Beyond biventricular pacing: Exploring the advantages of his-bundle pacing and left bundle branch pacing in heart failure-A systematic review and meta-analysis.

BACKGROUND: This meta-analysis compares His-Purkinje system pacing (HPSP), a novel cardiac resynchronization therapy (CRT) technique that targets the intrinsic conduction system of the heart, with conventional biventricular pacing (BiVP) in heart failure (HF) patients with left ventricular (LV) dysfunction and dyssynchrony. METHODS: We searched multiple databases up to May 2023 and identified 18 studies (five randomized controlled trials and 13 observational studies) involving 1291 patients. The outcome measures were QRS duration, left ventricular ejection fraction (LVEF) improvement, left ventricular end-diastolic diameter (LVEDD) change, HF hospitalization, and New York Heart Association (NYHA) functional class improvement. We used a random-effects model to calculate odds ratios (OR), and mean differences (MD) with 95% confidence intervals (CI). We also assessed the methodological quality of the studies. RESULTS: The mean LVEF was 30.7% and the mean follow-up duration was 8.1 months. Among LBBP, HBP, and BiVP, HBP provided the shortest QRS duration [MD: -18.84 ms, 95% CI: -28.74 to -8.94; p = 0.0002], while LBBP showed the greatest improvement in LVEF [MD: 5.74, 95% CI: 2.74 to 7.46; p < 0.0001], LVEDD [MD: -5.55 mm, 95% CI: -7.51 to -3.59; p < 0.00001], and NYHA functional class [MD: -0.58, 95% CI: -0.80 to --0.35; p < 0.00001]. However, there was no significant difference in HF hospitalization between HPSP and BiVP. CONCLUSION: LBBP as modality of HPSP demonstrated superior outcomes in achieving electrical ventricular synchrony and systolic function, as well as alleviating HF symptoms, compared to other pacing techniques.

Fascicular ventricular tachycardia arising from the left side His and its adjacent region: a subset of upper septal idiopathic left ventricular tachycardia.

AIMS: Fascicular ventricle tachycardia (FVT) arising from the proximal aspect of left His-Purkinje system (HPS) has not been specially addressed. Current study was to investigate its clinical, electrocardiographic, and electrophysiological characteristics. METHODS AND RESULTS: Eighteen patients who were identified as this rare FVT were consecutively enrolled, and their scalar electrocardiogram and electrophysiological data were collected and analysed. The ventricular tachycardia (VT) morphology was similar to sinus rhythm (SR) in eight patients, left bundle branch block type in one patient, right bundle branch block type in seven patients, and both narrow and wide QRS type in two patients. During VT, right-sided His potential preceded the QRS with His-ventricle (H-V) interval of 36.3 ± 12.4 ms, which was shorter than that during SR (-51.4 ± 8.6 ms) (P = 0.002). The earliest Purkinje potentials (PPs) were recorded within 7 ± 3 mm of left-side His and preceded the QRS by 49.1 ± 14.0 ms. Mapping along the left anterior fascicle and left posterior fascicle revealed an antegrade activation sequence in all with no P1 potentials recorded. In the two patients with two VT morphologies, the earliest PP was documented at the same site, and the activation sequence of HPS remained antegrade. Ablation at the earliest PP successfully eliminated the tachycardia, except one patient who developed complete atrial-ventricular block and two patients who abandoned ablations. After at least 12 months follow-up, 15 patients were free from any recurrences. CONCLUSIONS: Fascicular ventricle tachycardia arising from the proximal aspect of left HPS was featured by recording slightly shorter H-V interval and absence of P1 potentials. Termination of VT requires ablation at the left-sided His or its adjacent region.

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

BACKGROUND: His-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. METHODS: In 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. RESULTS: A 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%). CONCLUSION: The 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.

Pacing of the specialized His-Purkinje conduction system: 'back to the future'.

