RV1+RV3 Index to Differentiate Idiopathic Ventricular Arrhythmias Arising From Right Ventricular Outflow Tract and Aortic Sinus of Valsalva: A Multicenter Study.

BACKGROUND: This study aimed to investigate the predictive value of parameters of every precordial lead and their combinations in differentiating between idiopathic ventricular arrhythmias (IVAs) from the right ventricular outflow tract and aortic sinus of Valsalva (ASV). METHODS AND RESULTS: Between March 1, 2018, and December 1, 2021, consecutive patients receiving successful ablation of right ventricular outflow tract or ASV IVAs were enrolled. The amplitude and duration of the R wave and S wave were measured in every precordial lead during IVAs. These parameters were either summed, subtracted, multiplied, or divided to create different indexes. The index with the highest area under the curve to predict ASV IVAs was developed, compared with established indexes, and validated in an independent prospective multicenter cohort. A total of 150 patients (60 men; mean age, 45.3±16.4 years) were included in the derivation cohort. The RV1+RV3 index (summed R-wave amplitude in leads V1 and V3) had the highest area under the curve (0.942) among the established indexes. An RV1+RV3 index >1.3 mV could predict ASV IVAs with a sensitivity of 95% and a specificity of 83%. Its predictive performance was maintained in the validation cohort (N=109). In patients with V3 R/S transition, an RV1+RV3 index >1.3 mV could predict ASV IVAs, with an area under the curve of 0.892, 93% sensitivity, and 75% specificity. CONCLUSIONS: The RV1+RV3 index is a simple and novel criterion that accurately differentiates between right ventricular outflow tract and ASV IVAs. Its performance outperformed established indexes, making it a valuable tool in clinical practice.

Liquid Nitrogen Cryoballoon Ablation System for Paroxysmal Atrial Fibrillation: A Multicenter, Prospective, Single-Arm Clinical Trial.

Background: Cryoballoon ablation (CBA) has emerged as an effective treatment for atrial fibrillation (AF). Objectives: This study sought to assess the performance of a novel liquid nitrogen-driven CBA system and evaluate its safety and efficacy in the treatment of drug-resistant paroxysmal atrial fibrillation (PAF). Methods: This was a prospective multicenter single-arm clinical trial with 10 participating tertiary hospitals enrolling 176 patients with PAF. All participants received liquid nitrogen-driven CBA developed by the Cryofocus Medtech Company. Scheduled follow-up was performed before discharge and 3 months, 6 months, and 12 months after CBA. The primary endpoints were defined as 1) treatment success (freedom from antiarrhythmic drugs and atrial tachycardia at 12 months after CBA); and 2) immediate success rate of pulmonary vein isolation. The safety endpoint was the incidence of device- and procedure-related adverse events (AEs) and all-cause mortality. Results: A total of 172 participants were included, with an average age of 59.22 ± 9.25 years and 99 (57.56%) of them men. Immediate success rate was 97.67% (95% CI: 94.15%-99.36%) and 12-month treatment success rate was 82.56% (95% CI: 76.89%-88.23%), including a late recurrence rate of 13.61%. Incidences of device- and procedure-related AEs were 2.27% and 25.00%, respectively. Phrenic nerve palsy (PNP) occurred in 6 patients, of which 5 recovered during follow-up. Although the incidence of total severe AEs was 17.05%, including an all-cause mortality of 0.57%, only 1 case of permanent PNP was related to the CBA procedure. Conclusions: This premarketing prospective multicenter single-arm clinical trial demonstrated that the liquid nitrogen cryoablation system is safe and effective in the treatment of PAF.

Circumferential Pulmonary Vein Isolation With vs Without Additional Low-Voltage-Area Ablation in Older Patients With Paroxysmal Atrial Fibrillation: A Randomized Clinical Trial.

