The Role of Ferroptosis in Atrial Fibrillation: A Promising Future.

Atrial fibrillation (AF) is one of the most common cardiac arrhythmias, with its diagnosis being closely tied to higher rates of cardiovascular morbidity and mortality. AF is associated with a range of dangerous complications including stroke and heart failure, making it a key driver of healthcare spending and a major threat to global public health. The precise mechanisms that govern AF incidence and the onset of related complications, however, remain uncertain. Ferroptotic cell death has been the focus of rising interest in the cardiac arrhythmias, and there is recent evidence supporting a role for atrial ferroptosis as a mediator of AF development. Interventional strategies focused on ferroptotic activity, such as novel ferroptosis inhibitors, have also shown promise as a means of protecting against AF through their ability to reduce iron overload. In this review, we provide a summary of the proposed mechanisms whereby ferroptosis contributes to the pathophysiology of AF and their therapeutic implications.

Post translational modifications of connexin 43 in ventricular arrhythmias after myocardial infarction.

Ventricular arrhythmias are the leading cause of sudden cardiac death in patients after myocardial infarction (MI). Connexin43 (Cx43) is the most important gap junction channel-forming protein in cardiomyocytes. Dysfunction of Cx43 contributes to impaired myocardial conduction and the development of ventricular arrhythmias. Following an MI, Cx43 undergoes structural remodeling, including expression abnormalities, and redistribution. These alterations detrimentally affect intercellular communication and electrical conduction within the myocardium, thereby increasing the susceptibility to post-infarction ventricular arrhythmias. Emerging evidence suggests that post-translational modifications play essential roles in Cx43 regulation after MI. Therefore, Cx43-targeted management has the potential to be a promising protective strategy for the prevention and treatment of post infarction ventricular arrhythmias. In this article, we primarily reviewed the regulatory mechanisms of Cx43 mediated post-translational modifications on post-infarction ventricular arrhythmias. Furthermore, Cx43-targeted therapy have also been discussed, providing insights into an innovative treatment strategy for ventricular arrhythmias after MI.

Glucose fluctuations aggravate cardiomyocyte apoptosis by enhancing the interaction between Txnip and Akt.

BACKGROUND: Glucose fluctuations may be involved in the pathophysiological process of cardiomyocyte apoptosis, but the exact mechanism remains elusive. This study focused on exploring the mechanisms related to glucose fluctuation-induced cardiomyocyte apoptosis. METHODS: Diabetic rats established via an injection of streptozotocin were randomized to five groups: the controlled diabetic (CD) group, the uncontrolled diabetic (UD) group, the glucose fluctuated diabetic (GFD) group, the GFD group rats with the injection of 0.9% sodium chloride (NaCl) (GFD + NaCl) and the GFD group rats with the injection of N-acetyl-L-cysteine (NAC) (GFD + NAC). Twelve weeks later, cardiac function and apoptosis related protein expressions were tested. Proteomic analysis was performed to further analyze the differential protein expression pattern of CD and GFD. RESULTS: The left ventricular ejection fraction levels and fractional shortening levels were decreased in the GFD group, compared with those in the CD and UD groups. Positive cells tested by DAB-TUNEL were increased in the GFD group, compared with those in the CD group. The expression of Bcl-2 was decreased, but the expressions of Bax, cleaved caspase-3 and cleaved caspase-9 were increased in response to glucose fluctuations. Compared with CD, there were 527 upregulated and 152 downregulated proteins in GFD group. Txnip was one of the differentially expressed proteins related to oxidative stress response. The Txnip expression was increased in the GFD group, while the Akt phosphorylation level was decreased. The interaction between Txnip and Akt was enhanced when blood glucose fluctuated. Moreover, the application of NAC partially reversed glucose fluctuations-induced cardiomyocyte apoptosis. CONCLUSIONS: Glucose fluctuations lead to cardiomyocyte apoptosis by up-regulating Txnip expression and enhancing Txnip-Akt interaction.

Effects of Electrical Remodeling on Atrial Fibrillation in Diabetes Mellitus.

