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Wang Y, Li Q, Xu G, Yang Y, He F. Association between elevated serum parathyroid hormone and QTc interval prolongation in chronic kidney disease patients. Int Urol Nephrol 2025:10.1007/s11255-025-04479-1. [PMID: 40172614 DOI: 10.1007/s11255-025-04479-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2025] [Accepted: 03/21/2025] [Indexed: 04/04/2025]
Abstract
PURPOSE Heart rate-corrected (QTc) interval prolongation is frequently linked to fatal arrhythmias and sudden cardiac death in chronic kidney disease (CKD) patients. In this cross-sectional study, we assessed the prevalence of prolonged QTc intervals and identified clinical factors associated with them across different stages of kidney failure. METHODS 723 patients with CKD stages 2-5 who had electrocardiogram records available were analyzed retrospectively. QTc intervals were calculated by correcting the QT intervals for all patients included in the study. QTc interval prolongation defined as a QTc interval ˃ 440 ms was assessed for its prevalence and its association with various clinical factors. RESULTS A total of 723 patients with CKD stages 2-5 were finally included in this study, among which 420 (58.1%) were male. The average age of the participants was 48.2 ± 14.6 years old. In patients with CKD stages 2-4, the prevalence of QTc interval prolongation was 26%, 24.1%, and 37.8%, respectively. Among patients with CKD stage 5, those not on dialysis had a prevalence of 63%, while those undergoing dialysis had a prevalence of 74.3%. Multivariate logistic regression analysis revealed that elevated levels of parathyroid hormone (PTH) were significantly associated with an increased risk of QTc intervals prolongation in CKD patients (aOR = 1.384, 95% CI 1.173-1.632; P < 0.001). This suggests that higher PTH levels may contribute to QTc interval prolongation in this population. The patients were then grouped by CKD stages. Elevated PTH levels were independently associated with an increased risk of QTc interval prolongation specifically in CKD stages 4 and 5 patients who were not on dialysis. After adjusting for potential confounders, this association remained significant (CKD stage 4: aOR = 2.571, 95% CI 1.030-6.416; P < 0.001; CKD stage 5, non-dialysis: aOR = 1.333, 95% CI 1.063-1.671; P < 0.001). CONCLUSION In patients with CKD, the prevalence of QTc prolongation increases with advancing CKD stages. Specially, among patients with CKD stage 4 and stage 5 who were not on dialysis, elevated PTH levels were independently associated with an increased risk of QTc interval prolongation.
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Affiliation(s)
- Yanan Wang
- Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue. 1095, Wuhan, 430030, Hubei Province, China
| | - Qing Li
- Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue. 1095, Wuhan, 430030, Hubei Province, China
| | - Gang Xu
- Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue. 1095, Wuhan, 430030, Hubei Province, China
| | - Yi Yang
- Department of Public Health, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
| | - Fan He
- Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue. 1095, Wuhan, 430030, Hubei Province, China.
- Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, China.
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Campos RN, Moreira DAR, da Fonseca GM. Effect of dapagliflozin, a sodium-glucose co-transporter 2 inhibitor, on ventricular repolarization electrocardiographic parameters in type 2 diabetes patients: DAPA - ECG study. FRONTIERS IN CLINICAL DIABETES AND HEALTHCARE 2025; 6:1537005. [PMID: 40230406 PMCID: PMC11994709 DOI: 10.3389/fcdhc.2025.1537005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/29/2024] [Accepted: 03/11/2025] [Indexed: 04/16/2025]
Abstract
Background Type 2 diabetes (T2DM) is a chronic metabolic disorder that affects approximately 10.5% of the world's population and is an independent risk factor for cardiovascular complications, including sudden cardiac death (SCD). Inhibitors of sodium-glucose co-transporter type 2 (iSGLT2), particularly dapagliflozin, have emerged as promising treatments in patients with T2DM and with heart failure and chronic kidney disease, demonstrating the ability to significantly reduce major cardiovascular events. However, the exact mechanisms that promote the observed benefits are still not fully understood. Objective In this study, we sought to understand the mechanisms associated with the benefits of dapagliflozin by evaluating various electrophysiological parameters of the electrocardiogram (ECG) in patients with T2DM. A randomized, multicenter, prospective study with 174 patients with T2DM divided into two groups: one receiving dapagliflozin plus optimized guideline directed medical therapy (GDMT) and the other optimized GDMT without SGLT2 inhibitors. Clinical, electrocardiographic, laboratory, and echocardiographic evaluations were performed initially and after three months. Descriptive and inferential statistics were used, with a significance level of 0.05. Result This study shows that in patients treated with dapagliflozin plus GDMT, a significant reduction in the duration of the interval from the peak of the T wave to the end of the T wave (TpTe), the QTc interval, and the ratio between the TpTe/QT intervals was observed, with no change in other electrocardiographic variables such as QT interval dispersion, JT peak interval, or changes in the QRS complex and T wave axes (QRS-T angle). Conclusion In patients with T2DM, dapagliflozin significantly shortened the TpTe and QTc intervals, as well as the TpTe/QT ratio. These results suggest a reduction in ventricular electrical remodeling, highlighting a potential cardioprotective effect of dapagliflozin. Clinical trial registration https://clinicaltrials.gov/study/NCT06721442, identifier NCT06721442.
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Affiliation(s)
- Rodrigo Noronha Campos
- Dante Pazzanese Institute of Cardiology (IDPC), São Paulo, Brazil
- Beneficência Portuguesa Hospital, São Paulo, Brazil
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Tomek J, Zhou X, Martinez-Navarro H, Holmes M, Bury T, Berg LA, Tomkova M, Jo E, Nagy N, Bertrand A, Bueno-Orovio A, Colman M, Rodriguez B, Bers D, Heijma J. T-World: A highly general computational model of a human ventricular myocyte. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2025:2025.03.24.645031. [PMID: 40196542 PMCID: PMC11974879 DOI: 10.1101/2025.03.24.645031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 04/09/2025]
Abstract
Cardiovascular disease is the leading cause of death, demanding new tools to improve mechanistic understanding and overcome limitations of stem cell and animal-based research. We introduce T-World, a highly general virtual model of human ventricular cardiomyocyte suitable for multiscale studies. T-World shows comprehensive agreement with human physiology, from electrical activation to contraction, and is the first to replicate all key cellular mechanisms driving life-threatening arrhythmias. Extensively validated on unseen data, it demonstrates strong predictivity across applications and scales. Using T-World we revealed a likely sex-specific arrhythmia risk in females related to restitution properties, identified arrhythmia drivers in type 2 diabetes, and describe unexpected pro-arrhythmic role of NaV1.8 in heart failure. T-World demonstrates strong performance in predicting drug-induced arrhythmia risk and opens new opportunities for predicting and explaining drug efficacy, demonstrated by unpicking effects of mexiletine in Long QT syndrome 2. T-World is available as open-source code and an online app.
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Affiliation(s)
- Jakub Tomek
- Department of Anatomy, Physiology and Genetics (University of Oxford)
- Department of Pharmacology (UC Davis)
| | - Xin Zhou
- Department of Computer Science (University of Oxford)
| | | | - Maxx Holmes
- Department of Computer Science (University of Oxford)
| | - Thomas Bury
- Department of Physiology (McGill University)
| | | | | | - Emily Jo
- Department of Anatomy, Physiology and Genetics (University of Oxford)
| | - Norbert Nagy
- Department of Pharmacology and Pharmacotherapy (University of Szeged)
| | | | | | | | | | | | - Jordi Heijma
- Medical Physics and Biophysics (Medical University of Graz)
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Getnet M, Negash HK, Aragie H, Endale HT, Asefa T, Tesfaye W, Gela YY. Pooled prevalence and associated factors of ECG abnormality among type 2 diabetic patients in the last ten years: Systematic review and meta-analysis. PLoS One 2025; 20:e0319173. [PMID: 40080468 PMCID: PMC11906088 DOI: 10.1371/journal.pone.0319173] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2024] [Accepted: 01/28/2025] [Indexed: 03/15/2025] Open
Abstract
BACKGROUND Type 2 diabetes mellitus is a global epidemic affecting millions of individuals worldwide. It is considered a chronic metabolic disorder of impaired glucose homeostasis, associated with various long-term complications and poor prognosis of cardiovascular performance. Therefore, this systematic review aimed to determine the pooled prevalence of ECG abnormality among type 2 diabetic patients both in the hospital setting and the general population based on the existing literature. METHODS This systematic review has been conducted on the ECG abnormality of patients with Type 2 diabetes. Following the establishment of eligibility criteria, a literature search was conducted using three databases and two search engines. Included articles were then screened, critically appraised, and data extracted independently by two reviewers, and any disagreements were handled by the involvement of a third party. The quality of the included studies had been assessed using the New Castle Ottawa quality assessment scale tool. Pooled prevalence and sensitivity were determined by random effect analysis. Heterogeneity was assessed by Higgins's I2, and its presence was alleviated by using sub-group analysis. RESULT Following the identification of 32, 785 studies, 33 publications were eligible for the review with a sample size of 31, 449. The pooled prevalence of ECG abnormality among Type 2 diabetic patients was 31% (95% CI: 25, 36%). It was 26% (95% CI: 1, 51%), and 31% (95% CI: 24, 37%) in the hospital and general/ community population, respectively. Body mass index (AOR = 5.90; 95%CI: 4.96, 7.03), duration of diabetic mellitus (AOR = 9.21; 95%CI: 9.12, 9.31), and being hypertensive (AOR = 5.17; 95%CI: 4.90, 5.46), were significantly associated factors with ECG abnormality among patients with Type 2 diabetic mellitus. CONCLUSION The pooled prevalence of ECG abnormality among Type 2 diabetic mellitus patients was high, while its magnitude was higher among patients attending hospital settings than in the community. Duration of diabetic mellitus, high body mass index and presence of hypertension were significant factors in this review. Moreover, we advise more longitudinal researches to determine the incidence of ECG abnormality among patients with diabetes considering time duration and sex differences. ETHICAL CONSIDERATION Since our study was on the review of secondary data, ethical issues are not necessary.
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Affiliation(s)
- Mihret Getnet
- Department of Human Physiology, School of Medicine, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
- Department of Epidemiology and Biostatistics, Institute of Public Health, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Habtu Kifle Negash
- Department of Epidemiology and Biostatistics, Institute of Public Health, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
- Department of Human Anatomy, School of Medicine, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Hailu Aragie
- Department of Human Anatomy, School of Medicine, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Hiwot Tezera Endale
- Department of Medical Biochemistry, School of Medicine, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Tseganesh Asefa
- Department of Medical Nursing, School of Nursing, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Winta Tesfaye
- Department of Human Physiology, School of Medicine, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Yibeltal Yismaw Gela
- Department of Human Physiology, School of Medicine, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
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Rabkin SW. The QT interval in Parkinson's disease: a systematic review. J Geriatr Cardiol 2024; 21:855-864. [PMID: 39483261 PMCID: PMC11522711 DOI: 10.26599/1671-5411.2024.09.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2024] Open
Abstract
Background PD (PD) is associated with a twofold increase in the risk of death especially sudden death. A predisposing factor for cardiac sudden death is prolongation of the QT interval. This study evaluated the potential association between QT interval and PD. Methods A systematic search was conducted of Medline and EMBASE using the search terms "PD" AND "QT interval" OR "Cardiac Repolarization" to identify articles. Results Seven studies with persons with PD (n = 981) and control groups were identified. There was a significant difference in QT interval comparing patients with PD and persons without PD. The odds ratio showed a significant (P < 0.001) 2.6-fold (random effect) greater QTc prolongation in PD compared to control. Overall, there was a significantly longer QT in patients with PD than controls of 10.7 ± 2.8 ms. Data analysis did not show much publication bias. Focusing only on studies that related the QT interval to the severity of PD as assessed by Hoehn-Yahr classification (n = 6), there was a significant (P = 0.004) overall correlation between QT interval and the severity of PD. There was little publication bias. The data directly examining patients with PD taking any drug than might prolong QT do not support an association between these mediations and QT prolongation. Conclusion Individuals with PD have a longer QT interval than individuals without PD. The QT interval is associated with a greater severity of PD and a greater probability of developing more severe PD. The QT interval should be considered in assessment of PD and possibly as a target for the treatment of PD.
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Affiliation(s)
- Simon W Rabkin
- Division of Cardiology, University of British Columbia, Vancouver, BC V5Z 1M9, Canada
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Marx N, Federici M, Schütt K, Müller-Wieland D, Ajjan RA, Antunes MJ, Christodorescu RM, Crawford C, Di Angelantonio E, Eliasson B, Espinola-Klein C, Fauchier L, Halle M, Herrington WG, Kautzky-Willer A, Lambrinou E, Lesiak M, Lettino M, McGuire DK, Mullens W, Rocca B, Sattar N. 2023 ESC Guidelines for the management of cardiovascular disease in patients with diabetes. Eur Heart J 2023; 44:4043-4140. [PMID: 37622663 DOI: 10.1093/eurheartj/ehad192] [Citation(s) in RCA: 574] [Impact Index Per Article: 287.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/26/2023] Open
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Sun DK, Zhang N, Liu Y, Qiu JC, Tse G, Li GP, Roever L, Liu T. Dysglycemia and arrhythmias. World J Diabetes 2023; 14:1163-1177. [PMID: 37664481 PMCID: PMC10473954 DOI: 10.4239/wjd.v14.i8.1163] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 05/19/2023] [Accepted: 07/05/2023] [Indexed: 08/11/2023] Open
Abstract
Disorders in glucose metabolism can be divided into three separate but interrelated domains, namely hyperglycemia, hypoglycemia, and glycemic variability. Intensive glycemic control in patients with diabetes might increase the risk of hypoglycemic incidents and glucose fluctuations. These three dysglycemic states occur not only amongst patients with diabetes, but are frequently present in other clinical settings, such as during critically ill. A growing body of evidence has focused on the relationships between these dysglycemic domains with cardiac arrhythmias, including supraventricular arrhythmias (primarily atrial fibrillation), ventricular arrhythmias (malignant ventricular arrhythmias and QT interval prolongation), and bradyarrhythmias (bradycardia and heart block). Different mechanisms by which these dysglycemic states might provoke cardiac arr-hythmias have been identified in experimental studies. A customized glycemic control strategy to minimize the risk of hyperglycemia, hypoglycemia and glucose variability is of the utmost importance in order to mitigate the risk of cardiac arrhythmias.