Importance: The overall success rate of circumferential pulmonary vein isolation (CPVI) treatment in patients with paroxysmal atrial fibrillation (AF) remains suboptimal, especially in older patients. Objective: To explore the incremental benefit of low-voltage-area ablation after CPVI in older patients with paroxysmal AF. Design, Setting, and Participants: This randomized clinical trial was an investigator-initiated trial to compare the efficacy of additional low-voltage-area ablation beyond CPVI vs CPVI alone in older patients with paroxysmal AF. Participants were patients aged 65 to 80 years with paroxysmal AF who were referred for catheter ablation. They were enrolled in 14 tertiary hospitals in China from April 1, 2018, to August 3, 2020, and follow-up occurred through August 15, 2021. Interventions: Patients were randomized (1:1) to undergo CPVI plus low-voltage-area ablation or CPVI alone. Low-voltage areas were defined as areas with amplitude less than 0.5 mV in more than 3 adjacent points. If low-voltage areas existed, additional substrate ablation was performed in the CPVI plus group but not the CPVI alone group. Main Outcomes and Measures: The primary end point of the study was freedom from atrial tachyarrhythmia as documented by electrocardiogram during a clinical visit or lasting longer than 30 seconds during Holter recordings occurring after a single ablation procedure. Results: Among 438 patients who were randomized (mean [SD] age, 70.5 [4.4] years; 219 men [50%]), 24 (5.5%) did not complete the blanking period and were not included for efficacy analysis. After a median follow-up of 23 months, the recurrence rate of atrial tachyarrhythmia was significantly lower in the CPVI plus group (31/209 patients, 15%) compared with the CPVI alone group (49/205, 24%; hazard ratio [HR], 0.61; 95% CI, 0.38-0.95; P = .03). In subgroup analyses, among all patients with low-voltage area, CPVI plus substrate modification was associated with a 51% decreased risk of ATA recurrence compared with CPVI alone (HR, 0.49; 95% CI, 0.25-0.94; P = .03). Conclusions and Relevance: This study found that additional low-voltage-area ablation beyond CPVI decreased the ATA recurrence in older patients with paroxysmal AF compared with CPVI alone. Our findings merit further replication by larger trials with longer follow-up. Trial Registration: ClinicalTrials.gov Identifier: NCT03462628.

Intracardiac echocardiographic imaging with a cartosound module for guidance of left atrial appendage closure: a comparative study with transesophageal echocardiographic imaging.

PURPOSE: In most clinical trials, intracardiac echocardiography (ICE) has provided fewer views than the four standard views provided by transesophageal echocardiography (TEE) when assessing left atrial appendage closure (LAAC) devices. This study aimed to determine if ICE guided by the CartoSound system achieve adequate high-quality views and similar clinical outcomes as TEE during LAAC. METHODS: This study prospectively enrolled 202 patients who underwent LAAC using either ICE (n = 69), TEE (n = 121), or a combination of ICE and TEE (n = 12) as the procedural imaging under local anesthesia. A novel multi-angled "FLAVOR" approach was used for assessment in the ICE group. RESULTS: ICE allowed visualization of the implanted devices in all patients at all proposed angles with long-axis views while two-dimensional (2D) TEE showed short-axis views in 1 or 2 angles in 24.2% of cases, which was more prevalent when the pulmonary ridge was covered by the occluder. In the combined ICE-TEE cohort, 2D-TEE failed to detect peri-device leak in 1 patient. The complication rates were similar between the ICE and TEE groups. Shorter fluoroscopy time, lower radiation dose and contrast usage were founded in the ICE group. At first TEE follow-up, the rate and degree of peri-device leak were similar between the ICE and TEE groups. CONCLUSION: A systematic ICE protocol using a CartoSound module to guide LAAC was reliable for comprehensive long-axis imaging assessment compared with 2D/3D TEE under local anesthesia with a shorter fluoroscopy time, lower radiation dose, and less use of contrast.

Reduced- or Half-Dose Rivaroxaban Following Left Atrial Appendage Closure: A Feasible Antithrombotic Therapy in Patients at High Risk of Bleeding?

