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Left bundle branch pacing is the best approach to physiological pacing

      Keywords

      The last decade has seen the resurgence of conduction system pacing (CSP) for patients with symptomatic bradycardia and heart failure. His-bundle pacing (HBP) is now an accepted alternative to more traditional ventricular pacing sites (right ventricular [RV] apex/outflow tract, coronary sinus).
      • Kusumoto F.M.
      • Schoenfeld M.H.
      • Barrett C.
      • et al.
      2018 ACC/AHA/HRS guideline on the evaluation and management of patients with bradycardia and cardiac conduction delay: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines, and the Heart Rhythm Society.
      Although HBP is theoretically the ideal physiological pacing site, it has some inherent limitations. The implant technique requires greater expertise in targeting a small zone and can be challenging in patients with dilated hearts, resulting in long procedural and fluoroscopic times. The reported success rate for HBP varies from 56% to 95%, depending on the degree of conduction system disease present and the experience of the center.
      • Vijayaraman P.
      • Chung M.K.
      • Dandamudi G.
      • et al.
      His bundle pacing.
      • Sharma P.S.
      • Vijayaraman P.
      • Ellenbogen K.A.
      Permanent His bundle pacing: shaping the future of physiological ventricular pacing.
      • Bhatt A.G.
      • Musat D.L.
      • Milstein N.
      • et al.
      The efficacy of His bundle pacing: lessons learned from implementation for the first time at an experienced electrophysiology center.
      Successful HBP lead implantation is fraught with troubleshooting issues during follow-up.
      • Lustgarten D.L.
      • Sharma P.S.
      • Vijayaraman P.
      Troubleshooting and programming considerations for His bundle pacing.
      HBP leads typically have a low R-wave amplitude that may result in oversensing of atrial or His signals and undersensing of ventricular signals. High HBP capture thresholds at implant and/or during late follow-up may result in premature battery depletion and repeated generator replacements and the associated risks.
      • Poole J.E.
      • Gleva M.J.
      • Mela T.
      • et al.
      Complication rates associated with pacemaker or implantable cardioverter-defibrillator generator replacements and upgrade procedures: results from the REPLACE registry.
      The unpredictable, delayed rise in HBP capture thresholds are a major concern, resulting in higher lead revision rates.
      • Bhatt A.G.
      • Musat D.L.
      • Milstein N.
      • et al.
      The efficacy of His bundle pacing: lessons learned from implementation for the first time at an experienced electrophysiology center.
      ,
      • Zanon F.
      • Abdelrahman M.
      • Marcantoni L.
      • et al.
      Long term performance and safety of His bundle pacing: a multicenter experience.
      A subset of patients may also lose His capture during follow-up, resulting in RV septal pacing.
      No robust data regarding the long-term performance of HBP leads are available. In the largest observational, 2- center study, 844 patients who received HBP leads had a mean pacing capture threshold of 1.6 V at implant and 2 V at median follow-up of 3 years.
      • Zanon F.
      • Abdelrahman M.
      • Marcantoni L.
      • et al.
      Long term performance and safety of His bundle pacing: a multicenter experience.
