Long Non-coding RNA Involved in the Pathophysiology of Atrial Fibrillation.

BACKGROUND: Atrial fibrillation (AF) is a prevalent and chronic cardiovascular disorder associated with various pathophysiological alterations, including atrial electrical and structural remodeling, disrupted calcium handling, autonomic nervous system dysfunction, aberrant energy metabolism, and immune dysregulation. Emerging evidence suggests that long non-coding RNAs (lncRNAs) play a significant role in the pathogenesis of AF. OBJECTIVE: This discussion aims to elucidate the involvement of AF-related lncRNAs, with a specific focus on their role as miRNA sponges that modulate crucial signaling pathways, contributing to the progression of AF. We also address current limitations in AF-related lncRNA research and explore potential future directions in this field. Additionally, we summarize feasible strategies and promising delivery systems for targeting lncRNAs in AF therapy. CONCLUSION: In conclusion, targeting AF-related lncRNAs holds substantial promise for future investigations and represents a potential therapeutic avenue for managing AF.

Chinese expert consensus on the construction of the fluoroless cardiac electrophysiology laboratory and related techniques.

Transcatheter radiofrequency ablation has been widely introduced for the treatment of tachyarrhythmias. The demand for catheter ablation continues to grow rapidly as the level of recommendation for catheter ablation. Traditional catheter ablation is performed under the guidance of X-rays. X-rays can help display the heart contour and catheter position, but the radiobiological effects caused by ionizing radiation and the occupational injuries worn caused by medical staff wearing heavy protective equipment cannot be ignored. Three-dimensional mapping system and intracardiac echocardiography can provide detailed anatomical and electrical information during cardiac electrophysiological study and ablation procedure, and can also greatly reduce or avoid the use of X-rays. In recent years, fluoroless catheter ablation technique has been well demonstrated for most arrhythmic diseases. Several centers have reported performing procedures in a purposefully designed fluoroless electrophysiology catheterization laboratory (EP Lab) without fixed digital subtraction angiography equipment. In view of the lack of relevant standardized configurations and operating procedures, this expert task force has written this consensus statement in combination with relevant research and experience from China and abroad, with the aim of providing guidance for hospitals (institutions) and physicians intending to build a fluoroless cardiac EP Lab, implement relevant technologies, promote the standardized construction of the fluoroless cardiac EP Lab.

Puerarin Protects against Myocardial Ischemia/Reperfusion Injury by Inhibiting Ferroptosis.

This study investigated whether pretreatment with puerarin could alleviate myocardial ischemia/reperfusion (I/R) injury in a cardiomyocyte oxygen-glucose deprivation and reoxygenation (OGD/R) model and in a mouse I/R injury model. For in vitro experiments, H9C2 cells were divided into control, erastin, OGD/R, OGD/R + puerarin, and OGD/R + ferrostatin (Fer)-1 groups. Parameters related to ferroptosis included levels of malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), ATP, reactive oxygen species (ROS), glutathione (GSH), prostaglandin endoperoxide synthase (Ptgs) 2 mRNA, glutathione peroxidase (GPX) 4 protein and iron. In H9C2 cells, puerarin or Fer-1 pretreatment reduced ferroptosis, as indicated by decreased ROS and increased GSH, ATP levels. In vivo, wild-type mice were randomly divided into sham, I/R + vehicle, I/R + puerarin, and IR + Fer-1 groups. The I/R model was established by 30 min of left anterior descending artery occlusion followed by 24 h of reperfusion. Pretreatment with puerarin or Fer-1 significantly reduced infarct size in I/R mice, and decreased the activities of Myeloperoxidase (MPO) and cardiac enzymes such as creatine kinase MB isoenzyme (CK-MB), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) compared to those in the vehicle-treated group. Puerarin also reduced the production of MDA and 4-HNE, reduced the mRNA expression of Ptgs2 mRNA, and increased GPX4 protein expression. These results showed that puerarin exerted protective effects against myocardial I/R injury by inhibiting ferroptosis and inflammation, and therefore may have therapeutic potential for treatment of acute myocardial infarction.

