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Abdelhadi NA, Ragab KM, Elkholy M, Koneru J, Ellenbogen KA, Pillai A. Impact of Sodium-Glucose Co-Transporter 2 Inhibitors on Atrial Fibrillation Recurrence Post-Catheter Ablation Among Patients With Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis. J Cardiovasc Electrophysiol 2025; 36:673-682. [PMID: 39789826 PMCID: PMC11903381 DOI: 10.1111/jce.16544] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2024] [Revised: 11/13/2024] [Accepted: 12/04/2024] [Indexed: 01/12/2025]
Abstract
Atrial fibrillation (AF) is the most common cause of arrhythmia-induced cardiomyopathy. Effective management strategies include medical therapy for rate and rhythm control, catheter ablation (CA), and goal-directed medical therapy. Sodium-glucose co-transporter 2 inhibitors (SGLT2i), a novel class of antidiabetic drugs, have shown a promising impact in reducing cardiovascular events in diabetic and nondiabetic heart failure (HF) patients. It is unclear what impact SGLT2i use may have on AF recurrence following CA. To evaluate the effects of SGLT2i on preventing AF recurrence following CA and its impact on other cardiovascular outcomes. We performed a comprehensive literature search through multiple search engines (PubMed, Scopus, Web of Science, and Cochrane) to include eligible studies using the appropriate keywords until 10 April 2024. Our search yielded nine eligible studies with 16 857 patients. Our analysis reveals a significant reduction in AF recurrence after CA among patients receiving SGLT2i compared to non-SGLT2i medications (RR = 0.72, 95% CI [0.67-0.78], p < 0.00001). Additionally, SGLT2i therapy was associated with decreased all-cause hospitalizations and reduced risk of ischemic stroke. However, no significant difference in all-cause mortality was observed between SGLT2i and non-SGLT2i groups. Our study found that SGLT2 inhibitors significantly reduced AF recurrence post-CA in diabetic patients. Moreover, SGLT2i use was associated with lowered hospitalization and ischemic stroke risk. Though no significant difference in mortality was noted, the decrease in hospitalization suggests a possible favorable effect on cardiovascular events.
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Affiliation(s)
- Naser A Abdelhadi
- Division of Cardiac Electrophysiology, Virginia Commonwealth University, Richmond, Virginia, USA
| | | | - Mohammed Elkholy
- Department of Radiology, Beth Israel Deaconess Medical Center/Harvard University, Boston, Massachusetts, USA
| | - Jayanthi Koneru
- Division of Cardiac Electrophysiology, Virginia Commonwealth University, Richmond, Virginia, USA
| | - Kenneth A Ellenbogen
- Division of Cardiac Electrophysiology, Virginia Commonwealth University, Richmond, Virginia, USA
| | - Ajay Pillai
- Division of Cardiac Electrophysiology, Virginia Commonwealth University, Richmond, Virginia, USA
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Bao Y, Hu Y, Shi M, Zhao Z. SGLT2 inhibitors reduce epicardial adipose tissue more than GLP-1 agonists or exercise interventions in patients with type 2 diabetes mellitus and/or obesity: A systematic review and network meta-analysis. Diabetes Obes Metab 2025; 27:1096-1112. [PMID: 39639835 DOI: 10.1111/dom.16107] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Revised: 11/04/2024] [Accepted: 11/11/2024] [Indexed: 12/07/2024]
Abstract
BACKGROUND Epicardial adipose tissue (EAT) plays a significant role in several cardiovascular diseases. As a correctable risk factor and potential therapeutic target, reducing EAT has multiple cardiovascular benefits, especially in those with abnormal glucolipid metabolism. The objective of this research was to compare the effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) agonists, and exercise on the thickness of EAT and indicators of glucolipid metabolism in people with type 2 diabetes mellitus (T2DM), obesity, and T2DM with obesity. METHODS We searched four electronic databases: PubMed, EMBASE, the Cochrane Library, and Web of Science for articles before 31 January 2024, regardless of language. We included randomized controlled trials and a small number of case-control studies in this network meta-analysis. Differences in mean changes in EAT, body mass index, and glucolipid metabolism-related metrics were assessed. RESULTS A comprehensive analysis was conducted on 16 trials (15 randomized controlled trials and one case-control study), comprising a total of 867 people. SGLT2 inhibitors were significantly better at reducing EAT than placebo (standard mean different [SMD] = -0.85 cm [95% confidence interval (CI) -1.39, -0.31]); a similar result was observed for exercise compared with placebo (SMD = -0.78 cm [95% CI -1.37, -0.18]). SGLT2 inhibitors were also significantly better at reducing EAT than GLP-1 agonists and conventional hypoglycaemic therapy (e.g., metformin or insulin; SMD = -0.74 cm [95% CI -1.45, -0.02] and SMD = -1.69 cm [95% CI -2.38, -0.99], respectively). SGLT2 inhibitors were significantly better than placebo at reducing body mass index (MD = -0.90 kg/m2 [95% CI -1.14, -0.66]) and glycosylated haemoglobin (MD = -0.52% [95%CI -0.86, -0.18]). A similar result was observed when comparing GLP-1 agonists and placebo (MD = -0.48% [95% CI -0.93, -0.03]). Changes in total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol were not statistically significant between interventions. CONCLUSION SGLT2 inhibitors have a distinct advantage over both placebo and other therapies at lowering EAT thickness, a result supported by direct comparisons and surface under the cumulative ranking curve analysis. Therefore, SGLT2 inhibitors should be prioritized as a treatment to reduce EAT in individuals with aberrant glucolipid levels, such as patients with T2DM and/or obesity.
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Affiliation(s)
- Yu Bao
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China
| | - Yucai Hu
- Department of Cardiovascular Diseases, First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, China
| | - Menglong Shi
- Evidence-based Medicine Center, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Zhiqiang Zhao
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China
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Wang J, Shi H, Yang Y, Gong X. Crosstalk between ferroptosis and innate immune in diabetic kidney disease: mechanisms and therapeutic implications. Front Immunol 2025; 16:1505794. [PMID: 40092979 PMCID: PMC11906378 DOI: 10.3389/fimmu.2025.1505794] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Accepted: 02/10/2025] [Indexed: 03/19/2025] Open
Abstract
Diabetic kidney disease (DKD) is a prevalent complication of diabetes mellitus (DM), and its incidence is increasing alongside the number of diabetes cases. Effective treatment and long-term management of DKD present significant challenges; thus, a deeper understanding of its pathogenesis is essential to address this issue. Chronic inflammation and abnormal cell death in the kidney closely associate with DKD development. Recently, there has been considerable attention focused on immune cell infiltration into renal tissues and its inflammatory response's role in disease progression. Concurrently, ferroptosis-a novel form of cell death-has emerged as a critical factor in DKD pathogenesis, leading to increased glomerular filtration permeability, proteinuria, tubular injury, interstitial fibrosis, and other pathological processes. The cardiorenal benefits of SGLT2 inhibitors (SGLT2-i) in DKD patients have been demonstrated through numerous large clinical trials. Moreover, further exploratory experiments indicate these drugs may ameliorate serum and urinary markers of inflammation, such as TNF-α, and inhibit ferroptosis in DKD models. Consequently, investigating the interplay between ferroptosis and innate immune and inflammatory responses in DKD is essential for guiding future drug development. This review presents an overview of ferroptosis within the context of DKD, beginning with its core mechanisms and delving into its potential roles in DKD progression. We will also analyze how aberrant innate immune cells, molecules, and signaling pathways contribute to disease progression. Finally, we discuss the interactions between ferroptosis and immune responses, as well as targeted therapeutic agents, based on current evidence. By analyzing the interplay between ferroptosis and innate immunity alongside its inflammatory responses in DKD, we aim to provide insights for clinical management and drug development in this area.
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Affiliation(s)
- Jinyang Wang
- Department of Geriatric Integrative, Second Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China
| | - Haonan Shi
- School of Medicine, Shanghai University, Shanghai, China
| | - Ye Yang
- Department of Geriatric Integrative, Second Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China
| | - Xueli Gong
- Department of Pathophysiology, School of Basic Medical Science, Xinjiang Medical University, Urumqi, Xinjiang, China
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Bahrami P, Aromolaran KA, Aromolaran AS. Proarrhythmic Lipid Inflammatory Mediators: Mechanisms in Obesity Arrhythmias. J Cell Physiol 2025; 240:e70012. [PMID: 39943721 PMCID: PMC11822244 DOI: 10.1002/jcp.70012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2024] [Revised: 01/27/2025] [Accepted: 02/03/2025] [Indexed: 02/16/2025]
Abstract
The prevalence of obesity and associated metabolic disorders such as diabetes is rapidly increasing; therefore, concerns regarding their cardiovascular consequences, including cardiac arrhythmias, are rising. As obesity progresses, the excessively produced lipids accumulate in unconventional areas such as the epicardial adipose tissue (EAT) around the myocardium. Metabolic alterations in obesity contribute to the transformation of these ectopic fat deposits into arrhythmogenic substrates. However, despite advances in therapeutic approaches, particularly in lowering EAT volume and thickness through sodium-glucose co-transporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists, obese and diabetic patients still suffer from fatal arrhythmias that may lead to sudden cardiac death. Therefore, an investigation into how unappreciated underlying pathways such as lipid mediators contribute to the transformation of adipose tissues into proinflammatory and arrhythmogenic substrates is of significance. Leukotriene B4 (LTB4) is an eicosanoid derived from arachidonic acid and acts as a lipid mediator. LTB4 has recently been identified to be associated with cardiac ion channel modulations and arrhythmogenic conditions in diabetes. LTB4 increases circulatory free fatty acids (FFAs) and has been associated with adipocyte hypertrophy. LTB4 also interferes with insulin signaling pathways, instigating insulin resistance (IR). In addition, LTB4, as a potent chemoattractant, contributes to the mobilization of circulatory immune cells such as monocytes and promotes inflammatory macrophage polarization and macrophage dysfunction. Thus, this review provides a comprehensive overview of LTB4's underlying pathways in obesity; illustrates how these pathways might lead to alterations in cardiac ion channels, currents, and cardiac arrhythmias; and shows how they might pose a therapeutic target for metabolic-associated arrhythmias.
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Affiliation(s)
- Pegah Bahrami
- Nora Eccles Harrison Cardiovascular Research and Training Institute (CVRTI)University of Utah School of MedicineSalt Lake CityUtahUSA
| | - Kelly A. Aromolaran
- Nora Eccles Harrison Cardiovascular Research and Training Institute (CVRTI)University of Utah School of MedicineSalt Lake CityUtahUSA
| | - Ademuyiwa S. Aromolaran
- Nora Eccles Harrison Cardiovascular Research and Training Institute (CVRTI)University of Utah School of MedicineSalt Lake CityUtahUSA
- Division of Cardiothoracic Surgery, Department of Surgery, Nutrition & Integrative Physiology, Biochemistry & Molecular Medicine ProgramUniversity of Utah School of MedicineSalt Lake CityUtahUSA
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Morciano C, Gugliandolo S, Capece U, Di Giuseppe G, Mezza T, Ciccarelli G, Soldovieri L, Brunetti M, Avolio A, Splendore A, Pontecorvi A, Giaccari A, Cinti F. SGLT2 inhibition and adipose tissue metabolism: current outlook and perspectives. Cardiovasc Diabetol 2024; 23:449. [PMID: 39702365 PMCID: PMC11660748 DOI: 10.1186/s12933-024-02539-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2024] [Accepted: 12/09/2024] [Indexed: 12/21/2024] Open
Abstract
Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have emerged as important agents for the treatment of type 2 diabetes mellitus (T2DM). SGLT2 inhibitors have been associated with improved cardiovascular outcomes, not only through their immediate hemodynamic effects-such as glycosuria and (at least temporary) increased natriuresis-but also due to their multifaceted impact on metabolism. Recently, studies have also focused on the effects of SGLT2 inhibitors on adipose tissue. Aside from the well-documented effects on human adiposity, SGLT2i have shown, both in vitro and in murine models, the ability to reduce fat mass, upregulate genes related to browning of white adipose tissue, influence adipocyte size and fatty acid oxidation, and improve oxidative stress and overall metabolic health. In humans, even though data are still limited, recent evidence seems to confirm that the SGLT2i effects observed in cardiovascular outcome trials could be partially explained by their impact on adipose tissue. This review aims to clarify the impact of SGLT2i on adipose tissue, highlighting their role in metabolic health and their potential to transform treatment strategies for T2DM beyond glucose metabolism.
