Empagliflozin Prevent High-Glucose Stimulation Inducing Apoptosis and Mitochondria Fragmentation in H9C2 Cells through the Calcium-Dependent Activation Extracellular Signal-Regulated Kinase 1/2 Pathway.

A previous study showed that high-glucose (HG) conditions induce mitochondria fragmentation through the calcium-mediated activation of extracellular signal-regulated kinase 1/2 (ERK 1/2) in H9C2 cells. This study tested whether empagliflozin could prevent HG-induced mitochondria fragmentation through this pathway. We found that exposing H9C2 cells to an HG concentration decreased cell viability and increased cell apoptosis and caspase-3. Empagliflozin could reverse the apoptosis effect of HG stimulation on H9C2 cells. In addition, the HG condition caused mitochondria fragmentation, which was reduced by empagliflozin. The expression of mitochondria fission protein was upregulated, and fusion proteins were downregulated under HG stimulation. The expression of fission proteins was decreased under empagliflozin treatment. Increased calcium accumulation was observed under the HG condition, which was decreased by empagliflozin. The increased expression of ERK 1/2 under HG stimulation was also reversed by empagliflozin. Our study shows that empagliflozin could reverse the HG condition, causing a calcium-dependent activation of the ERK 1/2 pathway, which caused mitochondria fragmentation in H9C2 cells.

Long non-coding RNA FKSG29 regulates oxidative stress and endothelial dysfunction in obstructive sleep apnea.

Altered expressions of pro-/anti-oxidant genes are known to regulate the pathophysiology of obstructive sleep apnea (OSA).We aim to explore the role of a novel long non-coding (lnc) RNA FKSG29 in the development of intermittent hypoxia with re-oxygenation (IHR)-induced endothelial dysfunction in OSA. Gene expression levels of key pro-/anti-oxidant genes, vasoactive genes, and the FKSG29 were measured in peripheral blood mononuclear cells from 12 subjects with primary snoring (PS) and 36 OSA patients. Human monocytic THP-1 cells and human umbilical vein endothelial cells (HUVEC) were used for gene knockout and double luciferase under IHR exposure. Gene expression levels of the FKSG29 lncRNA, NOX2, NOX5, and VEGFA genes were increased in OSA patients versus PS subjects, while SOD2 and VEGFB gene expressions were decreased. Subgroup analysis showed that gene expression of the miR-23a-3p, an endogenous competitive microRNA of the FKSG29, was decreased in sleep-disordered breathing patients with hypertension versus those without hypertension. In vitro IHR experiments showed that knock-down of the FKSG29 reversed IHR-induced ROS overt production, early apoptosis, up-regulations of the HIF1A/HIF2A/NOX2/NOX4/NOX5/VEGFA/VEGFB genes, and down-regulations of the VEGFB/SOD2 genes, while the protective effects of FKSG29 knock-down were abolished by miR-23a-3p knock-down. Dual-luciferase reporter assays confirmed that FKSG29 was a sponge of miR-23a-3p, which regulated IL6R directly. Immunofluorescence stain further demonstrated that FKSGH29 knock-down decreased IHR-induced uptake of oxidized low density lipoprotein and reversed IHR-induced IL6R/STAT3/GATA6/ICAM1/VCAM1 up-regulations. The findings indicate that the combined RNA interference may be a novel therapy for OSA-related endothelial dysfunction via regulating pro-/anti-oxidant imbalance or targeting miR-23a-IL6R-ICAM1/VCAM1 signaling.

Device-related infection and mortality in patients with chronic kidney disease receiving cardiac implantable electronic devices: a propensity score-matched cohort study.

