His-bundle pacing is the best approach to physiological pacing

The complete electrical activation sequence of the human heart was first described by Durrer et al1Durrer D. van Dam R.T. Freud G.E. Janse M.J. Meijler F.L. Arzbaecher R.C. Total excitation of the isolated human heart.Circulation. 1970; 41: 899-912Crossref PubMed Scopus (1239) Google Scholar in the late 1960s and was based on mapping of the first 5 ms of left ventricular (LV) activation using 870 intramural electrodes. They noted 3 distinct endocardial areas excited synchronously in the LV, proving the trifascicular nature of the left conduction system (LCS): (1) high anterior paraseptal wall; (2) central left upper interventricular septum; and (3) distal posterior paraseptal wall. In a field in which electrical disturbances of 5–10 ms are associated with diverging clinical outcomes, the preservation and/or restoration of this intricate and perfectly specialized activation is the basis for physiological pacing. We propose that His-bundle pacing (HBP) is the only form of cardiac stimulation that can precisely reproduce this evolutionarily conserved form of intrinsic activation. With increased implementation, recent concerns have emerged whereby (1) HBP implantation is technically more challenging with a long learning curve2Keene D. Arnold A.D. Jastrzebski M. et al.His bundle pacing, learning curve, procedure characteristics, safety, and feasibility: insights from a large international observational study.J Cardiovasc Electrophysiol. 2019; 30: 1984-1993Crossref PubMed Scopus (51) Google Scholar; and (2) thresholds for His capture may unpredictably rise after device placement.3Kim J. Goldbarg S. Leung S. Yang H. Slotwiner D. Increased threshold in nonselective His-bundle pacing suspected to be caused by amiodarone.HeartRhythm Case Rep. 2019; 5: 112-114Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar In response to these issues (given current technology), left bundle branch area pacing (LBBAP) as pioneered by Huang et al4Huang W. Su L. Wu S. et al.A novel pacing strategy with low and stable output: pacing the left bundle branch immediately beyond the conduction block.Can J Cardiol. 2017; 33: 1736 e1731-1736 e1733Abstract Full Text Full Text PDF Scopus (208) Google Scholar has been introduced as a novel form of physiological pacing, potentially overcoming many of the limitations of HBP while maintaining all of the advantages.4Huang W. Su L. Wu S. et al.A novel pacing strategy with low and stable output: pacing the left bundle branch immediately beyond the conduction block.Can J Cardiol. 2017; 33: 1736 e1731-1736 e1733Abstract Full Text Full Text PDF Scopus (208) Google Scholar,5Zhang S. Zhou X. Gold M.R. Left bundle branch pacing: JACC review topic of the week.J Am Coll Cardiol. 2019; 74: 3039-3049Crossref PubMed Scopus (48) Google Scholar Although LBBAP may yield pacing thresholds more similar to myocardial pacing, whether this form of permanent pacing can be successfully targeted in all patients is unclear. Furthermore, there is a current knowledge gap about how to distinguish capture of the LCS from capture of the left ventricular septum (LVS) only. We respectfully submit that HBP is the best approach to fully achieve physiological pacing based on the following arguments:1.Only HBP results in complete recruitment of intrinsic LCS activation2.Available clinical evidence for HBP far outnumbers that for LBBAP3.Lack of definitive evidence and criteria for capture of the LCS4.Generalizability of LBBAP is unknown and largely untested outside of China, particularly in the presence of septal scar and ischemic substrates Is fascicular pacing adequate? Although multiple reports of LBBAP suggest recruitment of the common left bundle, many published illustrations of this technique do not demonstrate this in practice. The presence of a superior axis (seen in multiple published figures) is not consistent with capture of the LBB but rather left posterior fascicular pacing.6Li X. Li H. Ma W. et al.Permanent left bundle branch area pacing for atrioventricular block: feasibility, safety, and acute effect.Heart Rhythm. 