Clinical Characteristics and Comparative Proteomics Analysis of COVID-19-Related Atrioventricular Block.

Background: Atrioventricular block (AVB) is thought to be a rare cardiovascular complication of the coronavirus disease 2019 (COVID-19), though limited data are available beyond case reports. We aim to describe the baseline characteristics, proteomics profile, and outcomes for patients with COVID-19-related AVB. Methods: We prospectively recruited patients diagnosed with COVID-19-related AVB between November 2022 and March, 2023. Inclusion criteria were hospitalization for COVID-19 with the diagnosis of AVB. A total of 24 patients diagnosed with COVID-19 without AVB were recruited for control. We analyzed patient characteristics and outcomes and performed a comparative proteomics analysis on plasma samples of those patients and controls. Results: A total of 17 patients diagnosed with COVID-19-related AVB and 24 individuals diagnosed with COVID-19 infection without AVB were included. Among patients with COVID-19-related AVB, the proportion of concurrent pneumonia was significantly higher than controls (7/17 versus 2/24, p < 0.05). All 17 AVB patients (9 of permanent AVB, 8 of paroxysmal AVB) received permanent pacemaker implantation. No procedural-related complication occurred. In laboratory tests, the level of biomarkers indicating myocardial damage were substantially higher than controls, including high-sensitivity cardiac troponin-I (median 0.005 versus 0.002 ng/mL, p < 0.05), myoglobulin (median 39.0 versus 27.6 ng/mL, p < 0.05), and MB isoenzyme of creatine kinase (median 1.2 versus 0.8 U/L, p < 0.05). The level of N-terminal pro-b-type natriuretic peptide (median 241.0 versus 33.5 pg/mL, p < 0.05), C-reactive protein (median 4.8 versus 2.0 mg/L, p < 0.05), D-dimer (median 1.2 versus 0.2 µg/mL, p < 0.05), left ventricular end-diastolic diameter (median 49.3 versus 45.7 mm, p < 0.05) in patients with COVID-19-related AVB were significantly higher than controls. The level of albumin (median 41.9 versus 44.5 g/L, p < 0.05) was significantly lower than controls. In comparative proteomics analysis, we identified 397 human proteins. Several significantly altered plasma proteins related to inflammatory response (Serum amyloid A protein, C-reactive protein, Protein Adenosine 5'-monophosphate-activated protein kinase (AMPK), Alpha-2-macroglobulin), complement and coagulation cascades (Tetranectin, haptoglobin), and immune response (Neutrophil defensin 3, Fibrinogen beta chain) may contribute to the pathogenesis of COVID-19-related AVB. Conclusions: Patients with COVID-19-related AVB are more prone to have myocardial damage and concurrent pneumonia. Through laboratory tests and comparative proteomics analysis, we identified several differential expressed proteins (Serum amyloid A protein, Tetranectin, Neutrophil defensin 3) releated to the inflammatory response, complement and coagulation cascades, and immune response, which provides evidence of potential biomarkers and sheds light on the pathogenesis of COVID-19-related AVB.

Genetically predicted systemic inflammation and the risk of atrial fibrillation: A bidirectional two-sample Mendelian randomization study.

