Linking homocysteine and ferroptosis in cardiovascular disease: insights and implications.

Homocysteine (Hcy) is a metabolic intermediate product derived from methionine. Hyperhomocysteinemia is a condition associated with various diseases. Hcy is recognized as a risk factor for cardiovascular disease (CVD). Ferroptosis, a novel form of cell death, is primarily characterized by substantial iron accumulation and lipid peroxidation. Recent research indicates a close association between ferroptosis and the pathophysiological processes of tumors, neurological diseases, CVD, and other ailments. However, limited research has been conducted on the impact of Hcy on ferroptosis. Therefore, this paper aimed to investigate the potential roles and mechanisms of homocysteine and ferroptosis in the context of cardiovascular disease. By conducting comprehensive literature research and analysis, we aimed to summarize recent advancements in understanding the effects of homocysteine on ferroptosis in cardiovascular diseases. This research contributes to a profound understanding of this critical domain.

The heart rate response to the 6-min walk test in atrial fibrillation patients with or without beta-blockers: Referring to patients with sinus rhythm.

BACKGROUND: The aim was to evaluate the effect of beta-blockers (BB) on the response of heart rate (HR) to 6-min walk test (6MWT) in atrial fibrillation (AF) and whether the AF patients treated with BB have a similar HR response to 6MWT as the AF and sinus rhythm (SR) patients without BB treatment at the same resting HR level. METHODS: The before-after study involving 74 AF patients was to evaluate the effect of BB treatment (pre-BB and with BB). The comparison study included 74 BB-treated AF patients (with BB), 74 matched AF patients without BB (no BB), and 74 SR patients. The percentage increase amplitude of HR (HR-PIA) in 6MWT was calculated: [(the exercise HR - the resting HR)/(the resting HR)] × 100%. RESULTS: The before-after study showed that BB treatment decreased the resting and mean exercise HR (98.6 ± 15.2 vs. 85.5 ± 11.2 bpm and 121.3 ± 17.3 vs. 109.0 ± 16.7 bpm) during 6MWT. The comparison study demonstrated that against the SR, the AF with BB and no BB groups have higher mean exercise HR-PIA (28.2 ± 17.1% and 22.0 ± 9.6%, vs. 6.9 ± 3.7%) when their resting HR is similar. Moreover, the mean exercise HR-PIA was also significantly higher in the with BB group than in the no BB group. CONCLUSION: In AF patients with relatively higher resting HR, BB treatment could decrease the resting and exercise HR during 6MWT. However, BB treatment could not effectively attenuate the exercise HR rise as compared with AF without BB treatment, even with similar resting HR levels.

Development and Validation of a Novel Prognostic Model Predicting the Atrial Fibrillation Recurrence Risk for Persistent Atrial Fibrillation Patients Treated with Nifekalant During the First Radiofrequency Catheter Ablation.

BACKGROUND: This study aimed to establish and assess a prediction model for patients with persistent atrial fibrillation (AF) treated with nifekalant during the first radiofrequency catheter ablation (RFCA). METHODS: In this study, 244 patients with persistent AF from January 17, 2017 to December 14, 2017, formed the derivation cohort, and 205 patients with persistent AF from December 15, 2017 to October 28, 2018, constituted the validation cohort. The least absolute shrinkage and selection operator regression was used for variable screening and the multivariable Cox survival model for nomogram development. The accuracy and discriminative capability of this predictive model were assessed according to discrimination (area under the curve [AUC]) and calibration. Clinical practical value was evaluated using decision curve analysis. RESULTS: Body mass index, AF duration, sex, left atrial diameter, and the different responses after nifekalant administration were identified as AF recurrence-associated factors, all of which were selected for the nomogram. In the development and validation cohorts, the AUC for predicting 1-year AF-free survival was 0.863 (95% confidence interval (CI) 0.801-0.926) and 0.855 (95% CI 0.782-0.929), respectively. The calibration curves showed satisfactory agreement between the actual AF-free survival and the nomogram prediction in the derivation and validation cohorts. In both groups, the prognostic score enabled stratifying the patients into different AF recurrence risk groups. CONCLUSIONS: This predictive nomogram can serve as a quantitative tool for estimating the 1-year AF recurrence risk for patients with persistent AF treated with nifekalant during the first RFCA.

Prevalence estimates of the insulin resistance and associated prevalence of heart failure among United Status adults.