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Affiliation(s)
- Dong-Kun Sun
- Department of Cardiology, Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, China
| | - Nan Zhang
- Department of Cardiology, Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, China
| | - Ying Liu
- Department of Cardiology, Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, China
| | - Jiu-Chun Qiu
- Department of Cardiology, Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, China
| | - Gary Tse
- Department of Cardiology, Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, China
- Kent and Medway Medical School, Kent CT2 7NT, Canterbury, United Kingdom
- School of Nursing and Health Studies, Metropolitan University, Hong Kong 999077, China
| | - Guang-Ping Li
- Department of Cardiology, Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, China
| | - Leonardo Roever
- Department of Clinical Research, Federal University of Uberlândia, Uberlândia, 38400384, MG, Brazil
| | - Tong Liu
- Department of Cardiology, Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, China
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Sawarthia S, Patel R, Patil PP. A Cross-Sectional Study to Determine the Association of Corrected QT Interval With Microalbuminuria in Type 2 Diabetes Mellitus. Cureus 2023; 15:e38967. [PMID: 37313082 PMCID: PMC10260269 DOI: 10.7759/cureus.38967] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/13/2023] [Indexed: 06/15/2023] Open
Abstract
Introduction Cardiac autonomic neuropathy (CAN) is a frequent and life-threatening complication of type 2 diabetes. Failure to diagnose can lead to high mortality and morbidity. In patients who have diabetes mellitus, microalbuminuria is an independent marker for cardiovascular disease. This study aimed to assess the corrected QT interval with microalbuminuria in type 2 diabetes mellitus. The objective of this study was to estimate the corrected QT interval in subjects with type 2 diabetes mellitus and to determine the association of the corrected QT interval with microalbuminuria type 2 diabetes mellitus. Methodology Ninety-five adult patients (>18 years to 65 years) diagnosed with type 2 diabetes mellitus with microalbuminuria were included in this study. Data were collected on the proforma through history taking and a general physical and systemic examination. An electrocardiograph was taken on the day of admission; the most prolonged QT interval was measured, and the RR interval was calculated. The data were statistically analyzed using IBM SPSS Statistics for Windows, Version 24 (Released 2016; IBM Corp., Armonk, New York, United States). Results There was a significant difference in the corrected QT interval prolongation prevalence between diabetic patients with microalbuminuria and without microalbuminuria (P-value <0.001). The mean corrected QT interval distribution did not differ significantly across various age groups of cases studied with microalbuminuria (P-value 0.98). The distribution of mean corrected QT interval did not differ significantly between the group of male cases and group of female cases studied with microalbuminuria (P-value 0.66). The mean corrected QT interval distribution did not differ significantly across various duration of diabetes groups among the cases studied with microalbuminuria (P-value 0.60). The mean corrected QT interval distribution did not differ significantly across different types of anti-diabetic treatment groups among the cases studied with microalbuminuria (P-value 0.64). Conclusion Type 2 diabetes has been prevalent in Indian and Asian populations. The early management of type 2 diabetes is necessary since the early stages of the disease can reduce the risk of CAN. Therefore, these patients should be diagnosed as early as possible and treated to reduce associated mortality and risk and to improve quality of care.
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Affiliation(s)
- Sonali Sawarthia
- Internal Medicine, Bharati Vidyapeeth Medical College and Hospital, Pune, IND
| | - Rishi Patel
- Internal Medicine, Bharati Vidyapeeth Medical College and Hospital, Pune, IND
| | - Prajakta P Patil
- Internal Medicine, Bharati Vidyapeeth Medical College and Hospital, Pune, IND
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Aburisheh K, AlKheraiji MF, Alwalan SI, Isnani AC, Rafiullah M, Mujammami M, Alfadda AA. Prevalence of QT prolongation and its risk factors in patients with type 2 diabetes. BMC Endocr Disord 2023; 23:50. [PMID: 36859297 PMCID: PMC9976503 DOI: 10.1186/s12902-022-01235-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Accepted: 11/30/2022] [Indexed: 03/03/2023] Open
Abstract
BACKGROUND QT prolongation increases cardiovascular mortality in diabetes. The risk factors for QT prolongation vary across different studies. There is no data on the QT prolongation in patients with diabetes from the Arab region, where diabetes is highly prevalent. Here we aimed to assess the prevalence of QT prolongation and its associated risk factors in patients with type 2 diabetes from Saudi Arabia. METHOD This was a retrospective, cross-sectional, hospital-based file review study. Data were collected from the medical records of patients with type 2 diabetes aged above 14 years and underwent ECG examination, and laboratory investigations were done within one month of ECG. RESULTS The study included 782 patients with a prevalence of QTc prolongation of 13%. Patients with prolonged QTc interval were characterized by older age, higher BMI, longer diabetes duration, lower total cholesterol and LDL-C, and more diabetic nephropathy, hypertension, and CVD cases. They were also more in insulin treatment, antihypertensive medications, loop diuretics, and potassium-sparring diuretics. Logistic regression analysis revealed the odds of prolonged QTc interval increased significantly with CVD (OR = 1.761, 95% CI:1.021-3.036, p = 0.042), and usage of loop diuretics (OR = 2.245, 95% CI:1.023-4.923, p = 0.044) after adjusting for age, gender, and duration of diabetes. CONCLUSION The risk factors associated with QTc prolongation in patients with type 2 diabetes are CVD, and loop diuretics. Age, BMI, and diabetes duration were more in people with QTc prolongation, whereas total cholesterol and LDL-C levels were lower. More patients had diabetic nephropathy, hypertension, and CVD with prolonged QTc.
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Affiliation(s)
- Khaled Aburisheh
- University Diabetes Center, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia
| | - Mohammad F AlKheraiji
- University Diabetes Center, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia
| | - Saleh I Alwalan
- University Diabetes Center, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia
| | - Arthur C Isnani
- Obesity Research Center, College of Medicine, King Saud University, P.O. Box 2925, Riyadh, 11461, Saudi Arabia
| | - Mohamed Rafiullah
- Strategic Center for Diabetes Research, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Muhammad Mujammami
- University Diabetes Center, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia
- Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Assim A Alfadda
- Obesity Research Center, College of Medicine, King Saud University, P.O. Box 2925, Riyadh, 11461, Saudi Arabia.
- Strategic Center for Diabetes Research, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
- Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
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Dominic SK, Henry RA, Kartha N, Pillai G. The Association Between Microalbuminuria and QTc Prolongation in Patients With Type 2 Diabetes Mellitus: A Single-Centre Study From South India. Cureus 2023; 15:e35646. [PMID: 37009348 PMCID: PMC10065364 DOI: 10.7759/cureus.35646] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/01/2023] [Indexed: 03/05/2023] Open
Abstract
BACKGROUND One of the most significant complications of type 2 diabetes mellitus (T2DM) is diabetic nephropathy, the leading cause of end-stage renal disease. Another important clinical marker in patients with type 2 diabetes is QTc interval prolongation. We aimed to study the association between QTc interval prolongation and microalbuminuria in patients with T2DM. OBJECTIVE The primary objective of this study was to examine the association between QTc interval prolongation and microalbuminuria in patients with T2DM. The secondary objective was to correlate the prolongation of the QTc interval with the duration of T2DM. MATERIALS AND METHODS This study was conducted as a single-centre, prospective, observational study in a tertiary-care centre in South India, Amrita Institute of Medical Sciences and Research Center. The study was conducted over two years, between April 2020 and April 2022. Patients aged more than 18 with T2DM with and without microalbuminuria were recruited into the study and control groups, and various parameters, including QTC intervals, were recorded. RESULTS A total of 120 patients were enrolled in the study, with 60 patients with microalbuminuria forming the study group and 60 patients without microalbuminuria forming the control group. There was a statistically significant association between microalbuminuria with a prolonged QTc interval, hypertension, a longer duration of T2DM, higher haemoglobin AIc (HbA1c) levels, and higher serum creatinine values.
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Yehia H, Youssef G, Gamil M, Elsaeed M, Sadek KM. Electrocardiographic substrates of arrhythmias in patients with end-stage and chronic kidney diseases: a case-control study. Egypt Heart J 2023; 75:13. [PMID: 36802307 PMCID: PMC9943799 DOI: 10.1186/s43044-023-00338-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Accepted: 02/10/2023] [Indexed: 02/23/2023] Open
Abstract
BACKGROUND Cardiovascular disease (CVD) is the most common cause of death in patients with renal diseases. Cardiac arrhythmia and sudden cardiac death are particularly important, and the burden is higher in patients on hemodialysis. The aim of this study is to compare specific ECG changes as markers of arrhythmias in patients with CKD and patients with end-stage renal disease (ESRD); all without clinically manifest heart disease, with normal control subjects. RESULTS Seventy-five ESRD patients on regular hemodialysis, 75 patients with stage 3-5 CKD and 40 healthy control subjects were included. All candidates were subjected to thorough clinical evaluation and laboratory tests including serum creatinine, glomerular filtration rate calculation, serum potassium, magnesium, calcium, phosphorus, iron, parathyroid hormone, and total iron binding capacity (TIBC). Resting twelve-lead ECG was done to calculate P wave dispersion (P-WD), corrected QT interval, QTc dispersion, Tpeak-Tend interval (Tp-e), and Tp-e/QT. Patients with ESRD had a significantly higher QTc dispersion (p < 0.001) and P-WD (p = 0.001) when compared to the other 2 groups. In the ESRD group, males had a significantly higher P-WD (p = 0.045), insignificantly higher QTc dispersion (p = 0.445), and insignificantly lower Tp-e/QT ratio (p = 0.252) as compared to females. Multivariate linear regression analysis for ESRD patients showed that serum creatinine (β = 0.279, p = 0.012) and transferrin saturation (β = - 0.333, p = 0.003) were independent predictors of increased QTc dispersion while ejection fraction (β = 0.320, p = 0.002), hypertension (β = - 0.319, p = 0.002), hemoglobin level (β = - 0.345, p = 0.001), male gender (β = - 0.274, p = 0.009) and TIBC (β = - 0.220, p = 0.030) were independent predictors of increased P wave dispersion. In the CKD group, TIBC (β = - 0.285, p = 0.013) was an independent predictor of QTc dispersion while serum calcium (β = 0.320, p = 0.002) and male gender (β = - 0.274, p = 0.009) were independent predictors of Tp-e/QT ratio. CONCLUSIONS Patients with stage 3-5 CKD and those with ESRD on regular hemodialysis exhibit significant ECG changes that are considered substrates for ventricular as well as supraventricular arrhythmias. Those changes were more evident in patients on hemodialysis.
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Affiliation(s)
- Hesham Yehia
- grid.7776.10000 0004 0639 9286Cairo University, Cairo, Egypt ,grid.7776.10000 0004 0639 9286Cardiovascular Department, Kasr Al Ainy School of Medicine, Cairo University, Cairo, Egypt
| | - Ghada Youssef
- Cairo University, Cairo, Egypt. .,Cardiovascular Department, Kasr Al Ainy School of Medicine, Cairo University, Cairo, Egypt.
| | - Mona Gamil
- grid.7776.10000 0004 0639 9286Cairo University, Cairo, Egypt ,grid.7776.10000 0004 0639 9286Internal Medicine Department, Kasr Al Ainy School of Medicine, Cairo University, Cairo, Egypt
| | - Mahmoud Elsaeed
- grid.7776.10000 0004 0639 9286Cairo University, Cairo, Egypt ,grid.7776.10000 0004 0639 9286Internal Medicine Department, Kasr Al Ainy School of Medicine, Cairo University, Cairo, Egypt
| | - Khaled M. Sadek
- grid.7776.10000 0004 0639 9286Cairo University, Cairo, Egypt ,grid.7776.10000 0004 0639 9286Internal Medicine Department, Kasr Al Ainy School of Medicine, Cairo University, Cairo, Egypt
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Welten SJGC, Elders PJM, Remmelzwaal S, Doekhie R, Kee KW, Nijpels G, van der Heijden AA. Prolongation of the heart rate-corrected QT interval is associated with cardiovascular diseases: Systematic review and meta-analysis. Arch Cardiovasc Dis 2023; 116:69-78. [PMID: 36690508 DOI: 10.1016/j.acvd.2022.11.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Revised: 11/03/2022] [Accepted: 11/07/2022] [Indexed: 01/09/2023]
Abstract
BACKGROUND Conflicting findings have described the association between prolonged heart rate-corrected QT interval (QTc) and cardiovascular disease. AIMS To identify articles investigating the association between QTc and cardiovascular disease morbidity and mortality, and to summarize the available evidence for the general and type 2 diabetes populations. METHODS A systematic search was performed in PubMed and Embase in May 2022 to identify studies that investigated the association between QTc prolongation and cardiovascular disease in both the general and type 2 diabetes populations. Screening, full-text assessment, data extraction and risk of bias assessment were performed independently by two reviewers. Effect estimates were pooled across studies using random-effect models. RESULTS Of the 59 studies included, 36 qualified for meta-analysis. Meta-analysis of the general population studies showed a significant association for: overall cardiovascular disease (fatal and non-fatal) (hazard ratio [HR] 1.68, 95% confidence interval [CI] 1.33-2.12; I2=69%); coronary heart disease (fatal and non-fatal) in women (HR 1.27, 95% CI 1.08-1.50; I2=38%; coronary heart disease (fatal and non-fatal) in men (HR 2.07, 95% CI 1.26-3.39; I2=78%); stroke (HR 1.59, 95% CI 1.29-1.96; I2=45%); sudden cardiac death (HR 1.60, 95% CI 1.14-2.25; I2=68%); and atrial fibrillation (HR 1.55, 95% CI 1.31-1.83; I2=0.0%). No significant association was found for cardiovascular disease in the type 2 diabetes population. CONCLUSION QTc prolongation was associated with risk of cardiovascular disease in the general population, but not in the type 2 diabetes population.