Background: Systemic inflammation has been proposed to be associated with the incidence of atrial fibrillation (AF), but whether it is a cause or a consequence of AF remains uncertain. We sought to explore the causal associations between systemic inflammation and AF using bidirectional Mendelian randomization (MR) analysis. Methods: Independent genetic variants strongly associated with AF were selected as instrumental variables from the largest genome-wide association study (GWAS) with up to 1,030,836 individuals. Regarding inflammation traits, genetic associations with 41 inflammatory cytokines and 5 inflammatory biomarkers were obtained from their corresponding GWASs databases. Effect estimates were primarily evaluated using the inverse-variance weighted (IVW) method, supplemented by sensitivity analyses using MR-Egger, weighted median, and MR-PRESSO methods. Results: In our initial MR analyses, we observed suggestive associations of genetically predicted interleukin-17 (IL-17), interleukin-2 receptor subunit alpha (IL-2rα), and procalcitonin (PCT) with AF. One standard deviation (SD) increase in IL-17, IL-2rα, and PCT caused an increase in AF risk by 6.3 % (OR 1.063, 95 %CI 1.011---1.118, p = 0.018), 4.9 % (OR 1.049, 95 %CI 1.007---1.094, p = 0.023) and 3.4 % (OR 1.034, 95 %CI 1.005---1.064, p = 0.022), respectively. Furthermore, our reverse MR analyses indicated that genetically predicted AF contributed to a suggestive increase in the levels of macrophage inflammatory protein-1ß (MIP1ß) (ß 0.055, 95 %CI 0.006 to 0.103, p = 0.028), while a decrease in the levels of fibrinogen (Fbg) (ß -0.091, 95 %CI -0.140 to -0.041, p < 0.001), which remained significant after multiple test correction. Conclusions: Our MR study identified several inflammatory biomarkers with suggestive causal associations regarding the upstream and downstream regulation of AF occurrence, offering new insights for therapeutic exploitation of AF. Further research is required to validate the underlying link between systemic inflammation and AF in larger cohorts.

A novel peptide-drug conjugate for glioma-targeted drug delivery.

The existence of the blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB) greatly limits the application of chemotherapy in glioma. To address this challenge, an optimal drug delivery system must efficiently cross the BBB/BBTB and specifically deliver therapeutic drugs into glioma cells while minimizing systemic toxicity. Here we demonstrated that glucose-regulated protein 78 (GRP78) and dopamine receptor D2 were highly expressed in patient-derived glioma tissues, and dopamine receptors were highly expressed on the BBB. Subsequently, we synthesized a novel "Y"-shaped peptide and compared the effects of different linkers on the receptor affinity and targeting ability of the peptide. A peptide-drug conjugate (pHA-AOHX-VAP-doxorubicin conjugate, pHA-AOHX-VAP-DOX) with a better affinity for glioma cells and higher solubility was derived for glioma treatment. pHA-AOHX-VAP-DOX could cross both BBB and BBTB via dopamine receptor and GRP78 receptor, and finally target glioma cells, significantly prolonging the survival time of nude mice bearing intracranial glioma. Furthermore, pHA-AOHX-VAP-DOX significantly reduced the toxicity of DOX and increased the maximum tolerated dose (MTD). Collectively, this work paves a new avenue for overcoming multiple barriers and effectively delivering chemotherapeutic agents to glioma cells while providing key evidence to identify potential receptors for glioma-targeted drug delivery.

Nowcasting and Forecasting Seasonal Influenza Epidemics - China, 2022-2023.

Background: Seasonal influenza resurged in China in February 2023, causing a large number of hospitalizations. While influenza epidemics occurred across China during the coronavirus disease 2019 (COVID-19) pandemic, the relaxation of COVID-19 containment measures in December 2022 may have contributed to the spread of acute respiratory infections in winter 2022/2023. Methods: Using a mathematical model incorporating influenza activity as measured by influenza-like illness (ILI) data for northern and southern regions of China, we reconstructed the seasonal influenza incidence from October 2015 to September 2019 before the COVID-19 pandemic. Using this trained model, we predicted influenza activities in northern and southern China from March to September 2023. Results: We estimated the effective reproduction number R e as 1.08 [95% confidence interval ( CI): 0.51, 1.65] in northern China and 1.10 (95% CI: 0.55, 1.67) in southern China at the start of the 2022-2023 influenza season. We estimated the infection attack rate of this influenza wave as 18.51% (95% CI: 0.00%, 37.78%) in northern China and 28.30% (95% CI: 14.77%, 41.82%) in southern China. Conclusions: The 2023 spring wave of seasonal influenza in China spread until July 2023 and infected a substantial number of people.

Association between nighttime heart rate and cardiovascular mortality in patients with implantable cardioverter-defibrillator: A cohort study.

