Cardiac autonomic neuropathy modified the association between obesity and hypoglycemia in type 2 diabetes.

BACKGROUND: Previous studies have shown that increasing body mass index (BMI) was associated with decreased hypoglycemia in type 2 diabetes, but it remains uncertain whether this finding could be applied to patients with and without cardiac autonomic neuropathy (CAN). METHODS: The study included 7789 participants with type 2 diabetes from action to control cardiovascular risk in diabetes (ACCORD) trail. CAN was defined as SDNN < 8.2 ms and RMSSD < 8.0 ms. Obesity was defined as BMI ≥ 30 kg/m2. Outcomes were identified as severe hypoglycemia requiring any assistance (HAA) or requiring medical assistance (HMA). We assessed the association between obesity and severe hypoglycemia in type 2 diabetes with or without CAN using COX regression models adjusted for baseline characteristics. RESULTS: Over a median follow-up of 4.7 years, a total of 893 participants developed HAA and 584 participants developed HMA. Compared with non-obesity, obesity was associated with lower risk of severe hypoglycemia (HAA: hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.38-0.68, P < 0.001; HMA: HR 0.57, 95% CI 0.40-0.82, P = 0.002) in CAN present group, but not in CAN absent group (HAA: HR 0.98, 95% CI 0.83-1.16, P = 0.830; HMA: HR 0.97, 95% CI 0.79-1.19, P = 0.754). Similarly, increasing BMI was associated with reduced severe hypoglycemic events in participants with CAN, but not in participants without CAN. CONCLUSIONS: CAN modifies the association between obesity and hypoglycemia in type 2 diabetes. Type 2 diabetic individuals with CAN who are under weight control should pay attention to hypoglycemic events. TRIAL REGISTRY: http://www. CLINICALTRIALS: gov . Unique identifier: NCT00000620.

Effects of a competence-based approach for clerkship teaching under alternating clinical placements: An explanatory sequential mixed-methods research.

BACKGROUND: It is unclear whether alternating placements during clinical clerkship, without an explicit emphasis on clinical competencies, would bring about optimal educational outcomes. METHODS: This is an explanatory sequential mixed-methods research. We enrolled a convenience sample of 41 eight-year programme medical students in Sun Yat-sen University who received alternating placements during clerkship. The effects of competence-based approach (n = 21) versus traditional approach (n = 20) to clerkship teaching were compared. In the quantitative phase, course satisfaction was measured via an online survey and academic performance was determined through final scores on summative assessment. Then, in the qualitative phase, students were invited for semi-structured interviews about their learning experiences, and the transcripts were used for thematic analysis. RESULTS: Quantitative findings showed that students in the study group rated high course satisfaction and performed significantly better in their final scores compared with those in the control group. Qualitative findings from thematic analysis showed that students were relatively neutral about their preference on placement models, but clearly perceived, capitalised, and appreciated that their competencies were being cultivated by an instructor who was regarded as a positive role model. CONCLUSION: A competence-based approach to clerkship teaching resulted in better course satisfaction and academic performance, and was perceived, capitalised, and appreciated by students.

A novel method for septal reduction therapy by three-dimensional guided transvenous intraseptal pulsed-field ablation.

BACKGROUND: Pulsed-field ablation (PFA) is a nonthermal method for achieving selective cell death with little inflammation response. However, there are no reports of PFA for septal reduction therapy (SRT). OBJECTIVE: The purpose of this study was to investigate the effectiveness and safety of PFA for SRT. METHODS: A novel transvenous intraseptal PFA method with 3-dimensional (3D) guidance was introduced in Yorkshire pigs. Electrocardiographic parameters, transthoracic echocardiography, and histopathology were used to evaluated. RESULTS: The maximum injury diameter of intramyocardial PFA increased with electric field intensity. After PFA, bipolar electrogram amplitude and pacing threshold measured by the PFA electrodes significantly decreased (F = 6.945, P = .007) or increased (F = 5.842, P = .024), respectively. In the ablated septal region, motion amplitude and systolic wall thickening rate significantly decreased and remained at low levels (motion amplitude: F = 20.793, P = .000; systolic wall thickening rate: F = 14.343, P = .000); however, septal thickness did not significantly change after PFA (F = 1.503, P = .248). Histologic examination showed specific cardiomyocyte death with gradually increased hyperchromatic cytoplasm and nuclear pyknosis, without obvious inflammatory cell infiltration in acute phase. TUNEL stain for fragmented DNA showed extensively positive in the ablation region 24 hours after PFA. During PFA, no sustained ventricular arrhythmia or atrioventricular conduction block occurred. CONCLUSION: A novel intraseptal PFA method with 3D guidance was described. Intraseptal PFA resulted in effective myocardial injury and local hypokinesis without significant acute edema. Histologic examination showed widely programmed cardiomyocyte death with little inflammatory cell infiltration.