2019; 16: 1766-1773Abstract Full Text Full Text PDF PubMed Scopus (92) Google Scholar,7Li Y. Chen K. Dai Y. et al.Left bundle branch pacing for symptomatic bradycardia: implant success rate, safety, and pacing characteristics.Heart Rhythm. 2019; 16: 1758-1765Abstract Full Text Full Text PDF PubMed Scopus (76) Google Scholar Only HBP results in complete anterograde activation of the trifascicular LCS. A recent high-resolution mapping study in an animal model highlights distal capture within the fascicles in the majority of cases.8Qian Z. Hou X. Wang Y. et al.Physiological left bundle branch pacing validated by ultra-high density ventricular mapping in a swine model.Circ Arrhythm Electrophysiol. 2020; 13: e007898Crossref PubMed Scopus (2) Google Scholar Although retrograde activation of the proximal system likely is better than myocardial pacing, whether this region of myocardium contributes substantially to synchronous cardiac contraction remains unclear. In 2018, Zanon et al9Zanon F. Ellenbogen K.A. Dandamudi G. et al.Permanent His-bundle pacing: a systematic literature review and meta-analysis.Europace. 2018; 20: 1819-1826Crossref PubMed Scopus (99) Google Scholar reported a systematic review of HBP in 17 single-arm and 9 comparative studies totaling 1438 patients. Mean implant success rate was approximately 85% across these studies. Among 8 studies reporting change in left ventricular ejection fraction (LVEF) after HBP, they found an average 5.9% increase after pacing (P = .001). The largest prospective cohort study comparing HBP with right ventricular pacing (RVP) evaluated the outcomes of 304 patients with successful HBP vs 433 RVP controls.10Abdelrahman M. Subzposh F.A. Beer D. et al.Clinical outcomes of His bundle pacing compared to right ventricular pacing.J Am Coll Cardiol. 2018; 71: 2319-2330Crossref PubMed Scopus (219) Google Scholar In that study, Abdelrahman et al10Abdelrahman M. Subzposh F.A. Beer D. et al.Clinical outcomes of His bundle pacing compared to right ventricular pacing.J Am Coll Cardiol. 2018; 71: 2319-2330Crossref PubMed Scopus (219) Google Scholar found that HBP was associated with a reduction in a composite of all-cause mortality, heart failure (HF) hospitalization, and need for upgrade to biventricular pacing (BiV) at mean follow-up of 4.3±3.9 years. The primary outcome was reduced by 29% in all-comers and 35% in patients with at least 20% ventricular pacing burden. Reduction in all-cause mortality nearly reached significance (hazard ratio HR 0.73; P = .058), and HF hospitalization was significantly reduced (HR 0.63; P = .021). Particularly when viewed in conjunction with other reports having ≥12-month outcomes (Table 1), there is now considerable evidence supporting HBP in clinical practice. Longer-term lead performance has now been reported with follow-up to 5 years. Although longitudinal follow-up consistently demonstrates rising thresholds prompting more frequent lead revisions than RVP, long-term clinical benefit with reduction in HF hospitalization is consistent,11Zanon F. Abdelrahman M. Marcantoni L. et al.Long term performance and safety of His bundle pacing: a multicenter experience.J Cardiovasc Electrophysiol. 2019; 30: 1594-1601Crossref PubMed Scopus (42) Google Scholar,12Vijayaraman P. Naperkowski A. Subzposh F.A. et al.Permanent His-bundle pacing: long-term lead performance and clinical outcomes.Heart Rhythm. 2018; 15: 696-702Abstract Full Text Full Text PDF PubMed Scopus (116) Google Scholar even in the setting of premature battery depletion. The summary of clinical evidence for LBBAP with ≥12-month median follow-up is given in Table 2, which includes a singular study with a subgroup of 8 patients who underwent LBBAP along with 44 HBP patients who had undergone atrioventricular (AV) nodal ablation. Median follow-up has been either none (acute immediate implantation) to 3 months.6Li X. Li H. Ma W. et al.Permanent left bundle branch area pacing for atrioventricular block: feasibility, safety, and acute effect.Heart Rhythm. 