Daytime-restricted feeding enhances running endurance without prior exercise in mice.

Physical endurance and energy conservation are essential for survival in the wild. However, it remains unknown whether and how meal timing regulates physical endurance and muscle diurnal rhythms. Here, we show that day/sleep time-restricted feeding (DRF) enhances running endurance by 100% throughout the circadian cycle in both male and female mice, compared to either ad libitum feeding or night/wake time-restricted feeding. Ablation of the circadian clock in the whole body or the muscle abolished the exercise regulatory effect of DRF. Multi-omics analysis revealed that DRF robustly entrains diurnal rhythms of a mitochondrial oxidative metabolism-centric network, compared to night/wake time-restricted feeding. Remarkably, muscle-specific knockdown of the myocyte lipid droplet protein perilipin-5 completely mimics DRF in enhancing endurance, enhancing oxidative bioenergetics and outputting rhythmicity to circulating energy substrates, including acylcarnitine. Together, our work identifies a potent dietary regimen to enhance running endurance without prior exercise, as well as providing a multi-omics atlas of muscle circadian biology regulated by meal timing.

[Feeding rhythm entrains circadian metabolism genes, but not the circadian clock, in brown adipose tissue].

The central circadian clock and feeding rhythm coordinately reset peripheral circadian clocks. Emerging evidence suggests that feeding rhythm resets peripheral circadian clocks in a tissue-specific manner. This study aimed to determine whether and how feeding rhythm regulates circadian rhythms of the circadian clock and metabolic genes in brown adipose tissue (BAT). We applied different regimens of time-restricted feeding (TRF) in wildtype and Per1/2 deficient C57BL/6 mice, and quantified the effects of sex, treatment duration, constant light, and circadian clock on circadian rhythms of the BAT circadian clock and metabolic genes by RT-qPCR; Representative circadian clock genes are Bmal1, Nr1d1, Dbp, and Per2, and representative metabolic genes are uncoupling protein 1 (Ucp1), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (Pfkfb3) that controls the flux through glycolysis, pyruvate dehydrogenase kinase isozyme 4 (Pdk4) gating the tricarboxylic acid cycle, and carnitine palmitoyltransferase 1A (Cpt1a) that controls mitochondrial fatty acid oxidation. The results showed that, daytime-restricted feeding (DRF) moderately shifted the phase of the BAT circadian clock in female mice within 7 or 36 d, and resulted in the loss of circadian rhythm in Dbp and Per2 transcripts in males. DRF induced de novo oscillation of the Ucp1 transcript, and shifted the phase of representative metabolic genes, such as Pfkfb3, Pdk4, and Cpt1a, more than 7 h. Constant light is known to disrupt the synchrony of the central circadian clock. The results showed that constant light promoted phase entrainment of the circadian clock by DRF in BAT, but abolished the oscillation of the metabolic genes (except for Pdk4). Despite combined treatment with Per1/2 deficiency and constant darkness, DRF was sufficient to drive circadian rhythms of Bmal1 and Dbp, but not those of Nr1d1, Ucp1, Pfkfb3, and Cpt1a. Overall, the circadian clock of BAT has weak adaptation to altered feeding rhythms and sex differences. The central circadian clock antagonizes DRF in the entrainment of the BAT circadian clock, whereas DRF resets circadian rhythms of metabolic genes, such as Ucp1, Pfkfb3, and Cpt1a, in a circadian clock-dependent manner.

Knockdown of hepatocyte Perilipin-3 mitigates hepatic steatosis and steatohepatitis caused by hepatocyte CGI-58 deletion in mice.