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Affiliation(s)
- Cassandra Morciano
- Centro Malattie Endocrine e Metaboliche, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
- Dipartimento di Scienze Cliniche e Sperimentali, Medicina Interna - Università degli studi di Brescia, Brescia, BS, Italy
| | - Shawn Gugliandolo
- Centro Malattie Endocrine e Metaboliche, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Umberto Capece
- Centro Malattie Endocrine e Metaboliche, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Gianfranco Di Giuseppe
- Centro Malattie Endocrine e Metaboliche, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Teresa Mezza
- Centro Malattie Endocrine e Metaboliche, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
- Pancreas Unit, CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy
| | - Gea Ciccarelli
- Centro Malattie Endocrine e Metaboliche, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Laura Soldovieri
- Centro Malattie Endocrine e Metaboliche, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Michela Brunetti
- Centro Malattie Endocrine e Metaboliche, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Adriana Avolio
- Centro Malattie Endocrine e Metaboliche, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Amelia Splendore
- Centro Malattie Endocrine e Metaboliche, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Alfredo Pontecorvi
- Centro Malattie Endocrine e Metaboliche, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Andrea Giaccari
- Centro Malattie Endocrine e Metaboliche, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy.
| | - Francesca Cinti
- Centro Malattie Endocrine e Metaboliche, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
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Tang KX, Liao XB, Yuan LQ, He SQ, Wang M, Mei XL, Zhou ZA, Fu Q, Lin X, Liu J. An enhanced deep learning method for the quantification of epicardial adipose tissue. Sci Rep 2024; 14:24947. [PMID: 39438553 PMCID: PMC11496533 DOI: 10.1038/s41598-024-75659-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2024] [Accepted: 10/07/2024] [Indexed: 10/25/2024] Open
Abstract
Epicardial adipose tissue (EAT) significantly contributes to the progression of cardiovascular diseases (CVDs). However, manually quantifying EAT volume is labor-intensive and susceptible to human error. Although there have been some deep learning-based methods for automatic quantification of EAT, they are mostly uninterpretable and fail to harness the complete anatomical characteristics. In this study, we proposed an enhanced deep learning method designed for EAT quantification on coronary computed tomography angiography (CCTA) scan, which integrated both data-driven method and specific morphological information. A total of 108 patients who underwent routine CCTA examinations were included in this study. They were randomly assigned to training set (n = 60), validation set (n = 8), and test set (n = 40). We quantified and calculated the EAT volume based on the CT attenuation values within the predicted pericardium. The automatic method demonstrated strong agreement with expert manual quantification, yielding a median Dice score coefficients (DSC) of 0.916 (Interquartile Range (IQR): 0.846-0.948) for 2D slices. Meanwhile, the median DSC for the 3D volume was 0.896 (IQR: 0.874-0.908) between these two measures, with an excellent correlation of 0.980 (p < 0.001) for EAT volumes. Additionally, our model's Bland-Altman analysis revealed a low bias of -2.39 cm³. The incorporation of pericardial anatomical structures into deep learning methods can effectively enhance the automatic quantification of EAT. The promising results demonstrate its potential for clinical application.
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Affiliation(s)
- Ke-Xin Tang
- Department of Radiology, the Second Xiangya Hospital, Central South University, No. 139 Middle Renmin Road, Furong District, Changsha, 410000, China
- Department of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Diseases, the Second Xiangya Hospital, Central South University, Changsha, China
| | - Xiao-Bo Liao
- Department of Cardiovascular Surgery, the Second Xiangya Hospital, Central South University, Changsha, China
| | - Ling-Qing Yuan
- Department of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Diseases, the Second Xiangya Hospital, Central South University, Changsha, China
| | - Sha-Qi He
- Department of Radiology, the Second Xiangya Hospital, Central South University, No. 139 Middle Renmin Road, Furong District, Changsha, 410000, China
| | - Min Wang
- Department of Cardiovascular Surgery, the Second Xiangya Hospital, Central South University, Changsha, China
| | - Xi-Long Mei
- Department of Radiology, the Second Xiangya Hospital, Central South University, No. 139 Middle Renmin Road, Furong District, Changsha, 410000, China
| | - Zhi-Ang Zhou
- Department of Cardiovascular Surgery, the Second Xiangya Hospital, Central South University, Changsha, China
| | - Qin Fu
- Department of Cardiovascular Surgery, the Second Xiangya Hospital, Central South University, Changsha, China
| | - Xiao Lin
- Department of Radiology, the Second Xiangya Hospital, Central South University, No. 139 Middle Renmin Road, Furong District, Changsha, 410000, China.
| | - Jun Liu
- Department of Radiology, the Second Xiangya Hospital, Central South University, No. 139 Middle Renmin Road, Furong District, Changsha, 410000, China.
- Clinical Research Center for Medical Imaging in Hunan Province, Changsha, China.
- Department of Radiology Quality Control Center in Hunan Province, Changsha, China.
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Liao L, Wang T, Zhang L, Wei Y, Fan X. Protective Mechanisms of SGLTi in Ischemic Heart Disease. J Cardiovasc Transl Res 2024; 17:1018-1035. [PMID: 38767796 DOI: 10.1007/s12265-024-10513-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Accepted: 04/11/2024] [Indexed: 05/22/2024]
Abstract
Ischemic heart disease (IHD) is a common clinical cardiovascular disease with high morbidity and mortality. Sodium glucose cotransporter protein inhibitor (SGLTi) is a novel hypoglycemic drug. To date, both clinical trials and animal experiments have shown that SGLTi play a protective role in IHD, including myocardial infarction (MI) and ischemia/reperfusion (I/R). The protective effects may be involved in mechanisms of energy metabolic conversion, anti-inflammation, anti-fibrosis, ionic homeostasis improvement, immune cell development, angiogenesis and functional regulation, gut microbiota regulation, and epicardial lipids. Thus, this review summarizes the above mechanisms and aims to provide theoretical evidence for therapeutic strategies for IHD.
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Affiliation(s)
- Lei Liao
- Department of Cardiology, the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China
| | - Tong Wang
- Key Laboratory of Medical Electrophysiology of Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, 646000, Sichuan, China
| | - Lu Zhang
- Department of Cardiology, the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China
| | - Yan Wei
- Key Laboratory of Medical Electrophysiology of Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, 646000, Sichuan, China.
| | - Xinrong Fan
- Department of Cardiology, the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China.
- Key Laboratory of Medical Electrophysiology of Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, 646000, Sichuan, China.
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Li Q, Muhib UR, Ma X, Liu Z, Gao F, Wang Z. Potential Mechanisms of Epicardial Adipose Tissue Influencing Heart Failure with Preserved Ejection Fraction. Rev Cardiovasc Med 2024; 25:311. [PMID: 39355598 PMCID: PMC11440401 DOI: 10.31083/j.rcm2509311] [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: 01/16/2024] [Revised: 02/28/2024] [Accepted: 04/09/2024] [Indexed: 10/03/2024] Open
Abstract
Heart failure (HF) is the predominant terminal stage and the leading cause of mortality in cardiac disease. Heart failure with preserved ejection fraction (HFpEF) affects roughly 50% of HF patients globally. Due to the global aging population, the prevalence, morbidity, and mortality of HFpEF have gradually increased. Epicardial adipose tissue (EAT), as a key visceral adipose tissue around the heart, affects cardiac diastolic function and exercise reserve capacity. EAT closely adheres to the myocardium and can produce inflammatory factors, neurotransmitters, and other factors through autocrine or paracrine mechanisms, affecting the heart function by inflammatory response, cardiac metabolism and energy supply, cardiomyocyte structure and electrical activity, and pericardial vascular function. Currently, research on the mechanism and treatment methods of HFpEF is constantly improving. EAT may play a multi-level impact on the occurrence and development of HFpEF. This review also summarizes the potential impact of EAT on the heart in HFpEF combined with other metabolism-related diseases such as obesity or diabetes over other obesity-related measures, such as body mass index (BMI) or other adipose tissue. Above all, this review comprehensively summarizes the potential mechanisms by which EAT may affect HFpEF. The objective is to enhance our comprehension and management of HFpEF. Future research should delve into the mechanistic relationship between EAT and HFpEF, and investigate interventions aimed at EAT to improve the prognosis of patients with HFpEF.
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Affiliation(s)
- Qiuxuan Li
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing Key Laboratory of Precision Medicine of Coronary Atherosclerotic Disease, Clinical Center for Coronary Heart Disease, 100029 Beijing, China
| | - Ur Rehman Muhib
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing Key Laboratory of Precision Medicine of Coronary Atherosclerotic Disease, Clinical Center for Coronary Heart Disease, 100029 Beijing, China
| | - Xiaoteng Ma
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing Key Laboratory of Precision Medicine of Coronary Atherosclerotic Disease, Clinical Center for Coronary Heart Disease, 100029 Beijing, China
| | - Zaiqiang Liu
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing Key Laboratory of Precision Medicine of Coronary Atherosclerotic Disease, Clinical Center for Coronary Heart Disease, 100029 Beijing, China
| | - Fei Gao
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing Key Laboratory of Precision Medicine of Coronary Atherosclerotic Disease, Clinical Center for Coronary Heart Disease, 100029 Beijing, China
| | - Zhijian Wang
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing Key Laboratory of Precision Medicine of Coronary Atherosclerotic Disease, Clinical Center for Coronary Heart Disease, 100029 Beijing, China
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Mauriello A, Ascrizzi A, Roma AS, Molinari R, Caturano A, Imbalzano E, D’Andrea A, Russo V. Effects of Heart Failure Therapies on Atrial Fibrillation: Biological and Clinical Perspectives. Antioxidants (Basel) 2024; 13:806. [PMID: 39061875 PMCID: PMC11273474 DOI: 10.3390/antiox13070806] [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: 05/28/2024] [Revised: 06/21/2024] [Accepted: 07/02/2024] [Indexed: 07/28/2024] Open
Abstract
Heart failure (HF) and atrial fibrillation (AF) are prevalent cardiovascular diseases that contribute significantly to morbidity, mortality, hospitalisation, and healthcare costs. It is not uncommon for these conditions to coexist and have mutually reinforcing effects. A critical factor in the aetiology of these conditions is oxidative stress, driven by reactive oxygen species (ROS), which contributes to atrial remodelling and fibrosis. The recent introduction of new drugs for the treatment of heart failure has also had an impact on the management of atrial fibrillation due to their influence on oxidative stress. The objective of this review is to analyse the effects of these therapies, including their role in mitigating ROS, on the prevention and treatment of AF in HF patients.
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Affiliation(s)
- Alfredo Mauriello
- Cardiology Unit, Department of Medical and Translational Sciences, University of Campania “Luigi Vanvitelli”, Monaldi Hospital, 80131 Naples, Italy; (A.M.); (A.A.); (A.S.R.); (R.M.)
- Cardiology and Intensive Care Unit, Department of Cardiology, Umberto I Hospital, 84014 Nocera Inferiore, Italy;
| | - Antonia Ascrizzi
- Cardiology Unit, Department of Medical and Translational Sciences, University of Campania “Luigi Vanvitelli”, Monaldi Hospital, 80131 Naples, Italy; (A.M.); (A.A.); (A.S.R.); (R.M.)
| | - Anna Selvaggia Roma
- Cardiology Unit, Department of Medical and Translational Sciences, University of Campania “Luigi Vanvitelli”, Monaldi Hospital, 80131 Naples, Italy; (A.M.); (A.A.); (A.S.R.); (R.M.)
| | - Riccardo Molinari
- Cardiology Unit, Department of Medical and Translational Sciences, University of Campania “Luigi Vanvitelli”, Monaldi Hospital, 80131 Naples, Italy; (A.M.); (A.A.); (A.S.R.); (R.M.)
| | - Alfredo Caturano
- Department of Clinical and Experimental Medicine, University of Messina, 98100 Messina, Italy;
| | - Egidio Imbalzano
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, 80131 Naples, Italy;
| | - Antonello D’Andrea
- Cardiology and Intensive Care Unit, Department of Cardiology, Umberto I Hospital, 84014 Nocera Inferiore, Italy;
| | - Vincenzo Russo
- Cardiology Unit, Department of Medical and Translational Sciences, University of Campania “Luigi Vanvitelli”, Monaldi Hospital, 80131 Naples, Italy; (A.M.); (A.A.); (A.S.R.); (R.M.)
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10
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Buttice L, Ghani M, Suthakar J, Gnanalingham S, Carande E, Kennedy BWC, Pitcher A, Gamble JHP, Ahmad M, Lewis A, Jüni P, Rider OJ, Stephens JW, Bray JJH. The effect of sodium-glucose cotransporter-2 inhibitors on inflammatory biomarkers: A meta-analysis of randomized controlled trials. Diabetes Obes Metab 2024; 26:2706-2721. [PMID: 38602398 DOI: 10.1111/dom.15586] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Revised: 03/22/2024] [Accepted: 03/23/2024] [Indexed: 04/12/2024]
Abstract
AIMS To conduct a meta-analysis of randomized controlled trials (RCTs) to assess the effect of sodium-glucose cotransporter-2 (SGLT2) inhibitors on inflammatory biomarkers. METHODS Medline, Embase and the Cochrane Library were searched for RCTs investigating the effect of SGLT2 inhibitors on inflammatory biomarkers, adipokine profiles and insulin sensitivity. RESULTS Thirty-eight RCTs were included (14 967 participants, 63.3% male, mean age 62 ± 8.6 years) with a median (interquartile range) follow-up of 16 (12-24) weeks. Meta-analysis showed that SGLT2 inhibitors significantly improved adiponectin, interleukin-6, tumour necrosis factor receptor-1 (vs. placebo alone: standardized mean difference [SMD] 0.34 [95% confidence interval {CI} 0.23, 0.45], mean difference [MD] -0.85 pg/mL [95% CI -1.32, -0.38], SMD -0.13 [95% CI -0.20, -0.06], respectively), leptin and homeostatic model assessment of insulin resistance index (vs. CONTROL SMD -0.20 [95% CI -0.33, -0.07], MD -0.83 [95% CI -1.32, -0.33], respectively). There were no significant changes in C-reactive protein (CRP), tumour necrosis factor-α, plasminogen activator inhibitor-1, fibroblast growth factor-21 or monocyte chemoattractant protein-1. CONCLUSIONS Our analysis shows that SGLT2 inhibitors likely improve adipokine biomarkers and insulin sensitivity, but there is little evidence that SGLT2 inhibitors improve other inflammatory biomarkers including CRP.
