Biventricular Pacing In Patients Research Articles

Electrocardiographic predictors of haemodynamic benefit from biventricular pacing: the role of atrioventricular timing measures

Abstract Background Patients with heart failure (HF) and left bundle branch block (LBBB) are selected for biventricular pacing (BVP) cardiac resynchronisation therapy (CRT) based on their 12-lead ECG QRS complex duration (QRSd). This is due to the long-held belief that BVP delivers its beneficial effects almost exclusively by reducing ventricular dyssynchrony. Recent work (1) suggests that atrioventricular delay (AVD) shortening is another key mechanism of benefit and, therefore, that atrioventricular timing may be an important CRT substrate. The ideal 12-lead ECG measure to facilitate patient selection that yields benefits from this mechanism is yet to be elucidated. Purpose We set out to establish whether incorporating a measure of AV delay provides additional benefit over and above using QRSd when using the 12-lead ECG to select patients who are likely to obtain haemodynamic benefit from BVP. Methods We identified patients in sinus rhythm with HF and LBBB meeting clinical criteria for CRT who had undergone implantation of a BVP device and had also undergone high-precision haemodynamic assessment of BVP. This is where pacing is alternated between atrium-only pacing (AAI) and DDD pacing using BVP multiple times for each of a full range of AVDs during continuous beat-by-beat blood pressure recording to determine the peak haemodynamic benefit of BVP in each patient. We extracted potentially predictive, pre-specified intrinsic (unpaced) ECG features that incorporated left or right AV timing to varying extents: PR interval (PR), end-of-p-wave-to-R-wave-peak-time-V6 (Pend-RWPTV6), start-of-p-wave-to-end-of-QRS (P-QRSend) as well as conventional QRSd. Pearson's test assessed the unadjusted correlation between intrinsic ECG intervals and BVP haemodynamic benefit(∆SBP). A multiparametric regression analysis model was constructed to account for confounders and interactions between different ECG features. Results 53 eligible patients were identified. 39 were male (73.6%), 31 had non-ischaemic aetiology (58.5%), mean LVEF was 27.6% ± SD 4.79 and mean LVEDD was 57.9± SD 9.4mm. Unadjusted correlations between intrinsic ECG features were not strong but favoured P-QRSend as a potentially predictive feature; R2 values: PR 0.28 (p=0.04), Pend-RWPTV6 0.19 (p=0.18), P-QRSend 0.27 (p=0.054), QRSd 0.045 (p=0.75). However, the multiparametric model revealed that utilising both PR interval and Pend-RWPTV6 in a predictive model showed better-adjusted correlation with BVP haemodynamic benefit (R2 0.54, p=0.04). Conclusion ECG features that incorporate either right (PR interval) or left (Pend-RWPTV6) AVD or both (P-QRSend) are superior to QRSd for predicting haemodynamic benefit from BVP in patients with HF and LBBB. This further reinforces the role of AVD shortening as a mechanism of benefit of BVP and suggests that selecting patients on the basis of AV timing may yield more overall benefit from CRT delivered by BVP or potentially conduction system pacing.ECG interval measurementCorrelation Graphs

Comparison of long-term risk of device-related complications between left bundle branch area pacing and biventricular pacing in candidates for resynchronization therapy

Abstract Introduction Cardiac resynchronization therapy (CRT) with biventricular pacing (BVP) is a well established therapy in patients with reduced left ventricular ejection fraction (LVEF), heart failure, and wide QRS. Left bundle branch area pacing (LBBAP) has recently been shown to be a feasible and effective alternative to BVP. Comparative data on the risk of complications between LBBAP and BVP among CRT candidates are lacking. Purpose The aim of this study was to compare the long-term risk of device-related complications between LBBAP and BVP in a cohort of patients undergoing CRT. Methods Prospective, multicenter, observational study enrolling 668 consecutive patients (71.2±10.0 years, 52.2% male, 59.4% NYHA class >II), with LVEF ≤35% (mean 33.4±4.3%) who underwent BVP (n=560) or LBBAP (n=108) for the first time for Class I or II indications for CRT from January 2020 to June 2023 at 6 Italian centers. Propensity matching for baseline characteristics yielded 90 matched pairs. Rate and nature of device-related complications occurring during follow-up were prospectively collected and compared between the two groups. Results During a mean follow-up of 18 months, device-related complications were observed in 14 patients: 11 in BVP (12.2%), and in 3 in LBBAP (3.3%) (p=0.026). Compared to BVP patients, LBBAP patients showed a higher cumulative survival free from first device–related complication (Figure). Complications related to coronary sinus lead were most frequently observed in BVP patients (36.4% of all complications). The rate of overall lead-related complications was 6.7 and 2.2% in BVP and LBBAP patients, respectively (p=0.149). Conclusion LBBAP was associated with a lower long-term risk of device-related complications compared with BVP in patients with CRT indications.

