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Peng H, Yuan J, Wang Z, Mo B, Wang Y, Wang Y, Wang Q. NR4A3 prevents diabetes induced atrial cardiomyopathy by maintaining mitochondrial energy metabolism and reducing oxidative stress. EBioMedicine 2024; 106:105268. [PMID: 39098108 PMCID: PMC11334830 DOI: 10.1016/j.ebiom.2024.105268] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Revised: 07/18/2024] [Accepted: 07/23/2024] [Indexed: 08/06/2024] Open
Abstract
BACKGROUND Atrial cardiomyopathy (ACM) is responsible for atrial fibrillation (AF) and thromboembolic events. Diabetes mellitus (DM) is an important risk factor for ACM. However, the potential mechanism between ACM and DM remains elusive. METHODS Atrial tissue samples were obtained from patients diagnosed with AF or sinus rhythm (SR) to assess alterations in NR4A3 expression, and then two distinct animal models were generated by subjecting Nr4a3-/- mice and WT mice to a high-fat diet (HFD) and Streptozotocin (STZ), while db/db mice were administered AAV9-Nr4a3 or AAV9-ctrl. Subsequently, in vivo and in vitro experiments were conducted to assess the impact of NR4A3 on diabetes-induced atrial remodeling through electrophysiological, biological, and histological analyses. RNA sequencing (RNA-seq) and metabolomics analysis were employed to unravel the downstream mechanisms. FINDINGS The expression of NR4A3 was significantly decreased in atrial tissues of both AF patients and diabetic mice compared to their respective control groups. NR4A3 deficiency exacerbated atrial hypertrophy and atrial fibrosis, and increased susceptibility to pacing-induced AF. Conversely, overexpression of NR4A3 alleviated atrial structural remodeling and reduced AF induction rate. Mechanistically, we confirmed that NR4A3 improves mitochondrial energy metabolism and reduces oxidative stress injury by preserving the transcriptional expression of Sdha, thereby exerting a protective influence on atrial remodeling induced by diabetes. INTERPRETATION Our data confirm that NR4A3 plays a protective role in atrial remodeling caused by diabetes, so it may be a new target for treating ACM. FUNDING This study was supported by the major research program of National Natural Science Foundation of China (NSFC) No: 82370316 (to Q-S. W.), No. 81974041 (to Y-P. W.), and No. 82270447 (to Y-P. W.) and Fundation of Shanghai Hospital Development Center (No. SHDC2022CRD044 to Q-S. W.).
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Affiliation(s)
- Hong Peng
- Department of Cardiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China
| | - Jiali Yuan
- Department of Cardiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China
| | - Zhengshuai Wang
- Department of Cardiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China
| | - Binfeng Mo
- Department of Cardiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China
| | - Yihui Wang
- The Department of Radiology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Yuepeng Wang
- Department of Cardiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.
| | - Qunshan Wang
- Department of Cardiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.
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Wang Q, Yuan J, Shen H, Zhu Q, Chen B, Wang J, Zhu W, Yorek MA, Hall DD, Wang Z, Song LS. Calpain inhibition protects against atrial fibrillation by mitigating diabetes-associated atrial fibrosis and calcium handling dysfunction in type 2 diabetes mice. Heart Rhythm 2024; 21:1143-1151. [PMID: 38395244 DOI: 10.1016/j.hrthm.2024.02.036] [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: 12/06/2023] [Revised: 02/13/2024] [Accepted: 02/15/2024] [Indexed: 02/25/2024]
Abstract
BACKGROUND Diabetes mellitus (DM) is a major risk factor for atrial structural remodeling and atrial fibrillation (AF). Calpain activity is hypothesized to promote atrial remodeling and AF. OBJECTIVE The purpose of this study was to investigate the role of calpain in diabetes-associated AF, fibrosis, and calcium handling dysfunction. METHODS DM-associated AF was induced in wild-type (WT) mice and in mice overexpressing the calpain inhibitor calpastatin (CAST-OE) using high-fat diet feeding followed by low-dose streptozotocin injection (75 mg/kg). DM and AF outcomes were assessed by measuring blood glucose levels, fibrosis, and AF susceptibility during transesophageal atrial pacing. Intracellular Ca2+ transients, spontaneous Ca2+ release events, and intracellular T-tubule membranes were measured by in situ confocal microscopy. RESULTS WT mice with DM had significant hyperglycemia, atrial fibrosis, and AF susceptibility with increased atrial myocyte calpain activity and Ca2+ handling dysfunction relative to control treated animals. CAST-OE mice with DM had a similar level of hyperglycemia as diabetic WT littermates but lacked significant atrial fibrosis and AF susceptibility. DM-induced atrial calpain activity and downregulation of the calpain substrate junctophilin-2 were prevented by CAST-OE. Atrial myocytes of diabetic CAST-OE mice exhibited improved T-tubule membrane organization, Ca2+ handling, and reduced spontaneous Ca2+ release events compared to littermate controls. CONCLUSION This study confirmed that DM promotes calpain activation, atrial fibrosis, and AF in mice. CAST-OE effectively inhibits DM-induced calpain activation and reduces atrial remodeling and AF incidence through improved intracellular Ca2+ homeostasis. Our results support calpain inhibition as a potential therapy for preventing and treating AF in DM patients.
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Affiliation(s)
- Qing Wang
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; The Collaborative Innovation Center, Jining Medical University, Jining, Shandong, China; Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa
| | - Jinxiang Yuan
- The Collaborative Innovation Center, Jining Medical University, Jining, Shandong, China; Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa
| | - Hua Shen
- Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa; Department of Cardiovascular Surgery, Chinese PLA General Hospital, Beijing, China
| | - Qi Zhu
- Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa; Department of Pharmacology, School of Pharmacy, Nantong University, Nantong, Jiangsu, China
| | - Biyi Chen
- Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa
| | - Jinxi Wang
- Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa
| | - Weizhong Zhu
- Department of Pharmacology, School of Pharmacy, Nantong University, Nantong, Jiangsu, China
| | - Mark A Yorek
- Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa; Department of Veterans Affairs Iowa City Health Care System, Iowa City, Iowa; Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, Iowa
| | - Duane D Hall
- Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa
| | - Zhinong Wang
- Department of Cardiothoracic Surgery, Changzheng Hospital, Naval Medical University, Shanghai, China.
| | - Long-Sheng Song
- Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa; Department of Veterans Affairs Iowa City Health Care System, Iowa City, Iowa; Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, Iowa.
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Sarkar A, Fanous KI, Marei I, Ding H, Ladjimi M, MacDonald R, Hollenberg MD, Anderson TJ, Hill MA, Triggle CR. Repurposing Metformin for the Treatment of Atrial Fibrillation: Current Insights. Vasc Health Risk Manag 2024; 20:255-288. [PMID: 38919471 PMCID: PMC11198029 DOI: 10.2147/vhrm.s391808] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2024] [Accepted: 06/05/2024] [Indexed: 06/27/2024] Open
Abstract
Metformin is an orally effective anti-hyperglycemic drug that despite being introduced over 60 years ago is still utilized by an estimated 120 to 150 million people worldwide for the treatment of type 2 diabetes (T2D). Metformin is used off-label for the treatment of polycystic ovary syndrome (PCOS) and for pre-diabetes and weight loss. Metformin is a safe, inexpensive drug with side effects mostly limited to gastrointestinal issues. Prospective clinical data from the United Kingdom Prospective Diabetes Study (UKPDS), completed in 1998, demonstrated that metformin not only has excellent therapeutic efficacy as an anti-diabetes drug but also that good glycemic control reduced the risk of micro- and macro-vascular complications, especially in obese patients and thereby reduced the risk of diabetes-associated cardiovascular disease (CVD). Based on a long history of clinical use and an excellent safety record metformin has been investigated to be repurposed for numerous other diseases including as an anti-aging agent, Alzheimer's disease and other dementias, cancer, COVID-19 and also atrial fibrillation (AF). AF is the most frequently diagnosed cardiac arrythmia and its prevalence is increasing globally as the population ages. The argument for repurposing metformin for AF is based on a combination of retrospective clinical data and in vivo and in vitro pre-clinical laboratory studies. In this review, we critically evaluate the evidence that metformin has cardioprotective actions and assess whether the clinical and pre-clinical evidence support the use of metformin to reduce the risk and treat AF.
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Affiliation(s)
- Aparajita Sarkar
- Department of Medical Education, Weill Cornell Medicine-Qatar, Doha, Qatar
| | - Kareem Imad Fanous
- Department of Medical Education, Weill Cornell Medicine-Qatar, Doha, Qatar
| | - Isra Marei
- Department of Pharmacology & Medical Education, Weill Cornell Medicine- Qatar, Doha, Qatar
| | - Hong Ding
- Department of Pharmacology & Medical Education, Weill Cornell Medicine- Qatar, Doha, Qatar
| | - Moncef Ladjimi
- Department of Biochemistry & Medical Education, Weill Cornell Medicine-Qatar, Doha, Qatar
| | - Ross MacDonald
- Health Sciences Library, Weill Cornell Medicine-Qatar, Doha, Qatar
| | - Morley D Hollenberg
- Department of Physiology & Pharmacology, and Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Todd J Anderson
- Department of Cardiac Sciences and Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Michael A Hill
- Dalton Cardiovascular Research Center & Department of Medical Pharmacology & Physiology, School of Medicine, University of Missouri, Columbia, Missouri, USA
| | - Chris R Triggle
- Department of Pharmacology & Medical Education, Weill Cornell Medicine- Qatar, Doha, Qatar
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Ragavan N, Thavalam R, Moorthy S. The Effect of Glycemic Status on P Wave Dispersion. Cureus 2024; 16:e58233. [PMID: 38745813 PMCID: PMC11092425 DOI: 10.7759/cureus.58233] [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: 04/14/2024] [Indexed: 05/16/2024] Open
Abstract
Background and aim The growing number of people with diabetes mellitus (DM) across the world is a public health concern. The diabetes epidemic involves enormous health costs to the patients, their careers, and society at large. Cardiovascular diseases such as atrial fibrillation (AF) often develop in the diabetic population. An increase in the P wave dispersion (PWD) has been established as an independent risk factor for the occurrence of AF, hence the present study was conducted to establish a possible relationship between PWD and the glycemic status of the individual to predict the occurrence of AF ahead of clinical symptomology. Methodology A comparative cross-sectional study was conducted at a tertiary care hospital after obtaining approval from the institutional ethics committee and written consent of each study subject. The main steps included the selection and categorization of the study population based on their glycemic status, collection of demographic data, performing ECGs calculating PWD using digital calipers, and recording the data systematically for evaluation. Results In this study, 234 patients with a mean age of 53.3 ± 13.1 years were studied, of which 121 (51.7%) were male and 113 (48.29%) were female. The 234 patients were divided into four groups based on their glycemic status - 74 uncontrolled DM patients (31.62%), 51 type 2 DM (T2DM) patients (21.78%), 56 prediabetes patients (23.93%), and 53 patients in the control group (22.64%; not a known case of diabetes with normal HbA1c and fasting blood sugar (FBS) levels). Minimal correlation was observed between FBS with PWD (r value 0.175) and age with PWD (r value 0.161), but statistical significance was observed only between age and PWD (p-value 0.014). The difference in means between the four different study groups was found to be not statistically significant (p-value- 0.104); hence, no intergroup variation was noted. Conclusion Advancing age and higher fasting blood sugars have shown minimal correlation with widening P-wave dispersion. With further studies involving larger populations, this can be a promising aid in identifying PWD as a probable early predictor of atrial arrhythmias among diabetic patients.
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Affiliation(s)
- Niranjan Ragavan
- Internal Medicine, Sri Ramachandra Institute of Higher Education and Research, Chennai, IND
| | - Rida Thavalam
- Internal Medicine, Sri Ramachandra Institute of Higher Education and Research, Chennai, IND
| | - Swathy Moorthy
- Internal Medicine, Sri Ramachandra Institute of Higher Education and Research, Chennai, IND
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Luo J, Li Z, Qin X, Zhang X, Liu X, Zhang W, Xu W, Liu B, Wei Y. Association of stress hyperglycemia ratio with in-hospital new-onset atrial fibrillation and long-term outcomes in patients with acute myocardial infarction. Diabetes Metab Res Rev 2024; 40:e3726. [PMID: 37712510 DOI: 10.1002/dmrr.3726] [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: 12/03/2022] [Revised: 01/14/2023] [Accepted: 08/18/2023] [Indexed: 09/16/2023]
Abstract
AIMS To investigate the predictive value and prognostic impact of stress hyperglycemia ratio (SHR) for new-onset atrial fibrillation (NOAF) complicating acute myocardial infarction (AMI). MATERIALS AND METHODS This retrospective study included 2145 AMI patients without AF history between February 2014 and March 2018. SHR was calculated using fasting blood glucose (mmol/L)/[1.59*HbA1c (%)-2.59]. The association between SHR and post-MI NOAF was assessed with multivariable logistic regression analyses. The primary outcome was a composite of cardiac death, heart failure hospitalisation, recurrent MI, and ischaemic stroke (MACE). Cox regression-adjusted hazard ratios with 95% confidence intervals (CI) were estimated for MACE. RESULTS A total of 245 (11.4%) patients developed NOAF. In the multivariable logistic regression analyses, SHR (each 10% increase) was significantly associated with increased risks of NOAF in the whole population (OR: 1.05, 95% CI: 1.01-1.10), particularly in non-diabetic individuals (OR:1.08, 95% CI: 1.01-1.17). During a median follow-up of 2.7 years, 370 (18.5%) MACEs were recorded. The optimal cut-off value of SHR for MACE prediction was 1.119. Patients with both high SHR (≥1.119) and NOAF possessed the highest risk of MACE compared to those with neither high SHR nor NOAF after multivariable adjustment (HR: 2.18, 95% CI: 1.39-3.42), especially for diabetics (HR: 2.63, 95% CI: 1.41-4.91). Similar findings were observed using competing-risk models. CONCLUSIONS SHR is an independent predictor of post-MI NOAF in non-diabetic individuals. Diabetic patients with both high SHR and NOAF had the highest risk of MACE, suggesting that therapies targeting SHR may be considered in these patients. TRIAL REGISTRATION ClinicalTrials.gov, NCT03533543.
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Affiliation(s)
- Jiachen Luo
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Zhiqiang Li
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Xiaoming Qin
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Xingxu Zhang
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Xiangdong Liu
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Wenming Zhang
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Wei Xu
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Baoxin Liu
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Yidong Wei
- Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
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Hamed M, Morcos R, Elbadawi A, Osman A, Jneid H, Khalife W, Maini B, Khalili H. Percutaneous Left Atrial Appendage Closure Among Patients With Diabetes (Insights from a National Database). Am J Cardiol 2023; 202:144-150. [PMID: 37437355 DOI: 10.1016/j.amjcard.2023.06.054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2023] [Revised: 05/17/2023] [Accepted: 06/11/2023] [Indexed: 07/14/2023]
Abstract
Atrial fibrillation is a major risk factor for stroke. Left atrial appendage closure (LAAC) has emerged as an alternative to anticoagulation for patients with high risk of bleeding. Diabetes mellitus (DM) is associated with adverse events after cardiac procedures. We sought to compare procedural and hospital outcomes in patients who underwent LAAC with and without DM. The Nationwide Inpatient Database was queried for patients with atrial fibrillation who underwent LAAC between January 1, 2016, and December 31, 2019. The primary outcome was all adverse events that included in-hospital death, acute myocardial infarction, cardiac arrest, stroke, pericardial effusion, pericardial tamponade, pericardiocentesis, pericardial window, and postprocedural hemorrhage requiring blood transfusion. Analysis included 62,220 patients who underwent LAAC from 2016 to 2019; 34.9% of patients had DM. There was a slight increase in the percentage of patients who underwent LAAC who had DM during the study period, from 29.92% to 34.93%. In unadjusted and adjusted analysis, there was no significant difference in all adverse events between patients with and without DM who underwent LAAC (9.18% vs 8.77%, respectively, adjusted p = 0.63), and no difference in length of stay. Patients with DM have higher risk of acute kidney injury (3.75 vs 1.96%, p <0.001). This nationwide retrospective study demonstrates that DM is not associated with an increase in adverse event rates in patients who underwent LAAC.