Comparative gene identification-58 (CGI-58), also known as α/ß hydrolase domain containing 5, is the co-activator of adipose triglyceride lipase that hydrolyzes triglycerides stored in the cytosolic lipid droplets. Mutations in CGI-58 gene cause Chanarin-Dorfman syndrome (CDS), an autosomal recessive neutral lipid storage disease with ichthyosis. The liver pathology of CDS manifests as steatosis and steatohepatitis, which currently has no effective treatments. Perilipin-3 (Plin3) is a member of the Perilipin-ADRP-TIP47 protein family that is essential for lipid droplet biogenesis. The objective of this study was to test a hypothesis that deletion of a major lipid droplet protein alleviates fatty liver pathogenesis caused by CGI-58 deficiency in hepatocytes. Adult CGI-58-floxed mice were injected with adeno-associated vectors simultaneously expressing the Cre recombinase and microRNA against Plin3 under the control of a hepatocyte-specific promoter, followed by high-fat diet feeding for 6 weeks. Liver and blood samples were then collected from these animals for histological and biochemical analysis. Plin3 knockdown in hepatocytes prevented steatosis, steatohepatitis, and necroptosis caused by hepatocyte CGI-58 deficiency. Our work is the first to show that inhibiting Plin3 in hepatocytes is sufficient to mitigate hepatocyte CGI-58 deficiency-induced hepatic steatosis and steatohepatitis in mice.

Prognostic value of interleukin-6 in atrial fibrillation: A cohort study and meta-analysis.

OBJECTIVE: The prognostic value of interleukin-6 (IL-6) in patients with atrial fibrillation (AF) has not been fully elucidated. Therefore, we conducted a cohort study and a meta-analysis to assess the predictive value of IL-6 for stroke and mortality in patients with AF. METHODS: A cohort study was performed in newly diagnosed non-valvular patients with AF. A total of 217 patients with AF were followed up for a mean of 27 months. A multivariate Cox regression analysis was used to evaluate the association between IL-6 and stroke/all-cause mortality. The incremental value was also assessed by adding IL-6 to the CHA2DS2-VASc score. Besides, a meta-analysis of all reported cohort studies and our cohort study was conducted to validate the association of circulating IL-6 and stroke/mortality in patients with AF. RESULTS: Our cohort study showed that elevated plasma level of IL-6 was an independent risk factor for predicting stroke [hazard ratio (HR)=3.81; 95% confidence interval (CI), 1.11-13.05; p=0.033] and all-cause mortality (HR=3.11; 95% CI, 1.25-7.72; p=0.015) in patients with AF. Adding IL-6 levels to CHA2DS2-VASc score showed limited improvement of the predictive power for stroke [area under curve (AUC) from 0.81 to 0.88, p=0.006]. Meta-analysis confirmed that increased circulating level of IL-6 was significantly associated with increased risk of stroke (pooled HR=1.97; 95% CI, 1.22-3.17; p=0.006) and all-cause mortality (pooled HR=2.73; 95% CI, 2.29-3.25; p<0.001). CONCLUSION: Increased circulating level of IL-6 was significantly associated with greater risk of stroke and all-cause mortality in patients with AF. Adding IL-6 biomarker to the CHA2DS2-VASc score may help to determine the management of AF treatment.

Impact of COVID-19 Pandemic on Mechanical Reperfusion in ST-Segment-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: A Multicenter Retrospective Study From a Non-epicenter Region.

Objective: The COVID-19 pandemic placed heavy burdens on emergency care and posed severe challenges to ST-segment-elevation myocardial infarction (STEMI) treatment. This study aimed to investigate the impact of COVID-19 pandemic on mechanical reperfusion characteristics in STEMI undergoing primary percutaneous coronary intervention (PPCI) in a non-epicenter region. Methods: STEMI cases undergoing PPCI from January 23 to March 29 between 2019 and 2020 were retrospectively compared. PPCI parameters mainly included total ischemic time (TIT), the period from symptom onset to first medical contact (S-to-FMC), the period from FMC to wire (FMC-to-W) and the period from door to wire (D-to-W). Furthermore, the association of COVID-19 pandemic with delayed PPCI risk was further analyzed. Results: A total of 14 PPCI centers were included, with 100 and 220 STEMI cases undergoing PPCI in 2020 and 2019, respectively. As compared to 2019, significant prolongations occurred in reperfusion procedures (P < 0.001) including TIT (420 vs. 264 min), S-to-FMC (5 vs. 3 h), FMC-to-W (113 vs. 95 min) and D-to-W (83 vs. 65 min). Consistently, delayed reperfusion surged including TIT ≥ 12 h (22.0 vs.3.6%), FMC-to-W ≥ 120 min (34.0 vs. 6.8%) and D-to-W ≥ 90 min (19.0 vs. 4.1%). During the pandemic, the patients with FMC-to-W ≥ 120 min had longer durations in FMC to ECG completed (6 vs. 5 min, P = 0.007), FMC to DAPT (24 vs. 21 min, P = 0.001), catheter arrival to wire (54 vs. 43 min, P < 0.001) and D-to-W (91 vs. 78 min, P < 0.001). The pandemic was significantly associated with high risk of delayed PPCI (OR = 7.040, 95% CI 3.610-13.729, P < 0.001). Conclusions: Even in a non-epicenter region, the risk of delayed STEMI reperfusion significantly increased due to cumulative impact of multiple procedures prolongation.