The conduction system of the human heart is composed of specialized cardiomyocytes that initiate and propagate the electric impulse with consequent rhythmic and synchronized contraction of the atria and ventricles, resulting in the normal cardiac cycle. Although the His-Purkinje system (HPS) was already described more than a century ago, there has been a recent resurgence of conduction system pacing (CSP), where pacing leads are positioned in the His bundle region and left bundle branch area to provide physiological cardiac activation as alternatives to the unnatural myocardial stimulation obtained with conventional right ventricular and biventricular pacing. In this review, we describe the fundamental anatomical and pathophysiological aspects of the specialized HPS along with the CSP technique's nuts and bolts to highlight its potential benefits in everyday clinical practice.

Electrophysiological demonstration of nonselective His-Purkinje system capture with para-Hisian pacing.

BACKGROUND: The adverse effects of conventional right ventricular (RV) apical pacing prompted the search for more physiological pacing sites, such as selective and nonselective His bundle pacing (HBP), a variant of nonselective HBP (para-Hisian pacing), and mid-septal pacing. However, knowledge of their true benefit on the physiology of ventricular activation, lead stability, and pacing thresholds is limited. METHODS AND RESULTS: We included 152 consecutive patients (mean age 61 ± 24, 63% men) in this retrospective study. Of these, 137 patients with different bradyarrhythmias underwent active fixation lead implantation at the RV apex (n = 54), para-Hisian region (n = 66), or mid interventricular septum (n = 17). Fifteen patients with ventricular preexcitation due to an accessory pathway not undergoing pacing were included as controls. A 12­lead ECG was recorded in all patients, and cardiac electrical synchrony was assessed using the Synchromax® cross-correlation cardiac synchrony index (CSI). RESULTS: QRS duration was prolonged in all pacing sites: from 114 ± 28 to 160 ± 29 (RV apex), from 110 ± 28 to 122 ± 29 (para-Hisian), and from 121 ± 24 to 154 ± 30 (mid interventricular septum). The CSI was significantly improved only in patients undergoing para-Hisian pacing, despite a slight widening of the QRS interval. There was no difference in pacing thresholds and sensed R-wave voltage between pacing sites. Only 1 lead, implanted at the para-Hisian region (1.5%), was dislodged towards the mid septum 48 h after implantation but did not require repositioning. CONCLUSIONS: QRS duration was not associated with changes in CSI, meaning that QRS width does not significantly affect electrical synchrony.

His bundle pacing shows similar ventricular electrical activation as sinus: selective and nonselective His pacing indistinguishable.

His bundle pacing utilizes the His-Purkinje system to produce more physiological activation compared with traditional pacing therapies, but differences in electrical activation between pacing techniques are not yet quantified in terms of activation pattern. Furthermore, clinicians distinguish between selective and nonselective His pacing, but measurable differences in electrical activation remain to be seen. Hearts isolated from seven dogs were perfused using the Langendorff method. Electrograms were recorded using two 64-electrode basket catheters in the ventricles and a 128-electrode sock situated around the ventricles during sinus rhythm (right atrial pacing), right ventricular (RV) pacing, biventricular cardiac resynchronization therapy (biV-CRT), selective His pacing (selective capture of the His bundle), and nonselective His pacing (capture of nearby myocardium and His bundle). Activation maps were generated from these electrograms. Total activation time (TAT) was measured from the activation maps, and QRS duration was measured from a one-lead pseudo-ECG. Results showed that TAT, QRS duration, and activation sequence were most similar between sinus, selective, and nonselective His pacing. Bland-Altman analyses showed highest levels of similarity between all combinations of sinus, selective, and nonselective His pacing. RV and biV-CRT activation patterns were distinct from sinus and had significantly longer TAT and QRS duration. Cumulative activation graphs were most similar between sinus, selective, and nonselective His pacing. In conclusion, selective pacing and nonselective His bundle pacing are more similar to sinus compared with RV and biV-CRT pacing. Furthermore, selective pacing and nonselective His bundle pacing are not significantly different electrically.NEW & NOTEWORTHY Our high-density epicardial and endocardial electrical mapping study demonstrated that selective pacing and nonselective His bundle pacing are more electrically similar to sinus rhythm compared with right ventricular and biventricular cardiac resynchronization therapy pacing. Furthermore, small differences between selective and nonselective His bundle pacing, specifically a wider QRS in nonselective His pacing, do not translate into significant differences in the global activation pattern.

