Diabetes and Arrhythmias: Pathophysiology, Mechanisms and Therapeutic Outcomes

Grisanti, Laurel A.

doi:10.3389/fphys.2018.01669

Cited by 111 publications

(101 citation statements)

References 194 publications

(222 reference statements)

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“…Second, potential contributors of DM to the induction of cardiac arrhythmias, including hyperglycemia or glucose fluctuations and autonomic dysfunction, activate multiple mechanisms that contribute to the development of cardiac arrhythmias. In addition, structural remodeling, including changes in the electrical conduction of the heart, and fibrosis promote and potentiate the progression of arrhythmia [20]. The main finding of our study, i.e., the incidence rates of NSVT and AF were significantly higher in HOCM patients with T2DM than in those without T2DM, was consistent with those of previous studies.…”

Section: Discussionsupporting

confidence: 92%

Impact of type 2 diabetes mellitus on mid-term mortality for hypertrophic cardiomyopathy patients who underwent septal myectomy

Wang

Cui

et al. 2020

Cardiovasc Diabetol

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Background: Type 2 diabetes mellitus is common in cardiovascular disease. It is associated with adverse clinical outcomes for patients who had undergone coronary artery bypass and valve operations. The aim of this study was to evaluate the impact of type 2 diabetes mellitus on the midterm outcomes of patients with hypertrophic cardiomyopathy who underwent septal myectomy. Methods: We retrospectively analyzed the data of 67 hypertrophic cardiomyopathy patients with type 2 diabetes mellitus who underwent septal myectomy from two medical centers in China from 2011 to 2018. A propensity scorematched cohort of 134 patients without type 2 diabetes mellitus was also analyzed. Results: During a median follow-up of 28.0 (interquartile range: 13.0-3.0) months, 9 patients died. The cause of death of all of these patients was cardiovascular, particularly sudden cardiac death in 3 patients. Patients with type 2 diabetes mellitus had a higher rate of sudden cardiac death (4.5% vs. 0.0%, p = 0.04). The Kaplan-Meier survival analysis revealed that the rates of predicted 3-year survival free from cardiovascular death (98.1% vs. 95.1%, p = 0.14) were similar between the two groups. However, the rates of predicted 3-year survival free from sudden cardiac death (100% vs. 96.7%, p = 0.01) were significantly higher in hypertrophic cardiomyopathy patients without type 2 diabetes mellitus than in those with type 2 diabetes mellitus. Furthermore, after adjustment for age and sex, only N-terminal pro-brain natriuretic peptide (hazards ratio: 1.002, 95% confidence interval: 1.000-1.005, p = 0.02) and glomerular filtration rate ≤ 80 ml/min (hazards ratio: 3.23, 95% confidence interval: 1.34-7.24, p = 0.047) were independent risk factors for hypertrophic cardiomyopathy patients with type 2 diabetes mellitus.

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Section: Discussionsupporting

confidence: 92%

Impact of type 2 diabetes mellitus on mid-term mortality for hypertrophic cardiomyopathy patients who underwent septal myectomy

Wang

Cui

et al. 2020

Cardiovasc Diabetol

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“…The metabolic syndrome characterized by obesity, hypertension, insulin resistance, and dyslipidaemia has been proposed to be associated with increased risk of atrial fibrillation [29]. It has been hypothesized that metabolic syndrome causes a transformation of the epicardial adipose tissue leading to proinflammatory mediators causing endothelial dysfunction, and fibrosis, which in turn leads to the development of structural and electrical atrial remodelling [30][31][32][33]. In a nationwide populationbased study, body weight status and diabetes had synergistic effects on the risk of new-onset atrial fibrillation [34].…”

Section: Discussionmentioning

confidence: 99%

Risk of atrial fibrillation in persons with type 2 diabetes and the excess risk in relation to glycaemic control and renal function: a Swedish cohort study

