Kingdom
| | - Eylem Levelt
- Multidisciplinary Cardiovascular Research Centre and Biomedical Imaging Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds LF9 7TF, United Kingdom
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29
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Hu BY, Wang J, Yang ZG, Ren Y, Jiang L, Xie LJ, Liu X, Gao Y, Shen MT, Xu HY, Shi K, Li ZL, Xia CC, Peng WL, Deng MY, Li H, Guo YK. Cardiac magnetic resonance feature tracking for quantifying right ventricular deformation in type 2 diabetes mellitus patients. Sci Rep 2019; 9:11148. [PMID: 31366951 PMCID: PMC6668453 DOI: 10.1038/s41598-019-46755-y] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2019] [Accepted: 06/14/2019] [Indexed: 02/05/2023] Open
Abstract
To determine the feasibility of deformation analysis in the right ventricle (RV) using cardiovascular magnetic resonance myocardial feature tracking (CMR-FT) in type 2 diabetes mellitus (T2DM) patients. We enrolled 104 T2DM patients, including 14 with impaired right ventricular ejection fraction (RVEF) and 90 with preserved RVEF, and 26 healthy controls in this prospective study. CMR was used to determine RV feature-tracking parameters. RV strain parameters were compared among the controls, patients with preserved and reduced RVEF. Binary logistic regression was used to predict RV dysfunction. Receiver operating characteristic analysis was used to assess the diagnostic accuracy. The agreement was tested by Bland-Altman analysis. Compared with controls, longitudinal and circumferential global peak strain (PS) and PS at mid-ventricular, apical slices were significantly decreased in T2DM patients with or without reduced RVEF (p < 0.05). Within the T2DM patients, the global longitudinal PS (GLPS) and the longitudinal PS at mid-ventricular segments were significantly reduced in the reduced RVEF group than in preserved RVEF groups (p < 0.05). GLPS was an independent predictor of RV dysfunction (odds ratio: 1.246, 95% CI: 1.037-1.496; p = 0.019). The GLPS demonstrated greater diagnostic accuracy (area under curve: 0.716) to predict RV dysfunction. On Bland-Altman analysis, global circumferential PS and GLPS had the best intra- and inter-observer agreement, respectively. In T2DM patients, CMR-FT could quantify RV deformation and identify subclinical RV dysfunction in those with normal RVEF. Further, RV strain parameters are potential predictors for RV dysfunction in T2DM patients.
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Affiliation(s)
- Bi-Yue Hu
- Department of Radiology, West China Hospital, Sichuan University, 37# Guo Xue Xiang, Chengdu, Sichuan, 610041, China
- Department of Radiology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China
| | - Jin Wang
- Department of Radiology, West China Hospital, Sichuan University, 37# Guo Xue Xiang, Chengdu, Sichuan, 610041, China
| | - Zhi-Gang Yang
- Department of Radiology, West China Hospital, Sichuan University, 37# Guo Xue Xiang, Chengdu, Sichuan, 610041, China.
| | - Yan Ren
- Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, 37# Guo Xue Xiang, Chengdu, Sichuan, 610041, China
| | - Li Jiang
- Department of Radiology, West China Hospital, Sichuan University, 37# Guo Xue Xiang, Chengdu, Sichuan, 610041, China
| | - Lin-Jun Xie
- Department of Radiology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China
| | - Xi Liu
- Department of Radiology, West China Hospital, Sichuan University, 37# Guo Xue Xiang, Chengdu, Sichuan, 610041, China
| | - Yue Gao
- Department of Radiology, West China Hospital, Sichuan University, 37# Guo Xue Xiang, Chengdu, Sichuan, 610041, China
| | - Meng-Ting Shen
- Department of Radiology, West China Hospital, Sichuan University, 37# Guo Xue Xiang, Chengdu, Sichuan, 610041, China
| | - Hua-Yan Xu
- Department of Radiology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China
| | - Ke Shi
- Department of Radiology, West China Hospital, Sichuan University, 37# Guo Xue Xiang, Chengdu, Sichuan, 610041, China
| | - Zhen-Lin Li
- Department of Radiology, West China Hospital, Sichuan University, 37# Guo Xue Xiang, Chengdu, Sichuan, 610041, China
| | - Chun-Chao Xia
- Department of Radiology, West China Hospital, Sichuan University, 37# Guo Xue Xiang, Chengdu, Sichuan, 610041, China
| | - Wan-Lin Peng
- Department of Radiology, West China Hospital, Sichuan University, 37# Guo Xue Xiang, Chengdu, Sichuan, 610041, China
| | - Ming-Yan Deng
- Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, 37# Guo Xue Xiang, Chengdu, Sichuan, 610041, China
| | - Hong Li
- Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, 610041, China
| | - Ying-Kun Guo
- Department of Radiology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China.
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Gulsin GS, Brady EM, Swarbrick DJ, Athithan L, Henson J, Baldry E, McAdam J, Marsh AM, Parke KS, Wormleighton JV, Levelt E, Yates T, Bodicoat D, Khunti K, Davies MJ, McCann GP. Rationale, design and study protocol of the randomised controlled trial: Diabetes Interventional Assessment of Slimming or Training tO Lessen Inconspicuous Cardiovascular Dysfunction (the DIASTOLIC study). BMJ Open 2019; 9:e023207. [PMID: 30928925 PMCID: PMC6475184 DOI: 10.1136/bmjopen-2018-023207] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
INTRODUCTION Despite their young age and relatively short duration of disease, younger adults with type 2 diabetes (T2D) already have diastolic dysfunction and may be at risk of incipient heart failure. Whether weight loss or exercise training improve cardiac dysfunction in people with T2D remains to be established. METHODS AND ANALYSIS Prospective, randomised, open-label, blind endpoint trial. The primary aim of the study is to determine if diastolic function can be improved by either a meal replacement plan or a supervised exercise programme, compared with guideline-directed care. A total of 90 obese participants with T2D (aged 18-65 years), diabetes duration <12 years and not on insulin treatment will be randomised to either guideline-directed clinical care with lifestyle coaching, a low-energy meal replacement diet (average ≈810 kcal/day) or a supervised exercise programme for 12 weeks. Participants undergo glycometabolic profiling, cardiopulmonary exercise testing, echocardiography and MRI scanning to assesses cardiac structure and function and dual-energy X-ray absorptiometry scanning for body composition. Key secondary aims are to assess the effects of the interventions on glycaemic control and insulin resistance, exercise capacity, blood pressure, changes in body composition and association of favourable cardiac remodelling with improvements in weight loss, exercise capacity and glycometabolic control. ETHICS AND DISSEMINATION The study has full ethical approval, and data collection was completed in August 2018. The study results will be submitted for publication within 6 months of completion. TRIAL REGISTRATION NUMBER NCT02590822; Pre-results.
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Affiliation(s)
- Gaurav Singh Gulsin
- Department of Cardiovascular Sciences, University of Leicester and the Leicester NIHR Biomedical Research Centre, Glenfield Hospital, Leicester, UK
| | - Emer M Brady
- Diabetes Research Centre, University of Leicester and the Leicester NIHR Biomedical Research Centre, Leicester General Hospital, Leicester, UK
| | - Daniel J Swarbrick
- Department of Cardiovascular Sciences, University of Leicester and the Leicester NIHR Biomedical Research Centre, Glenfield Hospital, Leicester, UK
| | - Lavanya Athithan
- Department of Cardiovascular Sciences, University of Leicester and the Leicester NIHR Biomedical Research Centre, Glenfield Hospital, Leicester, UK
| | - Joseph Henson
- National College of Sport and Exercise Medicine, University of Loughborough, Loughborough, UK
| | - Emma Baldry
- Diabetes Research Centre, University of Leicester and the Leicester NIHR Biomedical Research Centre, Leicester General Hospital, Leicester, UK
| | - John McAdam
- Department of Cardiovascular Sciences, University of Leicester and the Leicester NIHR Biomedical Research Centre, Glenfield Hospital, Leicester, UK
| | - Anna-Marie Marsh
- Department of Cardiovascular Sciences, University of Leicester and the Leicester NIHR Biomedical Research Centre, Glenfield Hospital, Leicester, UK
| | - Kelly S Parke
- Department of Cardiovascular Sciences, University of Leicester and the Leicester NIHR Biomedical Research Centre, Glenfield Hospital, Leicester, UK
| | - Joanne V Wormleighton
- Department of Cardiovascular Sciences, University of Leicester and the Leicester NIHR Biomedical Research Centre, Glenfield Hospital, Leicester, UK
| | - Eylem Levelt
- University of Leeds, Multidisciplinary Cardiovascular Research Centre and Biomedical Imaging Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, Leeds, UK
| | - Thomas Yates
- Diabetes Research Centre, University of Leicester and the Leicester NIHR Biomedical Research Centre, Leicester General Hospital, Leicester, UK
- National College of Sport and Exercise Medicine, University of Loughborough, Loughborough, UK
| | - Danielle Bodicoat
- Diabetes Research Centre, University of Leicester and the Leicester NIHR Biomedical Research Centre, Leicester General Hospital, Leicester, UK
| | - Kamlesh Khunti
- Diabetes Research Centre, University of Leicester and the Leicester NIHR Biomedical Research Centre, Leicester General Hospital, Leicester, UK
| | - Melanie J Davies
- Diabetes Research Centre, University of Leicester and the Leicester NIHR Biomedical Research Centre, Leicester General Hospital, Leicester, UK
| | - Gerry P McCann
- Department of Cardiovascular Sciences, University of Leicester and the Leicester NIHR Biomedical Research Centre, Glenfield Hospital, Leicester, UK
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Gulsin GS, Athithan L, McCann GP. Diabetic cardiomyopathy: prevalence, determinants and potential treatments. Ther Adv Endocrinol Metab 2019; 10:2042018819834869. [PMID: 30944723 PMCID: PMC6437329 DOI: 10.1177/2042018819834869] [Citation(s) in RCA: 72] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2018] [Accepted: 02/08/2019] [Indexed: 12/18/2022] Open
Abstract
The prevalence of type 2 diabetes (T2D) has reached a pandemic scale. These patients are at a substantially elevated risk of developing cardiovascular disease, with heart failure (HF) being a leading cause of morbidity and mortality. Even in the absence of traditional risk factors, diabetes still confers up to a twofold increased risk of developing HF. This has led to identifying diabetes as an independent risk factor for HF and recognition of the distinct clinical entity, diabetic cardiomyopathy. Despite a wealth of research interest, the prevalence and determinants of diabetic cardiomyopathy remain uncertain. This limited understanding of the pathophysiology of diabetic heart disease has also hindered development of effective treatments. Tight blood-glucose and blood-pressure control have not convincingly been shown to reduce macrovascular outcomes in T2D. There is, however, emerging evidence that T2D is reversible and that the metabolic abnormalities can be reversed with weight loss. Increased aerobic exercise capacity is associated with significantly lower cardiovascular and overall mortality in diabetes. Whether such lifestyle modifications as weight loss and exercise may ameliorate the structural and functional derangements of the diabetic heart has yet to be established. In this review, the link between T2D and myocardial dysfunction is explored. Insights into the structural and functional perturbations that typify the diabetic heart are first described. This is followed by an examination of the pathophysiological mechanisms that contribute to the development of cardiovascular disease in T2D. Lastly, the current and emerging therapeutic strategies to prevent or ameliorate cardiac dysfunction in T2D are evaluated.
