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Song R, Liu F, Shi X, Sun S, Chen J, Gao H. Effects of new hypoglycemic drugs on patients with heart failure: a systematic review and network meta-analysis. Postgrad Med J 2025; 101:330-350. [PMID: 39487697 DOI: 10.1093/postmj/qgae148] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Revised: 03/08/2024] [Accepted: 10/12/2024] [Indexed: 11/04/2024]
Abstract
BACKGROUND Currently, there is no relevant study comparing sodium-dependent glucose transporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), and dipeptidyl peptidase inhibitor (DPP4i) head to head to evaluate their comprehensive impact on heart failure patients. METHODS We conducted a comprehensive literature search across multiple databases. Utilizing the risk of bias tool from the Cochrane Collaboration, the methodological quality of included studies was critically assessed and potential publication bias was examined via funnel plots. RESULTS All results are presented as mean difference; 95% confidence interval (MD; 95% CI). The network meta-analysis indicated that in regards to left ventricular function, there is a big difference in the left ventricular ejection fraction (LVEF) of Empagliflozin 25 mg (13.64; 0.26, 27.01) compared to Canagliflozin 100 mg; and significant differences in the left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV) of Dapagliflozin 10 mg (-0.76; -1.27, -0.25 and -0.95; -1.86, -0.05), Vildagliptin 50 mg (-1.05; -1.47, -0.63 and -1.12; -2.19, -0.05), and Sitagliptin 100 mg (-1.34; -2.31, -0.38 and -1.89; -3.50, -0.27) compared to Empagliflozin 10 mg. In terms of the quality of life, there are significant differences in the N-terminal pro-B-type natriuretic peptide (NT-proBNP) and the Quality of life score of Sitagliptin 100 mg (408.08; 213.59, 602.57 and 3.74; 1.57, 5.92) compared to Dapagliflozin 5 mg. In terms of the cardiovascular outcome events, there is a significant difference in the heart failure rehospitalization rate of Dapagliflozin 10 mg (0.45; 0.25, 0.82) and Empagliflozin 10 mg (0.48; 0.28, 0.81) compared to Liraglutide 1.8 mg. Further significant differences are found in the all-cause mortality of Dapagliflozin 10 mg (0.81; 0.66, 0.98) compared to Vildagliptin 50 mg; the cardiovascular death of Albiglutide 30 mg (0.49; 0.28, 0.86) compared to Exenatide 2 mg; and the arrhythmic events of Liraglutide 1.8 mg (0.49; 0.26, 0.90) compared to Empagliflozin 10 mg. The network meta-analysis of SGLT2i, GLP-1RA, and DPP4i as a class of drugs showed that GLP-1RA is superior to SGLT2i in improving LVEF and reducing myocardial infarction/acute coronary syndrome, whereas DPP4i is superior to SGLT2i in improving LVEDV and LVESV. CONCLUSIONS GLP-1RA is superior to SGLT2i in improving LVEF and reducing myocardial infarction/acute coronary syndrome, whereas DPP4i is superior to SGLT2i in improving LVEDV and LVESV. Key message What is already known on this topic-It has been confirmed that three new hypoglycemic drugs have a protective effect on the cardiovascular system. Studies have shown that sodium-dependent glucose transporter 2 inhibitors (SGLT2i) can improve cardiovascular outcomes and enhance the quality of life of heart failure patients. Currently, SGLT2i is widely used in the clinical treatment of heart failure, and related studies have shown that glucagon-like peptide-1 receptor agonists (GLP-1RA) and dipeptidyl peptidase inhibitor (DPP4i) also play important roles in the treatment of heart failure. What this study adds-However, there is no relevant research on whether these drugs' clinical efficacy is dose-dependent. How this study might affect research, practice, or policy-This study included different doses of hypoglycemic drugs and used a network meta-analysis method to comprehensively evaluate the effects of three hypoglycemic drugs on heart function, quality of life, and prognosis in heart failure patients, providing a basis for clinical practice.
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Affiliation(s)
- Ruirui Song
- Department of Cardiology, Shandong University of Traditional Chinese Medicine, Second Affiliated Hospital, No. 1 Jingba Road Jinan, Shandong Province 250001, China
| | - Fang Liu
- Department of Cardiology, Shandong University of Traditional Chinese Medicine, Second Affiliated Hospital, No. 1 Jingba Road Jinan, Shandong Province 250001, China
| | - Xiaojing Shi
- Department of Cardiology, Shandong University of Traditional Chinese Medicine, Second Affiliated Hospital, No. 1 Jingba Road Jinan, Shandong Province 250001, China
| | - Songtao Sun
- Department of Cardiology, Shandong University of Traditional Chinese Medicine, Second Affiliated Hospital, No. 1 Jingba Road Jinan, Shandong Province 250001, China
| | - Jun Chen
- Department of Cardiology, Shandong University of Traditional Chinese Medicine, Second Affiliated Hospital, No. 1 Jingba Road Jinan, Shandong Province 250001, China
| | - Hongmei Gao
- Department of Cardiology, Shandong University of Traditional Chinese Medicine, Second Affiliated Hospital, No. 1 Jingba Road Jinan, Shandong Province 250001, China
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Zhang Z, Liu S, Xian J, Zhang Y, Zhang C, Wang Z, Deng H, Feng J, Yao L. Effect of Hypoglycemic Drugs on Patients with Heart Failure with or without T2DM: A Bayesian Network Meta-analysis. Rev Cardiovasc Med 2025; 26:26154. [PMID: 40160590 PMCID: PMC11951290 DOI: 10.31083/rcm26154] [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: 08/16/2024] [Revised: 11/29/2024] [Accepted: 12/04/2024] [Indexed: 04/02/2025] Open
Abstract
Background Anti-diabetic drugs have been noted to have a cardioprotective effect in patients with diabetes and heart failure (HF). The purpose of this study was to perform a Bayesian network meta-analysis to evaluate the impact of various anti-diabetic drugs on the prognosis of HF patients with and without diabetes. Methods We searched PubMed, Embase, Cochrane, and Web of Science for randomized controlled trials (RCTs) published before November 2024 that investigated the use of anti-diabetic medications in patients with HF. Primary outcomes included re-admission due to HF, all-cause death, cardiovascular death, serum N-terminal pro-brain natriuretic peptide (NTpro-BNP) levels, and left ventricular ejection fraction (LVEF). A Bayesian network meta-analysis was used to compare the effectiveness of different anti-diabetic drugs. Results A total of 33 RCTs involving 29,888 patients were included. Sotagliflozin was the most effective in reducing the risk of re-admission due to HF and all-cause death, with a cumulative probability of 0.84 and 0.83, respectively. Liraglutide reduced the risk of cardiovascular death in HF patients with a cumulative probability of 0.97 and had the best efficacy in reducing NTpro-BNP levels with a cumulative probability of 0.69. Empagliflozin was best in improving LVEF in HF patients, with a cumulative probability of 0.69. Conclusions This Bayesian network meta-analysis demonstrates that sotagliflozin may be the best option for HF patients with and without diabetes. However, due to the small number of articles in this study, our results must be treated cautiously. Subsequently, there is an urgent need for more high-quality studies to validate our findings.
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Affiliation(s)
- Zhaolun Zhang
- Department of Cardiovascular Medicine, The Affiliated Hospital of Southwest Medical University, 646000 Luzhou, Sichuan, China
| | - Siqi Liu
- Department of Cardiovascular Medicine, The Affiliated Hospital of Southwest Medical University, 646000 Luzhou, Sichuan, China
| | - Jiawen Xian
- Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, 646000 Luzhou, Sichuan, China
| | - Yali Zhang
- Department of Cardiovascular Medicine, The Affiliated Hospital of Southwest Medical University, 646000 Luzhou, Sichuan, China
| | - Chunyu Zhang
- Department of Cardiovascular Medicine, The Affiliated Hospital of Southwest Medical University, 646000 Luzhou, Sichuan, China
| | - Zhiyuan Wang
- Institute of Cardiovascular Research, Southwest Medical University, 646000 Luzhou, Sichuan, China
| | - Hongmei Deng
- Institute of Cardiovascular Research, Southwest Medical University, 646000 Luzhou, Sichuan, China
| | - Jian Feng
- Department of Cardiovascular Medicine, The Affiliated Hospital of Southwest Medical University, 646000 Luzhou, Sichuan, China
| | - Lei Yao
- Provincial Key Laboratory for Human Disease Gene Study, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, 610072 Chengdu, Sichuan, China
- The Center for Medical Genetics, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, 610072 Chengdu, Sichuan, China
- Department of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, 610072 Chengdu, Sichuan, China
- Research Unit for Blindness Prevention, Chinese Academy of Medical Sciences (2019RU026), Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, 610072 Chengdu, Sichuan, China
- Medical Experiment Center, The Affiliated Hospital of Southwest Medical University, 646000 Luzhou, Sichuan, China
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Guo X, Feng H, Cai L, Zheng J, Li Y. DPP-IV as a potential candidate in anti-obesity and obesity-related diseases treatment. Biomed Pharmacother 2024; 180:117464. [PMID: 39326107 DOI: 10.1016/j.biopha.2024.117464] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Revised: 09/09/2024] [Accepted: 09/19/2024] [Indexed: 09/28/2024] Open
Abstract
Along with social development and lifestyle changes, the number of overweight and obese patients worldwide is rising annually. Obesity is a chronic metabolic disease with complex etiology. Dipeptidyl peptidase IV (DPP-IV) is a novel adipokine with significantly elevated expression in the visceral fat of obese patients. DPP-IV is a molecule that regulates metabolic homeostasis and inflammatory processes. Through its enzymatic activity, it plays a significant part in achieving hypoglycemic and weight loss effects through various pathways. DPP-IV and DPP-IV inhibitors also have pleiotropic effects in modulating obesity-related diseases by reducing obesity-related inflammation, ameliorating inflammatory bowel disease (IBD), improving hepatic steatosis and lowering cardiovascular risk, and even decreasing the risk of novel coronavirus disease-19 (COVID-19). This paper reviews the mechanisms of action based on DPP-IV targets in obesity and metabolic homeostasis, as well as their active role in the treatment of chronic diseases associated with obesity.
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Affiliation(s)
- Xin Guo
- Department of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong 510080, China.
| | - Huolun Feng
- School of Medicine, South China University of Technology, Guangzhou, Guangdong 510006, China.
| | - Liyang Cai
- Department of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong 510080, China.
| | - Jiabin Zheng
- Department of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong 510080, China.
| | - Yong Li
- Department of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong 510080, China.
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Tromp J, Lam CSP, Alemayehu W, de Filippi CR, Melenovský V, Sliwa K, Lopatin Y, Arango JL, Bahit MC, Roessig L, O'Connor CM, Shah P, Westerhout CM, Voors AA, Pieske B, Armstrong PW. Biomarker profiles associated with reverse ventricular remodelling in patients with heart failure and a reduced ejection fraction: Insights from the echocardiographic substudy of the VICTORIA trial. Eur J Heart Fail 2024; 26:2231-2239. [PMID: 39078607 DOI: 10.1002/ejhf.3397] [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: 05/23/2024] [Revised: 07/05/2024] [Accepted: 07/09/2024] [Indexed: 07/31/2024] Open
Abstract
AIMS Reverse ventricular remodelling, defined as a decrease in left ventricular end-systolic volume indexed to body surface area (LVESVI) or an increase in left ventricular ejection fraction (LVEF), is associated with improved clinical outcomes in patients with heart failure with reduced ejection fraction (HFrEF). However, the underlying pathophysiological mechanisms remain unclear. METHODS AND RESULTS We evaluated paired core-lab assessed echocardiograms and measurements of 92 biomarkers at baseline and 8 months thereafter in 419 participants with HFrEF. Reverse ventricular remodelling was defined as a >5% LVEF increase or >15% LVESVI relative decrease between baseline and 8 months. We evaluated the association between baseline biomarkers and their changes with reverse ventricular remodelling in the prospectively randomized controlled VICTORIA (Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction) trial. Of 419 patients (median age 66 [interquartile range 57-74] years, 27.4% women), 206 (49.2%) had reverse ventricular remodelling (either a 5% LVEF increase or a 15% LVESVI decrease). There were no differences in baseline biomarker concentrations between patients with versus those without reverse ventricular remodelling on follow-up. However, in patients with reverse ventricular remodelling there were significant decreases in biomarkers relating to inflammation and cardiac metabolism; particularly the tumour necrosis factor superfamily member 13B (ratio 0.82, 95% confidence interval [CI] 0.77-0.88), growth differentiation factor-15 (ratio 0.74, 95% CI 0.66-0.84), and insulin-like growth factor binding protein 7 (ratio 0.80, 95% CI 0.73-0.88). CONCLUSIONS Reverse ventricular remodelling in patients with HFrEF is associated with a decrease of biomarkers related to inflammation and cardiac metabolism.
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Affiliation(s)
- Jasper Tromp
- Saw Swee Hock School of Public Health National University of Singapore and National University of Singapore and National University Health System, Singapore, Singapore
- National Heart Centre Singapore, Duke-National University of Singapore, Singapore, Singapore
- Department of Cardiology, University Medical Centre Groningen, Groningen, The Netherlands
| | - Carolyn S P Lam
- National Heart Centre Singapore, Duke-National University of Singapore, Singapore, Singapore
| | | | - Christopher R de Filippi
- The Inova Center of Outcomes Research, Inova Heart and Vascular Institute, Falls Church, VA, USA
| | - Vojtěch Melenovský
- Department of Cardiology, Institute for Clinical and Experimental Medicine-IKEM, Prague, Czech Republic
| | - Karen Sliwa
- Hatter Institute for Cardiovascular Research in Africa, Faculty of Health Sciences, Department of Medicine and Cardiology, University of Cape Town, Cape Town, South Africa
| | - Yuri Lopatin
- Volgograd State Medical University, Regional Cardiology Centre Volgograd, Volgograd, Russian Federation
| | - Juan Luis Arango
- Unidad de Cirugía Cardiovascular de Guatemala, Guatemala City, Guatemala
| | - M Cecilia Bahit
- INECO Neurociencias Oroño, Fundación INECO, Rosario, Argentina
| | | | - Christopher M O'Connor
- The Inova Center of Outcomes Research, Inova Heart and Vascular Institute, Falls Church, VA, USA
| | - Palak Shah
- The Inova Center of Outcomes Research, Inova Heart and Vascular Institute, Falls Church, VA, USA
| | | | - Adriaan A Voors
- Department of Cardiology, University Medical Centre Groningen, Groningen, The Netherlands
- University of Groningen, Groningen, The Netherlands
| | - Burkert Pieske
- Charité University Medicine, German Heart Center, Berlin, Germany
| | - Paul W Armstrong
- University of Alberta, Canadian VIGOUR Centre, Edmonton, AB, Canada
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Nikolaidou A, Ventoulis I, Karakoulidis G, Anastasiou V, Daios S, Papadopoulos SF, Didagelos M, Parissis J, Karamitsos T, Kotsa K, Ziakas A, Kamperidis V. Hypoglycemic Drugs in Patients with Diabetes Mellitus and Heart Failure: A Narrative Review. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:912. [PMID: 38929529 PMCID: PMC11205945 DOI: 10.3390/medicina60060912] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Revised: 05/26/2024] [Accepted: 05/27/2024] [Indexed: 06/28/2024]
Abstract
Over the last few years, given the increase in the incidence and prevalence of both type 2 diabetes mellitus (T2DM) and heart failure (HF), it became crucial to develop guidelines for the optimal preventive and treatment strategies for individuals facing these coexisting conditions. In patients aged over 65, HF hospitalization stands out as the predominant reason for hospital admissions, with their prognosis being associated with the presence or absence of T2DM. Historically, certain classes of glucose-lowering drugs, such as thiazolidinediones (rosiglitazone), raised concerns due to an observed increased risk of myocardial infarction (MI) and cardiovascular (CV)-related mortality. In response to these concerns, regulatory agencies started requiring CV outcome trials for all novel antidiabetic agents [i.e., dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and sodium-glucose cotransporter-2 inhibitors (SGLT2is)] with the aim to assess the CV safety of these drugs beyond glycemic control. This narrative review aims to address the current knowledge about the impact of glucose-lowering agents used in T2DM on HF prevention, prognosis, and outcome.