Ahmadi

Svensson

Pivodic

et al. 2020

Cardiovasc Diabetol

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Background: To examine the incidence of atrial fibrillation in individuals with type 2 diabetes compared with ageand sex-matched controls from the general population and its variation in relation to glycaemic control and renal function. Methods:A total of 421,855 patients with type 2 diabetes from the Swedish National Diabetes Registry and 2,131,223 controls from the Swedish Population Registry, matched for age, sex and county, were included and followed from Results: Overall, 8.9% of individuals with type 2 diabetes and 7.0% of controls were diagnosed with atrial fibrillation during follow-up, unadjusted incidence risk ratio (IRR) 1.35 (95% 1.33-1.36). Women < 55 years old with type 2 diabetes had an IRR of 2.36 (95% CI 2.10-2.66), in relation to controls, whereas the corresponding value for men < 55 years old with type 2 diabetes was IRR 1.78 (95% CI 1.67-1.90). In the fully adjusted Cox regression, the risk of type 2 diabetes on incident atrial fibrillation was 28% greater vs controls, hazard ratio (HR) 1.28 (95% CI 1.26-1.30), p < 0.0001. The excess risk of atrial fibrillation in individuals with type 2 diabetes increased with worsening glycaemic control and renal complications. For individuals with HbA1c ≤ 6.9% (≤ 52 mmol/mol) and normoalbuminuria the excess risk vs controls was still increased, adjusted HR 1.16 (95% CI 1.14-1.19); p < 0.0001. Conclusions:Individuals with type 2 diabetes had an overall 35% higher risk of atrial fibrillation compared to ageand sex-matched controls from the general population. The excess risk for atrial fibrillation increased with renal complications or with poor glycaemic control. Individuals with type 2 diabetes with good glycaemic control and normoalbuminuria had slightly increased risk.

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“…A common focal point is the case of Diabetes Mellitus (DM) where a changed metabolic state and altered mitochondrial balance caused by elevated blood glucose levels, glucose fluctuation, and hypoglycemia can set the stage for cardiac arrhythmias (Grisanti, 2018). The altered energy metabolism and increased oxidative stress in DM cardiomyocytes have proven to influence intracellular Ca 2+ handling, activate Ca 2+ /calmodulindependent protein kinase II (CaMKII), and cause mitochondriainduced cell death and fibrosis (El Hadi et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial Dysfunction as Substrate for Arrhythmogenic Cardiomyopathy: A Search for New Disease Mechanisms

et al. 2019

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Arrhythmogenic cardiomyopathy (ACM) is a familial heart disease, associated with ventricular arrhythmias, fibrofatty replacement of the myocardial mass and an increased risk of sudden cardiac death (SCD). Malignant ventricular arrhythmias and SCD largely occur in the pre-clinical phase of the disease, before overt structural changes occur. To prevent or interfere with ACM disease progression, more insight in mechanisms related to electrical instability are needed. Currently, numerous studies are focused on the link between cardiac arrhythmias and metabolic disease. In line with that, a potential role of mitochondrial dysfunction in ACM pathology is unclear and mitochondrial biology in the ACM heart remains understudied. In this review, we explore mitochondrial dysfunction in relation to arrhythmogenesis, and postulate a link to typical hallmarks of ACM. Mitochondrial dysfunction depletes adenosine triphosphate (ATP) production and increases levels of reactive oxygen species in the heart. Both metabolic changes affect cardiac ion channel gating, electrical conduction, intracellular calcium handling, and fibrosis formation; all well-known aspects of ACM pathophysiology. ATP-mediated structural remodeling, apoptosis, and mitochondria-related alterations have already been shown in models of PKP2 dysfunction. Yet, the limited amount of experimental evidence in ACM models makes it difficult to determine whether mitochondrial dysfunction indeed precedes and/or accompanies ACM pathogenesis. Nevertheless, current experimental ACM models can be very useful in unraveling ACM-related mitochondrial biology and in testing potential therapeutic interventions.

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Diabetes and Arrhythmias: Pathophysiology, Mechanisms and Therapeutic Outcomes

Cited by 111 publications

References 194 publications

Impact of type 2 diabetes mellitus on mid-term mortality for hypertrophic cardiomyopathy patients who underwent septal myectomy

Impact of type 2 diabetes mellitus on mid-term mortality for hypertrophic cardiomyopathy patients who underwent septal myectomy

Risk of atrial fibrillation in persons with type 2 diabetes and the excess risk in relation to glycaemic control and renal function: a Swedish cohort study

Mitochondrial Dysfunction as Substrate for Arrhythmogenic Cardiomyopathy: A Search for New Disease Mechanisms

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