Protocol for setup and circadian analysis of inverted feeding in mice.

Inverted feeding is a paradigm to study synchronization of circadian clocks by feeding rhythm in tissues more directly. Here, we provide a protocol for performing inverted feeding in mice and analyzing circadian rhythmicity in mouse tissues. We describe setting up inverted feeding and performing tissue dissection, followed by RNA extraction and gene expression analysis, and lastly R software-based analysis of circadian rhythmicity. This protocol can be combined with the use of CircaMetDB database for mechanistic studies of inverted feeding. For complete details on the use and execution of this protocol, please refer to Xin et al. (2021).

Identification of Long Non-Coding RNA and Circular RNA Expression Profiles in Atrial Fibrillation.

BACKGROUND: Long non-coding RNA (lncRNA) and circular RNA (circRNA) have both been found to play important roles in cardiovascular diseases, including myocardial infarction, heart failure, and atherosclerosis. However, the role of lncRNA and circRNA in atrial fibrillation (AF) has rarely been investigated. This study aimed to identify lncRNA and circRNA expression profiles in AF patients. METHODS: Atrial tissues from seven patients with AF and seven matched controls were collected. The lncRNA and circRNA expression profiles of atrial tissues were identified using Hiseq/Proton RNA sequencing. Validation was performed by reverse transcription quantitative real-time PCR (qRT-PCR) on 35 pairs of AF patients and controls. Gene Ontology (GO) categories and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. A competing endogenous RNA (ceRNA) network was constructed. RESULTS: A total of 557 lncRNAs and 280 circRNAs were significantly differentially expressed with fold change >1.5 (p<0.05). An lncRNA Voltage Dependent Anion Channel 2 Pseudogene 2 (VDAC2P2) and two circRNAs chr13_41887361_41865736_-21625 and chr13_100368574_100301460_-67114 were validated, using qRT-PCR, to have significantly different expression levels. GO and KEGG pathway analysis showed that some pathways such as ribosome and chromatin modification, Rap1 signalling and cardiac muscle contraction were involved in the pathogenesis of AF. Competing endogenous RNAs were predicted based on constructional network analysis. The LncRNA-miRNA-mRNA and circRNA-miRNA-mRNA networks were constructed by co-expressing lncRNA/circRNA and mRNAs, which were competitively combined with miRNAs. CONCLUSION: This study characterised lncRNA and circRNA expression and their interaction with mRNA and miRNA in AF.

Plasma Level of Interferon-γ Predicts the Prognosis in Patients With New-Onset Atrial Fibrillation.