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Affiliation(s)
- Anastasia Nikolaidou
- 1st Department of Cardiology, AHEPA University Hospital, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (A.N.); (G.K.); (V.A.); (S.D.); (S.-F.P.); (M.D.); (T.K.); (A.Z.)
| | - Ioannis Ventoulis
- Department of Occupational Therapy, University of Western Macedonia, Keptse Area, 50200 Ptolemaida, Greece;
| | - Georgios Karakoulidis
- 1st Department of Cardiology, AHEPA University Hospital, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (A.N.); (G.K.); (V.A.); (S.D.); (S.-F.P.); (M.D.); (T.K.); (A.Z.)
| | - Vasileios Anastasiou
- 1st Department of Cardiology, AHEPA University Hospital, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (A.N.); (G.K.); (V.A.); (S.D.); (S.-F.P.); (M.D.); (T.K.); (A.Z.)
| | - Stylianos Daios
- 1st Department of Cardiology, AHEPA University Hospital, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (A.N.); (G.K.); (V.A.); (S.D.); (S.-F.P.); (M.D.); (T.K.); (A.Z.)
| | - Spyridon-Filippos Papadopoulos
- 1st Department of Cardiology, AHEPA University Hospital, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (A.N.); (G.K.); (V.A.); (S.D.); (S.-F.P.); (M.D.); (T.K.); (A.Z.)
| | - Matthaios Didagelos
- 1st Department of Cardiology, AHEPA University Hospital, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (A.N.); (G.K.); (V.A.); (S.D.); (S.-F.P.); (M.D.); (T.K.); (A.Z.)
| | - John Parissis
- Emergency Medicine Department, Attikon University Hospital, National and Kapodistrian University of Athens, Rimini 1, Chaidari, 10679 Athens, Greece;
| | - Theodoros Karamitsos
- 1st Department of Cardiology, AHEPA University Hospital, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (A.N.); (G.K.); (V.A.); (S.D.); (S.-F.P.); (M.D.); (T.K.); (A.Z.)
| | - Kalliopi Kotsa
- Division of Endocrinology and Metabolism, Diabetes Center, 1st Department of Internal Medicine, AHEPA University Hospital, School of Medicine, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece;
| | - Antonios Ziakas
- 1st Department of Cardiology, AHEPA University Hospital, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (A.N.); (G.K.); (V.A.); (S.D.); (S.-F.P.); (M.D.); (T.K.); (A.Z.)
| | - Vasileios Kamperidis
- 1st Department of Cardiology, AHEPA University Hospital, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (A.N.); (G.K.); (V.A.); (S.D.); (S.-F.P.); (M.D.); (T.K.); (A.Z.)
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Ibrahim M, Ba-Essa EM, Baker J, Cahn A, Ceriello A, Cosentino F, Davies MJ, Eckel RH, Van Gaal L, Gaede P, Handelsman Y, Klein S, Leslie RD, Pozzilli P, Del Prato S, Prattichizzo F, Schnell O, Seferovic PM, Standl E, Thomas A, Tuomilehto J, Valensi P, Umpierrez GE. Cardio-renal-metabolic disease in primary care setting. Diabetes Metab Res Rev 2024; 40:e3755. [PMID: 38115715 PMCID: PMC11320716 DOI: 10.1002/dmrr.3755] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Revised: 09/26/2023] [Accepted: 11/23/2023] [Indexed: 12/21/2023]
Abstract
In the primary care setting providers have more tools available than ever before to impact positively obesity, diabetes, and their complications, such as renal and cardiac diseases. It is important to recognise what is available for treatment taking into account diabetes heterogeneity. For those who develop type 2 diabetes (T2DM), effective treatments are available that for the first time have shown a benefit in reducing mortality and macrovascular complications, in addition to the well-established benefits of glucose control in reducing microvascular complications. Some of the newer medications for treating hyperglycaemia have also a positive impact in reducing heart failure (HF). Technological advances have also contributed to improving the quality of care in patients with diabetes. The use of technology, such as continuous glucose monitoring systems (CGM), has improved significantly glucose and glycated haemoglobin A1c (HbA1c) values, while limiting the frequency of hypoglycaemia. Other technological support derives from the use of predictive algorithms that need to be refined to help predict those subjects who are at great risk of developing the disease and/or its complications, or who may require care by other specialists. In this review we also provide recommendations for the optimal use of the new medications; sodium-glucose co-transporter-2 inhibitors (SGLT2i) and Glucagon-like peptide-receptor agonists 1 (GLP1RA) in the primary care setting considering the relevance of these drugs for the management of T2DM also in its early stage.
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Affiliation(s)
- Mahmoud Ibrahim
- EDC, Centre for Diabetes Education, Charlotte, North Carolina, USA
| | | | - Jason Baker
- Weill Cornell Medicine, New York, New York, USA
| | - Avivit Cahn
- The Diabetes Unit & Endocrinology and Metabolism Unit, Hadassah Hebrew University Hospital, Jerusalem, Israel
| | | | - Francesco Cosentino
- Unit of Cardiology, Department of Medicine Solna, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden
| | - Melanie J Davies
- Diabetes Research Centre, University of Leicester, Leicester, UK
- NIHR Leicester Biomedical Research Centre, Leicester, UK
| | - Robert H Eckel
- University of Colorado Anschutz Medical Campus and University of Colorado Hospital, Aurora, Colorado, USA
| | - Luc Van Gaal
- Department of Endocrinology, Diabetology, and Metabolism, Antwerp University Hospital, Antwerp, Belgium
| | - Peter Gaede
- Department of Cardiology and Endocrinology, Slagelse Hospital, Slagelse, Denmark
| | | | - Samuel Klein
- Washington University School of Medicine, Saint Louis, Missouri, USA
- Sansum Diabetes Research Institute, Santa Barbara, California, USA
| | - Richard David Leslie
- Blizard Institute, Centre of Immunobiology, Barts and the London School of Medicine, Queen Mary, University of London, London, UK
| | - Paolo Pozzilli
- Blizard Institute, Centre of Immunobiology, Barts and the London School of Medicine, Queen Mary, University of London, London, UK
- Campus Bio-Medico University, Rome, Italy
| | - Stefano Del Prato
- University of Pisa and Sant'Anna School of Advanced Studies, Pisa, Italy
| | | | - Oliver Schnell
- Forschergruppe Diabetes eV at the Helmholtz Centre, Munich-Neuherberg, Germany
| | - Petar M Seferovic
- Serbian Academy of Sciences and Arts, University of Belgrade Faculty of Medicine and Belgrade University Medical Center, Belgrade, Serbia
| | - Eberhard Standl
- Forschergruppe Diabetes eV at the Helmholtz Centre, Munich-Neuherberg, Germany
| | | | - Jaakko Tuomilehto
- Public Health Promotion Unit, Finnish Institute for Health and Welfare, Helsinki, Finland
- Department of Public Health, University of Helsinki, Helsinki, Finland
- Diabetes Research Unit, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Paul Valensi
- Polyclinique d'Aubervilliers, Aubervilliers and Paris Nord University, Bobigny, France
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Destere A, Merino D, Lavrut T, Rocher F, Viard D, Drici MD, Gérard AO. Drug-induced cardiac toxicity and adverse drug reactions, a narrative review. Therapie 2024; 79:161-172. [PMID: 37957054 DOI: 10.1016/j.therap.2023.10.008] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Accepted: 09/05/2023] [Indexed: 11/15/2023]
Abstract
Drug-induced cardiotoxicity is a primary concern in both drug development and clinical practice. Although the heart is not a common target for adverse drug reactions, some drugs still cause various adverse cardiac events, with sometimes severe consequences. Direct cardiac toxicity encompasses functional and structural changes of the cardiovascular system due to possible exposure to medicines. This phenomenon extends beyond cardiovascular drugs to include non-cardiovascular drugs including anticancer drugs such as tyrosine kinase inhibitors, anthracyclines and immune checkpoint inhibitors (ICIs), as well as various antipsychotics, venlafaxine, and even some antibiotics (such as macrolides). Cardiac ADRs comprise an array of effects, ranging from heart failure and myocardial ischemia to valvular disease, thrombosis, myocarditis, pericarditis, arrhythmias, and conduction abnormalities. The underlying mechanisms may include disturbances of ionic processes, induction of cellular damage via impaired mitochondrial function, and even hypercoagulability. To mitigate the impact of drug-induced cardiotoxicity, multi-stage evaluation guidelines have been established, following the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines for in vitro and in vivo testing. Despite preclinical safeguards, post-marketing surveillance remains critical, as certain cardiotoxic drugs may escape initial scrutiny. Indeed, historical data show that cardiovascular ADRs contribute to almost 10% of market withdrawals. The impact of drug-induced cardiotoxicity on cardiac issues, particularly heart failure, is often underestimated, with incidence rates ranging from 11.0% to over 20.0%. We here comprehensively examine different patterns of drug-induced cardiotoxicity, highlighting current concerns and emerging pharmacovigilance signals. Understanding the underlying mechanisms and the associated risk factors is critical in order to promptly identify, effectively manage, and proactively prevent drug-induced cardiac adverse events. Collaborative efforts between physicians and cardiologists, coupled with thorough assessment and close monitoring, are essential to ensuring patient safety in the face of potential drug-induced cardiotoxicity.
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Affiliation(s)
- Alexandre Destere
- Université Côte d'Azur Medical Center, Department of Clinical Pharmacology, 06000 Nice, France; Université Côte d'Azur, Inria, CNRS, Laboratoire J.A.-Dieudonné, Maasai team, 06000 Nice, France
| | - Diane Merino
- Université Côte d'Azur Medical Center, Department of Clinical Pharmacology, 06000 Nice, France; Department of Child and Adolescent Psychiatry, Children's Hospitals of Nice CHU-Lenval, 06000 Nice, France; Université Côte d'Azur Medical Center, Department of Psychiatry, 06000 Nice, France
| | - Thibaud Lavrut
- Université Côte d'Azur Medical Center, Department of Clinical Pharmacology, 06000 Nice, France
| | - Fanny Rocher
- Université Côte d'Azur Medical Center, Department of Clinical Pharmacology, 06000 Nice, France
| | - Delphine Viard
- Université Côte d'Azur Medical Center, Department of Clinical Pharmacology, 06000 Nice, France
| | - Milou-Daniel Drici
- Université Côte d'Azur Medical Center, Department of Clinical Pharmacology, 06000 Nice, France.
| | - Alexandre O Gérard
- Université Côte d'Azur Medical Center, Department of Clinical Pharmacology, 06000 Nice, France; Université Côte d'Azur Medical Center, Department of Nephrology, 06000 Nice, France; Université Côte d'Azur, CNRS, Laboratory of Molecular Physio Medicine (LP2M), UMR 7370, 06000 Nice, France
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8
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Wong KCK, Ismail HS, Connelly KA, Verma S, Ng MY, Deva DP, Yan AT, Jimenez-Juan L. Relationship between saxagliptin use and left ventricular diastolic function assessed by cardiac MRI. Acta Diabetol 2024; 61:91-97. [PMID: 37691025 DOI: 10.1007/s00592-023-02177-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: 07/07/2023] [Accepted: 08/18/2023] [Indexed: 09/12/2023]
Abstract
AIMS Type 2 diabetes mellitus (T2DM) increases the risk of major cardiovascular events. In SAVOR-TIMI53 trial, the excess heart failure (HF) hospitalization among patients with T2DM in the saxagliptin group remains poorly understood. Our aim was to evaluate left ventricular (LV) diastolic function after 6 months of saxagliptin treatment using cardiac magnetic resonance imaging (CMR) in patients with T2DM. METHODS In this prospective study, 16 T2DM patients without HF were prescribed saxagliptin as part of routine guideline-directed management. CMR performed at baseline and 6 months after initiation of saxagliptin treatment were evaluated in a blinded fashion. We assessed LV diastolic function by measuring LV peak filling rate with correction for end-diastolic volume (PFR/LVEDV), time to peak filling rate with correction for cardiac cycle (TPF/RR), and early diastolic strain rate parameters [global longitudinal diastolic strain rate (GLSR-E), global circumferential diastolic strain rate (GCSR-E)] by feature tracking (FT-CMR). RESULTS Among the 16 patients (mean age of 59.9, 69% males, mean hemoglobin A1c 8.3%, mean left ventricular ejection fraction 57%), mean PFR was 314 ± 108 ml/s at baseline and did not change over 6 months (- 2.7, 95% CI - 35.6, 30.2, p = 0.86). There were also no significant changes in other diastolic parameters including PFR/EDV, TPF, TPF/RR, and GLSR-E and GCSR-E (all p > 0.50). CONCLUSION In T2DM patients without HF receiving saxagliptin over 6 months, there were no significant subclinical changes in LV diastolic function as assessed by CMR.
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Affiliation(s)
- Kathy C K Wong
- Department of Medical Imaging, St. Michael's Hospital, 30 Bond Street, Toronto, M5B 1W8, Canada
- Department of Medical Imaging, University of Toronto, Toronto, Canada
- Department of Diagnostic Radiology, The University of Hong Kong, Pok Fu Lam, Hong Kong
| | - Huda S Ismail
- Department of Medical Imaging, St. Michael's Hospital, 30 Bond Street, Toronto, M5B 1W8, Canada
- Department of Medical Imaging, University of Toronto, Toronto, Canada
| | - Kim A Connelly
- Division of Cardiology, St. Michael's Hospital, 30 Bond Street, Toronto, M5B 1W8, Canada
- Department of Medicine, University of Toronto, Toronto, Canada
- Keenan Research Centre for Biomedical Science in the Li Ka Shing Knowledge Institute of Unity Health Toronto, Toronto, Canada
| | - Subodh Verma
- Keenan Research Centre for Biomedical Science in the Li Ka Shing Knowledge Institute of Unity Health Toronto, Toronto, Canada
- Division of Cardiac Surgery, St. Michael's Hospital, Toronto, Canada
- Department of Surgery and Pharmacology and Toxicology, University of Toronto, Toronto, Canada
| | - Ming-Yen Ng
- Department of Diagnostic Radiology, The University of Hong Kong, Pok Fu Lam, Hong Kong
- Division of Cardiac Imaging, HKU-Shenzhen Hospital, Shenzhen, China
| | - Djeven P Deva
- Department of Medical Imaging, St. Michael's Hospital, 30 Bond Street, Toronto, M5B 1W8, Canada
- Department of Medical Imaging, University of Toronto, Toronto, Canada
- Keenan Research Centre for Biomedical Science in the Li Ka Shing Knowledge Institute of Unity Health Toronto, Toronto, Canada
| | - Andrew T Yan
- Department of Medical Imaging, St. Michael's Hospital, 30 Bond Street, Toronto, M5B 1W8, Canada.
- Department of Medical Imaging, University of Toronto, Toronto, Canada.
- Division of Cardiology, St. Michael's Hospital, 30 Bond Street, Toronto, M5B 1W8, Canada.
- Department of Medicine, University of Toronto, Toronto, Canada.
| | - Laura Jimenez-Juan
- Department of Medical Imaging, St. Michael's Hospital, 30 Bond Street, Toronto, M5B 1W8, Canada.
- Department of Medical Imaging, University of Toronto, Toronto, Canada.
- Keenan Research Centre for Biomedical Science in the Li Ka Shing Knowledge Institute of Unity Health Toronto, Toronto, Canada.
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9
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McDowell K, Adamson C, Jackson C, Campbell R, Welsh P, Petrie MC, McMurray JJV, Jhund PS, Herring N. Neuropeptide Y is elevated in heart failure and is an independent predictor of outcomes. Eur J Heart Fail 2024; 26:107-116. [PMID: 37937329 DOI: 10.1002/ejhf.3085] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Revised: 10/17/2023] [Accepted: 11/04/2023] [Indexed: 11/09/2023] Open
Abstract
AIMS Neuropeptide Y (NPY) is the most abundant neuropeptide found in the heart and is released alongside norepinephrine following prolonged sympathetic activation, a process that is implicated in the pathophysiology of heart failure (HF). In patients with severely impaired left ventricular ejection fraction (LVEF) undergoing cardiac resynchronization therapy, higher levels of NPY measured in coronary sinus blood, are associated with poorer outcome. The aim was to examine the association of peripheral venous NPY levels and outcomes in a HF population with a range of LVEF, using a highly sensitive and specific assay. METHODS AND RESULTS The association between NPY and the composite outcome of cardiovascular death or HF hospitalization, its components, and all-cause mortality was examined using Cox regression analyses among 833 patients using a threshold of elevated NPY identified through binary recursive partitioning adjusted for prognostic variables including estimated glomerular filtration rate (eGFR), ejection fraction and B-type natriuretic peptide (BNP). The mean value of NPY was 25.8 ± 18.2 pg/ml. Patients with high NPY levels (≥29 pg/ml) compared with low values were older (73 ± 10 vs. 71 ± 11 years), more often male (58.5% vs. 55.6%), had higher BNP levels (583 [261-1096] vs. 440 [227-829] pg/ml), lower eGFR (46.4 ± 13.9 vs. 52.4 ± 11.7 ml/min/1.73 m2 ), and were more often treated with diuretics. There was no associated risk of HF hospitalization with NPY levels ≥29 vs. <29 pg/ml. Higher NPY levels were associated with a greater risk of cardiovascular and all-cause death (adjusted hazard ratio 1.56 [95% confidence interval 1.21-2.10], p = 0.003 and 1.30 [1.04-1.62], p = 0.02, respectively). There was no associated risk of HF hospitalization with higher NPY levels. CONCLUSIONS Peripherally measured NPY is an independent predictor of all-cause and cardiovascular death even after adjustment for other prognostic variables, including BNP.