2019; 16: 1766-1773Abstract Full Text Full Text PDF PubMed Scopus (92) Google Scholar,13Hou X. Qian Z. Wang Y. et al.Feasibility and cardiac synchrony of permanent left bundle branch pacing through the interventricular septum.Europace. 2019; 21: 1694-1702Crossref PubMed Scopus (84) Google Scholar,14Vijayaraman P. Subzposh F.A. Naperkowski A. et al.Prospective evaluation of feasibility and electrophysiologic and echocardiographic characteristics of left bundle branch area pacing.Heart Rhythm. 2019; 16: 1774-1782Abstract Full Text Full Text PDF PubMed Scopus (127) Google Scholar Given this complete lack of evidence-based outcomes in intermediate and long-term follow-up, it is only prudent to withhold broader application of LBBAP at the present time until more data are available.Table 1Studies of HBP with median or mean follow-up ≥12 months (n = 19 studies)AuthorYearN∗Number of patients in whom HBP was attempted.Average follow-up (mo)Study typeInclusionClinical outcomeDeshmukh et al21Deshmukh P. Casavant D.A. Romanyshyn M. Anderson K. Permanent, direct His-bundle pacing: a novel approach to cardiac pacing in patients with normal His-Purkinje activation.Circulation. 2000; 101: 869-877Crossref PubMed Scopus (435) Google Scholar20001823Single-center cohortSystolic HF, AVN ablation, narrow QRSImproved LV volumes, fractional shortening, CT ratioDeshmukh and Romanyshyn44Deshmukh P.M. Romanyshyn M. Direct His-bundle pacing: present and future.Pacing Clin Electrophysiol. 2004; 27: 862-870Crossref PubMed Scopus (139) Google Scholar20045442Single-center cohortSystolic HF , persistent AF, narrow QRSImproved LVEF, functional class; subset with CPT showed longer exercise time, higher O2 uptake, later et M. A. et of ventricular by permanent pacing after atrioventricular in a study right ventricular pacing.J Am Coll Cardiol. PubMed Scopus Google ablation, narrow QRSImproved functional reduced and et His or pacing left ventricular in atrioventricular block: a 16: PubMed Scopus Google narrow QRSImproved LVEF, in functional or et P. Naperkowski A. Ellenbogen K.A. Dandamudi G. insights of atrioventricular block: from permanent His bundle Clin Electrophysiol. PubMed Scopus Google or AVN ablation, narrow and in nodal and with only rise in thresholds in et W. Su L. Wu S. et of permanent His bundle pacing with atrioventricular in patients with heart failure with and reduced left ventricular ejection Am 2017; PubMed Scopus Google cohortSystolic HF, AVN ablation, narrow QRSImproved LVEF, LV volumes, functional class; reduced et P. Subzposh F.A. Naperkowski A. and His bundle 2017; PubMed Scopus Google ablation, narrow QRSImproved LVEF, functional et P. Dandamudi G. D. Ellenbogen K.A. His bundle pacing: and echocardiographic from long-term Clin Electrophysiol. 2017; PubMed Scopus Google narrow et P. Naperkowski A. Subzposh F.A. et al.Permanent His-bundle pacing: long-term lead performance and clinical outcomes.Heart Rhythm. 2018; 15: 696-702Abstract Full Text Full Text PDF PubMed Scopus (116) Google AF, narrow of pacing reduced HF higher rate of lead and et Naperkowski A. et al.Permanent His bundle pacing for cardiac in patients with heart failure and right bundle branch Arrhythm Electrophysiol. 2018; PubMed Scopus Google LVEF, functional et al10Abdelrahman M. Subzposh F.A. Beer D. et al.Clinical outcomes of His bundle pacing compared to right ventricular pacing.J Am Coll Cardiol. 2018; 71: 2319-2330Crossref PubMed Scopus (219) Google AF, narrow with reduction of of HF hospitalization, or upgrade compared to et K. His-bundle pacing for cardiac feasibility study in of left ventricular Rhythm. 2017; Full Text Full Text PDF PubMed Scopus Google in LVEF, et Dandamudi G. et al.Permanent His-bundle pacing as an to biventricular pacing for cardiac a multicenter Rhythm. 2018; 15: Full Text Full Text PDF PubMed Scopus Google in LVEF, et D. M. et al.Permanent His bundle pacing feasibility in clinical from an J. 2019; 71: PubMed Scopus (2) Google narrow in patients with at stable et W. Su L. Wu S. et outcomes of His bundle pacing in patients with heart failure with left bundle branch 2019; PubMed Scopus Google LVEF, LV volumes, functional class; stable thresholds at 3 et F. Abdelrahman M. Marcantoni L. et al.Long term performance and safety of His bundle pacing: a multicenter experience.J Cardiovasc Electrophysiol. 