Comment on \u201cUpdated Meta\u2010Analysis of Left Bundle Branch Area Pacing Versus Right Ventricular Pacing in Conduction System Disorders: Insights From New Evidence\u201d

Safety and efficacy of left bundle branch area pacing compared with right ventricular pacing in patients with bradyarrhythmia and conduction system disorders: Systematic review and meta-analysis

Right ventricular pacing (RVP) has long been the standard therapy for bradyarrhythmias but may induce ventricular dyssynchrony and adverse cardiac remodeling. Physiologic pacing strategies that preserve the native conduction system, particularly left bundle branch area pacing (LBBAP), have emerged as promising alternatives. This study aimed to evaluate the comparative efficacy and safety of LBBAP versus RVP through an updated meta-analysis. Following PRISMA guidelines, we systematically searched PubMed, Cochrane CENTRAL, and ClinicalTrials.gov for relevant studies published through June 2025. Studies comparing LBBAP and RVP in patients undergoing pacemaker implantation were included. Pooled estimates were calculated using random-effects models. A total of 40 studies comprising 8290 patients were included. LBBAP was associated with significantly shorter QRS duration compared with RVP (30 studies, n = 5510; MD -35.56 ms, 95% CI -41.88 to -29.24; p < 0.0001). Structural remodeling also favored LBBAP, with greater improvement in left ventricular ejection fraction (16 studies, n = 1693; MD +3.77%, 95% CI 2.43-5.12; p < 0.0001) and greater reduction in left ventricular end-diastolic diameter (13 studies, n = 1666; MD -2.33 mm, 95% CI -3.59 to -1.07; p < 0.0001). Clinically, LBBAP was associated with lower heart failure hospitalization (RR 0.38, 95% CI 0.29-0.52; p < 0.0001) and reduced all-cause mortality (RR 0.55, 95% CI 0.41-0.72; p < 0.0001), along with greater reduction in NT-proBNP levels. LBBAP provides superior electrical synchrony, improved cardiac remodeling, and favorable clinical outcomes compared with RVP, while maintaining a comparable procedural safety profile.

The field of cardiac pacing has undergone significant evolution with the introduction and adoption of conduction system pacing (CSP) and leadless pacemakers (LLPMs). These innovations provide benefits over conventional pacing methods including avoiding lead related complications and achieving more physiological cardiac activation. This review critically assesses the latest advancements in CSP and LLPMs, including their benefits, challenges, and potential for future growth. CSP, especially of the left bundle branch area, enhances ventricular depolarization and cardiac mechanics. Recent studies show CSP to be favorable over traditional pacing in various patient populations, with an increase in its global adoption. Nevertheless, challenges related to lead placement and long-term maintenance persist. Meanwhile, LLPMs have emerged in response to complications from conventional pacemaker leads. Two main types, Aveir and Micra, have demonstrated improved outcomes and adoption over time. The incorporation of new technologies allows LLPMs to cater to broader patient groups, and their integration with CSP techniques offers exciting potential. The advancements in CSP and LLPMs present a transformative shift in cardiac pacing, with evidence pointing towards enhanced clinical outcomes and reduced complications. Future innovations and research are likely to further elevate the clinical impact of these technologies, ensuring improved patient care for those with conduction system disorders.