      HBP was free of any complications in 91% of patients. However, a careful appraisal of the data highlights the concerns noted in about 35%–40% of the patients. Pacing thresholds were ≥2.5 V at 1 ms in 28% of patients at median follow-up. Follow-up electrocardiography showed septal pacing in 9% of patients. Lead revision was required in 7.6% of patients. Median time for battery replacement was 5.8 years.
      • Zanon F.
      • Abdelrahman M.
      • Marcantoni L.
      • et al.
      Long term performance and safety of His bundle pacing: a multicenter experience.
      The quest for an optimal pacing site led to a novel CSP technique described by Huang et al
      • Huang 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.
      in 2017, where the pacing lead was implanted deep in the RV basal septum to capture the left bundle branch (LBB) area in a patient with heart failure and left bundle branch block (LBBB). Since its original description, few studies have demonstrated the feasibility of left bundle branch area pacing (LBBAP) (Table 1).
      • Chen K.
      • Li Y.
      • Dai Y.
      • et al.
      Comparison of electrocardiogram characteristics and pacing parameters between left bundle branch pacing and right ventricular pacing in patients receiving pacemaker therapy.
      • Zhang J.
      • Wang Z.
      • Cheng L.
      • et al.
      Immediate clinical outcomes of left bundle branch area pacing vs conventional right ventricular pacing.
      • Hou X.
      • Qian Z.
      • Wang Y.
      • et al.
      Feasibility and cardiac synchrony of permanent left bundle branch pacing through the interventricular septum.
      • Li X.
      • Li H.
      • Ma W.
      • et al.
      Permanent left bundle branch area pacing for atrioventricular block: feasibility, safety, and acute effect.
      • Li Y.
      • Chen K.
      • Dai Y.
      • et al.
      Left bundle branch pacing for symptomatic bradycardia: implant success rate, safety, and pacing characteristics.
      • Vijayaraman P.
      • Subzposh F.A.
      • Naperkowski A.
      • et al.
      Prospective evaluation of feasibility and electrophysiologic and echocardiographic characteristics of left bundle branch area pacing.
      • Zhang W.
      • Huang J.
      • Qi Y.
      • et al.
      Cardiac resynchronization therapy by left bundle branch area pacing in patients with heart failure and left bundle branch block.
      • Hasumi E.
      • Fujiu K.
      • Nakanishi K.
      • Komuro I.
      Impacts of left bundle/peri-left bundle pacing on left ventricular contraction.
      • Cai B.
      • Huang X.
      • Li L.
      • et al.
      Evaluation of cardiac synchrony in left bundle branch pacing: insights from echocardiographic research.
      • Jiang Z.
      • Chang Q.
      • Wu Y.
      • Ji L.
      • Zhou X.
      • Shan Q.
      Typical BBB morphology and implantation depth of 3830 electrode predict QRS correction by left bundle branch area pacing.
      • Wang J.
      • Liang Y.
      • Wang W.
      • et al.
      Left bundle branch area pacing is superior to right ventricular septum pacing concerning depolarization-repolarization reserve.
      LBBAP is rapidly emerging as an alternative for failed HBP cases or as a primary strategy (in some centers) for CSP. Both anatomy (narrow target for His bundle [HB] vs wide target for left bundle branch area [LBBA]) and histology (His encased in fibrous, electrically nonconducting tissue vs LBB embedded in myocardium) favor LBBA over HB for physiological pacing.
      Table 1Published studies on left bundle branch area pacing
      Study (year)DesignSample sizeStudy populationSuccess rateMean paced QRSd (ms)Mean LVAT (ms)LBB potentialFollow-up (mo)Lead complicationsOutcomes
      Chen et al (2018)Prospective