BACKGROUND: Chronic kidney disease (CKD) was reported to be a risk factor of cardiac implantable electronic device (CIED) infection. The application of bundled skin antiseptic preparation before CIED implantation decreased the risk of CIED infection, even in patients undergoing complex procedures. However, the effect of bundled skin antiseptic preparation to prevent CIED infection in patients with CKD was not tested. METHODS: Between July 2012 and December 2019, 1668 patients receiving CIEDs comprised this retrospective cohort study and were categorized into two groups by the diagnosis of CKD: group with CKD (n = 750, 45%) and group without CKD (n = 918, 55%). The primary outcome was clinical CIED infection, including major and minor infection, and the secondary outcomes were cardiovascular mortality and all-cause mortality. Propensity score matching (PSM) was applied to reduce selection bias between the study groups. RESULTS: During a 4-year follow-up period, 30 patients (1.8%) had a CIED infection. After PSM, the incidence of CIED infection was similar between the patients with CKD and without CKD (1.0% vs. 1.8%). The incidences of cardiovascular mortality and all-cause mortality were higher in patients with CKD compared to patients without CKD (6.5% vs. 3.0%, P = 0.009; 22.8% vs. 11.8%, P < 0.001, respectively). CONCLUSION: The incidence of clinical CIED infection in patients with CKD was as lower as in patients without CKD after applying the bundled skin antiseptic preparation strategy. The cumulative incidences of cardiovascular mortality and all-cause mortality were significantly higher in the matched CIED recipients with CKD compared to the matched cohort without CKD.

Delta Increment in Pacing QRS Duration Predicts Cardiovascular Mortality in Patients with Pre-Existing Bundle Branch Block Receiving Permanent Pacemakers.

Background: The clinical implication of pre-existing intraventricular conduction disturbance (IVCD) in permanent pacemaker (PPM) recipients is unknown. Objectives: To explore the clinical outcomes in patients with pre-existing IVCD after implantation of PPMs. Methods: A total of 1424 patients who received PPMs were categorized into three groups by pre-procedural electrocardiography: patients without IVCD (n = 1045), patients with right bundle branch block (RBBB) (n = 309), and patients with left bundle branch block (LBBB) (n = 70). The primary outcome was cardiovascular (CV) mortality. Receiver operating characteristic curve analysis was performed to determine the optimal cut-off values of variable in predicting CV mortality. Results: During follow-up, there was no significant difference in CV mortality between patients with and without IVCD. In multivariate analysis, independent predictors of CV mortality were age [hazard ratio (HR): 1.03; 95% confidence interval (95% CI): 1.00-1.05; p = 0.026], history of heart failure [HR: 1.98; 95% CI: 1.19-3.29; p = 0.009], chronic kidney disease [HR: 1.75; 95% CI: 1.11-2.74; p = 0.015] and increment in pacing QRS duration [HR: 1.01; 95% CI: 1.00-1.04; p = 0.038]. Delta increments in pacing QRS duration ≥ 43 msec [HR: 2.91; 95% CI: 1.23-6.83; p = 0.014] in patients with pre-existing RBBB, and ≥ 33 msec [HR: 11.44; 95% CI: 2.03-64.30; p = 0.006] in patients with pre-existing LBBB were independent determinants of CV mortality. Conclusions: There was no difference in CV mortality between patients with or without IVCD. However, wider pacing QRS duration increased the risk of CV mortality in PPM recipients, and delta increment in pacing QRS duration increased the risk of CV mortality in patients with pre-existing IVCD.

Feature and impact of guideline-directed medication prescriptions for heart failure with reduced ejection fraction accompanied by chronic kidney disease.