Triglyceride-glucose index and the risk of heart failure: Evidence from two large cohorts and a mendelian randomization analysis.

BACKGROUND: The relationship between triglyceride-glucose (TyG) index, an emerging marker of insulin resistance, and the risk of incident heart failure (HF) was unclear. This study thus aimed to investigate this relationship. METHODS: Subjects without prevalent cardiovascular diseases from the prospective Kailuan cohort (recruited during 2006-2007) and a retrospective cohort of family medicine patients from Hong Kong (recruited during 2000-2003) were followed up until December 31st, 2019 for the outcome of incident HF. Separate adjusted hazard ratios (aHRs) summarizing the relationship between TyG index and HF risk in the two cohorts were combined using a random-effect meta-analysis. Additionally, a two-sample Mendelian randomization (MR) of published genome-wide association study data was performed to assess the causality of observed associations. RESULTS: In total, 95,996 and 19,345 subjects from the Kailuan and Hong Kong cohorts were analyzed, respectively, with 2,726 cases of incident HF in the former and 1,709 in the latter. Subjects in the highest quartile of TyG index had the highest risk of incident HF in both cohorts (Kailuan: aHR 1.23 (95% confidence interval: 1.09-1.39), PTrend <0.001; Hong Kong: aHR 1.21 (1.04-1.40), PTrend =0.007; both compared with the lowest quartile). Meta-analysis showed similar results (highest versus lowest quartile: HR 1.22 (1.11-1.34), P < 0.001). Findings from MR analysis, which included 47,309 cases and 930,014 controls, supported a causal relationship between higher TyG index and increased risk of HF (odds ratio 1.27 (1.15-1.40), P < 0.001). CONCLUSION: A higher TyG index is an independent and causal risk factor for incident HF in the general population. CLINICAL TRIAL REGISTRATION: URL: https://www.chictr.org.cn ; Unique identifier: ChiCTR-TNRC-11,001,489.

Comparisons of electrophysiological characteristics, pacing parameters and mid- to long-term effects in right ventricular septal pacing, right ventricular apical pacing and left bundle branch area pacing.

BACKGROUND: As a near-physiological pacing innovation, left bundle branch area pacing (LBBAP) has drawn much attention recently. This study was aimed to investigate the electrophysiological characteristics, unipolar/bipolar pacing parameters and mid- to long-term effects and safety of three different pacing methods and identify possible predictors of adverse left ventricular remodeling. METHODS: Ninety-two patients were divided into the LBBAP group, right ventricular septal pacing (RVSP) group and right ventricular apical pacing (RVAP) group. Baseline information, electrophysiological, pacing and echocardiographic parameters were collected. RESULTS: The three pacing methods were performed with a similar high success rate. The paced QRSd was significantly different among the LBBAP, RVSP and RVAP groups (105.93 ± 15.85 ms vs. 143.63 ± 14.71 ms vs. 155.39 ± 14.17 ms, p < 0.01). The stimulus to left ventricular activation time (Sti-LVAT) was the shortest in the LBBAP group, followed by the RVSP and RVAP groups (72.80 ± 12.07 ms vs. 86.29 ± 8.71 ms vs. 94.14 ± 10.14 ms, p < 0.001). LBBAP had a significantly lower tip impedance during the procedure and 3-month follow up as compared to RVSP and RVAP (p < 0.001). Higher bipolar captured thresholds were observed in LBBAP during the procedure (p < 0.001). Compared to the baseline values, there was a greater reduction in left ventricular end-diastolic dimension (LVEDD) in the LBBAP group (p = 0.046) and a significant enlargement in LVEDD in the RVAP group (p = 0.008). Multiple regression analysis revealed that the Sti-LVAT was a significant predictor of LVEDD at 12 months post-procedure. At the 24-h post-procedure, significant elevations were observed in the cTnI levels in LBBAP (p < 0.001) and RVSP (p < 0.05). More transient RBB injury was observed in LBBAP. But no significant difference was found in cardiac composite endpoints among three groups (p > 0.05). CONCLUSIONS: LBBAP demonstrated a stable captured threshold, a low tip impedance and a high R-wave amplitude during the 12-month follow-up. Left ventricular remodeling was improved at 12 months post-procedure through LBBAP. The Sti-LVAT was a significant predictor of left ventricular remodeling. LBBAP demonstrated its feasibility, effectiveness, safety and some beneficial electrophysiological characteristics during this mid- to long-term follow-up, which should be confirmed by further studies.