Effect of metformin on adverse outcomes in T2DM patients: Systemic review and meta-analysis of observational studies.

Background: The cardiovascular protection effect of metformin on patients with type 2 diabetes mellitus (T2DM) remains inconclusive. This systemic review and meta-analysis were to estimate the effect of metformin on mortality and cardiovascular events among patients with T2DM. Methods: A search of the Pubmed and EMBASE databases up to December 2021 was performed. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled by a random-effects model with an inverse variance method. Results: A total of 39 studies involving 2473009 T2DM patients were adopted. Compared to non-metformin therapy, the use of metformin was not significantly associated with a reduced risk of major adverse cardiovascular event (MACE) (HR = 1.06, 95%CI 0.91-1.22; I 2 = 82%), hospitalization (HR = 0.85, 95%CI 0.64-1.13; I 2 = 98%), heart failure (HR = 0.86, 95%CI 0.60-1.25; I 2 = 99%), stroke (HR = 1.16, 95%CI 0.88-1.53; I 2 = 84%), and risk of AMI (HR = 0.88, 95%CI 0.69-1.14; I 2 = 88%) in T2DM patients. Metformin was also not associated with significantly lowered risk of MACE compared to dipeptidyl peptidase-4 inhibitor (DPP-4i) in T2DM patients (HR = 0.95, 95%CI 0.73-1.23; I 2 = 84%). Conclusions: The effect of metformin on some cardiovascular outcomes was not significantly better than the non-metformin therapy or DPP-4i in T2DM patients based on observational studies.

Effectiveness and Safety of DOACs vs. Warfarin in Patients With Atrial Fibrillation and Frailty: A Systematic Review and Meta-Analysis.

Background: Patients with atrial fibrillation (AF) and frailty are a considerable group in clinical practice. However, existing studies provide insufficient evidence of anticoagulation strategies for these patients. Therefore, we conducted a meta-analysis to determine the effectiveness and safety outcomes of direct oral anticoagulants (DOACs) for these patients. Methods: Randomized controlled trials or observational studies reporting the data about the DOACs and warfarin therapy among frail AF patients were included. The search was performed in the PubMed and Embase databases up to March 2022. Frailty was defined using the most widely used claims-based frailty index or the cumulative deficit model-based frailty index. Results: A total of 4 studies involving 835,520 patients were included. Compared with warfarin, DOACs therapy reduced the risks of stroke or systemic embolism (HR = 0.79, 95%CI: 0.69-0.90), ischemic stroke (HR = 0.79, 95%CI: 0.71-0.87), hemorrhagic stroke (HR = 0.52, 95%CI: 0.35-0.76), and all-cause death (HR = 0.90, 95%CI: 0.84-0.96). In safety outcomes, DOACs was significantly associated with reduced risks of major bleeding (HR = 0.79, 95%CI: 0.64-0.97) and intracranial hemorrhage (HR = 0.58, 95%CI: 0.52-0.65) compared to warfarin, but there were no statistically differences in gastrointestinal bleeding (HR = 0.97, 95%CI: 0.73-1.29). Conclusions: DOACs exerted superior effectiveness and safety outcome than warfarin in AF patients with frailty.

An electrographic AV optimization for the maximum integrative atrioventricular and ventricular resynchronization in CRT.