Background: With respect to total mortality and cardiovascular mortality, the feature and impact of guideline-directed medication (GDM) prescriptions for heart failure with reduced ejection fraction (HFrEF) with chronic kidney disease (CKD) are unknown. Therefore, we aimed to determine these aspects. Methods: GDM prescriptions and their impact on discharged patients with and without CKD were analyzed. To analyze differences in one-year clinical outcomes, propensity score matching was conducted on a cohort of patients with concomitant HFrEF and CKD who received more and fewer GDM prescriptions. Results: A total of 1509 patients were enrolled in Taiwan's HFrEF registry from May 2013 to October 2014, and 1275 discharged patients with complete one-year follow-up were further analyzed. Of these patients, 468 (36.7%) had moderate CKD, whereas 249 (19.5%) had advanced CKD. Patients with advanced CKD received fewer prescribed GDMs than other patients. Multivariate analysis revealed that peripheral arterial occlusive disease, thyroid disorder, advanced HF at discharge, diastolic blood pressure, digoxin use, and fewer prescribed GDMs were independent predictors of one-year total mortality. After propensity score matching, patients with fewer prescribed GDMs had higher one-year total mortality rate than those with more prescribed GDMs (P=0.036). Conclusions: CKD at discharge from HF hospitalization was associated with fewer GDM prescriptions, particularly in patients with more advanced CKD. The propensity-matched analysis indicated that more GDM prescriptions led to better clinical outcomes in HFrEF patients with CKD. Careful interpretation of changes in renal function during HF hospitalization may improve GDM prescriptions.

Is it possible to expect left ventricular ejection fraction improvement in patients with known advanced heart diseases in the case of right atrial flutter treated by ablation?

BACKGROUND: Atrial flutter (AFL)-related tachycardia-induced cardiomyopathy (TICM) is a treatable cause of heart failure (HF). This study aims to explore the effect of AFL ablation on left ventricular (LV) function in right AFL patients with or without advanced heart diseases. METHODS: Between January 2013 and December 2019, 149 patients underwent ablation for persistent AFL. Among them, 60 patients with persistent right atrial (RA) flutter had symptomatic HF and elevated natriuretic peptide levels. Group 1 consisted of 35 patients without advanced heart diseases, and group 2 consisted of 25 patients with prior history of ischemic cardiomyopathy (ICM), dilated cardiomyopathy (DCM) or surgery for valvular heart disease (VHD). Follow-up echocardiography was performed 6 months later. Improvement of LV performance was defined as LV ejection fraction (EF) increase ≥50% of baseline EF without clinical HF symptoms or LVEF recovery to ≥60%. RESULTS: Group 2 had larger LV end-diastolic volume (LVEDV) and LV end-systolic volume than group 1. At follow-up, group 2 had larger LV end-systolic volume than group 1. Group 1 had more increase in LVEF than group 2 (21.7 ± 15.2% vs 4.1 ± 13.2%; P < .001). A receiver operating characteristic curve was constructed to determine the discrimination threshold of baseline LVEDV (137 mL) in the overall study group for improvement of LV performance after ablation (P = .005). CONCLUSIONS: Successful ablation for right AFL could achieve more reversal of LV dysfunction in patients without advanced heart diseases. Pre-ablation LVEDV ≥ 137 mL was associated with no improvement of LV performance after ablation.

Diagnosis and Treatment for embolic stroke of undetermined source: Consensus statement from the Taiwan stroke society and Taiwan society of cardiology.

Cryptogenic stroke comprises about one-quarter of ischemic strokes with high recurrence rate; however, studies specifically investigating the features and treatment of this stroke subtype are rare. The concept of 'embolic stroke of undetermined source' (ESUS) may facilitate the development of a standardized approach to diagnose cryptogenic stroke and improve clinical trials. Since recent large randomized control trials failed to demonstrate a reduction in stroke recurrence with anticoagulants, anti-platelet agents remain the first-line treatment for ESUS patients. Nevertheless, patients with high risk of stroke recurrence (e.g., those with repeated embolic infarcts despite aspirin treatment) require a more extensive survey of stroke etiology, including cardiac imaging and prolonged cardiac rhythm monitoring. Anticoagulant treatments may still benefit some subgroups of high-risk ESUS patients, such as those with multiple infarcts at different arterial territories without aortic atheroma, the elderly, or patients with high CHA2D2-VASc or HOVAC scores, atrial cardiopathy or patent foramen ovale. Several important ESUS clinical trials are ongoing, and the results are anticipated. With rapid progress in our understanding of ESUS pathophysiology, new subcategorizations of ESUS and assignment of optimal treatments for each ESUS subgroup are expected in the near future.