2019; 30: 1594-1601Crossref PubMed Scopus (42) Google AF, narrow in capture thresholds at 3 with thresholds than et P. Ellenbogen K.A. J. cardiac to electrical Arrhythm Electrophysiol. 2019; PubMed Scopus Google for His and LV LVEF, functional et K. A. A. et with His bundle Clin Electrophysiol. 2019; PubMed Scopus Google AF, LVEF, functional et P. et al.His pacing or biventricular pacing for cardiac in heart Am Coll Cardiol. 2019; 74: PubMed Scopus Google P. et His bundle pacing and biventricular pacing for cardiac a of the Rhythm. 2019; 16: Full Text Full Text PDF PubMed Scopus Google with superior than in that not = = = atrioventricular AVN = atrioventricular = biventricular CPT = = cardiac CT = HBP = His-bundle HF = heart = left bundle branch LV = left = left ventricular = left ventricular ejection = = of = right bundle branch RVP = right ventricular = of patients in whom HBP was in a Table of LBBAP with median or mean follow-up ≥12 months (n = of patients in whom His-bundle pacing was attempted.Average follow-up (mo)Study typeInclusionClinical et S. Wu S. L. et al.Feasibility and of His bundle pacing or left bundle pacing with atrioventricular in patients with persistent and Am 2019; PubMed Scopus Google AF, HF with AVN and in patients vs = LBBAP = left bundle branch area = other as in Table of patients in whom His-bundle pacing was in a = = = atrioventricular AVN = atrioventricular = biventricular CPT = = cardiac CT = HBP = His-bundle HF = heart = left bundle branch LV = left = left ventricular = left ventricular ejection = = of = right bundle branch RVP = right ventricular = = LBBAP = left bundle branch area = other as in Table The in current of HBP are the model lead and the model introduced the as for mapping the His and may have in right the to be with or to all current is the of of to the His-bundle The approach to implant has been described K. 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Zanon F. et al.Permanent His bundle pacing: from a His for of implant and Rhythm. 2018; 15: Full Text Full Text PDF PubMed Scopus Google Scholar and nonselective HBP have been to be associated with on synchrony as by myocardial and better than septal J. J. Hou X. et of the of and His bundle pacing on cardiac electrical and 2018; 20: PubMed Scopus Google Scholar and HBP are associated with similar ventricular characteristics and of electrical of which superior to myocardial K. P. et and nonselective His bundle, but not pacing ventricular electrical synchrony by Rhythm. 2019; Google Scholar clinical outcomes, in a study patients at there was in time to all-cause or HF hospitalization patients with nonselective HBP vs patients with in HF hospitalization (HR P = with nearly in the D. Subzposh F.A. et al.Clinical outcomes of nonselective His bundle Clin Electrophysiol. 2019; 5: PubMed Scopus Google Scholar In to HBP, the associated with LBBAP are more in the in lead with change that likely of capture but are to even on In this may of the or of the lead in the interventricular In to HBP, vs pacing with stimulation of the and can change the of even in a narrow S. Zhou X. Gold M.R. Left bundle branch pacing: JACC review topic of the week.J Am Coll Cardiol. 2019; 74: 3039-3049Crossref PubMed Scopus (48) Google Scholar The pacing and to be for this A particularly for HBP was that it be to significantly narrow the of patients with bundle branch In HBP was reported in a with left bundle branch in whom a lead not be for for cardiac HBP was associated with and a that consistent with P. J. M. through His bundle pacing in a with the atrioventricular Clin Electrophysiol. PubMed Scopus Google Scholar The has now been in a of K. His-bundle pacing for cardiac feasibility study in of left ventricular Rhythm. 