BACKGROUND: Patients with atrial fibrillation are at increased risk of stroke and mortality. It is not clear if inflammatory biomarkers are associated with stroke and mortality in patients with atrial fibrillation. We aimed to evaluate the predictive value of three inflammatory biomarkers (interleukin [IL]-9, IL-10, and interferon [IFN]-γ) for stroke and mortality in atrial fibrillation. METHOD: A total of 232 patients with new-onset atrial fibrillation were enrolled and 217 patients were completely followed-up. Peripheral plasma concentrations of cytokines (IL-9, IL-10, and IFN-γ) were measured using Luminex xMAP assays. The association between dichotomous groups of cytokines and outcomes were evaluated by a Cox proportional hazards model. The incremental value of inflammatory biomarkers, in addition to the CHA2DS2-VASc score, was also assessed. RESULTS: Patients were followed-up for a median duration of 27 (interquartile range [IQR], 23-30) months. The elevated plasma level of IFN-γ was an independent risk factor for stroke (hazard ratio [HR], 4.02 [IQR, 1.06-15.34]; p=0.042) and all-cause mortality (HR, 3.93 [IQR, 1.43-10.78]; p=0.008) in patients with atrial fibrillation. Adding high IFN-γ to the CHA2DS2-VASc score showed improvement in discrimination and reclassification prediction for stroke and mortality. However, IL-9 and IL-10 had no statistically significant association with stroke and all-cause mortality in patients with atrial fibrillation. CONCLUSIONS: In this "real-world" cohort of patients with atrial fibrillation, we have shown for the first time that plasma levels of IFN-γ could provide incremental prognostic value supplementary to that obtained from the CHA2DS2-VASc scores for predicting of stroke and all-cause mortality.

Reduced serum levels of oestradiol and brain derived neurotrophic factor in both diabetic women and HFD-feeding female mice.

The estrogen levels in the pre and post menstrual phases interact with brain-derived neurotrophic factor in a complex manner, which influences the overall state of the body. To study the role of oestradiol and brain-derived neurotrophic factor in modulating obesity related type 2 diabetes and the interactions between two factors, we enrolled 15 diabetic premenopausal women and 15 diabetic postmenopausal women respectively, the same number of healthy pre and postmenopausal women were recruited as two control groups. The fasting blood glucose, insulin, lipids, estrogen, and brain-derived neurotrophic factor levels were measured through clinical tests. Additionally, we set up obese female mouse model to mimic human trial stated above, to verify the relationship between estrogen and brain-derived neurotrophic factor. Our findings revealed that there is a moderately positive correlation between brain-derived neurotrophic factor and oestradiol in females, and decreased brain-derived neurotrophic factor may worsen impaired insulin function. The results further confirmed that high fat diet-fed mice which exhibited impaired glucose tolerance, showed lower levels of oestradiol and decreased expression of brain-derived neurotrophic factor mRNA in the ventromedial hypothalamus. The level of brain-derived neurotrophic factor reduced on condition that the level of oestradiol is sufficiently low, such as women in postmenopausal period, which aggravates diabetes through feeding-related pathways. Increasing the level of brain-derived neurotrophic factor may help to alleviate the progression of the disease in postmenopausal women with diabetes.

Influence of Cognitive Behavioral Therapy on Mood and Quality of Life After Stent Implantation in Young and Middle-Aged Patients With Coronary Heart Disease.

Cognitive behavioral therapy (CBT), established only a few decades ago, is widely used by clinical psychologists. This study aimed to investigate the effects of CBT on mental status and quality of life (QOL) after percutaneous coronary intervention (PCI) in young and middle-aged patients with coronary heart disease (CHD). Seventy-five anxiety/depression patients (mean age, 52.2 ± 6.2 years, including 8 individuals < 45 years old) with CHD treated with PCI were randomly divided into a CBT group (n = 38) and control group (n = 37). The CBT group received 8 weeks of CBT in addition to the routine postoperative treatment that was also administered to control patients. The 17-item Hamilton Depression Rating Scale (HAM-D17), Hamilton anxiety scale (HAM-A), and Coronary Revascularization Outcome Questionnaire (CROQ-PTCA-POST, Chinese version) were administered before, 3 days, and 8 weeks after intervention. HAM-D17 and HAM-A scores were decreased after treatment, but were more substantially reduced in patients that underwent CBT than those in the control group (11.7 ± 4.5 versus 15.1 ± 3.9, P = 0.001 and 10.6 ± 3.4 versus 16.5 ± 4.6, P = 0.003, respectively). QOL was improved in both groups, but overall satisfaction was higher in the CBT group compared with control patients (89.3 ± 5.2 versus 77.8 ± 9.5, P < 0.05). CBT can relieve depression and anxiety after PCI in young and middle-aged patients with CHD. CBT can improve patient QOL.