Funding AcknowledgementsType of funding sources: None.BackgroundRight Ventricular Pacing (RVP) is well established as the widely accepted pacing method. However, its effects in ventricular function can be detrimental, causing electrical and mechanical dysynchrony and potential LVEF impairment. Left Bundle Branch Pacing (LBBP) is a new pacing strategy that appears to have better results preserving left ventricular function, by directly engaging the intrinsic conduction pathway of the heart.PurposeThe aim of this systematic review and meta-analysis is to compare the safety and efficacy of the two pacing methods (LBBP and RVP) in patients suffering from bradyarrhythmia and conduction system disorders.MethodsMedline, Embase and Pubmed databases were searched for studies comparing LBBP with RVP. Outcomes were QRSd (QRS duration), ventricular mechanical synchrony, LVEF changes, and Heart Failure Hospitalizations (HFH) to assess the efficacy, lead properties and complications to assess the safety. Two independent reviewers 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 and standard mean difference (WMD, SMD) with 95% confidence intervals (CIs) were used to report dichotomous and continuous variables respectively. Heterogeneity was assessed with the I² statistic.Results1318 articles were identified, and finally 25 trials with 4250 patients (2127 LBBP and 2123 RVP) were included in the analysis. Pooled analyses verified that QRSd is shorter in LBBP group both at implantation (WMD:-32.32, CI 95%:-35.18 to -29.45; I²=88%; P<.001) and at Follow Up (WMD: -32.20, CI 95%: -40.70 to -23.71; I²=92%; P<.001) and LBBP succeeded better interventricular mechanical synchrony (SMD:-2.04, CI 95%:-2.32 to -1.76; I²=21%; P<.001) than RVP. Intraventricular mechanical synchrony was also significantly better in LBBP vs RVP independently of the way of measurement in each study (SMD:-1.77, CI 95%:-2.45 to -1.09; I²=90%; P<.001) and in the subgroup analysis of the studies that implemented the same way of measurement (P<.001; I²=26%). LVEF alteration was not significant in the LBBP compared to native (P=.68; I²=52%), while in the RVP group showed a significant reduction (P<.001; I²=51%). LBBP showed, significantly better results in HFH (P<.001; I²=0%) and achieved similar pacing thresholds (P=.86) and higher R wave amplitudes (P<.05) than RVP while lead related complications had no difference between the two groups (LBBP=1.90% vs RVP=1.72%; P=0.71).ConclusionsTo our knowledge this is the first meta-analysis that assess the safety and efficacy of LBBP in such an important number of patients. LBBP preserves ventricular electrical and mechanical synchrony, shows a reduction in HFH compared to RVP and has excellent pacing parameters, without compromising safety.

His bundle pacing improves left ventricular diastolic function in patients with heart failure with preserved systolic function

Electrogenesis in the heart begins in the sinoatrial node and proceeds down the conduction system to originate the heartbeat. Conduction system disorders lead to slow heart rates that are insufficient to support the circulation, necessitating implantation of electronic pacemakers. The typical electronic pacemaker consists of a subcutaneous generator and battery module attached to one or more endocardial leads. New leadless pacemakers can be implanted directly into the right ventricular apex, providing single-chamber pacing without a subcutaneous generator. Modern pacemakers are generally reliable, and their programmability provides options for different pacing modes tailored to specific clinical needs. Advances in device technology will probably include alternative energy sources and dual-chamber leadless pacing in the not-too-distant future. Although effective, current electronic devices have limitations related to lead or generator malfunction, lack of autonomic responsiveness, undesirable interactions with strong magnetic fields, and device-related infections. Biological pacemakers, generated by somatic gene transfer, cell fusion, or cell transplantation, provide an alternative to electronic devices. Somatic reprogramming strategies, which involve transfer of genes encoding transcription factors to transform working myocardium into a surrogate sinoatrial node, are furthest along in the translational pipeline. Even as electronic pacemakers become smaller and less invasive, biological pacemakers might expand the therapeutic armamentarium for conduction system disorders.

The pacemaker (PCM) timing is a basic feature of the stimulation system. The device tries to bring the function of the heart with the conduction system disorder as close as possible to its original physiologically correct state. The main function of the PCM is a bradyarrhythmia therapy. Current devices are programmable and can adequately respond to any fluctuations in a heart rate from required values. Common parts of these devices are algorithms for the atrial tachycardias detection such as atrial fibrillation. The interpretation of a fast heart rate is affected by the pacemaker timing and different refractory intervals, especially in the case of tachycardias of lower frequencies. In this paper we discuss the effect of different atrial event frequencies to the adequate PCM response according to the timing behavior of the device. We prove our hypotheses by an experimental verification on the phantom of the pacemaker system by the in vitro method. The obtained results are compared with the case report from clinical practice. We set limit intervals for the detection of atrial tachycardias and verify the rate of the activation of the PCM program response for different frequencies. Finally, we discuss the behavior of cardiac implantable electronic devices (CIEDs) during the detection of signals of higher frequencies.

High-degree AV-Block requiring pacemaker (PM) implantation is a frequent complication after transcatheter tricuspid valve replacement (TTVR), which represents a relative contra-indication to standard right ventricular (RV) lead placement. We report our experience in this patient cohort and compared different PM strategies prioritising interventional valve sparing options. Consecutive patients treated with the EVOQUE system (Edwards Lifesciences) at our centre between January 2024 and May 2025 were included in this retrospective single centre analysis. Successful implantation of a valve sparing PM and feasibility of PM implantation were assessed. This analysis included 39 patients (mean age 77.3 years, 74.4% women, 8 patients with pre-existing PM). High-degree AV-Block requiring PM implantation occurred in 28.2% in our cohort (11/39 patients), the de-novo PM implantation rate was 35.5% (11/31 patients). Complete or incomplete right bundle branch block (RBBB) was the most frequent conduction system disorder after TTVR (11/31 patients). Median time from TTVR to PM implantation was six days [IQR: 2.5-13]. PM implantation was feasible in 11/11 patients (100%), no surgical lead placement was necessary. Implantation of a valve sparing PM was successful in 10/11 patients (90.9%). Leadless PM were implanted in 3/11, coronary sinus lead PM in 7/11 patients. In one patient both interventional valve sparing PM approaches failed and a standard RV lead across the EVOQUE system was implanted. High-degree AV-Block after TTVR is a frequent complication and PM implantation in these patients demands careful consideration. Valve sparing PM approaches appear feasible and were achieved with reasonable success rates in our cohort.

