Fasting plasma glucose level and in-hospital cardiac arrest in patients with acute coronary syndrome: findings from the CCC-ACS project.

BACKGROUND: The prognosis of patients with coronary artery disease is adversely affected by elevated fasting plasma glucose (FPG) levels. However, the relationship between FPG levels and in-hospital cardiac arrest (IHCA) remains unclear. OBJECTIVES: The objective of this study was to investigate the association between FPG levels and IHCA in patients diagnosed with acute coronary syndrome (ACS). METHODS: Data from a total of 31,726 ACS patients fitted with inclusion and exclusion criteria across 241 hospitals in the Improving Care for Cardiovascular Disease in China-ACS project from November 2014 to July 2019 were collected. Different logistic regression models were utilized to examine the associations of FPG levels with IHCA. Sensitivity analyses were then conducted to assess the robustness of the findings. Marginal effect analyses were also employed to evaluate the impact of different therapies. RESULTS: A total of 335 cases of IHCA and 293 in-hospital mortality were recorded throughout the study. A non-linear relationship between FPG levels and IHCA was identified after adjusting for the covariates. Specifically, a significant association was found between elevated FPG levels (≥6.1 mmol/L) and an increased risk of IHCA. These findings remained consistent across different subgroup analyses including both the diabetic and non-diabetic patients. Additionally, the marginal effect analyses revealed that percutaneous coronary intervention could lower the high FPG-related risk. CONCLUSIONS: The study findings showed a positive correlation between FPG levels and a higher incidence of IHCA, irrespective of the presence of diabetes.

Randomized Controlled Trial Comparing Training of Transseptal Puncture With or Without Intracardiac Echocardiography.

BACKGROUND: Intracardiac echocardiography (ICE) has been widely used in the catheter ablation of atrial fibrillation (AF). However, the value of ICE in the training of transseptal puncture (TSP) is unclear. METHODS: ICE-Training Study was a single-center, parallel-group, unmasked, randomized controlled trial registered in ChineseClinicalTrials.gov. Participants were randomly assigned (1:1) to different groups (1) the ICE simulator training group (ICE-ST), in which TSP was trained and performed under the guidance of both ICE and x-ray; and (2) the conventional simulator training group (Con-ST), in which TSP was trained and performed only under the guidance of x-ray. The trainees need to undergo the training stage and the evaluation stage. RESULTS: From October 2022 to December 2022, 18 consecutive fellows (age 32.4 ± 4.4 years, 12 males) without experience of TSP were included. The training period (16.9 ± 6.6 vs. 29.6 ± 8.7 times, p = 0.003) and the fluoroscopy time (120.3 ± 25.3 vs. 189.3 ± 40.2 s, p < 0.001) of the ICE-ST group was significantly shorter than that of the Con-ST group. No significant difference was found in the comprehensive performance of TSP in the ICE-ST group (composite score 96.7 ± 5.7) and the Con-ST group (composite score 95.9 ± 6.3, p = 0.62), but the selection of TSP sites in the ICE-ST group was commonly better than that in the Con-ST group. CONCLUSIONS: ICE could improve the efficiency of TSP training and optimize the site of TSP to facilitate catheter manipulation in the ablation. TRIAL REGISTRATION: ChineseClinicalTrials.gov identifier: ChiCTR2200058377.

Plasma Proteomic Insights for Identification of Novel Predictors and Potential Drug Targets in Atrial Fibrillation: A Prospective Cohort Study and Mendelian Randomization Analysis.