BACKGROUND: Although studies have shown that an increased resting heart rate measured randomly at a single point of the day has been associated with adverse cardiovascular outcomes, the utility of continuous monitoring of nighttime heart rate (NTHR) has remained largely uninvestigated. OBJECTIVE: This study aimed to explore the association between NTHR and cardiovascular mortality. METHODS: The Study of Home Monitoring System Safety and Efficacy in Cardiac Implantable Electronic Device-implanted Patients, which is a prospective cohort study, enrolled patients with implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy defibrillator between 2010 and 2015. Baseline NTHR was measured during the programmed sleep period from 30 to 60 days after implantation. The primary outcome was cardiovascular mortality, fitted by a restricted cubic spline function. RESULTS: A total of 534 implantable cardioverter-defibrillator recipients with sinus rhythm during the detection window were included in the study. The mean baseline NTHR was 59.6 ± 8.0 beats/min. During the follow-up period of 60.4 ± 21.8 months, 88 (16.5%) patients experienced cardiovascular mortality. After considering potential confounders, a linear association was observed. Each 1 beat/min increase in NTHR was associated with a 7.8%, 10.1%, and 5.7% increase in the risk of cardiovascular mortality in the total population, patients with heart failure, and patients without heart failure, respectively. CONCLUSION: Continuous monitoring of NTHR may identify patients at high risk of cardiovascular mortality in a timely manner, with the potential for "preemptive" action. TRIAL REGISTRATION: No. ChiCTR-ONRC-13003695.

Progression of Device-Detected Atrial High-Rate Episodes and the Risk of All-Cause Mortality.

Atrial high-rate episodes (AHREs) are prevalent in approximately 1/3 of patients with cardiac implanted electronic devices and are associated with an increased risk of several adverse outcomes. This study aimed to explore the factors associated with AHRE progression and the risk of all-cause mortality. At least 1 day with AHRE burden ≥15 minutes was identified in 124 of 343 recipients (36.2%) of an implantable cardioverter defibrillator or cardiac resynchronization therapy device. We included patients whose AHRE burden at the time of first detection was ≥15 minutes but <24 hours (n = 107). Various cut-off values (15 minutes, 6 hours, and 24 hours) of daily AHRE burden were analyzed. During an average follow-up of 4.2 years, 60 patients (56.1%) experienced ≥1 progression to greater AHRE burden. Patients with hypertension or greater AHRE burden at first detection were associated with faster progression. In addition, 27 deaths (45%) occurred among 60 patients with AHRE progression, compared with 25.5% (12 of 47) for those without progression. After multivariable adjustment, AHRE progression was independently associated with all-cause mortality (hazard ratio 2.56, 95% confidence interval 1.23 to 5.35, p = 0.012). Notably, AHRE progression within 1 month after their first detection was associated with an increased risk for all-cause mortality (hazard ratio 4.01, 95% confidence interval 1.76 to 9.16, p = 0.001) compared with patients without progression. However, a similar risk was not observed among patients with AHRE progression occurring after 1 month after their first detection. In conclusion, >1/2 of the patients with AHRE progressed to a greater burden over time. Continuous monitoring of the AHRE burden may help identify patients at great risk for death.

A systematic review and meta-analysis of pain neuroscience education for chronic low back pain: short-term outcomes of pain and disability.