Revealing the Influences of Sex Hormones and Sex Differences in Atrial Fibrillation and Vascular Cognitive Impairment.

The impacts of sex differences on the biology of various organ systems and the influences of sex hormones on modulating health and disease have become increasingly relevant in clinical and biomedical research. A growing body of evidence has recently suggested fundamental sex differences in cardiovascular and cognitive function, including anatomy, pathophysiology, incidence and age of disease onset, symptoms affecting disease diagnosis, disease severity, progression, and treatment responses and outcomes. Atrial fibrillation (AF) is currently recognized as the most prevalent sustained arrhythmia and might contribute to the pathogenesis and progression of vascular cognitive impairment (VCI), including a range of cognitive deficits, from mild cognitive impairment to dementia. In this review, we describe sex-based differences and sex hormone functions in the physiology of the brain and vasculature and the pathophysiology of disorders therein, with special emphasis on AF and VCI. Deciphering how sex hormones and their receptor signaling (estrogen and androgen receptors) potentially impact on sex differences could help to reveal disease links between AF and VCI and identify therapeutic targets that may lead to potentially novel therapeutic interventions early in the disease course of AF and VCI.

Sarcomeres Morphology and Z-Line Arrangement Disarray Induced by Ventricular Premature Contractions through the Rac2/Cofilin Pathway.

The most common ventricular premature contractions (VPCs) originate from the right ventricular outflow tract (RVOT), but the molecular mechanisms of altered cytoskeletons of VPC-induced cardiomyopathy remain unexplored. We created a RVOT bigeminy VPC pig model (n = 6 in each group). Echocardiography was performed. The histopathological alternations in the LV myocardium were analyzed, and next generation sequencing (NGS) and functional enrichment analyses were employed to identify the differentially expressed genes (DEGs) responsible for the histopathological alternations. Finally, a cell silencing model was used to confirm the key regulatory gene and pathway. VPC pigs had increased LV diameters in the 6-month follow-up period. A histological study showed more actin cytoskeleton disorganization and actin accumulation over intercalated disc, Z-line arrangement disarray, increased ß-catenin expression, and cardiomyocyte enlargement in the LV myocardium of the VPC pigs compared to the control pigs. The NGS study showed actin cytoskeleton signaling, RhoGDI signaling, and signaling by Rho Family GTPases and ILK Signaling presented z-scores with same activation states. The expressions of Rac family small GTPase 2 (Rac2), the p-cofilin/cofilin ratio, and the F-actin/G-actin ratio were downregulated in the VPC group compared to the control group. Moreover, the intensity and number of actin filaments per cardiomyocyte were significantly decreased by Rac2 siRNA in the cell silencing model. Therefore, the Rac2/cofilin pathway was found to play a crucial role in the sarcomere morphology and Z-line arrangement disarray induced by RVOT bigeminy VPCs.

Double Twist.

A rare complication about "Twiddler syndrome" is reported, and an interesting image about "double twist" is presented. A 78-year-old woman received a single-chamber implantable cardioverter defibrillator (ICD) for secondary prevention of ventricular arrhythmia. After she played mahjong (a traditional Chinese board game) overnight, her ICD lead sense amplitude decreased suddenly and did not recover. The intracardiac electrogram of ICD also found ventricular lead noise before this episode. Chest radiography revealed a twisted lead at the ICD pocket and a twisted and retracted ICD lead in the right atrium. An old ICD lead could not be straightened and removed, and a new ICD lead was implanted at the right ventricle. Anti-coagulation was used to prevent thrombosis for the old ICD lead.

The implications of catheter ablation for solitary atrial flutter in preventing stroke risk: a nationwide population-based cohort study.