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Affiliation(s)
| | | | | | | | - Elliott Carande
- Grange University Hospital, Cwmbran, UK
- Institute of Life Sciences 2, Swansea Bay University Health Board and Swansea University Medical School, Swansea, UK
| | | | - Alex Pitcher
- Oxford Heart Centre, John Radcliffe Hospital, Oxford, UK
| | | | | | - Andrew Lewis
- Oxford Heart Centre, John Radcliffe Hospital, Oxford, UK
- Oxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK
| | - Peter Jüni
- Nuffield Department of Population Health (NDPH), University of Oxford, Oxford, UK
| | - Oliver J Rider
- Oxford Heart Centre, John Radcliffe Hospital, Oxford, UK
- Oxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK
| | - Jeffrey W Stephens
- Institute of Life Sciences 2, Swansea Bay University Health Board and Swansea University Medical School, Swansea, UK
- Diabetes Research Group, School of Medicine, Swansea University, Swansea, UK
| | - Jonathan J H Bray
- University College London (UCL), London, UK
- Institute of Life Sciences 2, Swansea Bay University Health Board and Swansea University Medical School, Swansea, UK
- Oxford Heart Centre, John Radcliffe Hospital, Oxford, UK
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11
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Noh HJ, Cha SJ, Kim CH, Choi SW, Lee CH, Hwang JK. Efficacy of dapagliflozin in improving arrhythmia-related outcomes after ablation for atrial fibrillation: a retrospective single-center study. Clin Res Cardiol 2024; 113:924-932. [PMID: 38358416 DOI: 10.1007/s00392-024-02389-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Accepted: 01/31/2024] [Indexed: 02/16/2024]
Abstract
BACKGROUND Atrial fibrillation (AF) is a widespread type of sustained arrhythmia that poses significant health risks. Catheter ablation is the preferred treatment; however, arrhythmia recurrence remains challenging. Sodium-glucose co-transporter 2 inhibitors, particularly dapagliflozin (DAPA), have exhibited cardiovascular benefits. However, to date, the influence of these inhibitors on AF post-ablation remains unclear. METHODS We analyzed the records of 272 patients who underwent catheter ablation for AF from January 2018 to December 2022. Patients were divided into the control (n = 199) and DAPA (n = 73) groups based on DAPA prescription post-ablation. The primary outcome was total atrial arrhythmia recurrence after a 3-month blanking period. RESULTS The mean age was 72.19 ± 5.45 years; 86.8% of the patients were men. At 18 months post-ablation, 36.2% and 9.5% of the patients in the control and DAPA groups, respectively, reported atrial arrhythmia. Multivariate analysis revealed that DAPA use was associated with a significantly reduced risk of arrhythmia recurrence (adjusted hazard ratio [aHR]: 0.15, 95% confidence interval [CI]: 0.07-0.32, p < 0.001). After propensity score-matching (PSM) in 65 pairs, arrhythmia recurrence was lower in the DAPA group compared with the control (8.3% versus 30.8%, aHR: 0.17, 95% CI: 0.06-0.51, p = 0.002). Freedom from total arrhythmia recurrence was significantly higher in the DAPA group compared with the control group in both the overall and PSM population (log-rank test p < 0.01). CONCLUSION DAPA administration post-ablation was associated with significantly reduced atrial arrhythmia recurrence rates, indicating its potential as an adjunct therapy for enhancing the success of AF ablation.
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Affiliation(s)
- Hyeong Jun Noh
- Division of Cardiology, Department of Internal Medicine, Veterans Health Service Medical Center, (05368) #53 Jinhawngdo-Ro 61 Gil, Gangdong-Gu, Seoul, Republic of Korea
| | - Sung Joo Cha
- Division of Cardiology, Department of Internal Medicine, Veterans Health Service Medical Center, (05368) #53 Jinhawngdo-Ro 61 Gil, Gangdong-Gu, Seoul, Republic of Korea
| | - Chee Hae Kim
- Division of Cardiology, Department of Internal Medicine, Veterans Health Service Medical Center, (05368) #53 Jinhawngdo-Ro 61 Gil, Gangdong-Gu, Seoul, Republic of Korea
| | - Suk-Won Choi
- Division of Cardiology, Department of Internal Medicine, Veterans Health Service Medical Center, (05368) #53 Jinhawngdo-Ro 61 Gil, Gangdong-Gu, Seoul, Republic of Korea
| | - Chang Hoon Lee
- Division of Cardiology, Department of Internal Medicine, Veterans Health Service Medical Center, (05368) #53 Jinhawngdo-Ro 61 Gil, Gangdong-Gu, Seoul, Republic of Korea
| | - Jin Kyung Hwang
- Division of Cardiology, Department of Internal Medicine, Veterans Health Service Medical Center, (05368) #53 Jinhawngdo-Ro 61 Gil, Gangdong-Gu, Seoul, Republic of Korea.
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12
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Mashayekhi M, Safa BI, Gonzalez MSC, Kim SF, Echouffo-Tcheugui JB. Systemic and organ-specific anti-inflammatory effects of sodium-glucose cotransporter-2 inhibitors. Trends Endocrinol Metab 2024; 35:425-438. [PMID: 38423898 PMCID: PMC11096060 DOI: 10.1016/j.tem.2024.02.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2023] [Revised: 02/01/2024] [Accepted: 02/02/2024] [Indexed: 03/02/2024]
Abstract
Inflammation plays an essential role and is a common feature in the pathogenesis of many chronic diseases. The exact mechanisms through which sodium-glucose cotransporter-2 (SGLT2) inhibitors achieve their much-acclaimed clinical benefits largely remain unknown. In this review, we detail the systemic and tissue- or organ-specific anti-inflammatory effects of SGLT2 inhibitors using evidence from animal and human studies. We discuss the potential pathways through which SGLT2 inhibitors exert their anti-inflammatory effects, including oxidative stress, mitochondrial, and inflammasome pathways. Finally, we highlight the need for further investigation of the extent of the contribution of the anti-inflammatory effects of SGLT2 inhibition to improvements in cardiometabolic and renal outcomes in clinical studies.
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Affiliation(s)
- Mona Mashayekhi
- Vanderbilt University Medical Center, Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Nashville, TN, USA
| | - Bilgunay Ilkin Safa
- Vanderbilt University Medical Center, Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Nashville, TN, USA
| | - Matthew S C Gonzalez
- Vanderbilt University Medical Center, Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Nashville, TN, USA
| | - Sangwon F Kim
- Johns Hopkins University School of Medicine, Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Baltimore, MD, USA
| | - Justin B Echouffo-Tcheugui
- Johns Hopkins University School of Medicine, Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Baltimore, MD, USA.
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13
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Cinti F, Leccisotti L, Sorice GP, Capece U, D'Amario D, Lorusso M, Gugliandolo S, Morciano C, Guarneri A, Guzzardi MA, Mezza T, Capotosti A, Indovina L, Ferraro PM, Iozzo P, Crea F, Giordano A, Giaccari A. Dapagliflozin treatment is associated with a reduction of epicardial adipose tissue thickness and epicardial glucose uptake in human type 2 diabetes. Cardiovasc Diabetol 2023; 22:349. [PMID: 38115004 PMCID: PMC10731727 DOI: 10.1186/s12933-023-02091-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Accepted: 12/11/2023] [Indexed: 12/21/2023] Open
Abstract
OBJECTIVE We recently demonstrated that treatment with sodium-glucose cotransporter-2 inhibitors (SGLT-2i) leads to an increase in myocardial flow reserve in patients with type 2 diabetes (T2D) with stable coronary artery disease (CAD). The mechanism by which this occurs is, however, unclear. One of the risk factors for cardiovascular disease is inflammation of epicardial adipose tissue (EAT). Since the latter is often increased in type 2 diabetes patients, it could play a role in coronary microvascular dysfunction. It is also well known that SGLT-2i modify adipose tissue metabolism. We aimed to investigate the effects of the SGLT-2i dapagliflozin on metabolism and visceral and subcutaneous adipose tissue thickness in T2D patients with stable coronary artery disease and to verify whether these changes could explain observed changes in myocardial flow. METHODS We performed a single-center, prospective, randomized, double-blind, controlled clinical trial with 14 T2D patients randomized 1:1 to SGLT-2i dapagliflozin (10 mg daily) or placebo. The thickness of visceral (epicardial, mediastinal, perirenal) and subcutaneous adipose tissue and glucose uptake were assessed at baseline and 4 weeks after treatment initiation by 2-deoxy-2-[18F]fluoro-D-glucose Positron Emission Tomography/Computed Tomography during hyperinsulinemic euglycemic clamp. RESULTS The two groups were well-matched for baseline characteristics (age, diabetes duration, HbA1c, BMI, renal and heart function). Dapagliflozin treatment significantly reduced EAT thickness by 19% (p = 0.03). There was a significant 21.6% reduction in EAT glucose uptake during euglycemic hyperinsulinemic clamp in the dapagliflozin group compared with the placebo group (p = 0.014). There were no significant effects on adipose tissue thickness/metabolism in the other depots explored. CONCLUSIONS SGLT-2 inhibition selectively reduces EAT thickness and EAT glucose uptake in T2D patients, suggesting a reduction of EAT inflammation. This could explain the observed increase in myocardial flow reserve, providing new insights into SGLT-2i cardiovascular benefits.
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Affiliation(s)
- Francesca Cinti
- Centro Malattie Endocrine e Metaboliche, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS and Università Cattolica del Sacro Cuore, Rome, Italy
| | - Lucia Leccisotti
- UOC di Medicina Nucleare, Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS and Università Cattolica del Sacro Cuore, Rome, Italy
| | - Gian Pio Sorice
- Centro Malattie Endocrine e Metaboliche, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS and Università Cattolica del Sacro Cuore, Rome, Italy
- Sezione di Medicina Interna, Endocrinologia, Andrologia e Malattie Metaboliche, Dipartimento di Medicina di Precisione e Rigenerativa e Area Jonica - (DiMePRe-J), Università Degli Studi di Bari "Aldo Moro", Bari, Italy
| | - Umberto Capece
- Centro Malattie Endocrine e Metaboliche, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS and Università Cattolica del Sacro Cuore, Rome, Italy
| | - Domenico D'Amario
- Dipartimento di Scienze Cardiovascolari, UOC Di Cardiologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, and Università Cattolica del Sacro Cuore, Rome, Italy
- Università del Piemonte Orientale , Dipartimento Medicina Translazionale, Novara, Italy
| | - Margherita Lorusso
- UOC di Medicina Nucleare, Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS and Università Cattolica del Sacro Cuore, Rome, Italy
| | - Shawn Gugliandolo
- Centro Malattie Endocrine e Metaboliche, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS and Università Cattolica del Sacro Cuore, Rome, Italy
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Cassandra Morciano
- Centro Malattie Endocrine e Metaboliche, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS and Università Cattolica del Sacro Cuore, Rome, Italy
- Dipartimento di Scienze Cliniche e Sperimentali, Medicina Interna - Università degli Studi di Brescia, Brescia, BS, Italy
| | - Andrea Guarneri
- UOC di Medicina Nucleare, Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS and Università Cattolica del Sacro Cuore, Rome, Italy
| | - Maria Angela Guzzardi
- Istituto di Fisiologia Clinica, Consiglio Nazionale delle Ricerche (CNR), Pisa, Italy
| | - Teresa Mezza
- Centro Malattie Endocrine e Metaboliche, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS and Università Cattolica del Sacro Cuore, Rome, Italy
- Pancreas Unit, CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy
| | - Amedeo Capotosti
- UOSD Fisica Medica e Radioprotezione, Dipartimento di Diagnostica per Immagini, Fondazione Policlinico Universitario A. Gemelli IRCCS, Radioterapia Oncologica ed Ematologia, Rome, Italy
| | - Luca Indovina
- UOSD Fisica Medica e Radioprotezione, Dipartimento di Diagnostica per Immagini, Fondazione Policlinico Universitario A. Gemelli IRCCS, Radioterapia Oncologica ed Ematologia, Rome, Italy
| | - Pietro Manuel Ferraro
- U.O.S. Terapia Conservativa della Malattia Renale Cronica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Patricia Iozzo
- Istituto di Fisiologia Clinica, Consiglio Nazionale delle Ricerche (CNR), Pisa, Italy
| | - Filippo Crea
- Dipartimento di Scienze Cardiovascolari, UOC Di Cardiologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, and Università Cattolica del Sacro Cuore, Rome, Italy
| | - Alessandro Giordano
- UOC di Medicina Nucleare, Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS and Università Cattolica del Sacro Cuore, Rome, Italy.
| | - Andrea Giaccari
- Centro Malattie Endocrine e Metaboliche, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS and Università Cattolica del Sacro Cuore, Rome, Italy.