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Affiliation(s)
- Sabrina J G C Welten
- Department of General Practice, Amsterdam University Medical Centre, Vrije Universiteit Amsterdam, 1081 BT Amsterdam, The Netherlands; Health Behaviours & Chronic Diseases, Amsterdam Public Health Research Institute, 1081 BT Amsterdam, The Netherlands.
| | - Petra J M Elders
- Department of General Practice, Amsterdam University Medical Centre, Vrije Universiteit Amsterdam, 1081 BT Amsterdam, The Netherlands; Health Behaviours & Chronic Diseases, Amsterdam Public Health Research Institute, 1081 BT Amsterdam, The Netherlands
| | - Sharon Remmelzwaal
- Department of General Practice, Amsterdam University Medical Centre, Vrije Universiteit Amsterdam, 1081 BT Amsterdam, The Netherlands; Health Behaviours & Chronic Diseases, Amsterdam Public Health Research Institute, 1081 BT Amsterdam, The Netherlands; Department of Epidemiology and Data Science, Amsterdam University Medical Centre, Vrije Universiteit Amsterdam, Amsterdam Public Health Research Institute, 1081 HV Amsterdam, The Netherlands
| | - Roos Doekhie
- Department of General Practice, Amsterdam University Medical Centre, Vrije Universiteit Amsterdam, 1081 BT Amsterdam, The Netherlands
| | - Kok Wai Kee
- National Healthcare Group Polyclinics, Singapore, 138543
| | - Giel Nijpels
- Department of General Practice, Amsterdam University Medical Centre, Vrije Universiteit Amsterdam, 1081 BT Amsterdam, The Netherlands; Health Behaviours & Chronic Diseases, Amsterdam Public Health Research Institute, 1081 BT Amsterdam, The Netherlands
| | - Amber A van der Heijden
- Department of General Practice, Amsterdam University Medical Centre, Vrije Universiteit Amsterdam, 1081 BT Amsterdam, The Netherlands; Health Behaviours & Chronic Diseases, Amsterdam Public Health Research Institute, 1081 BT Amsterdam, The Netherlands
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Camanho LEM. Revisiting the QT Interval: An Old Marker for a New Disease? Arq Bras Cardiol 2023; 120:e20220878. [PMID: 36790307 PMCID: PMC10389110 DOI: 10.36660/abc.20220878] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Affiliation(s)
- Luiz Eduardo Montenegro Camanho
- Hospital Pró-CardíacoRio de JaneiroRJBrasilHospital Pró-Cardíaco – Serviço de Arritmias e Estimulação Cardíaca Artificial, Rio de Janeiro, RJ – Brasil
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Mistry S, Gouripeddi R, Reno CM, Abdelrahman S, Fisher SJ, Facelli JC. Detecting hypoglycemia-induced electrocardiogram changes in a rodent model of type 1 diabetes using shape-based clustering. PLoS One 2023; 18:e0284622. [PMID: 37200277 PMCID: PMC10194943 DOI: 10.1371/journal.pone.0284622] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Accepted: 04/04/2023] [Indexed: 05/20/2023] Open
Abstract
Sudden death related to hypoglycemia is thought to be due to cardiac arrhythmias. A clearer understanding of the cardiac changes associated with hypoglycemia is needed to reduce mortality. The objective of this work was to identify distinct patterns of electrocardiogram heartbeat changes that correlated with glycemic level, diabetes status, and mortality using a rodent model. Electrocardiogram and glucose measurements were collected from 54 diabetic and 37 non-diabetic rats undergoing insulin-induced hypoglycemic clamps. Shape-based unsupervised clustering was performed to identify distinct clusters of electrocardiogram heartbeats, and clustering performance was assessed using internal evaluation metrics. Clusters were evaluated by experimental conditions of diabetes status, glycemic level, and death status. Overall, shape-based unsupervised clustering identified 10 clusters of ECG heartbeats across multiple internal evaluation metrics. Several clusters demonstrating normal ECG morphology were specific to hypoglycemia conditions (Clusters 3, 5, and 8), non-diabetic rats (Cluster 4), or were generalized among all experimental conditions (Cluster 1). In contrast, clusters demonstrating QT prolongation alone or a combination of QT, PR, and QRS prolongation were specific to severe hypoglycemia experimental conditions and were stratified heartbeats by non-diabetic (Clusters 2 and 6) or diabetic status (Clusters 9 and 10). One cluster demonstrated an arrthymogenic waveform with premature ventricular contractions and was specific to heartbeats from severe hypoglycemia conditions (Cluster 7). Overall, this study provides the first data-driven characterization of ECG heartbeats in a rodent model of diabetes during hypoglycemia.
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Affiliation(s)
- Sejal Mistry
- Department of Biomedical Informatics, University of Utah, Salt Lake City, Utah, United States of America
| | - Ramkiran Gouripeddi
- Department of Biomedical Informatics, University of Utah, Salt Lake City, Utah, United States of America
- Center for Clinical and Translational Science, University of Utah, Salt Lake City, Utah, United States of America
| | - Candace M Reno
- Division of Endocrinology, Metabolism, and Diabetes, Department of Internal Medicine, University of Utah, Salt Lake City, Utah, United States of America
| | - Samir Abdelrahman
- Department of Biomedical Informatics, University of Utah, Salt Lake City, Utah, United States of America
| | - Simon J Fisher
- Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, University of Kentucky, Lexington, Kentucky, United States of America
| | - Julio C Facelli
- Department of Biomedical Informatics, University of Utah, Salt Lake City, Utah, United States of America
- Center for Clinical and Translational Science, University of Utah, Salt Lake City, Utah, United States of America
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Hung WC, Yu TH, Wu CC, Lee TL, Tang WH, Chen CC, Lu IC, Chung FM, Lee YJ, Hsu CC. Nonalcoholic Fatty Liver Disease Is Related to Abnormal Corrected QT Interval and Left Ventricular Hypertrophy in Chinese Male Steelworkers. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:14555. [PMID: 36361436 PMCID: PMC9657484 DOI: 10.3390/ijerph192114555] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Revised: 11/03/2022] [Accepted: 11/04/2022] [Indexed: 06/16/2023]
Abstract
OBJECTIVES Nonalcoholic fatty liver disease (NAFLD) has been associated with an increased risks of corrected QT (QTc) prolongation and left ventricular hypertrophy (LVH), both of which are associated with the development of cardiovascular disease. Rotating night shift work and a higher risk of incident NAFLD have been reported in male steelworkers. This study aimed to investigate the association of the severity of NAFLD with a prolonged QTc interval and LVH in a large cohort of Chinese male steelworkers. METHODS We examined baseline data of 2998 male steel workers aged 26 to 71 years at two plants. All workers at both plants received regular health assessments, including 12-lead ECG and echocardiography. Abdominal ultrasonography was performed to evaluate the severity of NAFLD. QTc prolongation was defined as follows: normal ≤ 430 ms, borderline 431-450 ms, and abnormal ≥ 451 ms. LVH was defined as a left ventricular mass index (LVMI) >131 g/m2. Associations of NAFLD with an abnormal QTc interval and LVH were examined using univariate and multivariate analyses. RESULTS The QTc interval and the LVMI were significantly correlated with the NAFLD fibrosis score, and the severity of NAFLD was correlated with an abnormal QTc interval and LVH (p for trend < 0.05). Multivariate analysis showed that in comparison to the workers without NAFLD, the odds ratios of having an abnormal QTc interval and LVH were 2.54 (95% CI: 1.22-5.39, p = 0.013) times and 2.23 (95% CI: 1.02-5.01, p = 0.044) times higher in the workers with moderate/severe NAFLD. CONCLUSIONS NAFLD may be closely associated with the risks of an abnormal QTc interval and LVH, suggesting that regular electrocardiogram and echocardiogram monitoring could be used to evaluate the risk of arrhythmia and LVH in male steelworkers with NAFLD.
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Affiliation(s)
- Wei-Chin Hung
- Division of Cardiology, Department of Internal Medicine, E-Da Hospital, Kaohsiung 82445, Taiwan
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung 82445, Taiwan
| | - Teng-Hung Yu
- Division of Cardiology, Department of Internal Medicine, E-Da Hospital, Kaohsiung 82445, Taiwan
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung 82445, Taiwan
| | - Cheng-Ching Wu
- Division of Cardiology, Department of Internal Medicine, E-Da Hospital, Kaohsiung 82445, Taiwan
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung 82445, Taiwan
- Division of Cardiology, Department of Internal Medicine, E-Da Cancer Hospital, Kaohsiung 82445, Taiwan
| | - Thung-Lip Lee
- Division of Cardiology, Department of Internal Medicine, E-Da Hospital, Kaohsiung 82445, Taiwan
- School of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung 82445, Taiwan
| | - Wei-Hua Tang
- Division of Cardiology, Department of Internal Medicine, Taipei Veterans General Hospital, Yuli Branch, Hualien 98142, Taiwan
- Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan
| | - Chia-Chi Chen
- Department of Pathology, E-Da Hospital, Kaohsiung 82445, Taiwan
- College of Medicine, I-Shou University, Kaohsiung 82445, Taiwan
| | - I-Cheng Lu
- Department of Occupational Medicine, E-Da Hospital, Kaohsiung 82445, Taiwan
| | - Fu-Mei Chung
- Division of Cardiology, Department of Internal Medicine, E-Da Hospital, Kaohsiung 82445, Taiwan
| | | | - Chia-Chang Hsu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Hospital, Kaohsiung 82445, Taiwan
- Health Examination Center, E-Da Dachang Hospital, Kaohsiung 80794, Taiwan
- The School of Chinese Medicine for Post Baccalaureate, College of Medicine, I-Shou University, Kaohsiung 82445, Taiwan
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Wei F, Zhang Y, Wang X, Huo J. Effects of high glucose and insulin on the electrophysiological properties of cardiomyocytes derived from human-induced pluripotent stem cells. ZHONG NAN DA XUE XUE BAO. YI XUE BAN = JOURNAL OF CENTRAL SOUTH UNIVERSITY. MEDICAL SCIENCES 2022; 47:610-618. [PMID: 35753731 PMCID: PMC10929917 DOI: 10.11817/j.issn.1672-7347.2022.210408] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Indexed: 06/15/2023]
Abstract
OBJECTIVES The risk of arrhythmia increases in diabetic patients. However, the effects of hyperglycemia and insulin therapy on the electrophysiological properties of human cardiomyocytes remain unclear. This study is to explore the effects of high glucose and insulin on the electrophysiological properties and arrhythmias of cardiomyocytes derived from human-induced pluripotent stem cells (hiPSC-CMs). METHODS Immunofluorescent staining and flow cytometry were used to analyze the purity of hiPSC-CMs generated from human skin fibroblasts of a healthy donor. The hiPSC-CMs were divided into 3 group (treated with normal medium, high glucose and insulin for 4 days): a control group (NM group, containing 5 mmol/L glucose), a high glucose group (HG group, containing 15 mmol/L glucose), and a high glucose combined with insulin (HG+INS group, containing 15 mmol/L glucose+100 mg/L insulin). Electrophysiological changes of hiPSC-CMs were detected by microelectrode array (MEA) before or after treatment with glucose and insulin, including beating rate (BR), field potential duration (FPD) (similar to QT interval in ECG), FPDc (FPD corrected by BR), spike amplitude and conduction velocity (CV). Effects of sotalol on electrophysiological properties and arrhythmias of hiPSC-CMs were also evaluated. RESULTS The expression of cardiac-specific marker of cardiac troponin T was high in the hiPSC-CMs. The purity of hiPSC-CMs was 99.06%. Compared with the NM group, BR was increased by (9.14±0.8)% in the HG group (P<0.01). After treatment with high glucose, FPD was prolonged from (460.4±9.0) ms to (587.6±23.7) ms in the HG group, while it was prolonged from (462.5±14.5) ms to (512.6±17.6) ms in the NM group. Compared with the NM group, FPD of hiPSC-CMs was prolonged by (16.8±1.4)% in the HG group (P<0.01). The FPDc of hiPSC-CMs was prolonged from (389.1±13.7) ms to (478.3±31.5) ms in the HG group, and that was prolonged from (387.7±21.6) ms to (422.6±32.9) ms in the NM group. Compared with the NM group, the FPDc of hiPSC-CMs was prolonged by (13.9±1.3)% in HG group (P<0.01). The spike amplitude and CV remained unchanged between the HG group and the NM group (P>0.05). Ten µmol/L of sotalol can induce significant arrhythmias from all wells in the HG group. After treatment with insulin and high glucose, compared with the HG group, BR was increased by (8.3±0.5)% in the HG+INS group (P<0.05). The FPD was prolonged from (463.4±9.7) ms to (532.6±12.8) ms in the HG+INS group, while it was prolonged from (460.4±9.0) ms to (587.6±23.7) ms in the HG group. Compared with the HG group, the FPD of hiPSC-CMs was shortened by (12.7±1.9)% in the HG+INS group (P<0.01). The FPDc of hiPSC-CMs was prolonged from (387.4±4.1) ms to (422.4±10.0) ms in the HG+INS group, and that was prolonged from (384.8±4.0) ms to (476.3±11.5) ms in HG group. Compared with the HG group, the FPDc of hiPSC-CMs was shortened by (14.7±1.1)% in HG group (P<0.01). After the insulin treatment, the spike amplitude of hiPSC-CMs was increased from (3.12±0.46) mV to (4.35±0.64) mV in the HG+INS group, while it was enhanced from (3.06±0.35) mV to (3.33±0.41) mV in the HG group. The spike amplitude of hiPSC-CMs was increased by (30.8±3.7)% in the HG+INS group compared with that in the HG group (P<0.05). The CV in the HG+INS group was increased from (0.23±0.08) mm/ms to (0.32±0.08) mm/ms after insulin treatment, which was increased from (0.21±0.04) mm/ms to (0.30±0.07) mm/ms in the HG group, but there was no significant difference in CV between the HG+INS group and the HG group (P>0.05). The induction experiment showed that 10 μmol/L of sotalol could prolong the FPDc of hiPSC-CMs by (78.9±11.6)% in the HG+INS group, but no arrhythmia was induced in each well. CONCLUSIONS High glucose can induce FPD/FPDc of hiPSC-CMs prolongation and increase the risk of arrhythmia induced by drugs. Insulin can reduce the FPD/FPDc prolongation and the risk of induced arrhythmia by high glucose.These results are important to understand the electrophysiological changes of the myocardium in diabetic patients and the impact of insulin therapy on its electrophysiology. Further study on the mechanism may provide new ideas and methods for the treatment of acquired and even inherited long QT syndrome.
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Affiliation(s)
- Feng Wei
- Department of Structural Heart Disease, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061.
- Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education, Xi'an 710061.