The optimal antithrombotic strategy after percutaneous left atrial appendage closure (LAAC) has not yet been established. The advisability of administering low-dose direct oral anticoagulation after LAAC to patients at high risk of bleeding is uncertain. Thus, in the present study, we evaluated the safety and effectiveness of reduced-(15 mg) or half-dose rivaroxaban (10 mg) versus warfarin regarding real-world risks of thromboembolism, bleeding, and device-related thrombosis (DRT) after LAAC. Patients with non-valvular atrial fibrillation and HASBLED ≥ 3 who had undergone successful LAAC device implantation from October 2014 to April 2020 were screened and those who had received 10 mg or 15 mg rivaroxaban or warfarin therapy were enrolled. The patients were followed up 45 days and 6 months after LAAC to evaluate outcomes, including death, thromboembolism, major bleeding, and DRT. Of 457 patients with HASBLED ≥ 3 who had undergone LAAC, 115 had received warfarin and 342 rivaroxaban (15 mg: N = 164; 10 mg: N = 178). There were no significant differences in the incidence of thromboembolism or DRT between the warfarin and both doses of rivaroxaban groups (all p > 0.05). The incidence of major bleeding was significantly higher in the warfarin group than in either the reduced- or half-dose rivaroxaban groups (warfarin vs. rivaroxaban 15 mg: 2.6% vs. 0%, p = 0.030; warfarin vs. rivaroxaban 10 mg: 2.6% vs. 0%, p = 0.038). Either reduced- or half-dose rivaroxaban may be an effective and safe alternative to warfarin therapy in patients with LAAC and who are at high risk of bleeding, the risk of thromboembolism being similar and of major bleeding lower for both doses of rivaroxaban.

Rationale and study design for empirical additional lesions for premature ventricular complex from the outflow tract: a multi-center, prospective randomized trial (EASE-PVC study).

BACKGROUND: Late recurrence after ablation remains a significant issue in patients with premature ventricular complexes (PVCs) who undergo catheter ablation. In this study, we aimed to test the hypothesis that empirical additional ablation (EAA) would improve the long-term control of PVCs from outflow tracts (OT-PVCs) compared with the approach of limited single point ablation at the assumptive location. METHODS: EASE-PVC study (ChiCTR2200055340) is a prospective multi-center, randomized, and controlled trial designed to assess the effectiveness and safety of empirical additional ablation in patients with OT-PVCs. After successful elimination of OT-PVCs, the patients will be randomized into two groups. In patients randomized to the EAA group, additional lesion applications at sites surrounding the successful ablation site will be delivered empirically. For patients randomized to the control group, no additional empiric ablation will be performed around the successful ablation site. The primary endpoint will be freedom from PVC recurrence at 3 months following ablation, without antiarrhythmic drug therapy. CONCLUSIONS: The EASE-PVC study is designed to compare the effectiveness and safety of two different strategies for ablation in patients with OT-PVCs, namely empirical additional ablation strategy versus conventional single point ablation strategy. This prospective, multi-center, and randomized controlled trial, with comparative data evaluating procedural and long-term follow-up results, aims to elucidate the superiority of empirical additional ablation for the long-term control of OT-PVCs compared with the traditional single point ablation strategy. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trials Registry Identifier: ChiCTR2200055340.

Serine active site containing protein 1 depletion alters lipid metabolism and protects against high fat diet-induced obesity in mice.

OBJECTIVE: Although the serine active site containing 1 (SERAC1) protein is essential for cardiolipin remodeling and cholesterol transfer, its physiological role in whole-body energy metabolism remains unclear. Thus, we investigated the role of SERAC1 in lipid distribution and metabolism in mice. METHODS: CRISPR/Cas9 was used to create homozygous Serac1 knockout mice. A range of methods, including electron microscopy, histological analysis, DNA sequencing, glucose and insulin tolerance tests, and biochemical analysis of serum lipid levels, were used to assess lipid distribution and rates of lipid synthesis in mice. RESULTS: We found that Serac1 depletion in mice prevented high-fat diet-induced obesity but did not affect energy expenditure. The liver was affected by Serac1 depletion, but adipose tissues were not. Serac1 depletion was shown to impair cholesterol transfer from the liver to the serum and led to an imbalance in cholesterol distribution. The livers from mice with Serac1 depletion showed increased cholesterol synthesis because the levels of cholesterol synthesis enzymes were upregulated. Moreover, the accumulation of hepatic lipid droplets in mice with Serac1 depletion were decreased, suggesting that SERAC1 depletion may decrease the risk for hepatic steatosis in high fat diet-induced mice. CONCLUSION: Our findings demonstrate that SERAC1 can serve as a potential target for the treatment or prevention of diet-induced hepatic lipid metabolic disorders.

Premature Ventricular Contractions From the Left Anterior Fascicle: Electrocardiographic and Electrophysiological Characteristics, Mapping Strategy, and Immediate and Long-Term Catheter Ablation Results.