BACKGROUND: The triglyceride glucose (TyG) index, a metric for estimating insulin resistance (IR), is linked with cardiovascular disease (CVD) morbidity and mortality among the population regardless of diabetic status. However, IR prevalence and the association between the TyG index and heart failure (HF) in Americans is unclear. METHODS: The Nation Health and Nutrition Examination Survey (NHANES) (2009-2018) dataset was used. IR was defined by homeostatic model assessment of insulin resistance (HOMA-IR) > 2.0 and 1.5. The TyG index was calculated as Ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. A weighted logistic regression was applied to evaluate the association between the TyG index and the prevalence of HF. RESULTS: This study comprised 12,388 people, including 322 (2.6%) individuals with HF. The average prevalence of IR was found to be 13.9% and 22.7% for cutoff values greater than 2.0 and 1.5, respectively. HOMA-IR and the TyG index showed a moderate correlation (r = 0.30). There is a significant positive association between the TyG index and HF prevalence (per 1-unit increment; adjusted OR [aOR]: 1.34; 95% confidence interval [CI]: 1.02-1.76). Patients with higher TyG values were associated with a prevalence of HF (OR:1.41; 95% CI: 1.01,1.95) (quartiles 4 vs 1-3). The TyG index is associated with a higher prevalence of dyslipidemia, coronary heart disease, and hypertension but not a stroke (cerebrovascular disease). CONCLUSIONS: Our results show that IR does not considerably increase from 2008 to 2018 in American adults. A moderate correlation is noted between HOMA-IR and the TyG index. TyG index is associated with the prevalence of HF, as were other cardiovascular diseases.

Association of serum copper (Cu) with cardiovascular mortality and all-cause mortality in a general population: a prospective cohort study.

BACKGROUND: Copper (Cu) homeostasis and Cu-induced cell death are gaining recognition as crucial processes in the pathogenesis of cardiovascular disease (CVD). Circulating Cu associated with CVD and mortality is yet to be fully elucidated. OBJECTIVE: This national prospective cohort study is to estimate relationship between serum Cu and the risk of CVD and all-cause mortality. METHODS: This study included participants from the National Health and Nutrition Examination Survey 2011-2016. Weighted Cox proportional hazards regression analysis and exposure-response curves were applied. RESULTS: This included 5,412 adults, representing 76,479,702 individuals. During a mean of 5.85 years of follow-up (31,653 person-years), 96 CVD and 356 all-cause mortality events occurred. Age and sex-adjusted survival curves showed that individuals with higher levels of serum Cu experienced increased CVD and all-cause death rates (tertiles, p < 0.05). Compared with the participant in tertile 1 of serum Cu (< 16.31 mol/L), those in tertile 3 (≥ 19.84 mol/L) were significantly associated with CVD mortality (HR: 7.06, 95%CI: 1.85,26.96), and all-cause mortality (HR: 2.84, 95% CI: 1.66,4.87). The dose-response curve indicated a linear relationship between serum Cu and CVD mortality (p -nonlinear = 0.48) and all-cause (p -nonlinear = 0.62). A meta-analysis included additional three prospective cohorts with 13,189 patients confirmed the association between higher serum Cu and CVD (HR: 2.08, 95% CI: 1.63,2.65) and all-cause mortality (HR: 1.89, 95%CI: 1.58,2.25). CONCLUSION: The present study suggests excessive serum Cu concentrations are associated with the risk of CVD and all-cause mortality in American adults. Our findings and the causal relationships require further investigation.

CBL aggravates Ang II-induced cardiac hypertrophy via the VHL/HIF-1α pathway.

CBL (Casitas B cell lymphoma), an important ubiquitin protein ligase, is involved in protein folding, protein maturation, and proteasome-dependent protein catabolism in different cells. However, its role in cardiac hypertrophy is still unclear. In this study, we found that expression of CBL is increased in an Ang II-induced mouse cardiac hypertrophy animal model and in Ang II-treated H9C2 cells. Interference with CBL expression attenuates the degree of myocardial hypertrophy as well as the expression of hypertrophy-related genes in H9C2 cells. Further research found that CBL aggravates myocardial hypertrophy by activating HIF-1α, which is an aggravating factor for hypertrophy. The effect of CBL on promoting myocardial hypertrophy was reversed by interference with HIF-1α. Mechanistically, we found that CBL directly interacted with and degraded VHL by increasing its ubiquitination level, which is a widely accepted regulatory factor of HIF-1α. Finally, our results showed that CBL was partially dependent on degradation of VHL and that activation of HIF-1α promoted myocardial hypertrophy. Collectively, these findings suggest that strategies based on activation of the CBL/HIF-1α axis might be promising for the treatment of hypertrophic cardiomyopathy.