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Affiliation(s)
- Kirsty McDowell
- BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, UK
| | - Carly Adamson
- BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, UK
| | - Colette Jackson
- BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, UK
| | - Ross Campbell
- BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, UK
| | - Paul Welsh
- BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, UK
| | - Mark C Petrie
- BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, UK
| | - John J V McMurray
- BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, UK
| | - Pardeep S Jhund
- BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, UK
| | - Neil Herring
- Department of Physiology, Anatomy and Genetics, British Heart Foundation Centre of Excellence, University of Oxford, Oxford, UK
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10
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Lagunas-Rangel FA, Liao S, Williams MJ, Trukhan V, Fredriksson R, Schiöth HB. Drosophila as a Rapid Screening Model to Evaluate the Hypoglycemic Effects of Dipeptidyl Peptidase 4 (DPP4) Inhibitors: High Evolutionary Conservation of DPP4. Biomedicines 2023; 11:3032. [PMID: 38002032 PMCID: PMC10669173 DOI: 10.3390/biomedicines11113032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Revised: 11/09/2023] [Accepted: 11/10/2023] [Indexed: 11/26/2023] Open
Abstract
Dipeptidyl peptidase 4 (DPP4) inhibitors, commonly known as gliptins, have been an integral part of the treatment of type 2 diabetes mellitus (T2DM) for several years. Despite their remarkable efficacy in lowering glucose levels and their compatibility with other hypoglycemic drugs, recent studies have revealed adverse effects, prompting the search for improved drugs within this category, which has required the use of animal models to verify the hypoglycemic effects of these compounds. Currently, in many countries the use of mammals is being significantly restricted, as well as cost prohibitive, and alternative in vivo approaches have been encouraged. In this sense, Drosophila has emerged as a promising alternative for several compelling reasons: it is cost-effective, offers high experimental throughput, is genetically manipulable, and allows the assessment of multigenerational effects, among other advantages. In this study, we present evidence that diprotin A, a DPP4 inhibitor, effectively reduces glucose levels in Drosophila hemolymph. This discovery underscores the potential of Drosophila as an initial screening tool for novel compounds directed against DPP4 enzymatic activity.
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Affiliation(s)
- Francisco Alejandro Lagunas-Rangel
- Department of Surgical Sciences, Functional Pharmacology and Neuroscience, Uppsala University, 751 24 Uppsala, Sweden; (F.A.L.-R.); (S.L.); (M.J.W.)
| | - Sifang Liao
- Department of Surgical Sciences, Functional Pharmacology and Neuroscience, Uppsala University, 751 24 Uppsala, Sweden; (F.A.L.-R.); (S.L.); (M.J.W.)
| | - Michael J. Williams
- Department of Surgical Sciences, Functional Pharmacology and Neuroscience, Uppsala University, 751 24 Uppsala, Sweden; (F.A.L.-R.); (S.L.); (M.J.W.)
| | | | - Robert Fredriksson
- Department of Pharmaceutical Biosciences, Uppsala University, 751 24 Uppsala, Sweden;
| | - Helgi B. Schiöth
- Department of Surgical Sciences, Functional Pharmacology and Neuroscience, Uppsala University, 751 24 Uppsala, Sweden; (F.A.L.-R.); (S.L.); (M.J.W.)
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11
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Marx N, Federici M, Schütt K, Müller-Wieland D, Ajjan RA, Antunes MJ, Christodorescu RM, Crawford C, Di Angelantonio E, Eliasson B, Espinola-Klein C, Fauchier L, Halle M, Herrington WG, Kautzky-Willer A, Lambrinou E, Lesiak M, Lettino M, McGuire DK, Mullens W, Rocca B, Sattar N. 2023 ESC Guidelines for the management of cardiovascular disease in patients with diabetes. Eur Heart J 2023; 44:4043-4140. [PMID: 37622663 DOI: 10.1093/eurheartj/ehad192] [Citation(s) in RCA: 563] [Impact Index Per Article: 281.5] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/26/2023] Open
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12
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Grigorescu ED, Lăcătușu CM, Floria M, Cazac GD, Onofriescu A, Sauciuc LA, Ceasovschih A, Crețu I, Mihai BM, Șorodoc L. Effects of Incretin-Based Treatment on the Diastolic (Dys)Function in Patients with Uncontrolled Type 2 Diabetes Mellitus: A Prospective Study with 1-Year Follow-Up. Diagnostics (Basel) 2023; 13:2817. [PMID: 37685355 PMCID: PMC10487011 DOI: 10.3390/diagnostics13172817] [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: 07/28/2023] [Revised: 08/19/2023] [Accepted: 08/29/2023] [Indexed: 09/10/2023] Open
Abstract
Left ventricular diastolic dysfunction (DD) is a subclinical cardiac abnormality in patients with type 2 diabetes mellitus (T2DM) that can progress to heart failure (HF) and increase cardiovascular risk. This prospective study evaluated the DD in T2DM patients without atherosclerotic cardiovascular disease after one year of incretin-based drugs added to standard treatment. Of the 138 enrolled patients (49.30% male, mean age 57.86 ± 8.82, mean T2DM history 5 years), 71 were started on dipeptidyl peptidase-4 inhibitor sitagliptin/saxagliptin, 21 on glucagon-like peptide-1 receptor agonist exenatide, and 46 formed the control group (metformin and sulphonylurea/acarbose). At baseline, 71 patients had grade 1 DD, another 12 had grade 2 and 3 DD, and 15 had indeterminate DD. After one year, DD was evidenced in 50 cases. Diastolic function improved in 9 cases, and 27 patients went from grade 1 to indeterminate DD. The active group benefited more, especially patients treated with exenatide; their metabolic and inflammation profiles also improved the most. An in-depth analysis of echocardiographic parameters and paraclinical results in the context of literature data justifies the conclusion that early assessment of diastolic function in T2DM patients is necessary and the benefits of affordable incretin-based treatment may extend to subclinical cardiovascular manifestations such as DD.
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Affiliation(s)
- Elena-Daniela Grigorescu
- Unit of Diabetes, Nutrition and Metabolic Diseases, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania; (E.-D.G.); (A.O.); (B.-M.M.)
| | - Cristina-Mihaela Lăcătușu
- Unit of Diabetes, Nutrition and Metabolic Diseases, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania; (E.-D.G.); (A.O.); (B.-M.M.)
- Clinical Center of Diabetes, Nutrition and Metabolic Diseases, “Sf. Spiridon” County Clinical Emergency Hospital, 700111 Iași, Romania
| | - Mariana Floria
- Department of Internal Medicine, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania; (M.F.); (A.C.); (L.Ș.)
- Medical Clinic, “Sf. Spiridon” County Clinical Emergency Hospital, 700111 Iași, Romania
| | - Georgiana-Diana Cazac
- Unit of Diabetes, Nutrition and Metabolic Diseases, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania; (E.-D.G.); (A.O.); (B.-M.M.)
- Clinical Center of Diabetes, Nutrition and Metabolic Diseases, “Sf. Spiridon” County Clinical Emergency Hospital, 700111 Iași, Romania
| | - Alina Onofriescu
- Unit of Diabetes, Nutrition and Metabolic Diseases, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania; (E.-D.G.); (A.O.); (B.-M.M.)
- Clinical Center of Diabetes, Nutrition and Metabolic Diseases, “Sf. Spiridon” County Clinical Emergency Hospital, 700111 Iași, Romania
| | - Livia-Amira Sauciuc
- Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania;
| | - Alexandr Ceasovschih
- Department of Internal Medicine, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania; (M.F.); (A.C.); (L.Ș.)
- Medical Clinic, “Sf. Spiridon” County Clinical Emergency Hospital, 700111 Iași, Romania
| | - Ioana Crețu
- Crețu R. Ioana PFA, 1 Mărului, 707020 Aroneanu, Romania;
| | - Bogdan-Mircea Mihai
- Unit of Diabetes, Nutrition and Metabolic Diseases, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania; (E.-D.G.); (A.O.); (B.-M.M.)
- Clinical Center of Diabetes, Nutrition and Metabolic Diseases, “Sf. Spiridon” County Clinical Emergency Hospital, 700111 Iași, Romania
| | - Laurențiu Șorodoc
- Department of Internal Medicine, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania; (M.F.); (A.C.); (L.Ș.)
- Medical Clinic, “Sf. Spiridon” County Clinical Emergency Hospital, 700111 Iași, Romania
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Wu W, Li G, Zhou W, Wang E, Zhao X, Song X, Zhao Y. Comparison of Composition, Free-Radical-Scavenging Capacity, and Antibiosis of Fresh and Dry Leave Aqueous Extract from Michelia shiluensis. Molecules 2023; 28:5935. [PMID: 37630187 PMCID: PMC10457956 DOI: 10.3390/molecules28165935] [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: 07/02/2023] [Revised: 08/01/2023] [Accepted: 08/05/2023] [Indexed: 08/27/2023] Open
Abstract
Numerous plants of medicinal value grow on Hainan Island (China). Given the lack of knowledge on the phytochemical and pharmacological properties of Michelia shiluensis Chun and Y. F. Wu (M. shiluensis), the application of natural antioxidants and antimicrobials in the food industry has attracted increasing interest. This study aimed to compare the chemical composition, free-radical-scavenging capacity, and antibiosis of aqueous extracts of the fresh and dried leaves of M. shiluensis. The aqueous extract of the leaves of M. shiluensis was obtained using steam distillation, and its chemical components were separated and identified via gas chromatography-mass spectrometry (GC-MS). The free-radical-scavenging capacity and antibiosis were determined. Further, 28 and 20 compounds were isolated from the fresh leaf aqueous extract of M. shiluensis (MSFLAE) and dried leaf aqueous extract of M. shiluensis (MSDLAE), respectively. The free-radical-scavenging capacity of MSFLAE and MSDLAE was determined by the 2,2-diphenyl-1 picrylhydrazyl (DPPH) method, which was 43.43% and 38.74%, respectively. The scavenging capacity of MSFLAE and MSDLAE determined by the 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonate (ABTS)) method was 46.90% and 25.99%, respectively. The iron ion reduction capacity of MSFLAE and MSDLAE was determined by the ferric-reducing antioxidant power (FRAP) method as 94.7 and 62.9 μmol Fe2⁺/L, respectively. This indicated that the two leaf aqueous extracts had a certain free-radical-scavenging capacity, and the capacity of MSFLAE was higher than that of MSDLAE. The antibiosis of the two leaf aqueous extracts on the three foodborne pathogenic bacteria was low, but the antimicrobial effects on Gram-positive bacteria were better than those on Gram-negative bacteria. The antibiosis of MSFLAE on Escherichia coli and Staphylococcus aureus was greater than that of MSDLAE. Finally, MSFLAE and MSDLAE both had certain free-radical-scavenging capacities and antibiosis, confirming that the use of this plant in the research and development of natural antioxidants and antibacterial agents was reasonable. Plant aqueous extracts are an essential source of related phytochemistry and have immense pharmacological potential.
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Affiliation(s)
| | | | | | | | | | | | - Ying Zhao
- Hainan Key Laboratory of Biology of Tropical Flowers and Trees Resources, Forestry Institute, Hainan University, Haikou 570228, China; (W.W.); (G.L.); (W.Z.); (E.W.); (X.Z.); (X.S.)
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14
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Pieske B, Pieske-Kraigher E, Lam CSP, Melenovský V, Sliwa K, Lopatin Y, Arango JL, Bahit MC, O'Connor CM, Patel MJ, Roessig L, Morris DA, Kropf M, Westerhout CM, Zheng Y, Armstrong PW. Effect of vericiguat on left ventricular structure and function in patients with heart failure with reduced ejection fraction: The VICTORIA echocardiographic substudy. Eur J Heart Fail 2023; 25:1012-1021. [PMID: 36994634 DOI: 10.1002/ejhf.2836] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2022] [Revised: 03/24/2023] [Accepted: 03/27/2023] [Indexed: 03/31/2023] Open
Abstract
AIM Vericiguat significantly reduced the primary composite outcome of heart failure (HF) hospitalization or cardiovascular death in the VICTORIA trial. It is unknown if these outcome benefits are related to reverse left ventricular (LV) remodelling with vericiguat in patients with HF with reduced ejection fraction (HFrEF). The aim of this study was to compare the effects of vericiguat versus placebo on LV structure and function after 8 months of therapy in patients with HFrEF. METHODS AND RESULTS Standardized transthoracic echocardiography (TTE) was performed at baseline and after 8 months of therapy in a subset of HFrEF patients in VICTORIA. The co-primary endpoints were changes in LV end-systolic volume index (LVESVI) and LV ejection fraction (LVEF). Quality assurance and central reading were performed by an echocardiographic core laboratory blinded to treatment assignment. A total of 419 patients (208 vericiguat, 211 placebo) with high-quality paired TTE at baseline and 8 months were included. Baseline clinical characteristics were well balanced between treatment groups and echocardiographic characteristics were representative of patients with HFrEF. LVESVI significantly declined (60.7 ± 26.8 to 56.8 ± 30.4 ml/m2 ; p < 0.01) and LVEF significantly increased (33.0 ± 9.4% to 36.1 ± 10.2%; p < 0.01) in the vericiguat group, but similarly in the placebo group (absolute changes for vericiguat vs. placebo: LVESVI -3.8 ± 15.4 vs. -7.1 ± 20.5 ml/m2 ; p = 0.07 and LVEF +3.2 ± 8.0% vs. +2.4 ± 7.6%; p = 0.31). The absolute rate per 100 patient-years of the primary composite endpoint at 8 months tended to be lower in the vericiguat group (19.8) than the placebo group (29.6) (p = 0.07). CONCLUSIONS In this pre-specified echocardiographic study, significant improvements in LV structure and function occurred over 8 months in both vericiguat and placebo in a high-risk HFrEF population with recent worsening HF. Further studies are warranted to define the mechanisms of vericiguat's benefit in HFrEF.
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Affiliation(s)
- Burkert Pieske
- Charité University Medicine, German Heart Center, Berlin, Germany
| | | | - Carolyn S P Lam
- National Heart Centre Singapore and Duke-National University of Singapore, Singapore, Singapore
| | - Vojtěch Melenovský
- Department of Cardiology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Karen Sliwa
- Cape Heart Institute, University of Cape Town, Cape Town, South Africa
| | - Yuri Lopatin
- Volgograd State Medical University, Volgograd Regional Cardiology Center, Volgograd, Russian Federation
| | - Juan Luis Arango
- Unidad de Cirugía Cardiovascular de Guatemala, Guatemala City, Guatemala
| | - M Cecilia Bahit
- INECO Neurociencias Oroño, Fundación INECO, Rosario, Argentina
| | | | | | | | - Daniel A Morris
- Charité University Medicine, German Heart Center, Berlin, Germany
| | - Martin Kropf
- Charité University Medicine, German Heart Center, Berlin, Germany
| | | | - Yinggan Zheng
- Canadian VIGOUR Centre, University of Alberta, Edmonton, AB, Canada
| | - Paul W Armstrong
- Canadian VIGOUR Centre, University of Alberta, Edmonton, AB, Canada
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15
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Li J, Liu Y, Hao P. Re-evaluation of dipeptidyl peptidase-4 inhibitors in patients with heart failure and diabetes mellitus. Diabetes Res Clin Pract 2023:110798. [PMID: 37356725 DOI: 10.1016/j.diabres.2023.110798] [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: 04/21/2023] [Revised: 06/13/2023] [Accepted: 06/20/2023] [Indexed: 06/27/2023]
Abstract
OBJECTIVES The question of whether dipeptidyl peptidase-4 inhibitors (DPP-4i) should be preferred as new glucose-lowering agents in heart failure is controversial. This studyaimed to evaluate the effects of DPP-4i treatment on all-cause mortality and cardiovascular outcomes in patients with heart failure. METHODS We searched for available studies of DPP-4i therapy in heart failure and performed a pooled analysis. Outcomes included all-cause mortality, cardiovascular death, hospitalization for heart failure, left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), acute coronary syndrome, and acute myocardial infarction. RESULTS Treatment with DPP-4i did not reduce the risk of all-cause death, cardiovascular death, or hospitalization for heart failure. Subgroup analyses showed that DPP-4i significantly reduced all-cause mortality in trials with >40% female patients (OR 0.30, 95% CI [0.16, 0.58], P=0.0003) and in trials with >20% patients with heart failure with preserved ejection fraction (HFpEF) (OR 0.34, 95% CI [0.19, 0.60], P=0.0003). Changes in LVEF and LVEDV showed no statistical differences between the 2 groups. Accordingly, DPP-4i did not alter the risk of acute coronary syndrome and acute myocardial infarction. CONCLUSIONS DPP-4i may reduce all-cause mortality in heart failure patients in subgroups of women and HFpEF and has a high coronary safety profile.