Atrial fibrillation (AF) is one of the most common arrhythmias in medical practice. Diabetes mellitus (DM) is one of the independent risk factors for atrial fibrillation. The increased morbility of atrial fibrillation in diabetes mellitus is related to both structural and electrical remodeling of atrium. Based on studies of atrial electrophysiological changes in diabetes mellitus, this article focuses on the electrical remodeling of atrial cardiomyocytes, including remodeling of sodium channels, calcium channels, potassium channels and other channels, to provide the basis for the clinical management of antiarrhythmic drugs in diabetic patients with atrial fibrillation.

Calcineurin/NFATc3 pathway mediates myocardial fibrosis in diabetes by impairing enhancer of zeste homolog 2 of cardiac fibroblasts.

BACKGROUND: Diabetes is associated with myocardial fibrosis, while the underlying mechanisms remain elusive. The aim of this study is to investigate the underlying role of calcineurin/nuclear factor of activated T cell 3 (CaN/NFATc3) pathway and the Enhancer of zeste homolog 2 (EZH2) in diabetes-related myocardial fibrosis. METHODS: Streptozotocin (STZ)-injected diabetic rats were randomized to two groups: the controlled glucose (Con) group and the diabetes mellitus (DM) group. Eight weeks later, transthoracic echocardiography was used for cardiac function evaluation, and myocardial fibrosis was visualized by Masson trichrome staining. The primary neonatal rat cardiac fibroblasts were cultured with high-glucose medium with or without cyclosporine A or GSK126. The expression of proteins involved in the pathway was examined by western blotting. The nuclear translocation of target proteins was assessed by immunofluorescence. RESULTS: The results indicated that high glucose treatment increased the expression of CaN, NFATc3, EZH2 and trimethylates lysine 27 on histone 3 (H3K27me3) in vitro and in vivo. The inhibition of the CaN/NFATc3 pathway alleviated myocardial fibrosis. Notably, inhibition of CaN can inhibit the nuclear translocation of NFATc3, and the expression of EZH2 and H3K27me3 protein induced by high glucose. Moreover, treatment with GSK126 also ameliorated myocardial fibrosis. CONCLUSION: Diabetes can possibly promote myocardial fibrosis by activating of CaN/NFATc3/EZH2 pathway.

Deep learning-mediated prediction of concealed accessory pathway based on sinus rhythmic electrocardiograms.

BACKGROUND: Concealed accessory pathway (AP) may cause atrial ventricular reentrant tachycardia impacting the health of patients. However, it is asymptomatic and undetectable during sinus rhythm. METHODS: To detect concealed AP with electrocardiography (ECG) images, we collected normal sinus rhythmic ECG images of concealed AP patients and healthy subjects. All ECG images were randomly allocated to the training and testing datasets, and were used to train and test six popular convolutional neural networks from ImageNet pre-training and random initialization, respectively. RESULTS: We screened 152 ECG recordings in concealed AP group and 600 ECG recordings in control group. There were no statistically significant differences in ECG characteristics between control group and concealed AP group in terms of PR interval and QRS interval. However, the QT interval and QTc were slightly higher in control group than in concealed AP group. In the testing set, ResNet26, SE-ResNet50, MobileNetV3_large_100, and DenseNet169 achieved a sensitivity rate more than 87.0% with a specificity rate above 98.0%. And models trained from random initialization showed similar performance and convergence with models trained from ImageNet pre-training. CONCLUSION: Our study suggests that deep learning could be an effective way to predict concealed AP with normal sinus rhythmic ECG images. And our results might encourage people to rethink the possibility of training from random initialization on ECG image tasks.

Comparison of the Anterior Septal Line and Mitral Isthmus Line for Perimitral Atrial Flutter Ablation Using Robotic Magnetic Navigation.