Emergency catheter ablation: A feasible option for acute treatments of patients with unstable pre-excited atrial fibrillation.

BACKGROUND: Pre-excited atrial fibrillation (AF) is associated with increased risk of life-threatening events. However, at times, patients with pre-excited AF still repetitively suffer from hemodynamic disturbance, with resistance to acute treatments of antiarrhythmic therapy and cardioversion. METHODS: To evaluate the feasibility in correcting hemodynamic disturbance, patients with pre-excited AF who underwent catheter ablation of accessory pathway as an emergency procedure, were retrospectively collected from two centers of China. The medical records of patients were analyzed and summarized in this case series. RESULTS: Five patients with pre-excited AF who received emergency catheter ablation of accessory pathway, were collected from two contributor centers and reported in this case series. All collected patients still repetitively suffered from hemodynamic disturbance induced by rapid anterograde conduction of AF via pathway, even guideline recommended acute interventions of intravenous antiarrhythmic therapy and cardioversion had been performed. Finally, as an emergency procedure, catheter ablation of accessory pathway was performed in collected patients. Correspondingly, the hemodynamic unstable status was greatly relieved. Meanwhile, all collected patients with high risk of pre-excited AF were combined with left-sided accessory pathway, with shortest RR interval of widened pre-excited QRS complex less than 250 ms. Thus, combination with left-sided pathway is proposed as an indicator for the increased risk of life-threatening events in patients with high risk of pre-excited AF. CONCLUSIONS: Emergency catheter ablation of accessory pathway is an effective option for the acute managements of patients with high risk of pre-excited AF in unstable hemodynamics, which is resistant to antiarrhythmic therapy and cardioversion.

C-reactive protein and atrial fibrillation: Insights from epidemiological and Mendelian randomization studies.

BACKGROUND AND AIMS: This study aimed to investigate the role of C-reactive protein (CRP) in atrial fibrillation (AF) from epidemiological and genetic perspectives. METHODS AND RESULTS: Individual-level data from the Kailuan cohort recruited between 2006 and 2017 were included. Serum CRP levels were measured at baseline and at biennial follow-up visits, and incident AF was ascertained from biennial 12-lead ECG assessment and medical records. Cox proportional hazards models were used to assess the association between baseline CRP levels or cumulative exposure to CRP and incident AF. A meta-analysis including nine prospective cohort studies and our current study was also conducted. Mendelian randomization (MR) analysis was performed to evaluate the aetiological role of CRP in AF. In our observational study (n = 86,424), high baseline CRP levels (>3 mg/L), compared with low CRP (<1 mg/L), were not significantly associated with AF risk (HR: 1.18; 95% CI: 0.99-1.40). High cumulative exposure to CRP (HR: 1.49; 95%CI: 1.01-2.21) was significantly associated with an increased risk of AF. Our meta-analysis suggested a positive association between elevated CRP levels and incident AF (relative risk: 1.27; 95% CI: 1.14-1.42). However, no significant association between genetically determined CRP and AF risk was observed in the MR analysis. CONCLUSION: Evidence from observational studies suggested that elevated serum CRP levels were positively associated with incident AF, while the causal effects of CRP on AF were not supported by the MR analysis. CLINICAL TRIAL REGISTRATION: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR-TNRC-11001489.