Background: Left anterior fascicle (LAF) premature ventricular contractions (PVC) are rarely reported. We described the electrocardiographic and electrophysiological characteristics of PVCs originating from LAF and evaluated the results of catheter ablation. Methods: The baseline AH and HV intervals were recorded during normal sinus rhythm (NSR), and the HV interval of LAF-PVC was measured during the procedure. During the index procedure, the conduction interval from the earliest Purkinje potential (PP) site to the His was labeled as time A, the conduction interval from the earliest site to the onset of the QRS as time B, then the HV interval during NSR (HV NSR ) is A + B, and the HV interval during PVC (HV PVC ) is B-A; a predicted PP time was calculated using HV NSR and HV PVC . The calculated formula is as follows: Predicted target PP = (HV NSR + HV PVC )/2. During the repeat procedure, the mapping strategy only focuses on the earliest retrograde PP due to the injury or block of LAF sustained at the index procedure. Results: Notably, 24 patients with LAF-PVC were included. The ECG characteristics of PVC exhibited right bundle branch block (RBBB) morphology with right-axis deviation (RAD) in 18 patients and only RAD in 6 patients. The QRS durations of NSR and PVC were 78.8 ± 7.9 and 106.8 ± 12.3 ms, respectively. There was no significant difference between the predicted and mapped PP site (31.5 ± 8.1 vs. 30.6 ± 7.8 ms; P = 0.17). There was a significant difference between the mean axis deviation before and after ablation (46.3 ± 25.4° vs. 18.3 ± 44.1°; P = 0.001); however, only 10 patients had a complete LAF block. Eight patients had a recurrence, the QRS morphology of LAF-PVC became narrower (95.9 ± 17.2 vs. 105.3 ± 16.9 ms, P = 0.003), and 4 patients's PVC QRS morphology was similar to NSR. During the repeat procedure, the earliest retrograde PP interval was longer than the index procedure in four patients (12.0 ± 1.9 vs. 37.8 ± 1.1 ms; P < 0.001). Conclusion: The target PP site for ablation of the LAF region can be calculated using the HV interval during NSR and PVC at the index procedure. The mapping strategy at repeat procedures focused on the earliest retrograde PP interval.

Outcome and safety of intracardiac echocardiography guided left atrial appendage closure within zero-fluoroscopy atrial fibrillation ablation procedures.

BACKGROUND: Simultaneous atrial fibrillation (AF) catheter ablation and left atrial appendage closure (LAAC) are sometimes recommended for both rhythm control and stroke prevention. However, the advantages of intracardiac echocardiography (ICE) guidance for this combined procedure have been scarcely reported. We aim to evaluate the clinical outcomes and safety of ICE-guided LAAC within a zero-fluoroscopy catheter ablation procedure. METHODS AND RESULTS: From April 2019 to April 2020, 56 patients with symptomatic AF underwent concomitant catheter ablation and LAAC. ICE with a multi-angled imaging protocol mimicking the TEE echo windows was used to guide LAAC. Successful radiofrequency catheter ablation and LAAC were achieved in all patients. Procedure-related adverse event rate was 3.6%. During the 12-month follow-up, 75.0% of patients became free of arrhythmia recurrences and oral anticoagulants were discontinued in 96.4% of patients. No ischemic stroke occurred despite two cases of device-related thrombosis versus an expected stroke rate of 4.8% based on the CHA2 DS2 -VASc score. The overall major bleeding events rate was 1.8%, which represented a relative reduction of 68% versus an expected bleeding rate of 5.7% based on the HAS-BLED score of the patient cohort. The incidence of iatrogenic atrial septal defect secondary to single transseptal access dropped from 57.9% at 2 months to 4.2% at 12 months TEE follow-up. CONCLUSION: The combination of catheter ablation and LAAC under ICE guidance was safe and effective in AF patients with high stroke risk. ICE with our novel protocol was technically feasible for comprehensive and systematic assessment of device implantation.

Assessment of High-Power Catheter Ablation in Patients With Atrial Fibrillation: A Meta-Analysis.

