Abstract
Introduction
A conventional right ventricular (RV) apical pacing is a safe, effective, and an established therapy in bradyarrhythmia; yet, it results in nonphysiological dyssynchronous electromechanical ventricular activation causing heart failure, atrial fibrillation, and cardiomyopathy in a subset of patients. 1 The data from the MOST (MOde Selection Trial) and DAVID (Dual Chamber and VVI Implantable Defibrillator) trials showed that in patients where pacing requirement was >40%, the likelihood of deterioration in systolic function and also the risk of heart failure hospitalization (HFH) was higher. 2 An alternative site like mid- and high-septal pacing was envisaged and tried but could not address this issue properly. His bundle pacing (HBP) has surfaced as a physiological alternative to RV pacing. This review on physiological pacing discusses the various anatomical and physiological aspects, hardware and technique, advantages and disadvantages along with the future prospects and directions.
Anatomy of His Bundle
The bundle of His is a chord-like structure measuring on an average of 20 mm in length by 4 mm in diameter. It arises as an anterosuperior extension from the compact atrioventricular (AV) node, penetrates into the fibrous body of septum, emerges out after getting encased in a fibrous sheath, and then passes along the posterior and inferior margins of the membranous interventricular septum. At the very crest of the muscular interventricular septum, the His bundle (HB) continues as the right bundle (Figure 1). The left bundle (LB) fans out as it descends in the subendocardium of the septal surface of the left ventricle into three interconnecting fascicles after the proximal 2 cm. Anatomically (Figure 2), HB has got 3 variants with Type I being the most common (47%). In Type I, AV bundle is covered by a thin layer of myocardial fibers and runs along the lower border of the membranous septum. In Type II (32%), the AV bundle is insulated by thick myocardial fibers and is markedly separated from the membranous septum. In Type III (21%), the AV bundle remains “naked” with no insulation from the surrounding myocardial fibers and runs beneath the endocardium. 3
Physiological Concept of HBP
The physiological concept of HBP is based upon the theories of longitudinal dissociation, output dependence, and virtual electrode polarization. HB comprises of the cells that are elongated and oblong in shape, partitioned intricately by collagen fibers making longitudinal division of HB unique in comparison to AV node. The fibers within the HB are arranged in strands predestined for the left or right bundle branches. Conduction delays within the HB are a common cause of bundle branch block (BBB) and positioning the pacing lead distal to the site of BBB can reverse it. Most traditionally considered “infrahisian” blocks are actually “intrahisian”.
In longitudinal dissociation, the electrotonic potential largely remains in a direction parallel to the running of these cells in HB and almost zero in a direction perpendicular to it. 4 In output dependence, the recruitment of distal fibers closely bordering the abnormal myocardium is stimulus dependent and with increase in stimulus strength there occurs a functional block mimicking the native conduction through the His Purkinje system. The patients with His Purkinje disease may have relatively proximal disease, and that pacing distal to the site of block overcomes the block resulting in narrow QRS. However, the virtual electrode polarization initially studied in the setting of defibrillation remains an alternative theory to explain HBP-mediated QRS narrowing.
History of HBP
Studies of HBP with Mean Follow-up >12 Months (n = 19 Studies)
(A) Fluoroscopic LAO projection showing HBP lead position (red arrow). (B) Local His potential unipolar EGM from pacing lead (yellow arrow). (C) His lead pacing resulting in narrow QRS 101 ms. (D) Intrinsic narrow QRS ECG and NS-HBP with recruitment of HBP resulting in narrow QRS.
Hardware and Technique of HBP
HBP is performed using the Select Secure (Model number 3830; 69 cm; Medtronic Inc, Minneapolis, Minnesota, USA) pacing lead delivered through a fixed-curve sheath (C315 His; Medtronic Inc). The delivery sheath over the wire is inserted into the RV. The wire is removed while pulling back the sheath toward the right atrium just beyond the tricuspid annulus. With a little clockwise torque, the distal curve points perpendicularly to the septum, and ensures a precise and secure lead fixation. The pacing lead is then advanced through the sheath with only the distal electrode/helix beyond the tip of the catheter. Recording is done of a unipolar His electrogram signal from the lead tip at a gain setting of 0.05 mV/mm and display either on Medtronic Pacing System Analyzer (model number 2290) at a sweep speed of 50 mm/s or through the EP system with the continuous 12-lead electrocardiogram (ECG) monitoring together with the unipolar signals from the lead (sweep speed, 100 mm/s; gain, 0.05 mV/mm). This is required in order to verify the capture of the conduction system and to compare the paced QRS morphology during various output maneuverers. An acceptable His signal is obtained when the atrial to ventricular electrogram ratio is of at least 1:2 or less (Figure 3). His signal may be seen even with larger A signals, but that is not an ideal site in view of greater chances of atrial oversensing and that pacing “relatively proximally” within the His may not correct a BBB.