Long-term outcomes of left bundle branch area pacing versus biventricular pacing in patients with heart failure and complete left bundle branch block.

Left bundle branch area pacing (LBBAP) has developed in an effort to improve cardiac resynchronization therapy (CRT). We aimed to compare the long-term clinical outcomes between LBBAP and biventricular pacing (BIVP) in patients with heart failure (HF) and complete left bundle branch block (CLBBB). Consecutive patients with HF and CLBBB requiring CRT received either LBBAP or BIVP were recruited at the Second Affiliated Hospital of Nanchang University from February 2018 to May 2019. We assessed their implant parameters, electrocardiogram (ECG), clinical outcomes at implant and during follow-up at 1, 3, 6, 12, and 24 months. Forty-one patients recruited including 21 for LBBAP and 20 for BIVP. Mean follow-up duration was 23.71 ± 4.44 months. LBBAP produced lower pacing thresholds, shorter procedure time and fluoroscopy duration compared to BIVP. The QRS duration was significantly narrower after LBBAP than BIVP (129.29 ± 31.46 vs. 156.85 ± 26.37 ms, p = 0.005). Notably, both LBBAP and BIVP significantly improved LVEF, LVEDD, NYHA class, and BNP compared with baseline. However, LBBAP significantly lowered BNP compared with BIVP (416.69 ± 411.39 vs. 96.07 ± 788.71 pg/ml, p = 0.007) from baseline to 24-month follow-up. Moreover, patients who received LBBAP exhibited lower number of hospitalizations than those in the BIVP group (p = 0.019). In addition, we found that patients with moderately prolonged left ventricular activation time (LVAT) and QRS notching in limb leads in baseline ECG respond better to LBBAP for CLBBB correction. LBBAP might be a relative safe and effective resynchronization therapy and as a supplement to BIVP for patients with HF and CLBBB.

Successful implantation of leadless pacemaker in a patient with giant right atrium and tricuspid valve stenosis.

With the steadily increasing amount of leadless pacemaker implantations performed worldwide, it has called attention to the delivery difficulty in patients with severe large right heart. Nevertheless, limited studies have reported leadless pacemaker implantation in patients with tricuspid stenosis. Here, we report the successful implantation of leadless pacemaker in a 60-year-old female patient with giant right atrium and tricuspid valve stenosis. It is highlighted that leadless pacemaker should not be discouraged even if there are tricuspid valve stenosis and giant right atrium.

Permanent Left Bundle Branch Area Pacing for High-Degree Atrioventricular Block in a 6-Year-Old Child with 2-Year Follow-Up.

The feasibility and safety of left bundle branch area pacing (LBBAP) used in pediatric patients with atrioventricular block (AVB) have not been well demonstrated. Currently, only several case reports for pediatric patients have been published since the advent of LBBAP, with 3 months to 1 year follow-up. Here, we present a case of LBBAP in a 6-year-old child with a high-degree AVB secondary to the transcatheter device closure of congenital ventricular septal defect. No procedure-related complications were observed, and the electrical parameters were stable at 2-year follow-up. Additionally, we performed a systematic literature review on pediatric patients with LBBAP. Fifteen cases were retrieved after systematically searching PubMed and Embase databases. No complications have been reported among these published cases. In conclusion, consistent with previous cases, our case with 2-year follow-up has demonstrated that LBBAP may be an alternative pacing modality from a very early age. However, given the limited evidence, the long-term outcomes of LBBAP in pediatric patients should be further investigated.

Long-term amlodipine-based combination therapy attenuates seasonal variation of blood pressure in hypertensive patients.