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Affiliation(s)
- Mohamed Hamed
- Department of Internal Medicine, Florida Atlantic University, Boca Raton, Florida
| | - Ramez Morcos
- Division of Cardiology, Florida Atlantic University, Boca Raton, Florida
| | - Ayman Elbadawi
- Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Ahmed Osman
- Division of Cardiology, Broward Health, Fort Lauderdale, Florida
| | - Hani Jneid
- Division of Cardiology, University of Texas Medical Branch, Galveston, Texas
| | - Wissam Khalife
- Division of Cardiology, University of Texas Medical Branch, Galveston, Texas
| | - Brijeshwar Maini
- Division of Cardiology, Florida Atlantic University, Boca Raton, Florida
| | - Houman Khalili
- Division of Cardiology, Florida Atlantic University, Boca Raton, Florida; Department of Cardiac Services, Memorial Healthcare System, Hollywood, Florida.
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Chan CS, Lin FJ, Chen YC, Lin YK, Higa S, Chen SA, Chen YJ. Glucagon-like Peptide-1 Receptor Activation Reduces Pulmonary Vein Arrhythmogenesis and Regulates Calcium Homeostasis. Int J Mol Sci 2023; 24:13100. [PMID: 37685906 PMCID: PMC10488086 DOI: 10.3390/ijms241713100] [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: 06/26/2023] [Revised: 08/20/2023] [Accepted: 08/21/2023] [Indexed: 09/10/2023] Open
Abstract
Glucagon-like peptide-1 (GLP-1) receptor agonists are associated with reduced atrial fibrillation risk, but the mechanisms underlying this association remain unclear. The GLP-1 receptor agonist directly impacts cardiac Ca2+ homeostasis, which is crucial in pulmonary vein (PV, the initiator of atrial fibrillation) arrhythmogenesis. This study investigated the effects of the GLP-1 receptor agonist on PV electrophysiology and Ca2+ homeostasis and elucidated the potential underlying mechanisms. Conventional microelectrodes and whole-cell patch clamp techniques were employed in rabbit PV tissues and single PV cardiomyocytes before and after GLP-1 (7-36) amide, a GLP-1 receptor agonist. Evaluations were conducted both with and without pretreatment with H89 (10 μM, an inhibitor of protein kinase A, PKA), KN93 (1 μM, an inhibitor of Ca2+/calmodulin-dependent protein kinase II, CaMKII), and KB-R7943 (10 μM, an inhibitor of Na+/Ca2+ exchanger, NCX). Results showed that GLP-1 (7-36) amide (at concentrations of 1, 10, and 100 nM) reduced PV spontaneous activity in a concentration-dependent manner without affecting sinoatrial node electrical activity. In single-cell experiments, GLP-1 (7-36) amide (at 10 nM) reduced L-type Ca2+ current, NCX current, and late Na+ current in PV cardiomyocytes without altering Na+ current. Additionally, GLP-1 (7-36) amide (at 10 nM) increased sarcoplasmic reticulum Ca2+ content in PV cardiomyocytes. Furthermore, the antiarrhythmic effects of GLP-1 (7-36) amide on PV automaticity were diminished when pretreated with H89, KN93, or KB-R7943. This suggests that the GLP-1 receptor agonist may exert its antiarrhythmic potential by regulating PKA, CaMKII, and NCX activity, as well as modulating intracellular Ca2+ homeostasis, thereby reducing PV arrhythmogenesis.
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Affiliation(s)
- Chao-Shun Chan
- Division of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan; (C.-S.C.); (Y.-K.L.)
- Division of Cardiology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei Medical University, Taipei 11031, Taiwan
| | - Fong-Jhih Lin
- Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan;
- Department of Biomedical Engineering, National Defense Medical Center, Taipei 11490, Taiwan;
| | - Yao-Chang Chen
- Department of Biomedical Engineering, National Defense Medical Center, Taipei 11490, Taiwan;
| | - Yung-Kuo Lin
- Division of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan; (C.-S.C.); (Y.-K.L.)
- Division of Cardiology, Department of Internal Medicine, Wan-Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan
| | - Satoshi Higa
- Cardiac Electrophysiology and Pacing Laboratory, Division of Cardiovascular Medicine, Makiminato Central Hospital, Okinawa 9012131, Japan;
| | - Shih-Ann Chen
- Heart Rhythm Center, Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan;
- Institute of Clinical Medicine and Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei 11217, Taiwan
- Cardiovascular Center, Taichung Veterans General Hospital, Taichung 40705, Taiwan
| | - Yi-Jen Chen
- Division of Cardiology, Department of Internal Medicine, Wan-Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
- Cardiovascular Research Center, Wan-Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan
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Hu WS, Yu TS, Lin CL. Statin versus ezetimibe-statin for incident atrial fibrillation among patients with type 2 diabetes mellitus with acute coronary syndrome and acute ischemic stroke. Medicine (Baltimore) 2023; 102:e33907. [PMID: 37335632 DOI: 10.1097/md.0000000000033907] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/21/2023] Open
Abstract
The objective was to assess the role of the combination approach with ezetimibe 10 mg/simvastatin 20 mg versus atorvastatin 40 mg in predicting atrial fibrillation (AF) in type 2 diabetes mellitus patients with acute coronary syndrome and acute ischemic stroke. The authors formed a cohort of diabetic patients with extensive vascular diseases between 2000 and 2018 using data from the National Health Insurance Research Database in Taiwan. AF was the outcome of interest in this study. Cox proportional hazards regression analysis was performed to estimate the hazard ratios and 95% confidence intervals in the analysis. After controlling for sex, age, comorbidities and medications, the patients coexisting with type 2 diabetes mellitus, acute coronary syndrome and acute ischemic stroke with ezetimibe 10 mg/simvastatin 20 mg treatment were not significantly at risk of AF, compared to the patients with atorvastatin 40 mg treatment (adjusted hazard ratio, 0.85; 95% confidence interval, 0.52-1.38). A similar effect for AF risk between ezetimibe 10 mg/simvastatin 20 mg and atorvastatin 40 mg users was observed in the current investigation.
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Affiliation(s)
- Wei-Syun Hu
- School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan
- Division of Cardiovascular Medicine, Department of Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Teng-Shun Yu
- Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan
| | - Cheng-Li Lin
- Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan
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Batta A, Hatwal J, Batta A, Verma S, Sharma YP. Atrial fibrillation and coronary artery disease: An integrative review focusing on therapeutic implications of this relationship. World J Cardiol 2023; 15:229-243. [PMID: 37274376 PMCID: PMC10237004 DOI: 10.4330/wjc.v15.i5.229] [Citation(s) in RCA: 44] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2023] [Revised: 03/05/2023] [Accepted: 05/06/2023] [Indexed: 05/19/2023] Open
Abstract
The incidence of both atrial fibrillation (AF) and coronary artery disease (CAD) increases with advancing age. They share common risk factors and very often coexist. Evidence points to an intricate relationship between atrial tissue excitability and neuronal remodeling with ischemia at the microcirculatory level. In this review, we delineated this complex relationship, identified a common theme between the two, and discussed how the knowledge of this relationship translates into a positive and meaningful impact in patient management. Recent research indicates a high prevalence of CAD among AF patients undergoing coronary angiography. Further, the incidence of AF is much higher in those suffering from CAD compared to age-matched adults without CAD underlying this reciprocal relationship. CAD adversely affects AF by promoting progression via re-entry and increasing excitability of atrial tissue as a result of ischemia and electrical inhomogeneity. AF in turn accelerates atherosclerosis via endothelial dysfunctional and inflammation and together with enhanced thrombogenicity and hypercoagulability contribute to micro and macrothrombi throughout cardiovascular system. In a nutshell, the two form a vicious cycle wherein one disease promotes the other. Most AF recommendations focuses on rate/rhythm control and prevention of thromboembolism. Very few studies have discussed the importance of unmasking coexistent CAD and how the treatment of underlying ischemia will impact the burden of AF in these patients. Inflammation and endothelial dysfunction remain central to both disease processes and form a handsome therapeutic target in the management of the two diseases. The relationship between AF and CAD is complex and much more than mere coincidence. The two diseases share common risk factor and pathophysiology. Hence, it is impractical to treat them in isolation. Accordingly, we share the implications of managing underlying ischemia and inflammation to positively impact and improve quality of life among AF patients.
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Affiliation(s)
- Akash Batta
- Department of Cardiology, Dayanand Medical College and Hospital, Ludhiana 141001, Punjab, India
| | - Juniali Hatwal
- Department of Internal Medicine, Post Graduate Institute of Medical Education & Research, Chandigarh 160012, India
| | - Akshey Batta
- Department of Medicine and Surgery, Sohana Multi Super Specialty Hospital, Mohali 160062, Punjab, India
| | - Samman Verma
- Department of Cardiology, Post Graduate Institute of Medical Education & Research, Chandigarh 160012, India
| | - Yash Paul Sharma
- Department of Cardiology, Post Graduate Institute of Medical Education & Research, Chandigarh 160012, India
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Kim S, Park SY, Kim B, Min C, Cho W, Yon DK, Kim JY, Han KD, Rhee EJ, Lee WY, Rhee SY. Association between antidiabetic drugs and the incidence of atrial fibrillation in patients with type 2 diabetes: A nationwide cohort study in South Korea. Diabetes Res Clin Pract 2023; 198:110626. [PMID: 36933806 DOI: 10.1016/j.diabres.2023.110626] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Revised: 03/08/2023] [Accepted: 03/13/2023] [Indexed: 03/18/2023]
Abstract
BACKGROUND Although diabetes is a risk factor for atrial fibrillation (AF), studies on the AF risk according to the antidiabetic drugs are lacking. This study evaluated the effects of antidiabetic drugs on AF incidence in Korean patients with type 2 diabetes. METHODS We included 2,515,468 patients with type 2 diabetes from the Korean National Insurance Service database without a history of AF who underwent health check-ups between 2009 and 2012. Newly diagnosed AF incidence was recorded until December 2018 according to the main antidiabetic drug combinations used in the real world. RESULTS Of the patients included (mean age, 62 ± 11 years; 60 % men), 89,125 were newly diagnosed with AF. Metformin (MET) alone (hazard ratio [HR] 0.959, 95 % CI 0.935-0.985) and MET combination therapy (HR < 1) significantly decreased the risk of AF compared to the no-medication group. The antidiabetic drugs consistently showing a protective effect against AF incidence were MET (HR 0.977, 95 % CI 0.964-0.99) and thiazolidinedione (TZD; HR 0.926, 95 % CI 0.898-0.956), even after adjusting for various factors. Moreover, this protective effect was more remarkable with MET and TZD combination therapy (HR 0.802, 95 % CI 0.754-0.853) than with other drug combinations. In the subgroup analysis, the preventive effect of MET and TZD treatment against AF remained consistent, regardless of age, sex, duration, and diabetes severity. CONCLUSION The combination therapy of MET and TZD is the most effective antidiabetic drug for preventing AF in patients with type 2 diabetes.
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Affiliation(s)
- Sunyoung Kim
- Department of Family Medicine, Kyung Hee University College of Medicine, Kyung Hee University Medical Center, Seoul, Republic of Korea; Center for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Center, Seoul, Republic of Korea
| | - So Young Park
- Department of Endocrinology and Metabolism, Kyung Hee University College of Medicine, Kyung Hee University Medical Center, Seoul, Republic of Korea
| | - Bongseong Kim
- Department of Biostatistics, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Chanyang Min
- Center for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Center, Seoul, Republic of Korea
| | - Wonyoung Cho
- Center for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Center, Seoul, Republic of Korea
| | - Dong Keon Yon
- Center for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Center, Seoul, Republic of Korea
| | - Joo Young Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Hanil General Hospital, Seoul, Republic of Korea
| | - Kyung-Do Han
- Department of Biostatistics, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Eun-Jung Rhee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Won-Young Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Sang Youl Rhee
- Center for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Center, Seoul, Republic of Korea; Department of Endocrinology and Metabolism, Kyung Hee University College of Medicine, Kyung Hee University Medical Center, Seoul, Republic of Korea.
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11
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Syed T, Patel NR. How can atrial fibrillation be detected and treated effectively? TRENDS IN UROLOGY & MEN'S HEALTH 2023. [DOI: 10.1002/tre.898] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
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12
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Kishima H, Mine T, Fukuhara E, Kitagaki R, Asakura M, Ishihara M. Efficacy of Sodium-Glucose Cotransporter 2 Inhibitors on Outcomes After Catheter Ablation for Atrial Fibrillation. JACC Clin Electrophysiol 2022; 8:1393-1404. [PMID: 36424008 DOI: 10.1016/j.jacep.2022.08.004] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Revised: 07/19/2022] [Accepted: 08/05/2022] [Indexed: 11/06/2022]
Abstract
BACKGROUND Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have recently been a significant focus of attention because of their multiple pleiotropic effects. However, the impact of SGLT2i on atrial fibrillation (AF) remains unclear. OBJECTIVES The goal of this study was to examine the effects of SGLT2i on AF after catheter ablation (CA). METHODS This prospective, randomized controlled study compared the suppressive effect of SGLT2i vs dipeptidyl peptidase-4 inhibitors on AF recurrence after CA. Eighty AF patients with type 2 diabetes mellitus were randomized (by a computer-generated random sequence) to the tofogliflozin group (20 mg/d) or the anagliptin group (200 mg/d) stratified according to left atrial diameter and AF type (paroxysmal AF [PAF] or non-paroxysmal atrial fibrillation [PAF]) at screening. The primary outcome was AF recurrence at 12 months after CA. RESULTS Seventy patients were analyzed (mean age 70.3 ± 8.1 years; 48 male; 30 with paroxysmal AF; 38 tofogliflozin treated). Recurrent AF was detected in 24 (34.3%) of 70 patients, and the AF recurrence ratio was higher in the anagliptin group than in the tofogliflozin group (15 of 32 patients [47%] vs 9 of 38 patients [24%]; P = 0.0417). Moreover, univariate analysis revealed that compared with the nonrecurrence group (n = 46), the recurrence group (n = 24) had a higher prevalence rate of non-PAF, elevated brain natriuretic peptide, higher urinary albumin-creatinine ratio, lower rate of SGLT2i use, larger left atrial diameter, elevated E wave, lower left ventricular ejection fraction, and lower rate of cryoballoon pulmonary vein isolation. CONCLUSIONS Compared with anagliptin, tofogliflozin achieved greater suppression of AF recurrence after CA in patients with type 2 diabetes mellitus.