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Affiliation(s)
- Gaurav S. Gulsin
- Department of Cardiovascular Sciences, University of Leicester and the Leicester NIHR Biomedical Research Centre, Leicester, UK
| | - Lavanya Athithan
- Department of Cardiovascular Sciences, University of Leicester and the Leicester NIHR Biomedical Research Centre, Leicester, UK
| | - Gerry P. McCann
- Department of Cardiovascular Sciences, University of Leicester and the Leicester NIHR Biomedical Research Centre, Glenfield Hospital, Groby Road, Leicester LE3 9QP, UK
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Vetrone LM, Zaccardi F, Webb DR, Seidu S, Gholap NN, Pitocco D, Davies MJ, Khunti K. Cardiovascular and mortality events in type 2 diabetes cardiovascular outcomes trials: a systematic review with trend analysis. Acta Diabetol 2019; 56:331-339. [PMID: 30456728 PMCID: PMC6394717 DOI: 10.1007/s00592-018-1253-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2018] [Accepted: 11/06/2018] [Indexed: 12/21/2022]
Abstract
AIMS To investigate cardiovascular disease and mortality trends in control arm participants of diabetes cardiovascular outcome trials (CVOTs). METHODS We electronically searched CVOTs published before October 2017. Data on all-cause mortality, cardiovascular mortality and events, and baseline characteristics were collected, along with study calendar years. Trends were estimated using negative binomial regressions and reported as rate ratio (RR) per 5-year intervals. RESULTS 26 CVOTs, conducted from 1961 to 2015, included 86788 participants with 6543 all-cause deaths, 3265 cardiovascular deaths, and 7657 3-point major adverse cardiovascular events (3-P MACE; combined endpoint of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke). In unadjusted analysis, there was an increasing trend for 3-P MACE rates over time (5-year RR 1.57; 95% CI 1.34, 1.84); a small increasing trend for cardiovascular disease mortality rates (1.13; 1.01, 1.26); and stable rates for all-cause death. Adjusting for age, sex, previous myocardial infarction, and diabetes duration, there was no evidence of trends for 3-P MACE or cardiovascular disease mortality rates, while reducing rates were observed for nonfatal myocardial infarction (5-year RR: 0.72; 0.54, 0.96), total stroke (0.76; 0.66, 0.88), and nonfatal stroke (0.60; 0.43, 0.82). CONCLUSIONS In contrast to real-world data, there was no evidence of an improvement in all-cause and cardiovascular mortality in type 2 diabetes participants included in control arms of randomised clinical trials across 5 decades. Further studies should investigate whether and how dissimilarities in populations, procedures, and assessments of exposures and outcomes explain the differences between real-world setting and clinical trials.
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Affiliation(s)
- Lorenzo M Vetrone
- Diabetes Research Centre, Leicester Diabetes Centre, Leicester General Hospital, Gwendolen Rd, Leicester, LE5 4PW, England, UK
- Servizio di Diabetologia, Catholic University School of Medicine, Largo Francesco Vito 1, 00198, Rome, Italy
| | - Francesco Zaccardi
- Diabetes Research Centre, Leicester Diabetes Centre, Leicester General Hospital, Gwendolen Rd, Leicester, LE5 4PW, England, UK.
| | - David R Webb
- Diabetes Research Centre, Leicester Diabetes Centre, Leicester General Hospital, Gwendolen Rd, Leicester, LE5 4PW, England, UK
| | - Sam Seidu
- Diabetes Research Centre, Leicester Diabetes Centre, Leicester General Hospital, Gwendolen Rd, Leicester, LE5 4PW, England, UK
| | - Nitin N Gholap
- University Hospital of Coventry and Warwickshire, Coventry, Clifford Bridge Rd, Coventry, CV2 2DX, England, UK
| | - Dario Pitocco
- Servizio di Diabetologia, Catholic University School of Medicine, Largo Francesco Vito 1, 00198, Rome, Italy
| | - Melanie J Davies
- Diabetes Research Centre, Leicester Diabetes Centre, Leicester General Hospital, Gwendolen Rd, Leicester, LE5 4PW, England, UK
| | - Kamlesh Khunti
- Diabetes Research Centre, Leicester Diabetes Centre, Leicester General Hospital, Gwendolen Rd, Leicester, LE5 4PW, England, UK
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MR extracellular volume mapping and non-contrast T1ρ mapping allow early detection of myocardial fibrosis in diabetic monkeys. Eur Radiol 2019; 29:3006-3016. [PMID: 30643944 PMCID: PMC6510861 DOI: 10.1007/s00330-018-5950-9] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2018] [Revised: 11/04/2018] [Accepted: 12/04/2018] [Indexed: 02/05/2023]
Abstract
Objective To detect diffuse myocardial fibrosis in different severity levels of left ventricular diastolic dysfunction (DD) in spontaneous type 2 diabetes mellitus (T2DM) rhesus monkeys. Methods Eighteen spontaneous T2DM and nine healthy monkeys were studied. Echocardiography was performed for diastolic function classification. Cardiac magnetic resonance (CMR) imaging was performed to obtain extracellular volume fraction (ECV) maps and T1ρ maps at two different spin-locking frequencies. ECV values, T1ρ values, and myocardial fibrosis index (mFI) values which are based on the dispersion of T1ρ, were calculated. Global peak diastolic longitudinal strain rates (GSrL) were also obtained. Results Echocardiography results showed mild DD in nine T2DM monkeys and moderate DD in the other nine. The global ECV values were significantly different among healthy animals as compared with animals with mild DD or moderate DD, and the ECV values of animals with moderate DD were significantly higher as compared with those of mild DD. The mFI values increased progressively from healthy animals to those with mild DD and then to those with moderate DD. Diastolic function indicators (e.g., early diastolic mitral annulus velocity, GSrL) correlated well with ECV and mFI. Conclusions Monkeys with T2DM exhibit increased ECV, T1ρ, and mFI values, which may be indicative of the expansion of extracellular volume and the deposition of excessive collagen. T1ρ mapping may have the potential to be used for diffuse myocardial fibrosis assessment. Key Points • Monkeys with T2DM exhibit increased ECV, T1ρ, and mFI values, which may be indicative of the expansion of extracellular volume and the deposition of excessive collagen. • The relationship between diastolic dysfunction and diffuse myocardial fibrosis may be demonstrated by imaging markers. • Non-contrast T1ρ mapping may have the potential to be used for diffuse myocardial assessment. Electronic supplementary material The online version of this article (10.1007/s00330-018-5950-9) contains supplementary material, which is available to authorized users.
