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Glucose fluctuations increase the incidence of AF by promoting cardiac fibrosis. Increased ROS levels caused by upregulation of Txnip expression may be a mechanism whereby in glucose fluctuations induce fibrosis.

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300TESHIMA Y et al. Circulation JournalOfficial Journal of the Japanese Circulation Society http://www. j-circ.or.jp iabetes mellitus (DM) is an independent risk factor of heart failure. The Framingham Heart Study reported that the frequency of heart failure is 2-fold higher in male diabetics and 5-fold higher in female diabetics than in age-matched control subjects. 1 An increase in reactive oxygen species (ROS) has been regarded as a dominant mechanism of cardiac dysfunction in patients with DM. 2-4 ROS are important intracellular signaling molecules and mediate various cellular functions, including activation of transcriptional factors, protein kinases, and ion channels; however, high levels of ROS are detrimental to cardiomyocytes. In physiological conditions, ROS levels are appropriately controlled by endogenous antioxidant systems to minimize oxidative cellular damage. Oxidative stress occurs when ROS production overwhelms antioxidant capacity in pathological conditions. It is apparent that ROS production and oxidative stress are increased in the diabetic heart, and oxidative stress induces various cardiovascular complications, including cardiac dysfunction, which is facilitated by inflammation, apoptosis, and fibrosis (Figure 1). [5][6][7][8] There is accumulating evidence that mitochondria and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase play a pivotal role in ROS production in the diabetic heart. In this review, we will summarize the mechanisms of ROS increase in the diabetic heart focusing on the roles of mitochondria and NADPH oxidase. Mitochondria Mitochondrial ROS Production in DMMitochondria not only provide energy, but also provoke apoptosis, which is regulated by mitochondrial dynamics. 9 Mitochondria also generate ROS as natural byproducts of oxygen metabolism in the electron transport chain. Under normal conditions, most of the electrochemical proton gradient is used to generate ATP through ATP synthase, and only 0.1% of the total oxygen consumption leaks from the respiratory chain to generate ROS. However, a high intracellular glucose concentration increases the flux of electron transfer donors (NADH and FADH2) into the mitochondrial respiratory chain by oxidizing glucose-derived pyruvate. The resulting hyperpolarization of the mitochondrial inner membrane potential partially inhibits electron transport in complex III and accumulates electrons to ubisemiquinone to generate superoxide. 10,11 Therefore, mitochondrial respiration is the principal source of ROS in Reactive oxygen species (ROS) are the main facilitators of cardiovascular complications in diabetes mellitus (DM), and the ROS level is increased in cultured cells exposed to high glucose concentrations or in diabetic animal models. Emerging evidence shows that mitochondria and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase are dominant mechanisms of ROS production in the diabetic heart. Hyperpolarization of the mitochondrial inner membrane potentials and impaired mitochondrial function promote ROS production ...

Background Atrial fibrillation (AF) is associated with heart failure (HF) rehospitalization in patients with heart failure with preserved ejection fraction (HFpEF). Objective We tested the hypothesis that catheter ablation of AF could reduce HF rehospitalization compared with conventional pharmacotherapy in patients with HFpEF. Methods Eighty‐five consecutive HFpEF (EF ≥ 50% and a history of HF hospitalization) patients diagnosed as AF by 12‐lead electrocardiogram were retrospectively analyzed. Thirty‐five patients who received catheter ablation (ABL group) were compared with 50 patients treated by antiarrhythmic drugs and/or beta‐blockers (CNT group). The primary endpoint was rehospitalization due to HF. Results The patients characteristics did not differ between the two groups including, age (71 ± 8 vs 71 ± 13 years; P = .637), female sex (34% vs 36%; P = .870), mean plasma brain natriuretic peptide (145 ± 112 vs 195 ± 153 pg/mL; P = .111), mean left ventricular ejection fraction (62% ± 8% vs 61% ± 9%; P = .624), and type of AF (nonparoxysmal AF 60% vs 62%; P = .852). Amiodarone was continued 40% (14 out of 35) and 40% (20 out of 70) in ABL and CNT groups, respectively (P = 1.000). Neither major complication nor major side effect was observed during the follow‐up period. During a mean follow‐up period of 792 ± 485 days, Kaplan‐Meier curve analysis showed that significantly more patients in the ABL group were free from HF rehospitalization (log‐rank P = .0039). Additionally, multivariate analysis revealed that catheter ablation of AF was the only preventive factor of HF rehospitalization (OR = 0.15; 95% CI: 0.04‐0.46; P < .001). Conclusions Catheter ablation of AF reduced HF rehospitalization compared with conventional pharmacotherapy in patients with HFpEF in our institute. Multicenter randomized study is warranted to confirm the result.