BACKGROUND: Atrioventricular (AV) delay could affect AV and ventricular synchrony in cardiac resynchronization therapy (CRT). Strategies to optimize AV delay according to optimal AV synchrony (AVopt-AV) or ventricular synchrony (AVopt-V) would potentially be discordant. This study aimed to explore a new AV delay optimization algorithm guided by electrograms to obtain the maximum integrative effects of AV and ventricular resynchronization (opt-AV). METHODS: Forty-nine patients with CRT were enrolled. AVopt-AV was measured through the Ritter method. AVopt-V was obtained by yielding the narrowest QRS. The opt-AV was considered to be AVopt-AV or AVopt-V when their difference was < 20 ms, and to be the AV delay with the maximal aortic velocity-time integral between AVopt-AV and AVopt-V when their difference was > 20 ms. RESULTS: The results showed that sensing/pacing AVopt-AV (SAVopt-AV/PAVopt-AV) were correlated with atrial activation time (Pend-As/Pend-Ap) (P < 0.05). Sensing/pacing AVopt-V (SAVopt-V/PAVopt-V) was correlated with the intrinsic AV conduction time (As-Vs/Ap-Vs) (P < 0.01). The percentages of patients with more than 20 ms differences between SAVopt-AV/PAVopt-AV and SAVopt-V/PAVopt-V were 62.9% and 57.1%, respectively. Among them, opt-AV was linearly correlated with SAVopt-AV/PAVopt-AV and SAVopt-V/PAVopt-V. The sensing opt-AV (opt-SAV) = 0.1 × SAVopt-AV + 0.4 × SAVopt-V + 70 ms (R2 = 0.665, P < 0.01) and the pacing opt-AV (opt-PAV) = 0.25 × PAVopt-AV + 0.5 × PAVopt-V + 30 ms (R2 = 0.560, P < 0.01). CONCLUSION: The SAVopt-AV/PAVopt-AV and SAVopt-V/PAVopt-V were correlated with the atrial activation time and the intrinsic AV conduction interval respectively. Almost half of the patients had a > 20 ms difference between SAVopt-AV/PAVopt-AV and SAVopt-V/PAVopt-V. The opt-AV could be estimated based on electrogram parameters.

Visit-to-Visit Blood Pressure Variability and Clinical Outcomes in Patients With Heart Failure With Preserved Ejection Fraction.

[Figure: see text].

Silence Is Golden.

Speech-induced atrial tachycardia (AT) is extremely rare. We presented a case of focal AT that could be triggered by speech and terminated with the cessation of conversation. An electrophysiological study showed that the outbreak was associated with left atrial pressure rose. Radiofrequency ablation at the left atrial posterior-superior wall (earliest activation site) resulted in the immediate termination of AT. These electrophysiological characteristics indicated that the cardiac autonomic nervous system and/or left atrial pressure might play essential roles in the occurrences of speech-induced AT.

Electrophysiological characteristics of epicardial to endocardial breakthrough in intractable cavotricuspid isthmus-dependent atrial flutter.

BACKGROUND: Epicardial to endocardial breakthrough (EEB) exists widely in atrial arrhythmia and is a cause for intractable cavotricuspid isthmus (CTI)-dependent atrial flutter (AFL). This study aimed to investigate the electrophysiological features of EEB in EEB-related CTI dependent AFL. METHODS: Six patients with EEB-related CTI-dependent AFL were identified among 142 consecutive patients who underwent CTI-dependent AFL catheter ablation with an ultra-high-density, high-resolution mapping system in three institutions. Activation maps and ablation procedure were analyzed. RESULTS: A total of seven EEBs were found in six patients. Four EEBs (including three at the right atrial septum and one in paraseptal isthmus) were recorded in three patients during tachycardia. The other three EEBs were identified at the inferolateral right atrium (RA) during pacing from the coronary sinus. The conduction characteristics through the EEB-mediated structures were evaluated in three patients. Two patients only showed unidirectional conduction. Activation maps indicated that CTI-dependent AFL with EEB at the atrial septum was actually bi-atrial macro-reentrant atrial tachycardia (BiAT). Intensive ablation at the central isthmus could block CTI bidirectionally in four cases. However, ablation targeted at the inferolateral RA EEB was required in two cases. Meanwhile, local potentials at the EEB location gradually split into two components with a change in activation sequence. CONCLUSIONS: EEB is an underlying cause for intractable CTI-dependent AFL. EEB-mediated structure might show unidirectional conduction. CTI-dependent AFL with EEB at the atrial septum may represent BiAT. Intensive ablation targeting the central isthmus or EEB at the inferolateral RA could block the CTI bidirectionally.

Automatic annotation of local activation time was improved in idiopathic right ventricular outflow tract ventricular arrhythmia by novel electrogram "Lumipoint" algorithm.