- Key Laboratory of Molecular Cardiology in Shaanxi Province, Xi'an 710061.
| | - Yushun Zhang
- Department of Structural Heart Disease, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061
| | - Xingye Wang
- Department of Structural Heart Disease, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061
| | - Jianhua Huo
- Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education, Xi'an 710061
- Key Laboratory of Molecular Cardiology in Shaanxi Province, Xi'an 710061
- Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China
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Metformin Reduces Potassium Currents and Prolongs Repolarization in Non-Diabetic Heart. Int J Mol Sci 2022; 23:ijms23116021. [PMID: 35682699 PMCID: PMC9181026 DOI: 10.3390/ijms23116021] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Revised: 05/14/2022] [Accepted: 05/24/2022] [Indexed: 01/27/2023] Open
Abstract
Metformin is the first choice drug for the treatment of type 2 diabetes due to positive results in reducing hyperglycaemia and insulin resistance. However, diabetic patients have higher risk of ventricular arrhythmia and sudden cardiac death, and metformin failed to reduce ventricular arrhythmia in clinical trials. In order to explore the mechanisms responsible for the lack of protective effect, we investigated in vivo the effect of metformin on cardiac electrical activity in non-diabetic rats; and in vitro in isolated ventricular myocytes, HEK293 cells expressing the hERG channel and human induced pluripotent stem cells derived cardiomyocytes (hIPS-CMs). Surface electrocardiograms showed that long-term metformin treatment (7 weeks) at therapeutic doses prolonged cardiac repolarization, reflected as QT and QTc interval duration, and increased ventricular arrhythmia during the caffeine/dobutamine challenge. Patch-clamp recordings in ventricular myocytes isolated from treated animals showed that the cellular mechanism is a reduction in the cardiac transient outward potassium current (Ito). In vitro, incubation with metformin for 24 h also reduced Ito, prolonged action potential duration, and increased spontaneous contractions in ventricular myocytes isolated from control rats. Metformin incubation also reduced IhERG in HEK293 cells. Finally, metformin incubation prolonged action potential duration at 30% and 90% of repolarization in hIPS-CMs, which is compatible with the reduction of Ito and IhERG. Our results show that metformin directly modifies the electrical behavior of the normal heart. The mechanism consists in the inhibition of repolarizing currents and the subsequent decrease in repolarization capacity, which prolongs AP and QTc duration.
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Effect of hyperglycaemia in combination with moxifloxacin on cardiac repolarization in male and female patients with type I diabetes. Clin Res Cardiol 2022; 111:1147-1160. [PMID: 35596784 PMCID: PMC9525410 DOI: 10.1007/s00392-022-02037-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Accepted: 05/05/2022] [Indexed: 11/20/2022]
Abstract
Background Patients with Type 1 diabetes mellitus have been shown to be at a two to ten-fold higher risk of sudden cardiac death (SCD) (Svane et al., Curr Cardiol 2020; 22:112) than the general population, but the underlying mechanism is unclear. Hyperglycaemia is a recognised cause of QTc prolongation; a state patients with type 1 diabetes are more prone to, potentially increasing their risk of ventricular arrhythmia. Understanding the QTc prolongation effect of both hyperglycaemia and the concomitant additive risk of commonly prescribed QTc-prolonging drugs such as Moxifloxacin may help to elucidate the mechanism of sudden cardiac death in this cohort. This single-blinded, placebo-controlled study investigated the extent to which hyperglycaemia prolongs the QTc in controlled conditions, and the potential additive risk of QTc-prolonging medications. Methods 21 patients with type 1 diabetes mellitus were enrolled to a placebo-controlled crossover study at a single clinical trials unit. Patients underwent thorough QTc assessment throughout the study. A ‘hyperglycaemic clamp’ of oral and intravenous glucose was administered with a target blood glucose of > 25 mM and maintained for 2 h on day 1 and day 3, alongside placebo on day 1 and moxifloxacin on day 3. Day 2 served as a control day between the two active treatment days. Thorough QTc assessment was conducted at matched time points over 3 days, and regular blood sampling was undertaken at matched time intervals for glucose levels and moxifloxacin exposure. Results Concentration-effect modelling showed that acute hyperglycaemia prolonged the QTc interval in female and male volunteers with type 1 diabetes by a peak mean increase of 13 ms at 2 h. Peak mean QTc intervals after the administration of intravenous Moxifloxacin during the hyperglycaemic state were increased by a further 9 ms at 2 h, to 22 ms across the entire study population. Regression analysis suggested this additional increase was additive, not exponential. Hyperglycaemia was associated with a significantly greater mean QTc-prolonging effect in females, but the mean peak increase with the addition of moxifloxacin was the same for males and females. This apparent sex difference was likely due to the exclusive use of basal insulin in the male patients, which provided a low level of exogenous insulin during the study assessments thereby mitigating the effects of hyperglycaemia on QTc. This effect was partially overcome by Moxifloxacin administration, suggesting both hyperglycaemia and moxifloxacin prolong QTc by different mechanisms, based on subinterval analysis. Conclusions Hyperglycaemia was found to be a significant cause of QTc prolongation and the additional effect of a QTc-prolonging positive control (moxifloxacin) was found to be additive. Given the high risk of sudden cardiac death in type 1 diabetes mellitus, extra caution should be exercised when prescribing any medication in this cohort for QTc effects, and further research needs to be undertaken to elucidate the exact mechanism underlying this finding and explore the potential prescribing risk in diabetes. Trial Registration NCT number: NCT01984827. Graphical abstract ![]()
Supplementary Information The online version contains supplementary material available at 10.1007/s00392-022-02037-8.
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Jiang A, Gu H, Feng Z, Ding Y, Xu X, Yin G, Zhang W, Shen Z, Li Q. Heart rate-corrected QT interval: A novel diagnostic biomarker for diabetic peripheral neuropathy. J Diabetes Investig 2022; 13:850-857. [PMID: 34932277 PMCID: PMC9077736 DOI: 10.1111/jdi.13738] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Revised: 12/15/2021] [Accepted: 12/17/2021] [Indexed: 11/28/2022] Open
Abstract
AIMS/INTRODUCTION To explore the relationship between heart rate-corrected QT (QTc) interval and diabetic peripheral neuropathy (DPN), and whether QTc interval has diagnostic utility for DPN beyond nerve conduction velocity. MATERIALS AND METHODS A total of 965 patients with diabetes, including 473 patients with DPN and 492 patients without DPN, underwent standard 12-lead electrocardiography and detailed assessments of peripheral neuropathy. RESULTS Patients with DPN had longer QTc intervals than those without. Among participants, from the first to fourth quartile of QTc interval, the proportion of patients with DPN appreciably increased and the nerve conduction velocity obviously decreased (P for trend <0.001). The univariate and multivariate analyses showed that prolonged QTc interval was closely associated with increased risk of DPN (univariable odds ratio 1.112, 95% confidence interval 1.097-1.127, P < 0.001; multivariable odds ratio 1.118, 95% confidence interval 1.099-1.137, P < 0.001). Receiver operating characteristic analysis for the diagnosis of DPN showed a greater area under the curve for QTc interval of 0.894 than the median nerve motor conduction velocity of 0.691, median nerve sensory conduction velocity of 0.664 and peroneal nerve motor conduction velocity of 0.692. The optimal cut-off point of QTc interval for DPN was 428.5 ms with sensitivity of 0.715 and specificity of 0.920 (P < 0.001). The combination of QTc interval and nerve conduction testing increased the area under the curve for the diagnosis of DPN (from 0.736 to 0.916; P < 0.001). CONCLUSIONS QTc interval with 428.5 ms has more reliable diagnostic utility for DPN than nerve conduction velocity, and prolonged QTc interval is closely associated with an increased risk of DPN.
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Affiliation(s)
- Ai‐jun Jiang
- Department of Endocrinology, Nanjing First HospitalNanjing Medical UniversityNanjingChina
| | - Heng Gu
- Nanjing Medical UniversityNanjingChina
| | - Zhan‐rong Feng
- Department of EndocrinologyShuyang Hospital of Traditional Chinese MedicineSuqianChina
| | - Ying Ding
- Department of EndocrinologyShuyang Hospital of Traditional Chinese MedicineSuqianChina
| | - Xiao‐hua Xu
- Department of Endocrinology, Nanjing First HospitalNanjing Medical UniversityNanjingChina
| | - Guo‐ping Yin
- Department of Endocrinology, Nanjing First HospitalNanjing Medical UniversityNanjingChina
| | - Wen‐li Zhang
- Department of Endocrinology, Nanjing First HospitalNanjing Medical UniversityNanjingChina
| | - Zi‐yang Shen
- Department of Endocrinology, Nanjing First HospitalNanjing Medical UniversityNanjingChina
| | - Qian Li
- Department of Endocrinology, Nanjing First HospitalNanjing Medical UniversityNanjingChina
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Bourazana A, Giamouzis G, Skoularigis J, Triposkiadis F, Xanthopoulos A. Glucose lowering does not necessarily reduce cardiovascular risk in type 2 diabetes. World J Cardiol 2022; 14:266-270. [PMID: 35582467 PMCID: PMC9048273 DOI: 10.4330/wjc.v14.i4.266] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Revised: 12/29/2021] [Accepted: 03/16/2022] [Indexed: 02/06/2023] Open
Abstract
Diabetes mellitus (DM) is a health condition characterized by glucose dysregulation and affects millions of people worldwide. The presentation of heart failure in diabetic cardiomyopathy extends over a wide phenotypic spectrum, commencing from asymptomatic, subclinical structural abnormalities to severely symptomatic biventricular dysfunction with increased mortality risk. Similarly, the spectrum of systolic dysfunction in diabetic-induced heart failure is diverse. DM leads also to cardiac electrical remodeling reacting on various targets. Dipeptidyl peptidase-4 (DPP-4) inhibitors reduce glucagon and blood glucose levels by raising levels of the endogenous hormones glucagon-like-peptide 1 and glucose-dependent insulinotropic peptide and constitute a safe and effective glucose lowering treatment option in patients with type 2 DM. Despite DPP-4 inhibitors' efficacy regarding glycemic control, their effect on cardiovascular outcomes (myocardial infarction, stroke, hospitalization for heart failure, hospitalization for unstable angina, hospitalization for coronary revascularization, and cardiovascular death) in diabetic patients has been neutral. The potential correlation between atrial flutter and DPP-4 inhibitors administration needs further investigation.
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Affiliation(s)
- Angeliki Bourazana
- Department of Cardiology, University Hospital of Larissa, Larissa 41110, Greece
| | - Grigorios Giamouzis
- Department of Cardiology, University Hospital of Larissa, Larissa 41110, Greece
| | - John Skoularigis
- Department of Cardiology, University Hospital of Larissa, Larissa 41110, Greece
| | | | - Andrew Xanthopoulos
- Department of Cardiology, University Hospital of Larissa, Larissa 41110, Greece.
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21
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Garcia-Gonzalez MA, Vallejo-Ruiz V, Atonal-Flores F, Flores-Hernandez J, Torres-Ramírez O, Diaz-Fonsecae A, Perez Vizcaino F, Lopez-Lopez JG. Sildenafil prevents right ventricular hypertrophy and improves heart rate variability in rats with pulmonary hypertension secondary to experimental diabetes. Clin Exp Hypertens 2022; 44:355-365. [DOI: 10.1080/10641963.2022.2050743] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Affiliation(s)
- Miguel Angel Garcia-Gonzalez
- Departamento de Farmacia, Benemerita Universidad Autonoma de Puebla, Laboratorio de Farmacia Clinica, Edificio FCQ10, Ciudad Universitaria, Col. Jardines de San Manuel, Puebla, Mexico
| | - Veronica Vallejo-Ruiz
- Instituto Mexicano del Seguro Social, Centro de Investigación Biomédica de Oriente, Laboratorio de Biología Molecular, Puebla, Mexico
| | - Fausto Atonal-Flores
- Departamento de Fisiología, Benemérita Universidad Autónoma de Puebla, Facultad de Medicina, Metepec, Mexico
| | - Jorge Flores-Hernandez
- Laboratorio de Neuromodulación, Benemerita Universidad Autonoma de Puebla, Fisiología, Puebla,Mexico
| | - Oswaldo Torres-Ramírez
- Departamento de Farmacia, Benemérita Universidad Autónoma de Puebla, Facultad de Ciencias Químicas, Puebla, Mexico
| | - Alfonso Diaz-Fonsecae
- Departamento de Farmacia, Benemérita Universidad Autónoma de Puebla, Facultad de Ciencias Químicas, Puebla, Mexico
| | - Francisco Perez Vizcaino
- Departamento de Farmacología y Toxicología, Universidad Complutense de Madrid, Escuela de Medicina, Puebla,Mexico
| | - Jose Gustavo Lopez-Lopez
- Departamento de Farmacia, Benemerita Universidad Autonoma de Puebla, Laboratorio de Farmacia Clinica, Edificio FCQ10, Ciudad Universitaria, Col. Jardines de San Manuel, Puebla, Mexico
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22
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Remme CA. Sudden cardiac death in diabetes and obesity: mechanisms and therapeutic strategies. Can J Cardiol 2022; 38:418-426. [PMID: 35017043 DOI: 10.1016/j.cjca.2022.01.001] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Revised: 01/05/2022] [Accepted: 01/05/2022] [Indexed: 02/07/2023] Open
Abstract
Ventricular arrhythmias and sudden cardiac death (SCD) occur most frequently in the setting of coronary artery disease, cardiomyopathy and heart failure, but are also increasingly observed in individuals suffering from diabetes mellitus and obesity. The incidence of these metabolic disorders is rising in Western countries, but adequate prevention and treatment of arrhythmias and SCD in affected patients is limited due to our incomplete knowledge of the underlying disease mechanisms. Here, an overview is presented of the prevalence of electrophysiological disturbances, ventricular arrhythmias and SCD in the clinical setting of diabetes and obesity. Experimental studies are reviewed, which have identified disease pathways and associated modulatory factors, in addition to pro-arrhythmic mechanisms. Key processes are discussed, including mitochondrial dysfunction, oxidative stress, cardiac structural derangements, abnormal cardiac conduction, ion channel dysfunction, prolonged repolarization and dysregulation of intracellular sodium and calcium homeostasis. In addition, the recently identified pro-arrhythmic effects of dysregulated branched chain amino acid metabolism, a common feature in patients with metabolic disorders, are addressed. Finally, current management options are discussed, in addition to the potential development of novel preventive and therapeutic strategies based on recent insight gained from translational studies.
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Affiliation(s)
- Carol Ann Remme
- Department of Experimental Cardiology, Amsterdam UMC, location AMC, Amsterdam, The Netherlands.
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23
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Mittal A, Garg R, Bahl A, Khullar M. Molecular Mechanisms and Epigenetic Regulation in Diabetic Cardiomyopathy. Front Cardiovasc Med 2022; 8:725532. [PMID: 34977165 PMCID: PMC8716459 DOI: 10.3389/fcvm.2021.725532] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Accepted: 11/15/2021] [Indexed: 12/25/2022] Open
Abstract
Diabetes mellitus (DM) is an important lifestyle disease. Type 2 diabetes is one of the prime contributors to cardiovascular diseases (CVD) and diabetic cardiomyopathy (DbCM) and leads to increased morbidity and mortality in patients with DM. DbCM is a typical cardiac disease, characterized by cardiac remodeling in the presence of DM and in the absence of other comorbidities such as hypertension, valvular diseases, and coronary artery disease. DbCM is associated with defective cardiac metabolism, altered mitochondrial structure and function, and other physiological and pathophysiological signaling mechanisms such as oxidative stress, inflammation, myocardial apoptosis, and autophagy. Epigenetic modifiers are crucial players in the pathogenesis of DbCM. Thus, it is important to explore the role of epigenetic modifiers or modifications in regulating molecular pathways associated with DbCM. In this review, we have discussed the role of various epigenetic mechanisms such as histone modifications (acetylation and methylation), DNA methylation and non-coding RNAs in modulating molecular pathways involved in the pathophysiology of the DbCM.