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Graham-Brown MPM, Adenwalla SF, Lai FY, Hunt WH, Parke K, Gulsin G, Burton JO, McCann GP. The reproducibility of cardiac magnetic resonance imaging measures of aortic stiffness and their relationship to cardiac structure in prevalent haemodialysis patients. Clin Kidney J 2018; 11:864-873. [PMID: 30524722 PMCID: PMC6275449 DOI: 10.1093/ckj/sfy042] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2018] [Accepted: 04/27/2018] [Indexed: 01/17/2023] Open
Abstract
BACKGROUND Aortic stiffness is one of the earliest signs of cardiovascular disease (CVD) in patients with chronic kidney disease and an independent predictor of mortality. It is thought to drive left ventricular (LV) remodelling, an established biomarker for mortality. The relationship between direct and indirect measures of aortic stiffness and LV remodelling is not defined in dialysis patients, nor are the reproducibility of methods used to assess aortic stiffness using cardiac magnetic resonance (CMR) imaging. METHODS Using 3T CMR, we report the results of (i) the interstudy, interobserver and intra-observer reproducibility of ascending aortic distensibility (AAD), descending aortic distensibility (DAD) and aortic pulse wave velocity (aPWV) in 10 haemodialysis (HD) patients and (ii) the relationship between AAD, DAD and aPWV and LV mass index (LVMi) and LV remodelling in 70 HD patients. RESULTS Inter- and intra-observer variability of AAD, DAD and aPWV were excellent [intraclass correlation (ICC) > 0.9 for all]. Interstudy reproducibility of AAD was excellent {ICC 0.94 [95% confidence interval (CI) 0.78-0.99]}, but poor for DAD and aPWV [ICC 0.51 (-0.13-0.85) and 0.51 (-0.31-0.89)]. AAD, DAD and aPWV associated with LVMi on univariate analysis (β = -0.244, P = 0.04; β =-0.315, P < 0.001 and β = 0.242, P = 0.04, respectively). Only systolic blood pressure, serum phosphate and a history of CVD remained independent determinants of LVMi on multivariable linear regression. CONCLUSIONS AAD is the most reproducible CMR-derived measure of aortic stiffness in HD patients. CMR-derived measures of aortic stiffness were not independent determinants of LVMi in HD patients. Whether one should target blood pressure over aortic stiffness to mitigate cardiovascular risk still needs determination.
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Affiliation(s)
- Matthew P M Graham-Brown
- John Walls Renal Unit, University Hospitals Leicester NHS Trust, Leicester, UK
- Department of Infection Immunity and Inflammation, School of Medicine and Biological Sciences, University of Leicester, Leicester, UK
- National Centre for Sport and Exercise Medicine, School of Sport, Exercise and Health Sciences, Loughborough University, Leicestershire, UK
- Correspondence and offprint requests to: Matthew P.M. Graham-Brown; E-mail:
| | - Sherna F Adenwalla
- Department of Cardiovascular Sciences, University of Leicester, Leicester, UK
| | - Florence Y Lai
- Department of Cardiovascular Sciences, University of Leicester, Leicester, UK
| | - William H Hunt
- Department of Cardiovascular Sciences, University of Leicester, Leicester, UK
| | - Kelly Parke
- Department of Cardiovascular Sciences, University of Leicester, Leicester, UK
| | - Gaurav Gulsin
- Department of Cardiovascular Sciences, University of Leicester, Leicester, UK
| | - James O Burton
- John Walls Renal Unit, University Hospitals Leicester NHS Trust, Leicester, UK
- Department of Infection Immunity and Inflammation, School of Medicine and Biological Sciences, University of Leicester, Leicester, UK
- Department of Cardiovascular Sciences, University of Leicester, Leicester, UK
| | - Gerry P McCann
- Department of Cardiovascular Sciences, University of Leicester, Leicester, UK
- NIHR Leicester Cardiovascular Biomedical Research Centre, Glenfield Hospital, Leicester, UK
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Singh A, Horsfield MA, Bekele S, Greenwood JP, Dawson DK, Berry C, Hogrefe K, Kelly DJ, Houston JG, Guntur Ramkumar P, Uddin A, Suzuki T, McCann GP. Aortic stiffness in aortic stenosis assessed by cardiovascular MRI: a comparison between bicuspid and tricuspid valves. Eur Radiol 2018; 29:2340-2349. [PMID: 30488106 PMCID: PMC6443917 DOI: 10.1007/s00330-018-5775-6] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2018] [Revised: 08/03/2018] [Accepted: 09/19/2018] [Indexed: 11/17/2022]
Abstract
Objectives To compare aortic size and stiffness parameters on MRI between bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV) patients with aortic stenosis (AS). Methods MRI was performed in 174 patients with asymptomatic moderate-severe AS (mean AVAI 0.57 ± 0.14 cm2/m2) and 23 controls on 3T scanners. Valve morphology was available/analysable in 169 patients: 63 BAV (41 type-I, 22 type-II) and 106 TAV. Aortic cross-sectional areas were measured at the level of the pulmonary artery bifurcation. The ascending and descending aorta (AA, DA) distensibility, and pulse wave velocity (PWV) around the aortic arch were calculated. Results The AA and DA areas were lower in the controls, with no difference in DA distensibility or PWV, but slightly lower AA distensibility than in the patient group. With increasing age, there was a decrease in distensibility and an increase in PWV. After correcting for age, the AA maximum cross-sectional area was higher in bicuspid vs. tricuspid patients (12.97 [11.10, 15.59] vs. 10.06 [8.57, 12.04] cm2, p < 0.001), but there were no significant differences in AA distensibility (p = 0.099), DA distensibility (p = 0.498) or PWV (p = 0.235). Patients with BAV type-II valves demonstrated a significantly higher AA distensibility and lower PWV compared to type-I, despite a trend towards higher AA area. Conclusions In patients with significant AS, BAV patients do not have increased aortic stiffness compared to those with TAV despite increased ascending aortic dimensions. Those with type-II BAV have less aortic stiffness despite greater dimensions. These results demonstrate a dissociation between aortic dilatation and stiffness and suggest that altered flow patterns may play a role. Key Points • Both cellular abnormalities secondary to genetic differences and abnormal flow patterns have been implicated in the pathophysiology of aortic dilatation and increased vascular complications associated with bicuspid aortic valves (BAV). • We demonstrate an increased ascending aortic size in patients with BAV and moderate to severe AS compared to TAV and controls, but no difference in aortic stiffness parameters, therefore suggesting a dissociation between dilatation and stiffness. • Sub-group analysis showed greater aortic size but lower stiffness parameters in those with BAV type-II AS compared to BAV type-I. Electronic supplementary material The online version of this article (10.1007/s00330-018-5775-6) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Anvesha Singh
- Department of Cardiovascular Sciences, University of Leicester and Cardiovascular Theme, NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Groby road, Leicester, LE3 9QP, UK.
| | | | - Soliana Bekele
- Department of Cardiovascular Sciences, University of Leicester and Cardiovascular Theme, NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Groby road, Leicester, LE3 9QP, UK
| | - John P Greenwood
- Multidisciplinary Cardiovascular Research Centre & The Division of Biomedical Imaging, Leeds Institute of Cardiovascular & Metabolic Medicine, Leeds University, Leeds, LS2 9JT, UK
| | - Dana K Dawson
- Cardiovascular Medicine Research Unit, School of Medicine and Dentistry, University of Aberdeen, Polwarth Building, Foresterhill, Aberdeen, AB25 2ZD, UK
| | - Colin Berry
- BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow, G12 8TA, UK
| | - Kai Hogrefe
- Cardiology Department, Kettering General Hospital Foundation Trust, Rothwell Rd, Kettering, NN16 8UZ, UK
| | - Damian J Kelly
- Cardiology Department, Royal Derby Hospital, Uttoxeter Rd, Derby, DE22 3NE, UK
| | - John G Houston
- Division of Molecular & Clinical Medicine, Ninewells Hospital and Medical School, Dundee, DD1 9SY, UK
| | - Prasad Guntur Ramkumar
- Division of Molecular & Clinical Medicine, Ninewells Hospital and Medical School, Dundee, DD1 9SY, UK
| | - Akhlaque Uddin
- Multidisciplinary Cardiovascular Research Centre & The Division of Biomedical Imaging, Leeds Institute of Cardiovascular & Metabolic Medicine, Leeds University, Leeds, LS2 9JT, UK
| | - Toru Suzuki
- Department of Cardiovascular Sciences, University of Leicester and Cardiovascular Theme, NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Groby road, Leicester, LE3 9QP, UK
| | - Gerry P McCann
- Department of Cardiovascular Sciences, University of Leicester and Cardiovascular Theme, NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Groby road, Leicester, LE3 9QP, UK
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Joubert M, Manrique A, Cariou B, Prieur X. Diabetes-related cardiomyopathy: The sweet story of glucose overload from epidemiology to cellular pathways. DIABETES & METABOLISM 2018; 45:238-247. [PMID: 30078623 DOI: 10.1016/j.diabet.2018.07.003] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/02/2018] [Revised: 06/28/2018] [Accepted: 07/12/2018] [Indexed: 02/07/2023]
Abstract
Type 2 diabetes (T2D) is a major risk factor for heart failure (HF). Although the number of cases of myocardial infarction in the T2D population has been reduced by 25% over the last 10 years, the incidence of HF is continuously increasing, making it the most worrying diabetes complication. This strongly reinforces the urgent need for innovative therapeutic interventions to prevent cardiac dysfunction in T2D patients. To this end, epidemiological, imaging and animal studies have aimed to highlight the mechanisms involved in the development of diabetic cardiomyopathy. Epidemiological observations clearly show that hyperglycaemia correlates with severity of cardiac dysfunction and mortality in T2D patients. Both animal and cellular studies have demonstrated that, in the context of diabetes, the heart loses its ability to utilize glucose, therefore leading to glucose overload in cardiomyocytes that, in turn, promotes oxidative stress, accumulation of advanced glycation end-products (AGEs) and chronic activation of the hexosamine pathway. These have all been found to activate apoptosis and to alter heart contractility, calcium signalling and mitochondrial function. Although, in the past, tight glycaemic control has failed to improve cardiac function in T2D patients, recent clinical trials have reported cardiovascular benefit with hypoglycaemic antidiabetic drugs of the SGLT2-inhibitor family. This review, based on clinical evidence from mechanistic studies as well as several large clinical trials, covers 15 years of research, and strongly supports the idea that hyperglycaemia and glucose overload play a central role in the pathophysiology of diabetic cardiomyopathy.