Time-dependent activation and repolarization changes following left bundle branch area pacing versus conventional biventricular pacing in patients with dyssynchronous heart failure

Abstract Background Cardiac Resynchronization Therapy (CRT) is the standard treatment for patients with dyssynchronous heart failure. Despite the effectiveness of conventional biventricular pacing (BiVP), 6-16% of patients develop ventricular tachyarrhythmias (VTAs) within a year of implantation. The relationship between BiVP and the development of VTAs is still under debate. During BiVP, the left-sided epicardium-to-endocardium activation creates a non-physiological activation and hence a non-physiological repolarization, which might trigger VTAs. A novel alternative treatment option to BiVP that on the contrary induces a left ventricular endocardium-to-epicardium activation, is left bundle branch area pacing (LBBAP). We hypothesized that LBBAP leads to a more homogenous repolarization than conventional BiVP. Purpose To compare time-dependent activation and repolarization changes in patients with dyssynchronous heart failure receiving LBBAP versus BiVP. Methods Patients eligible for CRT who underwent LBBAP (n=21) or BiVP (n=94) were retrospectively included. Standard 12-lead electrocardiograms obtained prior to implantation [baseline], shortly following implantation (0-2 days, [acute phase]), and after prolonged pacing during follow-up (31-180 days, [chronic phase]) were analyzed. QRS duration and QRS area were calculated through reconstruction of the vectorcardiogram and further analyzed together with corrected QT (QTc) and corrected Tpeak-Tend (Tp-e,c) intervals using a semi-automatic approach in MATLAB. Differences between LBBAP and BiVP patients were determined using the Mann-Whitney U-test. Time-dependent changes within groups were determined using the Wilcoxon signed-rank tests. Significance was defined as a p-value ≤0.05. Results (see figure): Compared to baseline, QRS duration and QRS area decreased significantly during the acute phase (both p < 0.01) and stabilized during chronic pacing for both BiVP and LBBAP patients. Differences in QRS duration or QRS area between LBBAP and BiVP were not significant at any of the time points. In the acute phase, BiVP resulted in a temporary and significant prolongation of both QTc and Tp-e,c compared to baseline (both p < 0.01). However, there was a subsequent shortening observed between the acute and chronic phases for both QTc and Tp-e,c (both p < 0.01). Compared to baseline, LBBAP acutely shortened Tp-e,c (p = 0.02) and tended to shorten QTc. During chronic pacing, LBBAP shortened QTc and Tp-e,c compared to baseline (p = 0.01 and p < 0.01). The decreases in QTc and Tp-e,c were larger in LBBAP than in BiVP patients in the acute and chronic pacing phase (all p <0.01). Conclusion CRT induces activation changes in both BiVP and LBBAP patients to a comparable extent. While BiVP leads to an acute increase in repolarization dispersions, LBBAP reduces markers of repolarization dispersion compared to baseline. The diminished dispersion of repolarization might contribute to an antiarrhythmic effect with LBBAP.

Enhancing Cardiac Pacing Strategies: A Review of Conduction System Pacing Compared to Right and Biventricular Pacing and their influence on myocardial function.

Traditional right ventricular pacing has been linked to the deterioration of both left ventricular diastolic and systolic function. This worsening often culminates in elevated rates of hospitalization due to heart failure, an increased risk of atrial fibrillation, and increased morbidity. While biventricular pacing has demonstrated clinical and echocardiographic improvements in patients afflicted with heart failure and left bundle branch block, it has also encountered significant challenges, such as a notable portion of non-responders and procedural failures attributed to anatomical complexities. In recent time, the interest has shifted towards conduction system pacing, initially His bundle pacing and more recently left bundle branch area pacing, as promising alternatives to the established methods. In contrast to other approaches, conduction system pacing offers the advantage of fostering more physiological and harmonized ventricular activation by directly stimulating the His-Purkinje network. This direct pacing results in a more synchronized systolic and diastolic function of left ventricle compared to right ventricular pacing and biventricular pacing. Of particular note is conduction system pacing's capacity to yield shorter QRS, conserve left ventricular ejection fraction, and reduced rates of mitral and tricuspid regurgitation when compared to right ventricular pacing. The efficacy of conduction system pacing has also been found to have better clinical and echocardiographic improvement than biventricular pacing in patients requiring cardiac resynchronization. This review will delve into myocardial function in conduction system pacing compared to right ventricular pacing and biventricular pacing.

Long-term efficacy of left bundle branch pacing and biventricular pacing in patients with heart failure complicated with left bundle branch block.

Left bundle branch pacing (LBBP) can physiologically correct complete left bundle branch block (CLBBB), and has become the best alternative to biventricular pacing (BiVP). To compare the efficacy of LBBP and BiVP in patients with heart failure (HF) complicated with CLBBB. This was a single-center retrospective study. Patients with HF complicated with CLBBB who underwent successful cardiac resynchronization therapy (CRT) in Wuhan Asian Heart Hospital from June 2018 to June 2023 were enrolled and divided into LBBP group and BiVP group according to the pacing method. The primary endpoints were the absolute increase of left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), and echocardiographic response rate. Secondary endpoints were all-cause mortality, heart failure hospitalization (HFH), NT-proBNP, paced QRS duration, pacing threshold, and procedural duration. A total of 120 patients were enrolled in this study, including 60 patients in LBBP group and 60 patients in BiVP group. The median follow-up time was 37 ± 19 months. Compared with BiVP group, LBBP group had a more significant increase in absolute LVEF (ΔLVEF) (14.8 ± 9.9% vs. 10.7 ± 9.0%, P = 0.02), a more significant reduction in LVEDD (56.9 ± 10.9 mm vs. 61.1 ± 10.8 mm, P = 0.03), and a higher echocardiographic super response rate (65% vs. 45%, P = 0.02). There were no significant differences in all-cause mortality (1.7% vs. 10.0%, P = 0.11) and HFH (6.7% vs. 13.3%, P = 0.22). In terms of paced QRS duration (128.7 ± 14.1 ms vs. 137.5 ± 16.5 ms, P = 0.002), pacing threshold (0.72 ± 0.21 V/0.4 ms vs. 1.39 ± 0.51 V/0.4 ms, P < 0.001), procedural duration (134.1 ± 32.2 min vs. 147.7 ± 39.4 min, P = 0.04), the LBBP group was superior to the BiVP group. In nonischemic cardiomyopathy (NICM) patients with HF combined with CLBBB and LVEF ≤ 35%, LBBP is better than BiVP.