PURPOSE: Precise automatic annotation of local activation time (LAT) is crucial for rapid high-density activation mapping in arrhythmia. However, it is still challenging in voltage-transitional areas where local low-amplitude near-field potentials are often obscured by large far-field potentials. The aim of this study was to explore the viability and validity of automatic identification of the earliest activation (EA) in idiopathic right ventricular outflow tract ventricular arrhythmias (RVOT VAs) using a novel Lumipoint algorithm. METHODS AND RESULTS: Twenty-seven patients with RVOT VAs were mapped with Rhythmia mapping system. Lumipoint algorithms were applied to reannotate the initial activation regions retrospectively. The results showed that LATs were reannotated in 35.0 ± 11.4% points in the initial activation area from bipolar activation breakout time (BBO) to the its 40 ms earlier timepoint. The automatically determined bipolar earliest activation time after Lumipoint reannotation (BEAT-lu: - 111.26 ± 12.13 ms) was significantly earlier than that before (BEAT: - 108.67 ± 12.25 ms, P = 0.000). Compared with manually corrected earliest activation time (EAT), the difference between EAT and BEAT-lu (DEAT-BEAT-lu: 6 (2-7) ms) was significantly smaller than that between EAT and BEAT (DEAT-BEAT/DEAT-UEA: 7 (4-11) ms, P = 0.000). The incidence of EAT and BEAT-lu being the same site was significantly higher than that between EAT and BEAT (48.15% vs 18.52%, P = 0.021). CONCLUSIONS: RVOT VAs often originate from voltage-transitional zone, and automatic annotation of LAT usually located at later high-amplitude far-field potential. Lumipoint algorithms could improve the accuracy of LAT automatic annotation, and it was plausible to ablate RVOT VAs just according to the automatically annotated BEAS-lu.

Long-Term Outcomes and Improvements in Quality of Life in Patients with Atrial Fibrillation Treated with Catheter Ablation vs. Antiarrhythmic Drugs.

BACKGROUND: Catheter ablation (CA) is a recognized first-line treatment for atrial fibrillation (AF) in selected patients; however, the differences between CA and antiarrhythmic drugs (AADs) in terms of long-term outcomes and quality of life (QoL) have not often been compared. OBJECTIVES: We performed a meta-analysis of randomized controlled trials (RCTs) to compare long-term outcomes and QoL with CA and AADs in the treatment of AF. METHODS: We searched the MEDLINE database for English-language RCTs of CA or AADs in AF from 1 January 2005 to 30 October 2019 with no other restrictions. We included studies that reported sample sizes and the long-term outcomes of interest as well as sample size, mean ± standard deviation or 95% confidence intervals (CIs) for QoL outcomes with CA and AADs. RESULTS: We identified 20 RCTs involving 5425 participants. Compared with patients who received only AADs, patients receiving CA had a significantly decreased risk of all-cause death (relative risk [RR] 0.72; 95% CI 0.58-0.90) and cardiovascular hospitalization (RR 0.85; 95% CI 0.79-0.91). We found a significant increase in the risk of cardiac tamponade (RR 5.86; 95% CI 1.77-19.44) but no difference in the risk of heart failure, stroke or transient ischemic attack, atrial tachycardia, bleeding or hematoma, and pulmonary vein stenosis. For long-term QoL after treatment, both therapies resulted in improved scores on the Medical Outcomes Study 36-Item Short Form Survey (SF-36): weighted mean differences (WMDs) for the physical component score (PCS) were 5.89 for CA and 4.26 for AADs and for the mental component score (MCS) were 7.12 for CA and 5.06 for AADs. At the end of follow-up, groups receiving CA had significantly higher scores in both areas. The change in PCS and MCS between baseline and end of follow-up was also significantly higher in the CA groups: WMD 1.51 for change in PCS and 1.49 for change in MCS. All eight SF-36 subscale scores improved for patients receiving CA, whereas patients receiving AADs recorded no improvement in the general health and bodily pain subscales. At the end of follow-up, CA groups had significantly higher scores than AAD groups in the following subscales: physical functioning, role limitations due to physical health problems, bodily pain, general health, vitality, and role limitations due to emotional problems. CONCLUSIONS: In the treatment of AF, CA appeared to be superior to AADs, decreasing the risk of all-cause death and cardiovascular hospitalization and improving the long-term QoL of patients with AF. CA was better tolerated and more effective than pharmacological therapy and allowed for improved QoL.

Efficacy and safety of xuezhikang once per day versus two times per day in patients with mild to moderate hypercholesterolaemia (APEX study): a protocol for a multicentre, prospective randomised controlled, open-label, non-inferiority study.