AIMS: The implications of ablation for atrial fibrillation in preventing stroke are controversial, and no studies have investigated whether ablation prevents ischaemic stroke (IS) in atrial flutter (AFL). METHODS AND RESULTS: This study analysed data contained in the Taiwan National Health Insurance Research Database for 16 765 patients with a first diagnosis of solitary AFL during 2001-2013. Eligible patients were divided into two groups according to whether or not they had received ablation. Propensity score matching (PSM) was performed to mitigate the effects of potential confounding factors. The primary outcome was occurrence of IS during follow-up. After 1:2 PSM, the analysis included 1037 patients in the ablation group and 2074 patients in the non-ablation group. The incidence of IS was lower in the ablation group compared to the non-ablation group [subdistribution hazard ratio (SHR) 0.61, 95% confidence interval (CI) 0.41-0.90] during the 2-year follow-up period but not thereafter (SHR 1.03, 95% CI 0.72-1.48). When grouping by stroke history, it revealed that ablation affected the incidence of stroke in patients without history of stroke (SHR 0.59, 95% CI 0.38-0.91) but not in patients with history of stroke. When each group was stratified by CHA2DS2-VASc score, ablation lowered the incidence of stroke in patients with CHA2DS2-VASc ≤3 (SHR 0.31, 95% CI 0.16-0.60) but not in patients with CHA2DS2-VASc ≥4 in the initial 2-year follow-up. CONCLUSION: The different incidence of IS in patients with/without ablation indicates that ablation reduces the risk of IS in AFL patients.

Clinical outcomes of solitary atrial flutter patients using anticoagulation therapy: a national cohort study.

AIMS: Anticoagulation therapy is indicated to prevent stroke in atrial flutter (AFL) and atrial fibrillation (AF) patients. However, the outcomes of solitary AFL patients may differ from those with AFL who develop AF during follow-up. This study aimed to investigate the differences in clinical outcomes: (i) among patients with solitary AFL, AF, and AFL developing AF thereafter and (ii) between solitary AFL patients with vs. without anticoagulation therapy. METHODS AND RESULTS: This nationwide cohort study enrolled patients with solitary AFL, solitary AF, and AFL developing AF from a 12 years National Health Insurance Research Database in Taiwan. There were 230 367 patients without anticoagulation therapy in the solitary AF cohort, 8064 in the solitary AFL cohort, and 4495 in the AFL with AF cohort. The AFL with AF and solitary AF cohorts had higher incidences of ischaemic stroke and major bleeding than the solitary AFL cohort. Solitary AFL patients with anticoagulation therapy had a lower ischaemic stroke rate than those without (P < 0.05) at the level of a CHA2DS2-VASc score ≥3. Solitary AFL patients with anticoagulation therapy had a higher intracranial haemorrhage rate than those without (P < 0.05) at the level of a CHA2DS2-VASc score ≤3. Net clinical outcomes including ischaemic stroke, systemic embolization, and major bleeding favoured anticoagulation use in solitary AFL patients with a CHA2DS2-VASc score ≥4. CONCLUSION: Solitary AFL patients without anticoagulation therapy had better clinical outcomes than AFL patients developing AF in this study. Anticoagulation therapy may offer the best net clinical outcome for solitary AFL patients with a CHA2DS2-VASc score ≥4.

Impact of multi-disciplinary treatment strategy on systolic heart failure outcome.