Efficacy of left bundle branch area pacing versus biventricular pacing in patients treated with cardiac resynchronization therapy: Select site – cohort study

BackgroundCardiac resynchronization therapy (CRT) is typically attempted with biventricular (BiV) pacing. One-third of patients are nonresponders. Left bundle branch area pacing (LBBAP) has been evaluated as an alternative means. ObjectiveThe purpose of this study was to assess the feasibility and clinical response of permanent LBBAP as an alternative to BiV pacing. MethodsOf 479 consecutive patients referred with heart failure, 50 with BiV-CRT and 51 with LBBAP-CRT were included in this analysis after study exclusions. Quality-of-Life (QoL) assessments, echocardiographic measurements, and New York Heart Association (NYHA) class were obtained at baseline and at 6-monthly intervals. ResultsThere were no differences in baseline characteristics between groups (all P > .05). Clinical outcomes such as left ventricular ejection fraction, left ventricular end-systolic volume, QoL, and NYHA class were significantly improved for both pacing groups compared to baseline. The LBBAP-CRT group showed greater improvement in left ventricular ejection fraction at 6 months (P = .001) and 12 months (P = .021), accompanied by greater reduction in left ventricular end-systolic volume (P = .007). QRS duration < 120 ms (baseline 160.82 ± 21.35 ms vs 161.08 ± 24.48 ms) was achieved in 30% in the BiV-CRT group vs 71% in the LBBAP-CRT group (P ≤ .001). Improvement in NYHA class (P = .031) and QoL index was greater (P = .014). Reduced heart failure admissions (P = .003) and health care utilization (P < .05) and improved lead performance (P < .001) were observed in the LBBAP-CRT group. ConclusionLBBAP-CRT is feasible and effective CRT. It results into a meaningful improvement in QoL and reduction in health care utilization. This can be offered as an alternative to BiV-CRT or potentially as first-line therapy.

Complications of left bundle branch area pacing compared with biventricular pacing in candidates for resynchronization therapy: Results of a propensity score–matched analysis from a multicenter registry

BackgroundCardiac resynchronization therapy (CRT) with biventricular pacing (BVP) is a well-established therapy in patients with reduced left ventricular ejection fraction, heart failure, and left bundle branch block. Left bundle branch area pacing (LBBAP) has recently been shown to be a feasible and effective alternative to BVP. Comparative data on the risk of complications between LBBAP and BVP among patients undergoing CRT are lacking. ObjectiveThe aim of this study was to compare the long-term risk of procedure-related complications between LBBAP and BVP in a cohort of patients undergoing CRT. MethodsThis prospective, multicenter, observational study enrolled 668 consecutive patients (mean age 71.2 ± 10.0 years; 52.2% male; 59.4% with New York Heart Association class III-IV heart failure symptoms) with left ventricular ejection fraction 33.4% ± 4.3% who underwent BVP (n = 561) or LBBAP (n = 107) for a class I or II indication for CRT. Propensity score matching for baseline characteristics yielded 93 matched pairs. The rate and nature of intraprocedural and long-term post-procedural complications occurring during follow-up were prospectively collected and compared between the 2 groups. ResultsDuring a mean follow-up of 18 months, procedure-related complications were observed in 16 patients: 12 in BVP (12.9%) and 4 in LBBAP (4.3%) (P = .036). Compared with patients who underwent LBBAP, those who underwent BVP showed a lower complication-free survival (P = .032). In multivariate analysis, BVP resulted an independent predictive factor associated with a higher risk of complications (hazard ratio 3.234; P = .042). Complications related to the coronary sinus lead were most frequently observed in patients who underwent BVP (50.0% of all complications). ConclusionLBBAP was associated with a lower long-term risk of device-related complications compared with BVP in patients with an indication for CRT.

Clinical outcomes of left bundle branch area pacing compared with biventricular pacing in patients with heart failure requiring cardiac resynchronization therapy: systematic review and meta-analysis

Abstract Background Biventricular pacing (BVP) is recommended from the most recent ESC guidelines as the first line pacing strategy in patients with heart failure (HF) that require cardiac resynchronization therapy (CRT). (1) Many studies have shown its beneficial effects regarding morbidity and mortality in this population. (2, 3) However, 10% of patients cannot be treated by BVP due to unsuitable coronary sinus vein, while 30-40% are non-responders to BVP and experience no benefit from this treatment.(4) Left bundle branch area pacing (LBBAP) is a new pacing modality (5) that can achieve narrow QRS and improve left ventricular function in patients with HF, by engaging the intrinsic conduction pathway of the heart. Also, it appears to have better results in electrical and mechanical synchrony compared with BVP. Purpose We conducted a systematic review and meta-analysis to compare the two pacing modalities in terms of hard clinical outcomes, in patients with heart failure that require CRT. Methods Medline, Embase, Cochrane Central Register of Controlled Trials and Web of Science databases were systematically searched for studies comparing LBBAP with BVP for CRT in patients with HF. Outcomes of interest were all-cause mortality, Heart Failure Hospitalizations (HFH) and New York Heart Association (NYHA) class improvement. Two independent investigators identified studies, extracted data, and assessed the risk of bias using the Cochrane Risk of Bias 2 tool for randomized clinical trials and the Newcastle-Ottawa-Scale for observational studies. Pairwise meta-analysis was conducted using random and fixed effects models. Risk Ratios (RRs) and weighted mean difference (WMD) with 95% confidence intervals (CIs) were used to report dichotomous and continuous variables respectively. Heterogeneity was assessed with the I² statistic. Results In total, 764 studies were retrieved and finally 9 trials with 992 individuals (365 in LBBAP and 627 in BVP group) were included in the analysis. The mean follow-up duration was 13 ± 5.82 months and the average procedural success rate in the LBBAP group was 89.8%. The baseline characteristics were similar between the two groups. Pooled analysis showed that the two methods had no difference in terms of all-cause mortality (RR:0.87 CI 95%:0.38 to 2.02; I²=0%; p=0.750, Figure 1) with 8 (2.4%) vs 17 (2.9%) events occurring in LBBAP and BVP group respectively. However, LBBAP was found to have significantly lower risk for HFH (RR:0.58 CI 95%:0.38 to 0.91; I²=0%; p=0.020, Figure 2A) and to achieve more improvement in NYHA class compared with BVP (WMD: -0.40, CI 95%: -0.68 to -0.12; I²=72%; p=0.005; Figure 2B). Conclusions To the best of our knowledge this is the first meta-analysis that assesses exclusively the clinical outcomes of LBBAP compared to BVP in such an important number of patients. LBBAP presents better outcomes in HFH and NYHA class improvement, but it has no difference in all-cause mortality in comparison with BVP.Figure 1.All-cause mortalityFigure 2.A.HFH B.NYHA class improvement