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Affiliation(s)
- Jiaoran Li
- National Key Laboratory for Innovation and Transformation of Luobing Theory, The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Department of Cardiology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, PR China
| | - Yanping Liu
- Department of Radiology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, PR China
| | - Panpan Hao
- National Key Laboratory for Innovation and Transformation of Luobing Theory, The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Department of Cardiology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, PR China.
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16
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Sridhar GR, Pandit K, Warrier S, Birla A. Sustained-Release Vildagliptin 100 mg in Type 2 Diabetes Mellitus: A Review. Cureus 2023; 15:e39204. [PMID: 37378205 PMCID: PMC10291938 DOI: 10.7759/cureus.39204] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/18/2023] [Indexed: 06/29/2023] Open
Abstract
Dipeptidyl peptidase-4 inhibitors (DPP4Is) were introduced into the management of type 2 diabetes mellitus (T2DM) as they are insulinotropic and have no inherent risk of hypoglycemia and no effect on body weight. Currently, 11 drugs in this class are available for the management of diabetes. Although they have a similar mechanism of action, they differ from one other in their binding mechanisms, which influences their therapeutic and pharmacological profiles. Vildagliptin's overall safety and tolerability profile was comparable to placebo throughout clinical studies, and real-world data in a large group of T2DM patients corroborated this finding. Therefore, DPP4Is like vildagliptin is a secure alternative for treating patients with T2DM. Vildagliptin treatment given as a once-daily (QD) 100 mg sustained release (SR) formulation fits the criteria of adherence and compliance. This SR formulation, given once daily has the potential to provide glycemic control like the vildagliptin 50 mg twice-daily (BD) formulation. This comprehensive review discusses the journey of vildagliptin as 50 mg BD therapy as well as 100 mg SR QD therapy.
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Affiliation(s)
- G R Sridhar
- Endocrinology, Endocrine and Diabetes Centre, Visakhapatnam, IND
| | - Kaushik Pandit
- Endocrinology, Diabetes and Metabolism, Belle Vue Clinic, Kolkata, IND
- Endocrinology, Diabetes and Metabolism, Institute of Post Graduate Medical Education & Research, Kolkata, IND
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Hsu CN, Hsuan CF, Liao D, Chang JKJ, Chang AJW, Hee SW, Lee HL, Teng SIF. Anti-Diabetic Therapy and Heart Failure: Recent Advances in Clinical Evidence and Molecular Mechanism. Life (Basel) 2023; 13:1024. [PMID: 37109553 PMCID: PMC10144651 DOI: 10.3390/life13041024] [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: 02/09/2023] [Revised: 03/19/2023] [Accepted: 03/20/2023] [Indexed: 04/29/2023] Open
Abstract
Diabetic patients have a two- to four-fold increase in the risk of heart failure (HF), and the co-existence of diabetes and HF is associated with poor prognosis. In randomized clinical trials (RCTs), compelling evidence has demonstrated the beneficial effects of sodium-glucose co-transporter-2 inhibitors on HF. The mechanism includes increased glucosuria, restored tubular glomerular feedback with attenuated renin-angiotensin II-aldosterone activation, improved energy utilization, decreased sympathetic tone, improved mitochondria calcium homeostasis, enhanced autophagy, and reduced cardiac inflammation, oxidative stress, and fibrosis. The RCTs demonstrated a neutral effect of the glucagon-like peptide receptor agonist on HF despite its weight-reducing effect, probably due to it possibly increasing the heart rate via increasing cyclic adenosine monophosphate (cAMP). Observational studies supported the markedly beneficial effects of bariatric and metabolic surgery on HF despite no current supporting evidence from RCTs. Bromocriptine can be used to treat peripartum cardiomyopathy by reducing the harmful cleaved prolactin fragments during late pregnancy. Preclinical studies suggest the possible beneficial effect of imeglimin on HF through improving mitochondrial function, but further clinical evidence is needed. Although abundant preclinical and observational studies support the beneficial effects of metformin on HF, there is limited evidence from RCTs. Thiazolidinediones increase the risk of hospitalized HF through increasing renal tubular sodium reabsorption mediated via both the genomic and non-genomic action of PPARγ. RCTs suggest that dipeptidyl peptidase-4 inhibitors, including saxagliptin and possibly alogliptin, may increase the risk of hospitalized HF, probably owing to increased circulating vasoactive peptides, which impair endothelial function, activate sympathetic tones, and cause cardiac remodeling. Observational studies and RCTs have demonstrated the neutral effects of insulin, sulfonylureas, an alpha-glucosidase inhibitor, and lifestyle interventions on HF in diabetic patients.
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Affiliation(s)
- Chih-Neng Hsu
- Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin 640, Taiwan
| | - Chin-Feng Hsuan
- Division of Cardiology, Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung 824, Taiwan
- Division of Cardiology, Department of Internal Medicine, E-Da Dachang Hospital, I-Shou University, Kaohsiung 824, Taiwan
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung 840, Taiwan
| | - Daniel Liao
- Graduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University, Taipei 100, Taiwan
| | - Jack Keng-Jui Chang
- Biological Programs for Younger Scholar, Academia Sinica, Taipei 115, Taiwan
| | - Allen Jiun-Wei Chang
- Graduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University, Taipei 100, Taiwan
| | - Siow-Wey Hee
- Department of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan
| | - Hsiao-Lin Lee
- Graduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University, Taipei 100, Taiwan
| | - Sean I. F. Teng
- Department of Cardiology, Ming-Sheng General Hospital, Taoyuan 330, Taiwan
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Michaud L, Seplowe M, Meir J, Aronow WS. Safety and cardiometabolic efficacy of novel antidiabetic drugs. Expert Opin Drug Saf 2023; 22:119-124. [PMID: 36877138 DOI: 10.1080/14740338.2023.2188190] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Accepted: 03/03/2023] [Indexed: 03/07/2023]
Abstract
INTRODUCTION There are three major drug classes discussed in this review: dipeptidyl dipeptidase-4 (DPP4) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAS), and sodium-glucose cotransporter-2 (SGLT2) inhibitors. A literature review of the landmark cardiovascular outcome trials from 2008 to 2021 was conducted. AREAS COVERED The cumulative data shown in this review suggest that in patients with Type 2 Diabetes (T2D), SGLT2 inhibitors and GLP-1 RAS may reduce cardiovascular (CV) risk. Specifically, in the heart failure (HF) population, SGLT2 inhibitors have shown a reduction in hospitalizations in some randomized controlled trials (RCTs). DPP4 inhibitors have not shown a similar reduction in CV risk and even exhibited an increase in hospitalizations for HF in one RCT. It is important to note that the DPP4 inhibitors did not demonstrate an increase in major CV events, with the exception of the increase in HF hospitalizations in the SAVOR TIMI 53 trial. EXPERT OPINION Future avenues of research to explore include the use of novel antidiabetic agents to reduce post-myocardial infarction (MI) CV risk and arrhythmias independent of their use as diabetic agents.
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Affiliation(s)
- Liana Michaud
- Department of Medicine, Westchester Medical Center, Valhalla, NY, USA
| | - Matthew Seplowe
- Department of Medicine, Westchester Medical Center, Valhalla, NY, USA
| | - Juliet Meir
- Department of Medicine, Westchester Medical Center, Valhalla, NY, USA
| | - Wilbert S Aronow
- Department of Cardiology, Westchester Medical Center, Valhalla, NY, USA
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19
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Seferović PM, Polovina M, Seferović J, Rosano G. Strength in synergy: Cardiometabolic effects of sacubitril/valsartan in heart failure and diabetes. Int J Cardiol 2023; 371:293-294. [PMID: 36115444 DOI: 10.1016/j.ijcard.2022.09.019] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2022] [Accepted: 09/08/2022] [Indexed: 02/06/2023]
Affiliation(s)
- Petar M Seferović
- Faculty of Medicine, Belgrade University, 8 Dr Subotica, 11000 Belgrade, Serbia; Serian Academy of Arts and Sciences, 35, Kneza Mihaila, 11000 Belgrade, Serbia.
| | - Marija Polovina
- Faculty of Medicine, Belgrade University, 8 Dr Subotica, 11000 Belgrade, Serbia; Department of Cardiology, University Clinical Centre of Serbia, 8 Koste Todorovica, 11000 Belgrade, Serbia
| | - Jelena Seferović
- Faculty of Medicine, Belgrade University, 8 Dr Subotica, 11000 Belgrade, Serbia; Department of Ednocrinology, University Clinical Centre of Serbia, 8 Koste Todorovica, 11000 Belgrade, Serbia
| | - Giuseppe Rosano
- Centre for Clinical & Basic Research, IRCCS San Raffaele Pisana, via della Pisana, 235, 00163, Rome, Italy
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20
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Li J, Ji C, Zhang W, Lan L, Ge W. Effect of new glucose-lowering drugs on stroke in patients with type 2 diabetes: A systematic review and Meta-analysis. J Diabetes Complications 2023; 37:108362. [PMID: 36462459 DOI: 10.1016/j.jdiacomp.2022.108362] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Revised: 11/20/2022] [Accepted: 11/23/2022] [Indexed: 11/29/2022]
Abstract
AIMS People with diabetes tend to face a higher risk of stroke. Randomized controlled trials (RCTs) have demonstrated the different outcomes of new glucose-lowering drugs marketed in recent years on cardiovascular outcome events. The effects of glucagon-like peptide-1 (GLP-1) agonists, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, and dipeptidyl peptidase-4 (DPP-4) inhibitors on stroke risk were evaluated in published RCTs. METHODS A search of Embase, Cochrane Library, and PubMed databases identified studies with stroke as an outcome event up to 3 December 2021. Risk ratios for stroke outcomes were analyzed using a fixed-effects model. I2 was used to assess the heterogeneity of the study. RESULTS 19 RCTs with 155,027 participants with type 2 diabetes were identified. Pooled analysis showed that compared to placebo, GLP-1 agonists reduced non-fatal stroke by 15 % (RR = 0.85, 95%CI 0.77-0.94, P = 0.002, I2 = 0 %) and total stroke (RR = 0.84, 95%CI 0.77-0.93, P = 0.000, I2 = 0 %) by 16 %. SGLT-2 inhibitors and DPP-4 inhibitors were not significantly associated with lower stroke risk. CONCLUSIONS This meta-analysis indicates that GLP-1 agonists have potential benefits for stroke. However, further studies are needed if GLP-1 agonists are to be used to reduce the risk of stroke in patients with type 2 diabetes. More research is also needed to investigate the effects of new glucose-lowering drugs on different stroke subtypes. SYSTEMATIC REVIEW REGISTRATION This protocol was registered on the International Prospective Register of Systematic Reviews (https://www.crd.york.ac.uk/PROSPERO/; registration number: CRD42022326382).
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Affiliation(s)
- Jiaxi Li
- School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China; Department of Pharmacy, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China
| | - Cheng Ji
- Department of Pharmacy, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China
| | - Wen Zhang
- Department of Radiology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China
| | - Linyan Lan
- School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China; Department of Pharmacy, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China
| | - Weihong Ge
- Department of Pharmacy, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China.
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Khadanga S, Barrett K, Sheahan KH, Savage PD. Novel Therapeutics for Type 2 Diabetes, Obesity, and Heart Failure: A REVIEW AND PRACTICAL RECOMMENDATIONS FOR CARDIAC REHABILITATION. J Cardiopulm Rehabil Prev 2023; 43:1-7. [PMID: 36576423 PMCID: PMC9801223 DOI: 10.1097/hcr.0000000000000761] [Citation(s) in RCA: 6] [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] [Indexed: 12/29/2022]
Abstract
BACKGROUND Cardiac rehabilitation (CR) has evolved over time not only to improve cardiorespiratory fitness through exercise but also to promote lifestyle-related behaviors to manage cardiovascular disease risk factors. Given the prevalence of obesity, diabetes mellitus, metabolic syndrome, and heart failure, CR serves as an ideal setting to monitor and, when indicated, intervene to ensure that individuals are optimally treated. PURPOSE The objective of this report was to review current antihyperglycemic agents and discuss the role for these medications in the care and treatment of individuals participating in CR. CONCLUSION There is strong evidence that the benefits provided by some antihyperglycemic medications go beyond glycemic control to include general cardiovascular disease risk reduction. Health care professionals in CR should be aware of the cardiovascular benefits of newer antihyperglycemic agents, as well as the treatment approach to patients with type 2 diabetes, obesity, and heart failure.
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Affiliation(s)
- Sherrie Khadanga
- Divisions of Cardiology (Dr Khadanga and Mr Savage) and Endocrinology (Drs Barrett and Sheahan), Department of Medicine, University of Vermont, Burlington; and University of Vermont Medical Center Cardiac Rehabilitation, Burlington (Dr Khadanga and Mr Savage)
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22
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Xu H, Wang D, Ramponi C, Wang X, Zhang H. The P21-Activated Kinase 1 and 2 As Potential Therapeutic Targets for the Management of Cardiovascular Disease. INTERNATIONAL JOURNAL OF DRUG DISCOVERY AND PHARMACOLOGY 2022:5. [PMID: 39899001 PMCID: PMC7617276 DOI: 10.53941/ijddp.v1i1.179] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/04/2025]
Abstract
Group I p21-activated kinases (Paks) are members of the serine/threonine protein kinase family. Paks are encoded by three genes (Pak 1 - 3) and are involved in the regulation of various biological processes. Pak1 and Pak2 are key members, sharing 91% sequence identity in their kinase domains. Recent studies have shown that Pak1/2 protect the heart from various types of stresses. Activated Pak1/2 participate in the maintenance of cellular homeostasis and metabolism, thus enhancing the adaptation and resilience of cardiomyocytes to stress. The structure, activation and function of Pak1/2 as well as their protective roles against the occurrence of cardiovascular disease are described in this review. The values of Pak1/2 as therapeutic targets are also discussed.
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Affiliation(s)
- Honglin Xu
- Michael Smith building, Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK
| | - Dingwei Wang
- Michael Smith building, Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK
| | - Chiara Ramponi
- Michael Smith building, Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK
| | - Xin Wang
- Michael Smith building, Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK
| | - Hongyuan Zhang
- Michael Smith building, Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK
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DeMarsilis A, Reddy N, Boutari C, Filippaios A, Sternthal E, Katsiki N, Mantzoros C. Pharmacotherapy of type 2 diabetes: An update and future directions. Metabolism 2022; 137:155332. [PMID: 36240884 DOI: 10.1016/j.metabol.2022.155332] [Citation(s) in RCA: 49] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Revised: 10/07/2022] [Accepted: 10/07/2022] [Indexed: 11/06/2022]
Abstract
Type 2 diabetes (T2D) is a widely prevalent disease with substantial economic and social impact for which multiple conventional and novel pharmacotherapies are currently available; however, the landscape of T2D treatment is constantly changing as new therapies emerge and the understanding of currently available agents deepens. This review aims to provide an updated summary of the pharmacotherapeutic approach to T2D. Each class of agents is presented by mechanism of action, details of administration, side effect profile, cost, and use in certain populations including heart failure, non-alcoholic fatty liver disease, obesity, chronic kidney disease, and older individuals. We also review targets of novel therapeutic T2D agent development. Finally, we outline an up-to-date treatment approach that starts with identification of an individualized goal for glycemic control then selection, initiation, and further intensification of a personalized therapeutic plan for T2D.
