BACKGROUND:The left bundle branch block (LBBB) morphology could be divided into concordant LBBB (con-LBBB; T waves concordant with QRS) or discordant LBBB (dis-LBBB; T waves discordant with QRS) types on the basis of the direction of T and QRS main waves except for true or non-true LBBB (non-tLBBB). In this study we aimed to investigate the influence of baseline LBBB morphology on success rate of left bundle branch pacing (LBBP), echocardiographic response, and clinical outcomes in patients who received LBBP-delivered cardiac resynchronization therapy. METHODS:Consecutive patients with heart failure (HF) and LBBB who attempted to receive LBBP-delivered cardiac resynchronization therapy were prospectively enrolled from 2019 to 2024. Baseline LBBB morphology was identified as con-LBBB, dis-LBBB, and non-tLBBB types. The primary end point was echocardiographic response at 6-month follow-up. Secondary end points included: (1) LBBP success; (2) echocardiographic super-response; (3) all-cause mortality and/or HF hospitalization. RESULTS:A total of 110 patients (32 with con-LBBB, 31 with dis-LBBB, and 47 with non-tLBBB) post cardiac resynchronization therapy were included. The LBBP success rate was highest in the con-LBBB group, followed by the dis-LBBB, and non-tLBBB group (84.4% vs 71.0% vs 51.1%; P = 0.007). After adjusting for confounders, con-LBBB was an independent predictor for LBBP success (odds ratio [OR], 3.90 [95% confidence interval (CI), 1.21-12.51]; P = 0.022), echocardiographic response (OR, 4.88 [95% CI, 1.26-18.81]; P = 0.021), and super-response (OR, 3.87 [95% CI, 1.40-10.69]; P = 0.009). During a mean follow-up of 20.2 ± 12.9 months, con-LBBB was associated with decreased all-cause mortality or HF hospitalization (hazard ratio, 0.08 [95% CI, 0.01-0.62]; P = 0.015). CONCLUSIONS:Baseline con-LBBB might be a useful predictor for LBBP success and favourable clinical outcomes.

BACKGROUND:Leadless pacemaker implantation traditionally relies on fluoroscopy and contrast-guided techniques. However, in patients with advanced chronic kidney disease, the use of contrast carries a risk of nephrotoxicity, and fluoroscopy leads to additional ionizing radiation exposure. CASE SUMMARY:We report a case of a 69-year-old man with occasional sinus arrest and end-stage renal disease on hemodialysis who successfully underwent implantation of an Aveir VR leadless pacemaker (Abbott, USA) entirely under transthoracic echocardiographic (TTE) guidance, without fluoroscopy or contrast. Using a Philips EPIQ system with an X5-1 transducer, key procedural steps-including navigation, septal positioning, pacing threshold testing, and final deployment-were completed under real-time ultrasound visualization. Post-procedural pacing parameters were optimal, and no complications occurred. Chest radiography confirmed appropriate device position. CONCLUSION:This case demonstrates the potential feasibility and safety of an ultrasound-guided implantation technique for the Aveir VR leadless pacemaker. It may offer a promising alternative for patients with contraindications to radiation or contrast agents. Larger studies are needed to validate and standardize this approach.

Background:The integration of large language models (LLMs) into cardio-oncology patient education holds promise for addressing the critical gap in accessible, accurate, and patient-friendly information. However, the performance of publicly available LLMs in this specialized domain remains underexplored. Objectives:This study evaluates the performance of three LLMs (ChatGPT-4, Kimi, DouBao) act as assistants for physicians in cardio-oncology patient education and examines the impact of prompt engineering on response quality. Methods:Twenty standardized questions spanning cardio-oncology topics were posed twice to three LLMs (ChatGPT-4, Kimi, DouBao): once without prompts and once with a directive to simplify language, generating 240 responses. These responses were evaluated by four cardio-oncology specialists for accuracy, comprehensiveness, helpfulness, and practicality. Readability and complexity were assessed using a Chinese text analysis framework. Results:Among 240 responses, 63.3% were rated "correct," 35.0% "partially correct," and 1.7% "incorrect." No significant differences in accuracy were observed between models (p = 0.26). Kimi demonstrated no incorrect responses. Significant declines in comprehensiveness (p = 0.03) and helpfulness (p < 0.01) occurred post-prompt, particularly for DouBao (accuracy: 57.5% vs. 7.5%, p < 0.01). Readability metrics (readability age, difficulty score, total word count, sentence length) showed no inter-model differences, but prompts reduced complexity (e.g., DouBao's readability age decreased from 12.9 ± 0.8 to 10.1 ± 1.2 years, p < 0.01). Conclusion:Publicly available LLMs provide largely accurate responses to cardio-oncology questions, yet their utility is constrained by inconsistent comprehensiveness and sensitivity to prompt design. While simplifying language improves readability, it risks compromising clinical relevance. Tailored fine-tuning and specialized evaluation frameworks are essential to optimize LLMs for patient education in cardio-oncology.