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Affiliation(s)
- Hideyuki Kishima
- Department of Cardiovascular and Renal Medicine, Hyogo College of Medicine, Nishinomiya, Japan; Internal Medicine, Kishima Hon-in Hospital, Yao, Japan.
| | - Takanao Mine
- Department of Cardiovascular and Renal Medicine, Hyogo College of Medicine, Nishinomiya, Japan
| | - Eiji Fukuhara
- Department of Cardiovascular and Renal Medicine, Hyogo College of Medicine, Nishinomiya, Japan
| | - Ryo Kitagaki
- Department of Cardiovascular and Renal Medicine, Hyogo College of Medicine, Nishinomiya, Japan
| | - Masanori Asakura
- Department of Cardiovascular and Renal Medicine, Hyogo College of Medicine, Nishinomiya, Japan
| | - Masaharu Ishihara
- Department of Cardiovascular and Renal Medicine, Hyogo College of Medicine, Nishinomiya, Japan
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13
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Gao X, Liu R, Wang P, Wang W, Zhao HQ. Relationship Between NT-proBNP Levels and Left Ventricular Ejection Fraction in Patients with Unstable Angina and Diabetes Mellitus and Preserved LVEF. Int Heart J 2022; 63:821-827. [DOI: 10.1536/ihj.22-160] [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: 11/18/2022]
Affiliation(s)
- Xiangyu Gao
- Department of Cardiology, Beijing Friendship Hospital, Capital Medical University
| | - Ruifeng Liu
- Department of Cardiology, Beijing Friendship Hospital, Capital Medical University
| | - Ping Wang
- Department of Cardiology, Beijing Friendship Hospital, Capital Medical University
| | - Wei Wang
- Department of Comprehensive Medicine, Beijing Friendship Hospital, Capital Medical University
| | - Hui-qiang Zhao
- Department of Cardiology, Beijing Friendship Hospital, Capital Medical University
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14
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Li J, Qi X, Ramos KS, Lanters E, Keijer J, de Groot N, Brundel B, Zhang D. Disruption of Sarcoplasmic Reticulum-Mitochondrial Contacts Underlies Contractile Dysfunction in Experimental and Human Atrial Fibrillation: A Key Role of Mitofusin 2. J Am Heart Assoc 2022; 11:e024478. [PMID: 36172949 DOI: 10.1161/jaha.121.024478] [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] [Indexed: 11/16/2022]
Abstract
Background Atrial fibrillation (AF) is the most common and progressive tachyarrhythmia. Diabetes is a common risk factor for AF. Recent research findings revealed that microtubule network disruption underlies AF. The microtubule network mediates the contact between sarcoplasmic reticulum and mitochondria, 2 essential organelles for normal cardiomyocyte function. Therefore, disruption of the microtubule network may impair sarcoplasmic reticulum and mitochondrial contacts (SRMCs) and subsequently cardiomyocyte function. The current study aims to determine whether microtubule-mediated SRMCs disruption underlies diabetes-associated AF. Methods and Results Tachypacing (mimicking AF) and high glucose (mimicking diabetes) significantly impaired contractile function in HL-1 cardiomyocytes (loss of calcium transient) and Drosophila (reduced heart rate and increased arrhythmia), both of which were prevented by microtubule stabilizers. Furthermore, both tachypacing and high glucose significantly reduced SRMCs and the key SRMC tether protein mitofusin 2 (MFN2) and resulted in consequent mitochondrial dysfunction, all of which were prevented by microtubule stabilizers. In line with pharmacological interventions with microtubule stabilizers, cardiac-specific knockdown of MFN2 induced arrhythmia in Drosophila and overexpression of MFN2 prevented tachypacing- and high glucose-induced contractile dysfunction in HL-1 cardiomyocytes and/or Drosophila. Consistently, SRMCs/MFN2 levels were significantly reduced in right atrial appendages of patients with persistent AF compared with control patients, which was aggravated in patients with diabetes. Conclusions SRMCs may play a critical role in clinical AF, especially diabetes-related AF. Furthermore, SRMCs can be regulated by microtubules and MFN2, which represent novel potential therapeutic targets for AF.
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Affiliation(s)
- Jin Li
- Department of Physiology Amsterdam UMC location Vrije Universiteit Amsterdam Amsterdam The Netherlands.,Amsterdam Cardiovascular Sciences Heart Failure and Arrhythmias Amsterdam The Netherlands.,Division of Metabolism, Endocrinology and Diabetes and Department of Internal Medicine University of Michigan Medical School Ann Arbor MI
| | - Xi Qi
- Human and Animal Physiology Wageningen University Wageningen The Netherlands
| | - Kennedy S Ramos
- Department of Physiology Amsterdam UMC location Vrije Universiteit Amsterdam Amsterdam The Netherlands.,Amsterdam Cardiovascular Sciences Heart Failure and Arrhythmias Amsterdam The Netherlands
| | - Eva Lanters
- Department of Cardiology Erasmus Medical Center Rotterdam The Netherlands
| | - Jaap Keijer
- Human and Animal Physiology Wageningen University Wageningen The Netherlands
| | - Natasja de Groot
- Department of Cardiology Erasmus Medical Center Rotterdam The Netherlands
| | - Bianca Brundel
- Department of Physiology Amsterdam UMC location Vrije Universiteit Amsterdam Amsterdam The Netherlands.,Amsterdam Cardiovascular Sciences Heart Failure and Arrhythmias Amsterdam The Netherlands
| | - Deli Zhang
- Department of Physiology Amsterdam UMC location Vrije Universiteit Amsterdam Amsterdam The Netherlands.,Human and Animal Physiology Wageningen University Wageningen The Netherlands
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15
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Lkhagva B, Lee TW, Lin YK, Chen YC, Chung CC, Higa S, Chen YJ. Disturbed Cardiac Metabolism Triggers Atrial Arrhythmogenesis in Diabetes Mellitus: Energy Substrate Alternate as a Potential Therapeutic Intervention. Cells 2022; 11:cells11182915. [PMID: 36139490 PMCID: PMC9497243 DOI: 10.3390/cells11182915] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Revised: 09/10/2022] [Accepted: 09/16/2022] [Indexed: 11/20/2022] Open
Abstract
Atrial fibrillation (AF) is the most common type of sustained arrhythmia in diabetes mellitus (DM). Its morbidity and mortality rates are high, and its prevalence will increase as the population ages. Despite expanding knowledge on the pathophysiological mechanisms of AF, current pharmacological interventions remain unsatisfactory; therefore, novel findings on the underlying mechanism are required. A growing body of evidence suggests that an altered energy metabolism is closely related to atrial arrhythmogenesis, and this finding engenders novel insights into the pathogenesis of the pathophysiology of AF. In this review, we provide comprehensive information on the mechanistic insights into the cardiac energy metabolic changes, altered substrate oxidation rates, and mitochondrial dysfunctions involved in atrial arrhythmogenesis, and suggest a promising advanced new therapeutic approach to treat patients with AF.
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Affiliation(s)
- Baigalmaa Lkhagva
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
| | - Ting-Wei Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan
| | - Yung-Kuo Lin
- Division of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
| | - Yao-Chang Chen
- Department of Biomedical Engineering, National Defense Medical Center, Taipei 11490, Taiwan
| | - Cheng-Chih Chung
- Division of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
| | - Satoshi Higa
- Cardiac Electrophysiology and Pacing Laboratory, Division of Cardiovascular Medicine, Makiminato Central Hospital, Okinawa 901-2131, Japan
| | - Yi-Jen Chen
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
- Cardiovascular Research Center, Wan-Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan
- Correspondence:
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16
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Shi W, Qin M, Wu S, Xu K, Zheng Q, Liu X. Usefulness of Triglyceride-glucose index for detecting prevalent atrial fibrillation in a type 2 diabetic population. Postgrad Med 2022; 134:820-828. [DOI: 10.1080/00325481.2022.2124088] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/14/2022]
Affiliation(s)
- Wenrui Shi
- Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 Huaihai West Road, Shanghai, China
| | - Mu Qin
- Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 Huaihai West Road, Shanghai, China
| | - Shaohui Wu
- Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 Huaihai West Road, Shanghai, China
| | - Kai Xu
- Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 Huaihai West Road, Shanghai, China
| | - Qidong Zheng
- Department of Cardiology, Yuhuan Second People’s Hospital, 18 Changle Road, Yuhuan, Zhejiang, China
| | - Xu Liu
- Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 Huaihai West Road, Shanghai, China
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17
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Inflammasome Signaling in Atrial Fibrillation. J Am Coll Cardiol 2022; 79:2349-2366. [DOI: 10.1016/j.jacc.2022.03.379] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 03/29/2022] [Accepted: 03/30/2022] [Indexed: 12/26/2022]
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18
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Markers of Inflammation, Oxidative Stress, and Fibrosis in Patients with Atrial Fibrillation. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2022; 2022:4556671. [PMID: 35651726 PMCID: PMC9150993 DOI: 10.1155/2022/4556671] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Revised: 05/01/2022] [Accepted: 05/05/2022] [Indexed: 11/17/2022]
Abstract
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in clinical practice. The pathogenesis of AF is linked to inflammatory reaction and oxidative stress, which leads to fibrosis of the atria and progression of the disease. The purpose of this study was to define the role of several biomarkers of inflammation, fibrosis, and oxidative stress (OxS). We included 75 patients with paroxysmal/persistent AF, who were admitted for electrical cardioversion or pulmonary vein isolation (PVI). High-sensitivity C-reactive protein (hsCRP), galectin-3 (Gal-3), myeloperoxidase (MPO), oxidized low-density lipoprotein (oxLDL), and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured before the procedures. We compared the results with those of 75 healthy age-, sex-, and blood pressure-matched individuals. The patients were followed up for 1 year after the intervention to establish the recurrence of AF and its association with the measured markers. Patients with AF had higher MPO (52.6 vs. 36.2 ng/ml, p < 0.001) and NT-proBNP (209.0 vs. 28.0 pg/ml, p < 0.001) compared to healthy subjects. Also, they showed significantly higher levels of hsCRP (1.5 vs. 1.1 mg/l, p = 0.001) and Gal-3 (11.4 vs. 9.7 mg/l, p = 0.003), while there was no difference found in oxLDL (71.5 vs. 71.7 U/l, p = 0.449). MPO (OR = 1.012, p = 0.014), hsCRP (OR = 1.265, p = 0.026), and weight (OR = 1.029, p = 0.013) were independently associated with AF in a multivariable logistic regression analysis. Patients with successful maintenance of sinus rhythm (SR) for one year had lower baseline MPO (40.5 vs. 84.3 ng/ml, p = 0.005) and NT-proBNP (127.5 vs. 694.0 pg/ml, p < 0.001) compared to patients with recurrent AF episodes, but there was no difference in hsCRP, Gal-3, or oxLDL between them. MPO (OR = 0.985, p = 0.010) was independently associated with AF recurrence during the follow-up period when adjusted for cofounders. Patients with AF had increased markers of inflammation and fibrosis, while there was no increase detected in the OxS marker oxLDL. MPO was independently associated with AF in a multivariate model. Inflammatory and fibrotic mechanisms are important factors in electrical and structural remodelling progress in the atria of patients with AF.
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19
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Peng Z, Zhao R, Liu Y, Yang Y, Yang X, Hua K. Effect of Preablation Glycemic Control on Outcomes of Atrial Fibrillation Patients With Diabetes Mellitus Following Valvular Surgery Combined With the Cox-Maze IV Procedure. Front Cardiovasc Med 2022; 9:898642. [PMID: 35647051 PMCID: PMC9130630 DOI: 10.3389/fcvm.2022.898642] [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: 03/17/2022] [Accepted: 04/22/2022] [Indexed: 12/04/2022] Open
Abstract
Background This study was performed to assess the effect of preablation glycemic control on atrial fibrillation recurrence rates after heart valve surgery concomitant with Cox-Maze IV ablation. Methods Twelve-month preablation trends in glycemic control were studied. Recurrence and clinical outcome data were obtained during a mean follow-up period of 36.7 ± 23.3 months postablation. Results Higher glycated hemoglobin (HbA1c) at the time of ablation was associated with higher postablation recurrence rates. The cumulative atrial fibrillation recurrence-free survival of patients with HbA1c ≥7.5% at the time of operation at 12, 24, 36 and 48 months was 97.1, 78.3, 54.2, and 36.3%, respectively (P < 0.001), and 100, 84.9, 37.2, and 16.2% for patients who preoperatively had an upward trend in HbA1c, respectively (P < 0.001). Conclusion Maintaining a downward trend in HbA1c during the 12-month period before the operation and an HbA1c value < 7.5% at the time of the operation reduced the recurrence of AF among patients who underwent heart valve surgery concomitant with the Cox-Maze IV procedure.
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Affiliation(s)
- Zhan Peng
- Department of Cardiovascular Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Rui Zhao
- National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yuhua Liu
- Department of Cardiovascular Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Yunxiao Yang
- Department of Cardiovascular Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Xiubin Yang
- Department of Cardiovascular Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
- *Correspondence: Xiubin Yang
| | - Kun Hua
- Department of Cardiovascular Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
- Kun Hua
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20
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Way KL, Birnie D, Blanchard C, Wells G, Dorian P, Jorstad HT, Daha IC, Suskin N, Oh P, Parkash R, Poirier P, Prince SA, Tulloch H, Pipe AL, Hans H, Wilson J, Comeau K, Vidal-Almela S, Terada T, Reed JL. The Physical Activity Levels and Sitting Time of Adults Living With Atrial Fibrillation: The CHAMPLAIN-AF Study. CJC Open 2022; 4:449-465. [PMID: 35607489 PMCID: PMC9123363 DOI: 10.1016/j.cjco.2022.01.004] [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: 09/15/2021] [Accepted: 01/06/2022] [Indexed: 11/28/2022] Open
Abstract
Background The primary goal of this study was to determine the time spent completing moderate-to-vigorous intensity physical activity (MVPA) among adults with atrial fibrillation (AF). Secondary aims examined MVPA and sitting time (ST) by AF subtypes (ie, paroxysmal, persistent, long-standing persistent, and permanent) and associations between MVPA or ST and knowledge, task self-efficacy, and outcome expectations. Methods An observational study was conducted in the Champlain region of Ontario, Canada. AF patients completed a survey to determine MVPA and ST using the Short-Form International Physical Activity Questionnaire. Results A total of 619 patients (66% male; median age 65 years [95% CI 64-67 years]) completed the survey. Median MVPA and ST were 100 (60-120) min/wk and 6 (5-6) h/d; 56% of patients were not meeting the Canadian 24H Movement Guidelines. Most patients (54%) did not know/were unsure of the MVPA recommendations, yet 72% thought physical activity should be part of AF management. Positive correlations were found between higher MVPA levels and the following: (i) speaking to a healthcare professional about engaging in physical activity for managing AF (ρ = 0.108, P = 0.017); (ii) greater confidence regarding ability to perform physical activity and muscle-strengthening exercise (ρ = 0.421, P < 0.01); and (iii) patient agreement that AF would be better managed if they were active (ρ = 0.205, P < 0.01). Conclusions Many AF patients do not meet the MVPA recommendations, which may be due to lack of physical activity knowledge. Exercise professionals may help educate patients on the benefits of physical activity, improve task-self efficacy, and integrate MVPA into patient lifestyles.
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Affiliation(s)
- Kimberley L. Way
- Exercise Physiology and Cardiovascular Health Lab, Division of Cardiac Prevention and Rehabilitation, University of Ottawa Heart Institute, Ottawa, Ontario, Canada
- Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong, Victoria, Australia
| | - David Birnie
- Arrhythmia Service, Division of Cardiology, Faculty of Medicine, Department of Medicine, University of Ottawa Heart Institute, Ottawa, Ontario, Canada
| | | | - George Wells
- School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Paul Dorian
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Harald T. Jorstad
- Heart Centre, Department of Cardiology, Amsterdam University Medical Centre, Amsterdam, The Netherlands
| | - Ioana C. Daha
- Department of Cardiology, Colentina Clinical Hospital, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Neville Suskin
- Lawson Heath Research Institute, Department of Medicine, Division of Cardiology, Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada
| | - Paul Oh
- University Health Network, Toronto Rehabilitation Institute, Toronto, Ontario, Canada
| | - Ratika Parkash
- Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
| | - Paul Poirier
- Faculty of Pharmacy, Université Laval, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec City, Quebec, Canada
| | - Stephanie A. Prince
- School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
- Centre for Surveillance and Applied Research, Public Health Agency of Canada, Ottawa, Ontario, Canada
| | - Heather Tulloch
- Division of Cardiac Prevention and Rehabilitation, University of Ottawa Heart Institute, Ottawa, Ontario, Canada
- Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Andrew L. Pipe
- Division of Cardiac Prevention and Rehabilitation, University of Ottawa Heart Institute, Ottawa, Ontario, Canada
- Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Harleen Hans
- Exercise Physiology and Cardiovascular Health Lab, Division of Cardiac Prevention and Rehabilitation, University of Ottawa Heart Institute, Ottawa, Ontario, Canada
| | - Janet Wilson
- Exercise Physiology and Cardiovascular Health Lab, Division of Cardiac Prevention and Rehabilitation, University of Ottawa Heart Institute, Ottawa, Ontario, Canada
- Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Katelyn Comeau
- Exercise Physiology and Cardiovascular Health Lab, Division of Cardiac Prevention and Rehabilitation, University of Ottawa Heart Institute, Ottawa, Ontario, Canada
- School of Human Kinetics, Faculty of Health Sciences, University of Ottawa, Ottawa, Ontario, Canada
| | - Sol Vidal-Almela
- Exercise Physiology and Cardiovascular Health Lab, Division of Cardiac Prevention and Rehabilitation, University of Ottawa Heart Institute, Ottawa, Ontario, Canada
- School of Human Kinetics, Faculty of Health Sciences, University of Ottawa, Ottawa, Ontario, Canada
- Institut du Savoir Montfort, Hôpital Montfort, Ottawa, Ontario, Canada
| | - Tasuku Terada
- Exercise Physiology and Cardiovascular Health Lab, Division of Cardiac Prevention and Rehabilitation, University of Ottawa Heart Institute, Ottawa, Ontario, Canada
| | - Jennifer L. Reed
- Exercise Physiology and Cardiovascular Health Lab, Division of Cardiac Prevention and Rehabilitation, University of Ottawa Heart Institute, Ottawa, Ontario, Canada
- School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
- School of Human Kinetics, Faculty of Health Sciences, University of Ottawa, Ottawa, Ontario, Canada
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21
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Papazoglou AS, Kartas A, Moysidis DV, Tsagkaris C, Papadakos SP, Bekiaridou A, Samaras A, Karagiannidis E, Papadakis M, Giannakoulas G. Glycemic control and atrial fibrillation: an intricate relationship, yet under investigation. Cardiovasc Diabetol 2022; 21:39. [PMID: 35287684 PMCID: PMC8922816 DOI: 10.1186/s12933-022-01473-0] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Accepted: 02/25/2022] [Indexed: 12/26/2022] Open
Abstract
Atrial fibrillation (AF) and diabetes mellitus (DM) constitute two major closely inter-related chronic cardiovascular disorders whose concurrent prevalence rates are steadily increasing. Although, the pathogenic mechanisms behind the AF and DM comorbidity are still vague, it is now clear that DM precipitates AF occurrence. DM also affects the clinical course of established AF; it is associated with significant increase in the incidence of stroke, AF recurrence, and cardiovascular mortality. The impact of DM on AF management and prognosis has been adequately investigated. However, evidence on the relative impact of glycemic control using glycated hemoglobin levels is scarce. This review assesses up-to-date literature on the association between DM and AF. It also highlights the usefulness of glycated hemoglobin measurement for the prediction of AF and AF-related adverse events. Additionally, this review evaluates current anti-hyperglycemic treatment in the context of AF, and discusses AF-related decision-making in comorbid DM. Finally, it quotes significant remaining questions and sets some future strategies with the potential to effectively deal with this prevalent comorbidity.