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14
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De Biase N, Mazzola M, Del Punta L, Di Fiore V, De Carlo M, Giannini C, Costa G, Paneni F, Mengozzi A, Nesti L, Gargani L, Masi S, Pugliese NR. Haemodynamic and metabolic phenotyping of patients with aortic stenosis and preserved ejection fraction: A specific phenotype of heart failure with preserved ejection fraction? Eur J Heart Fail 2023; 25:1947-1958. [PMID: 37655676 DOI: 10.1002/ejhf.3018] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2023] [Revised: 08/22/2023] [Accepted: 08/26/2023] [Indexed: 09/02/2023] Open
Abstract
AIMS Degenerative aortic valve stenosis with preserved ejection fraction (ASpEF) and heart failure with preserved ejection fraction (HFpEF) display intriguing similarities. This study aimed to provide a non-invasive, comparative analysis of ASpEF versus HFpEF at rest and during exercise. METHODS AND RESULTS We prospectively enrolled 148 patients with HFpEF and 150 patients with degenerative moderate-to-severe ASpEF, together with 66 age- and sex-matched healthy controls. All subjects received a comprehensive evaluation at rest and 351/364 (96%) performed a combined cardiopulmonary exercise stress echocardiography test. Patients with ASpEF eligible for transcatheter aortic valve replacement (n = 125) also performed cardiac computed tomography (CT). HFpEF and ASpEF patients showed similar demographic distribution and biohumoral profiles. Most patients with ASpEF (134/150, 89%) had severe high-gradient aortic stenosis; 6/150 (4%) had normal-flow, low-gradient ASpEF, while 10/150 (7%) had low-flow, low-gradient ASpEF. Both patient groups displayed significantly lower peak oxygen consumption (VO2 ), peak cardiac output, and peak arteriovenous oxygen difference compared to controls (all p < 0.01). ASpEF patients showed several extravalvular abnormalities at rest and during exercise, similar to HFpEF (all p < 0.01 vs. controls). Epicardial adipose tissue (EAT) thickness was significantly greater in ASpEF than HFpEF and was inversely correlated with peak VO2 in all groups. In ASpEF, EAT was directly related to echocardiography-derived disease severity and CT-derived aortic valve calcium burden. CONCLUSION Functional capacity is similarly impaired in ASpEF and HFpEF due to both peripheral and central components. Further investigation is warranted to determine whether extravalvular alterations may affect disease progression and prognosis in ASpEF even after valve intervention, which could support the concept of ASpEF as a specific sub-phenotype of HFpEF.
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Affiliation(s)
- Nicolò De Biase
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Matteo Mazzola
- Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa, Italy
| | - Lavinia Del Punta
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Valerio Di Fiore
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Marco De Carlo
- Cardiac, Thoracic and Vascular Department, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
| | - Cristina Giannini
- Cardiac, Thoracic and Vascular Department, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
| | - Giulia Costa
- Cardiac, Thoracic and Vascular Department, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
| | - Francesco Paneni
- Center for Translational and Experimental Cardiology (CTEC), Department of Cardiology, University Hospital Zurich and University of Zurich, Zurich, Switzerland
| | - Alessandro Mengozzi
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
- Center for Translational and Experimental Cardiology (CTEC), Department of Cardiology, University Hospital Zurich and University of Zurich, Zurich, Switzerland
| | - Lorenzo Nesti
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Luna Gargani
- Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa, Italy
| | - Stefano Masi
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
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15
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Anagnostopoulos I, Kousta M, Kossyvakis C, Paraskevaidis NT, Vrachatis D, Deftereos S, Giannopoulos G. Epicardial Adipose Tissue and Atrial Fibrillation Recurrence following Catheter Ablation: A Systematic Review and Meta-Analysis. J Clin Med 2023; 12:6369. [PMID: 37835012 PMCID: PMC10573952 DOI: 10.3390/jcm12196369] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Revised: 09/29/2023] [Accepted: 10/02/2023] [Indexed: 10/15/2023] Open
Abstract
(1)Introduction: Catheter ablation has become a cornerstone for the management of patients with atrial fibrillation (AF). Nevertheless, recurrence rates remain high. Epicardial adipose tissue (EAT) has been associated with AF pathogenesis and maintenance. However, the literature has provided equivocal results regarding the relationship between EAT and post-ablation recurrence.(2) Purpose: to investigate the relationship between total and peri-left atrium (peri-LA) EAT with post-ablation AF recurrence. (3) Methods: major electronic databases were searched for articles assessing the relationship between EAT, quantified using computed tomography, and the recurrence of AF following catheter ablation procedures. (4) Results: Twelve studies (2179 patients) assessed total EAT and another twelve (2879 patients) peri-LA EAT. Almost 60% of the included patients had paroxysmal AF and recurrence was documented in 34%. Those who maintained sinus rhythm had a significantly lower volume of peri-LA EAT (SMD: -0.37, 95%; CI: -0.58-0.16, I2: 68%). On the contrary, no significant difference was documented for total EAT (SMD: -0.32, 95%; CI: -0.65-0.01; I2: 92%). No differences were revealed between radiofrequency and cryoenergy pulmonary venous isolation. No publication bias was identified. (5) Conclusions: Only peri-LA EAT seems to be predictive of post-ablation AF recurrence. These findings may reflect different pathophysiological roles of EAT depending on its location. Whether peri-LA EAT can be used as a predictor and target to prevent recurrence is a matter of further research.
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Affiliation(s)
| | - Maria Kousta
- Cardiology Department, Athens General Hospital “G. Gennimatas”, 11527 Athens, Greece (C.K.)
| | - Charalampos Kossyvakis
- Cardiology Department, Athens General Hospital “G. Gennimatas”, 11527 Athens, Greece (C.K.)
| | | | - Dimitrios Vrachatis
- 2nd Department of Cardiology, National and Kapodistrian University of Athens, 15772 Athens, Greece
| | - Spyridon Deftereos
- 2nd Department of Cardiology, National and Kapodistrian University of Athens, 15772 Athens, Greece
| | - Georgios Giannopoulos
- 3rd Department of Cardiology, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
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16
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Requena-Ibanez JA, Santos-Gallego CG, Zafar MU, Badimon JJ. SGLT2-Inhibitors on HFpEF Patients. Role of Ejection Fraction. Cardiovasc Drugs Ther 2023; 37:989-996. [PMID: 35920946 DOI: 10.1007/s10557-022-07371-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/22/2022] [Indexed: 11/03/2022]
Abstract
Results from DELIVER trial and publication of EMPEROR-Preserved with sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with heart failure (HF) with ejection fraction (EF) > 40% represent a significant step forward in the treatment of HF with preserved EF (HFpEF). However, detailed analysis and attenuation of effect at higher EF levels have sparked some doubts about whether empagliflozin is effective across the entire spectrum of EF. HFpEF is no longer considered as one disease entity, but has been reconceptualized as a heterogenous group of phenotypes with derangements in multiple organ systems, driven by comorbidities. This heterogeneity suggests that it should not be considered as a single group in terms of treatment goals or clinical approach. Future research at the higher range of EF should ideally tailor investigations for unequivocally preserved EF (> 50%), consider the dynamic nature of EF over time, and use low-variability imaging techniques such as CMR. Furthermore, classifications based on pathophysiology and HF phenotypes beyond the EF construct will shape the design of future trials and help narrow down groups of patients who may respond to personalized treatment.
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Affiliation(s)
- Juan Antonio Requena-Ibanez
- Atherothrombosis Research Unit, Icahn School of Medicine at Mount Sinai, Mount Sinai Heart, New York, NY, 10029, USA
| | - Carlos G Santos-Gallego
- Atherothrombosis Research Unit, Icahn School of Medicine at Mount Sinai, Mount Sinai Heart, New York, NY, 10029, USA
| | - M Urooj Zafar
- Atherothrombosis Research Unit, Icahn School of Medicine at Mount Sinai, Mount Sinai Heart, New York, NY, 10029, USA
| | - Juan J Badimon
- Atherothrombosis Research Unit, Icahn School of Medicine at Mount Sinai, Mount Sinai Heart, New York, NY, 10029, USA.
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17
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Zain S, Shamshad T, Kabir A, Khan AA. Epicardial Adipose Tissue and Development of Atrial Fibrillation (AFIB) and Heart Failure With Preserved Ejection Fraction (HFpEF). Cureus 2023; 15:e46153. [PMID: 37900360 PMCID: PMC10612538 DOI: 10.7759/cureus.46153] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/28/2023] [Indexed: 10/31/2023] Open
Abstract
Epicardial adipose tissue (EAT) has been associated with the development of many cardiovascular abnormalities, of which the development of atrial fibrillation (AFIB) in this group of patients is not an uncommon finding. Several mechanisms have been proposed to explain the role of EAT in the development of AFIB. It involves cardiac remodeling owing to the underlying fatty infiltration and the subsequent inflammation and fibrosis. This leads to the formation of ectopic foci that can lead to AFIB. Some studies propose that structural and valvular heart disease and increased hemodynamic stress further augment the development of AFIB in patients with underlying EAT. The degree of development of AFIB is also related to EAT thickness and volume. Therefore, EAT quantification can be used as an imaging technique to predict cardiovascular outcomes in these patients. Obesity also plays an important role in the development of AFIB both as an independent factor and by leading to adipose tissue deposition on the epicardial tissue. Understanding the pathophysiology of EAT is important as it can lead to the development of therapies that can target obesity as a risk factor for preventing AFIB. Some promising therapies have already been investigated for decreasing the risk of AFIB in patients with EAT. Dietary changes and weight loss have been shown to reduce the deposition of fat on epicardial tissue. Antidiabetic drugs and statin therapy have also shown promising results. Bariatric surgery has been shown to decrease EAT volume on echocardiography in obese patients.
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Affiliation(s)
- Sarmad Zain
- Internal Medicine, Nishtar Medical University, Multan, PAK
| | - Talha Shamshad
- Internal Medicine, Nishtar Medical University, Multan, PAK
| | - Ahmad Kabir
- Internal Medicine, Nishtar Medical University, Multan, PAK
- Pulmonology & Critical Care, Ch. Pervaiz Elahi Institute of Cardiology Multan, Multan, PAK
| | - Ahmad Ali Khan
- Cardiology, Ch. Pervaiz Elahi Institute of Cardiology Multan, Multan, PAK
- Internal Medicine, Nishtar Medical University, Multan, PAK
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Shi YJ, Dong GJ, Guo M. Targeting epicardial adipose tissue: A potential therapeutic strategy for heart failure with preserved ejection fraction with type 2 diabetes mellitus. World J Diabetes 2023; 14:724-740. [PMID: 37383601 PMCID: PMC10294070 DOI: 10.4239/wjd.v14.i6.724] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Revised: 02/10/2023] [Accepted: 04/24/2023] [Indexed: 06/14/2023] Open
Abstract
Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome with various comorbidities, multiple cardiac and extracardiac pathophysiologic abnormalities, and diverse phenotypic presentations. Since HFpEF is a heterogeneous disease with different phenotypes, individualized treatment is required. HFpEF with type 2 diabetes mellitus (T2DM) represents a specific phenotype of HFpEF, with about 45%-50% of HFpEF patients suffering from T2DM. Systemic inflammation associated with dysregulated glucose metabolism is a critical pathological mechanism of HFpEF with T2DM, which is intimately related to the expansion and dysfunction (inflammation and hypermetabolic activity) of epicardial adipose tissue (EAT). EAT is well established as a very active endocrine organ that can regulate the pathophysiological processes of HFpEF with T2DM through the paracrine and endocrine mechanisms. Therefore, suppressing abnormal EAT expansion may be a promising therapeutic strategy for HFpEF with T2DM. Although there is no treatment specifically for EAT, lifestyle management, bariatric surgery, and some pharmaceutical interventions (anti-cytokine drugs, statins, proprotein convertase subtilisin/kexin type 9 inhibitors, metformin, glucagon-like peptide-1 receptor agonists, and especially sodium-glucose cotransporter-2 inhibitors) have been shown to attenuate the inflammatory response or expansion of EAT. Importantly, these treatments may be beneficial in improving the clinical symptoms or prognosis of patients with HFpEF. Accordingly, well-designed randomized controlled trials are needed to validate the efficacy of current therapies. In addition, more novel and effective therapies targeting EAT are needed in the future.