BACKGROUND: The evidence supporting the application of pain neuroscience education (PNE) in patients with chronic low back pain (LBP) remains some arguments. OBJECTIVE: This review aims to investigate the effect of PNE alone and combined with physical therapy or exercise for chronic LBP. METHODS: PubMed, Embase, Web of Science, and the Cochrane databases were searched from establishment to June 3, 2023. Randomized controlled trials (RCT) evaluating the effect of PNE in patients with chronic LBP were considered eligible. Data were analyzed using a random-effects model (I2 >50%) or a fixed-effects model (I2 <50%) and trials were appraised using the Cochrane ROB tool. Meta-regression was conducted to assess the moderator factors. RESULTS: Seventeen studies (1078 participants) were included in this review. PNE plus exercise and PNE plus physiotherapy both showed a reduction of short-term pain (mean differences [MD] -1.14 [-1.55, -0.72]; MD -1.15 [-1.67, -0.64]) and disability (standardized mean difference [SMD] -0.80 [-1.13, -0.47]; SMD -0.85 [-1.29, -0.40]) than physiotherapy or exercise alone. Meta-regression showed that only single PNE session duration was associated with a greater reduction in pain (P < .05). Subgroup results showed that a single PNE session exceeding 60 minutes (MD -2.04), 4 to 8 sessions (MD -1.34), intervention for 7 to 12 weeks (MD -1.32), and a group-based approach (MD -1.76) may be more beneficial. CONCLUSION: This review indicates that adding PNE to treatment programs would lead to more efficacious effects for chronic LBP. Additionally, we preliminarily extracted dose-effect relationships for PNE intervention, providing guidance for clinicians to design effective PNE sessions.

Quantitative analysis reveals influencing factors to facilitate successful anodal-ring capture in left bundle branch pacing.

AIMS: Left bundle branch pacing (LBBP) maintains left ventricular synchrony but induces right ventricular conduction delay (RVCD). Although anodal-ring capture (ARC) during bipolar LBBP improves RVCD, it is not achieved in all patients receiving LBBP. This study aimed to analyze the factors influencing ARC implementation. METHODS AND RESULTS: Patients receiving LBBP with intraoperative ARC testing were enrolled. Electrocardiographic parameters were measured, including stimulus-to-QRS duration (stim-QRSd), stimulus-to-left/right ventricular activation time (stim-LVAT/RVAT), and V6-V1 interpeak interval. The distribution of lead-tip sites was described as the corrected longitudinal and lateral distance (longit-/lat-dist). Relative angles of the LBBP lead were measured. Echocardiography in short-axis view was used to measure the intraseptal lead length. Intergroup comparisons, correlation analysis, and stepwise logistic regression were performed. In total, 105 patients were included, among which 65 (62%) patients achieved ARC at a pacing output ≤ 5.0 V/0.5 ms (average 3.1 V/0.5 ms). Anodal-ring capture further shortened the stim-QRSd by 13.1 ± 7.5 ms. Better unipolar-ring (cathodal) threshold and R-wave sensing in LBBP-ARC group indicated the critical role of ring-septum contact in ARC. Longer corrected longit-dist and shorter corrected lat-dist of lead-tip sites were positively correlated with higher success likelihood of ARC, likely due to the greater relative angle in which the lead enters the septum and consequently the longer intraseptal lead length and better ring-septum contact. CONCLUSION: This study elucidated the factors affecting the success likelihood of LBBP-ARC. These findings improve the understanding of LBBP-ARC, providing references for future research and clinical practice.

Distance between the lead-implanted site and tricuspid valve annulus in patients with left bundle branch pacing: Effects on postoperative tricuspid regurgitation deterioration.

BACKGROUND: Left bundle branch pacing (LBBP) is an alternative strategy for His-bundle pacing (HBP); however, little is known about tricuspid regurgitation (TR) deterioration after LBBP implantation. OBJECTIVES: The purpose of this study was to characterize the incidence of post-LBBP TR deterioration and identify predicting factors, especially lead position parameters. METHODS: Patients who received LBBP were continuously enrolled from January 2018 to August 2020. The progression of TR and the anatomic position of LBBP were characterized by echocardiography. RESULTS: A total of 89 patients were enrolled and assigned to 2 subgroups based on the degree of TR before LBBP implantation: 58 (65.2%) with relatively normal tricuspid valve (TV) function (grade 0/1 subgroup: with none/trivial or mild TR) and 31 (34.8%) with more severe TR (grade 2/3 subgroup: with moderate or severe TR). At 19.0 ± 6.5 months of follow-up, 29 patients (32.6%) had TR deterioration, and 23 of them were in the grade 0/1 subgroup. In the grade 0/1 subgroup, patients with TR deterioration had a shorter distance between the lead-implanted site and TV (Lead-TA-dist) than those without TR (19.0 ± 7.6 vs 23.9 ± 5.4; P = .006). The receiver operating characteristic (ROC) curve (area under the curve 0.721; 95% confidence interval [CI] 0.575-0.867; P = .005) indicated the favorable efficacy of Lead-TA-dist for predicting TR deterioration after LBBP. Lead-TA-dist ≤16.1 mm was independently associated with TR deterioration after LBBP (hazard ratio 0.20; 95% CI 0.06-0.76; P = .017). CONCLUSION: TR was a common complication of LBBP implantation. In patients with none/trivial or mild TR, Lead-TA-dist ≤16.1 mm was an independent predictor of TR deterioration after LBBP implantation.