Clinical Outcomes of Left Bundle Branch Area Pacing Compared with Biventricular Pacing in Patients with Heart Failure Requiring Cardiac Resynchronization Therapy: Systematic Review and Meta-Analysis

Clinical Outcomes of Left Bundle Branch Area Pacing Compared with Biventricular Pacing in Patients with Heart Failure Requiring Cardiac Resynchronization Therapy: Systematic Review and Meta-Analysis

Abstract 19063: An Updated Meta-Analysis Comparing Left Bundle Branch Area Pacing and Biventricular Pacing for Cardiac Resynchronization Therapy

Introduction: Left bundle branch area pacing (LBBAP) is a type of conduction system pacing that has been considered as an alternative to biventricular pacing (BVP) in patients requiring cardiac resynchronization therapy (CRT). Hypothesis: We performed a meta-analysis comparing the clinical and echocardiographic outcomes between LBBAP and BVP in patients requiring CRT. Methods: We performed a systematic literature review in Embase, PubMed, and SCOPUS for all the related articles until November 2022. The literature search yielded 44 publications, of which 6 studies fulfilled the inclusion criteria. The Inverse Variance random effects model was used for continuous variables to calculate Mean Difference (MD) and 95% confidence intervals (CI) and Mantel- Haenszel random effects model was used for dichotomous variables to calculate odds ratio (OR) and 95% confidence intervals (CI). Outcomes analyzed were changed in left ventricle ejection fraction (LVEF), left ventricle end-diastolic dimension (LVEDD), NYHA class, and QRS duration and patients with the echocardiographic response (as defined as LVEF improvement &gt;5%) and heart failure hospitalizations. Results: Over a mean follow up of 8+/-2 months, LBBAP when compared to BVP resulted in significant difference in LVEF improvement (MD = 5.78 % (95% CI [4.75%, 6.80%], P&lt;0.00001), QRS duration reduction (MD = -24.77 ms) (95% CI [-32.78, -16.77], P&lt;0.00001), NYHA class reduction (MD = -0.43, 95% CI [-0.78, -0.08], P=0.02) and number of patients with echocardiographic response (OR = 2.94, 95% CI [1.40-6.14], P=0.004) at follow up. There was no significant difference in LVEDD reduction (MD = -0.5 mm, 95% CI [-3.36, 2.37], P=0.73) and HF hospitalization rates (OR = 0.42, 95% CI [0.11-1.61], P=0.21) between the 2 groups. Conclusions: LBBAP is an effective alternative to BVP in patients with an indication for CRT.

Abstract 14047: Comparison of Left Bundle Branch Area Pacing and Biventricular Pacing in Patients With Left Ventricular Systolic Failure: A Systematic Review and Meta-Analysis

Introduction: There is limited data comparing the effectiveness of Left Bundle Branch Area Pacing (LBBAP) and traditional Biventricular Pacing (BiVP) in patients with left ventricular systolic failure. The aim of this study was to assess the electromechanical and clinical outcomes of both cardiac resynchronization (CRT) techniques. Hypothesis: LBBAP offers comparable or superior clinical outcomes compared to BiVP in patients with systolic left ventricular failure Methods: We conducted a systematic review of PubMed (MEDLINE), Embase, Google Scholar, Scopus, and Cochrane Central Register of Control Trials (CENTRAL) for studies comparing LBBAP with BiVP from inception till May 22, 2023. To evaluate categorical and continuous outcomes, risk ratios (RRs) and standardized mean differences (SMDs) with corresponding 95% confidence intervals (CIs) were calculated using RevMan version 5.4 software. Results: We selected 12 studies involving 3,004 patients (LBBP=1,242; BiVP=1,762) for our meta-analysis. The pooled results demonstrated significant improvements with LBBAP in left ventricular ejection fraction (LVEF) (SMD=0.40, 95%CI[0.25, 0.54], P&lt;0.00001), NYHA functional class (SMD=-0.44, 95%CI[-0.65, -0.23], P&lt;0.0001), reduction in QRS duration (SMD=-0.90, 95%CI[-1.14, -0.66], P&lt;0.00001), fewer heart failure hospitalizations (RR=0.72, 95%CI [0.62, 0.85], P&lt;0.0001), and improved survival (RR=0.73, 95%CI [0.58, 0.92], P=0.007). Additionally, LBBAP was associated with a lower pacing threshold at implantation (SMD=-1.03, 95%CI[-1.32, -0.74], P&lt;0.00001) as compared to BiVP. Conclusions: LBBAP was associated with significant improvements in both electromechanical and clinical outcomes, including LVEF, reduction in QRS duration, NYHA class, heart failure hospitalizations, and all-cause mortality in patients with systolic left ventricular failure.