Objectives: This study was to investigate whether long-term amlodipine-based combination therapy attenuates seasonal variation of office blood pressure (BP) in hypertensive patients. Methods: The data of 206 patients recruited in the Nanchang site of CHIEF trial were retrospectively analyzed. All patients received an amlodipine-based therapy for three years after reaching target BP with a 12-week titration treatment. Among them, 106 patients received amlodipine plus amiloride/hydrochlorothiazide (AA group) and 100 received amlodipine plus telmisartan (AT group) therapies. These patients were followed up every three months . The difference between the highest and lowest values of outdoor temperature in each three months was calculated as the seasonal temperature difference (T-d) and seasonal BP difference was calculated in the similar way. BP control rates in each season were calculated. Results: In the three years, the highest SBP and DBP values occurred in winter and the lowest values in summer. As a result, the BP control rate in summer was the highest and that in winter was the lowest, especially for SBP. Although T-d levels were similar during three following-up years, the seasonal SBP/DBP differences in 2011 were significantly lower than 2009 (10.03 ± 5.74/6.96 ± 3.72 vs 14.36 ± 8.19/9.78 ± 5.21 mmHg, P < .05), suggesting seasonal variation in BP was obviously reduced. Meanwhile, similar change was observed in AA and AT groups. Conclusions: Besides lower BP effectively, long-term amlodipine-based combination therapy could alleviate the seasonal BP variation in high-risk hypertensive patients.

Protective mechanism of SIRT1 on Hcy-induced atrial fibrosis mediated by TRPC3.

High plasma levels of homocysteine (Hcy) are regarded as a risk factor for atrial fibrillation (AF), which is closely associated with the pathological consequence of atrial fibrosis and can lead to heart failure with a high mortality rate; here, we show that atrial fibrosis is mediated by the relationship between canonical transient receptor potential 3 (TRPC3) channels and sirtuin type 1 (SIRT1) under the stimulation of Hcy. The left atrial appendage was obtained from patients with either sinus rhythm (SR) or AF and used to evaluate the relationship between the concentration of Hcy and a potential mechanism of cardiac fibrosis mediated by TRPC3 and SIRT1. We next performed transverse aortic constriction (TAC) in mouse to investigate the relationship. The mechanisms underlying atrial fibrosis involving TRPC3 and SIRT1 proteins were explored by co-IP, BLI and lentivirus transfection experiments. qPCR and WB were performed to analyse gene and protein expression, respectively. The higher level of atrial fibrosis was observed in the HH mouse group with a high Hcy diet. Such results suggest that AF patients may be more susceptible to atrial fibrosis and possess a high probability of progressing to hyperhomocysteinemia. Moreover, our findings are consistent with the hypothesis that TRPC3 channel up-regulation leads to abnormal accumulation of collagen, with the down-regulation of SIRT1 as an aetiological factor of high Hcy, which in turn predisposes to atrial fibrosis and strongly enhances the possibility of AF.

Downregulated CHI3L1 alleviates skeletal muscle stem cell injury in a mouse model of sepsis.

Sepsis is an acute systemic inflammatory response of the body to microbial infection and a life-threatening condition associated with multiple organ failure. Recent data suggest that sepsis survivors present with long-term myopathy due to the dysfunction of skeletal muscle stem cells and satellite cells. Accumulating studies have implicated chitinase-3-like-1 protein (CHI3L1) in a variety of infectious diseases, specifically sepsis. Therefore, the aim of the present study is to elucidate the potential mechanism by which CHI3L1 is involved in the injury of skeletal muscle stem cells in mouse models of sepsis. An in vitro cell model was developed by lipopolysaccharide (LPS) and in vivo mouse model of sepsis was induced by CRP-like protein (CLP). To elucidate the biological significance behind the silencing of CHI3L1, modeled skeletal muscle stem cells and mice were treated with siRNA against CHI3L1 or overexpressed CHI3L1. Highly expressed CHI3L1 was found in skeletal muscle tissues of mice with sepsis. Besides, siRNA-mediated silencing of CHI3L1 was revealed to increase Bcl-2 expression along with cell proliferation, while diminishing Bax expression, cell apopstosis as well as serum levels of TNF-α, IL-1ß, INF-γ, IL-10, and IL-6. Taken conjointly, this present study provided evidence suggesting that downregulation of CHI3L1 has the potential to prevent the injury of skeletal muscle stem cells in mice with sepsis. Collectively, CHI3L1 may serve as a valuable therapeutic strategy in alleviating sepsis.

Identification of atrial fibrillation-related circular RNAs and constructing the integrative regulatory network of circular RNAs, microRNAs and mRNAs by bioinformatics analysis.