      LBBAP vs RVP
      20SND: 75%

      AV/infranodal block: 20%
      NR111 ± 1069 ± 955%3A/C: NoneStable lead parameters
      Zhang et al (2019)Prospective

      LBBAP vs RVP
      23SND: 48%

      AVB: 38%
      87%112 ± 12NRNRNRA: None

      C: NR
      Acute success rate and pacing characteristics
      Hou et al (2019)Prospective56SND: 29%

      AVB: 37%

      AF with SVR: 34%
      NR118 ± 1176 ± 1467%4.5A: 1 lead dislodgment intraoperative

      C: None
      Stable lead parameters

      LBBAP patients with potential had LV mechanical synchrony similar to that of HBP based on phase analysis of gated SPECT MPI

      Stable LVEF
      Li et al (2019)Retrospective33AVB: 100%91%113 ± 1182 ± 1526.7%3A: 1 LV septal perforation

      C: None
      Stable lead parameters

      Stable LVEF
      Li et al (2019)Prospective87SND: 68%

      AVB: 32%
      80%113 ± 1079.7 ± 8.566%3A/C: NoneStable lead parameters
      Vijayaraman et al (2019)Prospective100SND: 23%

      AVB: 54%

      AVN ablation: 7%

      CRT: 11%

      HBP failure: 7%
      93%136 ± 1775 ± 1663%3A: 3 lead dislodgments within 24 h requiring revision; 3 LV septal perforations

      C: None
      Stable lead parameters
      Zhang et al (2019)Prospective11HF with reduced EF and LBBB: 100%NR129 ± 1680.9 ± 9.950%6.7A/C: NoneStable lead parameters

      Improvement in LVEF by >5% from baseline in all, >20% from baseline in 7 patients

      Improvement in LV synchrony by pulsed-wave Doppler and tissue synchronization imaging
      Hasumi et al (2019)Retrospective21Advanced AVB: 100%

      Failed HBP
      81%116 ± 8.3NRNR6A/C: NoneStable lead parameters
      Cai et al (2020)Prospective

      Observational

      LBBAP vs RVP
      40SND: 100%90%101 ± 8.79LBBAP with normal axis: 59 ± 6; left-axis deviation: 64 ± 4.580%Echocardiogram on day 3NRLBBAP preserved mechanical synchrony similar to native conduction

      LBBAP leads to favorable hemodynamic effects

      RVP resulted in electrical and mechanical dyssynchrony and worse hemodynamic effects
      Jiang et al (2020)Retrospective73BBB with QRSd >130 ms

      Atypical BBB:13.6%

      5 LBBB and 5 RBBB

      Typical BBB: 86.4%

      30 LBBB and

      33 RBBB
      30%

      82.5%
      133 ± 14

      118 ± 14
      103 ± 23

      85 ± 15
      10%

      28.6%
      NRA: 4 LV septal perforations

      C: None
      Typical BBB morphology (Strauss criteria) predicts successful QRS correction with LBBAP
      Wang et al (2020)Prospective

      Randomized

      LBBAP vs RVP
      66SND: 32%

      AVB: 54%

      AF with SVR: 14%
      94%121 ± 9.867.8 ± 6.875%6A: 1 lead perforation at 1 month requiring revision

      C: 2 lead dislodgments (1 at 2 mo, 1 at 4 mo)
      Stable lead parameters

      LBBAP resulted in narrower QRSd, shorter QT and QTc interval, lower QTD and QTcD shorter Tpeak-end interval compared with RVP, suggesting better depolarization-repolarization reserve
      Total5306 lead dislodgments

      9 septal perforations
      A = acute; AF with SVR = atrial fibrillation with slow ventricular rate; AV = atrioventricular; AVN = atrioventricular node; AVB = atrioventricular block; BBB = bundle branch block; C = chronic; CRT = cardiac resynchronization therapy; EF = ejection fraction; HBP = His-bundle pacing; HF = heart failure; LBB = left bundle branch; LBBAP = left bundle branch area pacing; LBBB = left bundle branch block; LV = left ventricle; LVAT = left ventricular activation time; LVEF = left ventricular ejection fraction; NR = not reported; QTc = corrected QT interval; QTD = QT dispersion; QTcD = corrected QT dispersion; RBBB = right bundle branch block; RVP = right ventricular pacing; SND = sinus node dysfunction; SPECT MPI = single photon emission computed tomography myocardial perfusion imaging.