BACKGROUND: Patients with reduced ejection fraction have high rates of mortality and readmission after hospitalization for heart failure. In Taiwan, heart failure disease management programs (HFDMPs) have proven effective for reducing readmissions for decompensated heart failure or other cardiovascular causes by up to 30%. However, the benefits of HFDMP in different populations of heart failure patients is unknown. METHOD: This observational cohort study compared mortality and readmission in heart failure patients who participated in an HFDMP (HFDMP group) and heart failure patients who received standard care (non-HFDMP group) over a 1-year follow-up period after discharge (December 2014 retrospectively registered). The components of the intervention program included a patient education program delivered by the lead nurse of the HFDMP; a cardiac rehabilitation program provided by a physical therapist; consultation with a dietician, and consultation and assessment by a psychologist. The patients were followed up for at least 1 year after discharge or until death. Patient characteristics and clinical demographic data were compared between the two groups. Cox proportional hazards regression analysis was performed to calculate hazard ratios (HRs) for death or recurrent events of hospitalization in the HFDMP group in comparison with the non-HFDMP group while controlling for covariates. RESULTS: The two groups did not significantly differ in demographic characteristics. The risk of readmission was lower in the HFDMP group, but the difference was not statistically significant (HR = 0.36, p = 0.09). In patients with ischemic cardiomyopathy, the risk of readmission was significantly lower in the HFDMP group compared to the non-HFDMP group (HR = 0.13, p = 0.026). The total mortality rate did not have significant difference between this two groups. CONCLUSION: The HFDMP may be beneficial for reducing recurrent events of heart failure hospitalization, especially in patients with ischemic cardiomyopathy. TRIAL REGISTRATION: Longitudinal case-control study ISRCTN98483065 , 24/09/2019, retrospectively registered.

Late fractionated potentials in catheter ablation for right ventricular outflow tract ventricular arrhythmias.

BACKGROUND: Endocardial late fractionated potentials during sinus rhythm mapping may reflect abnormal "subendocardial" substrates associated with right ventricular outflow tract (RVOT) ventricular arrhythmias (VAs). The aim of this study was to explore the clinical outcomes of catheter ablation guided by these late fractionated potentials for RVOT VAs in patients without structural heart disease. METHODS: From January 2016 to March 2018, 28 patients underwent catheter ablation for RVOT premature ventricular contractions (PVCs) or ventricular tachycardia (VT), guided by the EnSite NavX or Velocity V5.0 three-dimensional mapping system (Abbott, St. Paul, MN, USA). Among them, 10 patients (35.7%) were found to have endocardial late fractionated potentials during sinus rhythm mapping (Group 1). Group 2 was composed of 18 patients in whom no endocardial late fractionated potentials were seen. The burden of VAs, acute procedural success, and 3-month clinical outcomes were analyzed. RESULTS: The average duration of late fractionated potentials after the end of QRS during sinus rhythm mapping in group 1 was 45.00 ± 17.15 ms. Baseline demographics and morphology and burden of PVCs were similarly distributed between both groups. Group 1 had higher acute procedural success compared to group 2 (100% vs 66.7%; P = .039). Moreover, at 3-month follow-up, group 1 had lower total PVCs (49 (1-5986) versus 4316 (1-23231); P = .048), PVC burden (0% (0-5.9) vs 4.3% (0-18.9); P = .055), and higher clinical success (100% vs 55.6%; P = .025) compared to group 2. CONCLUSION: The identification and elimination of endocardial late fractionated potentials during sinus rhythm mapping could improve the acute success and short-term outcomes of ablation for RVOT VAs.

Common pulmonary vein on the recurrence of atrial tachyarrhythmia after pulmonary vein isolation.

AIMS: Catheter ablation has become an effective treatment modality for atrial fibrillation (AF). However, the relationship between common pulmonary vein (PV) and recurrent atrial tachyarrhythmia (ATA) after PV isolation (PVI) remains controversial. This study aimed to explore the function of common PV on the risk of recurrent ATA after PVI. METHODS: We identified a total of 191 patients who received radiofrequency catheter ablation for paroxysmal AF at our hospital between July 2010 and December 2017 for retrospective chart review. We collected the following data for analysis: results of preprocedural computed tomography, including the anatomy of PV and left atrial (LA) volume; the incidence of early- and late-onset recurrence of ATA. We compared these characteristics between the two groups defined by the presence or absence of the late-onset recurrence of ATA. RESULTS: Compared to the no ATA recurrence group, the ATA recurrence group had larger LA size, larger LA end-diastolic and systolic volumes, larger maximal diameter of PV, higher prevalence of common PV, and higher incidence of early-onset recurrence of ATA. In multivariate logistic regression analyses, presence of common PV and early-onset recurrence were independently associated with late-onset recurrence of ATA. Compared to patients without common PV, patients with common PV had larger diameter of PV and higher incidence of late-onset recurrent ATA. CONCLUSION: In patients with paroxysmal AF, early-onset recurrence of ATA and the presence of common PV were independently associated with late-onset recurrent ATA after radiofrequency catheter ablation.