Abstract 18037: Left Bundle Branch Area versus Biventricular Pacing in Cardiac Resynchronization Therapy: A Systematic Review and Meta-Analysis

Introduction: Cardiac resynchronization therapy (CRT) through biventricular pacing (BVP) is the standard treatment for heart failure with reduced ejection fraction (HFrEF) and left bundle-branch block (LBBB). Left bundle-branch area pacing (LBBAP) has emerged as a potentially more effective approach. However, its superiority over BVP remains unclear. Hypothesis: Is LBBAP more effective and safer than BVP for CRT in patients with HFrEF? Methods: We systematically searched PubMed, Embase, and Cochrane for randomized controlled trials (RCTs) or observational studies that reported adjusted effect estimates (i.e propensity score-matched populations or multivariate analysis), comparing the efficacy and safety of LBBAP versus BVP. We applied the random-effects model to calculate adjusted hazard ratio (aHR) and mean difference (aMD), with the corresponding 95% confidence interval. Heterogeneity was assessed using I 2 statistics. Statistical analysis was performed using R version 4.2.1. Results: Our analysis included 7 studies, yielding 2,743 patients, of whom 1,164 (42.4%) were assigned to LBBAP group. Compared with BVP, LBBAP was associated with a significant reduction of the composite of overall mortality and heart failure hospitalizations (aHR 0.67; 95% CI 0.56-0.80; I 2 =0%; p&lt;0.001; Figure 1A). Additionally, LBBAP demonstrated a significant increase in LVEF (aMD 5.77%; 95% CI 2.94-8.60; I 2 =68%; p&lt;0.001; Figure 1B) and shortening of QRS duration (aMD -25.71 ms; 95% CI -35.87 to -15.55; I 2 =0%; p&lt;0.001; Figure 2A) compared with BVP. Sub-analysis of patients with LBBB also demonstrated a significant reduction of the composite of overall mortality and heart failure hospitalizations (aHR 0.64; 95% CI 0.49 to 0.85; I 2 =0%; p&lt;0.001; Figure 2B) in LBBAP. Conclusions: This meta-analysis of RCTs and multivariable adjusted studies suggests that LBBAP is superior to BVP in patients with HFrEF undergoing CRT for both electrophysiological and clinical outcomes.

Left bundle branch area pacing vs biventricular pacing for cardiac resynchronization: A systematic review and meta-analysis

Left bundle branch area pacing (LBBAP) may offer greater physiological benefits than traditional biventricular pacing (BiVP). However, there are limited data comparing the efficacy of LBBAP vs BiVP in patients with systolic heart failure (HF). The purpose of this meta-analysis was to compare the feasibility and electromechanical and clinical outcomes of both LBBAP and BiVP. We conducted a systematic review of studies retrieved from various databases including PubMed, Embase, Google Scholar, Scopus, and Cochrane Central Register of Control Trials (CENTRAL) published up to May 22, 2023. The risk ratio (RR) and standardized mean difference (SMD) with corresponding 95% confidence intervals (CIs) were calculated for dichotomous and continuous outcomes, respectively. We included 12 studies with a total of 3004 patients (LBBAP = 1242, BiVP = 1762). Pooled results showed that LBBAP resulted in a significant increase in left ventricular ejection fraction (SMD 0.40, 95% CI 0.25, 0.54, P < .00001), echocardiographic response (RR 1.19, 95% CI 1.10 to 1.29, P < .0001), improvement in New York Heart Association functional class (SMD -0.44, 95% CI -0.65 to -0.23, P < .0001), QRS duration reduction (SMD -0.90, 95% CI -1.14 to -0.66, P < .00001), left ventricular end-diastolic diameter reduction (SMD -0.31, 95% CI -0.57 to -0.05, P = .02), fewer HF hospitalizations (RR 0.72, 95% CI 0.62, 0.85, P < .0001), and improved survival (RR 0.73, 95% CI 0.58, 0.92, P = .007). In addition, LBBAP was associated with shorter fluoroscopy time (SMD -0.94, 95% CI -1.42 to -0.47, P < .0001) and lower pacing threshold at implantation (SMD -1.03, 95% CI -1.32 to -0.74, P < .00001) and at 6 months (SMD -1.44, 95% CI -2.11 to -0.77, P < .0001) as compared with BiVP. Compared with BiVP, LBBAP was associated with better electromechanical and clinical outcomes, including left ventricular ejection fraction, QRS duration, echocardiographic response, New York Heart Association functional class, HF hospitalization, and all-cause mortality in patients with systolic HF.