Sub-pocket small-hole drainage for pocket hematoma after cardiac device implantation.

AIMS: Pocket hematoma is a common complication associated with cardiac device implantation, but there are limited strategies to deal with this problem. We aimed to evaluate the effectiveness of sub-pocket small-hole drainage (SSD) as a new way to manage severe pocket hematoma. METHODS: A total of 11 patients with severe pocket hematoma were selected for this case series study. The SSD procedure was performed and wound healing was monitored. RESULTS: The SSD procedure was successfully performed on all 11 patients. The time window for SSD was 10-14 days (mean 12.0 ± 1.3 days) after cardiac device implantation. On average, 18.3 ± 2.3 ml of hematoma was drained , with a mean procedural time of 21.3 ± 2.6 min. The patients were followed up for 4-12 months and all pockets healed well, without any complications such as pocket infection, bleeding, device exposure, and electrode fracture. CONCLUSION: Sub-pocket small-hole drainage is an alternative approach for dealing with severe pocket hematoma after cardiac device implantation.

Anatomical insights into posterior wall isolation in patients with atrial fibrillation: A hypothesis to protect the esophagus.

INTRODUCTION: Left atrial posterior wall (LAPW) isolation may be performed as an additional atrial fibrillation (AF) ablation strategy based on pulmonary vein isolation. A modified posterior-inferior line (MPL) was proposed for reducing esophageal injury. The aim of this study was to evaluate the anatomical characteristics of the MPL, compared with the conventional posterior line (CPL). METHODS AND RESULTS: Multidetector computed tomography was performed in 102 consecutive AF patients (male/female = 60/42) preoperative, and the parameters were evaluated as follows: the distance from MPL and CPL to the esophagus, fat pad presence and thickness in the course of MPL and CPL, and the esophageal route below CPL. The average distance from the MPL to the esophagus was longer than from CPL to the esophagus (3.7 ± 1.5 vs. 1.7 ± 0.4 mm, p < .001). Proportion of fat pad was higher in the course of MPL than CPL. The myocardium tissue and fat pad under MPL was thicker than under CPL (2.9 ± 1.1 vs. 1.6 ± 0.3 mm, p < .001; 1.4 ± 0.6 vs. 0.9 ± 0.2 mm, p < .001), respectively. In patients whose esophagus was unconfined in a triangular space at the left inferior pulmonary vein level, the average distance from MPL to esophagus was longer than the confined patients (4.0 ± 1.7 vs. 3.2 ± 1.0 mm, p = .001). CONCLUSION: The MPL was far away from the esophagus with thicker myocardium tissue and more fat pad than the CPL; thus, MPL could serve as a favorable alternative in linear ablation for LAPW isolation.

Coexistence of sinus bradycardia and junctional tachycardia in a patient with fibrotic atrial cardiomyopathy.

A 65-year-old woman was referred for catheter ablation in the treatment of persistent tachycardia after surgery for atrial fibrillation and mitral regurgitation. Bipolar voltage mapping of both atria revealed that severe and extensive atrial fibrosis isolated the sinoatrial node from the atrioventricular junction and led to the coexistence of sinus bradycardia and persistent junctional tachycardia.

Tailored ablation index for pulmonary vein isolation according to wall thickness within the ablation circle.