The unipolar pacing is tested starting at a high voltage (10 V/1ms) and documenting changes in QRS morphologies. The His and RV capture thresholds along with BBB correction thresholds are taken for the purpose of programming final output settings and follow-up. The lead is then fixed into position by giving 4 or 5 clockwise rotations. HB capture threshold is accepted if found to be <2.5 V/1.0 ms and if 1:1 His to ventricular conduction at a minimum of 120 bpm is demonstrable during pacing. 8 The QRS morphology of the paced rhythm is dependent upon stimulus strength output, position, and anatomy of HB. In case HB electrogram is not recordable during mapping, unipolar pacemapping is performed to identify the successful site.
Selective Versus Nonselective HBP
S-HBP is characterized by selective capture of His-Purkinje system without adjoining ventricular tissue. In S-HBP, the pacing spike QRS interval remains identical to the His ventricular interval, QRS/T wave complex remains concordant, and QRS width remains same even at lower pacing output.
Studies Showing HBP Feasibility: Safety and Comparison With RVP
S-HBP may seem more physiological than NS-HBP but NS-HBP gives better safety in patients with infrahisian blocks ensuring ventricular myocardium capture in case His capture is lost. In accordance with the recently published data from the Geisinger and Rush University HBP registries, there is not much difference in terms of primary endpoint of all-cause mortality or HFH (35% in the NS-HBP versus 19% in the S-HBP group,
Indications
The indication of HBP remains the same as recommended for right ventricular pacing (RVP) like sick sinus syndrome, permanent AF with AV node ablation, high-grade AV nodal, and even infranodal block. The potential role of HBP in heart failure is to prevent the development of pacing-induced cardiomyopathy and can be used as an alternative to biventricular pacing (BiVP) in patients of heart failure with left bundle branch block (LBBB) and those with narrow QRS and PR prolongation. HBP is recommended as class IIa for patients with LVEF between 36% and 50% requiring ventricular pacing (>40% of the time) and as class IIb for patients with AV block at the level of the AV node (2018 AHA/ACC/HRS). 11
HBP and RVP
RV apical pacing on long term is limited by deterioration of functional class, exercise capacity, and survival. Except for the benefit in improving LVEF, nonapical RV pacing has not proven beneficial in improving these parameters. The HBP, on the other hand, has not only resulted in significant improvement in left ventricular dimensions and consequent LVEF but also in New York Heart Association (NYHA) class, quality of life, and heart failure-related hospital admissions.12, 13 A reduction in left atrial dimensions due to physiological activation and relaxation of left ventricle has also been seen with HBP resulting in better functioning of left atrium and delaying onset of atrial fibrillation (Table 2).
HBP and QRS Normalization
Clinical Trials of LBBP
HBP Versus LBBP
HBP and BiVP
The left ventricular dysfunction in heart failure is associated with an increase in morbidity as well as mortality. In addition to optimal medical therapy, BiVP is now an established adjunctive therapy only in patients with broad QRS, especially LBBB. Despite advances in pharmacotherapy and device therapy, the 5- to 10-year survival rate still remains approximately 50% and 25%, respectively, and the readmission rate at 30 days is still 25%. BiVP produces nonphysiological activation patterns and is not a perfect resynchronization tool as it relies on slow cell-to-cell conduction which limits the degree of ventricular resynchronization that can be achieved. BVP induces ventricular dyssynchrony by epicardial to endocardial activation of the myocardium. Hence unfortunately, 30% of patients are nonresponsive to the BiVP and since HBP has been associated with narrowing of QRS in patients with BBB, this could be an alternative way to induce mechanical resynchronization and supplant traditional BiVP. 13 The feasibility of HBP in BiVP indicated patients were reported by Lustgarten et al 15 in 2010 and 3 years later by Barba Pichardo et al. 16 Sharma et al in their study found a marked improvement in LVEF as well as NYHA class and concluded that HBP can stand as a reasonable alternative to BiVP although the survival benefit data is lacking. 17
His resynchronization therapy provides twice as much reduction in left ventricular activation time (LVAT)-95 and left ventricular dyssynchrony index compared with BVP. The shortening of ventricular activation time is directly proportional to the improvement in function, and positioning of His lead at the site of greatest activation time reduction facilitates maximal improvements in myocardial performance. His resynchronization is achieved by recruiting LV conduction fibers, as suggested by Lustgarten et al pacing at a site distal to the split His recruited the LB. This suggests that the level of block/delay in the LB was likely within the HB fibers that were predestined to the LB. His pacing also has other potential advantages over BVP. It does not require the use of contrast and is not limited by diaphragmatic capture or the constraints of the coronary sinus anatomy.18, 19
His-Sync is the first randomized pilot trial of His-CRT and it did not demonstrate significant improvements in ECG or echocardiographic parameters as compared with BiV-CRT. The trial was designed with intention-to-treat, and with presence of high crossover rates it could not assess treatment efficacy directly. Longer curve and deflectable sheaths with septal orientation, and intraseptal fixation are likely to improve His correction rates and stability of thresholds. In patients who required crossover, half of patients showed nonspecific intraventricular conduction delay, which is unlikely to be corrected by His-CRT. Better patient selection may thus decrease crossover rates and larger prospective studies may further be useful. 20 The evidence for CRT in patients with nonspecific intraventricular conduction delay with wide QRS and RBBB is sparse with conflicting results and a recent demonstration of significant narrowing of QRS duration and improvement in LVEF in a patient of RBBB by HBP has paved the way for such technique in these groups of patients as well. Hence, attempted physiological pacing using HOT CRT strategy may pave the way forward to benefit not only these patients but also patients with ischemic cardiomyopathy with distal myocardial disease.