His-Purkinje system longitudinal dissociation: From bench to bedside. A case of output-dependent fascicular capture.

INTRODUCTION: Histological studies reported that the His bundle (HB) is partitioned into narrow cords by collagen running in its long axis, providing the anatomical setting necessary for its longitudinal dissociation. Further confirmations came from the demonstration that direct HB pacing normalizes the QRS axis and duration in subjects with proximal HB lesions causing bundle branch block. However, there is no evidence of the possibility of selective HB partitions pacing destined to the composition of branches and fascicles. METHODS AND RESULTS: We describe a case of intra-Hisian left bundle branch block in which permanent distal HB pacing corrects left ventricular delay and produces different QRS morphology at different voltage outputs, as an expression of different selective HB compartments recruitment. CONCLUSION: This case would strengthen the limited data in the literature about HB longitudinal dissociation.

Catheter ablation of the parahisian accessory pathways from the aortic cusps-Experience of 20 cases-Improving the mapping strategy for better results.

INTRODUCTION: Catheter ablation of the parahisian accessory pathways (PHAP) has been established as the definitive therapy for this type of arrhythmia. However, the PHAP proximity to the normal atrioventricular conduction system makes the procedure technically challenging. Here, we have reported a case series of 20 patients with PHAP who underwent aortic access ablation to evaluate the safety and efficacy of this approach in the PHAP ablation. METHODS AND RESULTS: The ablation through the aortic cusps was the successful approach in 13 of 20 (65%) of the cases. In 11 patients, the aortic approach was the initial strategy for ablation, and the accessory pathway was eliminated in seven (63.6%) of them. The aortic approach followed a failed right-sided attempt in nine patients. In six (66.7%) patients, the ablation was successful with the aortic approach. The only independent predictor for the successful ablation with each approach was the earliest ventricular activation before delta wave (predelta time) and a right-sided earliest ventricular activation of more than 23 ms had high sensitivity and specificity for right-sided success. Systematically using the two strategies (right and left approaches), the ablation of the PHAP was successful in 18 (90%) patients. CONCLUSION: The aortic approach seems to be a safe and effective strategy for the ablation of PHAP. It can be used when the right-sided approach fails or even considered as an initial strategy when the predelta time is less than 23 ms in the right septal region. When combining the right- and left-sided approaches, the success rate is high. We believe that the retrograde aortic approach remains a key tool for this challenging ablation.

The long-term therapeutic effects of His-Purkinje system pacing on bradycardia and cardiac conduction dysfunction compared with right ventricular pacing: A systematic review and meta-analysis.

AIMS: His-Purkinje system pacing has been demonstrated as a synchronized ventricular pacing strategy via pacing His-Purkinje system directly, which can decrease the incidence of adverse cardiac structure alteration compared with right ventricular pacing (RVP). The purpose of this meta-analysis was to compare the effects of His-Purkinje system pacing and RVP in patients with bradycardia and cardiac conduction dysfunction. METHODS: PubMed, Embase, Cochrane Library, and Web of Science were systematically searched from the establishment of databases up to 15 December 2019. Studies on long-term clinical outcomes of His-Purkinje system pacing and RVP were included. Chronic paced QRS duration, chronic pacing threshold, left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), all-cause mortality, and heart failure hospitalization were collected for meta-analysis. RESULTS: A total of 13 studies comprising 2348 patients were included in this meta-analysis. Compared with RVP group, patients receiving His-Purkinje system pacing showed improvement of LVEF (mean difference [MD], 5.65; 95% confidence interval [CI], 4.38-6.92), shorter chronic paced QRS duration (MD, - 39.29; 95% CI, - 41.90 to - 36.68), higher pacing threshold (MD, 0.8; 95% CI, 0.71-0.89) and lower risk of heart failure hospitalization (odds ratio [OR], 0.65; 95% CI, 0.44-0.96) during the follow-up. However, no statistical difference existed in LVEDV, LVESV and all-cause mortality between the two groups. CONCLUSION: Our meta-analysis suggests that His-bundle pacing is more suitable for the treatment of patients with bradycardia and cardiac conduction dysfunction.