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Affiliation(s)
- Anupam Mittal
- Department of Translational and Regenerative Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Rajni Garg
- Council of Scientific and Industrial Research - Institute of Microbial Technology, Chandigarh, India
| | - Ajay Bahl
- Department of Cardiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Madhu Khullar
- Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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24
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Hatamnejad MR, Bazrafshan H, Hosseinpour M, Izadpanah P, Kasravi MR, Bazrafshan M. Ventricular repolarization indicators in risk stratification of decompensated heart failure patients with ventricular systolic dysfunction. CASPIAN JOURNAL OF INTERNAL MEDICINE 2022; 13:533-545. [PMID: 35974927 PMCID: PMC9348206 DOI: 10.22088/cjim.13.3.533] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Revised: 09/04/2021] [Accepted: 02/26/2022] [Indexed: 11/10/2022]
Abstract
BACKGROUND Ventricular repolarization measurement by QTc interval and QT dispersion can recognize high-risk patients. Previous research tended to evaluate the act of repolarization indicators alone but this study aimed to elucidate their prognostic utility before and after modifying confounding parameters in risk stratification of different aspects of prognosis in decompensated heart failure patients with systolic dysfunction. METHODS Data of 98 variables were evaluated to determine their predictive value concerning arrhythmic events, in-hospital, and long-term mortality. RESULTS From 858 cases that presented with acute heart failure, 19.2% (n=165) were enrolled in the study. During hospitalization, arrhythmic events and cardiac-related mortality occurred in 56(33.9%) and 11(7%) patients, respectively. QTc and QT dispersion were independent predictors of arrhythmia and in-hospital mortality after adjustment of the variables (arrhythmic events: QTc interval OR 1.085, P=0.007, QT dispersion OR 1.077, P=0.007, in-hospital mortality: QTc interval OR 1.116, P=0.009, QT dispersion OR 1.067, P=0.011). After being discharged, they were tracked for 181±56 days. Within the 16 deaths in follow-up time, 6 sudden cardiac deaths were documented. Cox regression, defined QTc as the predictor of all-cause and sudden death mortality (all-cause: HR 1.041, 95% CI 1.015-1.067, P=0.002; sudden death: HR 1.063, 95% CI 1.023-1.105, P=0.002); nevertheless, efforts to demonstrate QT dispersion as the predictor failed. CONCLUSION The predictive nature of QT parameters was significant after modification of the variables; therefore, they should be measured for risk stratification of ventricular repolarization arrhythmia and death in decompensated heart failure patients.
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Affiliation(s)
- Mohammad Reza Hatamnejad
- Faculty of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
- Al-Zahra Charity Hospital, Department of Cardiology Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Hamed Bazrafshan
- Department of Cardiology, Shiraz University of Medical Sciences, Shiraz, Iran
- Al-Zahra Charity Hospital, Department of Cardiology Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Morteza Hosseinpour
- Faculty of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
- Al-Zahra Charity Hospital, Department of Cardiology Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Peyman Izadpanah
- Department of Cardiology, Shiraz University of Medical Sciences, Shiraz, Iran
- Al-Zahra Charity Hospital, Department of Cardiology Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | | | - Mehdi Bazrafshan
- Faculty of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
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25
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Lu CF, Ge XQ, Wang Y, Su JB, Wang XQ, Zhang DM, Xu F, Liu WS, Su M. The relationship between adenosine deaminase and heart rate-corrected QT interval in type 2 diabetic patients. Endocr Connect 2021; 10:894-901. [PMID: 34261041 PMCID: PMC8346184 DOI: 10.1530/ec-21-0199] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Accepted: 07/14/2021] [Indexed: 12/25/2022]
Abstract
BACKGROUND Prolonged heart rate-corrected QT (QTc) interval may reflect poor prognosis of patients with type 2 diabetes (T2D). Serum adenosine deaminase (ADA) levels are related to hyperglycemia, insulin resistance (IR) and inflammation, which may participate in diabetic complications. We investigated the association of serum ADA levels with prolonged QTc interval in a large-scale sample of patients with T2D. METHODS In this cross-sectional study, a total of 492 patients with T2D were recruited. Serum ADA levels were determined by venous blood during fasting. QTc interval was estimated from resting 12-lead ECGs, and prolonged QTc interval was defined as QTc > 440 ms. RESULTS In this study, the prevalence of prolonged QTc interval was 22.8%. Serum ADA levels were positively associated with QTc interval (r = 0.324, P < 0.0001). The proportion of participants with prolonged QTc interval increased significantly from 9.2% in the first tertile (T1) to 24.7% in the second tertile (T2) and 39.0% in the third tertile (T3) of ADA (P for trend < 0.001). After adjusting for other possible risk factors by multiple linear regression analysis, serum ADA level was still significantly associated with QTc interval (β = 0.217, t = 3.400, P < 0.01). Multivariate logistic regression analysis showed that female (OR 5.084, CI 2.379-10.864, P < 0.001), insulin-sensitizers treatment (OR 4.229, CI 1.290-13.860, P = 0.017) and ADA (OR 1.212, CI 1.094-1.343, P < 0.001) were independent contributors to prolonged QTc interval. CONCLUSIONS Serum ADA levels were independently associated with prolonged QTc interval in patients with T2D.
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Affiliation(s)
- Chun-feng Lu
- Department of Endocrinology, Affiliated Hospital 2 of Nantong University and First People’s Hospital of Nantong City, Nantong, China
| | - Xiao-qin Ge
- Department of Endocrinology, Affiliated Hospital 2 of Nantong University and First People’s Hospital of Nantong City, Nantong, China
| | - Yan Wang
- Department of Geriatrics, Affiliated Hospital 2 of Nantong University and First People’s Hospital of Nantong City, Nantong, China
| | - Jian-bin Su
- Department of Endocrinology, Affiliated Hospital 2 of Nantong University and First People’s Hospital of Nantong City, Nantong, China
- Correspondence should be addressed to J Su or X Wang: or
| | - Xue-qin Wang
- Department of Endocrinology, Affiliated Hospital 2 of Nantong University and First People’s Hospital of Nantong City, Nantong, China
- Correspondence should be addressed to J Su or X Wang: or
| | - Dong-mei Zhang
- Clinical Medicine Research Center, Affiliated Hospital 2 of Nantong University and First People’s Hospital of Nantong City, Nantong, China
| | - Feng Xu
- Department of Endocrinology, Affiliated Hospital 2 of Nantong University and First People’s Hospital of Nantong City, Nantong, China
| | - Wang-shu Liu
- Department of Endocrinology, Affiliated Hospital 2 of Nantong University and First People’s Hospital of Nantong City, Nantong, China
| | - Min Su
- Department of Endocrinology, Nantong Hospital of Traditional Chinese Medicine, Nantong Hospital Affiliated to Nanjing University of Chinese Medicine, Nantong, China
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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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27
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Myocardial repolarization is affected in patients with diabetic retinopathy. JOURNAL OF SURGERY AND MEDICINE 2021. [DOI: 10.28982/josam.955574] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
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Charamba B, Liew A, Coen E, Newell J, O’Brien T, Wijns W, Simpkin AJ. Modelling the relationship between continuously measured glucose and electrocardiographic data in adults with type 1 diabetes mellitus. Endocrinol Diabetes Metab 2021; 4:e00263. [PMID: 34277986 PMCID: PMC8279601 DOI: 10.1002/edm2.263] [Citation(s) in RCA: 4] [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: 11/18/2020] [Revised: 04/09/2021] [Accepted: 05/01/2021] [Indexed: 11/23/2022] Open
Abstract
INTRODUCTION Type 1 diabetes mellitus (T1DM) is associated with earlier onset of cardiovascular disease. Recent evidence has found hyperglycaemia appears to play a greater role in this association among T1DM compared to T2DM. This study investigates the relationship between glucose and QTc (a key cardiovascular measure) using data from continuous electrocardiogram (ECG) and glucose monitors. METHODS Seventeen adults with T1DM were recruited at a clinical facility in Ireland. A continuous glucose monitoring system was fitted to each participant that measured glucose every 5 min for 7 days. The participants simultaneously wore a vest with sensors to measure 12-lead ECG data every 10 min for 7 days. Area under the glucose curve (AUC), proportion of time spent in hypoglycaemia and hyperglycaemia, and mean daily absolute deviation of glucose were calculated. Mixed effects ANOVA and functional regression models were fitted to the data to investigate the aggregate and time-dependent association between glucose and QTc. RESULTS All participants were male with an average age of 52.5 (SD 3.8) years. Those with neuropathy had a significantly higher mean QTc compared to their counterparts. Mean QTc was significantly longer during hyperglycaemia. There was a significant positive association between QTc and time spent in hyperglycaemia. A negative association was found between QTc and time spent in hypoglycaemia. A functional model suggested a positive relationship between glucose and QTc at several times during the 7-day follow-up. CONCLUSION This study used sensor technology to investigate, with high granularity, the temporal relationship between glucose and ECG data over one week. QTc was found to be longer on average during hyperglycaemia.
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Affiliation(s)
- Beatrice Charamba
- School of Mathematics, Statistics and Applied MathematicsNational University of Ireland GalwayGalwayIreland
- Insight Centre for Data AnalyticsNational University of Ireland GalwayGalwayIreland
| | - Aaron Liew
- Endocrinology DivisionSaolta University Healthcare GroupPortiuncula University HospitalGalwayIreland
- Endocrinology DivisionGalway University HospitalSaolta University Healthcare GroupGalwayIreland
| | - Eileen Coen
- Endocrinology DivisionGalway University HospitalSaolta University Healthcare GroupGalwayIreland
| | - John Newell
- School of Mathematics, Statistics and Applied MathematicsNational University of Ireland GalwayGalwayIreland
- Insight Centre for Data AnalyticsNational University of Ireland GalwayGalwayIreland
| | - Timothy O’Brien
- Endocrinology DivisionGalway University HospitalSaolta University Healthcare GroupGalwayIreland
- Regenerative Medicine InstituteNational University of Ireland GalwayGalwayIreland
| | - William Wijns
- The Lambe Institute for Translational Medicine, Curam and the Smart Sensors LabNational University of Ireland GalwayGalwayIreland
| | - Andrew J. Simpkin
- School of Mathematics, Statistics and Applied MathematicsNational University of Ireland GalwayGalwayIreland
- Insight Centre for Data AnalyticsNational University of Ireland GalwayGalwayIreland
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29
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Graves JM, Vallejo JA, Hamill CS, Wang D, Ahuja R, Patel S, Faul C, Wacker MJ. Fibroblast growth factor 23 (FGF23) induces ventricular arrhythmias and prolongs QTc interval in mice in an FGF receptor 4-dependent manner. Am J Physiol Heart Circ Physiol 2021; 320:H2283-H2294. [PMID: 33929896 DOI: 10.1152/ajpheart.00798.2020] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Fibroblast growth factor 23 (FGF23) is a phosphate regulating protein hormone released by osteocytes. FGF23 becomes markedly elevated in chronic kidney disease (CKD), for which the leading cause of death is cardiovascular disease, particularly sudden cardiac death. Previously, we found that FGF23 increases intracellular Ca2+ in cardiomyocytes and alters contractility in mouse ventricles ex vivo via FGF receptor 4 (FGFR4). In the present study, we demonstrate that FGF23 induces cardiac arrhythmias and prolongs QTc interval in mice, and we tested whether these effects are mediated through FGFR4. In isolated Langendorff perfused hearts, FGF23 perfusion increased mechanical arrhythmias in the form of premature ventricular beats (PVBs), and induced runs of ventricular tachycardia in 6 of 11 animals, which were attenuated with pretreatment of an anti-FGFR4 blocking antibody. Ex vivo ECG analysis of isolated intact hearts showed increased ventricular arrhythmias and QTc prolongation after FGF23 infusion compared with vehicle. In vivo, injection of FGF23 into the jugular vein led to the emergence of premature ventricular contractions (PVCs) in 5 out of 11 experiments. FGF23 also produced a significant lengthening effect upon QTc interval in vivo. In vivo FGFR4 blockade ameliorated the arrhythmogenic and QTc prolonging effects of FGF23. Finally, FGF23 increased cardiomyocyte Ca2+ levels in intact left ventricular muscle which was inhibited by FGR4 blockade. We conclude that FGF23/FGFR4 signaling in the heart may contribute to ventricular arrhythmogenesis and repolarization disturbances commonly observed in patients with CKD via Ca2+ overload and may be an important therapeutic target to reduce cardiac mortality in CKD.NEW & NOTEWORTHY Here we provide direct evidence that fibroblast growth factor 23 (FGF23), a phosphaturic hormone elevated in chronic kidney disease, is proarrhythmic. FGF23 acutely triggered ventricular arrhythmias and prolonged corrected QT interval (QTc) in isolated mouse hearts and in vivo. FGF23 also increased Ca2+ levels in ventricular muscle tissue. Blockade of the FGF receptor 4 signaling pathway using a monoclonal antibody ameliorated ventricular arrhythmias, QTc prolongation, and elevated ventricular Ca2+ induced by FGF23, and may represent a potential therapeutic target in chronic kidney disease.