Left Bundle Branch Area Pacing Contributes to a Greater Acute Blood Pressure Reduction Compared to Right Ventricular Pacing.

Background: Several previous studies have explored the potential arterial blood pressure (BP) changes in patients undergoing right ventricular pacing (RVP), however, the relationship between left bundle branch area pacing (LBBAP) and BP variations remains unknown. This study aimed to examine the acute BP variations following LBBAP and RVP implantation in patients with bradycardia. Methods: We conducted a single-center retrospective study including all patients who underwent de-novo dual-chamber pacemaker implantation between January 2019 and June 2021. Patients were divided into two groups, LBBAP and RVP, and propensity score-matching (PSM) was used to balance confounding factors. Three time periods were defined according to the timing of the implant: baseline (within 24 hours before implantation), hyper-acute period (0-24 hours post-implantation), and acute period (24-48 hours post-implantation). BP was measured at least three times per period using an arm pressure cuff and then averaged for analysis, which allowed us to determine the acute impact of pacemaker implantation on BP. Results: From a cohort of 898 patients, 193 LBBAP receivers were matched to 193 RVP receivers. A significant decrease in systolic BP (SBP) after the implantation was observed in the study cohort, from baseline 137.3 ± 9.2 mmHg to the acute period of 127.7 ± 9.4 mmHg (p < 0.001). The LBBAP group exhibited a greater SBP reduction than the RVP group ( Δ 11.6 ± 6.2 mmHg vs. Δ 7.6 ± 5.8 mmHg, p < 0.001). In further subgroup analysis, LBBAP receivers who had high baseline SBP (p < 0.001) and those without using anti-hypertensive drugs (p = 0.045) appeared to have a higher magnitude of SBP reduction. Conclusions: Permanent pacemaker implantation may contribute to an acute decrease in systolic BP, which was more pronounced in LBBAP receivers. Future experimental and clinical investigations are necessary to explore the underlying mechanisms and the long-term hemodynamic effects of LBBAP versus RVP.

Long-term follow-up results of patients with left bundle branch pacing and exploration for potential factors affecting cardiac function.

Background: Left bundle branch pacing (LBBP) is an alternative strategy for His bundle pacing (HBP). This study aimed to analyze the long-term performance of LBBP and the potential factors affecting long-term cardiac function. Methods: Patients with LBBP were continuously enrolled from January 2018 to August 2020. Pacing parameters, electrocardiogram (ECG), and echocardiography were collected. The anatomic position of LBBP leads was described by echocardiographic and fluoroscopic parameters. Results: A total of 91 patients with a median follow-up of 18 months were enrolled. Most patients maintained stable pacing parameters during follow-up. The intra-septal position of the 3830 lead also remained stable as the distance from the lead tip to the left surface of the ventricular septum was 0.4 (0, 1.4) mm. The overall level of left ventricular ejection fraction (LVEF) slightly increased. 59 patients had improved LVEF (∆LVEF > 0), while 28 patients had unchanged or reduced LVEF (∆LVEF ≤ 0). The declines of baseline LVEF, ∆ Paced QRSd, and corrected longitudinal distance (longit-dist) of lead-implanted site correlated with LVEF improvement, and these three factors had negative linear correlations with ∆LVEF. Patients with tricuspid valve regurgitation (TVR) deterioration had longer follow-up duration (20.5 vs. 15.0 months, p = 0.01) and shorter Lead-TVA-dist (18.6 vs. 21.6 mm, p = 0.04) than those without TVR deterioration. Conclusion: Patients with LBBP generally remained stable in pacing performance, anatomic lead positions, and cardiac function in long-term follow-up. Baseline LVEF, ∆ Paced QRSd, and corrected longit-dist might be associated with potential LVEF decrease, which required further confirmation.