2017; Full Text Full Text PDF PubMed Scopus Google P. Casavant D.A. Romanyshyn M. Anderson K. Permanent, direct His-bundle pacing: a novel approach to cardiac pacing in patients with normal His-Purkinje activation.Circulation. 2000; 101: 869-877Crossref PubMed Scopus (435) Google A. P. J. M. by direct His-bundle pacing using an 15: PubMed Scopus Google et pacing biventricular pacing in cardiac a Rhythm. Full Text Full Text PDF PubMed Scopus Google P. Subzposh F.A. Naperkowski A. and His bundle 2017; PubMed Scopus Google W. Su L. Wu S. et of permanent His bundle pacing with atrioventricular in patients with heart failure with and reduced left ventricular ejection Am 2017; PubMed Scopus Google Dandamudi G. et al.Permanent His-bundle pacing as an to biventricular pacing for cardiac a multicenter Rhythm. 2018; 15: Full Text Full Text PDF PubMed Scopus Google P. Su L. Zhou X. et of to His bundle pacing in patients with left ventricular ejection fraction Rhythm. 2018; 15: Full Text Full Text PDF PubMed Scopus Google Y. Z. X. et to bundle pacing in patients for feasibility and intermediate term J Cardiol. 2018; Full Text Full Text PDF PubMed Scopus Google Naperkowski A. et al.Permanent His bundle pacing for cardiac in patients with heart failure and right bundle branch Arrhythm Electrophysiol. 2018; PubMed Scopus Google W. Su L. Wu S. et outcomes of His bundle pacing in patients with heart failure with left bundle branch 2019; PubMed Scopus Google P. Ellenbogen K.A. J. cardiac to electrical Arrhythm Electrophysiol. 2019; PubMed Scopus Google P. et of left ventricular ejection fraction by cardiac through His bundle pacing in patients with heart 2020; Google Scholar and was in an of HBP vs for P. et al.His pacing or biventricular pacing for cardiac in heart Am Coll Cardiol. 2019; 74: PubMed Scopus Google P. et His bundle pacing and biventricular pacing for cardiac a of the Rhythm. 2019; 16: Full Text Full Text PDF PubMed Scopus Google Scholar have been largely consistent across these with HBP is associated with success than in narrow and pacing are patients HBP for HF and in with particularly when as a for lead studies are to the of primary on clinical only a on LBBAP for patients with mean follow-up of W. Huang J. Y. et by left bundle branch area pacing in patients with heart failure and left bundle branch Rhythm. 2019; 16: Full Text Full Text PDF PubMed Scopus Google Scholar and other on the acute on synchrony in patients with a J. Wang Z. L. et clinical outcomes of left bundle branch area pacing vs right ventricular Cardiol. 2019; PubMed Scopus Google Scholar have been the of there was that pacing and there was an need to consistent criteria to LCS from We that the need for a is in patients with to with narrow in whom may be to pacing was first described by et M. Y. et al.Feasibility and acute of left ventricular septal pacing by approach through the interventricular Arrhythm Electrophysiol. PubMed Scopus Google Scholar Is LBBAP or pacing to physiological a with a right in lead of at least data on clinical outcomes with LBBAP or have been with even reports comparing these outcomes to RVP or X. Li H. Ma W. et al.Permanent left bundle branch area pacing for atrioventricular block: feasibility, safety, and acute effect.Heart Rhythm. 2019; 16: 1766-1773Abstract Full Text Full Text PDF PubMed Scopus (92) Google Scholar,7Li Y. Chen K. Dai Y. et al.Left bundle branch pacing for symptomatic bradycardia: implant success rate, safety, and pacing characteristics.Heart Rhythm. 2019; 16: 1758-1765Abstract Full Text Full Text PDF PubMed Scopus (76) Google Scholar,13Hou X. Qian Z. Wang Y. et al.Feasibility and cardiac synchrony of permanent left bundle branch pacing through the interventricular septum.Europace. 2019; 21: 1694-1702Crossref PubMed Scopus (84) Google W. Huang J. Y. et by left bundle branch area pacing in patients with heart failure and left bundle branch Rhythm. 2019; 16: Full Text Full Text PDF PubMed Scopus Google J. Wang Z. L. et clinical outcomes of left bundle branch area pacing vs right ventricular Cardiol. 