BACKGROUND: Ablation index (AI), a novel lesion quality marker, includes contact force, time, and power of radiofrequency (RF) application, but not regional variation in wall thickness within the wide antral catheter ablation (WACA) circle. This study explored the relationships among AI target value, atrial wall thickness, and gap formation within the WACA circle in patients with paroxysmal atrial fibrillation (PAF). METHODS: We evaluated 102 consecutive patients (mean age, 65 ± 9 years) with PAF who underwent AI-guided WACA for ipsilateral pulmonary vein isolation (PVI). Each WACA circle was subdivided into eight segments, and overall 7143 RF applications were delivered, including 125 gaps in PVI ablation lines. For each RF tag within the ablation circle, we collected data on ablation lesion depth surrogates (time of application, delivery power, impedance drop, average contact force, force-time integral [FTI], and AI) and left atrial wall thickness measured by multidetector computer tomography scanning. RESULTS: The anterior and roof walls were the thickest segments of the ablation circle, in which 85.8% of gaps concentrated, while the posterior and inferior walls were the thinnest. Gap formation was significantly associated with FTI, AI, wall thickness, FTI/wall thickness, and AI/wall thickness. AI/wall thickness had the highest predictive value for gap formation, with a cutoff of 195.6 au/mm for effective ablation. CONCLUSIONS: In AI-guided PVI of PAF, AI/wall thickness by normalizing myocardial thickness variation along the WACA circle was a strong predictor of gap formation, with a target of 195.6 au/mm appearing suitable for effective ablation.

Lung Auscultation of Hospitalized Patients with SARS-CoV-2 Pneumonia via a Wireless Stethoscope.

Objective: SARS-CoV-2 (originally named COVID-2019) pneumonia is currently prevalent worldwide. The number of cases has increased rapidly but the auscultatory characteristics of affected patients and how to use it to predict who is most likely to survive or die are not available. This study aims to describe the auscultatory characteristics and its clinical relativity of SARS-CoV-2 pneumonia by using a wireless stethoscope. Material and methods: A cross-sectional, observational, single-center case series of 30 consecutive hospitalized patients with confirmed SARS-CoV-2 pneumonia at Leishenshan Hospital in Wuhan, China, were enrolled from March 9 to April 5, 2020. Clinical, laboratory, radiological, treatment data and lung auscultation were collected and analyzed. Lung auscultation was acquired by a wireless electronic stethoscope. Auscultatory characteristics of the moderate, severe, and critically ill patients were compared. Results: Kinds of crackles including fine crackles and wheezing were heard and recorded in these patients. Velcro crackles were heard in most critically ill patients (6/10). Besides, patients with Velcro crackles were all dead (6/6). There was no positive lung auscultatory finding in the moderate group and little positive lung auscultatory findings (4/10) in the severe group. Conclusion: Velcro crackles can be auscultated by this newly designed electronic wireless stethoscope in most critically ill patients infected by SARS-CoV-2 and predicts a poor prognosis. Moderate and severe patients without positive auscultatory findings may have a better prognosis.

Alternating and gradually changing narrow QRS complex tachycardia in a patient with heart failure: What is the mechanism?

A 23-year-old woman with palpitations for 9 years was referred for catheter ablation. ECG showed an irregular narrow complex tachycardia with alternating and gradually changing QRS morphologies after alternating and changing RR intervals, with a clear pattern of 2 alternating QRS complexes. An electrophysiology study was performed and confirmed that the mechanism of tachycardia was an automatic left-side His-Purkinje system (HPS) ventricular tachycardia. The gradually changing type-2 QRS complexes was the conduction delayed in the left anterior fascicle due to the short RR interval or the short left-side HH interval. Nine months after the index electrophysiology study, the patient encounter a progressive of heart failure with increased heart rate to 130-150 bpm during rest. Radiofrequency ablation was performed at the upper-septum for eliminating the tachycardia and resulted in complete atrioventricular block. A permanent pacemaker with left bundle branch pacing was implanted. Twelve months after the ablation, the enlarged heart shrink to normal with normal left ventricular ejection fraction. In conclusion, careful interpretation of the ECG can identify the sinus P waves followed by irregular narrow complexes, thus avoiding misdiagnosis and unnecessary treatment. Unifocal HPS tachycardia could present with alternating and gradually changing narrow QRS complexes tachycardia and lead to tachycardia cardiomyopathy. Electrophysiology study and catheter ablation were useful for the diagnosis and treatment of HPS tachycardia but with high risk of atrioventricular block. However, successfully elimination the tachycardia would resolve and reverse the enlarged heart and deteriorative heart function.