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Affiliation(s)
- Andreas S Papazoglou
- First Department of Cardiology, AHEPA University Hospital, Aristotle University of Thessaloniki, St. Kiriakidi 1, 54636, Thessaloniki, Greece.,Athens Naval Hospital, Athens, Greece
| | - Anastasios Kartas
- First Department of Cardiology, AHEPA University Hospital, Aristotle University of Thessaloniki, St. Kiriakidi 1, 54636, Thessaloniki, Greece
| | - Dimitrios V Moysidis
- First Department of Cardiology, AHEPA University Hospital, Aristotle University of Thessaloniki, St. Kiriakidi 1, 54636, Thessaloniki, Greece
| | | | - Stavros P Papadakos
- First Department of Pathology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Alexandra Bekiaridou
- First Department of Cardiology, AHEPA University Hospital, Aristotle University of Thessaloniki, St. Kiriakidi 1, 54636, Thessaloniki, Greece
| | - Athanasios Samaras
- First Department of Cardiology, AHEPA University Hospital, Aristotle University of Thessaloniki, St. Kiriakidi 1, 54636, Thessaloniki, Greece
| | - Efstratios Karagiannidis
- First Department of Cardiology, AHEPA University Hospital, Aristotle University of Thessaloniki, St. Kiriakidi 1, 54636, Thessaloniki, Greece
| | - Marios Papadakis
- University Hospital Witten-Herdecke, University of Witten-Herdecke, Heusnerstrasse 40, 42283, Wuppertal, Germany.
| | - George Giannakoulas
- First Department of Cardiology, AHEPA University Hospital, Aristotle University of Thessaloniki, St. Kiriakidi 1, 54636, Thessaloniki, Greece
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22
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Xu J, Sun Y, Gong D, Fan Y. Impact of preexisting diabetes mellitus on cardiovascular and all-cause mortality in patients with atrial fibrillation: A meta-analysis. Front Endocrinol (Lausanne) 2022; 13:921159. [PMID: 35979438 PMCID: PMC9376236 DOI: 10.3389/fendo.2022.921159] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2022] [Accepted: 07/01/2022] [Indexed: 12/02/2022] Open
Abstract
OBJECTIVE To determine the impact of preexisting diabetes mellitus on cardiovascular and all-cause mortality in patients with atrial fibrillation (AF) by conducting a meta-analysis. METHODS PubMed and Embase databases were comprehensively searched for relevant studies publishing until May 19, 2022. Cohort studies or post-hoc analyses of clinical trials that investigated the association of diabetes mellitus with cardiovascular or all-cause mortality in AF patients were included. RESULTS A total of 21 studies with 526,136 AF patients were identified. The pooled prevalence of diabetes mellitus in patients with AF was 26%. The summary multivariable-adjusted risk ratio (RR) of all-cause mortality was 1.37 (95% confidence intervals [CIs] 1.23-1.53) for patients with diabetes versus those without diabetes. Moreover, diabetes mellitus was also associated with an increased risk of cardiovascular mortality (RR 1.46; 95% CI 1.34-1.58). Stratified analyses suggested that the impact of diabetes on all-cause and cardiovascular mortality was consistently observed in each named subgroup. CONCLUSION The presence of diabetes mellitus in patients with AF is associated with an increased risk of cardiovascular and all-cause mortality, even after adjustment for important confounding factors.
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Affiliation(s)
- Juan Xu
- Department of Oncology, Ganyu District People’s Hospital of Lianyungang City, Lianyungang, China
| | - Yimeng Sun
- Institute of Molecular Biology and Translational Medicine, The Affiliated People’s Hospital, Jiangsu University, Zhenjiang, China
| | - Dandan Gong
- Institute of Molecular Biology and Translational Medicine, The Affiliated People’s Hospital, Jiangsu University, Zhenjiang, China
- *Correspondence: Yu Fan, ; Dandan Gong,
| | - Yu Fan
- Institute of Molecular Biology and Translational Medicine, The Affiliated People’s Hospital, Jiangsu University, Zhenjiang, China
- *Correspondence: Yu Fan, ; Dandan Gong,
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23
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Alijla F, Buttia C, Reichlin T, Razvi S, Minder B, Wilhelm M, Muka T, Franco OH, Bano A. Association of diabetes with atrial fibrillation types: a systematic review and meta-analysis. Cardiovasc Diabetol 2021; 20:230. [PMID: 34876114 PMCID: PMC8653594 DOI: 10.1186/s12933-021-01423-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Accepted: 11/21/2021] [Indexed: 01/10/2023] Open
Abstract
Background Atrial fibrillation (AF) is a common arrhythmia classified as paroxysmal and non-paroxysmal. Non-paroxysmal AF is associated with an increased risk of complications. Diabetes contributes to AF initiation, yet its role in AF maintenance is unclear. We conducted a systematic review and meta-analysis to summarize the evidence regarding the association of diabetes with AF types. Methods We searched 5 databases for observational studies investigating the association of diabetes with the likelihood of an AF type (vs another type) in humans. Study quality was evaluated using the Newcastle–Ottawa Scale. Studies classifying AF types as paroxysmal (reference) and non-paroxysmal were pooled in a meta-analysis using random effects models. Results Of 1997 articles we identified, 20 were included in our systematic review. The population sample size ranged from 64 to 9816 participants with mean age ranging from 40 to 75 years and percentage of women from 24.8 to 100%. The quality of studies varied from poor (60%) to fair (5%) to good (35%). In the systematic review, 8 studies among patients with AF investigated the cross-sectional association of diabetes with non-paroxysmal AF (vs paroxysmal) of which 6 showed a positive association and 2 showed no association. Fourteen studies investigated the longitudinal association of diabetes with “more sustained” AF types (vs “less sustained”) of which 2 showed a positive association and 12 showed no association. In the meta-analysis of cross-sectional studies, patients with AF and diabetes were 1.31-times more likely to have non-paroxysmal AF than those without diabetes [8 studies; pooled OR (95% CI), 1.31 (1.13–1.51), I2 = 82.6%]. The meta-analysis of longitudinal studies showed that for patients with paroxysmal AF, diabetes is associated with 1.32-times increased likelihood of progression to non-paroxysmal AF [five studies; pooled OR (95% CI), 1.32 (1.07–1.62); I2 = 0%]. Conclusions Our findings suggest that diabetes is associated with an increased likelihood of non-paroxysmal AF rather than paroxysmal AF. However, further high quality studies are needed to replicate these findings, adjust for potential confounders, elucidate mechanisms linking diabetes to non-paroxysmal AF, and assess the impact of antidiabetic medications on AF types. These strategies could eventually help decrease the risk of non-paroxysmal AF among patients with diabetes. Supplementary Information The online version contains supplementary material available at 10.1186/s12933-021-01423-2.
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Affiliation(s)
- Fadi Alijla
- Institute of Social and Preventive Medicine (ISPM), University of Bern, Mittelstrasse 43, 3012, Bern, Switzerland
| | - Chepkoech Buttia
- Institute of Social and Preventive Medicine (ISPM), University of Bern, Mittelstrasse 43, 3012, Bern, Switzerland
| | - Tobias Reichlin
- Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Salman Razvi
- Department of Endocrinology, Gateshead Health NHS Foundation Trust, Gateshead, UK.,Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
| | - Beatrice Minder
- Public Health and Primary Care Library, University Library of Bern, University of Bern, Bern, Switzerland
| | - Matthias Wilhelm
- Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Taulant Muka
- Institute of Social and Preventive Medicine (ISPM), University of Bern, Mittelstrasse 43, 3012, Bern, Switzerland
| | - Oscar H Franco
- Institute of Social and Preventive Medicine (ISPM), University of Bern, Mittelstrasse 43, 3012, Bern, Switzerland
| | - Arjola Bano
- Institute of Social and Preventive Medicine (ISPM), University of Bern, Mittelstrasse 43, 3012, Bern, Switzerland. .,Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
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24
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Wei Y, Cui M, Liu S, Yu H, Feng J, Gao W, Li L. Increased hemoglobin A1c level associates with low left atrial appendage flow velocity in patients of atrial fibrillation. Nutr Metab Cardiovasc Dis 2021; 31:3176-3183. [PMID: 34629254 DOI: 10.1016/j.numecd.2021.07.024] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 07/15/2021] [Accepted: 07/23/2021] [Indexed: 11/29/2022]
Abstract
BACKGROUND AND AIMS High hemoglobin A1c (HbAlc) level is associated with increased cardiovascular disease risk and thromboembolic events [1]. The study sought to explored the association between HbAlc and left atrial appendage flow velocity (LAAV) among non-valvular atrial fibrillation (AF) patients. METHODS AND RESULTS A total of 249 consecutive non-valvular AF patients who underwent transesophageal echocardiography (TEE) were divided into two subgroups according to the median of LAAV level (<45 cm/s, ≥45 cm/s). Blood samples and other baseline clinical data of all patients were collected and analyzed. The low LAAV group included 126 patients and the high LAAV group included 123 patients. Patients in the low LAAV group were older and had a higher percentage of persistent AF, chronic heart failure, and higher CHA2DS2-VASc score (P < 0.05). HbAlc level in the low LAAV group was significantly higher than the high LAAV group [6.1 (5.7-6.5)% vs 5.9 (5.6-6.2)%, P = 0.010]. The low LAAV group had larger left atrial diameter (LAD), left atrial area (LAA), higher left atrial pressure (LAP), and lower left ventricular ejection fraction (LVEF) (P < 0.05). Spearman rank correlation analysis showed that the HbAlc level was negatively correlated with LAAV (r = -0.211, P = 0.001). Multivariate analysis indicated that female gender (OR = 2.233, 95% CI 1.110-4.492, P = 0.024), persistent AF (OR = 6.610, 95% CI 3.109-14.052, P < 0.001), and HbAlc (OR = 1.903, 95% CI 1.092-3.317, P = 0.023) were independent factors that associated with low LAAV in AF patients. CONCLUSION Increased HbAlc level is associated with decreased LAAV and may reflect a low contractile function of the left atrial appendage.
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Affiliation(s)
- Ying Wei
- Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Beijing, 100191, China; Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health, Beijing, 100191, China; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, 100191, China; Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing, 100191, China
| | - Ming Cui
- Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Beijing, 100191, China; Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health, Beijing, 100191, China; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, 100191, China; Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing, 100191, China
| | - Shuwang Liu
- Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Beijing, 100191, China; Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health, Beijing, 100191, China; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, 100191, China; Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing, 100191, China
| | - Haiyi Yu
- Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Beijing, 100191, China; Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health, Beijing, 100191, China; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, 100191, China; Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing, 100191, China
| | - Jieli Feng
- Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Beijing, 100191, China; Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health, Beijing, 100191, China; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, 100191, China; Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing, 100191, China
| | - Wei Gao
- Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Beijing, 100191, China; Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health, Beijing, 100191, China; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, 100191, China; Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing, 100191, China
| | - Lei Li
- Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Beijing, 100191, China; Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health, Beijing, 100191, China; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, 100191, China; Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing, 100191, China.
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25
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Gallego M, Zayas-Arrabal J, Alquiza A, Apellaniz B, Casis O. Electrical Features of the Diabetic Myocardium. Arrhythmic and Cardiovascular Safety Considerations in Diabetes. Front Pharmacol 2021; 12:687256. [PMID: 34305599 PMCID: PMC8295895 DOI: 10.3389/fphar.2021.687256] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Accepted: 06/15/2021] [Indexed: 12/20/2022] Open
Abstract
Diabetes is a chronic metabolic disease characterized by hyperglycemia in the absence of treatment. Among the diabetes-associated complications, cardiovascular disease is the major cause of mortality and morbidity in diabetic patients. Diabetes causes a complex myocardial dysfunction, referred as diabetic cardiomyopathy, which even in the absence of other cardiac risk factors results in abnormal diastolic and systolic function. Besides mechanical abnormalities, altered electrical function is another major feature of the diabetic myocardium. Both type 1 and type 2 diabetic patients often show cardiac electrical remodeling, mainly a prolonged ventricular repolarization visible in the electrocardiogram as a lengthening of the QT interval duration. The underlying mechanisms at the cellular level involve alterations on the expression and activity of several cardiac ion channels and their associated regulatory proteins. Consequent changes in sodium, calcium and potassium currents collectively lead to a delay in repolarization that can increase the risk of developing life-threatening ventricular arrhythmias and sudden death. QT duration correlates strongly with the risk of developing torsade de pointes, a form of ventricular tachycardia that can degenerate into ventricular fibrillation. Therefore, QT prolongation is a qualitative marker of proarrhythmic risk, and analysis of ventricular repolarization is therefore required for the approval of new drugs. To that end, the Thorough QT/QTc analysis evaluates QT interval prolongation to assess potential proarrhythmic effects. In addition, since diabetic patients have a higher risk to die from cardiovascular causes than individuals without diabetes, cardiovascular safety of the new antidiabetic drugs must be carefully evaluated in type 2 diabetic patients. These cardiovascular outcome trials reveal that some glucose-lowering drugs actually reduce cardiovascular risk. The mechanism of cardioprotection might involve a reduction of the risk of developing arrhythmia.