BACKGROUND: Perimitral atrial flutter (PMAFL) is one of the most common macro-reentrant left atrial tachycardias. Mitral isthmus (MI) linear ablation is a common strategy for the treatment of PMAFLs, and anterior septum (AS) linear ablation has emerged as a novel ablation approach. We aimed at assessing the effectiveness of AS linear ablation using robotic magnetic navigation for PMAFL ablation. METHODS: In this retrospective study, a total of 36 consecutive patients presented with AFL as the unique arrhythmia or accompanied with atrial fibrillation (AF) who underwent catheter ablation were enrolled. Patients were classified into two groups according to the different ablation strategies, the MI line group (10 patients) and the AS line group (26 patients). RESULTS: The clinical baseline characteristics of patients in the two groups were nearly identical. There were no significant differences in procedure time (148.7 ± 46.1 vs. 123.2 ± 30.1 min, P=0.058) or radiofrequency ablation time (25.9 ± 11.4 vs. 23.5 ± 12.6 min) between the two groups. Fluoroscopy time was longer in the MI line group (8.0 ± 4.4 vs. 5.1 ± 2.7 min, P=0.024), and the acute success rate was higher in the AS line group versus the MI line group (96.2% vs. 70%, P=0.025). The long-term freedom from arrhythmia survival rate was higher in the AS line group (73%) than in the MI line group (40%) after a mean follow-up time of 37.4 months with a 3-month blanking period (P=0.049). CONCLUSIONS: AS linear ablation is an effective and safe strategy for PMAFL ablation using robotic magnetic navigation.

The long-term efficacy and safety of combining ablation and left atrial appendage closure: A systematic review and meta-analysis.

BACKGROUND: Combined ablation and left atrial appendage closure (LAAC) is an alternative for atrial fibrillation patients with a high risk of stroke. However, the long-term outcomes of this combined procedure remain elusive. METHODS: PubMed, Embase, Cochrane Library, and Web of Science were systematically searched from the establishment of databases to 1 January 2021. Studies on the long-term (defined as a mean follow-up of approximately 12 months or longer) efficacy and safety outcomes of combined ablation and LAAC were included. RESULTS: A total of 16 studies comprising 1428 patients were enrolled. The pooled long-term freedom rate from atrial arrhythmia was 0.66 (95% confidence interval [CI]: 0.59-0.71), long-term successful rate sealing of LAAC was 1.00 (95% CI: 1.00-1.00), and ischemic stroke/transient ischemic attack/systemic embolism during follow-up was 0.01 (95% CI: 0.00-0.02). Meanwhile, of the periprocedural adverse events, phrenic nerve palsy, intracoronary air embolus, device embolization, and periprocedural death had a rate of 0.00 (95% CI: 0.00-0.00), procedure-related bleeding events of 0.03 (95% CI: 0.02-0.04), and pericardial effusion requiring or not requiring intervention of 0.00 (95% CI: 0.00-0.01). Moreover, for the long-term adverse events, device dislocation, intracranial bleeding, pericardial effusion requiring or not requiring intervention, and all-cause mortality had a rate of 0.00 (95% CI: 0.00-0.00), device embolization of 0.01 (95% CI: 0.00-0.01), and other bleeding events of 0.01 (95% CI: 0.00-0.03). CONCLUSION: This meta-analysis suggests that the combined atrial ablation and LAAC is an effective and safe strategy with long-term benefits.

His-Purkinje conduction system pacing: A systematic review and network meta-analysis in bradycardia and conduction disorders.

BACKGROUND: His-Purkinje conduction system pacing (HPCSP) has emerged as an effective alternative to overcome the limitations of right ventricular pacing (RVP) via physiological left ventricular activation, but there remains a paucity of comparative information for His bundle pacing (HBP) and left bundle branch pacing (LBBP). METHODS: A Bayesian random-effects network analysis was conducted to compare the relative effects of HBP, LBBP, and RVP in patients with bradycardia and conduction disorders. PubMed, Embase, Cochrane Library, and Web of Science were systematically searched from database inception until September 21, 2021. RESULTS: Twenty-eight studies involving 4160 patients were included in this meta-analysis. LBBP significantly improved success rate, pacing threshold, pacing impedance, and R-wave amplitude compared with HBP. LBBP also demonstrated a nonsignificant trend towards superior outcomes of lead complications, heart failure hospitalization, atrial fibrillation, and all-cause death. However, HBP was associated with significantly shorter paced QRS duration relative to LBBP. Despite higher success rates, shorter procedure/fluoroscopy duration, and fewer lead complications, patients receiving RVP were more likely to experience reduced left ventricular ejection fraction, longer paced QRS duration, and higher rates of heart failure hospitalization than those receiving HPCSP. No statistical differences were observed in the remaining outcome measures. CONCLUSIONS: This network meta-analysis demonstrates the efficacy and safety of HPCSP for the treatment of bradycardia and conduction disorders, with differences in pacing parameters, electrophysiology characteristics, and clinical outcomes between HBP and LBBP. Larger-scale, long-term comparative studies are warranted for further verification.