      Step-by-step approach to LBBAP implant technique

      LBBAP is performed using a SelectSecure 3830 pacing lead (Medtronic, Minneapolis, MN), delivered via either the fixed-curve C315-HIS sheath or the new SelectSite C304-HIS deflectable sheath (Medtronic). The 12-lead electrocardiographic recording and the intracardiac electrograms (EGMs) from the pacing lead are simultaneously displayed and continuously recorded on an electrophysiological recording system (Prucka CardioLab, GE Healthcare, Waukesha, WI). The steps in the implant procedure area as follows.
      • 1.
        The distal His-bundle potential is located on the right anterior oblique fluoroscopic view using the delivery sheath and the 3830 lead, and the fluoroscopic position is saved for reference. If the His-bundle potential is difficult to locate, the tricuspid annulus (defined anatomically or electrically) or prosthetic valves (when present) can be used as a reference.
      • 2.
        The sheath is turned clockwise and gently advanced 1.5–2 cm into the ventricle toward the RV basal septum (Figures 1A and 1B).
        Figure thumbnail gr1
        Figure 1A: Fluoroscopic right anterior oblique view. Asterisk indicates the distal His-bundle position. Inset shows distal His-bundle electrogram (EGM). The sheath and 3830 lead are advanced about 2 cm distal to the distal His-bundle EGM. B: The sheath and 3830 lead are advanced about 2 cm distal using the bioprosthetic aortic valve as a reference. C: Ideal site for lead fixation showing left bundle branch (LBB) QRS morphology with inferior lead and aVR/aVL discordance. D: After 4 turns, note QRSd narrowing and V1 morphology. E: After 2 more turns, unipolar tip pacing revealed stim-QRS latency of 20 ms, right bundle branch block morphology with rsRʹ in lead V1, and QRSd of 114 ms suggesting capture of left bundle branch area (LBBA). F: Unipolar ring pacing reveals right ventricular basal septal capture with LBB morphology and QRSd of 136 ms. G: Asterisk indicates LBB potential. LBB potential to QRS duration was 20 ms. H, I: Stimulus to peak of R wave in lead V5 (left ventricular activation time) at 5 and 1 V, respectively, was short and constant at 65 ms. J, K: Threshold testing during unipolar tip pacing showing transition from nonselective left bundle branch block area pacing (LBBAP) to selective LBBAP at 0.6 V at 0.4 ms. Asterisk indicates the discrete EGM with selective LBBA capture.
      • 3.
        Unipolar pacing is performed to assess for an ideal site for lead fixation: a paced morphology of QS complex with a notch in the nadir in lead V1 and/or presence of inferior lead and aVR/aVL discordance (R wave in lead II taller than lead III, negative aVR and positive aVL) (Figure 1C).
      • 4.
        If the above criteria are met, the lead is fixed to the RV septum by 1–2 rotations. Unipolar pacing is performed to confirm the ideal paced QRS morphology and importantly to rule out inadvertent repositioning of the lead in the RV outflow tract (Figure 1D). Baseline pacing impedance is documented.
      • 5.
        The sheath is gently advanced to abut the septum and rotated (typically counterclockwise) to make the sheath tip/lead perpendicular to the septum (approximately 1 0’ clock in the right anterior oblique view and 2–3 0’clock in the left anterior oblique view).
      • 6.
        With an assistant holding the sheath in this position (can also be done by a single operator), the pacing lead is rapidly rotated clockwise 4–5 turns, preferably using both hands, under fluoroscopy (Supplemental Video 1).
      • 7.
        Unipolar tip pacing is performed to assess the paced QRS morphology and pacing impedance. Further clockwise rotations are given, 1 or 2 at a time, until the paced QRS morphology resembles right bundle branch (RBB) conduction delay or right bundle branch block (RBBB) pattern in lead V1 (qR or rsRʹ) (Figure 1E). As the lead penetrates into the septum, initially the impedance gradually rises, and as the lead tip reaches the LBBA the impedance gradually falls by about 100 Ω. Unipolar ring pacing capture confirms the presence of the ring electrode in the septum (Figure 1F). LBB potential is recorded, when present (Figure 1G). The sensing, threshold, and impedances are recorded. LBBAP is confirmed by previously published criteria.
        • Huang W.
        • Chen X.
        • Su L.
        • Wu S.
        • Xia X.
        • Vijayaraman P.
        A beginner’s guide to permanent left bundle branch pacing.
      • 8.
        A septogram (1–2 mL of contrast injected through the sheath) can be performed in the left anterior oblique fluoroscopic view, to delineate the RV septal wall and confirm the lead depth in the interventricular septum (Supplemental Video 2). The distance between the screw tip and the ring electrode is 10.8 mm, which provides an approximate measure of lead depth in septum. Alternatively, unipolar ring pacing capture provides a rough estimate of lead depth in the septum. Lead depth can also be assessed on echocardiogram (Supplemental Video 3).