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Affiliation(s)
- Mónica Gallego
- Department of Physiology, Faculty of Pharmacy, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, Spain
| | - Julián Zayas-Arrabal
- Department of Physiology, Faculty of Pharmacy, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, Spain
| | - Amaia Alquiza
- Department of Physiology, Faculty of Pharmacy, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, Spain
| | - Beatriz Apellaniz
- Department of Physiology, Faculty of Pharmacy, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, Spain
| | - Oscar Casis
- Department of Physiology, Faculty of Pharmacy, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, Spain
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Zhang Z, Zhang X, Meng L, Gong M, Li J, Shi W, Qiu J, Yang Y, Zhao J, Suo Y, Liang X, Wang X, Tse G, Jiang N, Li G, Zhao Y, Liu T. Pioglitazone Inhibits Diabetes-Induced Atrial Mitochondrial Oxidative Stress and Improves Mitochondrial Biogenesis, Dynamics, and Function Through the PPAR-γ/PGC-1α Signaling Pathway. Front Pharmacol 2021; 12:658362. [PMID: 34194324 PMCID: PMC8237088 DOI: 10.3389/fphar.2021.658362] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Accepted: 04/16/2021] [Indexed: 12/06/2022] Open
Abstract
Background: Oxidative stress contributes to adverse atrial remodeling in diabetes mellitus. This remodeling can be prevented by the PPAR-γ agonist pioglitazone via its antioxidant and anti-inflammatory effects. In this study, we examined the molecular mechanisms underlying the protective effects of pioglitazone on atrial remodeling in a rabbit model of diabetes. Methods: Rabbits were randomly divided into control, diabetic, and pioglitazone-treated diabetic groups. Echocardiographic, hemodynamic, and electrophysiological parameters were measured. Serum PPAR-γ levels, serum and tissue oxidative stress and inflammatory markers, mitochondrial morphology, reactive oxygen species (ROS) production rate, respiratory function, and mitochondrial membrane potential (MMP) levels were measured. Protein expression of the pro-fibrotic marker TGF-β1, the PPAR-γ coactivator-1α (PGC-1α), and the mitochondrial proteins (biogenesis-, fusion-, and fission-related proteins) was measured. HL-1 cells were transfected with PGC-1α small interfering RNA (siRNA) to determine the underlying mechanisms of pioglitazone improvement of mitochondrial function under oxidative stress. Results: The diabetic group demonstrated a larger left atrial diameter and fibrosis area than the controls, which were associated with a higher incidence of inducible atrial fibrillation (AF). The lower serum PPAR-γ level was associated with lower PGC-1α and higher NF-κB and TGF-β1 expression. Lower mitochondrial biogenesis (PGC-1α, NRF1, and TFAM)-, fusion (Opa1 and Mfn1)-, and fission (Drp1)-related proteins were detected. Mitochondrial swelling, higher mitochondrial ROS, lower respiratory control rate, and lower MMP were observed. The pioglitazone group showed a reversal of structural remodeling and a lower incidence of inducible AF, which were associated with higher PPAR-γ and PGC-1α. The pioglitazone group had lower NF-κB and TGF-β1 expression levels, whereas biogenesis-, fusion-, and fission-related protein expression was higher. Further, mitochondrial structure and function were improved. In HL-1 cells, PGC-1α siRNA transfection blunted the effect of pioglitazone on Mn-SOD protein expression and MMP collapse in H2O2-treated cells. Conclusion: Diabetes mellitus induces adverse atrial structural, electrophysiological remodeling, and mitochondrial damage and dysfunction. Pioglitazone prevented these abnormalities through the PPAR-γ/PGC-1α pathway.
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Affiliation(s)
- Zhiwei Zhang
- Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, China
| | - Xiaowei Zhang
- Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, China
| | - Lei Meng
- Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, China
| | - Mengqi Gong
- Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, China
| | - Jian Li
- Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, China
| | - Wen Shi
- Department of Gastroenterology, The First Affiliated Hospital of Xi’an Jiao Tong University, Shanxi, China
| | - Jiuchun Qiu
- Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, China
| | - Yajuan Yang
- Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, China
| | - Jianping Zhao
- Department of Cardiology, Tianjin Hospital, Tianjin, China
| | - Ya Suo
- Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, China
| | - Xue Liang
- Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, China
| | - Xinghua Wang
- Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, China
| | - Gary Tse
- Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, China
| | - Ning Jiang
- Tianjin Key Laboratory of Exercise Physiology and Sports Medicine, Department of Health and Exercise Science, Tianjin University of Sport, Tianjin, China
| | - Guangping Li
- Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, China
| | - Yungang Zhao
- Tianjin Key Laboratory of Exercise Physiology and Sports Medicine, Department of Health and Exercise Science, Tianjin University of Sport, Tianjin, China
| | - Tong Liu
- Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, China
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Dogdus M, Dindas F, Akhan O, Yenercag M, Yildirim A, Abacioglu OO, Kilic S. Impaired left atrial strain in the presence of interatrial block in patients with type 2 diabetes mellitus. Int J Cardiovasc Imaging 2021; 37:2127-2134. [PMID: 33956284 DOI: 10.1007/s10554-021-02278-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Accepted: 05/04/2021] [Indexed: 10/21/2022]
Abstract
Type 2 diabetes mellitus (T2DM) is one of the most common chronic diseases, and is a risk factor for atrial cardiomyopathy. Interatrial block (IAB), as a predictor of AF, is correlated with the extent of LA fibrosis in the process of atrial cardiomyopathy. We have not encountered any study evaluating LA and LV functions with 3D-STE in the presence of IAB in the T2DM patients. The purpose of the present study was to compare the LA and LV myocardial functions in patients with T2DM with and without IAB by 3D-STE. A total of 175 consecutive patients with T2DM who were examined at outpatient clinics were enrolled in the study (85 patients with IAB and 90 patients without IAB). Surface 12-lead standard electrocardiograms (ECGs) were recorded. Clinical characteristics and laboratory values of the patients were obtained. Conventional 2D echocardiographic and 3D-STE analyses were performed. The mean age of the patients was 59 ± 8.7 years, and 112 (64%) of the patients were female. The LAS-r and LAS-active were significantly decreased in the IAB (+) group than in the IAB (-) group. Statistically significant strong negative linear correlations were observed between P-wave duration and 3D-LA strain values. Our results indicate that there is an impairment in LA myocardial dynamics in the presence of IAB in T2DM patients. According to these findings, we can say that it will be useful to evaluate the LA functions at the preclinical stage in the presence of IAB in patients with T2DM, when considering ischemic cardiovascular and cerebral events.
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Affiliation(s)
- Mustafa Dogdus
- Department of Cardiology, Training and Research Hospital, Usak University, 64100, Uşak, Turkey.
| | - Ferhat Dindas
- Department of Cardiology, Training and Research Hospital, Usak University, 64100, Uşak, Turkey
| | - Onur Akhan
- Department of Cardiology, Bilecik State Hospital, 11040, Bilecik, Turkey
| | - Mustafa Yenercag
- Department of Cardiology, Training and Research Hospital, Ordu University, 52200, Ordu, Turkey
| | - Arafat Yildirim
- Department of Cardiology, Adana Training and Research Hospital, University of Health Sciences, 01060, Adana, Turkey
| | - Ozge Ozcan Abacioglu
- Department of Cardiology, Adana Training and Research Hospital, University of Health Sciences, 01060, Adana, Turkey
| | - Salih Kilic
- Department of Cardiology, Adana Training and Research Hospital, University of Health Sciences, 01060, Adana, Turkey
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Varma N, Cygankiewicz I, Turakhia M, Heidbuchel H, Hu Y, Chen LY, Couderc J, Cronin EM, Estep JD, Grieten L, Lane DA, Mehra R, Page A, Passman R, Piccini J, Piotrowicz E, Piotrowicz R, Platonov PG, Ribeiro AL, Rich RE, Russo AM, Slotwiner D, Steinberg JS, Svennberg E. 2021 ISHNE/HRS/EHRA/APHRS collaborative statement on mHealth in Arrhythmia Management: Digital Medical Tools for Heart Rhythm Professionals: From the International Society for Holter and Noninvasive Electrocardiology/Heart Rhythm Society/European Heart Rhythm Association/Asia Pacific Heart Rhythm Society. J Arrhythm 2021; 37:271-319. [PMID: 33850572 PMCID: PMC8022003 DOI: 10.1002/joa3.12461] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Accepted: 08/03/2020] [Indexed: 02/06/2023] Open
Abstract
This collaborative statement from the International Society for Holter and Noninvasive Electrocardiology/Heart Rhythm Society/European Heart Rhythm Association/Asia Pacific Heart Rhythm Society describes the current status of mobile health ("mHealth") technologies in arrhythmia management. The range of digital medical tools and heart rhythm disorders that they may be applied to and clinical decisions that may be enabled are discussed. The facilitation of comorbidity and lifestyle management (increasingly recognized to play a role in heart rhythm disorders) and patient self-management are novel aspects of mHealth. The promises of predictive analytics but also operational challenges in embedding mHealth into routine clinical care are explored.
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Affiliation(s)
| | | | | | | | - Yufeng Hu
- Taipei Veterans General HospitalTaipeiTaiwan
| | | | | | | | | | | | | | | | - Alex Page
- University of RochesterRochesterNYUSA
| | - Rod Passman
- Northwestern University Feinberg School of MedicineChicagoILUSA
| | | | | | | | | | - Antonio Luiz Ribeiro
- Faculdade de MedicinaCentro de TelessaúdeHospital das Clínicasand Departamento de Clínica MédicaUniversidade Federal de Minas GeraisBelo HorizonteBrazil
| | | | | | - David Slotwiner
- Cardiology DivisionNewYork‐Presbyterian Queensand School of Health Policy and ResearchWeill Cornell MedicineNew YorkNYUSA
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Vrachatis DA, Papathanasiou KA, Kossyvakis C, Giotaki SG, Raisakis K, Iliodromitis KE, Reimers B, Stefanini GG, Cleman M, Sianos G, Lansky A, Deftereos SG, Giannopoulos G. Atrial fibrillation risk in patients suffering from type I diabetes mellitus. A review of clinical and experimental evidence. Diabetes Res Clin Pract 2021; 174:108724. [PMID: 33647332 DOI: 10.1016/j.diabres.2021.108724] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2020] [Revised: 01/31/2021] [Accepted: 02/09/2021] [Indexed: 12/12/2022]
Abstract
Atrial fibrillation (AF) and diabetes mellitus (DM) are commonly encountered in clinical practice. Although, the long term macrovascular and microvascular sequela of DM are well validated, the association between the less prevalent type 1 DM (T1DM) and atrial arrhythmogenesis is poorly understood. In the present review we highlight the current experimental and clinical data addressing this complex interaction. Animal studies support that T1DM, characterized by insulin deficiency and glycemic variability, impairs phosphatidylinositol 3‑kinase (PI3K)/protein kinase B signaling pathway. This pathway holds a central role in atrial electrical and structural remodeling responsible for arrhythmia initiation and maintenance. The molecular ''footprint'' of T1DM in atrial myocytes seems to involve a state of increased oxidative stress, impaired glucose transportation, ionic channel dysregulation and eventually fibrosis. On the contrary only a few clinical studies have examined the role of T1DM as an independent risk factor for AF development, and are discussed here. Further research is needed to solidify the real magnitude of this association and to investigate the clinical implications of PI3K molecular signaling pathway in atrial fibrillation management.
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Affiliation(s)
- Dimitrios A Vrachatis
- Humanitas Clinical and Research Center IRCCS, Milan, Italy; National and Kapodistrian University of Athens, Athens, Greece
| | | | | | | | | | | | | | | | - Michael Cleman
- Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA
| | - George Sianos
- Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Alexandra Lansky
- Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA
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Oláh A, Barta BA, Sayour AA, Ruppert M, Virág-Tulassay E, Novák J, Varga ZV, Ferdinandy P, Merkely B, Radovits T. Balanced Intense Exercise Training Induces Atrial Oxidative Stress Counterbalanced by the Antioxidant System and Atrial Hypertrophy That Is Not Associated with Pathological Remodeling or Arrhythmogenicity. Antioxidants (Basel) 2021; 10:antiox10030452. [PMID: 33803975 PMCID: PMC7999710 DOI: 10.3390/antiox10030452] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Revised: 03/10/2021] [Accepted: 03/11/2021] [Indexed: 12/16/2022] Open
Abstract
Although regular exercise training is associated with cardiovascular benefits, the increased risk of atrial arrhythmias has been observed after vigorous exercise and has been related to oxidative stress. We aimed at investigating exercise-induced atrial remodeling in a rat model of an athlete’s heart and determining sex-specific differences. Age-matched young adult rats were divided into female exercised, female control, male exercised, and male control groups. After exercised animals completed a 12-week-long swim training protocol, echocardiography and in vivo cardiac electrophysiologic investigation were performed. Additionally, atrial histological and gene expression analyses were carried out. Post-mortem atrial weight data and histological examination confirmed marked atrial hypertrophy. We found increased atrial gene expression of antioxidant enzymes along with increased nitro-oxidative stress. No gene expression alteration was found regarding markers of pathological remodeling, apoptotic, proinflammatoric, and profibrotic processes. Exercise training was associated with a prolonged right atrial effective refractory period. We could not induce arrhythmias by programmed stimulation in any groups. We found decreased expression of potassium channels. Female gender was associated with lower profibrotic expression and collagen density. Long-term, balanced exercise training-induced atrial hypertrophy is not associated with harmful electrical remodeling, and no inflammatory or profibrotic response was observed in the atrium of exercised rats.
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Affiliation(s)
- Attila Oláh
- Heart and Vascular Center, Semmelweis University; Városmajor str. 68, 1122 Budapest, Hungary; (B.A.B.); (A.A.S.); (M.R.); (E.V.-T.); (B.M.); (T.R.)
- Correspondence: ; Tel.: +36-1-458-6810; Fax: +36-1-458-6842
| | - Bálint András Barta
- Heart and Vascular Center, Semmelweis University; Városmajor str. 68, 1122 Budapest, Hungary; (B.A.B.); (A.A.S.); (M.R.); (E.V.-T.); (B.M.); (T.R.)
| | - Alex Ali Sayour
- Heart and Vascular Center, Semmelweis University; Városmajor str. 68, 1122 Budapest, Hungary; (B.A.B.); (A.A.S.); (M.R.); (E.V.-T.); (B.M.); (T.R.)
| | - Mihály Ruppert
- Heart and Vascular Center, Semmelweis University; Városmajor str. 68, 1122 Budapest, Hungary; (B.A.B.); (A.A.S.); (M.R.); (E.V.-T.); (B.M.); (T.R.)
| | - Eszter Virág-Tulassay
- Heart and Vascular Center, Semmelweis University; Városmajor str. 68, 1122 Budapest, Hungary; (B.A.B.); (A.A.S.); (M.R.); (E.V.-T.); (B.M.); (T.R.)
| | - Julianna Novák
- HCEMM-SU Cardiometabolic Immunology Research Group, Semmelweis University; Nagyvárad tér 4, 1089 Budapest, Hungary; (J.N.); (Z.V.V.)
| | - Zoltán V. Varga
- HCEMM-SU Cardiometabolic Immunology Research Group, Semmelweis University; Nagyvárad tér 4, 1089 Budapest, Hungary; (J.N.); (Z.V.V.)
- Department of Pharmacology and Pharmacotherapy, Semmelweis University; Nagyvárad tér 4, 1089 Budapest, Hungary;
| | - Péter Ferdinandy
- Department of Pharmacology and Pharmacotherapy, Semmelweis University; Nagyvárad tér 4, 1089 Budapest, Hungary;
- Pharmahungary Group, 6722 Szeged, Hungary
| | - Béla Merkely
- Heart and Vascular Center, Semmelweis University; Városmajor str. 68, 1122 Budapest, Hungary; (B.A.B.); (A.A.S.); (M.R.); (E.V.-T.); (B.M.); (T.R.)
| | - Tamás Radovits
- Heart and Vascular Center, Semmelweis University; Városmajor str. 68, 1122 Budapest, Hungary; (B.A.B.); (A.A.S.); (M.R.); (E.V.-T.); (B.M.); (T.R.)
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Varma N, Cygankiewicz I, Turakhia M, Heidbuchel H, Hu Y, Chen LY, Couderc J, Cronin EM, Estep JD, Grieten L, Lane DA, Mehra R, Page A, Passman R, Piccini J, Piotrowicz E, Piotrowicz R, Platonov PG, Ribeiro AL, Rich RE, Russo AM, Slotwiner D, Steinberg JS, Svennberg E. 2021 ISHNE/ HRS/ EHRA/ APHRS collaborative statement on mHealth in Arrhythmia Management: Digital Medical Tools for Heart Rhythm Professionals: From the International Society for Holter and Noninvasive Electrocardiology/Heart Rhythm Society/European Heart Rhythm Association/Asia Pacific Heart Rhythm Society. Ann Noninvasive Electrocardiol 2021; 26:e12795. [PMID: 33513268 PMCID: PMC7935104 DOI: 10.1111/anec.12795] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Accepted: 08/03/2020] [Indexed: 02/06/2023] Open
Abstract
This collaborative statement from the International Society for Holter and Noninvasive Electrocardiology/ Heart Rhythm Society/ European Heart Rhythm Association/ Asia Pacific Heart Rhythm Society describes the current status of mobile health ("mHealth") technologies in arrhythmia management. The range of digital medical tools and heart rhythm disorders that they may be applied to and clinical decisions that may be enabled are discussed. The facilitation of comorbidity and lifestyle management (increasingly recognized to play a role in heart rhythm disorders) and patient self-management are novel aspects of mHealth. The promises of predictive analytics but also operational challenges in embedding mHealth into routine clinical care are explored.