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Affiliation(s)
- M Joubert
- Diabetes care unit, Caen university hospital, 14033 Caen cedex, France; EA4650, UNICAEN, 14000 Caen, France
| | - A Manrique
- Nuclear medicine unit, Caen university hospital, 14033 Caen cedex, France; EA4650, UNICAEN, 14000 Caen, France
| | - B Cariou
- Institut du thorax, Inserm, CNRS, University of Nantes, CHU Nantes, 44000 Nantes, France
| | - X Prieur
- Institut du thorax, Inserm, CNRS, University of Nantes, 44000 Nantes, France.
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Gulsin GS, Swarbrick DJ, Hunt WH, Levelt E, Graham-Brown MPM, Parke KS, Wormleighton JV, Lai FY, Yates T, Wilmot EG, Webb DR, Davies MJ, McCann GP. Relation of Aortic Stiffness to Left Ventricular Remodeling in Younger Adults With Type 2 Diabetes. Diabetes 2018; 67:1395-1400. [PMID: 29661781 DOI: 10.2337/db18-0112] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2018] [Accepted: 04/09/2018] [Indexed: 11/13/2022]
Abstract
Individuals with type 2 diabetes have a three- to fivefold increased risk of developing heart failure. Diabetic cardiomyopathy is typified by left ventricular (LV) concentric remodeling, which is a recognized predictor of adverse cardiovascular events. Although the mechanisms underlying LV remodeling in type 2 diabetes are unclear, progressive aortic stiffening may be a key determinant. The aim of this study was to assess the relationship between aortic stiffness and LV geometry in younger adults with type 2 diabetes, using multiparametric cardiovascular MRI. We prospectively recruited 80 adults (aged 18-65 years) with type 2 diabetes and no cardiovascular disease and 20 age- and sex-matched healthy control subjects. All subjects underwent comprehensive bio-anthropometric assessment and cardiac MRI, including measurement of aortic stiffness by aortic distensibility (AD). Type 2 diabetes was associated with increased LV mass, concentric LV remodeling, and lower AD compared with control subjects. On multivariable linear regression, AD was independently associated with concentric LV remodeling in type 2 diabetes. Aortic stiffness may therefore be a potential therapeutic target to prevent the development of heart failure in type 2 diabetes.
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Affiliation(s)
- Gaurav S Gulsin
- Department of Cardiovascular Sciences, University of Leicester and Leicester National Institute for Health Research Biomedical Research Centre, Glenfield Hospital, Leicester, U.K
| | - Daniel J Swarbrick
- Department of Cardiovascular Sciences, University of Leicester and Leicester National Institute for Health Research Biomedical Research Centre, Glenfield Hospital, Leicester, U.K
| | - William H Hunt
- Department of Cardiovascular Sciences, University of Leicester and Leicester National Institute for Health Research Biomedical Research Centre, Glenfield Hospital, Leicester, U.K
| | - Eylem Levelt
- Department of Cardiovascular Sciences, University of Leicester and Leicester National Institute for Health Research Biomedical Research Centre, Glenfield Hospital, Leicester, U.K
| | | | - Kelly S Parke
- Department of Cardiovascular Sciences, University of Leicester and Leicester National Institute for Health Research Biomedical Research Centre, Glenfield Hospital, Leicester, U.K
| | - Joanne V Wormleighton
- Department of Cardiovascular Sciences, University of Leicester and Leicester National Institute for Health Research Biomedical Research Centre, Glenfield Hospital, Leicester, U.K
| | - Florence Y Lai
- Department of Cardiovascular Sciences, University of Leicester and Leicester National Institute for Health Research Biomedical Research Centre, Glenfield Hospital, Leicester, U.K
| | - Thomas Yates
- National Centre of Sport and Exercise Medicine, University of Loughborough, Loughborough, U.K
| | - Emma G Wilmot
- Department of Endocrinology and Diabetes, Royal Derby Hospital, Derby, U.K
| | - David R Webb
- Diabetes Research Centre, University of Leicester and Leicester National Institute for Health Research Biomedical Research Centre, Leicester General Hospital, Leicester, U.K
| | - Melanie J Davies
- Diabetes Research Centre, University of Leicester and Leicester National Institute for Health Research Biomedical Research Centre, Leicester General Hospital, Leicester, U.K
| | - Gerry P McCann
- Department of Cardiovascular Sciences, University of Leicester and Leicester National Institute for Health Research Biomedical Research Centre, Glenfield Hospital, Leicester, U.K.
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Levelt E, Gulsin G, Neubauer S, McCann GP. MECHANISMS IN ENDOCRINOLOGY: Diabetic cardiomyopathy: pathophysiology and potential metabolic interventions state of the art review. Eur J Endocrinol 2018; 178:R127-R139. [PMID: 29440374 PMCID: PMC5863473 DOI: 10.1530/eje-17-0724] [Citation(s) in RCA: 47] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2017] [Accepted: 02/12/2018] [Indexed: 12/22/2022]
Abstract
Heart failure is a major cause of morbidity and mortality in type 2 diabetes. Type 2 diabetes contributes to the development of heart failure through a variety of mechanisms, including disease-specific myocardial structural, functional and metabolic changes. This review will focus on the contemporary contributions of state of the art non-invasive technologies to our understanding of diabetic cardiomyopathy, including data on cardiac disease phenotype, cardiac energy metabolism and energetic deficiency, ectopic and visceral adiposity, diabetic liver disease, metabolic modulation strategies and cardiovascular outcomes with new classes of glucose-lowering therapies.
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Affiliation(s)
- Eylem Levelt
- British Heart Foundation Cardiovascular Research CentreUniversity of Leicester, Glenfield Hospital, Leicester, UK
- (E Levelt is now at Multidisciplinary Cardiovascular Research Centre and Biomedical Imaging Science DepartmentLeeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK)
- Correspondenceshould be addressed to E Levelt;
| | - Gaurav Gulsin
- British Heart Foundation Cardiovascular Research CentreUniversity of Leicester, Glenfield Hospital, Leicester, UK
| | - Stefan Neubauer
- University of Oxford Centre for Clinical Magnetic Resonance ResearchUniversity of Oxford, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, Oxford, UK
| | - Gerry P McCann
- British Heart Foundation Cardiovascular Research CentreUniversity of Leicester, Glenfield Hospital, Leicester, UK
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Clarke GD, Molina‐Wilkins M, Solis‐Herrera C, Mendez V, Monroy A, Cersosimo E, Chilton RJ, Abdul‐Ghani M, DeFronzo RA. Impaired left ventricular diastolic function in T2DM patients is closely related to glycemic control. Endocrinol Diabetes Metab 2018; 1:e00014. [PMID: 30815550 PMCID: PMC6354805 DOI: 10.1002/edm2.14] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2017] [Revised: 01/24/2018] [Accepted: 02/18/2018] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND Left ventricular (LV) diastolic dysfunction commonly is observed in individuals with type 2 diabetes mellitus (T2DM). We employed transthoracic echocardiography (TTE) and cardiac magnetic resonance imaging (CMRI) to investigate the hypothesis that LV diastolic dysfunction in T2DM is associated with poor glycemic control. METHODS Forty subjects, 21 with normal glucose tolerance (NGT) and 19 with T2DM, were studied with CMRI and TTE to assess LV function. Early-to-late transmitral flow ratio (E/A) and deceleration time (DecT) were assessed with both modalities. Normalized (to body surface area) end-diastolic volume (EDV/BSA) and normalized peak LV filling rate (pLVFR/BSA) were assessed with CMRI. Early transmitral flow velocity to septal velocity (E/e') and isovolumetric relaxation time (IVRT) were measured using TTE. Dimensional parameters were normalized to body surface area (BSA). RESULTS CMRI measurements demonstrated impaired E/A (1.13 ± 0.34 vs 1.62 ± 0.42, P < .001), increased DecT (174 ± 46 ms vs 146 ± 15, P = .005), as well as lower EDV/BSA (63 ± 10 vs 72 ± 9 mL/m2, P < .01) and pLVFR/BSA (189 ± 46 vs 221 ± 48 mL s-1 m-2, P < .05) in T2DM subjects. TTE measurements revealed lower E/A (1.1 ± 0.4 vs 1.4 ± 0.2, P < .001) and E/e' (6.8 ± 1.5 vs 8.7 ± 2.0, P < .0001) with higher DecT (203 ± 22 ms vs 179 ± 18, P < .001) and IVRT (106 ± 14 ms vs 92 ± 10, P < .001) in T2DM. Multiple parameters of LV function: E/ACMRI (r = -.50, P = .001), E/ATTE (r = -.46, P < .005), pLVFR/BSA (r = -.35, P < .05), E/e' (r = -.46, P < .005), EDV/BSACMRI (r = -.51, P < .0001), EDV/BSATTE (r = -.42, P < .01) were negatively correlated with HbA1c. All but E/e' also were inversely correlated with fasting plasma glucose (FPG). CONCLUSIONS Impaired LV diastolic function (DF) was found in T2DM subjects with both CMRI and TTE, and multiple LVDF parameters correlated negatively with HbA1c and FPG. These results indicate that impaired LVDF is inversely linked to glycemic control in T2DM patients.