A method to screen left ventricular dysfunction through ECG based on convolutional neural network.

OBJECTIVE: This study aims to develop an artificial intelligence-based method to screen patients with left ventricular ejection fraction (LVEF) of 50% or lesser using electrocardiogram (ECG) data alone. METHODS: Convolutional neural network (CNN) is a class of deep neural networks, which has been widely used in medical image recognition. We collected standard 12-lead ECG and transthoracic echocardiogram (TTE) data including the LVEF value. Then, we paired the ECG and TTE data from the same individual. For multiple ECG-TTE pairs from a single individual, only the earliest data pair was included. All the ECG-TTE pairs were randomly divided into the training, validation, or testing data set in a ratio of 9:1:1 to create or evaluate the CNN model. Finally, we assessed the screening performance by overall accuracy, sensitivity, specificity, positive predictive value, and negative predictive value. RESULTS: We retrospectively enrolled a total of 26 786 ECG-TTE pairs and randomly divided them into training (n = 21 732), validation (n = 2 530), and testing data set (n = 2 530). In the testing set, the CNN algorithm showed an overall accuracy of 73.9%, sensitivity of 69.2%, specificity of 70.5%, positive predictive value of 70.1%, and negative predictive value of 69.9%. CONCLUSION: Our results demonstrate that a well-trained CNN algorithm may be used as a low-cost and noninvasive method to identify patients with left ventricular dysfunction.

Association between CRT(D)/ICD and renal insufficiency: A systematic review and meta-analysis.

Cardiac resynchronization therapy with or without a defibrillator (CRT(D)) and implantable cardioverter defibrillator (ICD) may reduce the risk of arrhythmia or heart failure-specific mortality and improves the prognosis of patients with chronic kidney disease (CKD) or dialysis. The aim of this study was to perform a meta-analysis investigating the relationship between CRT(D)/ICD and renal insufficiency. Cochrane Library, Web of Science, Embase, and Pubmed were systematically searched from inception to 29 October 2019. We included studies that report all-cause mortality of patients with renal insufficiency who received CRT(D)/ICD therapy. Twenty-six studies (n = 119,263) were included, exploring the relationship between CRT(D)/ICD and renal insufficiency from two aspects: (1) Compared with ICD-only, CRT(D) was associated with lower risk of all-cause mortality in CKD patients (odds ratios (OR) = 0.67; 95% confidence interval (CI), 0.60 to 0.75). For non-primary prevention (secondary prevention or both), the analysis revealed a lower risk of all-cause mortality in the ICD group than in the no-ICD group (OR = 0.47; 95% CI, 0.40 to 0.55). (2) CKD increased all-cause mortality in comparison with control group (OR = 2.12; 95% CI, 1.85 to 2.44), and so did dialysis (OR = 2.53; 95% CI, 2.34 to 2.73). Furthermore, compared with CKD3 (eGFR: 30-59 ml/min/1.73 m2 ), CKD4/5 (eGFR <30 ml/min/1.73 m2 ) was observed to have a significantly higher risk of all-cause mortality (OR = 2.70; 95% CI, 1.93 to 3.80). This review shows a clear association between CRT(D)/ICD and renal insufficiency in the aspect of all-cause mortality, and may provide a reference for the clinical application of CRT(D)/ICD.

Modulation of SK Channels: Insight Into Therapeutics of Atrial Fibrillation.