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Affiliation(s)
- Antea DeMarsilis
- Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA
| | - Niyoti Reddy
- Department of Medicine, School of Medicine, Boston University, Boston, USA
| | - Chrysoula Boutari
- Second Propedeutic Department of Internal Medicine, Hippocration Hospital, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Andreas Filippaios
- Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA
| | - Elliot Sternthal
- Section of Endocrinology, VA Boston Healthcare System, Harvard Medical School, Boston, MA 02115, USA
| | - Niki Katsiki
- Department of Nutritional Sciences and Dietetics, International Hellenic University, Sindos, Greece; School of Medicine, European University Cyprus, Nicosia, Cyprus.
| | - Christos Mantzoros
- Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA; Section of Endocrinology, VA Boston Healthcare System, Harvard Medical School, Boston, MA 02115, USA
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24
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Katsiki N, Kazakos K, Triposkiadis F. Contemporary choice of glucose lowering agents in heart failure patients with type 2 diabetes. Expert Opin Pharmacother 2022; 23:1957-1974. [DOI: 10.1080/14656566.2022.2143263] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Affiliation(s)
- Niki Katsiki
- Department of Nutritional Sciences and Dietetics, International Hellenic University, Thessaloniki, Greece
- School of Medicine, European University Cyprus, Nicosia, Cyprus
| | - Kyriakos Kazakos
- Nursing Department, International Hellenic University, Thessaloniki, Greece
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Effects of DPP4 Inhibitor in Platelet Reactivity and Other Cardiac Risk Markers in Patients with Type 2 Diabetes and Acute Myocardial Infarction. J Clin Med 2022; 11:jcm11195776. [PMID: 36233642 PMCID: PMC9571017 DOI: 10.3390/jcm11195776] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Revised: 09/23/2022] [Accepted: 09/25/2022] [Indexed: 12/01/2022] Open
Abstract
Background: The management of acute myocardial infarction (AMI) presents several challenges in patients with diabetes, among them the higher rate of recurrent thrombotic events, hyperglycemia and risk of subsequent heart failure (HF). The objective of our study was to evaluate effects of DPP-4 inhibitors (DPP-4i) on platelet reactivity (main objective) and cardiac risk markers. Methods: We performed a single-center double-blind randomized trial. A total of 70 patients with type 2 diabetes (T2DM) with AMI Killip ≤2 on dual-antiplatelet therapy (aspirin plus clopidogrel) were randomized to receive sitagliptin 100 mg or saxagliptin 5 mg daily or matching placebo. Platelet reactivity was assessed at baseline, 4 days (primary endpoint) and 30 days (secondary endpoint) after randomization, using VerifyNow Aspirin™ assay, expressed as aspirin reaction units (ARUs); B-type natriuretic peptide (BNP) in pg/mL was assessed at baseline and 30 days after (secondary endpoint). Results: Mean age was 62.6 ± 8.8 years, 45 (64.3%) male, and 52 (74.3%) of patients presented with ST-segment elevation MI. For primary endpoint, there were no differences in mean platelet reactivity (p = 0.51) between the DPP-4i (8.00 {−65.00; 63.00}) and placebo (−14.00 {−77.00; 52.00}) groups, as well in mean BNP levels (p = 0.14) between DPP-4i (−36.00 {−110.00; 15.00}) and placebo (−13.00 {−50.00; 27.00}). There was no difference between groups in cardiac adverse events. Conclusions: DPP4 inhibitor did not reduce platelet aggregation among patients with type 2 diabetes hospitalized with AMI. Moreover, the use of DPP-4i did not show an increase in BNP levels or in the incidence of cardiac adverse events. These findings suggests that DPP-4i could be an option for management of T2DM patients with acute MI.
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ASFUROGLU KALKAN E, AYDOĞAN Bİ, DINÇER İ, GÜLLÜ S. Effects of DPP-4 inhibitors on brain natriuretic peptide, neuropeptide Y, glucagon like peptide-1, substance P levels and global longitudinal strain measurements in type 2 diabetes mellitus patients. JOURNAL OF HEALTH SCIENCES AND MEDICINE 2022. [DOI: 10.32322/jhsm.1133314] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Introduction: Previously, a significant relationship between saxagliptin treatment and increased rate of hospitalization for congestive heart failure was reported. We aimed to investigate effects of vildagliptin and saxagliptin on brain natriuretic peptide (BNP), neuropeptide Y (NPY), substance P (SP), glucagon like peptide-1 (GLP-1) levels and left ventricular global longitudinal strain (GLS), assessed by 3-dimensional speckle tracking echocardiography in uncontrolled type 2 Diabetes mellitus (T2DM).
Material and method: Thirty seven uncontrolled T2DM (HbA1c>7,5%) patients who were recently prescribed to either vildagliptin 50 mg BID (n=21) or saxagliptin 5 mg QD (n=16) were included in this study. Levels of BNP, NPY, SP, GLP-1 levels were measured at admission, first and third months of treatment. GLS was measured at admission and third month.
Results: In whole group, BNP and NPY values increased significantly at third month of treatment (p< 0.001, 0.004; respectively). In the vildagliptin group, BNP and NPY values increased significantly at third month of treatment (p=0.02 and p=0.04, respectively). In the saxagliptin group only BNP levels increased significantly (p=0.015). In both groups; SP, GLP-1 levels and GLS measurements did not change significantly during follow-up period.
Conclusion: The current study demonstrated that treatment with saxagliptin and vildagliptin, was associated with increased levels of BNP and NPY levels. No evidence of subclinical myocardial damage or cardiac dysfunction could be detected by GLS measurements. Since our study population had no previous clinical cardiac disorders, increases in BNP and NPY levels with these two DPP4 inhibitors can be considered as a safety signal.
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Affiliation(s)
- Emra ASFUROGLU KALKAN
- SAĞLIK BİLİMLERİ ÜNİVERSİTESİ, ANKARA ŞEHİR SAĞLIK UYGULAMA VE ARAŞTIRMA MERKEZİ, DAHİLİ TIP BİLİMLERİ BÖLÜMÜ
| | - Berna İmge AYDOĞAN
- ANKARA UNIVERSITY, SCHOOL OF MEDICINE, DEPARTMENT OF INTERNAL MEDICINE, DEPARTMENT OF INTERNAL MEDICINE, ENDOCRINOLOGY AND METABOLIC DISEASES
| | - İrem DINÇER
- ANKARA UNIVERSITY, SCHOOL OF MEDICINE, DEPARTMENT OF INTERNAL MEDICINE, DEPARTMENT OF CARDIOLOGY
| | - Sevim GÜLLÜ
- ANKARA UNIVERSITY, SCHOOL OF MEDICINE, DEPARTMENT OF INTERNAL MEDICINE, DEPARTMENT OF INTERNAL MEDICINE, ENDOCRINOLOGY AND METABOLIC DISEASES
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Arruda-Junior DF, Salles TA, Martins FL, Antonio EL, Tucci PJF, Gowdak LHW, Tavares CAM, Girardi AC. Unraveling the interplay between dipeptidyl peptidase 4 and the renin-angiotensin system in heart failure. Life Sci 2022; 305:120757. [PMID: 35780844 DOI: 10.1016/j.lfs.2022.120757] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Revised: 06/17/2022] [Accepted: 06/27/2022] [Indexed: 10/17/2022]
Abstract
AIMS Emerging evidence suggests the existence of a crosstalk between dipeptidyl peptidase 4 (DPP4) and the renin-angiotensin system (RAS). Therefore, combined inhibition of DPP4 and RAS may produce similar pharmacological effects rather than being additive. This study tested the hypothesis that combining an inhibitor of DPP4 with an angiotensin II (Ang II) receptor blocker does not provide additional cardioprotection compared to monotherapy in heart failure (HF) rats. MAIN METHODS Male Wistar rats were subjected to left ventricle (LV) radiofrequency ablation or sham operation. Six weeks after surgery, radiofrequency-ablated rats who developed HF were assigned into four groups and received vehicle (water), vildagliptin, valsartan, or both drugs, for four weeks by oral gavage. KEY FINDINGS Vildagliptin and valsartan in monotherapy reduced LV hypertrophy, alleviated cardiac interstitial fibrosis, and improved systolic and diastolic function in HF rats, with no additional effect of combination treatment. HF rats displayed higher cardiac and serum DPP4 activity and abundance than sham. Surprisingly, not only vildagliptin but also valsartan in monotherapy downregulated the catalytic function and expression levels of systemic and cardiac DPP4. Moreover, vildagliptin and valsartan alone or in combination comparably upregulate the components of the cardiac ACE2/Ang-(1-7)/MasR while downregulating the ACE/Ang II/AT1R axis. SIGNIFICANCE Vildagliptin or valsartan alone is as effective as combined to treat cardiac dysfunction and remodeling in experimental HF. DPP4 inhibition downregulates classic RAS components, and pharmacological RAS blockade downregulates DPP4 in the heart and serum of HF rats. This interplay between DPP4 and RAS may affect HF progression and pharmacotherapy.
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Affiliation(s)
- Daniel F Arruda-Junior
- Laboratório de Genética e Cardiologia Molecular, Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
| | - Thiago A Salles
- Laboratório de Genética e Cardiologia Molecular, Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
| | - Flavia L Martins
- Laboratório de Genética e Cardiologia Molecular, Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
| | - Ednei L Antonio
- Departamento de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil
| | - Paulo J F Tucci
- Departamento de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil
| | - Luís Henrique W Gowdak
- Laboratório de Genética e Cardiologia Molecular, Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
| | - Caio A M Tavares
- Unidade de Cardiogeriatria, Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil; Academic Research Organization (ARO), Hospital Israelita Albert Eistein, São Paulo, São Paulo, Brazil
| | - Adriana C Girardi
- Laboratório de Genética e Cardiologia Molecular, Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
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28
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Bora VR, Gohel D, Singh R, Patel BM. Evaluation of selected antidiabetics in cardiovascular complications associated with cancer cachexia. Mol Cell Biochem 2022; 478:807-820. [PMID: 36098898 DOI: 10.1007/s11010-022-04552-8] [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: 01/20/2022] [Accepted: 08/29/2022] [Indexed: 10/14/2022]
Abstract
So far, the cardio-protective potential of antidiabetics is proved, but their effect on cardiovascular complications associated with cancer cachexia is not explored until now. Insulin resistance and glucose intolerance along with systemic inflammation are prominent in cachexia but the potential effect of antidiabetic agents especially those belonging to biguanide, DPP4 inhibitors and SGLT2 on the heart are not studied till now. In present study, the effect of metformin, vildagliptin, teneligliptin, dapagliflozin and empagliflozin on cardiovascular complications associated with cancer cachexia by using B16F1 induced metastatic cancer cachexia and urethane-induced cancer cachexia was studied. These antidiabetic agents proved to be beneficial against cachexia-induced atrophy of the heart, preserved ventricular weights, maintained cardiac hypertrophic index, preserved the wasting of cardiac muscles assessed by HE staining, Masson trichrome staining, periodic acid Schiff staining and picro-Sirius red staining. Altered cardiac gene expression was attenuated after treatment with selected antidiabetics, thus preventing cardiac atrophy. Also, antidiabetic agents treatment improved the serum creatinine kinase MB, Sodium potassium ATPase and collagen in the heart. Reduction in blood pressure and heart rate was observed after treatment with antidiabetic agents. Results of our study show that the selected antidiabetics prove to be beneficial in attenuating the cardiac atrophy and helps in regulation of hemodynamic stauts in cancer cachexia-induced cardiovascular complications. Our study provides some direction towards use of selected antidiabetic agents in the management of cardiovascular complications associated with cancer cachexia and the study outcomes can be useful in desiging clinical trials.
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Affiliation(s)
- Vivek R Bora
- Department of Pharmacology, Institute of Pharmacy, Nirma University, Sarkhej- Gandhinagar Highway, Ahmedabad, Gujarat, 382481, India
| | - Dhruv Gohel
- Department of Biochemistry, M. S. University of Baroda, Vadodara, Gujarat, 390002, India
| | - Rajesh Singh
- Department of Biochemistry, M. S. University of Baroda, Vadodara, Gujarat, 390002, India
| | - Bhoomika M Patel
- Department of Pharmacology, Institute of Pharmacy, Nirma University, Sarkhej- Gandhinagar Highway, Ahmedabad, Gujarat, 382481, India.
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Chan YH, Chao TF, Chen SW, Kao YW, Huang CY, Chu PH. Association of acute increases in serum creatinine with subsequent outcomes in patients with type 2 diabetes mellitus treated with sodium-glucose cotransporter 2 inhibitor or dipeptidyl peptidase-4 inhibitor. EUROPEAN HEART JOURNAL. QUALITY OF CARE & CLINICAL OUTCOMES 2022:qcac040. [PMID: 35797996 DOI: 10.1093/ehjqcco/qcac040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
AIMS The frequency of an acute increase in serum creatinine (sCr) of >30%, following treatment of sodium-glucose cotransporter-2 inhibitors (SGLT2i) and its clinical implications in patients with type 2 diabetes remains unclear. METHODS AND RESULTS We used medical data from a multicenter health care provider in Taiwan and recruited 11,657 and 8,117 diabetic patients with baseline/follow-up sCr data available within 12 weeks of SGLT2i and dipeptidyl peptidase-4 inhibitor (DPP4i) treatment from June 1, 2016, to December 31, 2018. Participants receiving SGLT2i or DPP4i were categorized by initial sCr change into three groups:>30% sCr increase, 0-30% increase, or no-sCr increase. Participants receiving SGLT2i was associated with a higher proportion of sCr increase of 0-30% (52.7% vs. 42.6%) but a lower proportion of sCr increase of >30% (5.9% vs. 9.6%) when compared with DPP4i. In contrast to DPP4i, the mean estimated glomerular filtration rate over time became stable after 24 weeks in three categories of sCr increase following SGLT2i initiation. Compared with no sCr increase, an initial sCr increase of >30% was associated with a higher risk of major adverse cardiovascular events (adjusted hazard ratio [aHR]:2.91, [95% confidence interval [CI]:1.37-6.17]), heart failure hospitalization (HHF) (aHR:1.91,[95%CI:1.08-3.40]), and composite renal outcome (aHR:1.53,[95%CI:1.05-2.25]) in SGLT2i group; an initial sCr increase of >30% associated with a higher risk of HHF and composite renal outcome in DPP4i group after multivariate adjustment. Overall, participants receiving SGLT2i was associated with a lower risk of HHF (aHR:0.64,[95%CI:0.48-0.85]) and composite renal outcomes (aHR:0.40,[95%CI:0.34-0.48]) compared with DPP4i after multivariate adjustment, and the treatment benefit was persistent across three categories of sCr increase (P interaction>.05). CONCLUSIONS A modest increase in serum creatinine (<30%) was common following SGLT2i initiation, and was not associated with worse clinical outcomes, therefore should not stop therapy prematurely, but a larger increase in creatinine following drug therapy was not typical and should raise concern and review of the patient.
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Affiliation(s)
- Yi-Hsin Chan
- The Cardiovascular Department, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
- School of Traditional Chinese Medicine, College of Medicine, Chang-Gung University, Taoyuan City 33302, Taiwan
- Microscopy Core Laboratory, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan
| | - Tze-Fan Chao
- Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taiwan
- Institute of Clinical Medicine, Cardiovascular Research Center, National Yang Ming Chiao Tung University, Taipei, 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, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Yi-Wei Kao
- Graduate Institute of Business Administration, College of Management, Fu Jen Catholic University, Taipei, Taiwan
| | - Chien-Ying Huang
- The Cardiovascular Department, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan
| | - Pao-Hsien Chu
- The Cardiovascular Department, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
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Tadic M, Sala C, Saeed S, Grassi G, Mancia G, Rottbauer W, Cuspidi C. New antidiabetic therapy and HFpEF: light at the end of tunnel? Heart Fail Rev 2022; 27:1137-1146. [PMID: 33843015 PMCID: PMC9197886 DOI: 10.1007/s10741-021-10106-9] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/06/2021] [Indexed: 11/27/2022]
Abstract
New antidiabetic therapy that includes sodium-glucose co-transporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor (GLP-1R) agonists, and dipeptidyl peptidase 4 (DPP-4) inhibitors showed significant benefit on cardiovascular outcomes in patients with and without type 2 diabetes mellitus, and this was particularly confirmed for SGLT2 inhibitors in subjects with heart failure (HF) with reduced ejection fraction (HFrEF). Their role on patients with HF with preserved ejection fraction (HFpEF) is still not elucidated, but encouraging results coming from the clinical studies indicate their beneficial role. The role of GLP-1R agonists and particularly DPP-4 inhibitors is less clear and debatable. Findings from the meta-analyses are sending positive message about the use of GLP-1R agonists in HFrEF therapy and revealed the improvement of left ventricular (LV) diastolic function in HFpEF. Nevertheless, the relevant medical societies still consider their effect as neutral or insufficiently investigated in HF patients. The impact of DPP-4 inhibitors in HF is the most controversial due to conflicting data that range from negative impact and increased risk of hospitalization due to HF, throughout neutral effect, to beneficial influence on LV diastolic dysfunction. However, this is a very heterogeneous group of medications and some professional societies made clear discrepancy between saxagliptin that might increase risk of HF hospitalization and those DPP-4 inhibitors that have no effect on hospitalization. The aim of this review is to summarize current clinical evidence about the effect of new antidiabetic medications on LV diastolic function and their potential benefits in HFpEF patients.