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Affiliation(s)
- Geoffrey D. Clarke
- Department of RadiologyTexas Diabetes InstituteUniversity of Texas Health Science Center at San AntonioSan AntonioTXUSA
| | - Marjorie Molina‐Wilkins
- Diabetes DivisionDepartment of MedicineTexas Diabetes InstituteUniversity of Texas Health Science Center at San AntonioSan AntonioTXUSA
| | - Carolina Solis‐Herrera
- Diabetes DivisionDepartment of MedicineTexas Diabetes InstituteUniversity of Texas Health Science Center at San AntonioSan AntonioTXUSA
| | - Verna Mendez
- Diabetes DivisionDepartment of MedicineTexas Diabetes InstituteUniversity of Texas Health Science Center at San AntonioSan AntonioTXUSA
| | - Adriana Monroy
- Diabetes DivisionDepartment of MedicineTexas Diabetes InstituteUniversity of Texas Health Science Center at San AntonioSan AntonioTXUSA
| | - Eugenio Cersosimo
- Diabetes DivisionDepartment of MedicineTexas Diabetes InstituteUniversity of Texas Health Science Center at San AntonioSan AntonioTXUSA
| | - Robert J. Chilton
- Cardiology DivisionDepartment of MedicineTexas Diabetes InstituteUniversity of Texas Health Science Center at San AntonioSan AntonioTXUSA
| | - Muhammad Abdul‐Ghani
- Diabetes DivisionDepartment of MedicineTexas Diabetes InstituteUniversity of Texas Health Science Center at San AntonioSan AntonioTXUSA
| | - Ralph A. DeFronzo
- Diabetes DivisionDepartment of MedicineTexas Diabetes InstituteUniversity of Texas Health Science Center at San AntonioSan AntonioTXUSA
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Swoboda PP, Erhayiem B, Kan R, McDiarmid AK, Garg P, Musa TA, Dobson LE, Witte KK, Kearney MT, Barth JH, Ajjan R, Greenwood JP, Plein S. Cardiovascular magnetic resonance measures of aortic stiffness in asymptomatic patients with type 2 diabetes: association with glycaemic control and clinical outcomes. Cardiovasc Diabetol 2018; 17:35. [PMID: 29506523 PMCID: PMC5836381 DOI: 10.1186/s12933-018-0681-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2017] [Accepted: 02/27/2018] [Indexed: 01/24/2023] Open
Abstract
BACKGROUND We aimed to investigate in patients with type 2 diabetes whether aortic stiffness is: (i) associated with glycaemic control, (ii) associated with adverse outcomes and (iii) can be reversed on treatment with RAAS inhibition. METHODS Patients with type 2 diabetes (N = 94) and low vascular risk underwent assessment of cardiovascular risk and CMR assessment of ascending aortic distensibility (AAD), descending aortic distensibility (DAD) and aortic pulse wave velocity (PWV). Of these patients a subgroup with recent onset microalbuminuria (N = 25) were treated with renin-angiotensin-aldosterone system (RAAS) inhibition and imaging repeated after 1 year. All 94 patients were followed up for 2.4 years for major adverse cardiovascular disease (CVD) events including myocardial infarction detected on late gadolinium enhancement CMR. RESULTS Ascending aortic distensibility, DAD and PWV all had a significant association with age and 24 h systolic blood pressure but only AAD had a significant association with glycaemic control, measured as HbA1c (Beta - 0.016, P = 0.04). The association between HbA1c and AAD persisted even after correction for age and hypertension. CVD events occurred in 19/94 patients. AAD, but not DAD or PWV, was associated with CVD events (hazard ratio 0.49, 95% confidence interval 0.25-0.95, P = 0.01). On treatment with RAAS inhibition, AAD, but not DAD or PWV, showed significant improvement from 1.51 ± 1.15 to 1.97 ± 1.07 10-3 mmHg-1, P = 0.007. CONCLUSIONS Ascending aortic distensibility measured by CMR is independently associated with poor glycaemic control and adverse cardiovascular events. Furthermore it may be reversible on treatment with RAAS inhibition. AAD is a promising marker of cardiovascular risk in asymptomatic patients with type 2 diabetes and has potential use as a surrogate cardiovascular endpoint in studies of novel hypoglycaemic agents. Clinical trials registration https://clinicaltrials.gov/ct2/show/NCT01970319.
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Affiliation(s)
- Peter P. Swoboda
- Multidisciplinary Cardiovascular Research Centre & Division of Biomedical Imaging, Leeds Institute of Cardiovascular and Metabolic Medicine, LIGHT Laboratories, Clarendon Way, University of Leeds, Leeds, LS2 9JT UK
| | - Bara Erhayiem
- Multidisciplinary Cardiovascular Research Centre & Division of Biomedical Imaging, Leeds Institute of Cardiovascular and Metabolic Medicine, LIGHT Laboratories, Clarendon Way, University of Leeds, Leeds, LS2 9JT UK
| | - Rachel Kan
- Multidisciplinary Cardiovascular Research Centre & Division of Biomedical Imaging, Leeds Institute of Cardiovascular and Metabolic Medicine, LIGHT Laboratories, Clarendon Way, University of Leeds, Leeds, LS2 9JT UK
| | - Adam K. McDiarmid
- Multidisciplinary Cardiovascular Research Centre & Division of Biomedical Imaging, Leeds Institute of Cardiovascular and Metabolic Medicine, LIGHT Laboratories, Clarendon Way, University of Leeds, Leeds, LS2 9JT UK
| | - Pankaj Garg
- Multidisciplinary Cardiovascular Research Centre & Division of Biomedical Imaging, Leeds Institute of Cardiovascular and Metabolic Medicine, LIGHT Laboratories, Clarendon Way, University of Leeds, Leeds, LS2 9JT UK
| | - Tarique A. Musa
- Multidisciplinary Cardiovascular Research Centre & Division of Biomedical Imaging, Leeds Institute of Cardiovascular and Metabolic Medicine, LIGHT Laboratories, Clarendon Way, University of Leeds, Leeds, LS2 9JT UK
| | - Laura E. Dobson
- Multidisciplinary Cardiovascular Research Centre & Division of Biomedical Imaging, Leeds Institute of Cardiovascular and Metabolic Medicine, LIGHT Laboratories, Clarendon Way, University of Leeds, Leeds, LS2 9JT UK
| | - Klaus K. Witte
- Multidisciplinary Cardiovascular Research Centre & Division of Biomedical Imaging, Leeds Institute of Cardiovascular and Metabolic Medicine, LIGHT Laboratories, Clarendon Way, University of Leeds, Leeds, LS2 9JT UK
| | - Mark T. Kearney
- Multidisciplinary Cardiovascular Research Centre & Division of Biomedical Imaging, Leeds Institute of Cardiovascular and Metabolic Medicine, LIGHT Laboratories, Clarendon Way, University of Leeds, Leeds, LS2 9JT UK
| | - Julian H. Barth
- Leeds Teaching Hospitals NHS Trust, Great George Street, Leeds, UK
| | - Ramzi Ajjan
- Multidisciplinary Cardiovascular Research Centre & Division of Biomedical Imaging, Leeds Institute of Cardiovascular and Metabolic Medicine, LIGHT Laboratories, Clarendon Way, University of Leeds, Leeds, LS2 9JT UK
| | - John P. Greenwood
- Multidisciplinary Cardiovascular Research Centre & Division of Biomedical Imaging, Leeds Institute of Cardiovascular and Metabolic Medicine, LIGHT Laboratories, Clarendon Way, University of Leeds, Leeds, LS2 9JT UK
| | - Sven Plein
- Multidisciplinary Cardiovascular Research Centre & Division of Biomedical Imaging, Leeds Institute of Cardiovascular and Metabolic Medicine, LIGHT Laboratories, Clarendon Way, University of Leeds, Leeds, LS2 9JT UK
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Increased myocardial extracellular volume assessed by cardiovascular magnetic resonance T1 mapping and its determinants in type 2 diabetes mellitus patients with normal myocardial systolic strain. Cardiovasc Diabetol 2018; 17:7. [PMID: 29301529 PMCID: PMC5755204 DOI: 10.1186/s12933-017-0651-2] [Citation(s) in RCA: 44] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2017] [Accepted: 12/23/2017] [Indexed: 02/07/2023] Open
Abstract
Background Cardiac magnetic resonance (CMR) T1 mapping and tissue-tracking strain analysis are useful quantitative techniques that can characterize myocardial tissue and mechanical alterations, respectively, in patients with early diabetic cardiomyopathy. The purpose of this study was to assess the left ventricular myocardial T1 value, extracellular volume fraction (ECV), and systolic strain in asymptomatic patients with type 2 diabetes mellitus (T2DM) and their underlying relationships with clinical parameters. Methods We recruited 50 T2DM patients (mean age: 55 ± 7 years; 28 males) and 32 sex-, age-and BMI-matched healthy volunteers to undergo contrast-enhanced CMR examinations. The myocardial native T1, post-contrast T1 and ECV values of the left ventricle were measured from T1 and ECV maps acquired using the modified Look-Locker inversion recovery technique. The left ventricular global systolic strain and the strain rates were evaluated using routine cine images and tissue-tracking analysis software. The baseline clinical and biochemical indices were collected before the CMR examination. Results The myocardial ECV and native T1 values were significantly higher in the diabetic patients than in the controls. (ECV: 27.4 ± 2.5% vs. 24.6 ± 2.2%, p < 0.001; native T1: 1026.9 ± 30.0 ms vs. 1011.8 ± 26.0 ms, p = 0.022). However, the left ventricular global systolic strain, strain rate, volume, myocardial mass, ejection fraction, and left atrial volume were similar between the diabetic patients and the healthy controls. In the diabetic patients, the native T1 values were independently correlated with the hemoglobin A1c levels (standardized β = 0.368, p = 0.008). The ECVs were independently associated with the hemoglobin A1c levels (standardized β = 0.389, p = 0.002), angiotensin-converting enzyme inhibitor (ACEI) treatment (standardized β = − 0.271, p = 0.025) and HCT values (standardized β = − 0.397, p = 0.001). Conclusions Type 2 diabetes mellitus patients with normal myocardial systolic strain exhibit increased native T1 values and ECVs indicative of myocardial extracellular interstitial expansion, which might be related to poor glycemic control. The amelioration of myocardial interstitial matrix expansion might be associated with ACEI treatment. A valid assessment of the association of glucose control and ACEI treatment with myocardial fibrosis requires notably larger trials.