BACKGROUND: Currently, there are no reliable methods for predicting and preventing atrial fibrillation (AF) in its early stages. This study aimed to identify plasma proteins associated with AF to discover biomarkers and potential drug targets. METHODS: The UK Biobank Pharma Proteomics Project examined 2923 circulating proteins using the Olink platform, forming the basis of this prospective cohort study. The UK Biobank Pharma Proteomics Project included a randomly selected discovery cohort and the consortium-selected replication cohort. The study's end point was incident AF, identified using International Classification of Diseases, Tenth Revision codes. The association between plasma proteins and incident AF was evaluated using Cox proportional hazard models in both cohorts. Proteins present in both cohorts underwent Mendelian randomization analysis to delineate causal connections, utilizing cis-protein quantitative trait loci as genetic tools. The predictive efficacy of the identified proteins for AF was assessed using the area under the receiver operating characteristic curve, and their druggability was explored. RESULTS: Data from 38 784 participants were included in this study. Incident AF cases were identified in the discovery cohort (1894; 5.5%) within a median follow-up of 14.5 years and in the replication cohort (451; 10.6%) within a median follow-up of 14.4 years. Twenty-one proteins linked to AF were identified in both cohorts. Specifically, COL4A1 (collagen IV α-1; odds ratio, 1.11 [95% CI, 1.04-1.19]; false discovery rate, 0.016) and RET (proto-oncogene tyrosine-protein kinase receptor Ret; odds ratio, 0.96 [95% CI, 0.94-0.98]; false discovery rate, 0.013) demonstrated a causal link with AF, and RET is druggable. COL4A1 improved the short- and long-term predictive performance of established AF models, as evidenced by significant enhancements in the area under the receiver operating characteristic, integrated discrimination improvement, and net reclassification index, all with P values below 0.05. CONCLUSIONS: COL4A1 and RET are associated with the development of AF. RET is identified as a potential drug target for AF prevention, while COL4A1 serves as a biomarker for AF prediction. Future studies are needed to evaluate the effectiveness of targeting these proteins to reduce AF risk.

Stylet-driven leads compared with lumenless leads for left bundle branch area pacing: a systematic review and meta-analysis.

OBJECTIVE: Left bundle branch area pacing (LBBAP) is a novel physiological pacing method for treating left ventricular dyssynchrony. LBBAP is often delivered using lumenless leads (LLL). However, recent studies have also reported the use of style-driven leads (SDL). This study is the first systematic review comparing the outcomes of LBBAP with SDL vs. LLL. METHODS: The review and meta-analysis included all available comparative studies published on Embase, PubMed, Web of Science, CENTRAL, and Scopus up to 6th March 2024. RESULTS: Eight observational studies were included in the review. Meta-analysis showed that success rates of LBBAP performed with LLL and SDL were comparable (OR: 1.72 95% CI: 0.94, 3.17 I2 = 38%). Duration of implantation and total procedural duration were significantly lower in LBBAP performed with SDL. The pacing threshold was significantly higher, while pacing impedance was significantly lower in the SDL compared to the LLL group. Pacing QRS interval, R-wave amplitude, and stimulus to peak left ventricular activation time were similar in the two groups. Intra-operative and post-operative dislodgement were significantly higher in the SDL group, but no difference was noted in intra-operative perforation and pneumothorax risk. CONCLUSION: Limited evidence from observational studies with inherent selection bias shows that success rates for LBBAP may not differ between SDL and LLL. While implantation of SDL may be significantly faster, it carries a higher risk of lead dislodgement. Both SDL and LLL are associated with comparable pacing characteristics except for reduced pacing impedance with SDL.

Non-exercise Estimated Cardiorespiratory Fitness and Mortality Among Adults with Hypertension.

BACKGROUND: The non-exercise estimated cardiorespiratory fitness (eCRF) has been recognized as important predictor of mortality among general population. This study sought to evaluate the relationship between eCRF and mortality from all causes, cardiovascular disease (CVD), and cancer in hypertensive adults. METHODS: We included 27437 adults with hypertension from the National Health and Nutrition Examination Survey (NHANES) III and 10 NHANES cycles from 1999-2018. Multivariate Cox proportional hazards models were used to assess the hazard ratios (HRs) and 95% confidence intervals (CIs) of eCRF for mortality. RESULTS: A total of 8023 deaths were recorded throughout a median 8.6-year follow-up, including 2338 from CVD, and 1761 from cancer. The eCRF with per 1 metabolic equivalent increase was linked to decreased risk of all-cause (adjusted HR 0.78, 95% CI: 0.75-0.81) and CVD mortality (adjusted HR 0.79, 95% CI: 0.74-0.84), rather than cancer mortality (adjusted HR 0.94, 95% CI: 0.86-1.03). Moreover, a stronger protective effect of eCRF was observed for females (HR 0.66 (95% CI: 0.62-0.72) versus HR 0.78 (95% CI: 0.73-0.83), Pinteraction < 0.001 for all-cause mortality; HR 0.70 (95% CI: 0.61-0.80;) versus HR 0.82 (95% CI: 0.73-0.92), Pinteraction = 0.026 for CVD mortality) compared with males. Findings did not significantly differ in subgroup analyses and sensitivity analyses. CONCLUSIONS: Among adults with hypertension, eCRF was inversely related to all-cause and CVD mortality, but not cancer mortality. A significant interaction effect existed between sex and eCRF. Further studies are needed to verify this association in different population.