INTRODUCTION: Reduction in low-density lipoprotein cholesterol (LDL-C) improves clinical outcomes in patients with coronary artery disease. However, rates of lipid-lowering medication adherence are far from ideal. Reducing dosage frequency from multiple dosing to once-daily dosing may improve patients' medication adherence. Xuezhikang (XZK), an extract of Chinese red yeast rice, contains a family of naturally occurring statins and is traditionally prescribed as 600 mg two times per day. A comParative Efficacy study of XZK (APEX study) is designed to test the hypothesis that XZK prescribed 1200 mg once per day (OD group) is non-inferior to 600 mg two times per day (TD group) in patients with hypercholesterolaemia. METHODS AND ANALYSIS: The APEX study is a multicentre, prospective randomised controlled, open-label, non-inferiority study. We plan to recruit 316 patients aged ≥18 years with a diagnosis of mild to moderate hypercholesterolaemia for primary prevention. Patients will be randomised (1:1) to OD group and TD group. The OD group take XZK 1200 mg once per day after dinner while TD group take a traditional dose of 600 mg, two times per day after meals. Participants will have an 8-week medication period and be followed up at weeks 0, 4 and 8. The primary end point is the mean percentage change from baseline to week 8 in serum LDL-C. Secondary end points are safety and lipid-lowering effect on other lipoproteins and compliance. Data analyses will be on the intention-to-treat principle using non-inferiority analysis. ETHICS AND DISSEMINATION: The research had been approved by the Clinical Research and Laboratory Animal Ethics Committee of the First Affiliated Hospital, Sun Yat-sen University ((2017)286). The results will be reported through peer-reviewed journals, seminars and conference presentations. TRIAL REGISTRATION NUMBER: ChiCTR-IIR-17013660.

A novel cholchicine/gadolinium-loading tubulin self-assembly nanocarrier for MR imaging and chemotherapy of glioma.

To enhance the therapeutic efficiency and reduce side effects from drug delivery and chemotherapy, image-guided nanoscale systems have attracted tremendous attention in recent decades. In this study, we developed a novel method to fabricate a colchicine/gadolinium-loaded tubulin self-assembly nanocarrier (Col-Gd@Tub NC) for the image-guided chemotherapy of glioma. The Col-Gd@Tub NCs were spontaneously formed via tubulin self-assembly and were subsequently functionalized by colchicine and gadolinium elements. These resultant Col-Gd@Tub NCs with a diameter of 45 nm exhibited uniform particle size distribution and favorable stability without any leakage of gadolinium in water. Meanwhile, the introduction of gadolinium endowed Col-Gd@Tub NCs with high T 1-weighted MRI performance in vitro. After tail vein injection, Col-Gd@Tub NCs exhibited excellent MRI contrast capability and relatively long circulation time (∼12 h) and were finally cleared out from the bladder. More significantly, the binding colchicine still exerted an anti-tumor effect after the Col-Gd@Tub NCs were taken up by the tumor cells. These results show that the Col-Gd@Tub NCs may be served as a versatile nanoscale platform for the integration of biomedical imaging probes and therapeutic molecules for tumor therapy.

Prognostic Value of Cysteine-Rich Protein 61 Combined with N-Terminal Pro-B-Type Natriuretic Peptide for Mortality in Acute Heart Failure Patients with and without Chronic Kidney Disease.

BACKGROUND: The ability of most biomarkers, such as N-terminal pro-B-type natriuretic peptide (NT-proBNP), to predict prognosis in heart failure can be affected by the state of renal function; therefore, there is the need for a biomarker that can predict prognosis accurately without the influence of renal function. The prognostic value of cysteine-rich protein 61 (CYR61/CCN1) in acute heart failure (AHF) patients has been proven. METHODS: A total of 248 patients hospitalized with AHF were recruited in this study, and serum CCN1 levels, NT-proBNP levels, and other necessary data of patients were collected upon admission. The correlation of serum CCN1 with estimated glomerular filtration rate (eGFR) was investigated, and the logistic regression model was used to investigate the prognostic value of serum CCN1 for 3-month mortality. RESULTS: Fifty-four of 248 patients died (21.8%) during a 3-month follow-up. Serum CCN1 had no significant correlation with eGFR (rho = -0.088, p = 0.167). In the overall population and patients without chronic kidney disease, results showed that both serum CCN1 and NT-proBNP were significantly associated with 3-month mortality. In patients with chronic kidney disease, serum CCN1 was significantly associated with 3-month mortality in logistic regression analysis (odds ratio = 2.40, p = 0.002) while NT-proBNP was not. Further in tertile group comparison, in patients with chronic kidney disease, higher tertile levels of serum CCN1 had a significantly higher risk of 3-month mortality compared to the lower tertile ones (odds ratio = 4.17, p = 0.013), but that of NT-proBNP did not. CONCLUSION: Serum CCN1 level is not associated with eGFR, and it maintains the prognostic value in AHF patients with chronic kidney disease. CCN1 could be a potential novel prognostic biomarker in AHF patients with chronic kidney disease.