Electric-Pulse Current Stimulation Increases If Current in mShox2 Genetically Modified Canine Mesenchymal Stem Cells.

OBJECTIVE: We aimed to investigate the role of mShox2 in generating If pacemaker current in vitro by means of electric-pulse current stimulation (EPCS) of canine mesenchymal stem cells (cMSCs). METHODS: mShox2 genetically modified cMSCs were prepared with pLentis-mShox2 red fluorescent protein. After EPCS induction, we examined the kinetic characteristics of generated inward current by means of a patch clamp. We then evaluated the expression of pacemaker-related genes, such as Nkx2.5, Tbx3, HCN4, Cx43 and Cx45, by means of qRT-PCR and Western blotting. The morphological changes and the cardiomyogenic differentiation marker cTnT were investigated at the same time. RESULTS: The time- and voltage-dependent inward current recorded after mShox2 infection was confirmed to be If current. After EPCS induction, the detection rate of this If current was increased. The current amplitude and density were increased, and the channel activation curve shifted to the right. The pacemaker markers Tbx3, HCN4 and Cx45 were significantly upregulated, but the working myocardium markers Nkx2.5 and Cx43 were downregulated after mShox2 infection, and were more remarkable after EPCS induction. The cells became larger and assumed spindle and spider-like morphologies. cTnT was also detected in the experimental cells. CONCLUSIONS: Our results suggest that EPCS promotes the differentiation of mShox2 genetically modified cMSCs into pacemaker-like cells, which generates more If current.

Association of hemostatic markers with atrial fibrillation: a meta-analysis and meta-regression.

BACKGROUND: There is growing evidence that indicates the presence of a prothrombotic state in atrial fibrillation (AF). However, the role of hemostatic markers in AF remains inconclusive. METHODS: We conducted a meta-analysis of observational studies to evaluate the association between hemostatic markers and AF. A meta-regression was performed to explore potential sources of heterogeneity. RESULTS: A total of 59 studies met our inclusion criteria for the meta-analysis. For platelet activation, increased circulating platelet factor-4, ß-thromboglobulin (BTG) and P-selectin were significantly higher in AF cases compared with controls (standardized mean difference [SMD][95% confidence interval (CI)]: 1.72[0.96-2.49], 1.61[1.03-2.19] and 0.50[0.23-0.77], respectively). For coagulation activation, increased levels of plasma D-dimer, fibrinogen, thrombin-antithrombin, prothrombin fragment 1+2, and antithrombin-III were significantly associated with AF (SMD[95% CI]: 1.82[1.38-2.26], 0.72[0.55-0.89], 0.42[0.13-0.72], 1.00 [0.00-1.99] and 1.38[0.16-2.60], respectively). For fibrinolytic function, tissue-type plasminogen activator and plasminogen activator inhibitor-1 were significantly increased in AF cases compared with controls (SMD[95% CI]: 0.86[0.04-1.67] and 0.87[0.28-1.47], respectively) but the associations became nonsignificant after performing subgroup analysis by anticoagulants treatment status. For endothelial function, increased von Willebrand factor was significantly associated with AF (SMD, 0.79; 95% CI, 0.60-0.99); however, no association was observed for soluble thrombomodulin (SMD, 0.60; 95% CI, -0.13-1.33). CONCLUSIONS: Increased circulating hemostatic factors (PF-4, BTG, P-selectin, D-dimer, fibrinogen, TAT, F1+2, AT- III, and vWf) are significantly associated with AF. Future research is necessary to elucidate the precise mechanism of the prothrombotic state and how hemostatic markers promote thromboembolism in AF.

Comparison of the safety and efficacy of biodegradable polymer drug-eluting stents versus durable polymer drug-eluting stents: a meta-analysis.