Longitudinal Association Between Resting Heart Rate and Mortality in Atrial Fibrillation.

Rate control plays a fundamental role in the management of atrial fibrillation (AF), but the optimal target of resting heart rate (RHR) for reducing mortality remains uncertain. This study used longitudinal follow-up RHR data to evaluate the relationship between RHR and all-cause mortality. Data from the AFFIRM (Atrial Fibrillation Follow-up Investigation of Rhythm Management) study were retrospectively analyzed. The association between RHR and mortality was longitudinally analyzed using mean RHR (mRHR) and individual trajectory patterns, where the Cox proportional hazards model and group-based trajectory model were used. A total of 3,921 patients (mean age, 69.47 ± 8.09 years) with AF were included in our study. A total of 578 deaths were recorded during a median follow-up of 3.4 years. Cox regression analyses showed an mRHR ≥80 bpm was associated with an increased risk of mortality (adjusted hazard ratio: 2.01, 95% CI: 1.59-2.55). Consistent association was found in the subgroup analyses. The Kaplan-Meier analysis showed notably reduced survival probabilities for patients with mRHR ≥80 bpm. Patients were classified into four stable trajectories based on RHR during follow-up, with the classes >70 bpm associated with an elevated risk of mortality. In conclusion, longitudinally measured RHR ≥80 bpm was associated with an increased risk of mortality in patients with AF.

China Clinical Trials Registry Identifier: ChiCTR-OCH-13003729. Varying effect of atrial fibrillation ablation in patients with heart failure with preserved ejection fraction according to CHA2DS2-VASc score.

BACKGROUND: The impact of comorbidity burden on outcomes of radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF) in patients with heart failure and preserved ejection fraction (HFpEF) remains unclear. OBJECTIVE: The purpose of this study was to evaluate how comorbidity burden influences the association between RFCA and cardiovascular outcomes in AF patients with HFpEF. METHODS: AF patients with HFpEF from the prospective China-AF cohort, recruited between August 2011 and December 2020, were categorized into 2 groups based CHA2DS2-VASc score: low comorbidity burden (score ≤4) and high comorbidity burden (score >4). The associations between RFCA and cardiovascular outcomes and interaction effects of comorbidity burden on these associations were assessed. RESULTS: Among 1700 patients with median follow-up of 65.9 months, those in the low comorbidity burden group who received RFCA had a lower risk of composite events (cardiovascular death and ischemic stroke/transient ischemic attack [TIA]) (adjusted hazard ratio [HR] 0.35, 95% confidence interval [CI] 0.21-0.59] and all-cause death (adjusted HR 0.31, 95% CI 0.17-0.54) compared to those without RFCA. However, significant associations were not observed in the high comorbidity burden group. The differences between low and high comorbidity burden groups were significant, with interaction effects noted between comorbidity burden and RFCA for cardiovascular death (Pinteraction = 0.045) and ischemic stroke/TIA (Pinteraction = 0.010). RFCA was associated with a reduced risk of AF recurrence in both comorbidity burden groups. CONCLUSION: RFCA for AF is associated with reduced AF recurrence and improved cardiovascular outcomes in patients with HFpEF. However, these benefits may be limited for patients with a CHA2DS2-VASc score >4 (high comorbidity burden).

The integrated molecular and histological analysis defines subtypes of esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is highly heterogeneous. Our understanding of full molecular and immune landscape of ESCC remains limited, hindering the development of personalised therapeutic strategies. To address this, we perform genomic-transcriptomic characterizations and AI-aided histopathological image analysis of 120 Chinese ESCC patients. Here we show that ESCC can be categorized into differentiated, metabolic, immunogenic and stemness subtypes based on bulk and single-cell RNA-seq, each exhibiting specific molecular and histopathological features based on an amalgamated deep-learning model. The stemness subgroup with signature genes, such as WFDC2, SFRP1, LGR6 and VWA2, has the poorest prognosis and is associated with downregulated immune activities, a high frequency of EP300 mutation/activation, functional mutation enrichment in Wnt signalling and the highest level of intratumoural heterogeneity. The immune profiling by transcriptomics and immunohistochemistry reveals ESCC cells overexpress natural killer cell markers XCL1 and CD160 as immune evasion. Strikingly, XCL1 expression also affects the sensitivity of ESCC cells to common chemotherapy drugs. This study opens avenues for ESCC treatment and provides a valuable public resource to better understand ESCC.