Changes of repolarization parameters after left bundle branch area pacing and the association with echocardiographic response in heart failure patients.

Background: Left bundle branch area pacing (LBBAP) has become a safe and effective option for heart failure (HF) patients indicated for cardiac resynchronization therapy (CRT) and/or ventricular pacing, yet the response rate was only 70%. Repolarization parameters were demonstrated to be associated with cardiac mechanics and systolic function. This study aimed to investigate the effects of LBBAP on repolarization parameters and the potential association between those parameters and echocardiographic response. Methods and results: A total of 59 HF patients undergoing successful LBBAP were consecutively included. QTc, Tpeak-Tend (TpTe), and TpTe/QTc were measured before and after the implantation. The results turned out that the dispersion of ventricular repolarization (DVR) improved after LBBAP among the total population. Although trends of repolarization parameters varied according to different QRS configurations at baseline, the post-implant parameters showed no significant difference between groups. The association between repolarization parameters and LBBAP response was then evaluated among patients with wide QRS. Multivariate analysis demonstrated that post-implant TpTe was the independent predictor of LBBAP response (p < 0.05). Receiver operating characteristic analysis indicated an area under the curve of 0.77 (95% CI, 0.60-0.93) with a cutoff value of 81.2 ms (p < 0.01). Patients with post-implant TpTe<81.2 ms had a significantly higher rate of echocardiographic response (93.3 vs. 44.4%, p < 0.01). Further subgroup analysis indicated that the predictive value of post-implant TpTe for LBBAP response was more significant in non-left bundle branch block (LBBB) patients than in LBBB patients. Conclusion: LBBAP improved DVR significantly in HF patients. Post-implant TpTe was associated with the echocardiographic response after LBBAP among patients with wide QRS, especially for non-LBBB patients.

Quantitative distance and electrocardiographic parameters for lead-implanted site selection to enhance the success likelihood of left bundle branch pacing.

BACKGROUND: Left bundle branch pacing (LBBP) is a novel near-physiological pacing method that still lacks quantitative criteria to guide the selection of lead-implanted sites to enhance the success likelihood of lead deployments. This study aimed to quantitatively analyze the relationships of LBBP success likelihood to the distribution of lead-implanted sites and the lead-localization-pacing electrocardiographic (ECG) features. METHODS: All the lead-implanted sites in patients with finally successful LBBP were enrolled for analysis, including successful and failed sites. A novel coordinate system was invented to describe the sites' distribution as longitudinal distance (longit-dist) and lateral distance (lat-dist). Corrected distance parameters were generated to eliminate the cardiac dimension variations. The lead-localization-pacing ECG parameters were also collected, such as paced QRS duration (locat-QRSd), left ventricular activation time (locat-LVAT), LVAT/QRSd ratio (locat-LVAT/QRSd), and QRS directions. RESULTS: A total of 94 patients with 105 successful sites and 93 failed sites were enrolled. Longit-dist and corrected longit-dist of successful sites were significantly longer, while locat-QRSd and locat-LVAT were shorter and locat-LVAT/QRSd was lower than failed sites. There was a positive dose-response relationship between LBBP success likelihood and corrected longit-dist with a cut-off of 26.95 mm, whereas there were negative dose-response relationships of LBBP success likelihood to locat-QRSd, locat-LVAT, and locat-LVAT/QRSd with the cut-offs of 142 ms, 92 ms, and 64.7%, respectively. Downward QRS direction in II/III ECG leads was also associated with successful LBBP. CONCLUSION: Longit-dist, locat-QRSd, locat-LVAT, and locat-LVAT/QRSd were quantitative parameters to guide the selection of lead-implanted sites during LBBP implantation. Quantitative distance and electrocardiographic parameters for lead-implanted site selection to enhance the success likelihood of left bundle branch pacing. LBBP, left bundle branch pacing; Longit-dist, longitudinal distance; CL-apex-dist, distance from contraction line to apex; LBBB, left bundle branch block; IVCD, intraventricular conduction delay; Locat-QRSd, lead-localization-pacing QRS duration; Locat-LVAT, lead-localization-pacing left ventricular activation time; Locat-LVAT/QRSd, lead-localization-pacing LVAT/QRSd ratio.