QRS complex axis deviation changing in catheter ablation of left fascicular ventricular tachycardia.

AIMS: The mechanisms of the QRS complex axis deviation changing of idiopathic left fascicular ventricular tachycardia (FVT) during or after radiofrequency catheter ablation were investigated in this study, which were still not well defined. METHODS AND RESULTS: In the index procedure, FVTs characterized by right bundle branch block configuration and left-axis deviation (LAD-FVT) were ablated at the VT exit site guided by the earliest ventricular activation with fused presystolic Purkinje potential (PP) in 234 consecutive patients. A new type of FVT characterized by right-axis deviation (RAD-FVT) was identified after successful elimination of the LAD-FVT in 12 patients, including 9 patients during the index procedure and 3 patients during follow-up. The QRS duration of RAD-FVT was shorter than that of LAD-FVT (115.3 ± 15.2 vs. 125.3 ± 16.4 ms, P = 0.006). The RAD-FVTs showed an earliest ventricle activation site localized at anterior fascicle area in 11 patients and anterior-median fascicle area in 1. However, the earliest PP during the RAD-FVT was still identified within the posterior fascicular network. Elimination of the RAD-FVTs was successfully achieved by applying radiofrequency current at a more proximal site within the left posterior fascicular network guided by the earliest PP. After a mean of 1.6 ± 0.8 ablation procedures and median follow-up of 132 (range 19-216) months since the last procedure, no recurrence was observed in any patients. CONCLUSION: The axis deviation changing of QRS complex in FVT may be attributed to the different exit sites of the reentry.

Acute conduction recurrence of mitral isthmus: Incidence, clinical characteristics, and implications.

BACKGROUND: Data on the incidence, clinical characteristics, and implications of acute conduction recurrence during mitral isthmus (MI) ablation are scarce. METHODS: MI ablation was performed in patients with atrial fibrillation. After confirming bidirectional conduction block, the acute conduction recurrence of MI was systematically evaluated. Clinical and electrophysiological characteristics were analyzed. RESULTS: A total of 66 consecutive patients in whom bidirectional conduction block of MI was achieved were prospectively enrolled in a single center. Acute conduction recurrence of MI developed in 12 (18.2%) patients within 14.2 ± 11.5 minutes after the confirmation of bidirectional conduction block. There were two recurrent conduction breakthrough sites of MI along the course of the great cardiac vein (4.5 ± 3.5 min) in two patients and 11 along the course of the ligament of Marshall (LOM) (16.0 ± 11.6 min, P = .035) in 11 patients. LOM accounted for most (84.6%, 11/13) acute MI conduction recurrence. MI length, total ablation time, and procedure time for MI were greater in patients with acute conduction recurrence than in those without acute conduction recurrence. During follow-up, arrhythmia recurrences were less observed in patients with acute conduction when compared to patients without acute conduction recurrence (0% vs 26.4%, P = .055). CONCLUSION: Acute conduction recurrence, predominantly due to recurrent LOM conduction, was a common phenomenon during MI ablation, and its evaluation should therefore be the focus to improve MI ablation efficacy and durability.

Clinical efficacy and safety of radiofrequency catheter ablation for atrial fibrillation in patients aged ≥80 years.