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Ringle A, Dornhorst A, Rehman MB, Ruisanchez C, Nihoyannopoulos P. Evolution of subclinical myocardial dysfunction detected by two-dimensional and three-dimensional speckle tracking in asymptomatic type 1 diabetic patients: a long‑term follow-up study. Echo Res Pract 2017; 4:73-81. [PMID: 29167183 PMCID: PMC5704514 DOI: 10.1530/erp-17-0052] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2017] [Accepted: 11/03/2017] [Indexed: 12/19/2022] Open
Abstract
Background We sought to assess the long-term evolution of left ventricular (LV) function using two-dimensional (2D) and three-dimensional (3D) speckle tracking echocardiography (STE) for the detection of preclinical diabetic cardiomyopathy, in asymptomatic type 1 diabetic patients, over a 6-year follow-up. Design and methods Sixty-six asymptomatic type 1 diabetic patients with no cardiovascular risk factors were compared to 26 matched healthy controls. Conventional, 2D and 3D-STE were performed at baseline. A subgroup of 14 patients underwent a 6-year follow-up evaluation. Results At baseline, diabetic patients had similar LV ejection fraction (60 vs 61%; P = NS), but impaired longitudinal function, as assessed by 2D-global longitudinal strain (GLS) (−18.9 ± 2 vs −20.5 ± 2; P = 0.0002) and 3D-GLS (−17.5 ± 2 vs −19 ± 2; P = 0.003). At follow-up, diabetic patients had worsened longitudinal function compared to baseline (2D-GLS: −18.4 ± 1 vs −19.2 ± 1; P = 0.03). Global circumferential (GCS) and radial (GRS) strains were unchanged at baseline and during follow-up. Metabolic status did not correlate with GLS, whereas GCS and GRS showed a good correlation, suggestive of a compensatory increase of circumferential and radial functions in advanced stages of the disease – long-term diabetes (GCS: −26 ± 3 vs −23.3 ± 3; P = 0.008) and in the presence of microvascular complications (GRS: 38.8 ± 9 vs 34.3 ± 8; P = 0.04). Conclusions Subclinical myocardial dysfunction can be detected by 2D and 3D-STE in type 1 diabetic patients, independently of any other cardiovascular risk factors. Diabetic cardiomyopathy progression was suggested by a mild decrease in longitudinal function at the follow-up, but did not extend to a clinical expression of the disease, as no death or over heart failure was reported.
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Affiliation(s)
- Anne Ringle
- Department of Cardiology, Hôpital Saint Philibert, GHICL, Lille, France.,Department of Cardiology, Hammersmith Hospital, Imperial College NHS Trust, London, UK
| | - Anne Dornhorst
- Department of Diabetes and Endocrinology, Hammersmith Hospital, Imperial College NHS Trust, London, UK
| | - Michaela B Rehman
- Department of Cardiology, Hammersmith Hospital, Imperial College NHS Trust, London, UK.,Department of Cardiology, Centre Hospitalier Universitaire de Poitiers, Poitiers, France
| | - Cristina Ruisanchez
- Department of Cardiology, Hammersmith Hospital, Imperial College NHS Trust, London, UK.,Hospital Universitario Marques de Valdecilla, Santander, Cantabria, Spain
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van den Boomen M, Slart RHJA, Hulleman EV, Dierckx RAJO, Velthuis BK, van der Harst P, Sosnovik DE, Borra RJH, Prakken NHJ. Native T 1 reference values for nonischemic cardiomyopathies and populations with increased cardiovascular risk: A systematic review and meta-analysis. J Magn Reson Imaging 2017; 47:891-912. [PMID: 29131444 PMCID: PMC5873388 DOI: 10.1002/jmri.25885] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2017] [Accepted: 10/17/2017] [Indexed: 12/12/2022] Open
Abstract
Background Although cardiac MR and T1 mapping are increasingly used to diagnose diffuse fibrosis based cardiac diseases, studies reporting T1 values in healthy and diseased myocardium, particular in nonischemic cardiomyopathies (NICM) and populations with increased cardiovascular risk, seem contradictory. Purpose To determine the range of native myocardial T1 value ranges in patients with NICM and populations with increased cardiovascular risk. Study Type Systemic review and meta‐analysis. Population Patients with NICM, including hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM), and patients with myocarditis (MC), iron overload, amyloidosis, Fabry disease, and populations with hypertension (HT), diabetes mellitus (DM), and obesity. Field Strength/Sequence (Shortened) modified Look–Locker inversion‐recovery MR sequence at 1.5 or 3T. Assessment PubMed and Embase were searched following the PRISMA guidelines. Statistical Tests The summary of standard mean difference (SMD) between the diseased and a healthy control populations was generated using a random‐effects model in combination with meta‐regression analysis. Results The SMD for HCM, DCM, and MC patients were significantly increased (1.41, 1.48, and 1.96, respectively, P < 0.01) compared with healthy controls. The SMD for HT patients with and without left‐ventricle hypertrophy (LVH) together was significantly increased (0.19, P = 0.04), while for HT patients without LVH the SMD was zero (0.03, P = 0.52). The number of studies on amyloidosis, iron overload, Fabry disease, and HT patients with LVH did not meet the requirement to perform a meta‐analysis. However, most studies reported a significantly increased T1 for amyloidosis and HT patients with LVH and a significant decreased T1 for iron overload and Fabry disease patients. Data Conclusions Native T1 mapping by using an (Sh)MOLLI sequence can potentially assess myocardial changes in HCM, DCM, MC, iron overload, amyloidosis, and Fabry disease compared to controls. In addition, it can help to diagnose left‐ventricular remodeling in HT patients. Level of Evidence: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:891–912.
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Affiliation(s)
- Maaike van den Boomen
- Department of Radiology, University of Groningen, University Medical Center Groningen, the Netherlands; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard-MIT Health Science and Technology, USA
| | - Riemer H J A Slart
- Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, the Netherlands; Department of Biomedical Photonic Imaging, University of Twente, the Netherlands
| | - Enzo V Hulleman
- Department of Radiology, University of Groningen, University Medical Center Groningen, the Netherlands
| | - Rudi A J O Dierckx
- Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, the Netherlands
| | - Birgitta K Velthuis
- Department of Radiology, University of Utrecht, University Medical Center Utrecht, the Netherlands
| | - Pim van der Harst
- Department of Cardiology, University of Groningen, University Medical Center Groningen, the Netherlands
| | - David E Sosnovik
- Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, USA; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard-MIT Health Science and Technology, USA
| | - Ronald J H Borra
- Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Netherlands; Medical Imaging Centre of Southwest Finland, Turku University Hospital, Finland
| | - Niek H J Prakken
- Department of Radiology, University of Groningen, University Medical Center Groningen, the Netherlands
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Rosenbohm A, Schmid B, Buckert D, Rottbauer W, Kassubek J, Ludolph AC, Bernhardt P. Cardiac Findings in Amyotrophic Lateral Sclerosis: A Magnetic Resonance Imaging Study. Front Neurol 2017; 8:479. [PMID: 29021775 PMCID: PMC5623666 DOI: 10.3389/fneur.2017.00479] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2017] [Accepted: 08/29/2017] [Indexed: 12/12/2022] Open
Abstract
The objective of this study was to investigate the potential involvement of cardiac structure and function by cardiac magnetic resonance (CMR) imaging in amyotrophic lateral sclerosis (ALS) patients. Our study included 35 patients with ALS without a history of cardiac disease and an age- and gender-matched healthy control group (n = 34). All subjects received a CMR in a 1.5-T whole-body scanner. Patients were also screened with Holter monitoring, echocardiography, and a blood test of cardiac markers. Myocardial mass in ALS hearts was reduced compared to the control group, and ejection volumes in the left and right heart were severely decreased in ALS patients, as shown by echocardiography and CMR. The myocardium showed increased T1 enhancement in 77% of the patients compared to 27% of controls (p = 0.0001). A trend toward late gadolinium enhancement patterns consistent with myocardial fibrosis was observed in 23.5% of the patients (9.1% of controls). Holter monitoring was normal in all patients as well as troponin T. Cardiac involvement seems to be present in ALS patients without clinical cardiac symptoms and with a normal cardiac routine assessment. Structural myocardial defects in CMR may be due to sympathetic dysfunction and may account for reported cardiac deaths in late-stage ALS patients.