Atrial fibrillation (AF) is the most common cardiac arrhythmia with a high incidence of stroke. Many circular RNAs (circRNAs) have been demonstrated they are elated to various heart diseases and may play important roles in diagnostics or many pathophysiological processes. Nevertheless, there is Few studies on circRNAs functions in persistent AF. To identify AF-related circRNAs and construct the integrative regulatory network of circular RNAs, miRNAs, and mRNAs, we collected human right atrial appendage tissues from 5 patients suffering persistent AF (AF group) and 5 patients with normal sinus rhythm (NSR group) and characterized the global changes in circRNA expression with high-throughput sequencing technology. The differential expression of circRNAs and the interactions between circRNAs and microRNAs were analyzed. The microRNA expression file GSE68475 dataset was downloaded from the Gene Expression Omnibus (GEO) database to explore the differentially expressed microRNAs. The target genes of overlapped miRNAs were predicted by using DIANA-TarBase v8. We constructed the circRNA- miRNA-mRNA network using Cytoscape (version 3.4.0) and the network topology was analyzed by utilizing CentiScaPe app. Results showed that all of 600 differentially expressed circRNAs related to AF were screened, including 340 up-regulated and 260 down-regulated circRNAs. An integrative regulatory network was constructed, which included 30 circRNAs, 9 miRNAs and 130 target mRNAs of these miRNAs. It was concluded that that 30 circRNAs, including 8 upregulated circRNAs and 22 downregulated circRNAs, were predicted to highly possibly function as sponges of 9 miRNAs to regulate gene expression by using bioinformatics analysis. Moreover, the interactions of hsa-miR-339-5p with its related circRNAs and target mRNAs constructed the hub regulatory network in persistent AF by utilizing topology analysis. Our proposed regulatory network of circRNAs-miRNAs-mRNAs may provide new insight into the potential mechanism underlying persistent AF. Additionally, these important molecular may become novel biomarkers providing a new strategy in diagnosis and therapy of AF.

Different adiposity indices and their associations with hypertension among Chinese population from Jiangxi province.

BACKGROUND: To date, the best adiposity index that predicts or associates strongly with hypertension remains controversial. Therefore, we aimed to compare the performance of different adiposity indices [BMI (body mass index), WC (waist circumference), WHtR (waist-to-height ratio), ABSI (a body shape index), VAI (visceral adipose index), BFP (body fat percentage)] as associates and potential predictors of risk of hypertension among Chinese population. METHODS: A cross-sectional survey was conducted in Jiangxi province, China from 2013 to 2014. A total of 14,573 participants were included in the study. The physical measurements included body height, weight, WC, BFP and VAI. Multivariate logistic regression analysis was performed to assess the associations between different adiposity indices and the prevalence of hypertension. Receiver operating characteristic (ROC) analysis was also performed. RESULTS: All adiposity indices were independently and positively associated with the prevalence of hypertension in a dose response fashion. The area under the curves (AUCs) for WHtR, BFP and VAI were significantly larger than those for other adiposity indices in both males and females (all P < 0.01). For males, no statistically significant difference was found in AUCs among WHtR and BFP (0.653 vs. 0.647, P = 0.4774). The AUC of WHtR was significantly higher than VAI (0.653 vs. 0.636, P < 0.01). For females, the AUCs demonstrated that WHtR was significantly more powerful than BFP and VAI (both P < 0.05) for predicting hypertension [WHtR, 0.689 (0.677-0.702); BFP, 0.677 (0.664-0.690); VAI, 0.668 (0.655-0.680)]. Whereas no significant differences were found in AUCs for hypertension among BFP and VAI in both sexes (all P > 0.1). The AUCs for hypertension associated with each adiposity index declined with age in both males and females. For subjects aged < 65 years, WHtR still had the largest AUC. However, for participants aged ≥65 years, BMI had the largest AUC. CONCLUSION: The findings indicated that WHtR was the best for predicting hypertension, followed by BFP and VAI, especially in younger population.

A Hybrid Procedure Combining Mini-Thoracotomy with Interventional Endocardial Lead Implantation for Cardiac Resynchronization Therapy in Patients with Chronic Congestive Heart Failure: A Report of Four Cases.