AIM: To evaluate the clinical safety and efficacy of radiofrequency catheter ablation for atrial fibrillation (AF) in patients aged ≥80 years. METHODS: A total of 333 AF patients aged ≥60 years were enrolled, who underwent contact force-guided radiofrequency catheter ablation with uninterrupted anticoagulation. All patients were followed-up for at least 12 months. Success was defined by the absence of episodes of AF/atrial tachycardia lasting more than 30 seconds after a 3-month blanking period, without antiarrhythmic drugs. RESULTS: Compared to patients aged 60-79 years (Group 2, n = 244), patients aged ≥80 years (Group 1, n = 89) were presented with higher rate of diabetes (36.0% vs 22.1%, P = .011), lower body mass index (23.4 ± 3.1 vs 24.9 ± 3.4 kg/m2 , P = .001), lower creatinine clearance (56.9 ± 16.5 vs 83.3 ± 24.5 mL/min, P < .001), higher CHA2 DS2 -VASc score (4.3 ± 1.3 vs 3.3 ± 1.4, P < .001), and HAS-BLED score (2.2 ± 0.8 vs 1.8 ± 0.8, P < .001). Wide antral pulmonary vein isolation was achieved in all patients, and there was no significant difference in procedure time, ablation time, fluoroscopy time, and complications rate between two age groups (P > .05). After a mean follow-up of 24.4 ± 9.6 months, the overall success rate was 78.2% in Group 1 and 78.9% in Group 2 (P = .622). CONCLUSIONS: Radiofrequency ablation with contact force sensing catheters for AF is safe and effective in selected patients aged ≥80 years.

miR-20b-5p attenuates hypoxia-induced apoptosis in cardiomyocytes via the HIF-1α/NF-κB pathway.

Chronic hypoxia is a common inducer of end-stage cardiovascular disease. In cells under hypoxia, the hypoxia-inducible factor-1 (HIF-1) plays a vital role in regulating downstream target genes. However, the mechanism of hypoxia in cardiomyocytes is still unclear. In this study, we aimed to identify novel downstream epigenetic targets of HIF-1α in cardiomyocytes under hypoxia. H9c2 cells were exposed to hypoxia condition, and quantitative real-time PCR analysis was performed to evaluate the expression of miR-20b-5p. The results indicated that the expression of miR-20b-5p was down-regulated in H9c2 cells under low oxygen condition. Meanwhile, HIF-1α overexpression further down-regulated the miR-20b-5p expression in H9c2 cells transfected with HIF-1α plasmids. In addition, Annexin-V-FITC/PI flow cytometry analysis suggested that overexpression of miR-20b-5p attenuated cell apoptosis under hypoxia condition in H9c2 cells. Western blot analysis showed that the hypoxia apparently increased Bax and cleaved-caspase-3, but decreased Bcl-2 expression in H9c2 cells, indicating that hypoxia-induced NF-κB signaling pathway activation is mediated by miR-20b-5p. Hypoxia-induced H9c2 cell apoptosis was reduced after HIF-1α knockdown as shown by the flow cytometry analysis. In conclusion, we identified that miR-20b-5p plays an important role in mediating cardiomyocytes apoptosis under hypoxia, which is mediated by the HIF-1/NF-κB signaling pathway.

Circular RNA Ttc3 regulates cardiac function after myocardial infarction by sponging miR-15b.

The apoptotic death of cardiomyocytes critically contributes to cardiac remodeling after myocardial infarction (MI). Circular RNAs (circRNAs) are important regulators for a variety of biological functions. Circ-Ttc3 represents one of the top highest expressed circRNAs in the heart; however, its role in MI remains unknown. Herein, we found that circ-Ttc3 was markedly upregulated in the ischemic myocardium and the cardiomyocytes subjected to hypoxic insult. Forced expression of circ-Ttc3 in cardiomyocytes counteracted hypoxia-induced ATP depletion and apoptotic death, in sharp contrast to circ-Ttc3 knockdown. Accordingly, experiments with AAV9-cTnt-mediated knockdown of cardiac circ-Ttc3 in a rat model of MI recapitulated the in vitro findings, and showed the deterioration of cardiac dysfunction after MI. Furthermore, we identified that circ-Ttc3 sponged an endogenous miR-15b-5p to sequester and inhibit its activity, leading to the increased Arl2 expression. Conversely, knockdown of Arl2 partially abolished the beneficial effects of circ-Ttc3 overexpression on ATP production and apoptosis of cardiomyocytes. Thus, our findings revealed the cardioprotective role of circ-Ttc3 in MI. The miR-15b-Arl2 regulatory cascade underlies the protection against MI-induced cardiomyocyte apoptosis by circ-Ttc3.