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Affiliation(s)
- Yu-Jiao Shi
- Department of Cardiovascular Medicine, Xiyuan Hospital, Chinese Academy of Traditional Chinese Medicine, Beijing 100091, China
| | - Guo-Ju Dong
- Department of Cardiovascular Medicine, Xiyuan Hospital, Chinese Academy of Traditional Chinese Medicine, Beijing 100091, China
| | - Ming Guo
- Department of Cardiovascular Medicine, Xiyuan Hospital, Chinese Academy of Traditional Chinese Medicine, Beijing 100091, China
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19
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Oates CP, Santos-Gallego CG, Smith A, Basyal B, Moss N, Kawamura I, Musikantow DR, Turagam MK, Miller MA, Whang W, Dukkipati SR, Reddy VY, Koruth JS. SGLT2 inhibitors reduce sudden cardiac death risk in heart failure: Meta-analysis of randomized clinical trials. J Cardiovasc Electrophysiol 2023; 34:1277-1285. [PMID: 36950852 DOI: 10.1111/jce.15894] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2023] [Revised: 03/15/2023] [Accepted: 03/20/2023] [Indexed: 03/24/2023]
Abstract
INTRODUCTION Multiple randomized controlled trials have demonstrated sodium-glucose cotransporter-2 inhibitors (SGLT2i) decrease the composite endpoint of cardiovascular death or heart failure hospitalizations in all heart failure patients. It is uncertain whether SGLT2i impacts the risk of sudden cardiac death in patients with heart failure. METHODS A comprehensive search was performed to identify relevant data published before August 28, 2022. Trials were included if: (1) all patients had clinical heart failure (2) SGLT2i and placebo were compared (3) all patients received conventional medical therapy and (4) reported outcomes of interest (sudden cardiac death [SCD], ventricular arrhythmias, atrial arrhythmias). RESULTS SCD was reported in seven of the eleven trials meeting selection criteria: 10 796 patients received SGLT2i and 10 796 received placebo. SGLT2i therapy was associated with a significant reduction in the risk of SCD (risk ratios [RR]: 0.68; 95% confidence intervals [CI]: 0.48-0.95; p = .03; I2 = 0%). Absent dedicated rhythm monitoring, there were no significant differences in the incidence of sustained ventricular arrhythmias not associated with SCD (RR: 1.03; 95% CI: 0.83-1.29; p = .77; I2 = 0%) or atrial arrhythmias (RR: 0.91; 95% CI: 0.77-1.09; p = .31; I2 = 29%) between patients receiving an SGLT2i versus placebo. CONCLUSION SGLT2i therapy is associated with a reduced risk of SCD in patients with heart failure receiving contemporary medical therapy. Prospective trials are needed to determine the long-term impact of SGLT2i therapy on atrial and ventricular arrhythmias.
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Affiliation(s)
- Connor P Oates
- MedStar Heart and Vascular Institute, Georgetown University-Washington Hospital Center, Washington, District of Columbia, USA
| | - Carlos G Santos-Gallego
- Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Alex Smith
- MedStar Heart and Vascular Institute, Georgetown University-Washington Hospital Center, Washington, District of Columbia, USA
| | - Binaya Basyal
- MedStar Heart and Vascular Institute, Georgetown University-Washington Hospital Center, Washington, District of Columbia, USA
| | - Noah Moss
- Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Iwanari Kawamura
- Helmsley Center for Cardiac Electrophysiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Daniel R Musikantow
- Helmsley Center for Cardiac Electrophysiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Mohit K Turagam
- Helmsley Center for Cardiac Electrophysiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Marc A Miller
- Helmsley Center for Cardiac Electrophysiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - William Whang
- Helmsley Center for Cardiac Electrophysiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Srinivas R Dukkipati
- Helmsley Center for Cardiac Electrophysiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Vivek Y Reddy
- Helmsley Center for Cardiac Electrophysiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Jacob S Koruth
- Helmsley Center for Cardiac Electrophysiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
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20
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Ziyrek M, Dönmez E, Özcan S, Duran M, Tezcan H, İnce O, Özdemir E, Sahin I, Okuyan E. Effect of SGLT-2 inhibitors as an add-on therapy to metformin on P wave indices and atrial electromechanics in type 2 diabetes mellitus patients. Pacing Clin Electrophysiol 2023. [PMID: 37120828 DOI: 10.1111/pace.14704] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Revised: 02/21/2023] [Accepted: 04/06/2023] [Indexed: 05/02/2023]
Abstract
INTRODUCTION Sodium-glucose co-transporter 2 (SGLT-2) inhibitors have been shown to reduce the risk of atrial fibrillation (AF) occurrence in patients with diabetes mellitus (DM). In this prospective study, we aimed to analyze the effect of SGLT-2 inhibitors as an add-on therapy to metformin on P wave indices and atrial electromechanics in patients with type 2 DM. METHODS A total of 144 patients enrolled. Electrocardiographic indices were recorded on admission and at 3rd and 6th month of the combination therapy. P wave indices and atrial electromechanical coupling intervals were measured and compared. RESULTS Although decrease in P wave dispersion (62.78 ± 9.59 vs. 53.62 ± 10.65; p = .002) became significant at 6th month of combination therapy, significant decreases in P wave terminal force in V1 (37.79 ± 3.45 vs. 32.01 ± 5.74; p = .035), left atrial volume index (35.87 ± 6.57 vs. 31.33 ± 7.31; p = .042), left sided intra-atrial electromechanical delay (32.09 ± 9.17 vs. 27.61 ± 8.50; p = .016), right sided intra-atrial electromechanical delay (31.82 ± 4.92 vs. 27.65 ± 8.05; p = .042), and interatrial electromechanical delay (29.65 ± 7.52 vs. 25.96 ± 4.30; p = .044) were seen as early as 3rd month of treatment. Besides, there was no statistically significant difference between Empagliflozin and Dapagliflozin subgroups in terms of mentioned parameters. CONCLUSION SGLT-2 inhibitors as an add-on therapy to metformin were shown to significantly improve P wave indices and atrial electromechanics in type 2 DM patients as early as the 3rd month of treatment. It was thought that this may be one of the underlying mechanisms of the decrease in the frequency of AF with the use of SGLT2 inhibitors.
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Affiliation(s)
- Murat Ziyrek
- Department of Cardiology, Bağcılar Training and Research Hospital, İstanbul, Turkey
| | - Esra Dönmez
- Department of Cardiology, Bağcılar Training and Research Hospital, İstanbul, Turkey
| | - Sevgi Özcan
- Department of Cardiology, Bağcılar Training and Research Hospital, İstanbul, Turkey
| | - Mustafa Duran
- Department of Cardiology, Konya City Hospital, Karatay-Konya, Turkey
| | - Hüseyin Tezcan
- Department of Cardiology, Konya City Hospital, Karatay-Konya, Turkey
| | - Orhan İnce
- Department of Cardiology, Bağcılar Training and Research Hospital, İstanbul, Turkey
| | - Emrah Özdemir
- Department of Cardiology, Biruni University, İstanbul, Turkey
| | - Irfan Sahin
- Department of Cardiology, Bağcılar Training and Research Hospital, İstanbul, Turkey
| | - Ertugrul Okuyan
- Department of Cardiology, Bağcılar Training and Research Hospital, İstanbul, Turkey
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Kuang Z, Hou N, Kan C, Han F, Qiu H, Sun X. The protective effects of SGLT-2 inhibitors, GLP-1 receptor agonists, and RAAS blockers against renal injury in patients with type 2 diabetes. Int Urol Nephrol 2023; 55:617-629. [PMID: 36036316 DOI: 10.1007/s11255-022-03355-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Accepted: 08/21/2022] [Indexed: 10/15/2022]
Abstract
Diabetic kidney disease is one of the most severe complications of type 2 diabetes mellitus. Patients with diabetic kidney disease have a worse prognosis in terms of mortality and morbidity, compared with patients who have diabetes alone. Strict control of blood pressure and blood glucose is the primary method for prevention of initial kidney damage and delaying further progression of existing damage. Other management approaches include the use of exogenous drugs that can effectively protect the kidneys from diabetes, such as sodium-glucose transporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, and renin-angiotensin-aldosterone system blockers. These drugs may protect against kidney injury through various molecular mechanisms. This review focuses on renal impairment in patients with type 2 diabetes; it discusses the direct and indirect effects of sodium-glucose transporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, and renin-angiotensin-aldosterone system blockers on diabetic kidney disease. Finally, it discusses the effects of combination treatment with two or three types of drugs in patients with chronic kidney disease.
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Affiliation(s)
- Zengguang Kuang
- Department of Endocrinology and Metabolism, Affiliated Hospital of Weifang Medical University, 2428 Yuhe Road, Weifang, 261031, Shandong, China
- Branch of Shandong Provincial Clinical Research Center for Diabetes and Metabolic Diseases, Weifang, China
- Clinical Research Center, Affiliated Hospital of Weifang Medical University, Weifang, China
| | - Ningning Hou
- Department of Endocrinology and Metabolism, Affiliated Hospital of Weifang Medical University, 2428 Yuhe Road, Weifang, 261031, Shandong, China
- Branch of Shandong Provincial Clinical Research Center for Diabetes and Metabolic Diseases, Weifang, China
| | - Chengxia Kan
- Department of Endocrinology and Metabolism, Affiliated Hospital of Weifang Medical University, 2428 Yuhe Road, Weifang, 261031, Shandong, China
- Branch of Shandong Provincial Clinical Research Center for Diabetes and Metabolic Diseases, Weifang, China
- Clinical Research Center, Affiliated Hospital of Weifang Medical University, Weifang, China
| | - Fang Han
- Department of Pathology, Affiliated Hospital of Weifang Medical University, Weifang, China
| | - Hongyan Qiu
- Department of Endocrinology and Metabolism, Affiliated Hospital of Weifang Medical University, 2428 Yuhe Road, Weifang, 261031, Shandong, China.
- Branch of Shandong Provincial Clinical Research Center for Diabetes and Metabolic Diseases, Weifang, China.
- Clinical Research Center, Affiliated Hospital of Weifang Medical University, Weifang, China.
| | - Xiaodong Sun
- Department of Endocrinology and Metabolism, Affiliated Hospital of Weifang Medical University, 2428 Yuhe Road, Weifang, 261031, Shandong, China.
- Branch of Shandong Provincial Clinical Research Center for Diabetes and Metabolic Diseases, Weifang, China.
- Clinical Research Center, Affiliated Hospital of Weifang Medical University, Weifang, China.
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Myasoedova VA, Parisi V, Moschetta D, Valerio V, Conte M, Massaiu I, Bozzi M, Celeste F, Leosco D, Iaccarino G, Genovese S, Poggio P. Efficacy of cardiometabolic drugs in reduction of epicardial adipose tissue: a systematic review and meta-analysis. Cardiovasc Diabetol 2023; 22:23. [PMID: 36721184 PMCID: PMC9890718 DOI: 10.1186/s12933-023-01738-2] [Citation(s) in RCA: 26] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Accepted: 01/06/2023] [Indexed: 02/01/2023] Open
Abstract
BACKGROUND Epicardial adipose tissue (EAT) plays an important role in cardiometabolic risk. EAT is a modifiable risk factor and could be a potential therapeutic target for drugs that already show cardiovascular benefits. The aim of this study is to evaluate the effect of cardiometabolic drugs on EAT reduction. METHODS A detailed search related to the effect on EAT reduction due to cardiometabolic drugs, such as glucagon-like peptide-1 receptor agonist (GLP-1 RA), sodium-glucose cotransporter-2 inhibitors (SGLT2-i), and statins was conducted according to PRISMA guidelines. Eighteen studies enrolling 1064 patients were included in the qualitative and quantitative analyses. RESULTS All three analyzed drug classes, in particular GLP-1 RA, show a significant effect on EAT reduction (GLP-1 RA standardize mean difference (SMD) = - 1.005; p < 0.001; SGLT2-i SMD = - 0.552; p < 0.001, and statin SMD = - 0.195; p < 0.001). The sensitivity analysis showed that cardiometabolic drugs strongly benefit EAT thickness reduction, measured by ultrasound (overall SMD of - 0.663; 95%CI - 0.79, - 0.52; p < 0.001). Meta-regression analysis revealed younger age and higher BMI as significant effect modifiers of the association between cardiometabolic drugs and EAT reduction for both composite effect and effect on EAT thickness, (age Z: 3.99; p < 0.001 and Z: 1.97; p = 0.001, respectively; BMI Z: - 4.40; p < 0.001 and Z: - 2.85; p = 0.004, respectively). CONCLUSIONS Cardiometabolic drugs show a significant beneficial effect on EAT reduction. GLP-1 RA was more effective than SGLT2-i, while statins had a rather mild effect. We believe that the most effective treatment with these drugs should target younger patients with high BMI.