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Affiliation(s)
- Jonah M Graves
- Department of Biomedical Sciences, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri
| | - Julian A Vallejo
- Department of Biomedical Sciences, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri
| | - Chelsea S Hamill
- Department of Biomedical Sciences, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri
| | - Derek Wang
- Department of Biomedical Sciences, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri
| | - Rohan Ahuja
- Department of Biomedical Sciences, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri
| | - Shaan Patel
- Department of Biomedical Sciences, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri
| | - Christian Faul
- Division of Nephrology, Department of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama
| | - Michael J Wacker
- Department of Biomedical Sciences, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri
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30
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Zhang J, Yang J, Liu L, Li L, Cui J, Wu S, Tang K. Significant abnormal glycemic variability increased the risk for arrhythmias in elderly type 2 diabetic patients. BMC Endocr Disord 2021; 21:83. [PMID: 33906667 PMCID: PMC8077924 DOI: 10.1186/s12902-021-00753-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2020] [Accepted: 04/19/2021] [Indexed: 01/09/2023] Open
Abstract
BACKGROUND Little is known about whether the influence of glycemic variability on arrhythmia is related to age in type 2 diabetes mellitus (T2DM). Therefore, we aimed to compare the association between glycemic variability and arrhythmia in middle-aged and elderly T2DM patients. METHODS A total of 107 patients were divided into two groups: elderly diabetes mellitus group (EDM, n = 73) and middle-aged diabetes mellitus group (MDM, n = 34). The main clinical data, continuous glucose monitoring (CGM) and dynamic ECG reports were collected. The parameters including standard deviation of blood glucose (SDBG), largest amplitude of glycemic excursions (LAGE), mean amplitude of glycemic excursions (MAGE), absolute means of daily differences (MODD), time in range (TIR), time below range (TBR), time above range (TAR), coefficient of variation (CV) were tested for glycemic variability evaluation. RESULTS In terms of blood glucose fluctuations, MAGE (5.77 ± 2.16 mmol/L vs 4.63 ± 1.89 mmol/L, P = 0.026), SDBG (2.39 ± 1.00 mmol/L vs 2.00 ± 0.82 mmol/L, P = 0.048), LAGE (9.53 ± 3.37 mmol/L vs 7.84 ± 2.64 mmol/L, P = 0.011) was significantly higher in EDM group than those of MDM group. The incidences of atrial premature beat, couplets of atrial premature beat, atrial tachycardia and ventricular premature beat were significantly higher in EDM group compared with the MDM group (all P < 0.05). Among patients with hypoglycemia events, the incidences of atrial premature beat, couplets of atrial premature beat, atrial tachycardia and ventricular premature beat (all P < 0.05) were significantly higher in the EDM group than those in the MDM group. In EDM group, TIR was negatively correlated with atrial tachycardia in the MAGE1 layer and with atrial tachycardia and ventricular premature beat in the MAGE2 layer, TBR was significantly positively correlated with atrial tachycardia in the MAGE2 layer (all P < 0.05). In MDM group, TAR was positively correlated with ventricular premature beat and atrial tachycardia in the MAGE2 layer (all P < 0.05). CONCLUSIONS The study demonstrated the elderly patients had greater glycemic variability and were more prone to arrhythmias. Therefore, active control of blood glucose fluctuation in elderly patients will help to reduce the risk of severe arrhythmia.
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Affiliation(s)
- Jianbo Zhang
- Department of General Medicine, Qilu Hospital of Shandong University, No.107, Wen Hua Xi Road, Jinan, Shandong, China
- Department of Emergency and Chest Pain Center, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
| | - Jianmin Yang
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, department of Cardiology, Qilu Hospital of Shandong University, Jinan, Shandong, China
| | - Liwei Liu
- Department of General Medicine, Qilu Hospital of Shandong University, No.107, Wen Hua Xi Road, Jinan, Shandong, China
| | - Liyan Li
- Department of Endocrinology and Metabolism, First People's Hospital of Jinan City, Jinan, Shandong, China
| | - Jiangyin Cui
- Department of General Medicine, Qilu Hospital of Shandong University, No.107, Wen Hua Xi Road, Jinan, Shandong, China
| | - Shuo Wu
- Department of General Medicine, Qilu Hospital of Shandong University, No.107, Wen Hua Xi Road, Jinan, Shandong, China
- Department of Emergency and Chest Pain Center, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
| | - Kuanxiao Tang
- Department of General Medicine, Qilu Hospital of Shandong University, No.107, Wen Hua Xi Road, Jinan, Shandong, China.
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Erken Pamukcu H, Hepşen S, Şahan HF, Biçer T, Çakal E, Çimen T, Efe TH, Sunman H. Diabetic microvascular complications associated with myocardial repolarization heterogeneity evaluated by Tp-e interval and Tp-e/QTc ratio. J Diabetes Complications 2020; 34:107726. [PMID: 32912812 DOI: 10.1016/j.jdiacomp.2020.107726] [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: 04/23/2020] [Revised: 07/30/2020] [Accepted: 08/23/2020] [Indexed: 12/15/2022]
Abstract
INTRODUCTION The heterogeneity in myocardial repolarization increases the risk of ventricular arrhythmias and sudden death in patients with diabetes mellitus (DM). The Tp-e interval and Tp-e/QTc ratio are found to be useful in the prediction of ventricular arrhythmias. In this study, we aimed to investigate the Tp-e interval and Tp-e/QTc ratio in diabetic patients with and without microvascular complications. MATERIALS AND METHODS This cross-sectional observational study included patients with type 2 DM who presented to the endocrinology outpatient clinic. Diabetic microvascular complications were evaluated. The Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio were also calculated. RESULTS A total of 240 patients with type 2 DM (148 patients had microvascular complications) were included in the study. Diabetic neuropathy rate was 30.4%, diabetic nephropathy rate was 38.4%, and diabetic retinopathy rate was 21.7%. Upon comparing patients according to Tp-e/QTc ratio, the median Tp-e/QTc interval of the group of patients with complications was 0.21 (0.19-0.23) and the median Tp-e/QTc ratio of the group of patients without complications was 0.19 (0.18-0.20) (p < 0.001). When patients were grouped according to the presence and severity of retinopathy, the Tp-e/QTc ratio was more prolonged in the proliferative retinopathy group [0.27 (0.23-0.30)] than the non-proliferative retinopathy group [0.20 (0.19-0.22), p < 0.001]. When patients were grouped according to the presence and severity of nephropathy, the Tp-e/QTc ratio was more prolonged in the macroalbuminuria and microalbuminuria group than the normoalbuminuric group [0.25 (0.21-0.30), 0.23 (0.19-0.24), and 0.19 (0.20-0.22), respectively, p = 0.002]. CONCLUSIONS Our study is the first to demonstrate the association of the Tp-e interval and Tp-e/QTc ratio with the presence and severity of microvascular complications in patients with type 2 DM.
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Affiliation(s)
- Hilal Erken Pamukcu
- University of Health Sciences, Dışkapı Yıldırım Beyazıt Training and Research Hospital, Department of Cardiology, Ankara.
| | - Sema Hepşen
- University of Health Sciences, Dışkapı Yıldırım Beyazıt Training and Research Hospital, Department of Endocrinology and Metabolism, Ankara
| | - Haluk Furkan Şahan
- University of Health Sciences, Dışkapı Yıldırım Beyazıt Training and Research Hospital, Department of Cardiology, Ankara
| | - Tolga Biçer
- University of Health Sciences, Dışkapı Yıldırım Beyazıt Training and Research Hospital, Department of Ophthalmology, Ankara
| | - Erman Çakal
- University of Health Sciences, Dışkapı Yıldırım Beyazıt Training and Research Hospital, Department of Endocrinology and Metabolism, Ankara
| | - Tolga Çimen
- University of Health Sciences, Dışkapı Yıldırım Beyazıt Training and Research Hospital, Department of Cardiology, Ankara
| | - Tolga Han Efe
- University of Health Sciences, Dışkapı Yıldırım Beyazıt Training and Research Hospital, Department of Cardiology, Ankara
| | - Hamza Sunman
- University of Health Sciences, Dışkapı Yıldırım Beyazıt Training and Research Hospital, Department of Cardiology, Ankara
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Vasheghani M, Sarvghadi F, Beyranvand MR, Emami H. The relationship between QT interval indices with cardiac autonomic neuropathy in diabetic patients: a case control study. Diabetol Metab Syndr 2020; 12:102. [PMID: 33292470 PMCID: PMC7678155 DOI: 10.1186/s13098-020-00609-0] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2020] [Accepted: 11/05/2020] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND Long QT interval (QT) and abnormal QT dispersion (QTd) are associated with sudden death. The relationship between cardiac autonomic neuropathy (CAN) and QT indices in type 2 diabetic patients were investigated. METHODS Totally 130 diabetic subjects (mean age 50.87 ± 13.9 years) were included (70 individuals with and 60 individuals without CAN). All participants had sinus cardiac rhythm. The patients who had diseases or take drugs that cause orthostatic hypotension (OH), cardiac arrhythmia and QT prolongation were excluded. After interview and examination, standard and continuous ECG was taken in supine position with deep breathing and standing up position. CAN diagnosis was based on Ewing's tests. QT, QT corrected (QTc), minimum QT (QT min), maximum QT (QT max) and mean ± SD of QT (QT mean) and QTd were assessed from standard ECG. QTc was calculated by Bazett's formula from V2 lead. QTc > 440 ms in men and QTc > 460 ms in women and QTd > 80 ms were considered abnormal. RESULTS In patients with CAN, 21.5% were symptomatic. The prevalence of abnormal QTc and QTd was 11.3% and 28.7%, respectively. There was no significant difference between the patients with or without CAN in terms of long QTc and abnormal QTd. However, the mean ± SD of QT max, QT mean and QTd was higher in the patients with CAN (P value < 0.03). The used cut points for QTc and QTd have high specificity (79% for both) and low sensitivity (30% and 37%, respectively). To use QTc and QTd as screening test for CAN in T2DM patients, the cutoff points 380 and 550 ms are suggested, respectively. CONCLUSION The prevalence of asymptomatic CAN was 3.7 times that of symptomatic CAN. In patients with CAN the QT max, QT mean and QTd were higher than those without CAN. There was no association between CAN and long QTc and abnormal QTd.
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Affiliation(s)
- Maryam Vasheghani
- Chronic Respiratory Diseases Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Farzaneh Sarvghadi
- Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Beyranvand
- Department of Cardiology, Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Department of Cardiology, Taleghani Educational Hospital, Tabnak St. Velenjak Region, Chamran High Way, 1985711151 Tehran , Iran
| | - Habib Emami
- Tobacco Prevention and Control Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Ravichandran S, Srivastav S, Haridas Kamble P, Shukla R, Sharma P, Sharma R. Effect of Vitamin D status on QTc interval in type 2 diabetes mellitus. J Basic Clin Physiol Pharmacol 2020; 32:163-167. [PMID: 34005842 DOI: 10.1515/jbcpp-2019-0085] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2019] [Accepted: 02/18/2020] [Indexed: 12/30/2022]
Abstract
OBJECTIVES Diabetes mellitus (DM) is associated with autonomic neuropathy and metabolic abnormalities. These predispose the patients to prolongation of QTc and risk of arrhythmias and sudden cardiac death. Vitamin D may also cause QTc prolongation. We hypothesized that concomitant Vitamin D deficiency and Type 2 DM may act in synergy to prolong QTc interval. METHODS Newly diagnosed Type 2 DM patients were recruited from Department of Endocrinology. Lead II ECG was acquired for 5 min during supine rest using a digital data acquisition system. QTc interval extraction was performed using software. 25-hydroxy Vitamin D estimation was done using Chemiluminescence method. Patients were divided into two groups- Vitamin D deficient and insufficient (VDD/I) and optimal (VDO) as per standard criteria. QTc intervals were compared between the two groups. RESULTS Sixty-five patients participated in the study. Age was comparable between the groups (p=0.67, Unpaired t-test). There was no significant difference amongst QTc intervals between the groups (p=0.19, Mann Whitney test). Also, there was no significant correlation between Vitamin D levels and QTc intervals assessed using Spearman's correlation coefficient. CONCLUSIONS While it seems plausible, coexisting Vitamin D deficiency and Type 2 DM probably do not act in synergy to prolong QTc interval. These findings merit future research on larger cohorts to investigate the relationship between Vitamin D status and newly diagnosed Type 2 DM on QTc intervals.
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Affiliation(s)
- Suresh Ravichandran
- Department of Physiology, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
| | - Shival Srivastav
- Department of Physiology, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
| | | | - Ravindra Shukla
- All India Institute of Medical Sciences, Endocrinology and Metabolism, Jodhpur, Rajasthan, India
| | - Praveen Sharma
- All India Institute of Medical Sciences Jodphur, Department of Biochemistry, Jodhpur, Rajasthan, India
| | - Rajesh Sharma
- Department of Physiology, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
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Nashawi M, Sheikh O, Battisha A, Ghali A, Chilton R. Neural tone and cardio-renal outcomes in patients with type 2 diabetes mellitus: a review of the literature with a focus on SGLT2 inhibitors. Heart Fail Rev 2020; 26:643-652. [PMID: 33169337 DOI: 10.1007/s10741-020-10046-w] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/19/2020] [Indexed: 12/18/2022]
Abstract
Recent clinical trials involving the systemic effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) have revealed beneficial outcomes pertaining to the microvascular sequelae of type 2 diabetes mellitus (T2DM) such as nephropathy, as well as macrovascular effects such as major adverse cardiovascular effects (MACE). Such findings have spurred the elevation of these agents to level A-tiers of recommendation within clinical guidelines addressing the management of complicated T2DM. While the mechanisms of SGLTi (-flozin drugs) are still being elucidated, a paucity of data exists within the literature appraising the role of neuromodulation and associated mechanisms in the aforementioned outcome studies. Given the role of the nervous system in orchestrating the pathologic processes that hamper cardio-renal status, insight into this topic offers an expanded perspective on T2DM. In this review we investigate the mechanisms by which SGLTi improve cardio-renal function in T2DM patients with emphases on neural tone and nervous system physiology.
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Affiliation(s)
- Mouhamed Nashawi
- Division of Medicine-Cardiology, UT Health San Antonio, 7872, 7703 Floyd Curl Drive, San Antonio, TX, 78229, USA.
| | - Omar Sheikh
- Division of Medicine-Cardiology, UT Health San Antonio, 7872, 7703 Floyd Curl Drive, San Antonio, TX, 78229, USA
| | - Ayman Battisha
- Department of Internal Medicine, University of Massachusetts Medical School-Bay State, 759 Chestnut Street, Springfield, MA, 01199, USA
| | - Abdullah Ghali
- Division of Medicine-Cardiology, UT Health San Antonio, 7872, 7703 Floyd Curl Drive, San Antonio, TX, 78229, USA
| | - Robert Chilton
- Division of Medicine-Cardiology, UT Health San Antonio, 7872, 7703 Floyd Curl Drive, San Antonio, TX, 78229, USA
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35
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Liu P, Wang L, Han D, Sun C, Xue X, Li G. Acquired long QT syndrome in chronic kidney disease patients. Ren Fail 2020; 42:54-65. [PMID: 31878817 PMCID: PMC6968512 DOI: 10.1080/0886022x.2019.1707098] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2019] [Revised: 11/30/2019] [Accepted: 12/01/2019] [Indexed: 12/19/2022] Open
Abstract
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in chronic kidney disease (CKD) patients. QT interval prolongation is a congenital or acquired condition that is associated with an increased risk of torsade de pointes (TdP), sudden cardiac death (SCD), and all-cause mortality in the general population. The prevalence of acquired long QT syndrome (aLQTS) is high, and various acquired conditions contribute to the prolonged QT interval in patients with CKD. More notably, the prolonged QT interval in CKD is an independent risk factor for SCD and all-cause mortality. In this review, we focus on the epidemiological characteristics, risk factors, underlying mechanisms and treatments of aLQTS in CKD, promoting the management of aLQTS in CKD patients.