The variability and burden of severe sleep apnea and the relationship with atrial fibrillation occurrence: analysis of pacemaker-detected sleep apnea.

STUDY OBJECTIVES: This was a pilot study to evaluate the long-term variability and burden of respiratory disturbance index (RDI) detected by pacemaker and to investigate the relationship between RDI and atrial fibrillation (AF) event in patients with pacemakers. METHODS: This was a prospective study enrolling patients implanted with a pacemaker that could calculate the night-to-night RDI. The mean follow-up was 348 ± 34 days. The RDI variability was defined as the standard deviation of RDI (RDI-SD). RDI burden was referred to as the percentage of nights with RDI ≥ 26. The patient with RDI ≥ 26 in more than 75% nights was considered to have a high sleep apnea (SA) burden. An AF event was defined as a daily AF duration > 6 h. RESULTS: Among 30 patients, the mean RDI of the whole follow-up period was 24.5 ± 8.6. Nine (30%) patients were diagnosed with high SA burden. Patients with high SA burden had a higher BMI (26.7 ± 4.8 vs 23.2 ± 3.9, p = 0.036), a higher prevalence of hypertension (86% vs 39%, p = 0.031), and a larger left ventricular diastolic diameter (49.2 mm vs 46.7 mm, p = 0.036). The RDI-SD in patients with a higher burden was significantly greater than that in the patients with less burden (10.7 ± 4.9 vs 5.7 ± 1.4, p = 0.036). Linear regression showed that participants with a higher RDI tended to have a higher SD (R = 0.661; p < 0.001). The mean RDI (OR = 1.118, 95%CI 1.008-1.244, p = 0.044) was associated with AF occurrence. CONCLUSION: Using a metric such as burden of severe SA may be more appropriate to demonstrate a patient's true disease burden.

Relationship of paced left bundle branch pacing morphology with anatomic location and physiological outcomes.

BACKGROUND: Left bundle branch pacing (LBBP) is an emerging physiological pacing modality. However, little is known about pacing at different locations on the left bundle branch (LBB). OBJECTIVE: The purpose of this study was to explore pacing and physiological characteristics associated with different LBBP locations. METHODS: The study included 68 consecutive patients with normal unpaced QRS duration and successful LBBP implantation. Patients were divided into 3 groups according to the paced QRS complex as left bundle branch trunk pacing (LBTP), left posterior fascicular pacing (LPFP), or left anterior fascicular pacing (LAFP). Electrocardiographic (ECG) characteristics, pacing parameters, and fluoroscopic localization were collected and analyzed. RESULTS: There were 17 (25.0%), 35 (51.5%), and 16 (23.5%) patients in the LBTP, LPFP, and LAFP groups, respectively. All subgroups had relatively narrow paced QRS complex (128.6 ± 9.1 ms vs 133.7 ± 11.2 ms vs 134.8 ± 9.6 ms; P = .170), fast left ventricular activation (70.4 ± 9.0 ms vs 70.6 ± 10.2 ms vs 71.0 ± 9.0 ms; P = .986), as well as low and stable pacing thresholds. Delayed right ventricular activation and interventricular dyssynchrony were similar between groups. Fluoroscopic imaging indicated that the lead tip was located most commonly in the basal-middle region of the septum (67.7%), and this was independent of paced QRS morphology group (88.2% vs 57.1% vs 68.8%; P = .106). CONCLUSION: Pacing at different sites of the LBB resulted in similar intraventricular and interventricular electrical synchrony in patients with an intact conduction system. Fluoroscopic imaging alone could not predict specific LBBP paced ECG morphology.