BACKGROUND:Cardiac resynchronization therapy (CRT) response in heart failure (HF) patients is multifactorial, with limited data on its association with activities of daily living assessed by the Barthel index (BI). OBJECTIVE:This prospective observational study investigated the predictive value of BI for CRT response and long-term clinical outcomes in non-ischemic HF patients with left bundle branch block (LBBB). METHODS:A total of 271 consecutive non-ischemic HF patients undergoing CRT with left ventricular ejection fraction (LVEF) ≤ 35% and LBBB were enrolled. BI was evaluated pre-implantation. The primary endpoint was CRT response (absolute LVEF improvement ≥ 5% at 6 months). The secondary composite endpoint included all-cause mortality and HF hospitalization (HFH). RESULTS:Among 249 patients completing 6-month follow-up, the CRT response rate was 68.67%. Multivariate logistic regression identified BI (per 5-point increment; OR = 1.37, 95% CI:1.12-1.67, p = 0.002) as an independent predictor of CRT response, with an optimal cutoff of 95. Combining BI with left ventricular end-diastolic diameter and left bundle branch area pacing achieved the highest predictive efficacy (AUC = 0.78). Over a median 33.94-month follow-up, BI > 95 was associated with an 88% reduced risk of the composite endpoint (adjusted HR = 0.116, p < 0.001), driven primarily by marked HFH reduction. A non-significant trend toward lower all-cause mortality was observed, accompanied by sustained LVEF improvement (29.81% ± 5.01% to 51.71% ± 11.30%). CONCLUSION:BI might be a simple, cost-effective independent predictor for CRT response and improved LVEF and prognosis in non-ischemic HF patients with LBBB.

BACKGROUND:Risk stratification of sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM) remains challenging. High-sensitivity cardiac troponin I (hs-cTnI) specifically reflects myocardial damage whereas its relationship with SCD risk in HCM is unclear. OBJECTIVE:This study aimed to investigate the prognostic value of hs-cTnI on enhancing SCD risk stratification in HCM. METHODS:This cohort study consecutively enrolled 705 patients with confirmed diagnosis of HCM. The baseline and clinical follow-up data were collected. The primary end point was defined as SCD or SCD-equivalent events including witnessed arrhythmic cardiac arrest and sustained ventricular tachycardia or ventricular fibrillation requiring intervention. RESULTS:The final analysis included 559 patients with a median age of 53.0 years, 66.2% male, 16.1% with an implantable cardioverter-defibrillator (ICD), and a median hs-cTnI level of 0.021 ng/mL. The mean follow-up was 862 days, with 51 patients (9.1%) experiencing SCD events. The hs-cTnI showed a significant nonlinear association with SCD risk and remained as an independent predictor (adjusted hazard ratio 2.93 [95% confidence interval 1.89‒4.54], P < .0001). The optimal threshold value of hs-cTnI for increased risk of SCD was 0.0405 ng/mL. The addition of hs-cTnI to the conventional risk score model significantly improved the predictive performance (C-statistic increased from 0.752 to 0.813; P = .007). Patients with both elevated risk score and hs-cTnI had the worst prognosis (P < .0001). CONCLUSION:The hs-cTnI could be an independent predictor of SCD risk for patients with HCM. Integrating hs-cTnI into SCD risk assessment may provide additional indication of ICD implantation for primary prevention.