Left Pulmonary Vein Trunk Length as a Robust Predictor of Long-Term Success of Atrial Fibrillation Catheter Ablation.

Background: Radiofrequency catheter ablation (RFCA) is a commonly used treatment for atrial fibrillation (AF), but the long-term recurrence rate remains relatively high. Given the inconsistent results regarding the role of left pulmonary vein (PV) ostial anatomy in post-ablative recurrence of RFCA in previous studies, we sought to investigate the role of left PV trunk length using an alternative methodology. Methods: A total of 369 AF patients undergoing catheter ablation were included. The left/right trunk length (LTL/RTL) of the PV was measured from pre-ablative computed tomography (CT) using three-dimensional reconstruction techniques. We constructed three multivariable Cox models, with the inclusion of the LTL, RTL, and no LTL/RTL, and used the Delong test, integrated discrimination index (IDI), and net reclassification index (NRI) to assess model improvement. We identified optimal cut-off values for LTL with the receiver operating characteristic (ROC) curve, and estimated outcomes using the Kaplan-Meier survival curve. We also used subgroup analysis to evaluate interactions. Results: The results of the Delong test, IDI, and NRI indicated that LTL had a favorable impact on the performance of the multivariate model. Subsequently, the multivariate Cox regression analysis identified LTL as a significant risk factor for post-ablative recurrence of AF (adjusted hazard ratio (HR) = 1.08, 95% CI: 1.05-1.12, p < 0.001). According to the ROC curve, the optimal cut-off value for LTL is 11.15 mm, and the Kaplan-Meier estimator revealed different outcomes (p < 0.001). We calculated p for interaction between LTL and other factors, and no significant interaction terms were observed. Conclusions: LTL is a robust prognostic indicator for post-ablative outcome in AF patients receiving RFCA, with a longer LTL indicating a higher risk of recurrence.

Protocol for a randomized controlled trial of intensive blood pressure control on cardiovascular risk reduction in patients with atrial fibrillation: Rationale and design of the CRAFT trial.

BACKGROUND: Co-morbid hypertension is strong predictor of adverse cardiovascular (CV) outcomes in patients with atrial fibrillation (AF) but the optimal target for blood pressure (BP) control in this patient population has not been clearly defined. METHODS: The Cardiovascular Risk reduction in patients with Atrial Fibrillation Trial (CRAFT) is an investigator-initiated and conducted, international, multicenter, open-label, parallel-group, blinded outcome assessed, randomized controlled trial of intensive BP control in patients with AF. The aim is to determine whether intensive BP control (target home systolic blood pressure [SBP] <120 mmHg) is superior to standard BP control (home SBP <135 mmHg) on the hierarchical composite outcome of time to CV death, number of stroke events, time to the first stroke, number of myocardial infarction (MI) events, time to the first MI, number of heart failure hospitalization (HFH) events, and time to the first HFH. A sample size of 1,675 patients is estimated to provide 80% power to detect a win-ratio of 1.50 for intensive versus standard BP control on the primary composite outcome. Study visits are conducted at 1, 2, 3, and 6 months postrandomization, and every 6 months thereafter during the study. CONCLUSIONS: This clinical trial aims to provide reliable evidence of the effects of intensive BP control in patients with AF. TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov (NCT04347330).

Impact of sodium-glucose cotransporter 2 inhibitor on recurrence and cardiovascular outcomes after catheter ablation for atrial fibrillation in patients with heart failure.