Lead performance and clinical outcomes of patients with permanent His-Purkinje system pacing: a single-centre experience.

AIMS: His-Purkinje system (HPS) pacing, including His bundle (HB) and left bundle branch (LBB) pacing, has emerged as a highlighted topic in recent years. Comparisons in lead performance and clinical outcomes between HB and LBB pacing were seldom reported. We aimed to investigate the mid-long-term lead performance and clinical outcomes of permanent HPS pacing patients in our centre. METHODS AND RESULTS: Permanent HB pacing was implemented by placing the pacing lead helix at the HB area. Left bundle branch pacing was achieved by placing the lead helix in the left-side sub-endocardium of the interventricular septum. Pacing parameters, 12-lead ECG, echocardiography, and clinical outcomes were evaluated during follow-up. A total of 64 patients with HB pacing and 185 with LBB pacing were included. Left bundle branch pacing exhibited a slightly longer paced QRS duration than HB pacing (117.7 ± 11.0 vs. 113.7 ± 19.8 ms, P = 0.04). Immediate post-operation, LBB pacing had a significant higher R-wave amplitude (16.5 ± 7.5 vs. 4.3 ± 3.6 mV, P < 0.001) and lower capture threshold (0.5 ± 0.1 vs. 1.2 ± 0.8 V, P < 0.001) compared with HB pacing. During follow-up, an increase in capture threshold of >1.0 V from baseline was found in eight (12.5%) patients in the HB pacing group and none in LBB pacing. Paced QRS morphology changed from Qr to QS in lead V1 in seven patients (3.8%) with LBB pacing. Both HB and LBB pacing preserved cardiac function in patients with left ventricular ejection fraction (LVEF) over 50%. In patients with LVEF <50%, both HB and LBB pacing improved clinical outcomes during follow-up. CONCLUSION: His-Purkinje system pacing produced favourable electrical synchrony and improved cardiac function in patients with heart failure. Left bundle branch pacing showed superior pacing parameters over HB pacing. Lead micro-displacement with changes in paced QRS morphology posts a concern in LBB pacing.

Novel Strategy for Predicting Conduction Abnormalities During Transcatheter Closure of Perimembranous Ventricular Septal Defect in Adults.

BACKGROUND: In this study we evaluated the feasibility and efficacy of predicting conduction system abnormalities under 3-dimensional (3D) electroanatomic mapping guidance during transcatheter closure of perimembranous ventricular septal defects (pmVSDs) in adults.Methods and Results:The distribution of the His-Purkinje system (HPS) close to the margins of pmVSDs in the left ventricle was identified using 3D electroanatomic mapping and near-field HPS was further confirmed by different pacing protocols. Of the 20 patients in the study, 17 (85%) were successfully treated by transcatheter intervention. The minimum distance between the margins of the pmVSD and near-field HPS, as measured by 3D electroanatomic mapping, ranged from 1.3 to 3.9 mm (mean [± SD] 2.5±0.7 mm). Five patients with a minimum distance <2 mm had a higher risk (3/5; 60%) for adverse arrhythmic events, whereas patients with a distance >2 mm were at a much lower risk (1/15; 6.7%) of procedure-related conduction block (P=0.032). No other adverse events were recorded during the follow-up period (median 30 months). CONCLUSIONS: A minimum distance between the pmVSD and near-field HPS <2 mm was associated with a relatively high risk of closure-related conduction block. 3D electroanatomic mapping may be helpful in guiding decision making for transcatheter closure and reduce the incidence of adverse arrhythmic events.