Low left ventricular ejection fraction (LEF) frequently remains undetected until progression to symptomatic heart failure, underscoring the need for scalable screening strategies. Although artificial intelligence-enabled electrocardiography (AI-ECG) has shown promise, existing approaches rely solely on end-to-end black-box models with limited interpretability or on tabular systems dependent on commercial ECG measurement algorithms with suboptimal performance. We introduced ECG-based Predictor-Driven LEF (ECGPD-LEF), a structured framework that integrates foundation model-derived diagnostic probabilities with interpretable modeling for detecting LEF from ECG. Trained on the benchmark EchoNext dataset comprising 72,475 ECG-echocardiogram pairs and evaluated in predefined independent internal (n=5,442) and external (n=16,017) cohorts, our framework achieved robust discrimination for moderate LEF (internal AUROC 88.4

BACKGROUND:Pacing-induced cardiomyopathy (PICM) occurs in some patients requiring a high burden of right ventricular pacing (RVP). Whether left bundle branch area pacing (LBBAP) might be superior to biventricular pacing delivering cardiac resynchronization therapy remains unclear. OBJECTIVE:The present study aimed to evaluate the effectiveness of LBBAP compared with BiVP in patients with PICM. METHODS:This prospective, 2-center observational study enrolled consecutive patients with PICM who underwent upgrading to either LBBAP or BiVP. LBBAP was further classified into left bundle branch pacing (LBBP) and left ventricular septal pacing (LVSP). The primary end point was the change in left ventricular ejection fraction (LVEF) from baseline to 6-month follow-up. Other echocardiographic parameters, N-terminal pro-B-type natriuretic peptide levels, New York Heart Association functional class, and clinical events (all-cause mortality, heart failure hospitalization, and malignant ventricular arrhythmias) were evaluated during follow-up. RESULTS:In total, 78 patients were included in the final analysis (33% patients with LVEF < 35%), including 40 patients with LBBAP (30 with LBBP and 10 with LVSP) and 38 patients with BiVP. At the 6-month follow-up, LVEF improvement was significantly greater in patients with LBBAP than those with BiVP (9.59 ± 7.48% vs 4.91 ± 7.73%; P = .008), and higher in LBBP than LVSP (10.62 ± 7.28% vs 6.47 ± 7.57). During a mean follow-up duration of 20.5 ± 12.5 months, clinical outcomes did not differ between BiVP and LBBAP groups (26.3% vs 17.5%; adjusted hazard ratio = 1.57 [0.55-4.48], P = .395) after adjustment for confounders. CONCLUSIONS:PICM upgrading to LBBAP or BiVP demonstrated similar clinical outcomes, but upgrading to LBBAP was associated with greater improvement in LVEF.

BACKGROUND:S wave in lead V5/6 has been reported as a marker indicated for successful left bundle branch (LBB) capture. This study aimed to evaluate the value of the S wave in lead V5/6 in predicting the long-term clinical outcomes in heart failure (HF) patients treated with left bundle area pacing (LBBAP). METHODS:Consecutive HF patients receiving LBBAP were prospectively enrolled and followed at least 2 years. ECG were analyzed to identify the S wave in lead V5/6. The composite end point was all-cause mortality, HF hospitalization, and malignant ventricular arrhythmias. Non-response to LBBAP delivered cardiac resynchronization therapy (CRT) was defined as left ventricular ejection fraction improvement <5% at 6 months after implantation. RESULTS:A total of 57 patients were included with the mean age of 59.90 ± 12.57 years and 39 (68.42%) males. S wave in V5/6 was observed in 38 patients. During a mean follow up of 29.84 ± 12.51 months, Kaplan-Meier curves showed a 77.8% reduction in risk of composite end point for V5/6 with S (HR 0.222; 95% CI 0.065, 0.756; log-rank, p = 0.0069). Multivariate Cox regression analysis revealed that V5/6 with S was associated with a lower risk of the composite end point by 69.0% (adjusted HR 0.31; 95% CI 0.09, 1.05; p = 0.041). The non-response rate of LBBAP was 22.58% in V5/6 with S and 58.82% in V5/6 without S (p = 0.012). CONCLUSION:S wave in lead V5 and/or V6 after LBBAP predicts better clinical outcomes, and has a better response rate of LBBAP for CRT in HF patients.

Severe vascular complications associated with pacemaker implantation rarely occur and then might be misjudged. We presented a case with an atypical and confusing presentation of arteriovenous fistulae after pacemaker implantation that was relatively late recognized post-procedure. Endovascular repairment was performed and a good clinical outcome was reached.