Background: High-power radiofrequency (RF) catheter ablation was considered as a promising alternative strategy to conventional-power ablation in the treatment of patients with atrial fibrillation (AF). This study sought to compare the efficacy and safety of high-power energy delivery to that of conventional-power setting in AF catheter ablation. Methods: We performed a systematic review of relevant literature in Pubmed, Embase, Cochrane library, and Google Scholar database. Sixteen eligible studies totaling 3,307 patients (1,929 for high-power ablation; 1,378 for conventional-power ablation) met inclusion criteria. Results: During a median 12 month follow-up, high-power ablation showed a significantly higher AF/atrial tachycardia-free survival rate in comparison with conventional-power ablation (risk ratio [RR] 1.09, 95% CI 1.02 to 1.15, p = 0.008). Notably, a high-power strategy convincingly decreased the procedure time (weighted mean difference [WMD] -46.11 min, 95% CI -59.15 to -33.07, p < 0.001) and RF ablation time (WMD -19.19 min, 95% CI -24.47 to -13.90, p < 0.001), along with reduced fluoroscopy time (WMD -7.82 min, 95% CI -15.13 to -0.68, p = 0.036). In addition, there was no perceptible difference in the potential risk of procedure-related complications between these two approaches (RR 0.81, 95% CI 0.48 to 1.37, p = 0.428). Conclusions: High-power RF catheter ablation was associated with an improvement in long-term sinus rhythm maintenance for treatment of AF, without exacerbating the risk of adverse events during the procedure. Impressively, high-power pulmonary vein isolation had the potential to shorten the application duration and minimize fluoroscopic exposure.

Catheter ablation of premature ventricular complexes associated with left ventricular false tendons.

BACKGROUND: Clinical studies have suggested that there is a significant correlation between left ventricular (LV) false tendon and premature ventricular complexes (PVCs). OBJECTIVE: This study aimed to investigate the electrophysiological characteristics and the outcome of radiofrequency catheter ablation (RFCA) for this category of PVCs. METHODS: From a total of 2284 patients with idiopathic PVCs who underwent catheter ablation at 6 institutions in China, intracardiac echocardiography (ICE) was used during the procedure in 346 cases; 10 patients (2.9%) with PVCs associated with false tendon were retrospectively reviewed and enrolled in the present study. Activation mapping and pace mapping were performed to localize the origin of PVCs. ICE was used in all patients. If the false tendon was directly visualized and identified, we attempted to identify the distinct relationship with the PVC origin. RESULTS: The PVCs were successfully eliminated by ablation in all patients. The target sites were confirmed to be related to false tendon. The origin of PVCs was located at the attachment of the false tendon to the papillary muscle, LV septum, or LV apex. At the target site, high-frequency Purkinje potentials were observed preceding local ventricular activation in 7 patients. CONCLUSION: LV false tendon can be associated with PVCs, which can be cured by RFCA. An ICE-guided electroanatomical approach should be considered to improve the safety and feasibility of this procedure.

Evaluation of the Criteria to Distinguish Left Bundle Branch Pacing From Left Ventricular Septal Pacing.

OBJECTIVES: This study sought to assess the predictive value of the proposed electrocardiogram and intracardiac electrogram characteristics for confirmation of left bundle branch (LBB) capture. BACKGROUND: Previously proposed criteria to distinguish left bundle branch pacing (LBBP) and left ventricular septum (LVS) pacing (LVSP) have not been fully validated. METHODS: A His bundle pacing lead, an LBBP lead, and a multielectrode catheter at the LVS were placed. Direct LBB capture was defined as demonstration of retrograde His potential on the His bundle pacing lead and/or anterograde left conduction system potentials on the multielectrode catheter during LBBP. The routinely used parameters-His, LBB potential, time from stimulus to peak ventricular activation (Stim-LVAT), and paced QRS morphology during LVSP and LBBP at various depths and outputs were analyzed. RESULTS: Thirty patients (21 non-left bundle branch block [LBBB], 9 LBBB) who demonstrated direct LBB capture using the defined criteria were included. The proportion of paced right bundle branch block was 100% during LBB capture in all patients compared to 23.4% in non-LBBB and 44.4% in LBBB during LVSP. LBB potential was recorded in all patients during intrinsic rhythm (non-LBBB group) or His corrective pacing in LBBB. Paced QRS duration was longer during selective LBBP compared to nonselective LBBP or LVSP only. All patients with characteristics of selective LBBP or abrupt decrease in Stim-LVAT of ≥10 ms demonstrated LBB capture. CONCLUSIONS: Direct LBB capture can be confirmed by recording retrograde His potential and anterograde left conduction system potentials. Abrupt decrease in Stim-LVAT of ≥10 ms and demonstration of selective LBBP could be used as simple criteria to confirm LBB capture.