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia in the world. Although much technological progress in the treatment of AF has been made, there is an urgent need for better treatment of AF due to its high rates of morbidity and mortality. The anti-arrhythmic drugs currently approved for marketing have significant limitations and side effects such as life-threatening ventricular arrhythmias and hypotension. The small conductance Ca2+-activated K+ channels (SK channels) are dependent on intracellular Ca2+ concentrations, which tightly integrate with membrane potential. Given the predominant expression in the atria of many species, including humans, they are now emerging as a therapeutic target for treating AF. This review aimed to illustrate the characteristics and function of SK channels. Moreover, it discussed the regulation of SK channels and their potential as a therapeutic target of AF.

Glucose fluctuations promote vascular BK channels dysfunction via PKCα/NF-κB/MuRF1 signaling.

Glucose fluctuations may contribute to large conductance calcium activated potassium (BK) channel dysfunction. However, the underlying mechanisms remain elusive. The aim of this study was to investigate the molecular mechanisms involved in BK channel dysfunction as a result of glucose fluctuations. A rat diabetic model was established through the injection of streptozotocin. Glucose fluctuations in diabetic rats were induced via consumption and starvation. Rat coronary arteries were isolated and coronary vascular tensions were measured after three weeks. Rat coronary artery smooth muscle cells were isolated and whole-cell BK channel currents were recorded using a patch clamp technique. Human coronary artery smooth muscle cells in vitro were used to explore the underlying mechanisms. After incubation with iberiotoxin (IBTX), the Δ tensions (% Max) of rat coronary arteries in the controlled diabetes mellitus (C-DM), the uncontrolled DM (U-DM) and the DM with glucose fluctuation (GF-DM) groups were found to be 84.46 ± 5.75, 61.89 ± 10.20 and 14.77 ± 5.90, respectively (P < .05), while the current densities of the BK channels in the three groups were 43.09 ± 4.35 pA/pF, 34.23 ± 6.07 pA/pF and 17.87 ± 4.33 pA/pF, respectively (P < .05). The Δ tensions (% Max) of rat coronary arteries after applying IBTX in the GF-DM rats injected with 0.9% sodium chloride (NaCl) (GF-DM + NaCl) and the GF-DM rats injected with N-acetyl-L-cysteine (NAC) (GF-DM + NAC) groups were found to be 8.86 ± 1.09 and 48.90 ± 10.85, respectively (P < .05). Excessive oxidative stress and the activation of protein kinase C (PKC) α and nuclear factor (NF)-κB induced by glucose fluctuations promoted the decrease of BK-ß1 expression, while the inhibition of reactive oxygen species (ROS), PKCα, NF-κB and muscle ring finger protein 1 (MuRF1) reversed this effect. Glucose fluctuations aggravate BK channel dysfunction via the ROS overproduction and the PKCα/NF-κB/MuRF1 signaling pathway.

The long-term therapeutic effects of His-Purkinje system pacing on bradycardia and cardiac conduction dysfunction compared with right ventricular pacing: A systematic review and meta-analysis.

AIMS: His-Purkinje system pacing has been demonstrated as a synchronized ventricular pacing strategy via pacing His-Purkinje system directly, which can decrease the incidence of adverse cardiac structure alteration compared with right ventricular pacing (RVP). The purpose of this meta-analysis was to compare the effects of His-Purkinje system pacing and RVP in patients with bradycardia and cardiac conduction dysfunction. METHODS: PubMed, Embase, Cochrane Library, and Web of Science were systematically searched from the establishment of databases up to 15 December 2019. Studies on long-term clinical outcomes of His-Purkinje system pacing and RVP were included. Chronic paced QRS duration, chronic pacing threshold, left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), all-cause mortality, and heart failure hospitalization were collected for meta-analysis. RESULTS: A total of 13 studies comprising 2348 patients were included in this meta-analysis. Compared with RVP group, patients receiving His-Purkinje system pacing showed improvement of LVEF (mean difference [MD], 5.65; 95% confidence interval [CI], 4.38-6.92), shorter chronic paced QRS duration (MD, - 39.29; 95% CI, - 41.90 to - 36.68), higher pacing threshold (MD, 0.8; 95% CI, 0.71-0.89) and lower risk of heart failure hospitalization (odds ratio [OR], 0.65; 95% CI, 0.44-0.96) during the follow-up. However, no statistical difference existed in LVEDV, LVESV and all-cause mortality between the two groups. CONCLUSION: Our meta-analysis suggests that His-bundle pacing is more suitable for the treatment of patients with bradycardia and cardiac conduction dysfunction.