The coronary slow flow phenomenon (CSFP) is characterized by a delayed coronary blood flow in the absence of an obstructive coronary artery disease. Although the relation between the CSFP and myocardial ischemia has been reported previously, there is no knowledge about the relationship between the CSFP and the conduction system disorder. In this case report, we describe a patient with the CSFP presenting with complete heart block (CHB). The patient was a middle-aged woman with a history of diabetes, hypertension, and prior Coronary Care Unit admission presenting with dizziness, lightheadedness, and presyncope. Electrocardiography revealed CHB with no significant ST-T change. Cardiac enzymes and other routine lab tests were normal. The patient underwent temporary pacemaker implantation. Due to persistent atrioventricular block and suspicion of ischemic heart disease, she underwent coronary angiography, which showed the CSFP and no significant stenosis. The patient was discharged after permanent pacemaker implantation and remained asymptomatic at 3 months' follow-up.

Implantation of a leadless pacemaker in a patient with mechanical tricuspid valve

Chronic right ventricular myocardial pacing causes an asynchronous pattern of left ventricular activation, reduces left ventricular ejection fraction (LVEF), and may be associated with worsening of clinical outcomes in the long term. Although with the emergence of algorithms that minimize ventricular pacing it became possible to reduce the percentage of paced complexes in patients with sinus node dysfunction, permanent ventricular pacing is still inevitable in patients with high-degree atrioventricular (AV) block. The use of permanent conduction system pacing is a promising method for preserving the physiological activation of the ventricular myocardium and preventing the development of heart failure due to ventricular dyssynchrony. The aim. To analyze the immediate and long-term results of the use of conduction system pacing in patients with indications for permanent ventricular pacing. Materials and methods. This study included 18 patients with indications for permanentventricular pacing who were operated at the National Amosov Institute of Cardiovascular Surgery of the National Academy of Medical Sciences of Ukraine in the period from 01/01/2013 to 12/31/2022, in whom permanent conduction system pacing was used. There were 17 patients with bradyarrhythmias, of these 16 (88%) suffered from high-degree AV block (including 1 patient with Frederick’s syndrome and 1 (5%) patient with atrial ϐibrillation with slow ventricular response) and 1 (5%) patient with ischemic cardiomyopathy with left bundle branch block and ϐirstdegree AV block with indications for cardiac resynchronization therapy. The mean age of the patients was 55 ± 16 years (8 men, 10 women), LVEF at the time of the intervention was 56.42 ± 9.13 %, end diastolic volume 130.2 ± 23.8 ml, end systolic volume 55.1 ± 17.7 ml, diameter of the left atrium 4.01 ± 0.6 cm. The average QRS width before implantation was 116.5 ± 27.7 ms. In 6 (33%) patients, a special delivery system (С304-L69, Medtronic in 1 patient [5%], C315HIS in 5 [27%] patients) and 4.1F active ϐixation lead Medtronic 3830 Select Secure (69 or 74 cm) were used; in other cases (66%) standard 6F leads with active ϐixation and a lumen for a stylet without a delivery system were used. Results. The average follow-up period after implantation of pacemaker was 36.35 ± 29.65 months. During the observation period, LVEF was 57.07 ± 5.38 %, end diastolic volume111.5 ± 18.09 ml, end systolic volume 49.5 ± 13.4 ml, diameter of the left ventricle 3.9 ± 0.5 cm. The mean duration of paced QRS was 119.1 ± 10.09 ms. In 6 patients (33%), it was possible to demonstrate a change in the QRS width when the amplitude of ventricular stimulation was reduced, with 2 variants of transitions: 1) 4 (22%) patients with a transition from non-selective His bundle pacing (NSHBP) to selective His bundle pacing (SHBP), in 2 (11%) of these patients with a transition from SHBP with correction of right bundle branch block (RBBB) to SHBP without correction of RBBB, and then loss of capture of the myocardium of the ventricles; 2) 2 patients (11%) with a transition from NSHBP to myocardial septal ventricular pacing and further with a decrease in amplitude to the loss of capture of the myocardium of the ventricles. One (5%) patient with complete heart block had permanent non-selective left bundle branch area pacing. The other 11 (61%) patients met the criteria for parahisian pacing without visible transitions with a change in the amplitude of ventricular pacing. The average global longitudinal strain was -17.6 ± 2.7 %. The average interval from the stimulus to the peak of the R-wave in lead V6, which indicated the time of left ventricular activation, was 73.2 ± 8.7 ms. Pacing parameters were standardly set according to the primary indications, but with correction of the amplitude of ventricular stimulation relative to the thresholds of pacing of the conduction system. AV delay was corrected for the latency from the stimulus to the onset of the QRS in SHBP or for the duration of the “pseudodelta” wave in NSHBP which in both cases was the duration of the H-V interval. There were no complications in the acute or long-term postoperative period. Conclusions. Conduction system pacing is a challenge in the practice of cardiologist for treating life-threatening bradyarrhythmias and heart failure, but at the same time it is a safe method that provides physiological electrical and mechanical activation of the myocardium of the ventricles, that allows to effectively avoid the consequences of dyssynchrony due to permanent myocardial ventricular pacing.