Challenges and Potential Disadvantages of HBP
The potential target for lead placement in HBP is smaller than RVP, resulting in prolongation of procedural and fluoroscopy time. Although all operators experience an initial learning curve with HBP that can be overcome, even the experienced operators in the largest published series reported a 27% increase in procedure time (70.2 ± 34 versus 55.0 ± 25 min) and 39% increase in fluoroscopy duration (10.3 ± 6.5 versus 7.4 ± 5.1). Although this may be mitigated with further developments in delivery systems and techniques, it is likely that average HBP implant times will always exceed those of RVP.
Stability of HB lead as compared to RV apical lead needs further validation, and higher HBP capture thresholds are an apprehension for early battery depletion, necessitating the need for long-term performance leads and newer generator units with battery longevity. 21
The development of low infrahisian block, failure to map and capture the HB, low R wave amplitude, high pacing threshold, and extraction of lead remains the other potential challenges of HBP. 22
Left Bundle Branch Pacing
Left bundle branch pacing (LBBP) overcomes many of the limitations of HBP and can be considered as another excellent and an emerging modality. The direct capture of the LB was first demonstrated by Huang et al, which resulted in synchronized activation of ventricles (Table 3). For LBBP, either LB or 1 of its fascicles is captured along with the LV septal myocardium using 4.1F sized 3830 Select Secure Pacing Lead (Medtronic Inc). The lead is parked deep inside the interventricular septum about 1 to 1.5 cm below the bundle of His in right anterior oblique (RAO) view (Figure 4). The LB capture is ensured by unipolar-paced QRS showing qR pattern in lead V1, biphasic in lead II (Figure 5), and peak LVAT less than 80 ms. The LVAT determines the depth of lead engagement as it may be prolonged in patients with intraventricular conduction defects and ischemic cardiomyopathy with significant scar. The LB capture is also demonstrated by presence of LB potential characterized by a sharp high frequency signal preceding the local ventricular electrogram by 25 to 30 ms and is seen in almost all patients during sinus rhythm except infrahisian complete heart block and complete LBBB where there is no antegrade activation of LB. 23 In selective LB capture, a distinct isoelectric interval between LB potential and QRS onset is seen and there is change in paced QRS morphology from qR to rSR in lead V1 with fixed LVAT during unipolar threshold measurement. In non-selective LB capture, there is no distinct isoelectric segment and QRS onset is immediately after the pacing artefact with pseudo-delta wave.
Though a rapidly accepted technique due to the large area of LB (10-15 mm) to work with as compared to 2 mm area of HB, the complication of RBB injury, lead dislodgement, septal artery injury, thromboembolism, and lead perforation during procedure or later due to delayed migration of lead has been documented. Postprocedure echocardiography is advised for all patients to assess the depth of the lead and to look for exposed helix into the left ventricular (LV) cavity. The 3830 Select Secure Lead is not primarily meant for site selective septal pacing and lead stability but the lead extraction also remains a major concern and needs to be studied in further trials (Table 4).
Recent published data 24 talk of heterogeneous septal conduction across patients with surface LBBB pattern, ranging from no discrete block to complete conduction block. Focal and proximal conduction block at the level of the left-sided His fibers was frequently observed as the pathophysiological mechanism of LBBB (left intrahisian block). Henceforth, conduction block proximal to the LBB within the left-sided His fibers is most amenable to corrective HBP, where pacing circumvents the site of block with recruitment of latent Purkinje fibers.
Future Directions
HBP is a promising and an attractive option of physiological pacing; however, the long-term performance in patients especially with infranodal, intrahisian AV block, and BBB is yet to be validated in large prospective trials. Current limitations include the trained operators, optimal technology necessary to effectively deliver HBP, anatomical constraints, the high thresholds of HBP, extraction of a chronic HBP lead and LB lead, and impact of HBP/LBBP on ventricular arrhythmias in presence of myocardial scar. The development of implantation techniques and new tools like the delivery sheaths and design of lead specific for HBP and LBBP will continue to evolve to make procedure technically easier and less time consuming.
Conclusion
Permanent HBP is a physiological alternative to RVP with a potential to alleviate the unfavorable outcome of chronic RV pacing. It promotes an AV and intraventricular synchrony resulting not only in improvement in LVEF but also NYHA class, quality of life, and exercise capacity. HBP is safe, efficacious, feasible, and has shown promising results in the published data to make it to 2018 AHA/ACC/HRS guidelines even without randomized control trials. HBP represents an attractive physiological pacing option for patients who are conventional candidates for RV pacing as well as BiVP. It provides more definitive electrical resynchronization and can be considered in heart failure patients with wide QRS who are nonresponders to BiVP. However, randomized controlled clinical trials are necessary to firmly establish the role of physiological pacing in these unusual and unique situations.