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Affiliation(s)
- Veronika A Myasoedova
- Unit for the Study of Aortic, Valvular, and Coronary Pathologies, Centro Cardiologico Monzino IRCCS, Via Carlo Parea 4, 20138, Milan, Italy.
| | - Valentina Parisi
- Department of Translational Medical Sciences, Federico II University, Naples, Italy
| | - Donato Moschetta
- Unit for the Study of Aortic, Valvular, and Coronary Pathologies, Centro Cardiologico Monzino IRCCS, Via Carlo Parea 4, 20138, Milan, Italy
| | - Vincenza Valerio
- Unit for the Study of Aortic, Valvular, and Coronary Pathologies, Centro Cardiologico Monzino IRCCS, Via Carlo Parea 4, 20138, Milan, Italy
| | - Maddalena Conte
- Department of Translational Medical Sciences, Federico II University, Naples, Italy
- Casa Di Cura San Michele, Maddaloni, Italy
| | - Ilaria Massaiu
- Unit for the Study of Aortic, Valvular, and Coronary Pathologies, Centro Cardiologico Monzino IRCCS, Via Carlo Parea 4, 20138, Milan, Italy
| | - Michele Bozzi
- Unit for the Study of Aortic, Valvular, and Coronary Pathologies, Centro Cardiologico Monzino IRCCS, Via Carlo Parea 4, 20138, Milan, Italy
| | - Fabrizio Celeste
- Unit for the Study of Aortic, Valvular, and Coronary Pathologies, Centro Cardiologico Monzino IRCCS, Via Carlo Parea 4, 20138, Milan, Italy
| | - Dario Leosco
- Department of Translational Medical Sciences, Federico II University, Naples, Italy
| | - Guido Iaccarino
- Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy
| | - Stefano Genovese
- Unit for the Study of Aortic, Valvular, and Coronary Pathologies, Centro Cardiologico Monzino IRCCS, Via Carlo Parea 4, 20138, Milan, Italy
| | - Paolo Poggio
- Unit for the Study of Aortic, Valvular, and Coronary Pathologies, Centro Cardiologico Monzino IRCCS, Via Carlo Parea 4, 20138, Milan, Italy.
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23
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Bakkar NMZ, AlZaim I, El-Yazbi AF. Depot-specific adipose tissue modulation by SGLT2 inhibitors and GLP1 agonists mediates their cardioprotective effects in metabolic disease. Clin Sci (Lond) 2022; 136:1631-1651. [PMID: 36383188 DOI: 10.1042/cs20220404] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Revised: 10/23/2022] [Accepted: 10/31/2022] [Indexed: 01/03/2025]
Abstract
Sodium-glucose transporter-2 inhibitors (SGLT-2i) and glucagon-like peptide 1 (GLP-1) receptor agonists are newer antidiabetic drug classes, which were recently shown to decrease cardiovascular (CV) morbidity and mortality in diabetic patients. CV benefits of these drugs could not be directly attributed to their blood glucose lowering capacity possibly implicating a pleotropic effect as a mediator of their impact on cardiovascular disease (CVD). Particularly, preclinical and clinical studies indicate that SGLT-2i(s) and GLP-1 receptor agonists are capable of differentially modulating distinct adipose pools reducing the accumulation of fat in some depots, promoting the healthy expansion of others, and/or enhancing their browning, leading to the suppression of the metabolically induced inflammatory processes. These changes are accompanied with improvements in markers of cardiac structure and injury, coronary and vascular endothelial healing and function, vascular remodeling, as well as reduction of atherogenesis. Here, through a summary of the available evidence, we bring forth our view that the observed CV benefit in response to SGLT-2i or GLP-1 agonists therapy might be driven by their ameliorative impact on adipose tissue inflammation.
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Affiliation(s)
- Nour-Mounira Z Bakkar
- Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
| | - Ibrahim AlZaim
- Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
- Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
| | - Ahmed F El-Yazbi
- Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt
- Faculty of Pharmacy, Alalamein International University, Alamein, Egypt
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Theofilis P, Sagris M, Oikonomou E, Antonopoulos AS, Siasos G, Tsioufis K, Tousoulis D. The Anti-Inflammatory Effect of Novel Antidiabetic Agents. Life (Basel) 2022; 12:1829. [PMID: 36362984 PMCID: PMC9696750 DOI: 10.3390/life12111829] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Revised: 09/28/2022] [Accepted: 11/05/2022] [Indexed: 08/10/2023] Open
Abstract
The incidence of type 2 diabetes (T2DM) has been increasing worldwide and remains one of the leading causes of atherosclerotic disease. Several antidiabetic agents have been introduced in trying to regulate glucose control levels with different mechanisms of action. These agents, and sodium-glucose cotransporter-2 inhibitors in particular, have been endorsed by contemporary guidelines in patients with or without T2DM. Their widespread usage during the last three decades has raised awareness in the scientific community concerning their pleiotropic mechanisms of action, including their putative anti-inflammatory effect. In this review, we delve into the anti-inflammatory role and mechanism of the existing antidiabetic agents in the cardiovascular system and their potential use in other chronic sterile inflammatory conditions.
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Affiliation(s)
- Panagiotis Theofilis
- 1st Cardiology Department, “Hippokration” General Hospital, University of Athens Medical School, 11527 Athens, Greece
| | - Marios Sagris
- 3rd Cardiology Department, Thoracic Diseases Hospital “Sotiria”, University of Athens Medical School, 11527 Athens, Greece
| | - Evangelos Oikonomou
- 1st Cardiology Department, “Hippokration” General Hospital, University of Athens Medical School, 11527 Athens, Greece
- 3rd Cardiology Department, Thoracic Diseases Hospital “Sotiria”, University of Athens Medical School, 11527 Athens, Greece
| | - Alexios S. Antonopoulos
- 1st Cardiology Department, “Hippokration” General Hospital, University of Athens Medical School, 11527 Athens, Greece
| | - Gerasimos Siasos
- 1st Cardiology Department, “Hippokration” General Hospital, University of Athens Medical School, 11527 Athens, Greece
- 3rd Cardiology Department, Thoracic Diseases Hospital “Sotiria”, University of Athens Medical School, 11527 Athens, Greece
| | - Kostas Tsioufis
- 1st Cardiology Department, “Hippokration” General Hospital, University of Athens Medical School, 11527 Athens, Greece
| | - Dimitris Tousoulis
- 1st Cardiology Department, “Hippokration” General Hospital, University of Athens Medical School, 11527 Athens, Greece
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Theofilis P, Sagris M, Oikonomou E, Antonopoulos AS, Siasos G, Tsioufis K, Tousoulis D. The impact of SGLT2 inhibitors on inflammation: A systematic review and meta-analysis of studies in rodents. Int Immunopharmacol 2022; 111:109080. [PMID: 35908505 DOI: 10.1016/j.intimp.2022.109080] [Citation(s) in RCA: 53] [Impact Index Per Article: 17.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Revised: 06/28/2022] [Accepted: 07/18/2022] [Indexed: 12/17/2022]
Abstract
BACKGROUND Inhibition of sodium-glucose cotransporter-2 (SGLT2) has received remarkable attention due to the beneficial effects observed in diabetes mellitus, heart failure, and kidney disease. Several mechanisms have been proposed for these pleiotropic effects, including anti-inflammatory ones. Our systematic review and meta-analysis aimed to assess the effect of SGLT2 inhibition on inflammatory markers in experimental models. METHODS A literature search was conducted to detect studies examining the effect of SGLT2 inhibitors on inflammatory markers [interleukin-6 (IL-6), C reactive protein (CRP), tumor necrosis factor-α (TNF-α), and monocyte chemoattractant protein-1 (MCP-1)]. Consequently, a meta-analysis of the included studies was performed, assessing the differences in the levels of the inflammatory markers between the treatment groups as its primary outcome. Moreover, risk of bias, sensitivity analysis and publication bias were evaluated. RESULTS The systematic literature review yielded 30 studies whose meta-analysis suggested that treatment with an SGLT2 inhibitor resulted in decreases of IL-6 [standardized mean difference (SMD): -1.56, 95% CI -2.06 to -1.05), CRP (SMD: -2.17, 95% CI -2.80 to -1.53), TNF-α (SMD: -1.75, 95% CI -2.14 to -1.37), and MCP-1 (SMD: -2.04, 95% CI -2.91 to -1.17). The effect on CRP and TNF-α was of lesser magnitude in cases of empagliflozin use. Moderate-to-substantial heterogeneity and possible publication bias were noted. The findings remained largely unaffected after the sensitivity analyses, the exclusion of outlying studies, and trim-and-fill analyses. CONCLUSION The present meta-analysis suggests that SGLT2 inhibition results in reduction of inflammatory markers in animal models, further validating the suggested anti-inflammatory mechanism of action.
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Affiliation(s)
- Panagiotis Theofilis
- 1st Cardiology Department, "Hippokration" General Hospital, University of Athens Medical School, 11527 Athens, Greece
| | - Marios Sagris
- 1st Cardiology Department, "Hippokration" General Hospital, University of Athens Medical School, 11527 Athens, Greece
| | - Evangelos Oikonomou
- 1st Cardiology Department, "Hippokration" General Hospital, University of Athens Medical School, 11527 Athens, Greece; 3rd Cardiology Department, "Sotiria" Regional Hospital for Chest Diseases, University of Athens Medical School, 11527 Athens, Greece
| | - Alexios S Antonopoulos
- 1st Cardiology Department, "Hippokration" General Hospital, University of Athens Medical School, 11527 Athens, Greece
| | - Gerasimos Siasos
- 1st Cardiology Department, "Hippokration" General Hospital, University of Athens Medical School, 11527 Athens, Greece; 3rd Cardiology Department, "Sotiria" Regional Hospital for Chest Diseases, University of Athens Medical School, 11527 Athens, Greece
| | - Konstantinos Tsioufis
- 1st Cardiology Department, "Hippokration" General Hospital, University of Athens Medical School, 11527 Athens, Greece
| | - Dimitris Tousoulis
- 1st Cardiology Department, "Hippokration" General Hospital, University of Athens Medical School, 11527 Athens, Greece.
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Conte M, Petraglia L, Cabaro S, Valerio V, Poggio P, Pilato E, Attena E, Russo V, Ferro A, Formisano P, Leosco D, Parisi V. Epicardial Adipose Tissue and Cardiac Arrhythmias: Focus on Atrial Fibrillation. Front Cardiovasc Med 2022; 9:932262. [PMID: 35845044 PMCID: PMC9280076 DOI: 10.3389/fcvm.2022.932262] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Accepted: 06/13/2022] [Indexed: 01/02/2023] Open
Abstract
Atrial Fibrillation (AF) is the most frequent cardiac arrhythmia and its prevalence increases with age. AF is strongly associated with an increased risk of stroke, heart failure and cardiovascular mortality. Among the risk factors associated with AF onset and severity, obesity and inflammation play a prominent role. Numerous recent evidence suggested a role of epicardial adipose tissue (EAT), the visceral fat depot of the heart, in the development of AF. Several potential arrhythmogenic mechanisms have been attributed to EAT, including myocardial inflammation, fibrosis, oxidative stress, and fat infiltration. EAT is a local source of inflammatory mediators which potentially contribute to atrial collagen deposition and fibrosis, the anatomical substrate for AF. Moreover, the close proximity between EAT and myocardium allows the EAT to penetrate and generate atrial myocardium fat infiltrates that can alter atrial electrophysiological properties. These observations support the hypothesis of a strong implication of EAT in structural and electrical atrial remodeling, which underlies AF onset and burden. The measure of EAT, through different imaging methods, such as echocardiography, computed tomography and cardiac magnetic resonance, has been proposed as a useful prognostic tool to predict the presence, severity and recurrence of AF. Furthermore, EAT is increasingly emerging as a promising potential therapeutic target. This review aims to summarize the recent evidence exploring the potential role of EAT in the pathogenesis of AF, the main mechanisms by which EAT can promote structural and electrical atrial remodeling and the potential therapeutic strategies targeting the cardiac visceral fat.
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Affiliation(s)
- Maddalena Conte
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy.,Casa di Cura San Michele, Maddaloni, Italy
| | - Laura Petraglia
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
| | - Serena Cabaro
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
| | | | | | - Emanuele Pilato
- Department of Advanced Biomedical Science, University of Naples Federico II, Naples, Italy
| | - Emilio Attena
- Department of Cardiology, Monaldi Hospital, Naples, Italy
| | - Vincenzo Russo
- Chair of Cardiology, Department of Translational Medical Sciences, University of Campania "Luigi Vanvitelli" - Monaldi and Cotugno Hospital, Naples, Italy
| | - Adele Ferro
- Institute of Biostructure and Bioimaging, Consiglio Nazionale delle Ricerche, Naples, Italy
| | - Pietro Formisano
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
| | - Dario Leosco
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
| | - Valentina Parisi
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
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Shetty SS, Krumerman A. Putative protective effects of sodium-glucose cotransporter 2 inhibitors on atrial fibrillation through risk factor modulation and off-target actions: potential mechanisms and future directions. Cardiovasc Diabetol 2022; 21:119. [PMID: 35764968 PMCID: PMC9241300 DOI: 10.1186/s12933-022-01552-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Accepted: 06/08/2022] [Indexed: 02/07/2023] Open
Abstract
Atrial fibrillation, the most common cardiac arrhythmia, results in substantial morbidity and mortality related to its increased risks of stroke, heart failure, and impaired cognitive function. The incidence and prevalence of atrial fibrillation in the general population is rising, making atrial fibrillation treatment and management of its risk factors highly relevant clinical targets. One well-studied risk factor for the development of atrial fibrillation is diabetes mellitus. Inhibitors of sodium-glucose cotransporter 2 (SGLT2), common medications used to treat diabetes mellitus, have been observed to decrease the incidence of atrial fibrillation. This review discusses the SGLT2 and its role in glucose homeostasis, molecules inhibiting the transporter, possible physiological mechanisms responsible for the decreased incident atrial fibrillation in patients treated with SGLT2 inhibitors and proposes mechanistic studies to further our understanding of the biological processes involved.