Delayed pericardial effusion after left atrial appendage closure with the LAmbre device: Importance of a fully open umbrella.

INTRODUCTION: We aimed to investigate whether a modified implantation method facilitating a fully open umbrella can reduce the pericardial effusion/pericardial tamponade (PE/PT) rate after left atrial appendage closure (LAAC) with the LAmbre device compared with the conventional method (CM) in patients with non-valvular atrial fibrillation (NVAF). METHODS AND RESULTS: Patients with NVAF who received either isolated LAAC or combined catheter ablation and LAAC using the LAmbre device at the First Affiliated Hospital of Wenzhou Medical University from January 2018 to December 2019 were enrolled. CM was used for device implantation in the initial 59 patients, while a modified method (MM) was used in the remaining 165 patients. Successful implantation was achieved in 98.3% of patients in the CM group and 98.8% in the MM group. A higher rate of a fully open umbrella (98.8% vs. 69%, p < .001), less requirement for recapture (46% vs. 62.1%, p = .036), and a lower incidence of delayed PE/PT (1.2% vs. 8.6%, p = .005) were found in the MM group compared with the CM group. All of the five delayed PT events occurred in patients with combined treatment. An umbrella that was not fully open was the only factor associated with delayed PE/PT events in a multivariable Cox model. CONCLUSIONS: LAAC with the LAmbre device using an MM significantly increases the rate of a fully open umbrella and decreases the requirement for recapture and the incidence of delayed PE/PT. This method is more effective in patients with combined treatment.

Impact of QRS morphology on response to conduction system pacing after atrioventricular junction ablation.

AIMS: His-Purkinje conduction system pacing (HPCSP) utilizing His (HBP) or left bundle branch pacing (LBBP) in patients with atrial fibrillation (AF) and wide QRS duration has not been well studied. We assessed the benefit of left bundle branch block (LBBB) correction during HPCSP in AF patients undergoing atrioventricular junction (AVJ) ablation with LBBB, compared with those with narrow QRS duration. METHODS AND RESULTS: This is an observational study in consecutive patients with typical LBBB or narrow QRS duration in whom we attempted HPCSP after AVJ ablation for refractory AF with a left ventricular ejection fraction (LVEF) ≤ 50%. Echocardiographic responses and clinical outcomes were assessed at baseline and during 1 year of follow-up. A total of 178 patients were enrolled, of which 170 achieved AVJ ablation + permanent HPCSP (age 69.3 ± 10.1 years; LVEF 34.3 ± 7.7%), 133 (78.2%) patients had a narrow QRS duration, and 37 (21.2%) had an LBBB. The QRS duration changed from a baseline of 159.7 ± 16.6 ms to a paced QRS duration of 110.4 ± 12.7 ms in the LBBB cohort and from 95.6 ± 10.4 to 100.8 ± 14.5 ms (both P < 0.001) in the narrow QRS cohort after AVJ ablation and pacing. Compared with the narrow QRS cohort, the LBBB cohort showed a greater absolute increase in LVEF (+22.3% vs. +14.2%, P < 0.001), higher super responder rate (71.4% vs. 49.2%, P = 0.011), and greater New York Heart Association (NYHA) class improvement (-1.9 vs. -1.4, P < 0.001) at 1 year. CONCLUSION: Patients with LBBB have greater improvement in LVEF and NYHA class function than patients with narrow QRS from HPCSP after AVJ ablation.

Melatonin against Myocardial Ischemia-Reperfusion Injury: A Meta-analysis and Mechanism Insight from Animal Studies.