BACKGROUND: The impact of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on atrial fibrillation (AF) recurrence outcomes and adverse cardiovascular outcomes in heart failure (HF) patients after AF ablation is unknown. OBJECTIVE: We investigated whether SGLT2i reduces the risk of AF recurrence and adverse cardiovascular outcomes in HF patients after AF ablation. METHODS: HF patients with AF undergoing catheter ablation between January 2017 and December 2022 from the China-AF Registry were included. Patients were stratified into 2 groups on the basis of the use of SGLT2i at discharge and were 1:1 matched by propensity score, with SGLT2i using (n = 368) and non-SGLT2i using (n = 368) in each group. The primary outcome was AF recurrence after a 3-month blanking period. RESULTS: During a total of 1315 person-years of follow-up, AF recurred in 83 patients (22.6%) in the SGLT2i group and 132 patients (35.8%) in the non-SGLT2i group. SGLT2i was associated with a lower risk of AF recurrence (adjusted hazard ratio, 0.56; 95% CI, 0.43-0.74; P < .001). The composite risk of cardiovascular death, thrombotic events, or cardiovascular hospitalization was significantly lower in the SGLT2i group compared with those without SGLT2i (adjusted hazard ratio, 0.58; 95% CI, 0.41-0.80; P = .001). Although there was a trend toward benefit, the differences in all-cause mortality, cardiovascular death, or thrombotic events were insignificant between the 2 groups. CONCLUSION: The use of SGLT2i was associated with a lower risk of AF recurrence and the composite outcome of cardiovascular death, thrombotic events, or cardiovascular hospitalization after catheter ablation for AF in patients with HF.

Generation of a human induced pluripotent stem cell line ZZUNEUi030-A from a female patient carrying a heterozygous CALM2 (c.395 A > T) mutation.

Calmodulin mutations can cause life-threatening long QT syndrome involving CALM1, CALM2, and CALM3. In this study, human induced pluripotent stem cells ZZUNEUi030-A were derived from a female patient with heterozygous CALM2 gene c. 395A â†’ T by Sendai virus non-integrated reprogramming technology. The cell line showed a normal female karyotype (46, XX), expressed pluripotency markers, and had the ability to differentiate into three germ layers in vitro. ZZUNEUi030-A can be used as a cell disease model to study the pathogenesis of LQT caused by calmodulin mutations.

Discovery of 1,2,4-Triazole-3-thione Derivatives as Potent and Selective DCN1 Inhibitors for Pathological Cardiac Fibrosis and Remodeling.

DCN1, a critical co-E3 ligase during the neddylation process, is overactivated in many diseases, such as cancers, heart failure as well as fibrotic diseases, and has been regarded as a new target for drug development. Herein, we designed and synthesized a new class of 1,2,4-triazole-3-thione-based DCN1 inhibitors based the hit HD1 identified from high-throughput screening and optimized through numerous structure-activity-relationship (SAR) explorations. HD2 (IC50= 2.96 nM) was finally identified and represented a highly potent and selective DCN1 inhibitor with favorable PK properties and low toxicity. Amazingly, HD2 effectively relieved Ang II/TGFß-induced cardiac fibroblast activation in vitro, and reduced ISO-induced cardiac fibrosis as well as remodeling in vivo, which was linked to the inhibition of cullin 3 neddylation and its substrate Nrf2 accumulation. Our findings unveil a novel 1,2,4-triazole-3-thione-based derivative HD2, which can be recognized as a promising lead compound targeting DCN1 for cardiac fibrosis and remodeling.

Idiopathic ventricular arrhythmia originating from the vicinity of lateral tricuspid annulus: The precise origin and anatomic concerns.

BACKGROUND: Although the electrocardiographic and electrophysiological properties of ventricular arrhythmias (VAs) from the vicinity of the lateral tricuspid annulus (TA) have been reported in previous studies, their precise site of origin have not been addressed. OBJECTIVE: The purpose of this study was to describe the precise origin of lateral TA-VA and the relevant anatomy. METHODS: Consecutive patients with idiopathic lateral TA-VAs were reviewed and analyzed. Three-dimensional mapping system combined with intracardiac echocardiography (ICE) was used for anatomic reconstruction, mapping, and ablation. RESULTS: During the study period, 63 patients with lateral TA-VAs were included. Under ICE view, a prominent enfoldment structure was observed under the valve along the lateral TA. The muscular bundle was documented in all patients (100%) within the subvalvular enfoldment with an average number and diameter of 4 ± 2 and 4.10 ± 0.73 mm, respectively. Initial ablation was attempted via the anterograde approach in 15 patients but succeeded in none. To reach the ventricular side of the TA, the catheter needed to enter the ventricular chamber and retroflexed toward the atrial side with a reverse curve. The earliest activation site was found at the valvular end of muscular bundles in 51 of the 63 patients (80.9%) with a local activation time of -26.78 ± 4.63 ms. The VAs were eliminated after an average of 4 ± 2 seconds of ablation. CONCLUSION: The ventricular side adjacent to the lateral TA exhibits a subvalvular enfoldment-like structure, which is rich in muscular bundles and serves as the origin of TA-VAs in most patients. To reach the origins, a reverse technique is required.