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Affiliation(s)
- Syona S Shetty
- Montefiore Medical Center, 110 E 210th Street, Bronx, NY, USA.
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28
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Doukbi E, Soghomonian A, Sengenès C, Ahmed S, Ancel P, Dutour A, Gaborit B. Browning Epicardial Adipose Tissue: Friend or Foe? Cells 2022; 11:991. [PMID: 35326442 PMCID: PMC8947372 DOI: 10.3390/cells11060991] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Revised: 03/04/2022] [Accepted: 03/09/2022] [Indexed: 02/08/2023] Open
Abstract
The epicardial adipose tissue (EAT) is the visceral fat depot of the heart which is highly plastic and in direct contact with myocardium and coronary arteries. Because of its singular proximity with the myocardium, the adipokines and pro-inflammatory molecules secreted by this tissue may directly affect the metabolism of the heart and coronary arteries. Its accumulation, measured by recent new non-invasive imaging modalities, has been prospectively associated with the onset and progression of coronary artery disease (CAD) and atrial fibrillation in humans. Recent studies have shown that EAT exhibits beige fat-like features, and express uncoupling protein 1 (UCP-1) at both mRNA and protein levels. However, this thermogenic potential could be lost with age, obesity and CAD. Here we provide an overview of the physiological and pathophysiological relevance of EAT and further discuss whether its thermogenic properties may serve as a target for obesity therapeutic management with a specific focus on the role of immune cells in this beiging phenomenon.
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Affiliation(s)
- Elisa Doukbi
- INSERM, INRAE, C2VN, Aix-Marseille University, F-13005 Marseille, France; (E.D.); (A.S.); (S.A.); (P.A.); (A.D.)
| | - Astrid Soghomonian
- INSERM, INRAE, C2VN, Aix-Marseille University, F-13005 Marseille, France; (E.D.); (A.S.); (S.A.); (P.A.); (A.D.)
- Department of Endocrinology, Metabolic Diseases and Nutrition, Pôle ENDO, APHM, F-13005 Marseille, France
| | - Coralie Sengenès
- Stromalab, CNRS ERL5311, EFS, INP-ENVT, INSERM U1031, University of Toulouse, F-31100 Toulouse, France;
- Institut National de la Santé et de la Recherche Médicale, University Paul Sabatier, F-31100 Toulouse, France
| | - Shaista Ahmed
- INSERM, INRAE, C2VN, Aix-Marseille University, F-13005 Marseille, France; (E.D.); (A.S.); (S.A.); (P.A.); (A.D.)
| | - Patricia Ancel
- INSERM, INRAE, C2VN, Aix-Marseille University, F-13005 Marseille, France; (E.D.); (A.S.); (S.A.); (P.A.); (A.D.)
| | - Anne Dutour
- INSERM, INRAE, C2VN, Aix-Marseille University, F-13005 Marseille, France; (E.D.); (A.S.); (S.A.); (P.A.); (A.D.)
- Department of Endocrinology, Metabolic Diseases and Nutrition, Pôle ENDO, APHM, F-13005 Marseille, France
| | - Bénédicte Gaborit
- INSERM, INRAE, C2VN, Aix-Marseille University, F-13005 Marseille, France; (E.D.); (A.S.); (S.A.); (P.A.); (A.D.)
- Department of Endocrinology, Metabolic Diseases and Nutrition, Pôle ENDO, APHM, F-13005 Marseille, France
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29
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Konwerski M, Gąsecka A, Opolski G, Grabowski M, Mazurek T. Role of Epicardial Adipose Tissue in Cardiovascular Diseases: A Review. BIOLOGY 2022; 11:355. [PMID: 35336728 PMCID: PMC8945130 DOI: 10.3390/biology11030355] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Revised: 02/19/2022] [Accepted: 02/21/2022] [Indexed: 02/01/2023]
Abstract
Cardiovascular diseases (CVDs) are the leading causes of death worldwide. Epicardial adipose tissue (EAT) is defined as a fat depot localized between the myocardial surface and the visceral layer of the pericardium and is a type of visceral fat. EAT is one of the most important risk factors for atherosclerosis and cardiovascular events and a promising new therapeutic target in CVDs. In health conditions, EAT has a protective function, including protection against hypothermia or mechanical stress, providing myocardial energy supply from free fatty acid and release of adiponectin. In patients with obesity, metabolic syndrome, or diabetes mellitus, EAT becomes a deleterious tissue promoting the development of CVDs. Previously, we showed an adverse modulation of gene expression in pericoronary adipose tissue in patients with coronary artery disease (CAD). Here, we summarize the currently available evidence regarding the role of EAT in the development of CVDs, including CAD, heart failure, and atrial fibrillation. Due to the rapid development of the COVID-19 pandemic, we also discuss data regarding the association between EAT and the course of COVID-19. Finally, we present the potential therapeutic possibilities aiming at modifying EAT's function. The development of novel therapies specifically targeting EAT could revolutionize the prognosis in CVDs.
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Affiliation(s)
| | | | | | | | - Tomasz Mazurek
- 1st Chair and Department of Cardiology, Medical University of Warsaw, 02-097 Warszawa, Poland; (M.K.); (A.G.); (G.O.); (M.G.)
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30
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Aslan B, Akyüz A, Işık F, Boyraz B, İnci Ü, Yıldız H, Çap M, Karahan MZ, Araç E, Okşul M, Kaya İ. The effect of empagliflozin on p wave peak time and other p wave parameters in patients with diabetes mellitus. Pacing Clin Electrophysiol 2022; 45:323-329. [PMID: 35175628 DOI: 10.1111/pace.14463] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2021] [Revised: 01/26/2022] [Accepted: 02/06/2022] [Indexed: 11/28/2022]
Abstract
BACKGROUND Empagliflozin is a selective SGLT2 inhibitor and provides a significant reduction in hospitalizations in HF patients and a reduction in combined cardiovascular deaths regardless of diabetes. The mechanisms of favorable effects remain unclear. Improvement in left ventricular diastolic function and a decrease in filling pressure are any mechanisms of positive effects. These effects may show themselves with some changes on the ECG. So, we aimed to evaluate the effect of empagliflozin on P wave parameters in type 2 diabetes mellitus patients without heart failure. METHOD Fifty-three patients were included in the study. The electrocardiographic and echocardiographic evaluations were examined at the baseline and end of the 3rd month for all patients. RESULTS The median age of all patients was 55 (45-64 IOR). After treatment, LA volume (p 0.001) and diameter (p=0.001) in both the parasternal long-axis (p=0.001) and the apical four-chamber view decreased. E/e' and sPAP were significantly decreased after treatment. PWDmax, PWDmin, and PWdis (p=0.017) were significantly shorter after treatment. The PWPT in lead Dıı and V1 were significantly shorter after treatment. CONCLUSION We found shortening of PWPT, PWdis, and PWD as reflections of improvements in LA volume and LV diastolic function on ECG after empagliflozin treatment. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Burhan Aslan
- Diyarbakır Gazi Yaşargil Education and Research Hospital, Health and Science University, Department of Cardiology, Turkey
| | - Abdurrahman Akyüz
- Diyarbakır Gazi Yaşargil Education and Research Hospital, Health and Science University, Department of Cardiology, Turkey
| | - Ferhat Işık
- Diyarbakır Gazi Yaşargil Education and Research Hospital, Health and Science University, Department of Cardiology, Turkey
| | | | - Ümit İnci
- Diyarbakır Gazi Yaşargil Education and Research Hospital, Health and Science University, Department of Cardiology, Turkey
| | - Halil Yıldız
- Diyarbakır Gazi Yaşargil Education and Research Hospital, Health and Science University, Department of Cardiology, Turkey
| | - Murat Çap
- Diyarbakır Gazi Yaşargil Education and Research Hospital, Health and Science University, Department of Cardiology, Turkey
| | - Mehmet Zülküf Karahan
- Diyarbakır Gazi Yaşargil Education and Research Hospital, Health and Science University, Department of Cardiology, Turkey
| | - Eşref Araç
- Diyarbakır Gazi Yaşargil Education and Research Hospital, Health and Science University, Department of General Medicine and Endocrine, Turkey
| | - Metin Okşul
- Diyarbakır Gazi Yaşargil Education and Research Hospital, Health and Science University, Department of Cardiology, Turkey
| | - İlyas Kaya
- Diyarbakır Gazi Yaşargil Education and Research Hospital, Health and Science University, Department of Cardiology, Turkey
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31
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Kolesnik E, Scherr D, Rohrer U, Benedikt M, Manninger M, Sourij H, von Lewinski D. SGLT2 Inhibitors and Their Antiarrhythmic Properties. Int J Mol Sci 2022; 23:1678. [PMID: 35163599 PMCID: PMC8835896 DOI: 10.3390/ijms23031678] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2022] [Revised: 01/23/2022] [Accepted: 01/24/2022] [Indexed: 12/13/2022] Open
Abstract
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are gaining ground as standard therapy for heart failure with a class-I recommendation in the recently updated heart failure guidelines from the European Society of Cardiology. Different gliflozins have shown impressive beneficial effects in patients with and without diabetes mellitus type 2, especially in reducing the rates for hospitalization for heart failure, yet little is known on their antiarrhythmic properties. Atrial and ventricular arrhythmias were reported by clinical outcome trials with SGLT2 inhibitors as adverse events, and SGLT2 inhibitors seemed to reduce the rate of arrhythmias compared to placebo treatment in those trials. Mechanistical links are mainly unrevealed, since hardly any experiments investigated their impact on arrhythmias. Prospective trials are currently ongoing, but no results have been published so far. Arrhythmias are common in the heart failure population, therefore the understanding of possible interactions with SGLT2 inhibitors is crucial. This review summarizes evidence from clinical data as well as the sparse experimental data of SGLT2 inhibitors and their effects on arrhythmias.
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Affiliation(s)
- Ewald Kolesnik
- Department of Cardiology, University Heart Centre Graz, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria
| | - Daniel Scherr
- Department of Cardiology, University Heart Centre Graz, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria
| | - Ursula Rohrer
- Department of Cardiology, University Heart Centre Graz, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria
| | - Martin Benedikt
- Department of Cardiology, University Heart Centre Graz, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria
| | - Martin Manninger
- Department of Cardiology, University Heart Centre Graz, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria
| | - Harald Sourij
- Department of Endocrinology and Diabetology, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria
| | - Dirk von Lewinski
- Department of Cardiology, University Heart Centre Graz, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria
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32
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Not only how much, but also how to, when measuring epicardial adipose tissue. Magn Reson Imaging 2021; 86:149-151. [PMID: 34813891 DOI: 10.1016/j.mri.2021.11.004] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Revised: 10/21/2021] [Accepted: 11/15/2021] [Indexed: 12/13/2022]
Abstract
Epicardial Adipose Tissue (EAT) is drawing increasing attention. As a quantifiable, modifiable, and potentially new cardiovascular therapeutic target, its accurate measurement is particularly relevant. In Cardiac Magnetic Resonance (CMR) different methods can be used to assess EAT burden. We take advantage of CMR-studies of EMPATROPISM trial to assess EAT through three different methods, evaluate the effect of Empagliflozin and look for significant difference in the ability to detect changes in serial measurements. In some settings such as treatment-induced changes or patient follow-up, multi-slice method of EAT evaluation provides higher accuracy to detect significant differences, otherwise unnoticed by single-slice approaches.
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33
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Curtain JP, Docherty KF, Jhund PS, Petrie MC, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Bengtsson O, Langkilde AM, Sjöstrand M, Solomon SD, McMurray JJV. Effect of dapagliflozin on ventricular arrhythmias, resuscitated cardiac arrest, or sudden death in DAPA-HF. Eur Heart J 2021; 42:3727-3738. [PMID: 34448003 PMCID: PMC8455345 DOI: 10.1093/eurheartj/ehab560] [Citation(s) in RCA: 135] [Impact Index Per Article: 33.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Revised: 07/12/2021] [Accepted: 08/02/2021] [Indexed: 12/24/2022] Open
Abstract
AIMS The aim of this study was to examine the effect of dapagliflozin on the incidence of ventricular arrhythmias and sudden death in patients with heart failure and reduced ejection fraction (HFrEF). METHODS AND RESULTS In a post hoc analysis of DAPA-HF, we examined serious adverse event reports related to ventricular arrhythmias or cardiac arrest, in addition to adjudicated sudden death. The effect of dapagliflozin, compared with placebo, on the composite of the first occurrence of any serious ventricular arrhythmia, resuscitated cardiac arrest, or sudden death was examined using Cox proportional hazards models. A serious ventricular arrhythmia was reported in 115 (2.4%) of the 4744 patients in DAPA-HF (ventricular fibrillation in 15 patients, ventricular tachycardia in 86, 'other' ventricular arrhythmia/tachyarrhythmia in 12, and torsade de pointes in 2 patients). A total of 206 (41%) of the 500 cardiovascular deaths occurred suddenly. Eight patients survived resuscitation from cardiac arrest. Independent predictors of the composite outcome (first occurrence of any serious ventricular arrhythmia, resuscitated cardiac arrest or sudden death), ranked by chi-square value, were log-transformed N-terminal pro-B-type natriuretic peptide, history of ventricular arrhythmia, left ventricular ejection fraction, systolic blood pressure, history of myocardial infarction, male sex, body mass index, serum sodium concentration, non-white race, treatment with dapagliflozin, and cardiac resynchronization therapy. Of participants assigned to dapagliflozin, 140/2373 patients (5.9%) experienced the composite outcome compared with 175/2371 patients (7.4%) in the placebo group [hazard ratio 0.79 (95% confidence interval 0.63-0.99), P = 0.037], and the effect was consistent across each of the components of the composite outcome. CONCLUSIONS Dapagliflozin reduced the risk of any serious ventricular arrhythmia, cardiac arrest, or sudden death when added to conventional therapy in patients with HFrEF. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov unique identifier: NCT03036124 (DAPA-HF).