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Affiliation(s)
- Marijana Tadic
- Klinik Für Innere Medizin II, Universitätsklinikum Ulm, Albert-Einstein Allee 23, 89081, Ulm, Germany.
| | - Carla Sala
- Department of Clinical Sciences and Community Health, University of Milano and Fondazione Ospedale Maggiore IRCCS Policlinico Di Milano, Milan, Italy
| | - Sahrai Saeed
- Department of Heart Disease, Haukeland University Hospital, Bergen, Norway
| | - Guido Grassi
- Clinica Medica, University of Milan-Bicocca, Milan, Italy
| | - Giuseppe Mancia
- Milano and Policlinico Di Monza, University of Milano-Bicocca, Monza, Italy
| | - Wolfang Rottbauer
- Klinik Für Innere Medizin II, Universitätsklinikum Ulm, Albert-Einstein Allee 23, 89081, Ulm, Germany
| | - Cesare Cuspidi
- Clinica Medica, University of Milan-Bicocca, Milan, Italy
- Istituto Auxologico Italiano, IRCCS, Milan, Italy
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31
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Chadha M, Das AK, Deb P, Gangopadhyay KK, Joshi S, Kesavadev J, Kovil R, Kumar S, Misra A, Mohan V. Expert Opinion: Optimum Clinical Approach to Combination-Use of SGLT2i + DPP4i in the Indian Diabetes Setting. Diabetes Ther 2022; 13:1097-1114. [PMID: 35334083 PMCID: PMC8948458 DOI: 10.1007/s13300-022-01219-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Accepted: 02/01/2022] [Indexed: 12/20/2022] Open
Abstract
The Asian-Indian phenotype of type 2 diabetes mellitus is uniquely characterized for cardio-metabolic risk. In the context of implementing patient-centric holistic cardio-metabolic risk management as a priority, the choice of various combinations of antidiabetic agents should be individualized. Combined therapy with two classes of antidiabetic agents, namely, dipeptidyl peptidase 4 inhibitors and sodium-glucose co-transporter-2 inhibitors, target several pathophysiological pathways. The wide-ranging clinical outcomes associated with this combination, including improvement of glycemia and adiposity, reduction of metabolic and vascular risk, safety, and simplicity for sustainable compliance, are extremely relevant to the Asian Indian patient population living with T2DM. In this review we describe the available evidence in detail and present a rational practical guidance for the optimum clinical use of this combination in this patient population.
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Affiliation(s)
- Manoj Chadha
- Endocrinology, P.D. Hinduja Hospital, Mumbai, India
| | - Ashok Kumar Das
- Endocrinology, Pondicherry Institute of Medical Science, Puducherry, India
| | - Prasun Deb
- Endocrinology, Krishna Institute of Medical Sciences, Hyderabad, India
| | | | - Shashank Joshi
- Endocrinology, Joshi Clinic and Lilavati Hospital and Research Centre, Mumbai, India
| | | | - Rajiv Kovil
- Department of Diabetology, Dr Kovil’s Diabetes Care Centre, Mumbai, India
| | | | - Anoop Misra
- Fortis-C-DOC Centre of Excellence for Diabetes, Metabolic Diseases and Endocrinology, National Diabetes, Obesity and Cholesterol Foundation (N-DOC), Diabetes Foundation (India) (DFI), New Delhi, India
| | - Viswanathan Mohan
- Dr Mohan’s Diabetes Specialities Centre and Madras Diabetes Research Foundation, Chennai, India
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32
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McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, Burri H, Butler J, Čelutkienė J, Chioncel O, Cleland JG, Coats AJ, Crespo-Leiro MG, Farmakis D, Gilard M, Heyman S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CS, Lyon AR, McMurray JJ, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GM, Ruschitzka F, Skibelund AK. Guía ESC 2021 sobre el diagnóstico y tratamiento de la insuficiencia cardiaca aguda y crónica. Rev Esp Cardiol 2022. [DOI: 10.1016/j.recesp.2021.11.027] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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Paracrine signal emanating from stressed cardiomyocytes aggravates inflammatory microenvironment in diabetic cardiomyopathy. iScience 2022; 25:103973. [PMID: 35281739 PMCID: PMC8905320 DOI: 10.1016/j.isci.2022.103973] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Revised: 12/17/2021] [Accepted: 02/18/2022] [Indexed: 11/21/2022] Open
Abstract
Myocardial inflammation contributes to cardiomyopathy in diabetic patients through incompletely defined underlying mechanisms. In both human and time-course experimental samples, diabetic hearts exhibited abnormal ER, with a maladaptive shift over time in rodents. Furthermore, as a cardiac ER dysfunction model, mice with cardiac-specific p21-activated kinase 2 (PAK2) deletion exhibited heightened myocardial inflammatory response in diabetes. Mechanistically, maladaptive ER stress-induced CCAAT/enhancer-binding protein homologous protein (CHOP) is a novel transcriptional regulator of cardiac high-mobility group box-1 (HMGB1). Cardiac stress-induced release of HMGB1 facilitates M1 macrophage polarization, aggravating myocardial inflammation. Therapeutically, sequestering the extracellular HMGB1 using glycyrrhizin conferred cardioprotection through its anti-inflammatory action. Our findings also indicated that an intact cardiac ER function and protective effects of the antidiabetic drug interdependently attenuated the cardiac inflammation-induced dysfunction. Collectively, we introduce an ER stress-mediated cardiomyocyte-macrophage link, altering the macrophage response, thereby providing insight into therapeutic prospects for diabetes-associated cardiac dysfunction.
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34
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Piepoli MF, Adamo M, Barison A, Bestetti RB, Biegus J, Böhm M, Butler J, Carapetis J, Ceconi C, Chioncel O, Coats A, Crespo-Leiro MG, de Simone G, Drexel H, Emdin M, Farmakis D, Halle M, Heymans S, Jaarsma T, Jankowska E, Lainscak M, Lam CSP, Løchen ML, Lopatin Y, Maggioni A, Matrone B, Metra M, Noonan K, Pina I, Prescott E, Rosano G, Seferovic PM, Sliwa K, Stewart S, Uijl A, Vaartjes I, Vermeulen R, Verschuren WM, Volterrani M, Von Haehling S, Hoes A. Preventing heart failure: a position paper of the Heart Failure Association in collaboration with the European Association of Preventive Cardiology. Eur J Prev Cardiol 2022; 29:275-300. [PMID: 35083485 DOI: 10.1093/eurjpc/zwab147] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Revised: 08/15/2021] [Accepted: 08/18/2021] [Indexed: 02/05/2023]
Abstract
The heart failure epidemic is growing and its prevention, in order to reduce associated hospital readmission rates and its clinical and economic burden, is a key issue in modern cardiovascular medicine. The present consensus document aims to provide practical evidence-based information to support the implementation of effective preventive measures. After reviewing the most common risk factors, an overview of the population attributable risks in different continents is presented, to identify potentially effective opportunities for prevention and to inform preventive strategies. Finally, potential interventions that have been proposed and have been shown to be effective in preventing HF are listed.
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Affiliation(s)
- Massimo F Piepoli
- Cardiac Unit, Guglielmo da Saliceto Hospital, Piacenza, Italy
- Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy
| | - Marianna Adamo
- Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, ASST Spedali Civili di Brescia, Brescia, Italy
| | - Andrea Barison
- Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy
- Fondazione Toscana Gabriele Monasterio, Pisa, Italy
| | | | - Jan Biegus
- Department of Heart Diseases, Medical University, Wroclaw, Poland
| | - Michael Böhm
- Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Saarland University, Homburg/Saar, Germany
| | - Javed Butler
- Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA
| | - Jonathan Carapetis
- Telethon Kids Institute, University of Western Australia and Perth Children's Hospital, Perth, Australia
| | - Claudio Ceconi
- Department of Translational Medicine, University of Ferrara, Ferrara, Italy
| | - Ovidiu Chioncel
- University of Medicine Carol Davila, Bucharest, Romania
- Emergency Institute for Cardiovascular Diseases 'C.C. Iliescu', Bucharest, Romania
| | | | - Maria G Crespo-Leiro
- Complexo Hospitalario Universitario A Coruña (CHUAC): CIBERCV, Universidade da Coruña (UDC), Instituto Ciencias Biomedicas A Coruña (INIBIC), A Coruña, Spain
| | - Giovanni de Simone
- Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy
| | - Heinz Drexel
- Department of Medicine, Landeskrankenhaus Bregenz, Bregenz, Austria
- VIVIT, Landeskrankenhaus Feldkirch, Feldkirch, Austria
| | - Michele Emdin
- Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy
- Fondazione Toscana Gabriele Monasterio, Pisa, Italy
| | | | - Martin Halle
- Sport and Health Sciences, Policlinic for Preventive and Rehabilitative Sports Medicine, TUM School of Medicine, Munich, Germany
| | - Stephane Heymans
- Department of Cardiology, Maastricht University, CARIM School for Cardiovascular Diseases, Maastricht, Netherlands
- Centre for Molecular and Vascular Biology, Department of Cardiovascular Sciences, KU Leuven, Belgium
| | - Tiny Jaarsma
- Department of Health, Medicine and Caring Sciences, Linkoping University, Linköping, Sweden
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Ewa Jankowska
- Department of Heart Diseases, Wroclaw Medical University, Wroclaw, Poland
| | - Mitja Lainscak
- Division of Cardiology, General Hospital Murska Sobota and Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
- Faculty of Natural Sciences and Mathematics, University of Maribor, Maribor, Slovenia
| | - Carolyn S P Lam
- National Heart Centre Singapore, Duke-National University of Singapore, Singapore, Singapore
| | - Maja-Lisa Løchen
- Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway
| | - Yuri Lopatin
- Volgograd State Medical University, Regional Cardiology Centre, Volgograd, Russian Federation
| | | | | | - Marco Metra
- Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, ASST Spedali Civili di Brescia, Brescia, Italy
| | - Katharine Noonan
- Department of Translational Medicine, University of Ferrara, Ferrara, Italy
| | | | - Eva Prescott
- Bispebjerg Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark
| | | | - Petar M Seferovic
- Belgrade University Faculty of Medicine, Serbian Academy of Science and Arts, Belgrade, Serbia
| | - Karen Sliwa
- University of Cape Town, Cape Town, South Africa
| | - Simon Stewart
- Torrens University Australia, Adelaide, South Australia, Australia
| | - Alicia Uijl
- Centre for Molecular and Vascular Biology, Department of Cardiovascular Sciences, KU Leuven, Belgium
- Division of Heart & Lungs, Department of Cardiology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
- Division of Cardiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Ilonca Vaartjes
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Roel Vermeulen
- Division of Heart & Lungs, Department of Cardiology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - W M Verschuren
- National Institute for Public Health and the Environment, Bilthoven, the Netherlands
- Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands
| | | | - Stephan Von Haehling
- Department of Cardiology and Pneumology, Heart Center, University of Göttingen Medical Center, Göttingen, Germany
- German Center for Cardiovascular Research (DZHK), partner site Göttingen, Germany
| | - Arno Hoes
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
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Florentin M, Kostapanos MS, Papazafiropoulou AK. Role of dipeptidyl peptidase 4 inhibitors in the new era of antidiabetic treatment. World J Diabetes 2022; 13:85-96. [PMID: 35211246 PMCID: PMC8855136 DOI: 10.4239/wjd.v13.i2.85] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Revised: 07/29/2021] [Accepted: 01/26/2022] [Indexed: 02/06/2023] Open
Abstract
The last few years important changes have occurred in the field of diabetes treatment. The priority in the therapy of patients with diabetes is not glycemic control per se rather an overall management of risk factors, while individualization of glycemic target is suggested. Furthermore, regulatory authorities now require evidence of cardiovascular (CV) safety in order to approve new antidiabetic agents. The most novel drug classes, i.e., sodium-glucose transporter 2 inhibitors (SGLT2-i) and some glucagon-like peptide-1 receptor agonists (GLP-1 RA), have been demonstrated to reduce major adverse CV events and, thus, have a prominent position in the therapeutic algorithm of hyperglycemia. In this context, the role of previously used hypoglycemic agents, including dipeptidyl peptidase 4 (DPP-4) inhibitors, has been modified. DPP-4 inhibitors have a favorable safety profile, do not cause hypoglycemia or weight gain and do not require dose uptitration. Furthermore, they can be administered in patients with chronic kidney disease after dose modification and elderly patients with diabetes. Still, though, they have been undermined to a third line therapeutic choice as they have not been shown to reduce CV events as is the case with SGLT2-i and GLP-1 RA. Overall, DPP-4 inhibitors appear to have a place in the management of patients with diabetes as a safe class of oral glucose lowering agents with great experience in their use.
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Affiliation(s)
- Matilda Florentin
- Department of Internal Medicine, School of Medicine, University of Ioannina, Ioannina 45221, Greece
| | - Michael S Kostapanos
- Lipid Clinic, Department of General Medicine, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom
| | - Athanasia K Papazafiropoulou
- 1st Department of Internal Medicine and Diabetes Center, Tzaneio General Hospital of Piraeus, Athens 18536, Greece
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36
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McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, Burri H, Butler J, Čelutkienė J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GMC, Ruschitzka F, Kathrine Skibelund A. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). With the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail 2022; 24:4-131. [PMID: 35083827 DOI: 10.1002/ejhf.2333] [Citation(s) in RCA: 1218] [Impact Index Per Article: 406.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Accepted: 08/05/2021] [Indexed: 12/11/2022] Open
Abstract
Document Reviewers: Rudolf A. de Boer (CPG Review Coordinator) (Netherlands), P. Christian Schulze (CPG Review Coordinator) (Germany), Magdy Abdelhamid (Egypt), Victor Aboyans (France), Stamatis Adamopoulos (Greece), Stefan D. Anker (Germany), Elena Arbelo (Spain), Riccardo Asteggiano (Italy), Johann Bauersachs (Germany), Antoni Bayes-Genis (Spain), Michael A. Borger (Germany), Werner Budts (Belgium), Maja Cikes (Croatia), Kevin Damman (Netherlands), Victoria Delgado (Netherlands), Paul Dendale (Belgium), Polychronis Dilaveris (Greece), Heinz Drexel (Austria), Justin Ezekowitz (Canada), Volkmar Falk (Germany), Laurent Fauchier (France), Gerasimos Filippatos (Greece), Alan Fraser (United Kingdom), Norbert Frey (Germany), Chris P. Gale (United Kingdom), Finn Gustafsson (Denmark), Julie Harris (United Kingdom), Bernard Iung (France), Stefan Janssens (Belgium), Mariell Jessup (United States of America), Aleksandra Konradi (Russia), Dipak Kotecha (United Kingdom), Ekaterini Lambrinou (Cyprus), Patrizio Lancellotti (Belgium), Ulf Landmesser (Germany), Christophe Leclercq (France), Basil S. Lewis (Israel), Francisco Leyva (United Kingdom), AleVs Linhart (Czech Republic), Maja-Lisa Løchen (Norway), Lars H. Lund (Sweden), Donna Mancini (United States of America), Josep Masip (Spain), Davor Milicic (Croatia), Christian Mueller (Switzerland), Holger Nef (Germany), Jens-Cosedis Nielsen (Denmark), Lis Neubeck (United Kingdom), Michel Noutsias (Germany), Steffen E. Petersen (United Kingdom), Anna Sonia Petronio (Italy), Piotr Ponikowski (Poland), Eva Prescott (Denmark), Amina Rakisheva (Kazakhstan), Dimitrios J. Richter (Greece), Evgeny Schlyakhto (Russia), Petar Seferovic (Serbia), Michele Senni (Italy), Marta Sitges (Spain), Miguel Sousa-Uva (Portugal), Carlo G. Tocchetti (Italy), Rhian M. Touyz (United Kingdom), Carsten Tschoepe (Germany), Johannes Waltenberger (Germany/Switzerland) All experts involved in the development of these guidelines have submitted declarations of interest. These have been compiled in a report and published in a supplementary document simultaneously to the guidelines. The report is also available on the ESC website www.escardio.org/guidelines For the Supplementary Data which include background information and detailed discussion of the data that have provided the basis for the guidelines see European Heart Journal online.