Background:Conduction system disorders and arrhythmias may require pacemaker or ICD implantation in transthyretin amyloid cardiomyopathy (ATTR-CM).The optimal mode of pacing in ATTR-CM remains unknown.Objective: To compare electrical performance and clinical outcomes of conventional, resynchronisation and conduction system pacing in ATTR-CM. Methods:In this observational study, the effects of cardiac pacing were investigated in 250 consecutive ATTR-CM patients presenting at Inselspital Bern between June 2019 and February 2023.Results: During follow-up, 67 of 250 patients (26.8%) received a pacemaker.Implantation of conventional single-or dual-chamber (VVI/DDD) pacemakers was more common before ATTR-CM diagnosis (n=17/25; 68%), physiological pacing (CRT/CSP) was increasingly utilized thereafter [n=24/42 (57.1%)].Sick sinus syndrome [n=11/35 (31.4%) vs. 6/32 (18.8%] and higherdegree AV-block [n=20/35 (57.1%) vs. 9/32 (28.1%)] were more common indications for VVI/DDD, with pursuit of a pace/ablate strategy [n=12/32 (37.5%)] and heart failure [n=5/32 (15.6%)] contributing significantly to implantation of CRT/CSP.QRS duration width was significantly lower with CSP [122ms (IQR:120-139)], compared to CRT [155ms (IQR:141-160)] or VVI/DDD [160ms (IQR:144-180), p<0.001].While LV/LBBAP pacing capture thresholds were significantly lower after CSP [0.75V (IQR: 0.5-1.2)]compared to CRT [1.3V (IQR:1.0-1.6)p=0.049] at implantation, no significant differences for atrial or ventricular lead performance were observed during follow-up (p>0.05).Patients referred for CRT/CSP had a higher incidence of heart failure (p=0.014) and more common heart failure hospitalizations (p=0.03),however, mortality was not significantly different (p=0.28). Conclusions:Offering stable electrical performance and improved resynchronization, the effect of conduction system pacing on clinical outcomes warrants further exploration in ATTR-CM.

Aim. Many patients with conduction system disorders have associated heart conditions, especially ischemic heart disease. This study was designed to assess the prevalence and pattern of coronary artery disease (CAD) in patients with bradyarrhythmias requiring permanent pacemaker and association with CAD risk factors.Material and methods. This single-centre observational cohort study included 80 patients with mean age of 63±9.4 years, admitted with symptomatic bradyarrhythmias. Patients underwent coronary angiography after obtaining informed consent and prevalence and pattern of CAD were analyzed in them. CAD was defined as narrowing in major epicardial coronary arteries or their first order branches and obstructive CAD as ≥50% stenosis. CAD was further categorized as single vessel disease, double vessel disease and triple vessel disease and any association with conduction system disorders studied.Results. CAD was present in 56% patients and obstructive CAD in 37.5% patients. 19% patients had single vessel disease, while 18% had multi-vessel CAD. Obstructive LAD disease was seen in 25% of patients, followed by right coronary artery in 21.3% patients and LCX in 15% of patients. Heart team advised revascularization in majority (75%) of patients with obstructive CAD. AV nodal artery disease was found more in patients of complete heart block (p=0.0359). Among various risk-factors, dyslipidemia (56.7% vs 22%, p=0.0016), family history of CAD (63.3% vs 18%, p&lt;0.0001) and angina (53.3% vs 20%, p=0.0020) showed significant association with obstructive CAD. RWMA on echocardiography (50% vs 14%, p=0.0004) and lower mean left ventricular ejection fraction (52.7% vs 58.1%, p=0.0270) also showed significant association with obstructive CAD.Conclusion. In patients requiring permanent pacemaker, coexistent obstructive CAD was noted in 37.5% of the subjects. Causal association between obstructive CAD and conduction disturbances may not be established from this data, but the increased prevalence of atherosclerotic cardiovascular disease in patients having bradyarrhythmias implies the need for larger multi-center trials to understand the causal association and plan for earlier management.