Additional cavotricuspid isthmus block ablation may not improve the outcome of atrial fibrillation ablation.

AIMS: Pulmonary vein isolation (PVI) is an effective procedure for atrial fibrillation (AF). The role of additional cavotricuspid isthmus (CTI) block ablation remains controversial in AF patients without atrial flutter (AFL). Therefore, this study aimed to explore the clinical outcome of additional CTI block ablation in patients without AFL. METHODS: Between January 2013 and December 2017, a total of 139 patients who did not have documented AFL and who underwent catheter ablation for AF were recruited. Fifty-seven patients were classified in additional CTI block ablation group and 82 patients were classified in without CTI group. The incidence of early-onset and late-onset atrial arrhythmia recurrence was compared between the two groups. RESULTS: The additional CTI group had a higher prevalence of persistent or long-standing AF and larger left atrial volume. The additional CTI group had a higher incidence of late-onset atrial arrhythmia recurrence (38.6% vs 12.2%; P < .001). When compared to without CTI group, additional CTI therapy did not have a better outcome in terms of freedom of atrial arrhythmia in subgroup analysis. The incidence of early-onset and late-onset atrial arrhythmia recurrence did not differ between additional CTI group and without CTI group in paroxysmal AF patients and nonparoxysmal AF patients after propensity scoring matching. CONCLUSION: CTI block ablation in addition to PVI for AF patients without a history of AFL or inducible AFL during ablation may not improve the clinical outcome of AF ablation in the patients with larger LA volume, nonparoxysmal AF, or post-PVI inducible AF.

Left Atrial or Left Atrial Appendage Thrombus Resolution After Adjustment of Oral Anticoagulant Treatment.

BACKGROUND: There are few reports about non-vitamin K antagonist oral anticoagulant (NOAC) treatment for resolution of left atrium (LA) or left atrial appendage (LAA) thrombus. LAA thrombus is an important cause of cardiogenic cerebral thromboembolism, and the detection rate increases due to more and more patients receiving catheter ablation. However, the results from NOAC use for LA or LAA thrombus are still unknown in real-world practice. The aim of this study was to discover the resolution of LA or LAA thrombus after anticoagulant treatment in real-world practice. METHOD: From January 2013 to December 2016, a total 864 patients underwent transesophageal echocardiography (TEE), and 41 cases of LA or LAA thrombus were detected in our hospital. Among them, a total of 22 patients underwent follow-up TEE to detect the resolution of LA or LAA thrombus. RESULT: The average age of the study patients was 72.0 ± 11 years old, and 61% were male. The average CHA2DS2-VASc scores were 3.76 ± 2.01 points. A total of 22 patients underwent follow-up TEE, and 19 (86.4%) patients presented LA or LAA thrombus resolution. The average resolution duration was 258.47 ± 218.17 days. One-year all-cause mortality was 4.9%, and the incidence of ischemic stroke was 4.9%. Most physicians favored titration of the dosage of NOAC or warfarin in real-world practice. CONCLUSION: In real-world practice, most physicians favored titration of the dosage of NOAC or warfarin for LA or LAA thrombus. LA or LAA thrombus could exist if the patient received a reduced dose of NOAC. High frequency of LAA or LA thrombi could resolve, and a low incidence of ischemic stroke occurred after adjustment of oral anticoagulant treatment.

The Five-Year Clinical and Angiographic Follow-Up Outcomes of Intracoronary Transfusion of Circulation-Derived CD34+ Cells for Patients With End-Stage Diffuse Coronary Artery Disease Unsuitable for Coronary Intervention-Phase I Clinical Trial.