The clinical and electrophysiological characteristics of nonsustained repetitive monomorphic ventricular tachycardia from the left His-Purkinje system.

BACKGROUND: Repetitive monomorphic ventricular tachycardia (RMVT) arising from the left His-Purkinje system can occasionally be encountered during clinical practice. We describe eight cases as a unique entity in this study to characterize the clinical and electrophysiological features of the patients. METHODS: Eight patients with frequent palpitation (five men with median age of 28 years) were included in the study from January 2003 to July 2018. Twelve-lead ECG (Electrocardiogram), Holter, and echocardiographic tests were performed after medical history interrogations and physical examinations. Antiarrhythmic drug therapy was essential to all patients, and catheter ablation was attempted if the patients could not tolerate or were not responsive to drug therapy. RESULTS: No patients had a history of syncope and a family history of sudden cardiac death. ECGrecording was characterized by frequent ventricular extrasystoles, ventricular couplets, and salvos of nonsustained VT competitive with sinus rhythm. The QRS morphology of ectopic beats was in the right bundle branch block pattern with severe left axis deviation. The width of the QRS complex from ECG was 135 ms (120-140) during ventricular tachycardia. Verapamil had no effect on all VT individuals. Enlargement of the left ventricle was found in two patients. Four out of six cases were successful with catheter ablation treatment. CONCLUSION: RMVT arising from the left His-Purkinje system is a special arrhythmic and nonverapamil-sensitive entity. The electrophysiological mechanism of this treatment appears to be focal firing, which is amendable to catheter ablation in symptomatic and high-burden patients.

Voltage dependent conduction abnormalities in His bundle pacing in patients without His Purkinje system disease.

BACKGROUND: During His bundle (HB) pacing, the active fixation of HB lead may cause disruption of the enclosed conduction fibers and cause conduction delay. His Purkinje conduction delays have been shown to revert to normal with higher voltage pacing. OBJECTIVE: To determine if conduction delays seen with penetrative HB pacing are voltage dependent and can resolve with higher stimulus voltage. METHODS: In 17 patients undergoing HBP, the effect of voltage on a composite His Purkinje system-ventricular activation time (hVAT) as well as electrocardiographic (ECG) evidence of conduction delay, was systematically evaluated. RESULTS: There was highly significant prolongation of hVAT indicative of conduction delay in 13/17 patients. ECG changes of rightward delay were also seen in 9/13 patients. Both types of delays we manifest at lower voltages and we uniquely resolved by higher stimulation voltage. A pre-excitation like abnormality was also seen in 15/17 patients. This conduction abnormality was manifest at higher voltage without prolongation of hVAT. In 6/15 patients the pre-excitation like abnormality ceased at lower voltage. CONCLUSION: HB pacing is associated with evidence of significant conduction delay noted at low voltage, which resolves with higher stimulation voltage. The more common pre-excitation like abnormality appears to occur at high voltage and, in of itself, does not appear to prolong hVAT.

Longitudinal dissociation and transition in thickness of the His-Purkinje system cause various QRS waveforms of surface ECG under His bundle pacing: A simulation study based on clinical observations.