His-Purkinje Conduction System Pacing Optimized Trial of Cardiac Resynchronization Therapy vs Biventricular Pacing: HOT-CRT Clinical Trial

BackgroundHis-Purkinje conduction system pacing (HPCSP) using His bundle pacing (HBP) or left bundle branch pacing (LBBP) has emerged as an alternative to biventricular pacing (BVP) in patients requiring cardiac resynchronization therapy (CRT). ObjectivesThe aim of the study was to compare the feasibility and clinical efficacy of HOT-CRT (His-Purkinje conduction system pacing Optimized Trial of Cardiac Resynchronization Therapy) with BVP in patients with heart failure, reduced ejection fraction, and indication for CRT. MethodsThis was a prospective, randomized, controlled trial of HOT-CRT and BVP in patients with LVEF <50% and indications for CRT. If HPCSP resulted in incomplete electrical resynchronization, a coronary sinus (CS) lead was added. The primary outcome was the change in left ventricular ejection fraction (LVEF) at 6 months. The primary safety endpoint was freedom from major complications. ResultsA total of 100 patients (female 31%, aged 70 ± 12 years, LVEF 31.5% ± 9.0%) were randomized. HOT-CRT was successful in 48 of 50 (96%) and BVP-CRT in 41 of 50 (82%) patients (P = 0.03). QRS duration significantly decreased from 164 ± 26 ms to 137 ± 20 ms with HOT-CRT and 166 ± 28 ms to 141 ± 19 ms with BVP. Fluoroscopy results (18.8 ± 12.4 min vs 23.8 ± 12.4 min, P = 0.05) and procedure duration (119 ± 42 min vs 114 ± 36 min, P = 0.5) were similar. The primary outcome of change in LVEF at 6 months was greater in HOT-CRT than in BVP (12.4% ± 7.3% vs 8.0% ± 10.1%, P = 0.02). The primary safety endpoint was similar (98% vs 94%, P = 0.62). Echocardiographic response of improvement in LVEF >5% occurred in 80% vs 61% (P = 0.06). Complications occurred in 3 (6%) in HOT-CRT vs 10 (20%) in BVP (P = 0.03). ConclusionsHPCSP-guided CRT resulted in greater change in LVEF compared with BVP. Randomized clinical trials with long-term follow-up are necessary. (His-Purkinje Conduction System Pacing Optimized Trial of Cardiac Resynchronization Therapy [HOT-CRT]; NCT04561778)

Left bundle branch area pacing for heart failure patients requiring cardiac resynchronization therapy: A meta-analysis.

Left bundle branch area pacing (LBBP) is a novel conduction system pacing method to achieve effective physiological pacing and an alternative to cardiac resynchronization therapy (CRT) with biventricular pacing (BVP) for patients with heart failure with reduced ejection fraction (HFrEF). We conduted this meta-analysis and systemic review to review current data comparing BVP and LBBP in patients with HFrEF and indications for CRT. We searched PubMed/Medline, Web of Science, and Cochrane Library from the inception of the database to November 2022. All studies that compared LBBP with BVP in patients with HFrEF and indications for CRT were included. Two reviewers performed study selection, data abstraction, and risk of bias assessment. We calculated risk ratios (RRs) with the Mantel-Haenszel method and mean difference (MD) with inverse variance using random effect models. We assessed heterogeneity using the I2 index, with I2 > 50% indicating significant heterogeneity. Ten studies (9 observational studies and 1 randomized controlled trial; 616 patients; 15 centers) published between 2020 and 2022 were included. We observed a shorter fluoroscopy time (MD: 9.68, 95% confidence interval [CI]: 4.49-14.87, I2 = 95%, p < .01, minutes) as well as a shorter procedural time (MD 33.68, 95% CI: 17.80-49.55, I2 = 73%, p < .01, minutes) during the implantation of LBBP CRT compared to conventional BVP CRT. LBBP was shown to have a greater reduction in QRS duration (MD 25.13, 95% CI: 20.06-30.20, I2 = 51%, p < .01, milliseconds), a greater left ventricular ejection fraction improvement (MD: 5.80, 95% CI: 4.81-6.78, I2 = 0%, p < .01, percentage), and a greater left ventricular end-diastolic diameter reduction (MD: 2.11, 95% CI: 0.12-4.10, I2 = 18%, p = .04, millimeter). There was a greater improvement in New York Heart Association function class with LBBP (MD: 0.37, 95% CI: 0.05-0.68, I2 = 61%, p = .02). LBBP was also associated with a lower risk of a composite of heart failure hospitalizations (HFH) and all-cause mortality (RR: 0.48, 95% CI: 0.25-0.90, I2 = 0%, p = .02) driven by reduced HFH (RR: 0.39, 95% CI: 0.19-0.82, I2 = 0%, p = .01). However, all-cause mortality rates were low in both groups (1.52% vs. 1.13%) and similar (RR: 0.98, 95% CI: 0.21-4.68, I2 = 0%, p = .87). This meta-analysis of primarily nonrandomized studies suggests that LBBP is associated with a greater improvement in left ventricular systolic function and a lower rate of HFH compared to BVP. There was uniformity of these findings in all of the included studies. However, it would be premature to conclude based solely on the current meta-analysis alone, given the limitations stated. Dedicated, well-designed, randomized controlled trials and observational studies are needed to elucidate better the comparative long-term efficacy and safety of LBBP CRT versus BIV CRT.