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Affiliation(s)
- Peng Liu
- Department of Cardiovascular Medicine, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, P.R. China;
| | - Lu Wang
- Department of Cardiovascular Medicine, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, P.R. China;
- Department of Endocrinology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, P.R. China
| | - Dan Han
- Department of Cardiovascular Medicine, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, P.R. China;
| | - Chaofeng Sun
- Department of Cardiovascular Medicine, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, P.R. China;
| | - Xiaolin Xue
- Department of Cardiovascular Medicine, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, P.R. China;
| | - Guoliang Li
- Department of Cardiovascular Medicine, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, P.R. China;
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36
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Horváth B, Hézső T, Kiss D, Kistamás K, Magyar J, Nánási PP, Bányász T. Late Sodium Current Inhibitors as Potential Antiarrhythmic Agents. Front Pharmacol 2020; 11:413. [PMID: 32372952 PMCID: PMC7184885 DOI: 10.3389/fphar.2020.00413] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Accepted: 03/18/2020] [Indexed: 12/19/2022] Open
Abstract
Based on recent findings, an increased late sodium current (INa,late) plays an important pathophysiological role in cardiac diseases, including rhythm disorders. The article first describes what is INa,late and how it functions under physiological circumstances. Next, it shows the wide range of cellular mechanisms that can contribute to an increased INa,late in heart diseases, and also discusses how the upregulated INa,late can play a role in the generation of cardiac arrhythmias. The last part of the article is about INa,late inhibiting drugs as potential antiarrhythmic agents, based on experimental and preclinical data as well as in the light of clinical trials.
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Affiliation(s)
- Balázs Horváth
- Department of Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
- Faculty of Pharmacy, University of Debrecen, Debrecen, Hungary
| | - Tamás Hézső
- Department of Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Dénes Kiss
- Department of Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Kornél Kistamás
- Department of Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - János Magyar
- Department of Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
- Division of Sport Physiology, University of Debrecen, Debrecen, Hungary
| | - Péter P. Nánási
- Department of Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
- Department of Dental Physiology and Pharmacology, Faculty of Dentistry, University of Debrecen, Debrecen, Hungary
| | - Tamás Bányász
- Department of Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
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Fouda MA, Ghovanloo MR, Ruben PC. Cannabidiol protects against high glucose-induced oxidative stress and cytotoxicity in cardiac voltage-gated sodium channels. Br J Pharmacol 2020; 177:2932-2946. [PMID: 32077098 DOI: 10.1111/bph.15020] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2019] [Revised: 12/23/2019] [Accepted: 01/14/2020] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND AND PURPOSE Cardiovascular complications are the major cause of mortality in diabetic patients. However, the molecular mechanisms underlying diabetes-associated arrhythmias are unclear. We hypothesized that high glucose could adversely affect Nav 1.5, the major cardiac sodium channel isoform of the heart, at least partially via oxidative stress. We further hypothesized that cannabidiol (CBD), one of the main constituents of Cannabis sativa, through its effects on Nav 1.5, could protect against high glucose-elicited oxidative stress and cytotoxicity. EXPERIMENTAL APPROACH To test these ideas, we used CHO cells transiently co-transfected with cDNA encoding human Nav 1.5 α-subunit under control and high glucose conditions (50 or 100 mM for 24 hr). Several experimental and computational techniques were used, including voltage clamp of heterologous expression systems, cell viability assays, fluorescence assays and action potential modelling. KEY RESULTS High glucose evoked cell death associated with elevation in reactive oxygen species (ROS) right shifted the voltage dependence of conductance and steady-state fast inactivation, and increased persistent current leading to computational prolongation of action potential (hyperexcitability) which could result in long QT3 arrhythmia. CBD mitigated all the deleterious effects provoked by high glucose. Perfusion with lidocaine (a well-known sodium channel inhibitor with antioxidant effects) or co-incubation of Tempol (a well-known antioxidant) elicited protection, comparable to CBD, against the deleterious effects of high glucose. CONCLUSION AND IMPLICATIONS These findings suggest that, through its favourable antioxidant and sodium channel inhibitory effects, CBD may protect against high glucose-induced arrhythmia and cytotoxicity.
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Affiliation(s)
- Mohamed A Fouda
- Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada.,Department of Pharmacology and Toxicology, Alexandria University, Alexandria, Egypt
| | - Mohammad-Reza Ghovanloo
- Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada
| | - Peter C Ruben
- Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada
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38
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Migisha R, Agaba DC, Katamba G, Kwaga T, Tumwesigye R, Miranda SL, Muyingo A, Siedner MJ. Prevalence and Correlates of Cardiovascular Autonomic Neuropathy Among Patients with Diabetes in Uganda: A Hospital-Based Cross-sectional Study. Glob Heart 2020; 15:21. [PMID: 32489794 PMCID: PMC7218768 DOI: 10.5334/gh.765] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2019] [Accepted: 01/28/2020] [Indexed: 02/08/2023] Open
Abstract
Background Cardiovascular autonomic neuropathy (CAN) is a common complication in individuals with diabetes mellitus (DM) but often overlooked in clinical practice. The burden and correlates of CAN have not been extensively studied in low-income countries, particularly in sub-Saharan Africa. Objectives To determine the prevalence and correlates of CAN among adults in ambulatory diabetes care in southwestern Uganda. Method We conducted a cross-sectional study among adults with diabetes from November 2018 to April 2019. CAN was assessed using the five autonomic function tests: deep breathing, Valsalva maneuver, postural index on standing, change in blood pressure during standing and diastolic blood pressure response to isometric exercise. We estimated the prevalence of CAN and fit regression models to identify its demographic and clinical correlates. Results We enrolled 299 individuals. The mean age was 50.1 years (SD ± 9.8), mean HbA1c was 9.7 (SD ± 2.6) and 69.6% were female. CAN was detected in 156/299 (52.2%) of the participants on the basis of one or more abnormal cardiovascular autonomic reflex tests. Out of 299 participants, 88 (29.4%) were classified as early CAN while 61/299 (20.4%) and 7/299 (2.3%) were classified as definite and severe (advanced) CAN respectively. In multivariable regression models, age over 50 years (aOR 3.48, 95%CI 1.35 -8.99, p = 0.010), duration of diabetes over 10 years (aOR 4.09, 95%CI 1.78 -9.38, p = 0.001), and presence of diabetic retinopathy (aOR 2.25, 95%CI 1.16 -4.34, p = 0.016) were correlated with CAN. Conclusions Our findings reveal a high prevalence of CAN among individuals in routine outpatient care for diabetes mellitus in Uganda. Older age, longer duration of diabetes and coexistence of retinopathy are associated with CAN. Future work should explore the clinical significance and long term outcomes associated with CAN in this region.
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Affiliation(s)
- Richard Migisha
- Department of Physiology, Mbarara University of Science and Technology, Mbarara, UG
| | - David Collins Agaba
- Department of Physiology, Mbarara University of Science and Technology, Mbarara, UG
| | - Godfrey Katamba
- Department of Physiology, St. Augustine International University, Kampala, UG
| | - Teddy Kwaga
- Department of Ophthalmology, Mbarara University of Science and Technology, Mbarara, UG
| | - Raymond Tumwesigye
- Department of Nursing, Mbarara University of Science and Technology, Mbarara, UG
| | - Silvia Lopez Miranda
- Department of Physiology, Mbarara University of Science and Technology, Mbarara, UG
| | - Anthony Muyingo
- Department of Internal Medicine, Mbarara University of Science and Technology, Mbarara, UG
| | - Mark J. Siedner
- Department of Internal Medicine, Mbarara University of Science and Technology, Mbarara, UG
- Department of Medicine, Massachusetts General Hospital, Boston, US
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Association of QTc Interval with Risk of Cardiovascular Diseases and Related Vascular Traits: A Prospective and Longitudinal Analysis. Glob Heart 2020; 15:13. [PMID: 32489786 PMCID: PMC7218767 DOI: 10.5334/gh.533] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
Background: Prolonged heart rate corrected QT (QTc) interval was reported to be associated with cardiovascular diseases (CVDs). Objective: There exists little data on the association between QTc interval and cardiovascular risk in Asian populations. We prospectively investigated the association of QTc interval with CVDs and vascular traits in a large cohort of Chinese adults. Methods: A total of 7,605 participants aged 40 years or older from a well-defined community without CVDs at baseline were included and followed up for an average of 4.5 years. Association of baseline QTc interval with incident CVDs was evaluated using Cox regression analysis. Associations of QTc interval with brachial-ankle pulse wave velocity (baPWV), carotid intima-media thickness (CIMT), and risk of microalbuminuria and peripheral arterial diseases (PAD) were secondarily examined. Results: Prolonged QTc interval (≥460 ms in women and ≥450 ms in men) was associated with 51% higher risk of total major CVDs (hazard ratio [HR] = 1.51, 95% confidence interval [CI] [1.20, 1.90]), particularly, 48% increased risk of stroke (95% CI [1.16, 1.88]). Prolonged QTc interval was positively associated with baPWV (β = 38.10 cm/s, standard error [SE] = 8.04, P < 0.0001) and CIMT (β = 0.01 mm, SE = 0.01, P = 0.04). Prolonged QTc interval was associated with increased risk of incident microalbuminuria (odds ratio [OR] = 1.65, 95% CI [1.21, 2.24]) and PAD (2.49, 95% CI [1.35, 4.59]). Conclusions: Prolonged QTc interval is positively and significantly associated with increased risk of CVDs and related vascular traits in Chinese population.
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Bertero E, Sequeira V, Heymans S, Maack C. Response to 'The possible role of insulin and glucagon in patients with heart failure and Type 2 diabetes'. Eur Heart J 2020; 41:326-327. [PMID: 31329851 DOI: 10.1093/eurheartj/ehz243] [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: 11/12/2022] Open
Affiliation(s)
- Edoardo Bertero
- Department of Translational Science, Comprehensive Heart Failure Center, University Clinic Würzburg, Am Schwarzenberg 15, 97078 Würzburg, Germany
| | - Vasco Sequeira
- Department of Translational Science, Comprehensive Heart Failure Center, University Clinic Würzburg, Am Schwarzenberg 15, 97078 Würzburg, Germany
| | - Stephane Heymans
- Department of Cardiology, Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, P. Debyelaan 25, 6229 HX Maastricht, The Netherlands.,Netherlands Heart Institute, Moreelsepark 1, 3511EP Utrecht, The Netherlands.,Department of Cardiovascular Sciences, Leuven University, Herestraat 49, 3001 Leuven, Belgium
| | - Christoph Maack
- Department of Translational Science, Comprehensive Heart Failure Center, University Clinic Würzburg, Am Schwarzenberg 15, 97078 Würzburg, Germany
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Chang LH, Hwu CM, Chu CH, Won JGS, Chen HS, Lin LY. UPSTROKE TIME PER CARDIAC CYCLE IS ASSOCIATED WITH CARDIOVASCULAR PROGNOSIS IN TYPE 2 DIABETES. Endocr Pract 2019; 25:1109-1116. [PMID: 31241364 DOI: 10.4158/ep-2019-0078] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Objective: Upstroke time per cardiac cycle (UTCC) in the lower extremities has been found to be predictive of cardiovascular mortality in the general population. Therefore, the purpose of the study was to test the associations between increasing UTCC and outcomes in patients with type 2 diabetes. Methods: A total of 452 patients with type 2 diabetes (age, 67.5 ± 8.6 years; male, 54%) registered in a share-care program participated in the study at an outpatient clinic in Taipei Veterans General Hospital across a mean of 5.8 years. Primary outcomes were all-cause mortality hospitalization for coronary artery disease, stroke, revascularization, amputation, and diabetic foot syndrome. Secondary end-point outcome was all-cause mortality. Results: Increment of UTCC associations with primary and secondary outcomes were undertaken prior to baseline characteristic adjustments. A UTCC of 20.1% exhibited the greatest area under curve (AUC), sensitivity, and specificity balance to predict composite events in receiver operating curves (AUC, 0.63 [P = .001]; sensitivity, 67.7%; specificity, 54.9%). Sixty-four composite events and 17 deaths were identified from medical records. UTCC ≥20.1% was associated with the occurrence of composite events and an increased risk of mortality. For composite events, an adjusted hazard ratio (HR) of 2.45 and 95% confidence interval (CI) of 1.38 to 4.35 (P = .002) were calculated. For all-cause mortality, an adjusted HR of 1.91 and 95% CI of 0.33 to 10.99 (P = .467) were calculated. Conclusion: Increasing UTCC was associated with cardiovascular outcomes in patients with type 2 diabetes. Therefore, UTCC is advocated as a noninvasive screening tool for ambulatory patients with type 2 diabetes. Abbreviations: CAD = coronary artery disease; CI = confidence interval; eGFR = estimated glomerular filtration rate; HR = hazard ratio; PAD = peripheral artery disease; UTCC = upstroke time per cardiac cycle.
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Cunningham KS, Spears DA, Care M. Evaluation of cardiac hypertrophy in the setting of sudden cardiac death. Forensic Sci Res 2019; 4:223-240. [PMID: 31489388 PMCID: PMC6713129 DOI: 10.1080/20961790.2019.1633761] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2018] [Revised: 06/17/2019] [Accepted: 06/17/2019] [Indexed: 01/06/2023] Open
Abstract
Ventricular hypertrophy is a common pathological finding at autopsy that can act as a substrate for arrhythmogenesis. Pathologists grapple with the significance of ventricular hypertrophy when assessing the sudden and unexpected deaths of young people and what it could mean for surviving family members. The pathological spectrum of left ventricular hypertrophy (LVH) is reviewed herein. This article is oriented to the practicing autopsy pathologist to help make sense of various patterns of increased heart muscle, particularly those that are not clearly cardiomyopathic, yet present in the setting of sudden cardiac death. The article also reviews factors influencing arrhythmogenesis as well as genetic mutations most commonly associated with ventricular hypertrophy, especially those associated with hypertrophic cardiomyopathy (HCM).