Transcribed Ultraconserved Regions, Uc.323, Ameliorates Cardiac Hypertrophy by Regulating the Transcription of CPT1b (Carnitine Palmitoyl transferase 1b).

Transcribed ultraconserved regions (T-UCRs) are a novel class of long noncoding RNAs transcribed from UCRs, which exhibit 100% DNA sequence conservation among humans, mice, and rats. However, whether T-UCRs regulate cardiac hypertrophy remains unclear. We aimed to explore the effects of T-UCRs on cardiac hypertrophy. First, we performed long noncoding RNA microarray analysis on hearts of mice subjected to sham surgery or aortic banding and found that the T-UCR uc.323 was decreased significantly in mice with aortic banding-induced cardiac hypertrophy. In vitro loss- and gain-of-function experiments demonstrated that uc.323 protected cardiomyocytes against hypertrophy induced by phenylephrine. Additionally, we discovered that mammalian target of rapamycin 1 contributed to phenylephrine-induced uc.323 downregulation and uc.323-mediated cardiomyocyte hypertrophy. We further mapped the possible target genes of uc.323 through global microarray mRNA expression analysis after uc.323 knockdown and found that uc.323 regulated the expression of cardiac hypertrophy-related genes such as CPT1b (Carnitine Palmitoyl transferase 1b). Then, chromatin immunoprecipitation proved that EZH2 (enhancer of zeste homolog 2) bound to the promoter of CPT1b via H3K27me3 (trimethylation of lysine 27 of histone H3) to induce CPT1b downregulation. And overexpression of CPT1b could block uc.323-mediated cardiomyocyte hypertrophy. Finally, we found that uc.323 deficiency induced cardiac hypertrophy. Our results reveal that uc.323 is a conserved T-UCR that inhibits cardiac hypertrophy, potentially by regulating the transcription of CPT1b via interaction with EZH2.

Maf1 ameliorates cardiac hypertrophy by inhibiting RNA polymerase III through ERK1/2.

Rationale: An imbalance between protein synthesis and degradation is one of the mechanisms of cardiac hypertrophy. Increased transcription in cardiomyocytes can lead to excessive protein synthesis and cardiac hypertrophy. Maf1 is an RNA polymerase III (RNA pol III) inhibitor that plays a pivotal role in regulating transcription. However, whether Maf1 regulates of cardiac hypertrophy remains unclear. Methods: Cardiac hypertrophy was induced in vivo by thoracic aortic banding (AB) surgery. Both the in vivo and in vitro gain- and loss-of-function experiments by Maf1 knockout (KO) mice and adenoviral transfection were used to verify the role of Maf1 in cardiac hypertrophy. RNA pol III and ERK1/2 inhibitor were utilized to identify the effects of RNA pol III and ERK1/2. The possible interaction between Maf1 and ERK1/2 was clarified by immunoprecipitation (IP) analysis. Results: Four weeks after surgery, Maf1 KO mice exhibited significantly exacerbated AB-induced cardiac hypertrophy characterized by increased heart size, cardiomyocyte surface area, and atrial natriuretic peptide (ANP) expression and by exacerbated pulmonary edema. Also, the deficiency of Maf1 causes more severe cardiac dilation and dysfunction than wild type (WT) mice after pressure overload. In contrast, compared with adenoviral-GFP injected mice, mice injected with adenoviral-Maf1 showed significantly ameliorated AB-induced cardiac hypertrophy. In vitro study has demonstrated that Maf1 could significantly block phenylephrine (PE)-induced cardiomyocyte hypertrophy by inhibiting RNA pol III transcription. However, application of an RNA pol III inhibitor markedly improved Maf1 knockdown-promoted cardiac hypertrophy. Moreover, ERK1/2 was identified as a regulator of RNA pol III, and ERK1/2 inhibition by U0126 significantly repressed Maf1 knockdown-promoted cardiac hypertrophy accompanied by suppressed RNA pol III transcription. Additionally, IP analysis demonstrated that Maf1 could directly bind ERK1/2, suggesting Maf1 could interact with ERK1/2 and then inhibit RNA pol III transcription so as to attenuate the development of cardiac hypertrophy. Conclusions: Maf1 ameliorates PE- and AB-induced cardiac hypertrophy by inhibiting RNA pol III transcription via ERK1/2 signaling suppression.