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37
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Dysregulated Epicardial Adipose Tissue as a Risk Factor and Potential Therapeutic Target of Heart Failure with Preserved Ejection Fraction in Diabetes. Biomolecules 2022; 12:biom12020176. [PMID: 35204677 PMCID: PMC8961672 DOI: 10.3390/biom12020176] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Revised: 01/12/2022] [Accepted: 01/18/2022] [Indexed: 02/01/2023] Open
Abstract
Cardiovascular (CV) disease and heart failure (HF) are the leading cause of mortality in type 2 diabetes (T2DM), a metabolic disease which represents a fast-growing health challenge worldwide. Specifically, T2DM induces a cluster of systemic metabolic and non-metabolic signaling which may promote myocardium derangements such as inflammation, fibrosis, and myocyte stiffness, which represent the hallmarks of heart failure with preserved ejection fraction (HFpEF). On the other hand, several observational studies have reported that patients with T2DM have an abnormally enlarged and biologically transformed epicardial adipose tissue (EAT) compared with non-diabetic controls. This expanded EAT not only causes a mechanical constriction of the diastolic filling but is also a source of pro-inflammatory mediators capable of causing inflammation, microcirculatory dysfunction and fibrosis of the underlying myocardium, thus impairing the relaxability of the left ventricle and increasing its filling pressure. In addition to representing a potential CV risk factor, emerging evidence shows that EAT may guide the therapeutic decision in diabetic patients as drugs such as metformin, glucagon-like peptide‑1 (GLP-1) receptor agonists and sodium-glucose cotransporter 2 inhibitors (SGLT2-Is), have been associated with attenuation of EAT enlargement.
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38
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Piepoli MF, Adamo M, Barison A, Bestetti RB, Biegus J, Böhm M, Butler J, Carapetis J, Ceconi C, Chioncel O, Coats A, Crespo-Leiro MG, de Simone G, Drexel H, Emdin M, Farmakis D, Halle M, Heymans S, Jaarsma T, Jankowska E, Lainscak M, Lam CSP, Løchen ML, Lopatin Y, Maggioni A, Matrone B, Metra M, Noonan K, Pina I, Prescott E, Rosano G, Seferovic PM, Sliwa K, Stewart S, Uijl A, Vaartjes I, Vermeulen R, Monique Verschuren WM, Volterrani M, von Heahling S, Hoes A. Preventing heart failure: a position paper of the Heart Failure Association in collaboration with the European Association of Preventive Cardiology. Eur J Heart Fail 2022; 24:143-168. [PMID: 35083829 DOI: 10.1002/ejhf.2351] [Citation(s) in RCA: 41] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Revised: 08/15/2021] [Accepted: 08/18/2021] [Indexed: 12/16/2022] Open
Abstract
The heart failure epidemic is growing and its prevention, in order to reduce associated hospital readmission rates and its clinical and economic burden, is a key issue in modern cardiovascular medicine. The present position paper aims to provide practical evidence-based information to support the implementation of effective preventive measures. After reviewing the most common risk factors, an overview of the population attributable risks in different continents is presented, to identify potentially effective opportunities for prevention and to inform preventive strategies. Finally, potential interventions that have been proposed and have been shown to be effective in preventing heart failure are listed.
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Affiliation(s)
- Massimo F Piepoli
- Cardiac Unit, Guglielmo da Saliceto Hospital, Piacenza, Italy
- Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy
| | - Marianna Adamo
- Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, ASST Spedali Civili di Brescia, Brescia, Italy
| | - Andrea Barison
- Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy
- Fondazione Toscana Gabriele Monasterio, Pisa, Italy
| | | | - Jan Biegus
- Department of Heart Diseases, Medical University, Wroclaw, Poland
| | - Michael Böhm
- Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Saarland University, Homburg/Saar, Germany
| | - Javed Butler
- Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA
| | - Jonathan Carapetis
- Telethon Kids Institute, University of Western Australia and Perth Children's Hospital, Perth, Australia
| | - Claudio Ceconi
- Department of Translational Medicine, University of Ferrara, Ferrara, Italy
| | - Ovidiu Chioncel
- University of Medicine Carol Davila, Bucharest, Romania
- Emergency Institute for Cardiovascular Diseases 'C.C. Iliescu', Bucharest, Romania
| | | | - Maria G Crespo-Leiro
- Complexo Hospitalario Universitario A Coruña (CHUAC): CIBERCV, Universidade da Coruña (UDC), Instituto Ciencias Biomedicas A Coruña (INIBIC), A Coruña, Spain
| | - Giovanni de Simone
- Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy
| | - Heinz Drexel
- Department of Medicine, Landeskrankenhaus Bregenz, Bregenz, Austria
- VIVIT, Landeskrankenhaus Feldkirch, Feldkirch, Austria
| | - Michele Emdin
- Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy
- Fondazione Toscana Gabriele Monasterio, Pisa, Italy
| | | | - Martin Halle
- Sport and Health Sciences, Policlinic for Preventive and Rehabilitative Sports Medicine, TUM School of Medicine, Munich, Germany
| | - Stephane Heymans
- Department of Cardiology, Maastricht University, CARIM School for Cardiovascular Diseases, Maastricht, the Netherlands
- Centre for Molecular and Vascular Biology, Department of Cardiovascular Sciences, KU Leuven, Belgium
| | - Tiny Jaarsma
- Department of Health, Medicine and Caring Sciences, Linkoping University, Linköping, Sweden
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Ewa Jankowska
- Department of Heart Diseases, Wroclaw Medical University, Wroclaw, Poland
| | - Mitja Lainscak
- Division of Cardiology, General Hospital Murska Sobota and Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
- Faculty of Natural Sciences and Mathematics, University of Maribor, Maribor, Slovenia
| | - Carolyn S P Lam
- National Heart Centre Singapore, Duke-National University of Singapore, Singapore, Singapore
| | - Maja-Lisa Løchen
- Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway
| | - Yuri Lopatin
- Volgograd State Medical University, Regional Cardiology Centre, Volgograd, Russian Federation
| | | | | | - Marco Metra
- Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, ASST Spedali Civili di Brescia, Brescia, Italy
| | - Katharine Noonan
- Department of Translational Medicine, University of Ferrara, Ferrara, Italy
| | | | - Eva Prescott
- Bispebjerg Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark
| | | | - Petar M Seferovic
- Belgrade University Faculty of Medicine, Serbian Academy of Science and Arts, Belgrade, Serbia
| | - Karen Sliwa
- University of Cape Town, Cape Town, South Africa
| | - Simon Stewart
- Torrens University Australia, Adelaide, South Australia, Australia
| | - Alicia Uijl
- Centre for Molecular and Vascular Biology, Department of Cardiovascular Sciences, KU Leuven, Belgium
- Division of Heart & Lungs, Department of Cardiology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
- Division of Cardiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Ilonca Vaartjes
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Roel Vermeulen
- Division of Heart & Lungs, Department of Cardiology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - W M Monique Verschuren
- National Institute for Public Health and the Environment, Bilthoven, the Netherlands
- Institute for Risk Assessment Sciences, Utrecht University, Utrecht, the Netherlands
| | | | - Stephan von Heahling
- Department of Cardiology and Pneumology, Heart Center, University of Göttingen Medical Center, Göttingen, Germany
- German Center for Cardiovascular Research (DZHK), partner site Göttingen, Germany
| | - Arno Hoes
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
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Abstract
Type two diabetes mellitus (T2DM) represents a chronic condition with increasing prevalence worldwide among the older population. The T2DM condition increases the risk of micro and macrovascular complications as well as the risk of geriatric syndromes such as falls, fractures and cognitive impairment. The management of T2DM in the older population represents a challenge for the clinician, and a Comprehensive Geriatric Assessment should always be prioritized, in order to tailor the glycated hemoglobin target according to functional and cognitive status comorbidities, life expectancy and type of therapy. According to the most recent guidelines, older adults with T2DM should be categorized into three groups: healthy patients with good functional status, patients with complications and reduced functionality and patients at the end of life; for each group the target for glycemic control is different, also according to the type of treatment drug. The therapeutic approach should always begin with lifestyle changes; after that, several lines of therapy are available, with different mechanisms of action and potential effects other than glucose level reduction. Particular interest is growing in sodium-glucose cotransporter-2 inhibitors, due to their effect on the cardiovascular system. In this review, we evaluate the therapeutic options available for the treatment of older diabetic patients, to ensure a correct treatment approach.
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Kang SM, Park JH. Pleiotropic Benefits of DPP-4 Inhibitors Beyond Glycemic Control. Clin Med Insights Endocrinol Diabetes 2021; 14:11795514211051698. [PMID: 34733107 PMCID: PMC8558587 DOI: 10.1177/11795514211051698] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Accepted: 09/20/2021] [Indexed: 12/14/2022] Open
Abstract
Dipeptidyl peptidase (DPP)-4 inhibitors are oral anti-diabetic medications that block the activity of the ubiquitous enzyme DPP-4. Inhibition of this enzyme increases the level of circulating active glucagon-like peptide (GLP)-1 secreted from L-cells in the small intestine. GLP-1 increases the glucose level, dependent on insulin secretion from pancreatic β-cells; it also decreases the abnormally increased level of glucagon, eventually decreasing the blood glucose level in patients with type 2 diabetes. DPP-4 is involved in many physiological processes other than the degradation of GLP-1. Therefore, the inhibition of DPP-4 may have numerous effects beyond glucose control. In this article, we review the pleiotropic effects of DPP-4 inhibitors beyond glucose control, including their strong beneficial effects on the stress induced accelerated senescence of vascular cells, and the possible clinical implications of these effects.
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Affiliation(s)
- Seon Mee Kang
- Department of Internal Medicine, College of Medicine, Inje University, Busan, Republic of Korea
- Paik Institute for Clinical Research, Inje University, Busan, Republic of Korea
| | - Jeong Hyun Park
- Department of Internal Medicine, College of Medicine, Inje University, Busan, Republic of Korea
- Paik Institute for Clinical Research, Inje University, Busan, Republic of Korea
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Mannucci E, Nreu B, Montereggi C, Ragghianti B, Gallo M, Giaccari A, Monami M. Cardiovascular events and all-cause mortality in patients with type 2 diabetes treated with dipeptidyl peptidase-4 inhibitors: An extensive meta-analysis of randomized controlled trials. Nutr Metab Cardiovasc Dis 2021; 31:2745-2755. [PMID: 34364771 DOI: 10.1016/j.numecd.2021.06.002] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Revised: 06/07/2021] [Accepted: 06/07/2021] [Indexed: 12/17/2022]
Abstract
AIMS Meta-analyses of randomized trials on Dipeptidyl Peptidase-4 inhibitors (DPP4i) reported discordant results on major cardiovascular events (MACE), mortality, and heart failure. Aim of this meta-analysis of randomized trials is the assessment of the cardiovascular safety of DPP4i. DATA SYNTHESIS A Medline, Embase, Cochrane database search for sitagliptin, vildagliptin, omarigliptin, saxagliptin, alogliptin, trelagliptin, anagliptin, linagliptin, gemigliptin, evogliptin, and teneligliptin was performed up to up January 1st, 2020. All trials with a duration ≥24 weeks and comparing the effects of DPP4i with placebo or active drugs were collected. Mantel-Haenszel odds ratio (MH-OR) with 95% Confidence Interval (95% CI) was calculated for all outcomes defined above. A total of 182 eligible trials were identified. DPP-4i were not associated with an increased risk of MACE (MH-OR 0.99 [0.93, 1.04]), all-cause mortality (MH-OR 0.99 [0.93, 1.06]), and heart failure (MH-OR 1.05 [0.96, 1.15]) with no significant differences across individual molecules, except for saxagliptin, which was associated with an increased risk of heart failure. CONCLUSIONS As a class, DPP4i are not associated with any increase or reduction of MACE, all-cause mortality, and heart failure. Saxagliptin seems to be associated with an increased risk of hospitalization for heart failure.
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Affiliation(s)
| | - Besmir Nreu
- Diabetology, Careggi Hospital and University of Florence, Italy
| | | | | | - Marco Gallo
- Endocrinology and Metabolic Diseases Unit, AO SS. Antonio e Biagio e Cesare Arrigo, Alessandria, Italy
| | - Andrea Giaccari
- Centro per le Malattie Endocrine e Metaboliche, Fondazione Policlinico Universitario A. Gemelli UCSC and Università cattolica del Sacro Cuore, Rome, Italy
| | - Matteo Monami
- Diabetology, Careggi Hospital and University of Florence, Italy.