BACKGROUND:Left bundle branch area pacing (LBBAP) is safe and effective, but studies in older patients are lacking. This study compared the clinical and echocardiographic outcomes of LBBAP and right ventricular pacing (RVP) in patients aged ≥75 years. METHODS:This prospective observational study included older patients with symptomatic bradycardia who underwent LBBAP or RVP between 2019 and 2022. Clinical data, including pacing and electrophysiological characteristics, echocardiographic measurements, and device-related complications were collected. The primary endpoint was a composite of all-cause mortality, heart failure hospitalization, and upgrade to biventricular pacing. Secondary outcomes included changes in left ventricular ejection fraction (LVEF). RESULTS:Of 267 included patients, 110 underwent LBBAP and 157 underwent RVP. LBBAP was successful in 109 patients (success rate: 99.1%), with one patient eventually undergoing RVP. The pacing parameters of LBBAP were similar to those of RVP, except for a significantly narrower paced QRS duration (112.8 ± 11.6 vs. 138.3 ± 23.9 ms, p < .001). Ventricular lead implanting procedural duration was longer for LBBAP than RVP (14.0 vs. 6.0 min, p < .001), as was the fluoroscopy time (4.0 vs. 2.0 min, p < .001). During a mean follow-up period of 31.0 ± 16.8 months, the primary outcome incidence was significantly lower following LBBAP than RVP (15.1% vs. 21.1%; hazard ratio, 0.471; 95% confidence interval, 0.215-1.032; p = .036) in 149 patients (55.8%) with ventricular pacing burden > 20%. RVP reduced LVEF from 62.7 ± 4.1% at baseline to 59.8 ± 7.8% at the final follow-up (p = .001), whereas LBBAP preserved LVEF (61.4 ± 6.3% vs. 60.1 ± 7.4%, p = .429). CONCLUSION:LBBAP demonstrated improved clinical outcomes compared with RVP and maintained LVEF in older patients with high ventricular pacing burdens.

BackgroundLeft bundle branch pacing (LBBP) and left ventricular septal pacing (LVSP) are referred to as left bundle branch area pacing (LBBAP).ObjectiveThis study investigated whether long-term clinical outcomes differ in patients undergoing LBBP, LVSP, and biventricular pacing (BiVP) for cardiac resynchronization therapy (CRT).MethodsConsecutive patients with reduced left ventricular ejection fraction (LVEF<50%) undergoing CRT were prospectively enrolled if they underwent successful LBBP, LVSP, or BiVP. The primary composite endpoint was all-cause mortality or heart failure hospitalization (HFH). Secondary endpoints included all-cause mortality, HFH, and echocardiographic measures of reverse remodeling.ResultsA total of 259 patients (68 LBBP, 38 LVSP, and 153 BiVP) were followed for a mean duration of 28.8 ± 15.8 months. LBBP was associated with a significantly reduced risk of the primary endpoint by 78% compared to both BiVP [7.4% vs. 41.2%; adjusted hazard ratio (aHR) 0.22 (0.08, 0.57), p=0.002] and LVSP [7.4% vs. 47.4%; aHR 0.22 (0.08, 0.63), p=0.004]. The adjusted risk of all-cause mortality was significantly higher in LVSP than BiVP [31.6% vs. 7.2%, aHR 3.19 (1.38, 7.39); p=0.007] but comparable between LBBP and BiVP [2.9% vs. 7.2%, aHR 0.33 (0.07, 1.52), p=0.155]. Propensity score adjustment also obtained similar results. LBBP showed a higher rate of echocardiographic response (ΔLVEF ≥10%: 60.0% vs. 36.2% vs. 16.1%; p<0.001) than BiVP or LVSP.ConclusionLBBP yielded superior long-term clinical outcomes to BiVP and LVSP. The role of LVSP for CRT needs to be reevaluated due to its high mortality risk.

Patients with heart failure with mildly-reduced ejection fraction (HFmrEF) and left bundle branch block (LBBB) have worse outcomes than those without intraventricular conduction abnormality. Current guidelines only recommend cardiac resynchronization therapy (CRT) when LVEF is less than 35%. Left bundle branch pacing (LBBP) has been shown to better restore electrical synchrony and improve cardiac function than conventional biventricular CRT in HFrEF. Its efficacy in HFmrEF is rarely reported.