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Affiliation(s)
- Kristopher S. Cunningham
- Department of Laboratory Medicine and Pathobiology, Ontario Forensic Pathology Service, University of Toronto, Toronto, Canada
| | - Danna A. Spears
- University Health Network, Division of Cardiology – Electrophysiology, University of Toronto, Toronto, Canada
| | - Melanie Care
- Fred A. Litwin Family Centre in Genetic Medicine and Inherited Arrhythmia Clinic, University Health Network & Mount Sinai Hospital, University of Toronto, Toronto, Canada
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Massardo T, Araya AV, Prat H, Alarcón L, Berrocal I, Pino A, Cordero F, Jaimovich R, Fernández R, Herrera E, Carmona J, Castro A. Factors associated with silent myocardial ischemia, autonomic or peripheral neuropathies, and survival in diabetes mellitus type 2 patients without cardiovascular symptoms. Int J Diabetes Dev Ctries 2019. [DOI: 10.1007/s13410-019-00758-7] [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: 10/26/2022] Open
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Matsumoto T, Ohnishi H, Sato T, Miki T, Akasaka H, Hanawa N, Koyama M, Saitoh S, Miura T. Insulin Resistance is Associated with Longitudinal Changes of Cardiac Repolarization Heterogeneity in Apparently Healthy Subjects. Cardiol Ther 2019; 8:239-251. [PMID: 31273651 PMCID: PMC6828911 DOI: 10.1007/s40119-019-0140-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2019] [Indexed: 01/11/2023] Open
Abstract
INTRODUCTION Increased heterogeneity in ventricular repolarization is a risk factor of sudden cardiac death, but its natural history is unclear. Here we examined whether insulin resistance is associated with longitudinal change in ventricular repolarization heterogeneity in apparently healthy subjects. METHODS The study subjects were participants in health checkups in cohort 1 and cohort 2, which were followed up for 6 years and 5 years, respectively. Subjects with diabetes, cardiovascular disease, or renal disease at baseline were excluded from the analyses. As indices of insulin resistance, the homeostasis model assessment of insulin resistance (HOMA-IR) and triglyceride to HDL-cholesterol ratio (TG/HDL-C) were used in cohort 1 and cohort 2, respectively. Heterogeneity in ventricular repolarization was assessed by heart rate-corrected Tpeak-Tend interval in V5 (cTpTe), QT interval, and QT dispersion. In regression analyses, parameters with a skewed distribution were normalized by logarithmic transformation or by Box-Cox transformation. RESULTS In longitudinal analyses, Box-Cox-transformed cTpTe at the end of follow-up was weakly correlated with log HOMA-IR at baseline in cohort 1 (n = 153, r = - 0.207, 95% CI - 0.354 to - 0.050, p = 0.010) and with log TG/HDL-C at baseline in cohort 2 (n = 738, r = - 0.098, 95% CI - 0.169 to - 0.026, p = 0.008). Multiple regression analysis showed that indices of insulin resistance, but not glycosylated hemoglobin (HbA1c) or plasma glucose, at baseline were significant explanatory variables for cTpTe at the end of follow-up. Neither QT interval nor QT dispersion was correlated with metabolic parameters. CONCLUSION Insulin resistance may be involved in the longitudinal increase of ventricular repolarization heterogeneity in apparently healthy subjects.
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Affiliation(s)
- Tamaki Matsumoto
- Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Hirofumi Ohnishi
- Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
- Department of Public Health, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Tatsuya Sato
- Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
- Department of Cellular Physiology and Signal Transduction, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Takayuki Miki
- Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Hiroshi Akasaka
- Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
| | | | - Masayuki Koyama
- Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Shigeyuki Saitoh
- Division of Medical and Behavioral Subjects, Department of Nursing, Sapporo Medical University School of Health Sciences, Sapporo, Japan
| | - Tetsuji Miura
- Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
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Hegyi B, Bers DM, Bossuyt J. CaMKII signaling in heart diseases: Emerging role in diabetic cardiomyopathy. J Mol Cell Cardiol 2019; 127:246-259. [PMID: 30633874 DOI: 10.1016/j.yjmcc.2019.01.001] [Citation(s) in RCA: 95] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2018] [Accepted: 01/04/2019] [Indexed: 02/07/2023]
Abstract
Calcium/calmodulin-dependent protein kinase II (CaMKII) is upregulated in diabetes and significantly contributes to cardiac remodeling with increased risk of cardiac arrhythmias. Diabetes is frequently associated with atrial fibrillation, coronary artery disease, and heart failure, which may further enhance CaMKII. Activation of CaMKII occurs downstream of neurohormonal stimulation (e.g. via G-protein coupled receptors) and involve various posttranslational modifications including autophosphorylation, oxidation, S-nitrosylation and O-GlcNAcylation. CaMKII signaling regulates diverse cellular processes in a spatiotemporal manner including excitation-contraction and excitation-transcription coupling, mechanics and energetics in cardiac myocytes. Chronic activation of CaMKII results in cellular remodeling and ultimately arrhythmogenic alterations in Ca2+ handling, ion channels, cell-to-cell coupling and metabolism. This review addresses the detrimental effects of the upregulated CaMKII signaling to enhance the arrhythmogenic substrate and trigger mechanisms in the heart. We also briefly summarize preclinical studies using kinase inhibitors and genetically modified mice targeting CaMKII in diabetes. The mechanistic understanding of CaMKII signaling, cardiac remodeling and arrhythmia mechanisms may reveal new therapeutic targets and ultimately better treatment in diabetes and heart disease in general.
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Affiliation(s)
- Bence Hegyi
- Department of Pharmacology, University of California Davis, Davis, CA, USA
| | - Donald M Bers
- Department of Pharmacology, University of California Davis, Davis, CA, USA.
| | - Julie Bossuyt
- Department of Pharmacology, University of California Davis, Davis, CA, USA
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Rodrigues Junior L, Duque A, Massolar C, Rocha C, Da Rocha AM, Moreira RA. Carqueja (Baccharis trimera) essential oil chronic treatment induces ventricular repolarization disorder in healthy rats but not in type 2 diabetic rats. Pharmacognosy Res 2019. [DOI: 10.4103/pr.pr_54_19] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Skelin M, Javor E, Lucijanić M, Lucijanić T, Jakupović L, Rahelić D. The role of glucagon in the possible mechanism of cardiovascular mortality reduction in type 2 diabetes patients. Int J Clin Pract 2018; 72:e13274. [PMID: 30295381 DOI: 10.1111/ijcp.13274] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2018] [Accepted: 09/15/2018] [Indexed: 01/10/2023] Open
Abstract
AIM Type 2 diabetes (T2D) is one of the major public health issues worldwide. The main cause of mortality and morbidity among T2D patients are cardiovascular (CV) causes. Various antidiabetics are used in T2D treatment, but until recently they lacked clear evidence of the reduction in CV mortality and all-cause mortality as independent study end-points. The aim of this article was to present and critically evaluate potential mechanisms behind the remarkable results documented in trials with new antidiabetics for the treatment of T2D. METHODS Relevant data were collected using the MEDLINE, PubMed, EMBASE, Web of Science, Science Direct, and Scopus databases with the key words: "type 2 diabetes," "mortality," "glucagon," "empagliflozin," "liraglutide," "insulin" and "QTc." Searches were not limited to specific publication types or study designs. RESULTS The EMPA-REG OUTCOME trial with empagliflozin and LEADER trial with liraglutide presented remarkable results regarding the reduction in mortality in T2D treatment. However, the potential mechanism for those beneficial effects is difficult to determine. It is not likely that improvements in classic CV risk factors are responsible for the observed effect. A potential mechanism may be caused by the elevation of postprandial (PP) glucagon concentrations that can be seen with an empagliflozin and liraglutide therapy, which could have beneficial effects considering the myocardial electrical stability in T2D patients. CONCLUSION This hypothesis throws new light upon possible mechanisms of reduction in mortality in T2D patients.
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Affiliation(s)
- Marko Skelin
- Department of Pharmacy, General Hospital Šibenik, Šibenik, Croatia
| | - Eugen Javor
- Department of Pharmacy, Sestre Milosrdnice University Hospital Center, Zagreb, Croatia
| | - Marko Lucijanić
- Department of Hematology, Dubrava University Hospital, Zagreb, Croatia
| | - Tomo Lucijanić
- Department of Endocrinology, Diabetes and Clinical Pharmacology, Dubrava University Hospital, Zagreb, Croatia
| | - Lejsa Jakupović
- Healthcare Institution of Community Pharmacy Slavonski Brod, Slavonski Brod, Croatia
| | - Dario Rahelić
- Department of Endocrinology, Diabetes and Clinical Pharmacology, Dubrava University Hospital, Zagreb, Croatia
- School of Medicine, University of Zagreb, Zagreb, Croatia
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Liu P, Han D, Sun X, Tan H, Wang Z, Liu C, Zhang Y, Li B, Sun C, Shi R, Li G. Prevalence and risk factors of acquired long QT syndrome in hospitalized patients with chronic kidney disease. J Investig Med 2018; 67:289-294. [PMID: 30367011 DOI: 10.1136/jim-2018-000798] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/30/2018] [Indexed: 12/13/2022]
Abstract
Patients with chronic kidney disease (CKD) have a high risk of fatal arrhythmias. The extended severe corrected QT (QTc) interval is a hallmark of ventricular arrhythmias and sudden cardiac death. The objective of this study was to evaluate the prevalence of acquired long QT syndrome (aLQTS) in hospitalized patients with CKD and search for potential risk factors to improve clinical risk stratification in patients with CKD. Information about patients with CKD was retrospectively collected in our hospital between January 2013 and June 2017. The prevalence of aLQTS in different stages of CKD was evaluated. The common risk factors for QTc prolongation in patients with CKD were compiled, and multivariable logistic regression analysis was used to evaluate how each factor was related to aLQTS in CKD. A total of 804 patients with CKD (299 females, 37.2%) participated in our study. The prevalence of aLQTS among all 804 patients was 56.97%, and the prevalence of QTc prolongation (>500 ms) was 10.07%. Among the elderly, impaired kidney function, hemodialysis, low serum potassium and low left ventricular ejection fraction (LVEF) were associated with QTc prolongation in patients with CKD. The prevalence of aLQTS is much higher and increases with the decline of kidney function in hospitalized patients with CKD, which is related to older age, impaired kidney function, hemodialysis, serum potassium and low LVEF.
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Affiliation(s)
- Peng Liu
- First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Dan Han
- First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Xuanzi Sun
- First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Hui Tan
- First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Zhigang Wang
- First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Chao Liu
- First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Yali Zhang
- First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Bailin Li
- First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Chaofeng Sun
- First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Rui Shi
- First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Guoliang Li
- First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
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Kollu K, Altintepe L, Duran C, Topal M, Ecirli S. The assessment of P-wave dispersion and myocardial repolarization parameters in patients with chronic kidney disease. Ren Fail 2018; 40:1-7. [PMID: 29285964 PMCID: PMC6014377 DOI: 10.1080/0886022x.2017.1419962] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Objective: The risks of sudden death and cardiac arrhythmia are increased in patients with chronic kidney disease (CKD). Here, we aimed to evaluate the indicators of arrhythmias, such as p-wave dispersion (P-WD), QTc dispersion, Tp-e and Tp-e/QT ratio in patients with CKD stages 3–5 on no renal replacement therapy (RRT). Material and methods: One-hundred and thirty three patients with CKD stages 3–5 and 32 healthy controls were enrolled into the study. No patients received RRT. QTc dispersion, P-WD and Tp-e interval were measured using electrocardiogram and Tp-e/QT ratio was also calculated. Results: Mean age rates were found similar in patients and controls (60.8 ± 14.2 and 61 ± 12.9 y, p = .937, respectively). Compared patients with controls, P-WD (45.85 ± 12.42 vs. 21.17 ± 6.6 msec, p < .001), QTc-min (366.99 ± 42.31 vs. 387.15 ± 20.5 msec, p < .001), QTc dispersion (71.13 ± 27.95 vs. 41.25 ± 14.55 msec, p < .001), Tp-e maximum (81.04 ± 10.34 vs. 75.49 ± 10.9 msec, p < .001), Tp-e minimum (62.25 ± 7.58 vs. 54.8 ± 6.72 msec, p < .001) and Tp-e/QTc ratio (0.19 ± 0.02 vs. 0.18 ± 0.01, p = .001) were found to be different. QTc-max and Tp-e interval were found to be similar in both groups. Conclusion: P-WD and QTc dispersion, Tp-e interval and Tp-e/QTc ratio were found to be increased in with CKD stages 3–5 on no RRT.
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Affiliation(s)
- Korhan Kollu
- a The Department of Internal Medicine , Konya Health Application and Research Center, University of Health Sciences , Konya , Turkey
| | - Lutfullah Altintepe
- b The Division of Nephrology and Internal Medicine , Konya Health Application and Research Center, University of Health Sciences , Konya , Turkey
| | - Cevdet Duran
- c The Deparment of Internal Medicine, The Division of Endocrinology and Metabolism , Usak University, The School of Medicine , Usak , Turkey
| | - Mustafa Topal
- b The Division of Nephrology and Internal Medicine , Konya Health Application and Research Center, University of Health Sciences , Konya , Turkey
| | - Samil Ecirli
- d The Division of Internal Medicine , Konya Health Application and Research Center, University of Health Sciences , Konya , Turkey
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Kuzu F. The effect of type 2 diabetes on electrocardiographic markers of significant cardiac events. Pak J Med Sci 2018; 34:626-632. [PMID: 30034428 PMCID: PMC6041533 DOI: 10.12669/pjms.343.14562] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/04/2022] Open
Abstract
Background & Objectives: In diabetics, cardiac microvascular circulation disorder increases the risk of arrhythmia and sudden cardiac death. Tpeak-Tend (Tp-e) interval, Tp-e dispersion, and Tp-e/QT and Tp-e/QTc ratios measured by surface electrocardiogram (ECG) are new parameters used to evaluate ventricular arrhythmogenity. We aimed to compare QT dispersion (QTd), corrected QT dispersion (QTcd), P dispersion (Pd), Tp-e interval, Tp-e dispersion, and Tp-e/QT and Tp-e/QTc ratios in patients with type- 2 diabetes (T2D) with healthy population. Methods: Electrocardiographic parameters of a total of 100 patients diagnosed with T2D were retrospectively analyzed and compared with the ECG results of 100 healthy age-, sex-, and body weight and height-matched controls. Results: The Pd, QT interval, QTc interval, QTd, QTcd, Tp-e/QT, Tp-e/QT ratios were higher in the patients. A statistically significant correlation was found only between hemoglobin A1c and Tp-e dispersion, QTd, QTcd, Pd, Tp-e/QT and Tp-e/QTc parameters, in linear regression analysis. There was also a statistically significant positive correlation between the values of low-density lipoprotein, systolic blood pressure, and Tp-e dispersion. Conclusion: The risk of arrhythmia can be predicted by evaluating Tp-e interval, Tp-e dispersion, Tp-e/QT, and Tp-e/QTc ratio, suggesting heterogeneity of ventricular repolarization and P wave and Pd showing heterogeneity of atrial repolarization in diabetic patients.
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Affiliation(s)
- Fatih Kuzu
- Fatih Kuzu, MD. Department of Endocrinology and Metabolism, Dumlupinar University, Evliya Celebi Training and Research Hospital, Kutahya, Turkey
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