AIMS: His bundle pacing (HBP) is a feasible and reliable alternative to conventional right ventricular pacing (RVP), but associated ECG (electrocardiogram) changes have not been well-studied. This study aimed to determine the mechanisms underlying ECG changes associated with HBP using patient-specific multiscale heart simulations. METHODS: ECGs were recorded in two patients who were treated by HBP under a native rhythm and HBP at high and low voltages. We created patient-specific multiscale simulation heart models of these patients and performed ECG simulation under these conditions. Using these results and detailed information on the electrical field around the pacing lead, we investigated mechanisms underlying the observed ECG changes. RESULTS: Heart simulations successfully reproduced ECGs under a native rhythm for both cases. In case 1, nonselective HBP produced a left bundle branch (LBB) block pattern, which was reproduced as a selective right bundle branch (RBB) pacing. However, in case 2, ECG under nonselective HBP showed an RBB block pattern, which could not be reproduced by the commonly used framework. Findings on the electrical field and anatomy of the His bundle and its branches suggested that longitudinal dissociation of the His bundle and transition of thickness in the stem of the LBB caused a conduction delay in the RBB to produce these ECG changes in this patient. CONCLUSION: Variations in the anatomy of the His bundle and its branches may underlie the diverse ECG responses to HBP. These variations should be taken into account when performing this therapy.

Distinct Electrocardiographic Form of Idiopathic Ventricular Arrhythmia Originating From the Left Bundle Branch.

Most premature ventricular contractions (PVCs) arise from the right or left ventricular outflow tract. Some VPCs originate near the His-bundle region. However, there remains a paucity of information on PVCs originating directly from the cardiac conduction system. We describe 2 cases with idiopathic frequent PVCs that were mapped directly to the left bundle branch itself. We also provide an anatomic-based mapping and ablation approach for management of these uncommon and challenging arrhythmias. In both cases we were able to either eliminate or significantly suppress the ectopic source by applying radiofrequency at this location without causing any significant impairment of the atrioventricular conduction.

Paroxysmal atrioventricular block: Electrophysiological mechanism of phase 4 conduction block in the His-Purkinje system: A comparison with phase 3 block.

BACKGROUND: Paroxysmal atrioventricular (A-V) block is relatively rare, and due to its transient nature, it is often under recognized. It is often triggered by atrial, junctional, or ventricular premature beats, and occurs in the presence of a diseased His-Purkinje system (HPS). Here, we present a 45-year-old white male who was admitted for observation due to recurrent syncope and near-syncope, who had paroxysmal A-V block. The likely cellular electrophysiological mechanisms(s) of paroxysmal A-V block and its differential diagnosis and management are discussed. METHODS: Continuous electrocardiographic monitoring was done while the patient was in the cardiac unit. RESULTS: Multiple episodes of paroxysmal A-V block were documented in this case. All episodes were initiated and terminated with atrial/junctional premature beats. The patient underwent permanent pacemaker implantation and has remained asymptomatic since then. CONCLUSIONS: Paroxysmal A-V block is rare and often causes syncope or near-syncope. Permanent pacemaker implantation is indicated according to the current guidelines. Paroxysmal A-V block occurs in the setting of diseased HPS and is bradycardia-dependent. The detailed electrophysiological mechanisms, which involve phase 4 diastolic depolarization, and differential diagnosis are discussed.

Wenckebach pattern in right bundle branch block - benign or not?

A Mobitz type I block (Wenckebach phenomenon) with narrow QRS complex is almost always due to a lesion in the AV node. In a type I block with wide QRS complex (>0.12sec), the block can be in the His-Purkinje system in 60-70% of the cases. Even though the progressive PR prolongation with every conducted beat suggests Wenckebach phenomenon, one needs to pay attention to the accompanying QRS complex. In the setting of persistent right bundle branch block, axis change of subsequent conducted beat before an unconducted p suggests alternating fascicular block, giving clue to unreliable infra-Hisian conduction; and in the setting of symptoms, a pacemaker should be implanted. Infra-Hisian Wenckebach block is rare with only sparse literature reports. The present case report adds to these, suggesting that wide QRS with Wenckebach block on surface ECG may indicate infra-Hisian conduction abnormalities.

Capturing the His-Purkinje system is not possible from conventional right ventricular apical and nonapical pacing sites.