Comparison of admission glycemic variability and glycosylated hemoglobin in predicting major adverse cardiac events among type 2 diabetes patients with heart failure following acute ST-segment elevation myocardial infarction.

Background and Objectives: Hyperglycemia is associated with adverse outcomes in patients with acute myocardial infarction (AMI) as well as in patients with heart failure. However, the significance of admission glycemic variability (GV) in predicting outcomes among diabetes patients with heart failure (HF) following acute ST-segment elevation myocardial infarction (ASTEMI) remains unclear. This study aims to explore the prognostic value of admission GV and admission glycosylated hemoglobin (HbA1c) levels in individuals diagnosed with type 2 diabetes and HF following ASTEMI. Methods: We measured GV and HbA1c upon admission in 484 consecutive patients diagnosed with type 2 diabetes and HF following ASTEMI. GV, indicated as the mean amplitude of glycemic excursions (MAGE), was assessed utilizing a continuous glucose monitoring system (CGMS). admission MAGE values were categorized as < 3.9 or ≥ 3.9 mmol/L, while HbA1c levels were classified as < 6.5 or ≥ 6.5%. Participants were followed up prospectively for 12 months. The relationship of admission MAGE and HbA1c to the major adverse cardiac event (MACE) of patients with type 2 diabetes and HF following ASTEMI was analyzed. Results: Among the 484 enrolled patients, the occurrence of MACE differed significantly based on MAGE categories (< 3.9 vs. ≥ 3.9 mmol/L), with rates of 13.6% and 25.3%, respectively (P = 0.001). While MACE rates varied by HbA1c categories (< 6.5 vs. ≥ 6.5%) at 15.7% and 21.8%, respectively (P = 0.086). Patients with higher MAGE levels exhibited a notably elevated risk of cardiac mortality and an increased incidence of HF rehospitalization. The Kaplan-Meier curves analysis demonstrated a significantly lower event-free survival rate in the high MAGE level group compared to the low MAGE level group (log-rank test, P < 0.001), while HbA1c did not exhibit a similar distinction. In multivariate analysis, high MAGE level was significantly associated with incidence of MACE (hazard ratio 3.645, 95% CI 1.287-10.325, P = 0.015), whereas HbA1c did not demonstrate a comparable association (hazard ratio 1.075, 95% CI 0.907-1.274, P = 0.403). Conclusions: Elevated admission GV emerges as a more significant predictor of 1-year MACE in patients with type 2 diabetes and HF following ASTEMI, surpassing the predictive value of HbA1c.

Permanent pacemaker reduction using temporary-permanent pacemaker as a 1-month bridge after transcatheter aortic valve replacement: a prospective, multicentre, single-arm, observational study.