Glucose Fluctuations Promote Aortic Fibrosis through the ROS/p38 MAPK/Runx2 Signaling Pathway.

AIM: Glucose fluctuations may be responsible for, or further the onset of arterial hypertension, but the exact mechanisms remain unclear. The purpose of this study was to investigate the mechanisms behind and related to aortic fibrosis and aortic stiffening induced by glucose fluctuations. METHODS: Sprague-Dawley rats were injected with streptozotocin (STZ) and randomly divided into three treatment groups: controlled STZ-induced diabetes (C-STZ); uncontrolled STZ-induced diabetes (U-STZ); and STZ-induced diabetes with glucose fluctuations (STZ-GF). After 3 weeks, rat blood pressure (BP) was tested, and aortic fibrosis was detected by using the Masson trichrome staining technique. Levels of p38 mitogen-activated protein kinase (p38 MAPK), runt-related transcription factor 2 (Runx2), collagen type 1 (collagen I), and NADPH oxidases were determined by Western blot.Rat vascular smooth muscle cells in vitro were used to explore underlying mechanisms. RESULTS: The systolic BP of diabetic rats in the C-STZ, U-STZ, and STZ-GF groups was 127.67 ± 6.53, 150.03 ± 5.24, and 171.63 ± 3.53 mm Hg, respectively (p< 0.05). The mean BP of diabetic rats in the three groups was 91.20 ± 10.07, 117.29 ± 4.28, and 140.58 ± 2.14 mm Hg, respectively (p< 0.05). The diastolic BP of diabetic rats in the three groups was 73.20 ± 12.63, 101.93 ± 5.79, and 125.37 ± 4.62 mm Hg, respectively (p< 0.05). The ratios of fibrosis areas in the aortas of the three groups were 11.85 ± 1.23, 29.00 ± 0.87, and 48.36 ± 0.55, respectively (p< 0.05). The expressions of p38 MAPK, Runx2, and collagen I were significantly increased in the STZ-GF group. In vitro, applications of inhibitors of reactive oxygen species (ROS) and p38 MAPK successfully reversed glucose fluctuations that would have possibly induced aortic fibrosis. CONCLUSIONS: Blood glucose fluctuations aggravate aortic fibrosis via affecting the ROS/p38 MAPK /Runx2 signaling pathway.

Regulation of Coronary Arterial Large Conductance Ca2+-Activated K+ Channel Protein Expression and Function by n-3 Polyunsaturated Fatty Acids in Diabetic Rats.

AIM: The objective of this study was to examine the effects of n-3 polyunsaturated fatty acids (n-3 PUFAs) on coronary arterial large conductance Ca2+-activated K+ (BK) channel function in coronary smooth muscle cells (SMCs) of streptozotocin-induced diabetic rats. METHODS: The effects of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on coronary BK channel open probabilities were determined using the patch clamp technique. The mRNA and protein expressions of BK channel subunits were measured using qRT-PCR and Western blots. The coronary artery tension and coronary SMC Ca2+ concentrations were measured using a myograph system and fluorescence Ca2+ indicator. RESULTS: Compared to nondiabetic control rats, the BK channel function was impaired with a reduced response to EPA and DHA in freshly isolated SMCs of diabetic rats. Oral administration of n-3 PUFAs had no effects on protein expressions of BK channel subunits in nondiabetic rats, but significantly enhanced those of BK-ß1 in diabetic rats without altering BK-α protein levels. Moreover, coronary ring tension induced by iberiotoxin (a specific BK channel blocker) was increased and cytosolic Ca2+ concentrations in coronary SMCs were decreased in diabetic rats, but no changes were found in nondiabetic rats. CONCLUSIONS: n-3 PUFAs protect the coronary BK channel function and coronary vasoreactivity in diabetic rats as a result of not only increasing BK-ß1 protein expressions, but also decreasing coronary artery tension and coronary smooth muscle cytosolic Ca2+ concentrations.