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Affiliation(s)
| | - Benjamin Schmid
- Department of Neurology, University of Ulm, Ulm, Germany.,Department of Internal Medicine, Kreiskrankenhaus Ehingen, Ehingen, Germany
| | - Dominik Buckert
- Department of Internal Medicine II, University of Ulm, Ulm, Germany
| | | | - Jan Kassubek
- Department of Neurology, University of Ulm, Ulm, Germany
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Shetye AM, Nazir SA, Razvi NA, Price N, Khan JN, Lai FY, Squire IB, McCann GP, Arnold JR. Comparison of global myocardial strain assessed by cardiovascular magnetic resonance tagging and feature tracking to infarct size at predicting remodelling following STEMI. BMC Cardiovasc Disord 2017; 17:7. [PMID: 28056808 PMCID: PMC5217595 DOI: 10.1186/s12872-016-0461-6] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2016] [Accepted: 12/23/2016] [Indexed: 02/06/2023] Open
Abstract
Background To determine if global strain parameters measured by cardiovascular magnetic resonance (CMR) acutely following ST-segment Elevation Myocardial Infarction (STEMI) predict adverse left ventricular (LV) remodelling independent of infarct size (IS). Methods Sixty-five patients with acute STEMI (mean age 60 ± 11 years) underwent CMR at 1–3 days post-reperfusion (baseline) and at 4 months. Global peak systolic circumferential strain (GCS), measured by tagging and Feature Tracking (FT), and global peak systolic longitudinal strain (GLS), measured by FT, were calculated at baseline, along with IS. On follow up scans, volumetric analysis was performed to determine the development of adverse remodelling – a composite score based on development of either end-diastolic volume index [EDVI] ≥20% or end-systolic volume index [ESVI] ≥15% at follow-up compared to baseline. Results The magnitude of GCS was higher when measured using FT (−21.1 ± 6.3%) than with tagging (−12.1 ± 4.3; p < 0.001 for difference). There was good correlation of strain with baseline LVEF (r 0.64–to 0.71) and IS (ρ -0.62 to–0.72). Baseline strain parameters were unable to predict development of adverse LV remodelling. Only baseline IS predicted adverse remodelling – Odds Ratio 1.05 (95% CI 1.01–1.10, p = 0.03), area under the ROC curve 0.70 (95% CI 0.52–0.87, p = 0.04). Conclusion Baseline global strain by CMR does not predict the development of adverse LV remodelling following STEMI.
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Affiliation(s)
- Abhishek M Shetye
- Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Groby Road, Leicester, LE3 9QF, UK.,Oxford University Hospitals NHS Trust, Oxford, OX3 9DU, UK
| | - Sheraz A Nazir
- Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Groby Road, Leicester, LE3 9QF, UK
| | - Naveed A Razvi
- Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Groby Road, Leicester, LE3 9QF, UK.,Ipswich Hospital NHS trust, Ipswich, IP4 5PD, UK
| | - Nathan Price
- Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Groby Road, Leicester, LE3 9QF, UK.,Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM), University of Leeds, Leeds, LS2 9JT, UK
| | - Jamal N Khan
- Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Groby Road, Leicester, LE3 9QF, UK
| | - Florence Y Lai
- Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Groby Road, Leicester, LE3 9QF, UK
| | - Iain B Squire
- Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Groby Road, Leicester, LE3 9QF, UK
| | - Gerald P McCann
- Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Groby Road, Leicester, LE3 9QF, UK
| | - Jayanth R Arnold
- Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Groby Road, Leicester, LE3 9QF, UK.
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Shang Y, Zhang X, Leng W, Chen L, Lei X, Zhang T, Greiser A, Liang Z, Wang J. Assessment of Diabetic Cardiomyopathy by Cardiovascular Magnetic Resonance T1 Mapping: Correlation with Left-Ventricular Diastolic Dysfunction and Diabetic Duration. J Diabetes Res 2017; 2017:9584278. [PMID: 28791311 PMCID: PMC5534277 DOI: 10.1155/2017/9584278] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2017] [Revised: 05/09/2017] [Accepted: 05/28/2017] [Indexed: 01/11/2023] Open
Abstract
PURPOSE To quantify extracellular matrix expansion with the cardiovascular magnetic resonance (CMR) T1 mapping technique and the derived extracellular volume fraction (ECV) in diabetic cardiomyopathy (DbCM) patients and to detect the relationship among ECV, duration of diabetes, and diastolic function. MATERIALS Thirty-eight patients with diabetic cardiomyopathy (20 males, age 54.6 ± 8.6 years) and thirty-two matched normal controls (15 males, age 51.4 ± 13.6 years) were prospectively enrolled. All of them were scanned by T1 mapping to obtain the native and postcontrast T1 values of myocardium and blood, and ECV was calculated accordingly. All patients also underwent transthoracic echocardiographic tissue Doppler imaging to assess left-ventricular diastolic function. RESULTS There was a significant difference in ECV between the two groups (DbCMs 30.4 ± 2.9% versus controls 27.1 ± 2.4%, P < 0.001). The duration of diabetes was positively and strongly associated with ECV (R = 0.539, P = 0.0005). There was also a significant difference in ECV (P ≤ 0.001) among four groups (A, controls; B, DbCM patients with duration of diabetes <5 years; C, 5-10 years; and D, >10 years). ECV was negatively associated with LV E'/A' (R = -0.403, P = 0.012). CONCLUSION CMR T1 mapping can reflect myocardial extracellular matrix expansion in DbCM and can be a powerful technique for the early diagnosis of DbCM.
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Affiliation(s)
- Yongning Shang
- Department of Radiology, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Xiaochun Zhang
- Department of Radiology, Southwest Hospital, Third Military Medical University, Chongqing, China
- *Xiaochun Zhang:
| | - Weilling Leng
- Department of Endocrinology, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Liu Chen
- Department of Endocrinology, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Xiaotian Lei
- Department of Endocrinology, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Tianjing Zhang
- Northeast Asia MR Collaboration, Siemens Healthcare, Beijing, China
| | | | - Ziwen Liang
- Department of Endocrinology, Southwest Hospital, Third Military Medical University, Chongqing, China
- *Ziwen Liang: and
| | - Jian Wang
- Department of Radiology, Southwest Hospital, Third Military Medical University, Chongqing, China
- *Jian Wang:
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47
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Wong C, Chen S, Iyngkaran P. Cardiac Imaging in Heart Failure with Comorbidities. Curr Cardiol Rev 2017; 13:63-75. [PMID: 27492227 PMCID: PMC5324322 DOI: 10.2174/1573403x12666160803100928] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2016] [Revised: 06/30/2016] [Accepted: 07/05/2016] [Indexed: 01/19/2023] Open
Abstract
Imaging modalities stand at the frontiers for progress in congestive heart failure (CHF) screening, risk stratification and monitoring. Advancements in echocardiography (ECHO) and Magnetic Resonance Imaging (MRI) have allowed for improved tissue characterizations, cardiac motion analysis, and cardiac performance analysis under stress. Common cardiac comorbidities such as hypertension, metabolic syndromes and chronic renal failure contribute to cardiac remodeling, sharing similar pathophysiological mechanisms starting with interstitial changes, structural changes and finally clinical CHF. These imaging techniques can potentially detect changes earlier. Such information could have clinical benefits for screening, planning preventive therapies and risk stratifying patients. Imaging reports have often focused on traditional measures without factoring these novel parameters. This review is aimed at providing a synopsis on how we can use this information to assess and monitor improvements for CHF with comorbidities.
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Affiliation(s)
- Chiew Wong
- Flinders University, NT Medical School, Darwin Australia
| | - Sylvia Chen
- Flinders University, NT Medical School, Darwin Australia
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48
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Xie J, Cui K, Hao H, Zhang Y, Lin H, Chen Z, Huang X, Cao S, Liao W, Bin J, Kitakaze M, Liao Y. Acute hyperglycemia suppresses left ventricular diastolic function and inhibits autophagic flux in mice under prohypertrophic stimulation. Cardiovasc Diabetol 2016; 15:136. [PMID: 27659110 PMCID: PMC5034479 DOI: 10.1186/s12933-016-0452-z] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2016] [Accepted: 09/13/2016] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND Left ventricular (LV) dysfunction is closely associated with LV hypertrophy or diabetes, as well as insufficient autophagic flux. Acute or chronic hyperglycemia is a prognostic factor for patients with myocardial infarction. However, the effect of acute hyperglycemia on LV dysfunction of the hypertrophic heart and the mechanisms involved are still unclear. This study aimed to confirm our hypothesis that either acute or chronic hyperglycemia suppresses LV diastolic function and autophagic flux. METHODS The transverse aortic constriction (TAC) model and streptozocin-induced type 1 diabetic mellitus mice were used. LV function was evaluated with a Millar catheter. Autophagic levels and autophagic flux in the whole heart and cultured neonatal rat cardiomyocytes in response to hyperglycemia were examined by using western blotting of LC3B-II and P62. We also examined the effect of an autophagic inhibitor on LC3B-II and P62 protein expression and LC3 puncta. RESULTS In mice with TAC, we detected diastolic dysfunction as early as 30 min after TAC. This dysfunction was indicated by a greater LV end-diastolic pressure and the exponential time constant of LV relaxation, as well as a smaller maximum descending rate of LV pressure in comparison with sham group. Similar results were also obtained in mice with TAC for 2 weeks, in addition to increased insulin resistance. Acute hyperglycemic stress suppressed diastolic function in mice with myocardial hypertrophy, as evaluated by invasive LV hemodynamic monitoring. Mice with chronic hyperglycemia induced by streptozocin showed myocardial fibrosis and diastolic dysfunction. In high glucose-treated cardiomyocytes and streptozocin-treated mice, peroxisome proliferator-activated receptor-γ coactivator 1α was downregulated, while P62 was upregulated. Autophagic flux was also significantly inhibited in response to high glucose exposure in angiotensin-II treated cardiomyocytes. CONCLUSIONS Acute hyperglycemia suppresses diastolic function, damages mitochondrial energy signaling, and inhibits autophagic flux in prohypertrophic factor-stimulated cardiomyocytes.