AIMS: Myocardial reperfusion damage after severe ischemia was an important issue during a clinical practice. However, the exacted pathogenesis involved remained unclear and also lacks effective interventions. Melatonin was identified to exert protective effects for alleviating the myocardial I/R injury. This meta-analysis was determined to evaluate the efficacy of melatonin treatment against reperfusion insult and further summarize potential molecular and cellular mechanisms. METHODS AND RESULTS: 15 eligible studies with 211 animals (108 received melatonin and 103 received vehicle) were included after searching the databases of PubMed, MEDLINE, Embase, and Cochrane. Pretreatment with melatonin was associated with a significant lower infarct size in comparison with vehicle in myocardial I/R damage (WMD: -20.45, 95% CI: -25.43 to -15.47, p < 0.001; I 2 = 91.4%, p < 0.001). Evidence from subgroup analyses and sensitivity analysis indicated the robust and consistent cardioprotective effect of melatonin, while the metaregression also did not unmask any significant interactions between the pooled estimates and covariates (i.e., sample size, state, species, study type, route of administration, and duration of reperfusion, along with timing regimen of pretreatment). Accordingly, melatonin evidently increased EF (WMD: 17.19, 95% CI: 11.08 to 23.29, p < 0.001; I 2 = 77.0%, p < 0.001) and FS (WMD: 14.18, 95% CI: 11.22 to 17.15, p < 0.001; I 2 = 3.5%, p = 0.387) in the setting of reperfusion damage. CONCLUSIONS: Melatonin preadministration conferred a profound cardioprotection against myocardial I/R injury in preclinical studies.

Association between mitochondrial DNA haplogroup variation and coronary artery disease.

BACKGROUND AND AIMS: Mitochondrial DNA (mtDNA) haplogroups have been associated with the development of coronary artery disease (CAD) in European populations. However, the specific mtDNA haplogroups associated with CAD have not been investigated in Chinese populations. METHODS AND RESULTS: Here, we carried out a case-control study including 1036 and 481 CAD patients and 973 and 511 geographically matched asymptomatic control subjects in southern and northern China, respectively. After adjusting for age and gender, our results indicated that mtDNA haplogroups are not associated with the occurrence of CAD and its subcategories, acute coronary syndromes and stable coronary heart disease, in both southern and northern Chinese populations. By focusing on the southern Chinese population, we further revealed that mtDNA haplogroups are not associated with CAD severity. Type 2 diabetes (T2D) and hypertension are two key driving factors for the development of CAD, nonetheless, we found that the frequencies of the 12 studied mtDNA haplogroups did not differ between patients with and without T2D or hypertension. CONCLUSION: mtDNA haplogroups are not associated with the occurrence of CAD or its subcategories in Chinese populations. Other factors such as environment and nuclear genetic background may contribute to the occurrence of CAD.

Circumferential pulmonary vein antrum ablation for the treatment of paroxysmal atrial fibrillation: A randomized controlled trial.

BACKGROUND: It remains unclear whether the curative result of paroxysmal atrial fibrillation (PAF) is a result of pulmonary vein (PV) isolation, PV antrum modification (PVAM), or both. We hypothesized that sufficient antrum modification (PVAM) is as important as PV isolation (PVI) for atrial fibrillation (AF) control and that PVAM can be evaluated by quantified lesion deployment using a force-sensing catheter. METHODS AND RESULTS: Patients of symptomatic PAF were randomly assigned 2:1 into a PVAM group or a circumferential PV isolation (CPVI) group. In the PVAM group, circumferential quantitative ablation evaluated by automatical VisiTag module was performed. In the CPVI group, conventional circumferential ablation was performed to achieve the end point of all-PV isolation. In total, 180 patients with PAF were enrolled and randomly assigned to either the PVAM group (n = 120) or the CPVI group (n = 60). A total of 179 patients successfully underwent ablation. In the PVAM group, 68 patients achieved all PVI (PVAM-PVI), while 51 did not (PVAM-non-PVI). At 18 months, there was no significant difference in the maintenance of sinus rhythm between the PVAM and CPVI groups (84.9 vs 79.7%, P = .382). The PVAM-PVI subgroup demonstrated a higher arrhythmia-free survival compared with the PVAM-non-PVI subgroup (92.6 vs 74.5%, P = .006) and the CPVI group (92.6 vs 79.7%, P = .036). CONCLUSIONS: The trial shows that sufficient force-sensing guided PVAM can result in satisfying outcomes in PAF patients. Notably, sufficient PVAM with all-PV isolated will further increase the success rate.

Feasibility and Efficacy of His Bundle Pacing or Left Bundle Pacing Combined With Atrioventricular Node Ablation in Patients With Persistent Atrial Fibrillation and Implantable Cardioverter-Defibrillator Therapy.