Changes in left ventricular synchrony and systolic function in dilated cardiomyopathy patients with fragmented QRS complexes.

AIMS: Fragmented QRS (f-QRS) complexes are associated with adverse cardiovascular events in patients with coronary heart disease; however, the effects on patients with dilated cardiomyopathy (DCM) remain elusive. This study is to investigate the changes of left ventricular (LV) synchrony and systolic function in DCM patients with f-QRS complexes. METHODS AND RESULTS: Twenty DCM patients with f-QRS complexes and 29 DCM patients without f-QRS (n-QRS) complexes were enrolled. The LV segmental longitudinal, radial and circumferential time to peak strain and general longitudinal systolic strain, radial strain, circumferential strain were measured, respectively, by speckle tracking imaging. The LV segmental standard deviations and maximal differences were also calculated. The LV dyssynchrony was defined as the time in peak anteroseptal wall to posterior wall strain >130 ms or longitudinal strain delay index >25%. The mean QRS durations in f-QRS and n-QRS groups were not different (P = ns). The incidence of LV dyssynchrony was 15/20 (75%) vs. 5/29 (17%) in two groups (P < 0.01). Two patients died of sudden death in f-QRS group during 2 years follow-up; however, no death in n-QRS group (P < 0.05). Patients in f-QRS group showed worsening LV dyssynchrony in f-QRS group after 2 years follow-up (P < 0.05). Overall, LV function was comparable at baseline (P = ns), but had significantly worsened only in the f-QRS group (P < 0.05). CONCLUSION: The f-QRS complex is significantly associated with LV dyssynchrony in DCM patients and can be used as a reliable index to evaluate ventricular synchrony and predict the prognosis in DCM patients with narrow QRS complexes.

The role and mechanism of heme oxygenase-1 in arrhythmias.

The global incidence and prevalence of arrhythmias are continuously increasing. However, the precise mechanisms of underlying arrhythmogenesis and the optimal measures for effective treatment remain incompletely understood. The inducible form of heme oxygenase, known as heme oxygenase-1 (HO-1), is recognized as a potent antioxidant molecule capable of exerting anti-inflammatory and anti-apoptotic effects. Recent research indicates that HO-1 plays a role in preventing arrhythmias by mitigating cardiac remodeling, including electrical remodeling, ion remodeling, and structural remodeling. This review aimed to consolidate current knowledge regarding the involvement of HO-1 in arrhythmias and elucidate its underlying mechanisms of action.

The Role and Underlying Mechanisms of Exercise in Heart Failure.

Heart failure is a prevalent and life-threatening syndrome characterized by structural and/or functional abnormalities of the heart. As a global burden with high rates of morbidity and mortality, there is growing recognition of the beneficial effects of exercise on physical fitness and cardiovascular health. A substantial body of evidence supports the notion that exercise can play a protective role in the development and progression of heart failure and improve cardiac function through various mechanisms, such as attenuating cardiac fibrosis, reducing inflammation, and regulating mitochondrial metabolism. Further investigation into the role and underlying mechanisms of exercise in heart failure may uncover novel therapeutic targets for the prevention and treatment of heart failure.

Role of angiotensin receptor-neprilysin inhibitor in diabetic complications.

Diabetes mellitus is a prevalent disorder with multi-system manifestations, causing a significant burden in terms of disability and deaths globally. Angio-tensin receptor-neprilysin inhibitor (ARNI) belongs to a class of medications for treating heart failure, with the benefits of reducing hospitalization rates and mortality. This review mainly focuses on the clinical and basic investigations related to ARNI and diabetic complications, discussing possible physiological and molecular mechanisms, with insights for future applications.