Background: The permanent pacemaker (PPM) implantation and pacemaker dependency rates after transcatheter aortic valve replacement (TAVR) are highly variable as some of the conduction disturbances are reversible. It remains poorly investigated how to optimise temporary pacing in these patients. This study aimed to explore the potential reduction in the PPM implantation rate using temporary-permanent pacemaker (TPPM) as a 1-month bridge. Methods: This is a prospective, multicentre, single-arm, observational study. Consecutive patients undergoing TAVR from March 1, 2022 to March 1, 2023 in 13 tertiary hospitals in China were screened. Patients who developed high-degree atrioventricular block, complete heart block, or first-degree atrioventricular block plus new onset left bundle branch block during the TAVR procedure or within 1 month after TAVR were included to receive TPPM. Patients with pre-existing PPM implantation or indications for PPM implantation before the TAVR procedure were excluded. Patients with TPPM were monitored to determine whether the conduction disturbances persisted or recovered. The primary endpoint was the rate of freedom from indications for PPM implantation 1 month after TAVR. This study is registered with ChiCTR, ChiCTR2200057931. Findings: Of 688 patients who have undergone TAVR, 71 developed conduction disturbance and met the inclusion criteria, 1 patient withdrew due to noncompliance, 70 patients received TPPM and completed follow-up. There were 41 (58.6%) men and 29 (41.4%) women in the study, with a mean age of 74.3 ± 7.3 years. At 1 month follow-up, 75.7% (53/70) of the patients with TPPM did not require PPM implantation. For 688 patients who have undergone TAVR, the rate of PPM implantation at 1 month was 2.47% (17/688, 95% CI 1.55%-3.92%), representing a significant reduction in self-comparison with the rate at 48 h after TPPM (2.47% vs. 8.28% [95% CI 6.45%-10.58%], P < 0.0001). Similar results were obtained in the subgroup analysis of patients with HAVB/CHB. Multivariate analysis revealed the baseline PR interval, difference between the membranous septum length and implantation depth, and timing of postprocedural conduction disturbance occurrence were independent predictors of freedom from indications for PPM implantation at 1 month after TAVR. Interpretation: Using TPPM as a 1-month bridge allows for a buffer period to distinguish whether conduction disturbances are reversible or persistent, resulting in a significant reduction in the PPM implantation rate after TAVR when compared with the current strategy. However, this is an observational study, the results need to be confirmed in a randomized trial. Funding: Beijing Science and Technology Plan 2022 from Beijing Municipal Science & Technology Commission.

Frameshift variants in C10orf71 cause dilated cardiomyopathy in human, mouse, and organoid models.

Research advances over the past 30 years have confirmed a critical role for genetics in the etiology of dilated cardiomyopathies (DCMs). However, full knowledge of the genetic architecture of DCM remains incomplete. We identified candidate DCM causal gene, C10orf71, in a large family with 8 patients with DCM by whole-exome sequencing. Four loss-of-function variants of C10orf71 were subsequently identified in an additional group of492 patients with sporadic DCM from 2 independent cohorts. C10orf71 was found to be an intrinsically disordered protein specifically expressed in cardiomyocytes. C10orf71-KO mice had abnormal heart morphogenesis during embryonic development and cardiac dysfunction as adults with altered expression and splicing of contractile cardiac genes. C10orf71-null cardiomyocytes exhibited impaired contractile function with unaffected sarcomere structure. Cardiomyocytes and heart organoids derived from human induced pluripotent stem cells with C10orf71 frameshift variants also had contractile defects with normal electrophysiological activity. A rescue study using a cardiac myosin activator, omecamtiv mecarbil, restored contractile function in C10orf71-KO mice. These data support C10orf71 as a causal gene for DCM by contributing to the contractile function of cardiomyocytes. Mutation-specific pathophysiology may suggest therapeutic targets and more individualized therapy.

Impacts of Left Atrial Appendage Treatments on Mitral Valve Diseases during Surgical Ablations.

Background: Left atrial appendages (LAAs) play an important role in regulating left atrial function, and much evidence supports the possibility that changes in left atrial structure may cause or worsen mitral regurgitation. This study intended to investigate the outcomes of patients with mitral regurgitation who underwent left atrial appendage closure (resection or endocardial closure) during isolated surgical ablations. Methods: Patients with mild or moderate mitral regurgitation who received isolated surgical ablations for atrial fibrillation (AF) in our center from 2013 to 2022 were referred. During follow-up, each clinical visit was composed of medical interrogation, a 24 h Holter, and echocardiographic evaluation. Death, atrial fibrillation, worsening of mitral regurgitation, and stroke were evaluated as outcomes. Freedom from outcomes whose results were adjusted by inverse probability of treatment weighting for causal effects after acquiring propensity scores. Results: A total of 456 patients were enrolled in this study. During a median follow-up of 48 months, 30 deaths and 11 cases of stroke were observed. After adjustments, no significant differences in terms of death or stroke were observed among the three groups. Patients who underwent resection or endocardial closure during surgical ablations had a higher risk of mitral regurgitation worsening during follow-up (p < 0.05). During the whole follow-up, patients who underwent left atrial appendage interventions showed significantly larger left atrial and mitral annular diameters, as well as lower tethering height than those who had left atrial appendage preserved (all p < 0.05). Conclusions: Mitral regurgitation was more likely to get worse when patients with fundamental mitral diseases underwent LAA interventions during isolated surgical AF ablations. In the absence of LAA, the dilation of the left atrium and mitral annulus may ultimately lead to worsening of regurgitation.