His-Purkinje system pacing versus biventricular pacing in clinical efficacy: a systematic review and meta-analysis

BackgroundHis-Purkinje system pacing (HPSP), including his-bundle pacing (HBP) and left bundle branch area pacing (LBBaP), imitates the natural conduction of the heart as an alternative to biventricular pacing (BVP) in cardiac resynchronization therapy (CRT). However, the feasibility and efficacy of HPSP were currently only evidenced by studies with a limited sample size, so this study aimed to provide a comprehensive assessment through a systematic review and meta-analysis.MethodsIn order to compare the clinical outcomes associated with HPSP and BVP in patients for CRT, PubMed, EMBASE, Cochrane Library and Web of Science database were searched from inception to April 10, 2023. Clinical outcomes of interest including QRS duration (QRSd), left ventricular (LV) function and New York Heart Association (NYHA) functional classification, pacing threshold, echocardiographic and clinical response, hospitalization rate of HF and all-cause mortality were also extracted and summarized for meta-analysis.ResultsA total of 13 studies (ten observational studies and three randomized studies) involving 1,121 patients were finally included. The patients were followed up for 6–27 months. Compared with BVP, CRT patients treated by HPSP presented shorter QRSd [mean difference (MD): -26.23 ms, 95% confidence interval (CI): -34.54 to -17.92, P < 0.001, I2 = 91%], greater LV functional improvement with increased left ventricular ejection fraction (LVEF) (MD: 6.01, 95% CI: 4.81 to 7.22, P < 0.001, I2 = 0%), decreased left ventricular end-diastolic dimension (LVEDD) (MD: -2.91, 95% CI: -4.86 to -0.95, P = 0.004, I2 = 35%), and more improved NYHA functional classification (MD: -0.45, 95% CI: -0.67 to -0.23, P < 0.001, I2 = 70%). In addition, HPSP was more likely to have higher echocardiographic [odds ratio (OR): 2.76, 95% CI: 1.74 to 4.39, P < 0.001, I2 = 0%], clinical (OR: 2.10, 95% CI: 1.16 to 3.80, P = 0.01, I2 = 0%) and super clinical (OR: 3.17, 95% CI: 2.09 to 4.79, P < 0.001, I2 = 0%) responses than BVP, and a lower hospitalization rate of HF (OR: 0.34, 95% CI: 0.22 to 0.51, P < 0.001, I2 = 0%), while presented no difference (OR: 0.68, 95% CI: 0.44 to 1.06, P = 0.09, I2 = 0%) in all-cause mortality compared with BVP. With threshold change taking into account, BVP was less stable than LBBaP (MD: -0.12 V, 95% CI: -0.22 to -0.03, P = 0.01, I2 = 57%), but had no difference with HBP (MD: 0.11 V, 95% CI: -0.09 to 0.31, P = 0.28, I2 = 0%).ConclusionThe present findings suggested that HPSP was associated with greater improvement of cardiac function in patients with indication for CRT and was a potential alternative to BVP to achieve physiological pacing through native his-purkinje system.Graphical

Left bundle branch area pacing results in more physiological ventricular activation than biventricular pacing in patients with left bundle branch block heart failure.

Biventricular pacing (Biv) and left bundle branch area pacing (LBBAP) are methods of cardiac resynchronization therapy (CRT). Currently, little is known about how they differ in terms of ventricular activation. This study compared ventricular activation patterns in left bundle branch block (LBBB) heart failure patients using an ultra-high-frequency electrocardiography (UHF-ECG). This was a retrospective analysis including 80 CRT patients from two centres. UHF-ECG data were obtained during LBBB, LBBAP, and Biv. Left bundle branch area pacing patients were divided into non-selective left bundle branch pacing (NSLBBP) or left ventricular septal pacing (LVSP) and into groups with V6 R-wave peak times (V6RWPT) < 90 ms and ≥ 90 ms. Calculated parameters were: e-DYS (time difference between the first and last activation in V1-V8 leads) and Vdmean (average of V1-V8 local depolarization durations). In LBBB patients (n = 80) indicated for CRT, spontaneous rhythms were compared with Biv (39) and LBBAP rhythms (64). Although both Biv and LBBAP significantly reduced QRS duration (QRSd) compared with LBBB (from 172 to 148 and 152 ms, respectively, both P < 0.001), the difference between them was not significant (P = 0.2). Left bundle branch area pacing led to shorter e-DYS (24 ms) than Biv (33 ms; P = 0.008) and shorter Vdmean (53 vs. 59 ms; P = 0.003). No differences in QRSd, e-DYS, or Vdmean were found between NSLBBP, LVSP, and LBBAP with paced V6RWPTs < 90 and ≥ 90 ms. Both Biv CRT and LBBAP significantly reduce ventricular dyssynchrony in CRT patients with LBBB. Left bundle branch area pacing is associated with more physiological ventricular activation.

Repolarization changes following left bundle branch area pacing versus conventional biventricular pacing in patients with dyssynchronous heart failure

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Dutch Heart Foundation. Background Biventricular pacing (BiVP) is the standard treatment for patients with dyssynchronous heart failure. Despite the effectiveness of BiVP, 6% of patients develop ventricular tachyarrhythmia’s (VTAs) within one year following implantation. The relationship between BiVP and the development of VTAs is still under debate. The left-sided epicardium-to-endocardium activation during BiVP creates a nonphysiological activation and repolarization and might provoke VTAs. A relatively new treatment option is left bundle branch area pacing (LBBAP), in which the physiological activation of the left ventricle is restored. We hypothesize that LBBAP leads to a more homogenous repolarization compared to conventional BiVP. Purpose To compare time-dependent repolarization changes in patients with dyssynchronous heart failure receiving LBBAP versus BiVP. Methods Patients with dyssynchronous heart failure eligible for cardiac resynchronization therapy who underwent LBBAP (n=13) or BiVP (n=28) were retrospectively included. Standard 12-lead electrocardiograms (ECG) obtained prior to implantation [baseline], shortly following implantation (0-2 days,[acute]) and during follow-up (31-180 days, [FU]) were analyzed. The QT interval and Tpeak to Tend interval (Tpeak-Tend) were calculated using a semi-automatic approach in MATLAB. Repolarization differences between LBBAP and BiVP patients were determined using the Mann-Whitney U-test. Time-dependent changes within groups were determined using the Wilcoxon signed rank tests. Significance was defined as a p-value ≤0.05. Results The QT interval did not significantly change over time in BiVP patients, but it decreased immediately following implantation and during FU in LBBAP patients. At FU, QT interval was significantly lower in LBBAP than in BiVP patients (Figure 1, left panel). A slight increase in Tpeak-Tend interval over time in BiVP patients, while it tends to decrease over time in LBBAP patients can be seen in the right panel. Acutely and long term after implantation, Tpeak-Tend was significantly lower in LBBAP than in BiVP patients. Conclusion LBBAP is associated with lower QT and Tpeak-Tend intervals compared to BiVP during FU, suggesting that LBBAP leads to less heterogeneity of repolarization over time. These findings suggest a more physiological repolarization pattern in LBBAP compared to BiVP, which may decrease the risk of developing VTAs.