Association of Cyr61-cysteine-rich protein 61 and short-term mortality in patients with acute heart failure and coronary heart disease.

Aim: The protein CCN1/CYR61 exerts critical functions in myocardial ischemic injury. We sought to investigate the prognostic value of CCN1 in patients with acute heart failure (AHF) and coronary heart disease (CAD). Methodology: We prospectively enrolled 113 patients with AHF and CAD. Patients were followed for all-cause mortality during a 30-day follow-up. Logistic models were used to estimate the association of CCN1 concentrations with 30-day mortality. Results: In multivariate logistic regression model, CCN1 was a significant predictor of 30-day mortality independent of current markers. Enhanced Feedback for Effective Cardiac Treatment risk score was recommended as one of the selected multivariable risk scores to predict outcome in AHF. CCN1 improved risk stratification for all-cause mortality when added to the Enhanced Feedback for Effective Cardiac Treatment risk scores at 30 days. Conclusion: We found CCN1 is independently associated with 30-day mortality in patients with AHF and CAD.

Overdrive pacing mapping: An alternative approach used in scar associated localized atrial tachycardia.

BACKGROUND: Mapping and ablation of localized reentry atrial tachycardia (AT) can be challenging, especially in those with varying cycle length (CL). OBJECTIVE: We attempted to use the traditional maneuver of overdrive pacing to facilitate AT mapping. METHODS: Data were collected from 12 patients with localized ATs. All patients had prior cardiac surgery or prior atrial fibrillation ablation. Overdrive pacing mapping (ODPM) was performed to find independent local activity (ILA) and compared with conventional activation mapping (CAM) during ongoing AT to determine its accuracy and efficacy. Patients with macro-reentry AT around the tricuspid or mitral annulus were excluded. RESULTS: Twelve patients with 14 localized ATs were included. All 14 ATs including 4 (29%) with varying CL successfully completed ODPM and had the ILA, although two ATs terminated during ODP and required repeated mapping. Radiofrequency ablation focused on critical sites with ILA was successful in all 12 patients. Using CAM, however, 6 of 14 ATs (43%) mapping attempts were aborted due to AT termination (2 ATs) or varying CL (4 ATs), and only 5 of 8 (63%) located "critical sites" were ultimately confirmed by entrainment and ablation results. After 25 ± 9 months of follow-up, no patient had AT recurrence. CONCLUSION: Our preliminary results demonstrated that ODPM is superior to CAM in ATs that were poorly sustained or with varying CL and is a useful supplement to CAM.

Lycopene protects against pressure overload-induced cardiac hypertrophy by attenuating oxidative stress.

Oxidative stress is considered an important pathogenic process of cardiac hypertrophy. Lycopene is a kind of carotenoid antioxidant that protects the cardiovascular system, so we hypothesized that lycopene might inhibit cardiac hypertrophy by attenuating oxidative stress. Phenylephrine and pressure overload were used to set up the hypertrophic models in vitro and in vivo respectively. Our data revealed that treatment with lycopene can significantly block pressure overload-induced cardiac hypertrophy in in vitro and in vivo studies. Further studies demonstrated that lycopene can reverse the increase in reactive oxygen species (ROS) generation during the process of hypertrophy and can retard the activation of ROS-dependent pro-hypertrophic MAPK and Akt signaling pathways. In addition, protective effects of lycopene on the permeability transition pore opening in neonatal cardiomyocytes were observed. Moreover, we demonstrated that lycopene restored impaired antioxidant response element (ARE) activity and activated ARE-driven expression of antioxidant genes. Consequently, our findings indicated that lycopene inhibited cardiac hypertrophy by suppressing ROS-dependent mechanisms.