Transseptal approach versus retrograde aortic approach in mapping and ablation of ventricular arrhythmias from anterolateral papillary muscles.

INTRODUCTION: The anterior and lateral position of the anterolateral papillary muscle (ALPM) has found to be reached with better catheter stability and less mechanical bumping via the transseptal (TS) compared to the retrograde aortic (RA) approach. The aim of this study is to compare the TS and RA approaches on mapping and ablation of ventricular arrhythmias (VAs) arising from ALPMs. METHODS: Thirty-two patients with ALPM-VAs undergoing mapping and ablation via the TS approach were included and compared with 31 patients via the RA approach within the same period. Acute success was compared, as well as other outcomes including misinterpreted mapping results due to bumping, radiofrequency (RF) attempts, procedural time and success rate at 12-month follow-up. RESULTS: Acute success was achieved in more cases in the TS group (96.4% vs. 72.0%, p = .020). During activation mapping, bump-provoked premature ventricular complexes (PVCs) misinterpreted as clinical PVCs were more common in the RA group (30.0% vs. 58.3%, p = .036), leading to more RF attempts (3.5 ± 2.7 vs. 7.2 ± 6.8, p = .006). Suppression of VAs were finally achieved in the unsuccessful cases by changing to the alternative approach, but the procedural time was significantly less in the TS group (90.0 ± 33.0 vs. 113.7 ± 41.1 min, p = .027) with less need to change the approach, although follow-up success rates were similar (75.0% vs. 71.0%, p = .718). CONCLUSION: A TS rather than RA approach as the initial approach appears to facilitate mapping and ablation of ALPM-VAs, specifically by decreasing the possibility of misleading mapping results caused by bump-provoked PVC, and increase the acute success rate thereby.

Morphology and location of thrombus and sludge in patients with non-valvular atrial fibrillation.

BACKGROUND: Stroke and thromboembolism in nonvalvular atrial fibrillation (NVAF) primarily arise from thrombi or sludge in the left atrial appendage (LAA). Comprehensive insight into the characteristics of these formations is essential for effective risk assessment and management. METHODS: We conducted a single-center retrospective observational of 176 consecutive NVAF patients with confirmed atrial/appendage thrombus or sludge determined by a pre-ablation transesophageal echocardiogram (TEE) from December 2017 to April 2019. We obtained clinical and echocardiographic characteristics, including left atrial appendage emptying velocity (LAAeV) and filling velocity (LAAfV). Data analysis focused on identifying the morphology and location of thrombus or sludge. Patients were divided into the solid thrombus and sludge groups, and the correlation between clinical and echocardiographic variables and thrombotic status was analyzed. RESULTS: Morphological classification: In total, thrombi were identified in 78 patients, including 71 (40.3%) mass and 7 (4.0%) lamellar, while sludge was noted in 98 (55.7%). Location classification: 92.3% (72/78) of patients had thrombus confined to the LAA; 3.8% (3/78) had both LA and LAA involvement; 2.7% (2/78) had LA, LAA and RAA extended into the RA, the remained 1.2%(1/78) was isolated to RAA. 98.0% (96/98) of patients had sludge confined to the LAA; the remaining 2.0% (2/98) were present in the atrial septal aneurysm, which protrusion of interatrial septum into the RA. The thrombus and sludge groups showed low LAAeV (19.43 ± 9.59 cm/s) or LAAfV (17.40 ± 10.09 cm/s). Only LA dimension ≥ 40 mm was independently associated with the thrombus state in the multivariable model. CONCLUSION: This cohort study identified rare thrombus morphology and systematically summarized the classification of thrombus morphology. The distribution of thrombus and sludge outside limited to LAA was updated, including bilateral atrial and appendage involvement and rare atrial septal aneurysm sludge. LAAeV and LAAfV were of limited value in distinguishing solid thrombus from sludge. CLINICAL TRIAL NUMBER: ChiCTR-OCH-13,003,729.