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Affiliation(s)
| | | | | | | | - Yufeng Hu
- Taipei Veterans General HospitalTaipeiTaiwan
| | | | | | | | | | | | | | | | - Alex Page
- University of RochesterRochesterNYUSA
| | - Rod Passman
- Northwestern University Feinberg School of MedicineChicagoILUSA
| | | | | | | | | | - Antonio Luiz Ribeiro
- Faculdade de MedicinaCentro de Telessaúde, Hospital das Clínicas, and Departamento de Clínica MédicaUniversidade Federal de Minas GeraisBelo HorizonteBrazil
| | | | | | - David Slotwiner
- Cardiology DivisionNewYork‐Presbyterian Queens, and School of Health Policy and ResearchWeill Cornell MedicineNew YorkNYUSA
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Varma N, Cygankiewicz I, Turakhia M, Heidbuchel H, Hu Y, Chen LY, Couderc J, Cronin EM, Estep JD, Grieten L, Lane DA, Mehra R, Page A, Passman R, Piccini J, Piotrowicz E, Piotrowicz R, Platonov PG, Ribeiro AL, Rich RE, Russo AM, Slotwiner D, Steinberg JS, Svennberg E. 2021 ISHNE / HRS / EHRA / APHRS Collaborative Statement on mHealth in Arrhythmia Management: Digital Medical Tools for Heart Rhythm Professionals: From the International Society for Holter and Noninvasive Electrocardiology / Heart Rhythm Society / European Heart Rhythm Association / Asia Pacific Heart Rhythm Society. EUROPEAN HEART JOURNAL. DIGITAL HEALTH 2021; 2:7-48. [PMID: 36711170 PMCID: PMC9708018 DOI: 10.1093/ehjdh/ztab001] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
This collaborative statement from the International Society for Holter and Noninvasive Electrocardiology / Heart Rhythm Society / European Heart Rhythm Association / Asia Pacific Heart Rhythm Society describes the current status of mobile health ("mHealth") technologies in arrhythmia management. The range of digital medical tools and heart rhythm disorders that they may be applied to and clinical decisions that may be enabled are discussed. The facilitation of comorbidity and lifestyle management (increasingly recognized to play a role in heart rhythm disorders) and patient self-management are novel aspects of mHealth. The promises of predictive analytics but also operational challenges in embedding mHealth into routine clinical care are explored.
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Affiliation(s)
| | | | | | - Hein Heidbuchel
- Antwerp University and University Hospital, Antwerp, Belgium
| | - Yufeng Hu
- Taipei Veterans General Hospital, Taipei, Taiwan
| | | | | | | | | | | | | | | | - Alex Page
- University of Rochester, Rochester, NY, USA
| | - Rod Passman
- Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | | | | | | | | | - Antonio Luiz Ribeiro
- Faculdade de Medicina, Centro de Telessaúde, Hospital das Clínicas, and Departamento de Clínica Médica, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | | | - Andrea M Russo
- Cooper Medical School of Rowan University, Camden, NJ, USA
| | - David Slotwiner
- Cardiology Division, NewYork-Presbyterian Queens, and School of Health, Policy and Research, Weill Cornell Medicine, New York, NY, USA
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Activation of NADPH oxidase mediates mitochondrial oxidative stress and atrial remodeling in diabetic rabbits. Life Sci 2021; 272:119240. [PMID: 33600862 DOI: 10.1016/j.lfs.2021.119240] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Revised: 02/05/2021] [Accepted: 02/13/2021] [Indexed: 01/05/2023]
Abstract
AIMS The mechanisms of atrial fibrillation (AF) in diabetes mellitus (DM) involve a complex interplay between increased oxidative stress, mitochondrial dysfunction and atrial remodeling. In this study, we examined the effects of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation on mitochondrial oxidative stress and atrial remodeling in a rabbit model of diabetes mellitus (DM). MAIN METHODS Healthy rabbits were selected and randomly divided into control, diabetic and apocynin administration group. Parameters of echocardiography, atrial electrophysiology, oxidative stress and mitochondrial function were compared between the different groups. KEY FINDINGS Compared to the control group, the DM group showed higher activity of NADPH oxidase, increased oxidative stress, larger left atrial diameter, a reduction in atrial mean conduction velocity. These findings were associated with increased interstitial fibrosis of the atria and higher atrial fibrillation (AF) inducibility. Moreover, atrial ultrastructure and mitochondrial function such as the mitochondrial respiratory control rate (RCR) were impaired. NADPH oxidase inhibition using the pharmacological agent apocynin improved these changes. SIGNIFICANCE NADPH oxidase activity plays an important role in mitochondrial oxidative stress, which is associated with AF inducibility by promoting adverse atrial remodeling. The NADPH oxidase inhibitor apocynin can prevent these pathological changes and may be a potential drug for AF treatment.
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Cintra FD, Figueiredo MJDO. Atrial Fibrillation (Part 1): Pathophysiology, Risk Factors, and Therapeutic Basis. Arq Bras Cardiol 2021; 116:129-139. [PMID: 33566977 PMCID: PMC8159512 DOI: 10.36660/abc.20200485] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2020] [Accepted: 09/09/2020] [Indexed: 01/14/2023] Open
Abstract
A fibrilação atrial é a arritmia sustentada mais comum na prática clínica com predileção pelas faixas etárias mais avançadas. Com o envelhecimento populacional, as projeções para as próximas décadas são alarmantes. Além de sua importância epidemiológica, a fibrilação atrial é destacada por suas repercussões clínicas, incluindo fenômenos tromboembólicos, hospitalizações e maior taxa de mortalidade. Seu mecanismo fisiopatológico é complexo, envolvendo uma associação de fatores hemodinâmicos, estruturais, eletrofisiológicos e autonômicos. Desde os anos 1990, o estudo Framingham em análises multivariadas já demonstrou que, além da idade, a presença de hipertensão, diabetes, insuficiência cardíaca e doença valvar é preditor independente dessa normalidade do ritmo. Entretanto, recentemente, vários outros fatores de risco estão sendo implicados no aumento do número de casos de fibrilação atrial, tais como sedentarismo, obesidade, anormalidades do sono, tabagismo e uso excessivo de álcool. Além disso, as mudanças na qualidade de vida apontam para uma redução na recorrência de fibrilação atrial, tornando-se uma nova estratégia para o tratamento de excelência dessa arritmia cardíaca. A abordagem terapêutica envolve um amplo conhecimento do estado de saúde e hábitos do paciente, e compreende quatro pilares principais: mudança de hábitos de vida e tratamento rigoroso de fatores de risco; prevenção de eventos tromboembólicos; controle da frequência; e controle do ritmo. Pela dimensão de fatores envolvidos no cuidado ao paciente portador de fibrilação atrial, ações integradas com equipes multiprofissionais estão associadas aos melhores resultados clínicos.
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Darweesh RM, Baghdady YK, El Hossary H, Khaled M. Importance of left atrial mechanical function as a predictor of atrial fibrillation risk following cardiac surgery. Int J Cardiovasc Imaging 2021; 37:1863-1872. [PMID: 33591474 DOI: 10.1007/s10554-021-02163-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Accepted: 01/10/2021] [Indexed: 11/27/2022]
Abstract
Postoperative atrial fibrillation (POAF) after cardiac surgery is a major health problem that is associated with a significant financial burden and increased early morbidity and mortality. We investigated the accuracy of new echocardiographic derived indices to predict patients at higher risk of developing POAF. 84 consecutive patients (age 57.9 ± 6.9, 32% female) hospitalized for isolated CABG underwent comprehensive echocardiographic evaluation before surgery. Left atrial (LA) function was quantified through the assessment of phasic LA volumes to calculate LATEF. Speckle tracking echocardiography STE was used to measure LA reservoir strain, conduit strain and booster strain. Patients who developed POAF had increased LA volumes and impaired LA functions assessed by both the volumetric phasic changes and STE. By univariable analysis, all LA function parameters significantly predicted POAF. Multivariate regression analysis showed that age (P = 0.03, OR 1.134, 95% CI 1.012-1.271) and LATEF (P = 0.001, OR 0.814, 95% CI 0.725-0.914) were strong independent factors for POAF with LATEF showing the highest predictive accuracy. After multivariable adjustment to include LA strain indices to the base model, LA contractile strain LACtS (23.93 ± 4.19 vs 37.0 ± 3.35, p < 0.001) was the best discriminated for the highest predictive accuracy (OR 0.429, 95% CI 0.26-0.708). The ROC Curve was calculated for the greatest performance for prediction of POAF (AUC LACtS: 0.992; LATEF: 0.899). Adding new left atrial mechanics parameters is a more sensitive, independent tool that provides an incremental predictive value to discriminate patients at more risk for POAF.
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Bonora BM, Raschi E, Avogaro A, Fadini GP. SGLT-2 inhibitors and atrial fibrillation in the Food and Drug Administration adverse event reporting system. Cardiovasc Diabetol 2021; 20:39. [PMID: 33573667 PMCID: PMC7879696 DOI: 10.1186/s12933-021-01243-4] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2021] [Accepted: 02/08/2021] [Indexed: 02/07/2023] Open
Abstract
Background Sodium glucose cotransporter-2 inhibitors (SGLT2i) reduce the risk of heart failure and new data show they can prevent atrial fibrillation (AF). We examined the association between SGLT2i and AF in the Food and Drug Administration adverse event reporting system (FAERS). Methods We mined the FAERS from 2014q1 to 2019q4 to compare AF reporting for SGLT-2 i versus reports for other glucose lowering medications (ATC10 class). Several exclusions were sequentially applied for: concomitant medications; diabetes, cardiovascular or renal disease indication; reports for competing adverse events (genitourinary tract infections, ketoacidosis, Fournier’s gangrene, amputation). We provide descriptive statistics and calculated proportional reporting ratios (PRR). Results There were 62,098 adverse event reports for SGLT2i and 642,031 reports for other ATC10 drugs. The reporting of AF was significantly lower with SGLT2i than with other ATC10 drugs (4.8 versus 8.7/1000; p < 0.001) with a PRR of 0.55 (0.49–0.62). Results did not change substantially after excluding reports listing insulin (PRR 0.49) or anti-arrhythmics (PRR 0.59) as suspect or concomitant drugs, excluding reports with indications for cardiovascular disease (PRR 0.49) or renal disease (PRR 0.55), and those filed for competing adverse events (PRR 0.63). Results were always statistically significant whether the diabetes indication was specified. Negative and positive controls confirmed internal validity of the database. Conclusions In a large pharmacovigilance database, AF was robustly and consistently reported more frequently for diabetes medications other than SGLT2i. This finding complements available evidence from trials supporting a protective role of SGLT2i against the occurrence of AF.
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Affiliation(s)
| | - Emanuel Raschi
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Angelo Avogaro
- Department of Medicine, University of Padova, Via Giustiniani 2, 35128, Padova, Italy
| | - Gian Paolo Fadini
- Department of Medicine, University of Padova, Via Giustiniani 2, 35128, Padova, Italy.
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Lee TW, Lee TI, Lin YK, Chen YC, Kao YH, Chen YJ. Effect of antidiabetic drugs on the risk of atrial fibrillation: mechanistic insights from clinical evidence and translational studies. Cell Mol Life Sci 2021; 78:923-934. [PMID: 32965513 PMCID: PMC11072414 DOI: 10.1007/s00018-020-03648-y] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2020] [Revised: 08/18/2020] [Accepted: 09/12/2020] [Indexed: 12/13/2022]
Abstract
Diabetes mellitus (DM) is an independent risk factor for atrial fibrillation (AF), which is the most common sustained arrhythmia and is associated with substantial morbidity and mortality. Advanced glycation end product and its receptor activation, cardiac energy dysmetabolism, structural and electrical remodeling, and autonomic dysfunction are implicated in AF pathophysiology in diabetic hearts. Antidiabetic drugs have been demonstrated to possess therapeutic potential for AF. However, clinical investigations of AF in patients with DM have been scant and inconclusive. This article provides a comprehensive review of research findings on the association between DM and AF and critically analyzes the effect of different pharmacological classes of antidiabetic drugs on AF.
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Affiliation(s)
- Ting-Wei Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
| | - Ting-I Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
- Department of General Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Yung-Kuo Lin
- Division of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Division of Cardiovascular Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
| | - Yao-Chang Chen
- Department of Biomedical Engineering, National Defense Medical Center, Taipei, Taiwan
| | - Yu-Hsun Kao
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Department of Medical Education and Research, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
| | - Yi-Jen Chen
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
- Cardiovascular Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
- Taipei Heart Institute, Taipei Medical University, Taipei, Taiwan.
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Varma N, Cygankiewicz I, Turakhia MP, Heidbuchel H, Hu Y, Chen LY, Couderc JP, Cronin EM, Estep JD, Grieten L, Lane DA, Mehra R, Page A, Passman R, Piccini JP, Piotrowicz E, Piotrowicz R, Platonov PG, Ribeiro AL, Rich RE, Russo AM, Slotwiner D, Steinberg JS, Svennberg E. 2021 ISHNE/HRS/EHRA/APHRS Collaborative Statement on mHealth in Arrhythmia Management: Digital Medical Tools for Heart Rhythm Professionals: From the International Society for Holter and Noninvasive Electrocardiology/Heart Rhythm Society/European Heart Rhythm Association/Asia Pacific Heart Rhythm Society. CARDIOVASCULAR DIGITAL HEALTH JOURNAL 2021; 2:4-54. [PMID: 35265889 PMCID: PMC8890358 DOI: 10.1016/j.cvdhj.2020.11.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
This collaborative statement from the International Society for Holter and Noninvasive Electrocardiology/Heart Rhythm Society/European Heart Rhythm Association/Asia Pacific Heart Rhythm Society describes the current status of mobile health ("mHealth") technologies in arrhythmia management. The range of digital medical tools and heart rhythm disorders that they may be applied to and clinical decisions that may be enabled are discussed. The facilitation of comorbidity and lifestyle management (increasingly recognized to play a role in heart rhythm disorders) and patient self-management are novel aspects of mHealth. The promises of predictive analytics but also operational challenges in embedding mHealth into routine clinical care are explored.
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Key Words
- ACC, American College of Cardiology
- ACS, acute coronary syndrome
- AED, automated external defibrillator
- AF, atrial fibrillation
- AHA, American Heart Association
- AHRE, atrial high-rate episode
- AI, artificial intelligence
- APHRS, Asia Pacific Heart Rhythm Society
- BP, blood pressure
- CIED, cardiovascular implantable electronic device
- CPR, cardiopulmonary resuscitation
- EHR A, European Heart Rhythm Association
- EMR, electronic medical record
- ESUS, embolic stroke of unknown source
- FDA (U.S.), Food and Drug Administration
- GPS, global positioning system
- HCP, healthcare professional
- HF, heart failure
- HR, heart rate
- HRS, Heart Rhythm Society
- ICD, implantable cardioverter-defibrillator
- ILR, implantable loop recorder
- ISHNE, International Society for Holter and Noninvasive Electrocardiology
- JITAI, just-in-time adaptive intervention
- MCT, mobile cardiac telemetry
- OAC, oral anticoagulant
- PAC, premature atrial complex
- PPG, photoplethysmography
- PVC, premature ventricular complexes
- SCA, sudden cardiac arrest
- TADA, Technology Assissted Dietary Assessment
- VT, ventricular tachycardia
- arrhythmias
- atrial fibrillation
- comorbidities
- digital medicine
- heart rhythm
- mHealth
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Affiliation(s)
| | | | | | - Hein Heidbuchel
- Antwerp University and University Hospital, Antwerp, Belgium
| | - Yufeng Hu
- Taipei Veterans General Hospital, Taipei, Taiwan
| | | | | | | | | | | | | | | | - Alex Page
- University of Rochester, Rochester, NY, USA
| | - Rod Passman
- Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | | | | | | | | | - Antonio Luiz Ribeiro
- Faculdade de Medicina, Centro de Telessaúde, Hospital das Clínicas, and Departamento de Clínica Médica, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | | | | | - David Slotwiner
- Cardiology Division, NewYork-Presbyterian Queens, and School of Health Policy and Research, Weill Cornell Medicine, New York, NY, USA
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Varma N, Cygankiewicz I, Turakhia MP, Heidbuchel H, Hu YF, Chen LY, Couderc JP, Cronin EM, Estep JD, Grieten L, Lane DA, Mehra R, Page A, Passman R, Piccini JP, Piotrowicz E, Piotrowicz R, Platonov PG, Ribeiro AL, Rich RE, Russo AM, Slotwiner D, Steinberg JS, Svennberg E. 2021 ISHNE/HRS/EHRA/APHRS Expert Collaborative Statement on mHealth in Arrhythmia Management: Digital Medical Tools for Heart Rhythm Professionals: From the International Society for Holter and Noninvasive Electrocardiology/Heart Rhythm Society/European Heart Rhythm Association/Asia-Pacific Heart Rhythm Society. Circ Arrhythm Electrophysiol 2021; 14:e009204. [PMID: 33573393 PMCID: PMC7892205 DOI: 10.1161/circep.120.009204] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
This collaborative statement from the International Society for Holter and Noninvasive Electrocardiology/Heart Rhythm Society/European Heart Rhythm Association/Asia-Pacific Heart Rhythm Society describes the current status of mobile health technologies in arrhythmia management. The range of digital medical tools and heart rhythm disorders that they may be applied to and clinical decisions that may be enabled are discussed. The facilitation of comorbidity and lifestyle management (increasingly recognized to play a role in heart rhythm disorders) and patient self-management are novel aspects of mobile health. The promises of predictive analytics but also operational challenges in embedding mobile health into routine clinical care are explored.