BACKGROUND: A meta-analysis was conducted to assess the safety and efficacy of biodegradable polymer drug-eluting stents (BP-DESs). METHODS: PubMed, Science Direct, China National Knowledge Infrastructure, and Chongqing VIP databases were searched for randomized controlled trials comparing the safety and efficacy of BP-DESs versus durable polymer drug-eluting stents (DP-DESs). Efficacy included the prevalence of target lesion revascularization (TLR), target vessel revascularization (TVR), and late lumen loss (LLL), and safety of these stents at the end of follow-up for the selected research studies were compared. RESULTS: A total of 16 qualified original studies that addressed a total of 22,211 patients were included in this meta-analysis. In regard to efficacy, no statistically significant difference in TLR (odds ratio (OR) = 0.94, P = 0.30) or TVR (OR 1.01, P = 0.86) was observed between patients treated with BP-DESs and those with DP-DESs. However, there were significant differences in in-stent LLL (weighted mean difference [WMD] = -0.07, P = 0.005) and in-segment LLL (WMD = -0.03, P = 0.05) between patients treated with BP-DESs and with DP-DESs. In terms of safety, there was no significant difference in overall mortality (OR 0.97, P = 0.67), cardiac death (OR 0.99, P = 0.90), early stent thrombosis (ST) and late ST (OR 0.94, P = 0.76; OR 0.96, P = 0.73), or myocardial infarction (MI) (OR 0.99, P = 0.88) between patients treated with BP-DESs and with DP-DESs. However, there was a statistically significant difference in very late ST (OR 0.69, P = 0.007) between these two groups. In addition, the general trend of the rates of TVR and TLR of BP-DESs groups was lower than DP-DESs groups after a 1-year follow-up. CONCLUSION: BP-DESs are safe, efficient, and exhibit superior performance to DP-DESs with respect to reducing the occurrence of very late ST and LLL. The general trend of the rates of TVR and TLR of BP-DESs groups was lower than DP-DESs groups after a 1-year follow-up.

Triptolide improves early survival of mesenchymal stem cells transplanted into rat myocardium.

OBJECTIVE: To investigate whether triptolide can prolong the survival of rat mesenchymal stem cells (MSCs) transfected with the mouse hyperpolarization-activated cyclic nucleotide-gated channel 4 (mHCN4) gene in the myocardium. METHODS: Grafted cell survival was determined using a sex-mismatched cell transplantation model and analysis of Y chromosome-specific Sry gene expression from hearts harvested at different time points after cell transplantation. ELISA and RT-PCR were used to measure protein and mRNA levels, respectively, of nuclear factor (NF)-κB, IL-1ß, IL-6 and TNF-α. RESULTS: Donor cell numbers decreased over time. Pretreatment with triptolide improved graft survival both 24 (29.3 ± 0.9%) and 72 h (17.5 ± 1.2%) after transplantation of MSCs and resulted in a 2.5-fold increase in the total cell number 72 h after cell transplantation. The mRNA expression and protein content of NF-κB, IL-1ß, IL-6 and TNF-α were significantly reduced in the triptolide-treated group compared with the control groups. In addition, triptolide downregulated Bax but upregulated Bcl-2 in the injected region. CONCLUSIONS: Transient treatment with triptolide may significantly improve the early survival of MSCs in vivo. The mechanism underlying this effect involves attenuating the inflammatory response via inhibition of the NF-κB signaling pathway.

The immediate and follow-up results of transcatheter occlusion of the ruptured sinus of Valsalva aneurysm with duct occluder.

BACKGROUND: Percutaneous transcatheter closure is an alternative strategy to traditional conventional surgical repair for ruptured sinus of Valsalva aneurysm (RSVA). The immediate and follow-up results of transcatheter occlusion in 13 patients were reported. METHODS: From February 2004 to June 2009, a total of 13 patients (9 males, 4 females), ages 18-38 years, were involved in the report. The diagnosis of RSVA was made based on a combination of several imaging modalities. None of the patients had other associated congenital heart disease, and all underwent local anesthesia. Transthoracic echocardiography was used during the procedure. All patients received aspirin (100 mg/day) and clopidogrel (75 mg/day) for a 6-month period after the procedure. Enalapril (5-20 mg/day) was administered to the patients with heart failure and/or cardiac dilatation. Chest radiography, electrocardiogram, and transthoracic echocardiography were undertaken at intervals of 1, 6, 12, 24, 36, 48, and 60 months during the follow-up. RESULTS: The size of the duct occluder selected was up to 1-3 mm larger than the maximal diameter of the RSVA opening site. The devices were successfully deployed without any complications. On follow-up, no severe arrhythmia occurred; there was no device embolization, residual shunt, RVOT obstruction, new aortic regurgitation, or rupture site. Compared with the preoperative results, the cardiothoracic ratio and left ventricular were significantly decreased in the patients with cardiac dilatation (0.54 ± 0.05 vs 0.50 ± 0.04, P<.05 and 54.11 ± 2.32 vs 50.11 ± 2.47 mm, P<.01, respectively). CONCLUSIONS: Transcatheter closure is a safe and effective alternative in the treatment of RSVA. The mid-term follow-up outcomes are good.