2019; PubMed Scopus Google K. Li Y. Dai Y. et of characteristics and pacing left bundle branch pacing and right ventricular pacing in patients 2019; 21: PubMed Scopus Google Scholar The LBBAP and pacing can be at implant a left bundle is lead In recent studies of narrow a left bundle is at implant in as low as and to of X. Li H. Ma W. et al.Permanent left bundle branch area pacing for atrioventricular block: feasibility, safety, and acute effect.Heart Rhythm. 2019; 16: 1766-1773Abstract Full Text Full Text PDF PubMed Scopus (92) Google Scholar,7Li Y. Chen K. Dai Y. et al.Left bundle branch pacing for symptomatic bradycardia: implant success rate, safety, and pacing characteristics.Heart Rhythm. 2019; 16: 1758-1765Abstract Full Text Full Text PDF PubMed Scopus (76) Google Scholar the that many patients rather than LCS. In patients with complete the is more the left bundle can be after the is of a HBP and is as LV activation time have been to based on the X. Wu S. Su L. Su Y. Huang W. The characteristics of the and the in left bundle branch pacing.J Cardiovasc Electrophysiol. 2019; 30: Google Y. L. et left bundle branch area pacing: characteristics, and clinical Clin Electrophysiol. 2020; PubMed Scopus Google Scholar with mapping is In a recent study of patients was to the acute of was associated with in electrical by the and LV as F. J. et and of cardiac by left ventricular septal pacing.J Am Coll Cardiol. 2020; PubMed Scopus Google Scholar In a subset of results found HBP and In the an was of reduced cardiac by in a with vs HBP, which was more P. Ellenbogen K.A. Left ventricular septal left bundle branch pacing: a in cardiac Am Coll Cardiol. 2020; PubMed Scopus (3) Google Scholar is premature to whether pacing is to achieve benefit as conduction system has been is that septal pacing is not as as His-bundle and concerns for myocardial or scar septal activation remains an area of the LBBAP with and capture of LCS by narrow of ms is in that are by after the pacing Left septal mapping demonstrates activation the and is of a not by recruitment is and only myocardial capture is with in activation is and this may be to physiological more is may be to distinguish the of capture but in clinical outcome The of the clinical with LBBAP has emerged from China, based on the by Huang et W. Su L. Wu S. et al.A novel pacing strategy with low and stable output: pacing the left bundle branch immediately beyond the conduction block.Can J Cardiol. 2017; 33: 1736 e1731-1736 e1733Abstract Full Text Full Text PDF Scopus (208) Google Scholar narrow and the Huang technique has been and in a having and septal The presence of scar within the septum may as a to successful with with ischemic need to be In a have found a higher rate of failure in in patients with septal by Chen et of to bundle pacing in patients with left bundle branch at of Scholar and characteristics LBBAP may not be for patients with right bundle branch and for as activation may be the of to achieve septal pacing, with or on lead is unknown at the present the of is with HBP, it be that may present a of of the lead and beyond the LV may the lead to the and increase with endocardial pacing in the at the His bundle, which is in the central of the is distinct from myocardial capture and pacing of the current limitations with HBP is but limitations that are in the of a and are to the of this of may the of this pacing in the current that in of and with increased battery may these limitations in the for physiological with is to the a to the right or In it may be to in which the is the beyond the with of the can to the His the is with the in in to for of the while mapping at the with are the of His bundle pacing. the nonselective and is along all and with His that nonselective to after a and to in to capture to the of the His the His with with are are in nonselective capture to is to for of septal recruitment on the His In this nonselective to capture at and consistently at and of His capture at The are nonselective complete of with is on the for the in the is of an with and a later myocardial and with with is to an system to His In this His be in and on the system His is in the and in the the His is at the