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Affiliation(s)
- James P Curtain
- British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Scotland, UK
| | - Kieran F Docherty
- British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Scotland, UK
| | - Pardeep S Jhund
- British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Scotland, UK
| | - Mark C Petrie
- British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Scotland, UK
| | - Silvio E Inzucchi
- Section of Endocrinology, Yale School of Medicine, New Haven, CT, USA
| | - Lars Køber
- Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Mikhail N Kosiborod
- Saint Luke's Mid America Heart Institute, University of Missouri, Kansas City, MO, USA.,The George Institute for Global Health, University of New South Wales, Sydney, Australia
| | | | - Piotr Ponikowski
- Center for Heart Diseases, University Hospital, Wroclaw Medical University, Wroclaw, Poland
| | - Marc S Sabatine
- TIMI Study Group, Brigham and Women's Hospital, Boston, MA, USA.,D ivision of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA, USA
| | - Olof Bengtsson
- Lat e Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
| | - Anna Maria Langkilde
- Lat e Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
| | - Mikaela Sjöstrand
- Lat e Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
| | - Scott D Solomon
- D ivision of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA, USA
| | - John J V McMurray
- British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Scotland, UK
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34
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Posterior left atrial epicardial adipose tissue: scope of the problem and impact of new technology. Curr Opin Cardiol 2021; 37:54-61. [PMID: 34508033 DOI: 10.1097/hco.0000000000000923] [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] [Indexed: 11/27/2022]
Abstract
PURPOSE OF REVIEW Patients with persistent forms of atrial fibrillation are seeking treatments based on the promise of better restoration of sinus rhythm with newer therapies. Successful catheter ablation and maintenance of atrial fibrillation in this subgroup is negatively impacted by the presence of epicardial adipose tissue (EAT) associated with the posterior left atrium. RECENT FINDINGS EAT is now understood to be hormonally active and promotes adverse atrial remodelling, including fibrosis and myopathy. Despite being dominantly adipose tissue, it is known to be electrically active, comprising ganglia, neural tissue and ectopic atrial myocardium that may contribute to endo-epicardial dissociation and persistent electrical activity and atrial fibrillation despite good endocardial electrical silencing. Hybrid procedures that include direct epicardial ablation of the posterior wall, including the EAT, are associated with superior outcomes in nonparoxysmal atrial fibrillation. SUMMARY Therapies for persistent atrial fibrillation that also ablate the EAT as part of a well tolerated transmural posterior wall ablation may improve outcomes in this challenging subset of patients.
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35
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Effect of SGLT2-Inhibitors on Epicardial Adipose Tissue: A Meta-Analysis. Cells 2021; 10:cells10082150. [PMID: 34440918 PMCID: PMC8391573 DOI: 10.3390/cells10082150] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 08/06/2021] [Accepted: 08/09/2021] [Indexed: 02/06/2023] Open
Abstract
(1) Sodium-glucose cotransporter-2 inhibitors (SGLT2-i) reduce adipose tissue and cardiovascular events in patients with type 2 diabetes (T2D). Accumulation of epicardial adipose tissue (EAT) is associated with increased cardio-metabolic risks and obstructive coronary disease events in patients with T2D. (2) We performed a systematic review and meta-analysis of SGLT2-i therapy on T2D patients, reporting data on changes in EAT after searching the PubMed/MEDLINE, Embase, Science Direct, Scopus, Google Scholar, and Cochrane databases. A random effects or fixed effects model meta-analysis was then applied. (3) Results: A total of three studies (n = 64 patients with SGLT2-i, n = 62 with standard therapy) were included in the final analysis. SGLT2 inhibitors reduced EAT (SMD: -0.82 (-1.49; -0.15); p < 0.0001). An exploratory analysis showed that HbA1c was significantly reduced with SGLT2-i use, while body mass index was not significantly reduced with this drug. (4) Conclusions: This meta-analysis suggests that the amount of EAT is significantly reduced in T2D patients with SGLT2-i treatment.
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36
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Could Sodium/Glucose Co-Transporter-2 Inhibitors Have Antiarrhythmic Potential in Atrial Fibrillation? Literature Review and Future Considerations. Drugs 2021; 81:1381-1395. [PMID: 34297330 DOI: 10.1007/s40265-021-01565-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/26/2021] [Indexed: 12/11/2022]
Abstract
The global burden of atrial fibrillation (AF) is constantly increasing, necessitating novel and effective therapeutic options. Sodium glucose co-transporter 2 (SGLT2) inhibitors have been introduced in clinical practice as glucose-lowering medications. However, they have recently gained prominence for their potential to exert substantial cardiorenal protection and are being evaluated in large clinical trials including patients with type 2 diabetes and normoglycemic adults. In this review we present up-to-date available evidence in a pathophysiology-directed manner from cell to bedside. Preclinical and clinical data regarding a conceivable antiarrhythmic effect of SGLT2 inhibitors are beginning to accumulate. Herein we comprehensively present data that explore the potential pathophysiological link between SGLT2 inhibitors and AF. With regard to clinical data, no randomized controlled trials evaluating SGLT2 inhibitors effects on AF as a pre-specified endpoint are available. However, data from randomized controlled trial post-hoc analysis as well as observational studies point to a possible beneficial effect of SGLT2 inhibitors on AF. Meta-analyses addressing this question report inconsistent results and the real magnitude of AF prevention by SGLT2 inhibition remains unclear. Still, while (i) pathophysiologic mechanisms involved in AF might be favorably affected by SGLT2 inhibitors and (ii) emerging, yet inconsistent, clinical data imply that SGLT2 inhibitor-mediated cardiorenal protection could also exert antiarrhythmic effects, the argument of whether these novel drugs will reduce AF burden is unsettled and mandates appropriately designed and adequately sized randomized controlled studies.
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37
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Bonou M, Mavrogeni S, Kapelios CJ, Markousis-Mavrogenis G, Aggeli C, Cholongitas E, Protogerou AD, Barbetseas J. Cardiac Adiposity and Arrhythmias: The Role of Imaging. Diagnostics (Basel) 2021; 11:diagnostics11020362. [PMID: 33672778 PMCID: PMC7924558 DOI: 10.3390/diagnostics11020362] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Revised: 02/07/2021] [Accepted: 02/18/2021] [Indexed: 12/13/2022] Open
Abstract
Increased cardiac fat depots are metabolically active tissues that have a pronounced pro-inflammatory nature. Increasing evidence supports a potential role of cardiac adiposity as a determinant of the substrate of atrial fibrillation and ventricular arrhythmias. The underlying mechanism appears to be multifactorial with local inflammation, fibrosis, adipocyte infiltration, electrical remodeling, autonomic nervous system modulation, oxidative stress and gene expression playing interrelating roles. Current imaging modalities, such as echocardiography, computed tomography and cardiac magnetic resonance, have provided valuable insight into the relationship between cardiac adiposity and arrhythmogenesis, in order to better understand the pathophysiology and improve risk prediction of the patients, over the presence of obesity and traditional risk factors. However, at present, given the insufficient data for the additive value of imaging biomarkers on commonly used risk algorithms, the use of different screening modalities currently is indicated for personalized risk stratification and prognostication in this setting.
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Affiliation(s)
- Maria Bonou
- Department of Cardiology, Laiko General Hospital, 11527 Athens, Greece; (M.B.); (J.B.)
| | - Sophie Mavrogeni
- Department of Cardiology, Onassis Cardiac Surgery Center, 17674 Athens, Greece; (S.M.); (G.M.-M.)
| | - Chris J. Kapelios
- Department of Cardiology, Laiko General Hospital, 11527 Athens, Greece; (M.B.); (J.B.)
- Correspondence: ; Tel.: +30-213-2061032; Fax: +30-213-2061761
| | | | - Constantina Aggeli
- First Department of Cardiology, Hippokration General Hospital, Medical School of National & Kapodistrian University, 11527 Athens, Greece;
| | - Evangelos Cholongitas
- First Department of Internal Medicine, Medical School of National & Kapodistrian University, 11527 Athens, Greece;
| | - Athanase D. Protogerou
- Cardiovascular Prevention & Research Unit, Clinic and Laboratory of Pathophysiology, National & Kapodistrian University Athens School of Medicine, 11527 Athens, Greece;
| | - John Barbetseas
- Department of Cardiology, Laiko General Hospital, 11527 Athens, Greece; (M.B.); (J.B.)
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Ling AWC, Chan CC, Chen SW, Kao YW, Huang CY, Chan YH, Chu PH. The risk of new-onset atrial fibrillation in patients with type 2 diabetes mellitus treated with sodium glucose cotransporter 2 inhibitors versus dipeptidyl peptidase-4 inhibitors. Cardiovasc Diabetol 2020; 19:188. [PMID: 33158436 PMCID: PMC7648323 DOI: 10.1186/s12933-020-01162-w] [Citation(s) in RCA: 46] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2020] [Accepted: 10/27/2020] [Indexed: 12/17/2022] Open
Abstract
Background Sodium glucose cotransporter 2 inhibitor (SGLT2i) reduces the risk of hard cardiovascular endpoints in type 2 diabetes mellitus (T2DM) patients with/without established cardiovascular diseases. Whether SGLT2i is associated with a lower risk of new-onset atrial fibrillation (AF) in T2DM patients is unclear. We aimed to evaluate the risk of new-onset AF associated with the use of SGLT2i compared to dipeptidyl peptidase-4 inhibitor (DPP4i) among a longitudinal cohort of diabetic patients. Methods We used medical data from a multi-center healthcare provider in Taiwan, which included a total of 15,606 and 12,383 patients treated with SGLT2i and DPP4i, respectively, from June 1, 2016 to December 31, 2018. We used propensity-score weighting to balance covariates across study groups. Patients were followed up from the drug index date until the occurrence of new-onset AF, discontinuation of the index drug, or the end of the study period, whichever occurred first. Results Overall, 55%, 45%, and 0% of the patients were treated with empagliflozin, dapagliflozin, and canagliflozin, respectively. Most patients in the DPP4i group were prescribed with linagliptin (51%), followed by sitagliptin (24%), saxagliptin (13%), vildagliptin (8%) and alogliptin (5%). The use of SGLT2i was associated with a lower risk of new-onset AF compared with DPP4i after propensity-score weighting [hazard ratio: 0.61; 95% confidential interval: 0.50–0.73; P < 0.001]. Subgroup analysis revealed that the use of SGLT2i was associated with a lower risk of new-onset AF compared with DPP4i across several subgroups including old age, female in gender, the presence of cardiovascular disease, hemoglobin A1c \documentclass[12pt]{minimal}
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\begin{document}$$\ge$$\end{document}≥ 8%, and chronic kidney disease. The advantage of SGLT2i over DPP4i persisted with different SGLT2i (dapagliflozin or empagliflozin) and either low- or standard-dose SGLT2i. Conclusions SGLT2i was associated with a lower risk of new-onset AF compared with DPP4i among T2DM patients in real-world practice.
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Affiliation(s)
- Ann Wan-Chin Ling
- Cardiovascular Department, Chang Gung Memorial Hospital, Linkou, Taoyuan, 33305, Taiwan
| | - Cze-Ci Chan
- Cardiovascular Department, Chang Gung Memorial Hospital, Linkou, Taoyuan, 33305, Taiwan
| | - Shao-Wei Chen
- Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Chang Gung Memorial Hospital, Linkou Medical Center, Chang Gung University, Taoyuan City, Taiwan.,Center for Big Data Analytics and Statistics, Linkou Medical Center, Chang Gung Memorial Hospital, Taoyuan City, Taiwan
| | - Yi-Wei Kao
- Graduate Institute of Business Administration, College of Management, Fu Jen Catholic University, Taipei, Taiwan
| | - Chien-Ying Huang
- Cardiovascular Department, Chang Gung Memorial Hospital, Linkou, Taoyuan, 33305, Taiwan
| | - Yi-Hsin Chan
- Cardiovascular Department, Chang Gung Memorial Hospital, Linkou, Taoyuan, 33305, Taiwan. .,College of Medicine, Chang Gung University, Taoyuan, 33302, Taiwan. .,Microscopy Core Laboratory, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan.
| | - Pao-Hsien Chu
- Cardiovascular Department, Chang Gung Memorial Hospital, Linkou, Taoyuan, 33305, Taiwan. .,College of Medicine, Chang Gung University, Taoyuan, 33302, Taiwan.
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