猪繁殖与呼吸综合征(PRRS)是由猪繁殖与呼吸综合征病毒(PRRSV)引起的猪场最重要传染病之一,给全世界养猪业造成了持续的经济损害.减毒活疫苗免疫接种作为防控PRRS的有效手段在全世界范围内得到广泛应用.减毒活疫苗毒株是在猴源细胞系上连续传代获得的,导致其与亲本毒株在生物学特性上存在巨大差异,同时本实验室前期结果也提示HP-PRRSV野毒株和疫苗毒株在入胞途径上可能存在差异.Na+/H+交换的依赖是巨胞饮的标志性特征,阿米洛利(EIPA)是Na+/H+交换的特异性抑制剂,细胞骨架重排在病毒的入胞过程中发挥重要作用,细胞松弛素D(Cyt D)是肌动蛋白聚合的特异性抑制剂.分别利用EIPA和Cyt D预处理PAM和Marc-145细胞后接毒,对比强弱毒在两种细胞内病毒拷贝数、蛋白表达水平及子代病毒的释放上与空白对照组的差异.结果表明,PRRSV强弱毒均不利用巨胞饮途径感染Marc-145或者PAM细胞,但强弱毒在感染不同细胞时对肌动蛋白的依赖性存在明显的区别.本研究结果初步揭示了PRRSV野毒株和疫苗毒株入胞过程的差异,为进一步揭示PRRSV疫苗毒株致弱机制提供了前期基础.

Left bundle branch area pacing (LBBAP) has shown potential to be an alternative to biventricular pacing (BiVP) in patients with indications for cardiac resynchronization therapy (CRT). However, few studies focused on the long-term clinical outcomes of LBBAP versus BiVP.

Abstract Aims To investigate whether left bundle branch area pacing (LBBAP) can reduce the risk of new-onset atrial fibrillation (AF) compared with right ventricular pacing (RVP). Methods and results Patients with indications for dual-chamber pacemaker implant and no history of AF were prospectively enrolled if they underwent successful LBBAP or RVP. The primary endpoint was time to the first occurrence of AF detected by pacemaker programming or surface electrocardiogram. Follow-up at clinic visit was performed and multivariate Cox regression models were applied to evaluate the effect of LBBAP on new-onset AF. The final analysis included 527 patients (mean age 65.3 ± 12.6, male 47.3%), with 257 in the LBBAP and 270 in the RVP groups. During a mean follow-up of 11.1 months, LBBAP resulted in significantly lower incidence of new-onset AF (7.4 vs. 17.0%, P < 0.001) and AF burden (3.7 ± 1.9 vs. 9.3 ± 2.2%, P < 0.001) than RVP. After adjusting for confounding factors, LBBAP demonstrated a lower hazard ratio for new-onset AF compared with RVP {hazard ratio (HR) [95% confidence interval (CI)]: 0.278 (0.156, 0.496), P < 0.001}. A significant interaction existed between pacing modalities and the percentage of ventricular pacing (VP%) (P for interaction = 0.020). In patients with VP ≥ 20%, LBBAP was associated with decreased risk of new-onset AF compared with RVP [HR (95% CI): 0.199 (0.105, 0.378), P < 0.001]. The effect of pacing modalities was not pronounced in patients with VP < 20% [HR (95% CI): 0.751 (0.309, 1.823), P = 0.316]. Conclusion Left bundle branch area pacing demonstrated a reduced risk of new-onset AF compared with RVP. Patients with a high ventricular pacing burden might benefit from LBBAP.