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Affiliation(s)
- Niraj Varma
- Cleveland Clinic, OH (N.V., J.D.E., R.M., R.E.R.)
| | | | | | | | - Yu-Feng Hu
- Taipei Veterans General Hospital, Taiwan (Y.-F.H.)
| | | | | | | | | | | | | | - Reena Mehra
- Cleveland Clinic, OH (N.V., J.D.E., R.M., R.E.R.)
| | - Alex Page
- University of Rochester, NY (J.-P.C., A.P., J.S.S.)
| | - Rod Passman
- Northwestern University Feinberg School of Medicine, Chicago, IL (R. Passman)
| | | | - Ewa Piotrowicz
- National Institute of Cardiology, Warsaw, Poland (E.P., R. Piotrowicz)
| | | | | | - Antonio Luiz Ribeiro
- Faculdade de Medicina, Centro de Telessaúde, Hospital das Clínicas, and Departamento de Clínica Médica, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil (A.L.R.)
| | | | - Andrea M. Russo
- Cooper Medical School of Rowan University, Camden, NJ (A.M.R.)
| | - David Slotwiner
- Cardiology Division, New York-Presbyterian Queens, NY (D.S.)
| | | | - Emma Svennberg
- Karolinska University Hospital, Stockholm, Sweden (E.S.)
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Daios S, Savopoulos C, Kanellos I, Goudis CA, Nakou I, Petalloti S, Hadjidimitriou N, Pilalas D, Ziakas A, Kaiafa G. Circadian Pattern of Acute Myocardial Infarction and Atrial Fibrillation in a Mediterranean Country: A study in Diabetic Patients. MEDICINA (KAUNAS, LITHUANIA) 2021; 57:medicina57010041. [PMID: 33418926 PMCID: PMC7825022 DOI: 10.3390/medicina57010041] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/12/2020] [Revised: 12/30/2020] [Accepted: 12/31/2020] [Indexed: 05/13/2023]
Abstract
Background and objectives: The circadian pattern seems to play a crucial role in cardiovascular events and arrhythmias. Diabetes mellitus is a complex metabolic disorder associated with autonomic nervous system alterations and increased risk of microvascular and macrovascular disease. We sought to determine whether acute myocardial infarction (AMI) and atrial fibrillation (AF) follow a circadian pattern in diabetic patients in a Mediterranean country. Materials and Methods: This retrospective study included 178 diabetic patients (mean age: 67.7) with AMI or AF who were admitted to the coronary care unit. The circadian pattern of AMI and AF was identified in the 24-h period (divided in 3-h and 1-h intervals). Patients were also divided in 3 groups according to age; 40-65 years, 66-79 years and patients older than 80 years. A chi-square goodness-of-fit test was used for the statistical analysis. Results: AMI seems to occur more often in the midnight hours (21:00-23:59) (p < 0.001). Regarding age distribution, patients between 40 and 65 years were more likely to experience an AMI compared to other age groups (p < 0.001). Autonomic alterations, working habits, and social reasons might contribute to this phenomenon. AF in diabetic patients occurs more frequently at noon (12:00-14:59) (p = 0.019). Conclusions: Diabetic patients with AMI and AF seem to follow a specific circadian pattern in a Mediterranean country, with AMI occurring most often at midnight hours and AF mostly at noon. Autonomic dysfunction, glycemic fluctuations, intense anti-diabetic treatment before lunch, and patterns of insulin secretion and resistance may explain this pattern. More studies are needed to elucidate the circadian pattern of AMI and AF in diabetic patients to contribute to the development of new therapeutic approaches in this setting.
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Affiliation(s)
- Stylianos Daios
- First Propedeutic Department of Internal Medicine, Department of Medicine, Aristotle University of Thessaloniki, AHEPA University Hospital, Stilponos Kyriakidi Street, 54636 Thessaloniki, Greece; (S.D.); (I.K.); (S.P.); (N.H.); (D.P.); (G.K.)
- Cardiology Department, Serres General Hospital, 62120 Serres, Greece; (C.A.G.); (I.N.)
| | - Christos Savopoulos
- First Propedeutic Department of Internal Medicine, Department of Medicine, Aristotle University of Thessaloniki, AHEPA University Hospital, Stilponos Kyriakidi Street, 54636 Thessaloniki, Greece; (S.D.); (I.K.); (S.P.); (N.H.); (D.P.); (G.K.)
- Correspondence: ; Tel.: +30-2310994783; Fax: +30-2310285128
| | - Ilias Kanellos
- First Propedeutic Department of Internal Medicine, Department of Medicine, Aristotle University of Thessaloniki, AHEPA University Hospital, Stilponos Kyriakidi Street, 54636 Thessaloniki, Greece; (S.D.); (I.K.); (S.P.); (N.H.); (D.P.); (G.K.)
| | | | - Ifigeneia Nakou
- Cardiology Department, Serres General Hospital, 62120 Serres, Greece; (C.A.G.); (I.N.)
| | - Stergiani Petalloti
- First Propedeutic Department of Internal Medicine, Department of Medicine, Aristotle University of Thessaloniki, AHEPA University Hospital, Stilponos Kyriakidi Street, 54636 Thessaloniki, Greece; (S.D.); (I.K.); (S.P.); (N.H.); (D.P.); (G.K.)
- Cardiology Department, Serres General Hospital, 62120 Serres, Greece; (C.A.G.); (I.N.)
| | - Nicolas Hadjidimitriou
- First Propedeutic Department of Internal Medicine, Department of Medicine, Aristotle University of Thessaloniki, AHEPA University Hospital, Stilponos Kyriakidi Street, 54636 Thessaloniki, Greece; (S.D.); (I.K.); (S.P.); (N.H.); (D.P.); (G.K.)
| | - Dimitrios Pilalas
- First Propedeutic Department of Internal Medicine, Department of Medicine, Aristotle University of Thessaloniki, AHEPA University Hospital, Stilponos Kyriakidi Street, 54636 Thessaloniki, Greece; (S.D.); (I.K.); (S.P.); (N.H.); (D.P.); (G.K.)
| | - Antonios Ziakas
- First Department of Cardiology, Aristotle University of Thessaloniki, AHEPA University Hospital, 54636 Thessaloniki, Greece;
| | - Georgia Kaiafa
- First Propedeutic Department of Internal Medicine, Department of Medicine, Aristotle University of Thessaloniki, AHEPA University Hospital, Stilponos Kyriakidi Street, 54636 Thessaloniki, Greece; (S.D.); (I.K.); (S.P.); (N.H.); (D.P.); (G.K.)
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Meng T, Wang J, Tang M, Liu S, Ding L, Yan Y. Diabetes Mellitus Promotes Atrial Structural Remodeling and PARP-1/Ikkα/NF-κB Pathway Activation in Mice. Diabetes Metab Syndr Obes 2021; 14:2189-2199. [PMID: 34040405 PMCID: PMC8139946 DOI: 10.2147/dmso.s300616] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Accepted: 04/02/2021] [Indexed: 01/18/2023] Open
Abstract
BACKGROUND Diabetes mellitus (DM) has been demonstrated to be linked to atrial fibrillation (AF). However, the underlying mechanisms of the DM-associated increase in AF susceptibility and the potential effects of DM on atrial remodeling remain unclear. METHODS AND RESULTS Twenty-five C57BL/6 mice were randomly assigned to the normal/control group (Con, n=10) and model group (n=15). Mice in the model group were administered a high-fat diet combined with multiple injections of low-dose streptozocin (STZ) (35 mg/kg). Eleven mice were ultimately included in DM group. Left atrial tissue structural and inflammatory alterations were assessed. In our study, the atrial weights of DM mice were markedly heavier than those of mice in the Con group. DM mice exhibited significantly increased fasting plasma glucose, fasting insulin, and dyslipidaemia. Furthermore, H&E and Masson's staining revealed broadened interstitial spaces, myocyte disarray and atrial fibrosis in DM mice. The expression levels of the atrial inflammation-associated factor nuclear factor κB (NF-κB) and its pathway were significantly altered in the atria of DM mice. CONCLUSION DM could induce atrial structural remodeling and inflammation in mice.
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Affiliation(s)
- Tianyu Meng
- Department of Geriatrics, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, People’s Republic of China
| | - Jie Wang
- Department of Cardiovascular Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, People’s Republic of China
- Department of Hematology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, People’s Republic of China
| | - Manyun Tang
- Department of Cardiovascular Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, People’s Republic of China
| | - Shangyu Liu
- Clinical EP Lab & Arrhythmia Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, People’s Republic of China
| | - Ligang Ding
- Clinical EP Lab & Arrhythmia Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, People’s Republic of China
- Correspondence: Ligang Ding Clinical EP Lab & Arrhythmia Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, People’s Republic of China Email
| | - Yang Yan
- Department of Cardiovascular Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, People’s Republic of China
- Yang Yan Department of Cardiovascular Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, No. 277 Yanta West Road, Xi’an, Shaanxi, 710061, People’s Republic of ChinaTel +86-2985323869Fax +86-2985323869 Email
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Højager A, Tingsgaard JK, Andersen D, Søholm H, Taskiran M, Bock TG, Schoos MM. Silent atrial fibrillation detected by home-monitoring: Cardiovascular disease and stroke prevention in patients with diabetes. J Diabetes Complications 2020; 34:107711. [PMID: 32900590 DOI: 10.1016/j.jdiacomp.2020.107711] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2020] [Revised: 08/04/2020] [Accepted: 08/18/2020] [Indexed: 11/30/2022]
Abstract
OBJECTIVE Patients with silent and undiagnosed paroxysmal atrial fibrillation and flutter (AF) have increased risk of ischemic stroke. Patients with diabetes have a higher risk of both AF and ischemic stroke compared to patients without diabetes. Our aim was to investigate the prevalence of silent AF in patients with diabetes in an outpatient cohort and to identify the possible risk factors associated with AF. RESEARCH DESIGN AND METHODS This prospective observational study was performed in the outpatient diabetes clinic at a single University Hospital. We included 217 patients with type 1 or type 2 diabetes with at least one additional risk factor from the CHA2DS2VASc Score for Stroke Risk Assessment in Atrial Fibrillation. The primary outcome was prevalence of AF, with a duration of at least 30 s, recorded by a seven-day home-monitor, external loop recorder (ELR) in comparison to a standard resting ECG. Seventeen patients were excluded due to premature removal of the device. RESULTS In the final cohort of 200 patients the majority were male (58.5%) with a mean age of 66 ± 0.7 years. The mean BMI was 29 ± 6 and patients had a mean diabetes history of 23 ± 14 years with the majority diagnosed with type 2 diabetes (59%). Comorbidity was common with hypertension in 86%, and dyslipidemia in 80%. The total prevalence of silent AF [n = 20 (10%)] or flutter [n = 1 (0.5%)] was 10.5% using the ELR compared to a 0.0% detection-rate in the standard ECG method (p < 0.001). Higher age, male gender, albuminuria, and elevated systolic blood pressure were associated with AF in univariate analyses, but only age [OR 1.14 (95% CI = 1.00-2.04) (p = 0.048)], male gender [OR 4.9 (95% CI = 1.30-18.65) (p = 0.019)] and albuminuria [OR 2.7 (95% CI =1.08-6.98) (p = 0.034) were independently associated with AF. Mean CHA2DS2VASc Score was ≥2 (4.1, SD ± 1.6), and patients with AF were referred to further cardiac evaluation. CONCLUSION Undiagnosed, silent AF is common in high-risk cohort with a long history of diabetes followed in a University Hospital outpatient clinic. Non-invasive monitoring with ELR enhances detection of AF and identifies candidates for early anticoagulation treatment with the possible effect of stroke prevention.
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Affiliation(s)
- Anna Højager
- Department of Medicine, Zealand University Hospital, Denmark.
| | | | - Ditte Andersen
- Department of Medicine, Zealand University Hospital, Denmark
| | - Helle Søholm
- Department of Cardiology, Zealand University Hospital, Denmark; Department of Cardiology, Copenhagen University Hospital Rigshospitalet, Denmark
| | | | | | - Mikkel M Schoos
- Department of Cardiology, Zealand University Hospital, Denmark
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Abstract
The population suffering from coronary heart disease (CHD) complicated by atrial fibrillation (AF) is rising rapidly. A strong correlation between the two diseases has been reported, and the many common risk factors they share may play prominent roles in their development. In addition, CHD can directly promote the progression of AF by affecting reentry formation, focal ectopic activity, and neural remodeling. At the same time, AF also affects CHD through three aspects: 1) atherosclerosis, 2) the mismatch of blood supply and oxygen consumption, and 3) thrombosis. In conclusion, CHD and AF can aggravate each other and seem to form a vicious cycle. For patients with CHD complicated by AF, principal studies and guidelines have focused on antithrombotic treatment and rhythm control, which are paramount for these patients. Of note, our review sheds light on the strategies to break the cycle of the two diseases, which may be fundamental to treat these patients and optimize the benefit.
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Affiliation(s)
- Feng Liang
- Department of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Yi Wang
- Department of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Ling AWC, Chan CC, Chen SW, Kao YW, Huang CY, Chan YH, Chu PH. The risk of new-onset atrial fibrillation in patients with type 2 diabetes mellitus treated with sodium glucose cotransporter 2 inhibitors versus dipeptidyl peptidase-4 inhibitors. Cardiovasc Diabetol 2020; 19:188. [PMID: 33158436 PMCID: PMC7648323 DOI: 10.1186/s12933-020-01162-w] [Citation(s) in RCA: 46] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2020] [Accepted: 10/27/2020] [Indexed: 12/17/2022] Open
Abstract
Background Sodium glucose cotransporter 2 inhibitor (SGLT2i) reduces the risk of hard cardiovascular endpoints in type 2 diabetes mellitus (T2DM) patients with/without established cardiovascular diseases. Whether SGLT2i is associated with a lower risk of new-onset atrial fibrillation (AF) in T2DM patients is unclear. We aimed to evaluate the risk of new-onset AF associated with the use of SGLT2i compared to dipeptidyl peptidase-4 inhibitor (DPP4i) among a longitudinal cohort of diabetic patients. Methods We used medical data from a multi-center healthcare provider in Taiwan, which included a total of 15,606 and 12,383 patients treated with SGLT2i and DPP4i, respectively, from June 1, 2016 to December 31, 2018. We used propensity-score weighting to balance covariates across study groups. Patients were followed up from the drug index date until the occurrence of new-onset AF, discontinuation of the index drug, or the end of the study period, whichever occurred first. Results Overall, 55%, 45%, and 0% of the patients were treated with empagliflozin, dapagliflozin, and canagliflozin, respectively. Most patients in the DPP4i group were prescribed with linagliptin (51%), followed by sitagliptin (24%), saxagliptin (13%), vildagliptin (8%) and alogliptin (5%). The use of SGLT2i was associated with a lower risk of new-onset AF compared with DPP4i after propensity-score weighting [hazard ratio: 0.61; 95% confidential interval: 0.50–0.73; P < 0.001]. Subgroup analysis revealed that the use of SGLT2i was associated with a lower risk of new-onset AF compared with DPP4i across several subgroups including old age, female in gender, the presence of cardiovascular disease, hemoglobin A1c \documentclass[12pt]{minimal}
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\begin{document}$$\ge$$\end{document}≥ 8%, and chronic kidney disease. The advantage of SGLT2i over DPP4i persisted with different SGLT2i (dapagliflozin or empagliflozin) and either low- or standard-dose SGLT2i. Conclusions SGLT2i was associated with a lower risk of new-onset AF compared with DPP4i among T2DM patients in real-world practice.