Clinical efficacy and safety of transcatheter closure of ruptured sinus of valsalva aneurysm.

OBJECTIVES: To evaluate the clinical efficacy and safety of transcatheter closure (TCC) in patients with ruptured sinus of Valsalva aneurysm (RSVA). BACKGROUND: RSVA is a rare cardiovascular disease with a varied clinical presentation. The clinical efficacy and safety of TCC for RSVA still remain an ongoing concern. METHODS: From January 2009 to March 2013, 22 patients with RSVA were selected for TCC. Intracardiac pressure and size of cardiac chamber were measured before and post TCC. All patients were followed up by transthoracic echocardiography at 1, 3, 6, 12 months after procedure. RESULTS: RSVA was successfully occluded in 20 patients (19 cases with Amplatzer duct occluder and one with muscular ventricular septal defect occluder). Aortic root angiography showed no shunt in 18 cases and a small residual shunt in two cases. The pressures in the right atrium, right ventricle, and pulmonary artery were significantly decreased after the procedure (P < 0.01), and the aortic pressure was elevated (P < 0.001). The internal diameters of the right atrium, left atrium, and left ventricle were also significantly declined after the procedure (P < 0.05). No complications were found after 18.5 ± 6.5 (range 3-35) months follow-up. Two patients underwent acute surgical aortic valve replacement because of procedure-related aortic valve regurgitation. CONCLUSIONS: Our results indicate that TCC is a promising alternative therapy to surgery in appropriate patients with RSVA. However, rare but severe procedure-related complications should be considered in the risk assessment.

Association of inflammatory factors with occurrence and recurrence of atrial fibrillation: a meta-analysis.

BACKGROUND: The role of circulating inflammatory factors in atrial fibrillation (AF) occurrence and recurrence remains inconclusive. METHODS: We conducted a meta-analysis of observational studies evaluating the association of inflammatory factors with AF risk, postoperative AF (POAF) occurrence after coronary artery bypass grafting (CABG) surgery, and AF recurrence after electrical cardioversion (EC) or catheter ablation. RESULTS: Increased C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-α were significantly associated with AF risk (standardized mean difference [SMD] [95% confidence interval (CI)]: 0.95 [0.72-1.18], 0.89 [0.64-1.15] and 2.20 [1.17-3.23], respectively). In subgroup analysis, CRP was significantly associated with persistent and permanent AF risk, but not with paroxysmal AF. Increased preoperative CRP and IL-6 were associated with greater risk of post-CABG AF (SMD [95% CI]: 0.28 [0.02-0.54] and 1.03 [0.03-2.04], respectively). Consistent significant associations between CRP and AF recurrence were found in both patient subgroups who underwent EC (SMD, 0.56; 95% CI, 0.36-0.76) and ablation (SMD, 0.48; 95% CI, 0.11-0.86). IL-6 was significantly associated with AF recurrence after ablation (SMD, 0.55; 95% CI, 0.25-0.85), but not with the recurrence after EC (SMD, 0.85; 95% CI, -0.26-1.95). CONCLUSION: Increased circulating inflammatory factors, such as CRP and IL-6, are associated with greater AF risk in general population and patients who underwent CABG, as well as with AF recurrence after EC or ablation. Future research is warranted to elucidate the roles of other inflammatory markers, such as white blood cell, IL-8, and transforming growth factor-ß1, in occurrence and recurrence of well-established different clinical subtypes of AF.