The purpose of this article is to critically review the data accumulated to date from studies evaluating the hemodynamic and clinical effects of right ventricular apical pacing during conventional permanent cardiac pacing. The data from studies comparing the effects of right ventricular apical pacing and alternate site ventricular pacing are also reviewed. We conducted a MEDLINE and journal search of English-language reports published in the last decade and searched relevant papers. Although intraventricular conduction delay in the form of left bundle branch block (LBBB) has traditionally been viewed as an electrophysiologic abnormality, it has now become abundantly clear that it has profound hemodynamic effects due to ventricular dyssynchrony, especially in patients with heart failure. These deleterious effects can be significantly ameliorated by cardiac resynchronization therapy effected by biventricular or left ventricular pacing. However, not only is spontaneous LBBB harmful, but the iatrogenic variety produced by right ventricular apical pacing in patients with permanent pacemakers may be equally deleterious. In this review new evidence from recent studies is presented, which strongly suggests a harmful effect of our long-standing practice of producing an iatrogenic LBBB by conventional right ventricular apical pacing in patients receiving permanent pacemakers. This emerging strong new evidence about the adverse hemodynamic and clinical effects of right ventricular apical pacing would dictate a reassessment of our traditional approach to permanent cardiac pacing and direct our attention to alternate sites of pacing, such as the left ventricle and/or the right ventricular outflow tract or septum, if not for all patients, at least for those with left ventricular dysfunction. Indeed, current convincing data on alternate site ventricular pacing are encouraging and this approach should be actively pursued and further investigated in future studies. Not only is spontaneous permanent LBBB harmful to our patients, but the iatrogenic variety produced by right ventricular apical pacing during conventional permanent pacing may also be deleterious to some patients. The compelling evidence presented herein cannot be ignored; it may dictate a change of attitude toward right ventricular apical pacing directing our attention to alternate sites of ventricular pacing and avoidance of the right ventricular apex.

Changes in tricuspid regurgitation (TR), mitral regurgitation (MR), and left ventricular ejection fraction (LVEF) are frequently noted after right ventricular apical (RVA) pacemaker implantation but prior studies evaluating whether left bundle branch area (LBBA), deep septal (DS), or leadless pacemaker implantation modify risk for those changes are limited. This study aims to compare changes in TR, MR, and LVEF after implantation of RVA, LBBA, DS, and leadless pacemakers. Patients were included if they underwent de novo pacemaker implantation for sinus node dysfunction or atrioventricular block and received pre- and post-implant echocardiography. Change in TR, MR, and LVEF were analyzed using post-hoc adjusted Kruskal-Wallis and Chi-squared testing, and multivariable ordinal logistic regression. Among 386 consecutive patients (RV, n=185; LBBA, n=122; DS, n=43, leadless, n=36) the change in TR grade differed between pacemaker types (median [interquartile range] grade change: RVA 0[0,1], leadless 0[0,1], DS 0[0,1], LBBA 0[0,0]; p=0.01). In multivariable ordinal logistic regression, leadless (OR 2.41, p=0.01) and DS pacemakers (OR 2.44, p<0.01) predicted TR worsening compared to LBBA. The change in MR grade also differed between pacemaker types (grade change: RVA 0[0,1], leadless 0[0,1], DS 0[0,0], LBBA 0[-1,0]; p=0.03). The change in LVEF differed between pacemaker types (LVEF change: RVA -3[-9,3]%, leadless -5[-14,1]%, DS -3[-11,0]%, LBBA -1[-5,5]%; p<0.01). The change in TR and MR grade and LVEF following pacemaker implant varied by pacemaker type. Compared to implantation with RVA, leadless, and DS pacemakers, LBBA pacemaker implantation was associated with more favorable changes in valvular and ventricular function.