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Affiliation(s)
- Jiahe Xie
- State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, 1838 Guangzhou avenue north, Guangzhou, 510515 China
| | - Kai Cui
- State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, 1838 Guangzhou avenue north, Guangzhou, 510515 China
| | - Huixin Hao
- State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, 1838 Guangzhou avenue north, Guangzhou, 510515 China
| | - Yingxue Zhang
- State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, 1838 Guangzhou avenue north, Guangzhou, 510515 China
| | - Hairuo Lin
- State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, 1838 Guangzhou avenue north, Guangzhou, 510515 China
| | - Zhenhuan Chen
- State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, 1838 Guangzhou avenue north, Guangzhou, 510515 China
| | - Xiaobo Huang
- State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, 1838 Guangzhou avenue north, Guangzhou, 510515 China
| | - Shiping Cao
- State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, 1838 Guangzhou avenue north, Guangzhou, 510515 China
| | - Wangjun Liao
- Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515 Guangdong China
| | - Jianping Bin
- State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, 1838 Guangzhou avenue north, Guangzhou, 510515 China
| | - Masafumi Kitakaze
- State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, 1838 Guangzhou avenue north, Guangzhou, 510515 China
- Cardiovascular Division of the Department of Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan
| | - Yulin Liao
- State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, 1838 Guangzhou avenue north, Guangzhou, 510515 China
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Htike ZZ, Yates T, Brady EM, Webb D, Gray LJ, Swarbrick D, McCann GP, Khunti K, Davies MJ. Rationale and design of the randomised controlled trial to assess the impact of liraglutide on cardiac function and structure in young adults with type 2 diabetes (the LYDIA study). Cardiovasc Diabetol 2016; 15:102. [PMID: 27440110 PMCID: PMC4955217 DOI: 10.1186/s12933-016-0421-6] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2016] [Accepted: 07/06/2016] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND The prevalence of type 2 diabetes (T2DM) in younger adults is growing. Compared to the late onset T2DM, it is well recognized that the disease tends to behave more aggressively in the younger age group with evidence of premature micro and macrovasular diseases and shorter life span. This increased mortality is largely attributed to cardiovascular complications. In a recent pilot study, young adults with T2DM were found to have significantly lower peak diastolic strain rate (PEDSR) on cardiac MRI (CMR), a forerunner of diabetic cardiomyopathy. Liraglutide, a glucagon like peptide-1 (GLP-1) analogue, is one of the new classes of glucose lowering therapies licensed to be used in management of T2DM. In randomised controlled trials, liraglutide improves glycaemic control by 1-1.5 % with an added benefit of weight loss of 2-3 kg. In addition, there is emerging evidence elucidating the cardioprotective effects of GLP-1 analogues independent of glycaemic control. In a small study, liraglutide has also been shown to improve cardiac function in patients with coronary ischaemia or congestive heart failure. METHODS AND AIMS This is a prospective, randomised, open-label, blind end-point (PROBE) active-comparator trial. A total of 90 obese eligible participants with T2DM (18-50 years) will be randomised to either liraglutide 1.8 mg once daily or sitagliptin 100 mg once daily for 26 weeks. The primary aim is to assess whether liraglutide improves diastolic function compared to sitagliptin as measured by PEDSR using CMR. DISCUSSION Although newer classes of GLP-1 analogues are made available in recent years, there are very few published studies demonstrating the beneficial effect of GLP-1 analogues on cardiovascular endpoints. In a recently published LEADER study, liraglutide has shown superiority to placebo in a population of type 2 diabetes with high risk of cardiovascular disease. To the best of our knowledge, there are no published studies establishing the effect of liraglutide on cardiac function in younger patients with T2DM on a larger scale. The LYDIA study will comprehensively describe changes in various parameters of cardiac structure and function in patients treated with liraglutide aiming to provide new evidence on effect of liraglutide on diastolic function in young obese people with T2DM. Trial Registration ClinicalTrials.gov identifier: NCT02043054.
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Affiliation(s)
- Z. Z. Htike
- />NIHR Leicester-Loughborough Diet, Lifestyle and Physical Activity Biomedical Research Unit, Leicester Diabetes Centre, Leicester General Hospital, Leicester, UK and Health Sciences, University of Leicester, Leicester, UK
| | - T. Yates
- />NIHR Leicester-Loughborough Diet, Lifestyle and Physical Activity Biomedical Research Unit, Leicester Diabetes Centre, Leicester General Hospital, Leicester, UK and Health Sciences, University of Leicester, Leicester, UK
| | - E. M. Brady
- />NIHR Leicester-Loughborough Diet, Lifestyle and Physical Activity Biomedical Research Unit, Leicester Diabetes Centre, Leicester General Hospital, Leicester, UK and Health Sciences, University of Leicester, Leicester, UK
| | - D. Webb
- />NIHR Leicester-Loughborough Diet, Lifestyle and Physical Activity Biomedical Research Unit, Leicester Diabetes Centre, Leicester General Hospital, Leicester, UK and Health Sciences, University of Leicester, Leicester, UK
| | - L. J. Gray
- />NIHR Leicester-Loughborough Diet, Lifestyle and Physical Activity Biomedical Research Unit, Leicester Diabetes Centre, Leicester General Hospital, Leicester, UK and Health Sciences, University of Leicester, Leicester, UK
| | - D. Swarbrick
- />Department of Cardiovascular Sciences, Glenfield Hospital, University of Leicester, Leicester, UK
- />NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK
| | - G. P. McCann
- />Department of Cardiovascular Sciences, Glenfield Hospital, University of Leicester, Leicester, UK
- />NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK
| | - K. Khunti
- />NIHR Leicester-Loughborough Diet, Lifestyle and Physical Activity Biomedical Research Unit, Leicester Diabetes Centre, Leicester General Hospital, Leicester, UK and Health Sciences, University of Leicester, Leicester, UK
| | - M. J. Davies
- />NIHR Leicester-Loughborough Diet, Lifestyle and Physical Activity Biomedical Research Unit, Leicester Diabetes Centre, Leicester General Hospital, Leicester, UK and Health Sciences, University of Leicester, Leicester, UK
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Hensel KO. Non-ischemic diabetic cardiomyopathy may initially exhibit a transient subclinical phase of hyperdynamic myocardial performance. Med Hypotheses 2016; 94:7-10. [PMID: 27515189 DOI: 10.1016/j.mehy.2016.06.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2016] [Accepted: 06/02/2016] [Indexed: 01/14/2023]
Abstract
Cardiovascular complications are the key cause for mortality in diabetes mellitus. Besides ischemia-related cardiac malfunction there is growing evidence for non-ischemic diabetes-associated heart failure in both type 1 and type 2 diabetes mellitus. The underlying pathophysiology of non-ischemic diabetic cardiomyopathy (NIDC) is poorly understood and data on myocardial mechanics in early stages of the disease are rare. However, several studies in both human and experimental animal settings have reported prima facie unexplained features indicating myocardial hyperdynamics early in the course of the disease. The new hypothesis is that - other than previously thought - NIDC may be non-linear and initially feature an asymptomatic subclinical phase of myocardial hypercontractility that precedes the long-term development of diabetes-associated cardiac dysfunction and ultimately heart failure. Diabetes-induced metabolic imbalances may lead to a paradoxic inotropic increase and inefficient myocardial mechanics that finally result in a gradual deterioration of myocardial performance. In conclusion, diabetic patients should be screened regularly and early in the course of the disease utilizing ultra-sensitive myocardial deformation imaging in order to identify patients at risk for diabetes-associated heart failure. Moreover, hyperdynamic myocardial deformation might help distinguish non-ischemic from ischemic diabetic cardiomyopathy. Further studies are needed to illuminate the underlying pathophysiological mechanisms, the exact spatiotemporal evolvement of diabetic cardiomyopathy and its long-term relation to clinical outcome parameters.
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Affiliation(s)
- Kai O Hensel
- HELIOS University Hospital Wuppertal, Department of Pediatrics, Center for Clinical and Translational Research (CCTR), Witten/Herdecke University, Faculty of Health, Germany.
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