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Affiliation(s)
- Ann Wan-Chin Ling
- Cardiovascular Department, Chang Gung Memorial Hospital, Linkou, Taoyuan, 33305, Taiwan
| | - Cze-Ci Chan
- Cardiovascular Department, Chang Gung Memorial Hospital, Linkou, Taoyuan, 33305, Taiwan
| | - Shao-Wei Chen
- Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Chang Gung Memorial Hospital, Linkou Medical Center, Chang Gung University, Taoyuan City, Taiwan.,Center for Big Data Analytics and Statistics, Linkou Medical Center, Chang Gung Memorial Hospital, Taoyuan City, Taiwan
| | - Yi-Wei Kao
- Graduate Institute of Business Administration, College of Management, Fu Jen Catholic University, Taipei, Taiwan
| | - Chien-Ying Huang
- Cardiovascular Department, Chang Gung Memorial Hospital, Linkou, Taoyuan, 33305, Taiwan
| | - Yi-Hsin Chan
- Cardiovascular Department, Chang Gung Memorial Hospital, Linkou, Taoyuan, 33305, Taiwan. .,College of Medicine, Chang Gung University, Taoyuan, 33302, Taiwan. .,Microscopy Core Laboratory, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan.
| | - Pao-Hsien Chu
- Cardiovascular Department, Chang Gung Memorial Hospital, Linkou, Taoyuan, 33305, Taiwan. .,College of Medicine, Chang Gung University, Taoyuan, 33302, Taiwan.
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Epidemiology and treatment of atrial fibrillation in patients with type 2 diabetes in the UK, 2001-2016. Sci Rep 2020; 10:12468. [PMID: 32719438 PMCID: PMC7385086 DOI: 10.1038/s41598-020-69492-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Accepted: 07/13/2020] [Indexed: 11/08/2022] Open
Abstract
Patients with Type 2 diabetes mellitus (T2DM) have an increased risk of atrial fibrillation (AF). The current study aimed to investigate the prevalence and treatment of AF in patients with T2DM, assess the impact of direct oral anticoagulants (DOACs) introduction on oral anticoagulant (OACs) prescribing rates, and factors associated with OAC initiations in patients with T2DM and AF. The Health Improvement Network (THIN) database (2001-2016), was used to examine the annual prevalence and treatment of AF in T2DM. The impact of DOACs introduction on OAC prescribing rates were investigated using interrupted time series analysis (ITS). Factors associated with OAC initiations were also identified using multivariate logistic regression. The prevalence of AF increased from 2.7 [95% confidence intervals (CI) 2.5-2.8] in 2001 to 5.0 (4.9-5.1) in 2016 per 100 persons. OACs prescribing within 30-days of AF diagnosis increased from 21.5% in 2001 to 56.8% in 2016. ITS analysis showed that OAC prescribing increased after DOAC introduction (P < 0.001), however, no immediate change was observed (P = 0.29). T2DM patients with AF, aged 60-79, male gender and BMI ≥ 25 were more likely to receive OAC, adjusted OR 1.3 (1.2-1.5) for aged 60-79, 1.3 (1.2-1.4) for male gender and 2.0 (1.9-2.2) for BMI ≥ 25, respectively. This study highlighted an increase in prevalence of AF in patients with T2DM during the study period. Further studies are warranted to investigate factors contributing to the underuse of OAC in patients with T2DM and AF.
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Franco D, Aranega A, Dominguez JN. Non-coding RNAs and Atrial Fibrillation. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2020; 1229:311-325. [PMID: 32285421 DOI: 10.1007/978-981-15-1671-9_19] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Atrial fibrillation is the most frequent type of cardiac arrhythmia in humans, with an estimate incidence of 1-2% in the general population, rising up to 8-10% in the elderly. Cardiovascular risk factors such as diabetes, obesity, hypertension and hyperthyroidism can increase the occurrence of AF. The onset of AF triggers additional AF episodes, leading to structural and electrical remodeling of the diseased heart. Understanding the molecular bases of atrial fibrillation have greatly advance over the last decade demonstrating a pivotal role of distinct ion channels in AF pathophysiology. A new scenario has opened on the understanding of the molecular mechanisms underlying AF, with the discovery of non-coding RNAs and their wide implication in multiple disease states, including cardiac arrhythmogenic pathologies. microRNAs are small non-coding RNAs of 22-24 nucleotides that are capable of regulating gene expression by interacting with the mRNA transcript 3'UTRs and promoting mRNA degradation and/or protein translation blockage. Long non-coding RNAs are a more diverse group of non-coding RNAs, providing transcriptional and post-transcriptional roles and subclassified according to their functional properties. In this chapter we summarized current state-of-the-art knowledge on the functional of microRNAs and long non-coding RNAs as well as their cross-talk regulatory mechanisms in atrial fibrillation.
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Affiliation(s)
- Diego Franco
- Cardiovascular Development Group, Department of Experimental Biology, University of Jaen, Jaen, Spain.
| | - Amelia Aranega
- Cardiovascular Development Group, Department of Experimental Biology, University of Jaen, Jaen, Spain
| | - Jorge N Dominguez
- Cardiovascular Development Group, Department of Experimental Biology, University of Jaen, Jaen, Spain
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Xue X, Ling X, Xi W, Wang P, Sun J, Yang Q, Xiao J. Exogenous hydrogen sulfide reduces atrial remodeling and atrial fibrillation induced by diabetes mellitus via activation of the PI3K/Akt/eNOS pathway. Mol Med Rep 2020; 22:1759-1766. [PMID: 32705232 PMCID: PMC7411292 DOI: 10.3892/mmr.2020.11291] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Accepted: 05/14/2020] [Indexed: 11/06/2022] Open
Abstract
Diabetes mellitus (DM) facilitates atrial fibrosis and increases the risk of atrial fibrillation (AF). The underlying mechanism of DM in causing AF remains mostly unknown and potential therapeutic targets for DM‑induced AF are rarely reported. Hydrogen sulfide (H2S) has drawn considerable attention in recent years for its potential as a cardiovascular protector. Thus, the aim of the present study was to investigate the effect of H2S on DM‑induced AF and the mechanism of action. Sprague‑Dawley rats were divided into four groups, including the control group, the DM group, the H2S group and the DM+H2S group. The DM group and the DM+H2S group were administered streptozotocin to induce DM, whereas the other two groups were given citrate buffer as a control. The H2S group and the DM+H2S group were administered with an intraperitoneal injection of sodium hydrosulfide (precursor of H2S). AF inducibility, AF duration, atrial fibrosis and vital protein expression of oxidative stress were compared among the four groups. The DM group showed significantly higher AF incidence rates and duration (P<0.05). Histology results demonstrated severe atrial fibrosis in the DM group, and the PI3K/Akt/endothelial nitric oxide synthase (eNOS) pathway was significantly downregulated (P<0.05). However, when H2S was administered, the rats showed lower AF incidence and duration compared with the DM group. Additionally, H2S was able to mitigate the atrial fibrosis induced by DM, as well as the proliferation and migration of cardiac fibroblasts, as demonstrated by an MTT assay and real‑time cell analyzer migration experiment. Western blotting showed that the expression levels of the PI3K/Akt/eNOS pathway in the DM+H2S group were significantly upregulated compared with those of the DM group (P<0.05). In summary, DM status can lead to the structural remodeling of atrial fibrosis, facilitating AF incidence and persistence. Administration of H2S does not affect the glucose level, but can significantly mitigate atrial fibrosis and reduce the incidence of AF induced by DM, probably via activation of the PI3K/Akt/eNOS pathway.
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Affiliation(s)
- Xiaofei Xue
- Center for Comprehensive Treatment of Atrial Fibrillation, Department of Cardiothoracic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China
| | - Xinyu Ling
- Center for Comprehensive Treatment of Atrial Fibrillation, Department of Cardiothoracic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China
| | - Wang Xi
- Center for Comprehensive Treatment of Atrial Fibrillation, Department of Cardiothoracic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China
| | - Pei Wang
- Center for Comprehensive Treatment of Atrial Fibrillation, Department of Cardiothoracic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China
| | - Jianjun Sun
- Department of Rehabilitation, Elderly Rehabilitation Hospital, Suzhou Red Cross Society, Suzhou, Jiangsu 215009, P.R. China
| | - Qian Yang
- Center for Comprehensive Treatment of Atrial Fibrillation, Department of Cardiothoracic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China
| | - Jian Xiao
- Center for Comprehensive Treatment of Atrial Fibrillation, Department of Cardiothoracic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China
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Khaliq K, Ajibawo T, Bhandari R, Patel RS. Problematic Alcohol Use and Mortality Risk in Arrhythmia: Nationwide Study of 114,958 Hospitalizations. Cureus 2020; 12:e8194. [PMID: 32572353 PMCID: PMC7302717 DOI: 10.7759/cureus.8194] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Objectives To assess the risk of in-hospital mortality due to alcohol use disorder (AUD) and other cardiovascular risk factors in arrhythmia inpatients. Methods We included 114,958 patients (age, 15-54 years) by conducting a cross-sectional cohort study using the Nationwide Inpatient Sample (NIS, 2010-2014). These patients were primarily managed for arrhythmia and further grouped by comorbid AUD. A logistic regression model was used to measure the odds ratio (OR) of association of AUD and in-hospital mortality after adjusting for demographic confounders and cardiovascular risk factors. Results Mortality risk statistically increases with age as elders (45-54 years) had two times higher risk (95% confidence interval [CI] 1.49-3.09), whereas men had a lower risk (OR 0.8, 95% CI 0.74-0.96) of inpatient death. Comorbid atherosclerosis (OR 4.5, 95% CI 3.38-5.92) and diabetes (OR 1.4, 95% CI 1.18-1.67) increased mortality risk in arrhythmia inpatients. AUD significantly increased the risk of mortality in arrhythmia inpatients (OR 1.7, 95% CI 1.43-2.07). Conclusions AUD is an independent risk factor for mortality in arrhythmia inpatients, and it is elevated by 72% in such patients. Strategies to reduce alcohol consumption and abstinence should be focused to improve the health-related quality of life of at-risk patients.
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Affiliation(s)
- Khalida Khaliq
- Psychiatry/Medicine, North Tampa Behavioral Health, Tampa, USA
| | - Temitope Ajibawo
- Internal Medicine, Brookdale University Hospital Medical Center, New York City, USA
| | - Renu Bhandari
- Medicine, Manipal College of Medical Sciences, Kaski, NPL
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Hu WS, Lin CL. Comparison of New-Onset Diabetes Mellitus among Patients with Atrial Fibrillation or Atrial Flutter. Korean Circ J 2020; 50:527-532. [PMID: 32281320 PMCID: PMC7234853 DOI: 10.4070/kcj.2019.0367] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2019] [Revised: 02/07/2020] [Accepted: 02/19/2020] [Indexed: 11/11/2022] Open
Abstract
Background and Objectives The objective was to compare the rate of onset of diabetes mellitus (DM) in patients with atrial fibrillation (AF) as compared with atrial flutter (AFL). Methods The incidence of DM through the national cohort registry in 14,014 newly diagnosed AF and 14,014 newly diagnosed AFL was investigated. Propensity score matching was used to optimize comparability between these 2 groups. Further analysis with Cox model, Kaplan-Meier methods and competing risk analysis were used to compare the incidence of DM in patients with AF and AFL. Results The overall incidence of diabetes was higher among cases in AF cohort (1,653 diabetes cases, 11.7%) than in AFL cohort (1,448 diabetes cases, 10.3%). The risk of diabetes was 1.17-fold greater in the AF cohort compared with that in the AFL cohort (95% confidence interval [CI], 1.09–1.25; p<0.001). After adjustment for all relevant confounding factors in the competing risk regression model, the risk of diabetes remained significantly increased 1.16-fold in the AF cohort (95% CI, 1.09–1.25; p<0.001). Conclusions The message of higher incidence rate of DM in patients with AF compared to those with AFL was delivered in this study.
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Affiliation(s)
- Wei Syun Hu
- School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan.,Division of Cardiovascular Medicine, Department of Medicine, China Medical University Hospital, Taichung, Taiwan.
| | - Cheng Li Lin
- Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan
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Creta A, Providência R, Adragão P, de Asmundis C, Chun J, Chierchia G, Defaye P, Schmidt B, Anselme F, Finlay M, Hunter RJ, Papageorgiou N, Lambiase PD, Schilling RJ, Combes S, Combes N, Albenque JP, Pozzilli P, Boveda S. Impact of Type-2 Diabetes Mellitus on the Outcomes of Catheter Ablation of Atrial Fibrillation (European Observational Multicentre Study). Am J Cardiol 2020; 125:901-906. [PMID: 31973808 DOI: 10.1016/j.amjcard.2019.12.037] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2019] [Revised: 12/12/2019] [Accepted: 12/17/2019] [Indexed: 12/11/2022]
Abstract
Type-2 diabetes mellitus (DM) is associated with an increased risk of atrial fibrillation (AF). It is unclear whether DM is a risk factor for arrhythmia recurrence following catheter ablation of AF. We performed a nonrandomised, observational study in 7 high-volume European centres. A total of 2,504 patients who underwent catheter ablation of AF were included, and procedural outcomes were compared among patients with or without DM. Patients with DM (234) accounted for 9.3% of the sample, and were significantly older, had a higher BMI and suffered more frequently from persistent AF. Arrhythmia relapses at 12 months after AF ablation occurred more frequently in the DM group (32.0% vs 25.3%, p = 0.031). After adjusting for type of AF (i.e., paroxysmal vs persistent), during a median follow-up of 17 ± 16 months, atrial arrhythmia free-survival was lower in the diabetics with persistent AF (log-rank p = 0.003), and comparable for paroxysmal AF (log-rank p = 0.554). These results were confirmed in a propensity-matched analysis, and DM was also an independent predictor of AF recurrence on the multivariate analysis (hazard ratio 1.39; 95% confidence interval 95%1.07 to 1.88; p = 0.016). There was no significant difference in the rate of periprocedural complications among DM and non-DM patients (3.8% vs 6.3%, p = 0.128). Efficacy and safety of cryoballoon ablation were comparable to radiofrequency ablation in both DM and no-DM groups. In conclusion, catheter ablation of AF appears to be safe in patients with DM. However, DM is associated with higher rate of atrial arrhythmia relapse, particularly for patients with persistent AF.
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Affiliation(s)
- Antonio Creta
- Campus Bio-Medico University of Rome, Rome, Italy; Barts Heart Centre, St. Bartholomew's Hospital, London, United Kingdom.
| | - Rui Providência
- Barts Heart Centre, St. Bartholomew's Hospital, London, United Kingdom; Clinic Pasteur of Toulouse, Toulouse, France; Institute of Health Informatics Research, University College of London, London, United Kingdom
| | - Pedro Adragão
- Cardiology Department, Hospital de Santa Cruz, Lisbon, Portugal
| | - Carlo de Asmundis
- Heart Rhythm Management Centre, Universiteit Ziekenhuis Brussel, Postgraduate program in Cardiac Electrophysiology and Pacing, Vrije Universiteit Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium
| | - Julian Chun
- Cardioangiologisches Centrum Bethanien, Medizinische Klinik III, Markus Krankenhaus, Wilhelm-Epstein-Street 4, D-60431 Frankfurt am Main, Germany
| | - Gianbattista Chierchia
- Heart Rhythm Management Centre, Universiteit Ziekenhuis Brussel, Postgraduate program in Cardiac Electrophysiology and Pacing, Vrije Universiteit Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium
| | | | - Boris Schmidt
- Cardioangiologisches Centrum Bethanien, Medizinische Klinik III, Markus Krankenhaus, Wilhelm-Epstein-Street 4, D-60431 Frankfurt am Main, Germany
| | | | - Malcolm Finlay
- Barts Heart Centre, St. Bartholomew's Hospital, London, United Kingdom
| | - Ross Jacob Hunter
- Barts Heart Centre, St. Bartholomew's Hospital, London, United Kingdom
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