Ca²âº disorder caused by rapid electrical field stimulation can be modulated by CaMKIIδ expression in primary rat atrial myocytes.

Abnormalities in intracellular Ca(2+) handing are believed to contribute to arrhythmogenesis during atrial fibrillation (AF). Ca(2+)/calmodulin-dependent protein kinaseII δ (CaMKIIδ) overexpression was detected in atrial myocytes from patients and animal models with persistent AF. In the present study, we found that rapid electrical field stimulation applied to primary atrial myocytes altered the CaMKIIδ activity, not expression level, resulting in Ca(2+) disorder. By lentivirus mediated delivery of CaMKIIδ gene or siRNA into atrial myocytes, cells with different CaMKIIδ expression were generated. Changes of CaMKIIδ expression altered the sarcoplasmic reticulum (SR) Ca(2+) release and L-type Ca(2+) channels current (I(Ca)) in both steady and electrical stimulating state. These results revealed the important role of CaMKIIδ in Ca(2+) disorder caused by electrical field stimulation. It also provided a potential method to improve Ca(2+) disorder in AF by modulating CaMKIIδ expression level.

Clinical efficiency and safety analysis of transcatheter closure of multiple atrial septal defects in adults.

BACKGROUND: Transcatheter closure of atrial septal defects (ASDs) is currently a reliable alternative to surgery, even though challenging in patients with multiple ASDs. HYPOTHESIS: The aim of this study was to evaluate the clinical efficiency and safety of transcatheter closure in multiple ASDs. METHODS: Multiple ASDs were diagnosed by transthoracic echocardiography (TTE) or transesophageal echocardiography (TEE). The occlusive condition and distance between 2 adjacent ASDs were measured by TTE examination. Then, the number and size of the occluder(s) was determined. TTE examinations were performed after transcatheter closure as follow-up. RESULTS: The transcatheter procedure was successful in 15 patients with multiple ASDs, using a single occluder in 9 patients and 2 occluders in the remaining 6 patients. Overall, 21 ASD occluders were implanted. During a follow-up period of 6 mo to 5 y, a slight residual shunt was found in 1 patient without any symptoms; a moderate residual shunt was identified at the inferior vena cava and the occluder was removed by surgery 1 mo after procedure. Other complications, including endocarditis, arrhythmia, thromboembolism, and atrioventricular valve damage were not recorded in any of the 15 patients during the follow-up period. CONCLUSION: Transcatheter closure of multiple ASDs is safe and efficient. Two occluders are necessary for the distance of 2 ASDs more than 7 mm, and a single occluder is sufficient for those 7 mm or less.

[Prognostic impact of heart block during transcatheter closure of ventricular septal defect].

OBJECTIVE: To investigate the prognostic impact of heart block during the transcatheter closure of ventricular septal defect (VSD). METHODS: Forty three patients developed complete left or right bundle branch block (CLBBB, CRBBB), incomplete left or right bundle branch block (ILBBB, IRBBB), and atrioventricular block (AVB) during and within 1 week post procedure were followuped at 1, 6, 12, 24, 36, 48 and 60 months post procedure. Electrocardiogram, dynamic electrocardiogram and transthoracic echocardiography were made. RESULTS: Bundle branch block and atrioventricular block were detected in 26 patients (CLBBB n = 4, CRBBB n = 5, ILBBB n = 2, IRBBB n = 10 and third-degree AVB n = 5) during the transcatheter closure of VSD, and in 17 patients (CLBBB n = 5, CRBBB n = 2, first-degree AVB n = 3, second-degree I-type AVB n = 1 and third-degree AVB n = 6) within 1 week post procedure. Heart block disappeared in 33 patients (76.7%) before discharge, in 37 patients (86.1%) at 1 month and in 41 patients (95.4%) at 6 months post procedure. CLBBB or CRBBB was seen in two cases at 24 months after closure. There was no heart failure and serious cardiac dilatation during follow up. CONCLUSION: The heart block occurred during the periprocedure period of transcatheter closure of VSD was a benign phenomenon without prognostic importance.