Feasibility and efficacy of left bundle branch area pacing in patients indicated for cardiac resynchronization therapy.

AIMS: The present study was to evaluate the feasibility and clinical outcomes of left bundle branch area pacing (LBBAP) in cardiac resynchronization therapy (CRT)-indicated patients. METHODS AND RESULTS: LBBAP was performed via transventricular septal approach in 25 patients as a rescue strategy in 5 patients with failed left ventricular (LV) lead placement and as a primary strategy in the remaining 20 patients. Pacing parameters, procedural characteristics, electrocardiographic, and echocardiographic data were assessed at implantation and follow-up. Of 25 enrolled CRT-indicated patients, 14 had left bundle branch block (LBBB, 56.0%), 3 right bundle branch block (RBBB, 12.0%), 4 intraventricular conduction delay (IVCD, 16.0%), and 4 ventricular pacing dependence (16.0%). The QRS duration (QRSd) was significantly shortened by LBBAP (intrinsic 163.6 ± 29.4 ms vs. LBBAP 123.0 ± 10.8 ms, P < 0.001). During the mean follow-up of 9.1 months, New York Heart Association functional class was improved to 1.4 ± 0.6 from baseline 2.6 ± 0.6 (P < 0.001), left ventricular ejection fraction (LVEF) increased to 46.9 ± 10.2% from baseline 35.2 ± 7.0% (P < 0.001), and LV end-diastolic dimensions (LVEDD) decreased to 56.8 ± 9.7 mm from baseline 64.1 ± 9.9 mm (P < 0.001). There was a significant improvement (34.1 ± 7.4% vs. 50.0 ± 12.2%, P < 0.001) in LVEF in patients with LBBB. CONCLUSION: The present study demonstrates the clinical feasibility of LBBAP in CRT-indicated patients. Left bundle branch area pacing generated narrow QRSd and led to reversal remodelling of LV with improvement in cardiac function. LBBAP may be an alternative to CRT in patients with failure of LV lead placement and a first-line option in selected patients such as those with LBBB and heart failure.

Bilateral Bundle Branch Area Pacing to Achieve Physiological Conduction System Activation.

BACKGROUND: Left bundle branch pacing (LBBP) is a technique for conduction system pacing, but it often results in right bundle branch block morphology on the ECG. This study was designed to assess simultaneous pacing of the left and right bundle branch areas to achieve more synchronous ventricular activation. METHODS: In symptomatic bradycardia patients, the distal electrode of a bipolar pacing lead was placed at the left bundle branch area via a transventricular-septal approach. This was used to pace the left bundle branch area, while the ring electrode was used to pace the right bundle branch area. Bilateral bundle branch area pacing (BBBP) was achieved by stimulating the cathode and anode in various pacing configurations. QRS duration, delayed right ventricular activation time, left ventricular activation time, and interventricular conduction delay were measured. Pacing stability and short-term safety were assessed at 3-month follow-up. RESULTS: BBBP was successfully performed in 22 of 36 patients. Compared with LBBP, BBBP resulted in greater shortening of QRS duration (109.3±7.1 versus 118.4±5.7 ms, P<0.001). LBBP resulted in a paced right bundle branch block configuration, with a delayed right ventricular activation time of 115.0±7.5 ms and interventricular conduction delay of 34.0±8.8 ms. BBBP fully resolved the right bundle branch block morphology in 18 patients. In the remaining 4 patients, BBBP partially corrected the right bundle branch block with delayed right ventricular activation time decreasing from 120.5±4.7 ms during LBBP to 106.1±4.2 ms during BBBP (P=0.005). CONCLUSIONS: LBBP results in a relatively narrow QRS complex but with an interventricular activation delay. BBBP can diminish the delayed right ventricular activation, producing more physiological ventricular activation. Graphic Abstract: A graphic abstract is available for this article.