Left bundle branch area pacing produces more physiological ventricular activation than biventricular pacing in patients with heart failure and LBBB

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): National Institute for Research of Metabolic and Cardiovascular Diseases, Programme EXCELES, Ministry of Health of the Czech Republic, grant number NU21-02-00584. Introduction Biventricular pacing (BiV) is an established treatment for patients with heart failure and dyssynchronous ventricular activation. Left bundle branch area pacing (LBBAP) appears to be a promising alternative to BiV-CRT. To date, there is insufficient data regarding their effect on the reduction of ventricular dyssynchrony. Purpose To compare ventricular synchrony during spontaneous rhythm, BiV and LBBAP in patients with heart failure, reduced left ventricular ejection fraction (LVEF), and LBBB using ultra-high-frequency ECG (UHF-ECG). Methods This was a retrospective analysis of consecutive patients with indication to CRT from two centers. It included patients with heart failure, QRS of LBBB morphology, and LVEF ≤ 40%, treated by BiV and/or LBBAP-CRT. UHF-ECG data were obtained during spontaneous and paced rhythms. These parameters were calculated: eDYS (time difference between the first and last activation), Vdmean (average of V1-V8 local depolarization durations) and QRSd (measured from pacing artifact). Results Analyzes were performed on 80 spontaneous rhythms, 39 biventricular captures and 64 LBBAP, obtained from 80 patients. Their mean age was 74±10 years, 61% were men, mean LV ejection fraction was 31±9 %, and 32% had ischemic cardiomyopathy. Both BiV and LBBAP-CRT significantly reduced QRSd compared to the spontaneous rhythm (from 172 ms, 95% CI [168;176] to 146 ms [141;152] during BiV and 143 ms [139;149] during LBBAP). Also, the eDYS and Vdmean were significantly reduced by both BiV and LBBAP-CRT, i.e., the eDYS from 82 ms [76;86] during LBBB to 33 ms [28;37], p&amp;lt;0.001 during biventricular pacing and to 24 ms [20;28], p&amp;lt;0.001, during LBBAP and Vdmean from 71 ms [68;73] to 59 ms [56;61], p&amp;lt;0.001 during BiV and to 53 ms [51;55], p&amp;lt;0.001 during LBBAP. Although the QRSd did not differ between LBBAP and biventricular pacing (143ms [139;148] vs 146ms [141;152], p=NS), LBBAP compared to BiV led to significantly shorter eDYS (24ms [20;28] vs 33ms [28;38]; p&amp;lt;0.008 and Vdmean (53ms [51;55] vs 59ms [56;61], respectively; p&amp;lt;0.003}. Conclusions In patients with heart failure, LBBB and reduced LVEF, both BiV and LBBAP CRT significantly reduce ventricular dyssynchrony compared to the spontaneous rhythm. Our results indicate that LBBAP is associated with more physiological ventricular activation than BiV-CRT.

Comparison of Left Bundle Branch Area Pacing and Biventricular Pacing in Candidates for Resynchronization Therapy

BackgroundCardiac resynchronization therapy (CRT) with biventricular pacing (BVP) is a well established therapy in patients with reduced left ventricular ejection fraction (LVEF), heart failure, and wide QRS or expected frequent ventricular pacing. Left bundle branch area pacing (LBBAP) has recently been shown to be a safe alternative to BVP. ObjectivesThe aim of this study was to compare the clinical outcomes between BVP and LBBAP among patients undergoing CRT. MethodsThis observational study included patients with LVEF ≤35% who underwent BVP or LBBAP for the first time for Class I or II indications for CRT from January 2018 to June 2022 at 15 international centers. The primary outcome was the composite endpoint of time to death or heart failure hospitalization (HFH). Secondary outcomes included endpoints of death, HFH, and echocardiographic changes. ResultsA total of 1,778 patients met inclusion criteria: 981 BVP, 797 LBBAP. The mean age was 69 ± 12 years, 32% were female, 48% had coronary artery disease, and mean LVEF was 27% ± 6%. Paced QRS duration in LBBAP was significantly narrower than baseline (128 ± 19 ms vs 161 ± 28 ms; P < 0.001) and significantly narrower compared to BVP (144 ± 23 ms; P < 0.001). Following CRT, LVEF improved from 27% ± 6% to 41% ± 13% (P < 0.001) with LBBAP compared with an increase from 27% ± 7% to 37% ± 12% (P < 0.001) with BVP, with significantly greater change from baseline with LBBAP (13% ± 12% vs 10% ± 12%; P < 0.001). On multivariable regression analysis, the primary outcome was significantly reduced with LBBAP compared with BVP (20.8% vs 28%; HR: 1.495; 95% CI: 1.213-1.842; P < 0.001). ConclusionsLBBAP improved clinical outcomes compared with BVP in patients with CRT indications and may be a reasonable alternative to BVP.