BACKGROUND: We describe the application and effectiveness of transthoracic electrode implantation for epicardial left ventricular pacing in cardiac resynchronization therapy (CRT) for patients with chronic congestive heart failure. METHODS: We assessed four patients with chronic congestive heart failure for whom implantation of endocardial electrodes was contraindicated. The epicardial electrodes were implanted via a mini-thoracotomy in the fourth or fifth left intercostal space. We analyzed the surgical implantation technique and the short-term effectiveness of the procedure. RESULTS: The epicardial electrodes successfully were implanted in all four patients. The patients' hemodynamic status, cardiac function, and symptoms significantly improved. Patients I, II, III, and IV were discharged from the hospital on the 8, 11, 4, and 7 days, respectively, after the operation. Follow up lasted for 12 months. None of the patients presented with electrode fractures or surgical wound infections, and the pacing threshold and electrode impedance were normal. In one case, phrenic nerve stimulation occurred due to the low placement position of the electrode. When the electrode was moved slightly inward and upward, the sacral nerve stimulation sign disappeared, and no other complications were noted. One patient developed capsule infection, and the presence of an ectopic pacemaker was noted; therefore, a pacemaker replacement procedure was required. CONCLUSION: In CRT, the implantation of a left ventricular epicardial electrode through a left-sided small incision is safe, feasible, and effective. This hybrid surgery combining interventional and cardiac techniques can maximize the curative effect of CRT.

Surgical Treatment of Coronary Pseudoaneurysm: A Case Report and Literature Review.

A coronary pseudoaneurysm is a rare complication of chest trauma. In this report, we describe the case of a 65-year-old man with a mediastinal lesion. On admission, he complained of chest tightness and dry cough, and a pseudoaneurysm was confirmed in the left anterior descending branch of the coronary artery on chest computerized tomography, angiography, and coronary angiography. The patient had experienced chest trauma 5 years previously. With the help of extracorporeal bypass surgery, the pseudoaneurysm was resected under direct observation. The patient recovered well after surgery. Traumatic coronary artery pseudoaneurysms usually are asymptomatic and often misdiagnosed. Preoperative coronary angiography is a crucial diagnostic used for deciding appropriate surgical management.

Factors Associated with a Large Decline in Renal Function or Progression to Renal Insufficiency in Hospitalized Atrial Fibrillation Patients with Early-Stage CKD.

Clinicians must consider renal function when administering anticoagulants for atrial fibrillation (AF). Determination of risk factors for renal function decline may enable identification of patients who require closer monitoring. We investigated the characteristics associated with renal function decline in patients with AF. The study cohort consisted of 631 AF patients who had at least one readmission during the follow-up period and stages 1-3 chronic kidney disease (CKD). The primary outcome measure was large renal function decline (≥30% decrease from baseline estimated glomerular filtration rate [eGFR]). The secondary outcome measure was a final eGFR < 60 mL/minute/1.73 m2 for those with a baseline eGFR above this level. The mean eGFR was 74.4 ± 18.5 mL/minute/1.73 m2, and the mean follow-up time was 30.2 ± 13.2 months. The primary outcome occurred in 155 patients (24.6%) and was associated with congestive heart failure (CHF), proteinuria, type of AF, and left atrial diameter (LAD) ≥ 45 mm. Among 478 patients with a baseline eGFR ≥ 60 mL/minute/1.73 m2, 137 (28.7%) progressed to renal failure (eGFR < 60 mL/minute/1.73 m2). A decreasing eGFR was associated with age ≥ 75 years, CHF, lower baseline eGFR, and LAD ≥ 45 mm. CHF, proteinuria, type of AF, and LAD ≥ 45 mm were associated with eGFR decline ≥ 30% in AF patients with CKD stages 1-3. Advanced age, CHF, lower baseline eGFR, and LAD ≥ 45 mm were associated with progression to renal insufficiency. These results should be considered when identifying patients who require more frequent monitoring of eGFR.

FGF23 regulates atrial fibrosis in atrial fibrillation by mediating the STAT3 and SMAD3 pathways.