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McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, Burri H, Butler J, Čelutkienė J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GMC, Ruschitzka F, Kathrine Skibelund A, de Boer RA, Christian Schulze P, Abdelhamid M, Aboyans V, Adamopoulos S, Anker SD, Arbelo E, Asteggiano R, Bauersachs J, Bayes-Genis A, Borger MA, Budts W, Cikes M, Damman K, Delgado V, Dendale P, Dilaveris P, Drexel H, Ezekowitz J, Falk V, Fauchier L, Filippatos G, Fraser A, Frey N, Gale CP, Gustafsson F, Harris J, Iung B, Janssens S, Jessup M, Konradi A, Kotecha D, Lambrinou E, Lancellotti P, Landmesser U, Leclercq C, Lewis BS, Leyva F, Linhart A, Løchen ML, Lund LH, Mancini D, Masip J, Milicic D, Mueller C, Nef H, Nielsen JC, Neubeck L, Noutsias M, Petersen SE, Sonia Petronio A, Ponikowski P, Prescott E, Rakisheva A, Richter DJ, Schlyakhto E, Seferovic P, Senni M, Sitges M, Sousa-Uva M, Tocchetti CG, Touyz RM, Tschoepe C, Waltenberger J, Adamo M, Baumbach A, Böhm M, Burri H, Čelutkienė J, et alMcDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, Burri H, Butler J, Čelutkienė J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GMC, Ruschitzka F, Kathrine Skibelund A, de Boer RA, Christian Schulze P, Abdelhamid M, Aboyans V, Adamopoulos S, Anker SD, Arbelo E, Asteggiano R, Bauersachs J, Bayes-Genis A, Borger MA, Budts W, Cikes M, Damman K, Delgado V, Dendale P, Dilaveris P, Drexel H, Ezekowitz J, Falk V, Fauchier L, Filippatos G, Fraser A, Frey N, Gale CP, Gustafsson F, Harris J, Iung B, Janssens S, Jessup M, Konradi A, Kotecha D, Lambrinou E, Lancellotti P, Landmesser U, Leclercq C, Lewis BS, Leyva F, Linhart A, Løchen ML, Lund LH, Mancini D, Masip J, Milicic D, Mueller C, Nef H, Nielsen JC, Neubeck L, Noutsias M, Petersen SE, Sonia Petronio A, Ponikowski P, Prescott E, Rakisheva A, Richter DJ, Schlyakhto E, Seferovic P, Senni M, Sitges M, Sousa-Uva M, Tocchetti CG, Touyz RM, Tschoepe C, Waltenberger J, Adamo M, Baumbach A, Böhm M, Burri H, Čelutkienė J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gardner RS, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Piepoli MF, Price S, Rosano GMC, Ruschitzka F, Skibelund AK, ESC Scientific Document Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2021. [DOI: 10.1093/eurheartj/ehab368 order by 1-- gadu] [Show More Authors] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/10/2023] Open
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2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2021. [DOI: 10.1093/eurheartj/ehab368 order by 1-- #] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/10/2023] Open
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McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, Burri H, Butler J, Čelutkienė J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GMC, Ruschitzka F, Kathrine Skibelund A, de Boer RA, Christian Schulze P, Abdelhamid M, Aboyans V, Adamopoulos S, Anker SD, Arbelo E, Asteggiano R, Bauersachs J, Bayes-Genis A, Borger MA, Budts W, Cikes M, Damman K, Delgado V, Dendale P, Dilaveris P, Drexel H, Ezekowitz J, Falk V, Fauchier L, Filippatos G, Fraser A, Frey N, Gale CP, Gustafsson F, Harris J, Iung B, Janssens S, Jessup M, Konradi A, Kotecha D, Lambrinou E, Lancellotti P, Landmesser U, Leclercq C, Lewis BS, Leyva F, Linhart A, Løchen ML, Lund LH, Mancini D, Masip J, Milicic D, Mueller C, Nef H, Nielsen JC, Neubeck L, Noutsias M, Petersen SE, Sonia Petronio A, Ponikowski P, Prescott E, Rakisheva A, Richter DJ, Schlyakhto E, Seferovic P, Senni M, Sitges M, Sousa-Uva M, Tocchetti CG, Touyz RM, Tschoepe C, Waltenberger J, Adamo M, Baumbach A, Böhm M, Burri H, Čelutkienė J, et alMcDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, Burri H, Butler J, Čelutkienė J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GMC, Ruschitzka F, Kathrine Skibelund A, de Boer RA, Christian Schulze P, Abdelhamid M, Aboyans V, Adamopoulos S, Anker SD, Arbelo E, Asteggiano R, Bauersachs J, Bayes-Genis A, Borger MA, Budts W, Cikes M, Damman K, Delgado V, Dendale P, Dilaveris P, Drexel H, Ezekowitz J, Falk V, Fauchier L, Filippatos G, Fraser A, Frey N, Gale CP, Gustafsson F, Harris J, Iung B, Janssens S, Jessup M, Konradi A, Kotecha D, Lambrinou E, Lancellotti P, Landmesser U, Leclercq C, Lewis BS, Leyva F, Linhart A, Løchen ML, Lund LH, Mancini D, Masip J, Milicic D, Mueller C, Nef H, Nielsen JC, Neubeck L, Noutsias M, Petersen SE, Sonia Petronio A, Ponikowski P, Prescott E, Rakisheva A, Richter DJ, Schlyakhto E, Seferovic P, Senni M, Sitges M, Sousa-Uva M, Tocchetti CG, Touyz RM, Tschoepe C, Waltenberger J, Adamo M, Baumbach A, Böhm M, Burri H, Čelutkienė J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gardner RS, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Piepoli MF, Price S, Rosano GMC, Ruschitzka F, Skibelund AK, ESC Scientific Document Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2021. [DOI: 10.1093/eurheartj/ehab368 order by 8029-- -] [Show More Authors] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/10/2023] Open
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McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, Burri H, Butler J, Čelutkienė J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GMC, Ruschitzka F, Kathrine Skibelund A, de Boer RA, Christian Schulze P, Abdelhamid M, Aboyans V, Adamopoulos S, Anker SD, Arbelo E, Asteggiano R, Bauersachs J, Bayes-Genis A, Borger MA, Budts W, Cikes M, Damman K, Delgado V, Dendale P, Dilaveris P, Drexel H, Ezekowitz J, Falk V, Fauchier L, Filippatos G, Fraser A, Frey N, Gale CP, Gustafsson F, Harris J, Iung B, Janssens S, Jessup M, Konradi A, Kotecha D, Lambrinou E, Lancellotti P, Landmesser U, Leclercq C, Lewis BS, Leyva F, Linhart A, Løchen ML, Lund LH, Mancini D, Masip J, Milicic D, Mueller C, Nef H, Nielsen JC, Neubeck L, Noutsias M, Petersen SE, Sonia Petronio A, Ponikowski P, Prescott E, Rakisheva A, Richter DJ, Schlyakhto E, Seferovic P, Senni M, Sitges M, Sousa-Uva M, Tocchetti CG, Touyz RM, Tschoepe C, Waltenberger J, Adamo M, Baumbach A, Böhm M, Burri H, Čelutkienė J, et alMcDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, Burri H, Butler J, Čelutkienė J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GMC, Ruschitzka F, Kathrine Skibelund A, de Boer RA, Christian Schulze P, Abdelhamid M, Aboyans V, Adamopoulos S, Anker SD, Arbelo E, Asteggiano R, Bauersachs J, Bayes-Genis A, Borger MA, Budts W, Cikes M, Damman K, Delgado V, Dendale P, Dilaveris P, Drexel H, Ezekowitz J, Falk V, Fauchier L, Filippatos G, Fraser A, Frey N, Gale CP, Gustafsson F, Harris J, Iung B, Janssens S, Jessup M, Konradi A, Kotecha D, Lambrinou E, Lancellotti P, Landmesser U, Leclercq C, Lewis BS, Leyva F, Linhart A, Løchen ML, Lund LH, Mancini D, Masip J, Milicic D, Mueller C, Nef H, Nielsen JC, Neubeck L, Noutsias M, Petersen SE, Sonia Petronio A, Ponikowski P, Prescott E, Rakisheva A, Richter DJ, Schlyakhto E, Seferovic P, Senni M, Sitges M, Sousa-Uva M, Tocchetti CG, Touyz RM, Tschoepe C, Waltenberger J, Adamo M, Baumbach A, Böhm M, Burri H, Čelutkienė J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gardner RS, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Piepoli MF, Price S, Rosano GMC, Ruschitzka F, Skibelund AK, ESC Scientific Document Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2021. [DOI: 10.1093/eurheartj/ehab368 order by 8029-- #] [Show More Authors] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/10/2023] Open
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McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, Burri H, Butler J, Čelutkienė J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GMC, Ruschitzka F, Kathrine Skibelund A. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2021; 42:3599-3726. [PMID: 34447992 DOI: 10.1093/eurheartj/ehab368] [Citation(s) in RCA: 6970] [Impact Index Per Article: 1742.5] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, Burri H, Butler J, Čelutkienė J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GMC, Ruschitzka F, Kathrine Skibelund A, de Boer RA, Christian Schulze P, Abdelhamid M, Aboyans V, Adamopoulos S, Anker SD, Arbelo E, Asteggiano R, Bauersachs J, Bayes-Genis A, Borger MA, Budts W, Cikes M, Damman K, Delgado V, Dendale P, Dilaveris P, Drexel H, Ezekowitz J, Falk V, Fauchier L, Filippatos G, Fraser A, Frey N, Gale CP, Gustafsson F, Harris J, Iung B, Janssens S, Jessup M, Konradi A, Kotecha D, Lambrinou E, Lancellotti P, Landmesser U, Leclercq C, Lewis BS, Leyva F, Linhart A, Løchen ML, Lund LH, Mancini D, Masip J, Milicic D, Mueller C, Nef H, Nielsen JC, Neubeck L, Noutsias M, Petersen SE, Sonia Petronio A, Ponikowski P, Prescott E, Rakisheva A, Richter DJ, Schlyakhto E, Seferovic P, Senni M, Sitges M, Sousa-Uva M, Tocchetti CG, Touyz RM, Tschoepe C, Waltenberger J, Adamo M, Baumbach A, Böhm M, Burri H, Čelutkienė J, et alMcDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, Burri H, Butler J, Čelutkienė J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GMC, Ruschitzka F, Kathrine Skibelund A, de Boer RA, Christian Schulze P, Abdelhamid M, Aboyans V, Adamopoulos S, Anker SD, Arbelo E, Asteggiano R, Bauersachs J, Bayes-Genis A, Borger MA, Budts W, Cikes M, Damman K, Delgado V, Dendale P, Dilaveris P, Drexel H, Ezekowitz J, Falk V, Fauchier L, Filippatos G, Fraser A, Frey N, Gale CP, Gustafsson F, Harris J, Iung B, Janssens S, Jessup M, Konradi A, Kotecha D, Lambrinou E, Lancellotti P, Landmesser U, Leclercq C, Lewis BS, Leyva F, Linhart A, Løchen ML, Lund LH, Mancini D, Masip J, Milicic D, Mueller C, Nef H, Nielsen JC, Neubeck L, Noutsias M, Petersen SE, Sonia Petronio A, Ponikowski P, Prescott E, Rakisheva A, Richter DJ, Schlyakhto E, Seferovic P, Senni M, Sitges M, Sousa-Uva M, Tocchetti CG, Touyz RM, Tschoepe C, Waltenberger J, Adamo M, Baumbach A, Böhm M, Burri H, Čelutkienė J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gardner RS, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Piepoli MF, Price S, Rosano GMC, Ruschitzka F, Skibelund AK, ESC Scientific Document Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2021. [DOI: 10.1093/eurheartj/ehab368 order by 1-- -] [Show More Authors] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/10/2023] Open
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McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, Burri H, Butler J, Čelutkienė J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GMC, Ruschitzka F, Kathrine Skibelund A, de Boer RA, Christian Schulze P, Abdelhamid M, Aboyans V, Adamopoulos S, Anker SD, Arbelo E, Asteggiano R, Bauersachs J, Bayes-Genis A, Borger MA, Budts W, Cikes M, Damman K, Delgado V, Dendale P, Dilaveris P, Drexel H, Ezekowitz J, Falk V, Fauchier L, Filippatos G, Fraser A, Frey N, Gale CP, Gustafsson F, Harris J, Iung B, Janssens S, Jessup M, Konradi A, Kotecha D, Lambrinou E, Lancellotti P, Landmesser U, Leclercq C, Lewis BS, Leyva F, Linhart A, Løchen ML, Lund LH, Mancini D, Masip J, Milicic D, Mueller C, Nef H, Nielsen JC, Neubeck L, Noutsias M, Petersen SE, Sonia Petronio A, Ponikowski P, Prescott E, Rakisheva A, Richter DJ, Schlyakhto E, Seferovic P, Senni M, Sitges M, Sousa-Uva M, Tocchetti CG, Touyz RM, Tschoepe C, Waltenberger J, Adamo M, Baumbach A, Böhm M, Burri H, Čelutkienė J, et alMcDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, Burri H, Butler J, Čelutkienė J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GMC, Ruschitzka F, Kathrine Skibelund A, de Boer RA, Christian Schulze P, Abdelhamid M, Aboyans V, Adamopoulos S, Anker SD, Arbelo E, Asteggiano R, Bauersachs J, Bayes-Genis A, Borger MA, Budts W, Cikes M, Damman K, Delgado V, Dendale P, Dilaveris P, Drexel H, Ezekowitz J, Falk V, Fauchier L, Filippatos G, Fraser A, Frey N, Gale CP, Gustafsson F, Harris J, Iung B, Janssens S, Jessup M, Konradi A, Kotecha D, Lambrinou E, Lancellotti P, Landmesser U, Leclercq C, Lewis BS, Leyva F, Linhart A, Løchen ML, Lund LH, Mancini D, Masip J, Milicic D, Mueller C, Nef H, Nielsen JC, Neubeck L, Noutsias M, Petersen SE, Sonia Petronio A, Ponikowski P, Prescott E, Rakisheva A, Richter DJ, Schlyakhto E, Seferovic P, Senni M, Sitges M, Sousa-Uva M, Tocchetti CG, Touyz RM, Tschoepe C, Waltenberger J, Adamo M, Baumbach A, Böhm M, Burri H, Čelutkienė J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gardner RS, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Piepoli MF, Price S, Rosano GMC, Ruschitzka F, Skibelund AK, ESC Scientific Document Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2021. [DOI: 10.1093/eurheartj/ehab368 and 1880=1880] [Show More Authors] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/10/2023] Open
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McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, Burri H, Butler J, Čelutkienė J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GMC, Ruschitzka F, Kathrine Skibelund A, de Boer RA, Christian Schulze P, Abdelhamid M, Aboyans V, Adamopoulos S, Anker SD, Arbelo E, Asteggiano R, Bauersachs J, Bayes-Genis A, Borger MA, Budts W, Cikes M, Damman K, Delgado V, Dendale P, Dilaveris P, Drexel H, Ezekowitz J, Falk V, Fauchier L, Filippatos G, Fraser A, Frey N, Gale CP, Gustafsson F, Harris J, Iung B, Janssens S, Jessup M, Konradi A, Kotecha D, Lambrinou E, Lancellotti P, Landmesser U, Leclercq C, Lewis BS, Leyva F, Linhart A, Løchen ML, Lund LH, Mancini D, Masip J, Milicic D, Mueller C, Nef H, Nielsen JC, Neubeck L, Noutsias M, Petersen SE, Sonia Petronio A, Ponikowski P, Prescott E, Rakisheva A, Richter DJ, Schlyakhto E, Seferovic P, Senni M, Sitges M, Sousa-Uva M, Tocchetti CG, Touyz RM, Tschoepe C, Waltenberger J, Adamo M, Baumbach A, Böhm M, Burri H, Čelutkienė J, et alMcDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, Burri H, Butler J, Čelutkienė J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GMC, Ruschitzka F, Kathrine Skibelund A, de Boer RA, Christian Schulze P, Abdelhamid M, Aboyans V, Adamopoulos S, Anker SD, Arbelo E, Asteggiano R, Bauersachs J, Bayes-Genis A, Borger MA, Budts W, Cikes M, Damman K, Delgado V, Dendale P, Dilaveris P, Drexel H, Ezekowitz J, Falk V, Fauchier L, Filippatos G, Fraser A, Frey N, Gale CP, Gustafsson F, Harris J, Iung B, Janssens S, Jessup M, Konradi A, Kotecha D, Lambrinou E, Lancellotti P, Landmesser U, Leclercq C, Lewis BS, Leyva F, Linhart A, Løchen ML, Lund LH, Mancini D, Masip J, Milicic D, Mueller C, Nef H, Nielsen JC, Neubeck L, Noutsias M, Petersen SE, Sonia Petronio A, Ponikowski P, Prescott E, Rakisheva A, Richter DJ, Schlyakhto E, Seferovic P, Senni M, Sitges M, Sousa-Uva M, Tocchetti CG, Touyz RM, Tschoepe C, Waltenberger J, Adamo M, Baumbach A, Böhm M, Burri H, Čelutkienė J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gardner RS, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Piepoli MF, Price S, Rosano GMC, Ruschitzka F, Skibelund AK, ESC Scientific Document Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2021. [DOI: 10.1093/eurheartj/ehab368 order by 8029-- awyx] [Show More Authors] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/10/2023] Open
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Elsanhoury A, Nelki V, Kelle S, Van Linthout S, Tschöpe C. Epicardial Fat Expansion in Diabetic and Obese Patients With Heart Failure and Preserved Ejection Fraction-A Specific HFpEF Phenotype. Front Cardiovasc Med 2021; 8:720690. [PMID: 34604353 PMCID: PMC8484763 DOI: 10.3389/fcvm.2021.720690] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Accepted: 08/09/2021] [Indexed: 12/22/2022] Open
Abstract
Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome with diverse etiologies and pathophysiological factors. Obesity and type 2 diabetes mellitus (T2DM), conditions that coexist frequently, induce a cluster of metabolic and non-metabolic signaling derangements which are in favor to induce inflammation, fibrosis, myocyte stiffness, all hallmarks of HFpEF. In contrast to other HFpEF risk factors, obesity and T2DM are often associated with the generation of enlarged epicardial adipose tissue (EAT). EAT acts as an endocrine tissue that may exacerbate myocardial inflammation and fibrosis via various paracrine and vasocrine signals. In addition, an abnormally large EAT poses mechanical stress on the heart via pericardial restrain. HFpEF patients with enlarged EAT may belong to a unique phenotype that can benefit from specific EAT-targeted interventions, including life-style modifications and pharmacologically via statins and fat modifying anti-diabetics drugs; like metformin, sodium-glucose cotransporter 2 inhibitors, or glucagon-like peptide-1 receptor agonists, respectively.
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Affiliation(s)
- Ahmed Elsanhoury
- Berlin Institute of Health at Charite (BIH), Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Berlin, Germany
- German Center for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin, Germany
| | - Vivian Nelki
- Department of Cardiology, Campus Virchow Klinikum (CVK), Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Sebastian Kelle
- Department of Internal Medicine/Cardiology, German Heart Center Berlin, Berlin, Germany
| | - Sophie Van Linthout
- Berlin Institute of Health at Charite (BIH), Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Berlin, Germany
- German Center for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin, Germany
| | - Carsten Tschöpe
- Berlin Institute of Health at Charite (BIH), Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Berlin, Germany
- German Center for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin, Germany
- Department of Cardiology, Campus Virchow Klinikum (CVK), Charité Universitätsmedizin Berlin, Berlin, Germany
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