To the Editor: Tricuspid regurgitation (TR) is a known complication of cardiac implantable electrical device (CIED) implantation with a prevalence of up to 10–30%. Due to the detrimental effects of right ventricular pacing (RVP) on cardiac function, His bundle pacing (HBP) and left bundle branch area pacing (LBBAP) have been increasingly used as physiological pacing modalities. This observational study aimed to assess the lead-related significant TR (moderate and severe) in patients with HBP, LBBAP, right ventricular apical pacing (RVAP), and right ventricular septal pacing (RVSP) in bradycardia patients during the two-year follow-up. All consecutive patients with left ventricular ejection fraction (LVEF) over 40% who received pacemaker implantation due to bradycardia were enrolled if they underwent successful HBP or LBBAP or RVP from October 2018 to December 2020 in Fuwai Hospital. The pacing modality was decided by the two physicians who performed the implantation procedures. Patients were excluded for the final analysis if they received implantable cardioverter-defibrillator or biventricular pacing, or if they had a history of tricuspid annuloplasty. All patients signed written informed consent for an agreement of the implantation procedure and analysis of clinical data, and this study was approved by the Review Board of Fuwai Hospital (No. 2019-1223). Venous access was obtained via the left or right axillary or subclavian vein. LBBAP or HBP was performed using the 3830 lead (Select Secure system, Medtronic, Inc., Minneapolis, MN, USA). The procedure of HBP and LBBAP followed the previous descriptions.[1,2] The procedure of RVP followed a standard fashion by placing the ventricular lead at the RV apex or septum, and stylet-driven pacing leads were routinely used. All patients were followed every 6 months after pacemaker implantation. We collected the pacing parameters at the latest device follow up. Lead-related complications were routinely tracked. All patients underwent transthoracic echocardiography at baseline (1 or 2 days before the procedure) and during follow up by using Vivid E9 systems (GE Vingmed Ultrasound AS, Horten, Norway). Multiple echocardiographic views were evaluated to quantify TR and to assess if there was any limitation of tricuspid leaflet motion induced by the septal electrode. Grading of TR was identified based on the 2017 American Society of Echocardiography recommendations for valvular regurgitation.[3] In patients with LBBAP, the distance from the septal leaflet of the tricuspid valve (TV) to the electrode screwing site (electrode–tricuspid valve distance, E–T distance) was measured from a standard 4-chamber view. TR grade was interpreted by two experienced echocardiographers. In cases of disagreement, an invited echocardiographer examined the echocardiogram and reached an agreement on the grade. The primary endpoint for this study was the first occurrence of worsening of TR during follow up, which was defined as an increase in TR of at least one grade and the TR grade up to moderate or severe as compared with that at pre-implantation. Statistical analyses were performed with SPSS version 24.0 (SPSS, Inc., Chicago, IL, USA). Continuous variables were presented as the mean ± standard deviation (SD) and compared with analysis of variance (ANOVA) analysis. Nominal data were presented as numbers and percentages and were compared by chi-squared test. Kaplan–Meier survival methods were used to compare significant TR risk. Cox regression models for significant TR were used to assess the association between pacing strategies and risk of TR. Receiver operating characteristics (ROC) curves were used to determine the cut-off point of the best E–T distance. Two-tailed P-value of <0.05 was considered significant. During the study period, 608 consecutive patients who underwent permanent pacemaker implantation were finally enrolled (HBP, n = 44, LBBAP, n = 269, RVSP, n = 203, and RVAP, n = 92). Most clinical characteristics were comparable among the four groups, except for age, the prevalence of AVB, previous atrial fibrillation (AF), and percutaneous coronary intervention or coronary artery bypass grafting history. The prevalence of moderate TR at baseline was comparable among the four pacing groups. During the mean follow-up of 23.7 ± 4.8 months, significant TR progression differed significantly among four pacing groups (LBBAP 14.5% [39/269] vs. HBP 2.3% [1/44] vs. RVSP 5.9% [12/203] vs. RVAP 13.0% [12/92],χ2 = 12.898, P = 0.004). LBBAP demonstrated the highest risk of significant TR worsening as compared with other pacing modalities, while HBP had the lowest risk of significant TR progression. During the follow-up period, 4.3% (26/608) of the cohort's patients suffered heart failure hospitalization events (HBP 0% [0/44], LBBAP 1.9% [5/269], RVSP 5.9% [12/203], RVAP 