INTRODUCTION: Direct His bundle capture may negate ventricular electrical dyssynchrony induced by right ventricular (RV) apical pacing. We sought to evaluate if direct His bundle pacing is possible with conventional pacemaker lead implantation at various sites in the RV. METHODS: Consecutive patients underwent RV pacing using standard implantable active fixation pacing leads in a random order in the RV outflow tract, middle RV, and RV apex at stimulation threshold and at increasing voltages of 2.5, 5, 7.5, and 10 volts (V). At each location, QRS width and morphology on 12-lead electrocardiograph (ECG) were compared in sinus and paced rhythm at the different voltages. RESULTS: Twelve patients underwent a total of 2,160 paced QRS measurements. Progressive increases in stimulation voltage did not change QRS morphology or duration regardless of site of pacing (RV outflow tract, middle RV, and RV apex) in any of the 12 ECG leads. In addition, apart from the stimulation threshold between the RV outflow tract and RV apex, there was no statistically significant difference in QRS duration between the three pacing sites. CONCLUSION: In patients with a baseline normal QRS duration, none of the three conventional RV pacing sites were able to produce QRS narrowing and capture the His-Purkinje system. Furthermore, based on paced QRS duration as an indirect surrogate of electrical LV dyssynchrony, there was no clear advantage of one pacing site over another.

Cardiac conduction diseases: understanding the molecular mechanisms to uncover targets for future treatments.

INTRODUCTION: The cardiac conduction system (CCS) is crucial for maintaining adequate cardiac frequency at rest and modulation during exercise. Furthermore, the atrioventricular node and His-Purkinje system are essential for maintaining atrioventricular and interventricular synchrony and consequently maintaining an adequate cardiac output. AREAS COVERED: In this review article, we examine the anatomy, physiology, and pathophysiology of the CCS. We then discuss in detail the most common genetic mutations and the molecular mechanisms of cardiac conduction disease (CCD) and provide our perspectives on future research and therapeutic opportunities in this field. EXPERT OPINION: Significant advancement has been made in understanding the molecular mechanisms of CCD, including the recognition of the heterogeneous signaling at the subcellular levels of sinoatrial node, the involvement of inflammatory and autoimmune mechanisms, and the potential impact of epigenetic regulations on CCD. However, the current treatment of CCD manifested as bradycardia still relies primarily on cardiovascular implantable electronic devices (CIEDs). On the other hand, an If specific inhibitor was developed to treat inappropriate sinus tachycardia and sinus tachycardia in heart failure patients with reduced ejection fraction. More work is needed to translate current knowledge into pharmacologic or genetic interventions for the management of CCDs.

Ventricular activation pattern of left ventricular septal pacing in a canine model.

BACKGROUND: Left bundle branch pacing (LBBP) is a feasible and effective physiological pacing technique. The QRS morphology of left ventricular septal pacing (LVSP) is similar to that of LBBP. The ventricular activation pattern of LBBP is well-known, whereas the pattern of LVSP still needs further investigation. The present study aimed to determine ventricular activation pattern difference between LVSP and LBBP in a canine model. METHOD: All six canines underwent successful LBBP and LVSP through trans-ventricular septum using intracardiac echocardiography and intracardiac electrogram. Their hearts were isolated and stained with Lugol's iodine to determine the position of the pacing lead. The activation sequences of the left ventricular myocardium and His-Purkinje system were recorded by placing multiple electrode catheters. RESULTS: First, the left His-Purkinje system in LVSP was activated simultaneously from apical and basal regions to the left ventricular middle septal region, whereas the left ventricular septal myocardium was activated from the apical to basal region. The left His-Purkinje system activation in LBBP occurred in the direction of the apex from the pacing lead, but the left ventricular septal myocardium was activated in the apical to basal direction. Furthermore, the left intraventricular electrical synchrony was similar between LVSP and LBBP as determined by mapping the left ventricular septal to free wall activation time (46.7 ± 1.8 ms vs. 45.0 ± 1.4 ms, p = 0.11). CONCLUSION: The ventricular activation sequence of LVSP was similar to LBBP. LVSP can capture LBB due to the wide distribution of LBB. These findings suggest a rationale for clinical application of LVSP.