OBJECTIVES: This study investigated the clinical and angiographic long-term outcomes of intracoronary transfusion of circulation-derived CD34+ cells for patients with end-stage diffuse coronary artery disease unsuitable for coronary intervention. DESIGN AND SETTING: A single-center prospective randomized double-blinded phase I clinical trial. Thirty-eight patients undergoing CD34+ cell therapy were allocated into groups 1 (1.0 × 10 cells/each vessel; n = 18) and 2 (3.0 × 10 cells/each vessel; n = 20). PATIENTS: Those with end-stage diffuse coronary artery disease were unsuitable for percutaneous and surgical coronary revascularization. INTERVENTIONS: Intracoronary delivery of circulation-derived CD34+ cells. MEASUREMENTS AND MAIN RESULTS: We prospectively evaluated long-term clinical and echocardiographic/angiographic outcomes between survivors and nonsurvivors. By the end of 5-year follow-up, the survival rate and major adverse cardio/cerebrovascular event were 78.9% (30/38) and 36.8% (14/38), respectively. During follow-up period, 31.6% patients (12/38) received coronary stenting for reason of sufficient target vessel size grown-up after the treatment. Endothelial function was significantly reduced in the nonsurvivors than the survivors (p = 0.039). Wimasis image analysis of angiographic findings showed that the angiogenesis was significantly and progressively increased from baseline to 1 and 5 years (all p < 0.001). The 3D echocardiography showed left ventricular ejection fraction increased from baseline to 1 year and then remained stable up to 5 years, whereas left ventricular chamber diameter exhibited an opposite pattern to left ventricular ejection fraction among the survivors. The clinical scores for angina and heart failure were significantly progressively reduced from baseline to 1 and 5 years (all p < 0.001). CONCLUSIONS: CD34+ cell therapy for end-stage diffuse coronary artery disease patients might contribute to persistently long-term effects on improvement of left ventricular function, angina/heart failure, and amelioration of left ventricular remodeling.

Acute Inferior Wall ST Segment Elevation Myocardial Infarction Caused Atrial Lead Dysfunction Reversed by Primary Percutaneous Coronary Intervention.

The mechanism of atrial lead dysfunction varies in patients receiving pacemaker implantation and this needs to be investigated, especially when the causes are reversible. We report and discuss a 76-year-old female who had atrial lead dysfunction caused by acute myocardial infarction and who was recovered after primary percutaneous coronary intervention. The sequential electrocardiographic changes were demonstrated and the possible mechanisms were discussed.

Synthesis and Isomeric Effects of Ladder-Type Alkylated Terbenzodithiophene Derivatives.

A new class of heptacyclic ladder-type terbenzodithiophene (TBDT) structures merging three fused benzodithophenes was developed. Two TBDT conjugated isomers, named as syn-TBDT and anti-TBDT, where the two thienyl rings in the outmost BDT units are in the syn- and anti-fashion, are designed. Two decyl groups are introduced to their 6,13 and 7,14-positions to form four isomeric 6,13-syn-TBDT, 7,14-syn-TBDT, 6,13-anti-TBDT, and 7,14-anti-TBDT structures which are constructed by the DBU-induced 6-benzannulation involving propargyl-allenyl isomerization of the dieneyne moieties in the corresponding precursors followed by 6π-electrocyclization/aromatization, while isomeric TD-syn-TBDT and TD-anti-TBDT with four decyl groups substituted at 6,7,13,14-positions are synthesized via palladium-catalyzed dialkylacetylene insertion/C-H arylation of the corresponding iodobiaryl precursors. The intrinsic properties can be modulated by molecular manipulation of the main-chain and side-chain isomeric structures. anti-TBDT derivatives exhibit higher melting points, larger bandgaps, stronger intermolecular interactions, and higher mobility than the corresponding syn-TBDT analogues. These molecules can be further utilized as building blocks to make various TBDT-based materials for optoelectronic applications.