9.8% [9/92], χ2 = 13.946,P = 0.003), and no all-cause death events occurred. Two patients who received LBBAP suffered from perioperative septal perforation and received acute lead revision, and two patients in HBP experienced increased pacing threshold (increment of pacing threshold ≥1.0 V/0.4 ms) during the follow up and the pulse width of 1.0 ms was programmed. One of the patients in the RVAP group suffered chronic perforation and received late lead adjustment at a 3-month follow up. The univariate and multivariate analyses of risk factors of post-procedure significant TR worsening are shown in Table 1. When compared with RVP (including RVAP and RVSP), LBBAP conferred a 2.59-fold increased risk of significant TR worsening after adjustment for multiple clinical factors. HBP did not demonstrate a statistically significant decrease in the significant TR worsening risk. VP >40% was also an independent risk factor of significant TR worsening after pacemaker implantation in the whole study population. Table 1 - Univariate and multivariate analyses for the progression of TR in the overall cohort and LBBAP cohort. Variables Univariate analysis Multivariate analysis Hazard ratio (95% CI) P-value Hazard ratio (95% CI) P-value Overall cohort Pacing strategies HBP vs. RVP 0.25 (0.04–1.90) 0.183 0.24 (0.03–1.80) 0.164 LBBAP vs. RVP 3.06 (1.83–5.13) <0.001 2.59 (1.51–4.44) 0.001 Age (years) 1.02 (1.00–1.04) 0.049 1.12 (0.99–1.04) 0.156 Female 1.64 (1.00–2.69) 0.048 1.63 (0.98–2.69) 0.058 Atrial fibrillation 1.66 (1.01–2.73) 0.045 1.60 (0.96–2.67) 0.072 Ventricular pacing >40% 2.06 (1.18–3.58) 0.011 2.06 (1.15–3.70) 0.016 MI or coronary intervention 2.24 (1.22–4.13) 0.008 1.91 (0.99–3.68) 0.053 Operator 0.82 (0.60–1.11) 0.202 Baseline tricuspid regurgitation 0.80 (0.49–1.32) 0.380 LBBAP cohort Age (years) 1.02 (0.99–1.06) 0.196 1.00 (0.97–1.04) 0.948 Female 1.78 (0.79–3.97) 0.152 1.23 (0.52–2.91) 0.630 Atrial fibrillation 4.68 (2.12–10.33) <0.001 6.04 (2.50–14.60) <0.001 Ventricular pacing >40% 0.51 (0.23–1.10) 0.091 0.53 (0.21–1.39) 0.197 Previous MI or coronary intervention 1.64 (0.48–5.53) 0.457 Operator 0.75 (0.41–1.40) 0.336 Baseline tricuspid regurgitation 0.67 (0.36–1.25) 0.203 Distance from the base of TV leaflet 0.86 (0.76–0.97) 0.009 0.77 (0.68–0.91) 0.002 AF: Atrial fibrillation; CI: Confidence interval; HBP: His bundle pacing; LBBAP: Left bundle branch area pacing; MI: Myocardial infarction; RVP: Right ventricular pacing; TR: Tricuspid regurgitation; TV: Tricuspid valve. Compared with patients without significant worsening of TR, those with significant worsening of TR had a higher predicted prevalence of AF (50.0% vs. 24.9%, log-rank χ² = 9.952, P = 0.002) and a shorter E–T distance (20.2 ± 2.6 mm vs. 22.3 ± 2.6 mm, t value = 2.463, P = 0.010). Other clinical characteristics were comparable between patients with and without significantly worsening TR. As shown in Table 1, after adjustment of age, gender, VP >40%, and previous myocardial infarction or coronary disease history, the increased risk of significant TR progression was independently associated with AF (hazard ratio [HR] 6.04, 95% confidence interval [CI]: 2.50–14.60, P <0.001) and the E–T distance (HR 0.77, 95% CI: 0.68–0.91, P = 0.002) in patients received LBBAP implantation. However, VP >40% was no longer the independent risk factor of significant TR worsening after pacemaker implantation in patients who received LBBAP. ROC curve analysis was used to find the best cut-off value of the E–T distance influencing the risk of significant post-procedure TR progression. According to the cut-off value of 20 mm E–T distance, patients with LBBAP were divided into proximal LBBAP (E–T distance <20 mm) and distal LBBAP groups (E–T distance ≥20 mm). Kaplan–Meier analysis showed that distal LBBAP was related to significantly decreased risk of significant post-procedure TR progression (18.6% vs. 61.4%; χ² = 7.713, P = 0.006 by Log-rank test) when compared with proximal LBBAP. Pacing parameters and paced QRS duration were comparable between proximal and distal LBBAP. The present study demonstrated the risk of significant TR progression in bradycardia patients with LBBAP and comparison among four pacing modalities: HBP, LBBAP, RVSP, and RVAP. Our study found that LBBAP was associated with an increased risk of significant TR as compared with RVP. The risk of LBBAP-related significant TR progression was negatively associated with the E–T distance in the RV septum. AF was the other factor associated with an increased risk of LBBAP-related significant TR progression. Four pacing approaches demonstrated a different association between pacing lead and TV. HBP-related TR progression is very rare due to the location of His bundle. In some patients with HBP, the pacing lead may be positioned on the atrial side. Therefore, the TV function mostly remains