Background Persistent atrial fibrillation may lead to a higher probability of inappropriate shocks in heart failure patients with an implantable cardioverter-defibrillator (ICD). The aim of this study was to evaluate the impact of His-Purkinje conduction system pacing combined with atrioventricular node ablation in improving heart function and preventing inappropriate shock therapy in these patients. Methods and Results A total of 86 consecutive patients with persistent atrial fibrillation and heart failure who had indications for ICD implantation were enrolled from January 2010 to March 2018. His-Purkinje conduction system pacing with ICD and atrioventricular node ablation was attempted in 55 patients, and the remaining patients underwent ICD implantation only. Left ventricular (LV) ejection fraction, LV end-systolic volume, New York Heart Association (NYHA) classification, shock therapies, and drug therapy were assessed during follow-up. Overall, 31 patients received ICD implantation with optimal drug therapy (group 1). atrioventricular node ablation combined with His-Purkinje conduction system pacing was successfully achieved in 52 patients (group 2). During follow-up, patients in group 2 had lower incidence of inappropriate shock (15.6% versus 0%, P<0.01) and adverse events (P=0.011). Meanwhile, improvement in LV ejection fraction and reduction in LV end-systolic volume were significantly higher in group 2 than in group 1 (15% versus 3%, P<0.001; and 40 versus 2 mL, P<0.01, respectively). NYHA functional class improved in both groups from a baseline 2.57±0.68 to 1.73±0.74 in group 1 and 2.73±0.59 to 1.42±0.53 in group 2 (P<0.01). Conclusions His-Purkinje conduction system pacing combined with atrioventricular node ablation is feasible and safe with a high success rate in persistent atrial fibrillation patients with heart failure and ICD indication. It can significantly reduce the incidence of inappropriate shocks and improve LV function.

Young Patients with Unknown Stroke and Little P Wave in ECG.

Here we report two young patients with atrial fibrillation/atrial flutter complicated with cardiogenic cerebral embolism. Electrophysiological study revealed a large area of low-voltage zone or area of electric silence in both sides of the atrium during restoration of sinus rhythm, and the echocardiogram showed loss of mechanical function of the atrium. The electrical-mechanical dysfunction of the atrium was considered to be the cause of embolic event in this type of patient who was "very low" stroke risk atrial fibrillation or atrial flutter. The idiopathic, fibrotic atrial cardiomyopathy may be underlying in these patients.

Long-term outcomes of His bundle pacing in patients with heart failure with left bundle branch block.

OBJECTIVES: His bundle pacing (HBP) can potentially correct left bundle branch block (LBBB). We aimed to assess the efficacy of HBP to correct LBBB and long-term clinical outcomes with HBP in patients with heart failure (HF). METHODS: This is an observational study of patients with HF with typical LBBB who were indicated for pacing therapy and were consecutively enrolled from one centre. Permanent HBP leads were implanted if the LBBB correction threshold was <3.5V/0.5 ms or 3.0 V/1.0 ms. Pacing parameters, left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV) and New York Heart Association (NYHA) Class were assessed during follow-up. RESULTS: In 74 enrolled patients (69.6±9.2 years and 43 men), LBBB correction was acutely achieved in 72 (97.3%) patients, and 56 (75.7%) patients received permanent HBP (pHBP) while 18 patients did not receive permanent HBP (non-permanent HBP), due to no LBBB correction (n=2), high LBBB correction thresholds (n=10) and fixation failure (n=6). The median follow-up period of pHBP was 37.1 (range 15.0-48.7) months. Thirty patients with pHBP had completed 3-year follow-up, with LVEF increased from baseline 32.4±8.9% to 55.9±10.7% (p<0.001), LVESV decreased from a baseline of 137.9±64.1 mL to 52.4±32.6 mL (p<0.001) and NYHA Class improvement from baseline 2.73±0.58 to 1.03±0.18 (p<0.001). LBBB correction threshold remained stable with acute threshold of 2.13±1.19 V/0.5 ms to 2.29±0.92 V/0.5 ms at 3-year follow-up (p>0.05). CONCLUSIONS: pHBP improved LVEF, LVESV and NYHA Class in patients with HF with typical LBBB.