High fibroblast growth factor 23 (FGF23) concentrations are a strong predictor of atrial fibrillation (AF), but researchers have not clearly determined the mechanism by which FGF23 causes atrial fibrosis in patients with AF. This study aims to elucidate the mechanism by which FGF23 induces atrial fibrosis in patients with AF. Immunohistochemistry was used to study the expression of FGF23, FGFR4, and fibrotic factors in patients with a normal sinus rhythm (SR) and patients with AF. Cardiac fibroblasts (CFs) were cocultured with different concentrations of the recombinant FGF23 protein. Compared with the SR group, the levels of FGF23, FGFR4, α-smooth muscle actin (α-SMA), and collagen-1 were significantly increased in the AF group. Exposure to high concentrations of the recombinant FGF23 protein increased the accumulation of reactive oxygen species (ROS) and activated α-SMA, collagen-1, signal transducer and activator of transcription 3 (STAT3) and SMAD3 signaling in cultured CFs. The levels of fibrotic proteins in CFs stimulated with high concentrations of the recombinant FGF23 protein were reversed by N-acetylcysteine (NAC, a ROS inhibitor), ship information system 3 (a SMAD3 inhibitor), and Stattic (a STAT3 inhibitor). Furthermore, compared to untreated CFs, CFs treated with the recombinant FGF23 protein were characterized by an increased interaction between STAT3 and SMAD3. Based on these results, FGF23 induces atrial fibrosis in patients with AF by increasing ROS production and subsequently activating STAT3 and SMAD3 signaling.

Relationship of sleep duration on workdays and non-workdays with blood pressure components in Chinese hypertensive patients.

Objectives: This study aimed to assess the relationship of sleep duration on workdays and non-workdays with BP components [systolic BP (SBP), diastolic (DBP), pulse pressure (PP), and mean arterial pressure (MAP)] among Chinese hypertensive adults. Methods: The study included 3,376 hypertensive patients without antihypertensive treatment. Self-reported sleep durations on workdays and non-workdays were measured by the questionnaire. Multiple linear regression analyses were performed to evaluate the association of sleep duration with BP components. Results: Overall, compared with a sleep duration of 5-9 h, individuals who slept ≥10 h on both workdays and non-workdays were positively correlated with SBP [ß (95% CIs) = 3.99 (1.06, 6.93) and 4.33 (1.79, 6.87)] and PP [ß (95% CIs) = 3.25 (0.71, 5.79) and 3.05 (0.85, 5.25)], but not with DBP. Moreover, individuals who slept ≥10 h only on non-workdays had higher MAP [ß (95% CIs) = 2.30 (0.63, 3.97)]. The stratified analyses showed that subjects with a BMI ≥24 kg/m2 in the longer sleep duration group (≥10 h) only on workdays compared to the reference group had higher SBP, DBP and MAP (all P for interaction <0.05). The effect of longer sleep duration on BP components showed no difference in the following subgroups: sex, age, smoking and drinking (all P for interaction >0.05). Conclusion: Compared with a sleep duration of 5-9 h, longer sleep duration (≥10 h) on workdays and non-workdays was associated with high SBP and PP among Chinese hypertensive adults without antihypertensive treatment.

Pacemaker Dysfunction due to a Large Thrombus on Ventricular Lead.

BACKGROUND: Pacemaker lead-related thrombosis is a rare but severe complication in patients with pacing lead implantation in the right ventricle. We present a case with recurrent syncope after single-chamber implantable cardioverter defibrillator (ICD) implantation. Pacing lead-related thrombosis was observed during open-heart surgery. This induced intermittent pacemaker dysfunction and recurrent syncope. CASE PRESENTATION: A 67-year-old male patient presented with frequent episodes of syncope and a history of dilated cardiomyopathy and paroxysmal ventricular tachycardia. Normal coronary angiography was found, and therefore a single-chamber ICD was implanted into the right ventricle to prevent cardiac events in 2013. However, he was referred to our hospital because of recurrent syncope 3 to 4 years after ICD implantation. A comprehensive investigation was performed to find out the etiology for the recurrent syncope. Pacing lead thrombosis was finally observed during open-heart surgery, which can introduce intermittent pacemaker dysfunction. After the thrombus was removed and the lead was separated from the posterior leaflet of the tricuspid valve, the ICD functioned normally after reprogramming. Oral anticoagulant was prescribed after discharging. During the 1-year follow-up period, this patient was free of syncope. CONCLUSIONS: This case illustrated that pacemaker lead-associated thrombosis should be considered when the cardiac implantable electronic device fails to prevent patients from having cardiac events. Oral anticoagulant might be important for preventing thrombosis among patients with ICD implantation into the right ventricle.