stable after the HBP procedure. In this study, the lowest TR progression was observed in the HBP group (2.3%) during follow up. The prevalence of significant TR progression in patients with RVP in our study was consistent with the previous results,[4] and RVSP demonstrated less prevalence of post-procedure significant TR worsening than RVAP in our study. The less TR progression risk in patients with RVSP may be caused by mild mechanical and electrical dyssynchrony and less lead-related interference as compared with RVAP. The association of LBBAP with significant TR progression has been focused on in this study. In previous studies, Vijayaraman et al[1] reported 7% (4/55) of TR progression in patients with LBBAP. In their study, the E–T distance was 22.0 mm on average, and they reported a moderate TR due to the impingement of the septal leaflet by the LBBAP lead (E–T distance 11 mm). Our results observed a negative association between E–T distance and TR progression. Therefore, we surmised that the short E–T distance might contribute to the occurrence of LBBAP-related significant TR progression. The higher risk of significant TR progression in patients with short E–T distance might be due to the mechanical TV interference. Recently, Su et al[5] reported the occurrence of TR worsening of 12.3% in their single-center experience of 560 patients with LBBAP after 1-year follow up. Our study identified a cut-off point of 20 mm of E–T distance and found that distal LBBAP (E–T distance ≥20 mm) was associated with decreased risk of significant TR progression. In patients with LBBAP, AF was a risk factor associated with LBBAP-related significant TR progression. AF can cause the enlarged right atrium and tricuspid annular dilation and diastolic dysfunction of LV. Our study observed the association between AF and significant TR progression in patients with LBBAP but not in the whole study population with four pacing forms. In contrast, high VP percentage was another risk factor of post-CIED TR progression in the whole study population but not in patients with LBBAP. We speculated that the impact of dyssynchrony on TR progression due to high VP percentage in patients with non-physiological RVP was reduced in patients with LBBAP, and then the impact of AF on TR progression appeared obviously. Several limitations in this study need to be mentioned. First, the non-randomized study design was the major limitation and our findings might be overstated due to the unrecognized confounders. Second, the sample size was not comparable among the four pacing modality groups, and HBP or RVAP group had a relatively small sample size. However, the incidence of significant TR worsening was consistent with previous studies. Third, the postoperative TR outcomes could be impacted by the pacing electrode selection and lead reserve length. Additionally, RV function was not routinely evaluated in this study, which will be focused in the future study. Overall, LBBAP might be associated with an increased risk of lead-related significant TR as compared with other pacing strategies based on the two-year follow-up results, and the E–T distance might influence the risk of LBBAP-related significant TR progression. The distal LBBAP (with E–T distance ≥20 mm) may achieve equal pacing efficacy to proximal LBBAP and confer a comparable risk of significant TR progression with RVP. Funding This work was supported by grants from the National Natural Science Foundation of China to Xiaohan Fan (No. 81970284), and the project for the Distinguishing Academic Discipline of Fuwai Hospital (No. 2022-FWQN16) to Xiaofei Li. Conflicts of interest None.

Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) and Classical Swine Fever Virus (CSFV) are two important pathogens, which cause serious impact on swine industry worldwide. In our previous research, rPRRSV-E2, the recombinant PRRSV expressing CSFV E2 protein, could provide sufficient protection against the lethal challenge of highly pathogenic PRRSV and CSFV, and could maintained genetically stable in vitro. Here, to evaluate the virulence reversion potential risk, rPRRSV-E2 had been continuously passaged in vivo, the stability of E2 expression and virulence of the passage viruses were analyzed. The results showed that no clinical symptoms or pathological changes could be found in the inoculated groups, and there were no significant differences of viraemia among the test groups. Sequencing and IFA analysis showed that the coding gene of exogenous CSFV E2 protein existed in the passaged viruses without any sequence mutations, deletions or insertions, and could expressed steadily. It could be concluded that the foreign CSFV E2 gene in the genome of rPRRSV-E2 could be maintained genetically stable in vivo, and rPRRSV-E2 strain had relatively low level of potential risk for virulence reversion.