The importance of identifying conduction breakthrough sites across the mitral isthmus by elaborate mapping for mitral isthmus linear ablation.

AIMS: Mitral isthmus (MI) ablation is challenging. We hoped to close those conduction breakthrough sites (CBS) across the MI by elaborate mapping. METHODS AND RESULTS: After the initial linear ablation, elaborately mapping large areas above and below the MI line and inside the coronary sinus (CS) was sequentially performed to identify the CBS. The shortest distance from the CBS to the MI line was measured. The distant CBS (D-CBS) was identified as those CBS >5.0 mm away from the MI line. We prospectively enrolled 177 consecutive patients. Bidirectional conduction blockage across MI was obtained in 50 (28.2%) patients after the initial linear ablation and was achieved in additional 115 (65.0%) patients following elaborate mapping and reinforcement ablation. After initial linear ablation, 272 CBS (2.14 ± 0.99 CBS/person) were identified, and 226 (83.1%) of them were characterized as D-CBS, including 98 sites (36.0%) >10.0 mm and 39 sites (14.3%) >15.0 mm away. Endocardial and epicardial (CS) reinforcement ablation eliminated 119/272 (43.8%) and 58/272 (21.3%) CBS, respectively. Among the 177 eliminated CBS, 138 D-CBS (78.0%, 11.2 ± 5.6 mm) were confirmed in 95 (74.8%) patients. Moreover, CBS along the course of ligament of Marshall was closed by endocardial ablation more frequently than that along the course of great cardiac vein (52.6%% vs. 35.1%, P = 0.004). Eventually, CS ablation was required only in 64 (38.8%) patients. CONCLUSION: Distant CBS, accounted for the majorities of the residual conduction across the MI after initial ablation, could be effectively identified and accurately eliminated by elaborate mapping and ablation around the MI ablation line.

Comparison of transthoracic echocardiography with computed tomography in evaluation of pulmonary veins.

BACKGROUND: Transesophageal echocardiography may be used to assess pulmonary veins for atrial fibrillation ablation. No study focused on the role of transthoracic echocardiography (TTE) in evaluating the diameter and anatomy of pulmonary veins. METHODS: Among 142 atrial fibrillation patients (57.7% men; mean age, 60.5) hospitalised for catheter ablation, we assessed pulmonary veins and compared the measurements by TTE with cardiac computed tomography (CT) before ablation. Among 17 patients who had follow-up examinations, the second measurements were also studied. RESULTS: TTE identified and determined the diameters of 140 (98.6%) right and 140 (98.6%) left superior PVs, and 136 (95.7%) right and 135 (95.1%) left inferior PVs. A separate middle PV ostia was identified in 14 out of the 22 patients (63.6%) for the right side and in 2 out of 4 (50.0%) for the left side. The PV diameters before ablation assessed by CT vs. TTE were 17.96 vs. 18.07 mm for right superior, 15.92 vs. 15.51 mm for right inferior, 18.54 vs. 18.42 mm for left superior, and 15.56 vs. 15.45 mm for left inferior vein. The paired differences between the assessments of CT and TTE were not significant (P ≥ 0.31) except for the right inferior vein with a CT-minus-TTE difference of 0.41 mm (P = 0.018). The follow-up PV diameters by both CT (P ≥ 0.069) and TTE (P ≥ 0.093) were not different from baseline measurements in the 17 patients who had follow-up measurements. CONCLUSIONS: With a better understanding of PV anatomy in TTE imaging, assessing PV diameters by non-invasive TTE is feasible. However, the clear identification of anatomic variation might still be challenging.