      Approach to a challenging implant

      If the LBBAP criteria are not met despite adequate lead depth in the septum or the lead will not penetrate deep into septum (unwinds or backspins) possibly due to fibrosis (Supplemental Video 4), the lead should be repositioned to a distal location on the septum. Typically, 8–12 turns are needed to reach left ventricular (LV) subendocardium to capture the LBBA.
      The If C315-HIS sheath does not provide enough reach to get to the ideal location, the deflectable C304-HIS sheath can be used for better reach and maneuverability. Figure 2, Figure 3, Figure 4 show successful LBBAP in various case scenarios.
      Figure thumbnail gr2
      Figure 2A 64-year-old woman with rheumatic valvular heart disease, mechanical aortic and mitral valve replacement 25 years ago, and severe aortic stenosis who received a bioprosthetic aortic valve complicated by complete heart block. A: Electrocardiogram (ECG) showing atrial fibrillation with complete heart block, right bundle branch block, and left anterior fascicular block (LAFB) escape with QRSd of 142 ms. B: ECG rhythm strip after left bundle branch area (LBBA) pacing lead implant during VVI bipolar pacing. Note the change in QRS morphology in lead V1 from QS to Qr at 3 V at 0.4 ms, with further narrowing of QRSd. This is due to loss of ring/anodal capture. C: Follow-up ECG of presenting rhythm 1 month later in the device clinic at 2 V at 0.4 ms. Threshold was 0.5 V at 0.4 ms. Pacing shows right bundle branch (RBB) conduction delay and normal axis with relatively narrow QRSd of 124 ms. LBBA pacing resulted in partial correction of RBB and complete correction of LAFB.
      Figure thumbnail gr3
      Figure 3A 21-year-old woman with congenital aortic and mitral valve stenosis underwent mechanical aortic and mitral valve replacement complicated by complete heart block. A, B: Electrocardiograms (ECGs) showing complete heart block with alternating right bundle branch block/left anterior fascicular block and left bundle branch block escape rhythm. C: ECG rhythm strip after left bundle branch area (LBBA) pacing lead implant during VVI bipolar pacing. Note the change in QRS morphology in lead V1 from QS to rsrʹ at 1.5 V at 0.4 ms. This is due to loss of ring/anodal capture. D: Follow-up ECG of presenting rhythm 1 month later in the device clinic at 2 V at 0.4 ms. This was the final pacing configuration, with QRSd of 110 ms and QS in V1 suggesting anodal and LBBA capture. Threshold was 0.7 V at 0.4 ms. Echocardiogram 9 months later showed normal left ventricular ejection fraction despite 100% ventricular pacing (not shown).
      Figure thumbnail gr4
      Figure 4A 65-year-old woman with ischemic cardiomyopathy, ejection fraction (EF) 20% despite guideline-directed medical therapy, New York Heart Association (NYHA) functional class III, chronic left bundle branch block (LBBB) on home intravenous milrinone therapy referred for cardiac resynchronization therapy. Despite several attempts, the coronary sinus lead implant failed. A bailout left bundle branch area pacing lead was implanted. A: ECG showing sinus rhythm and LBBB with QRSd 156 ms. B: Pacing with AV delay set at 40 ms resulted in Left bundle branch area (LBBA) capture with right bundle branch block (rsRʹ) in lead V1 with QRSd of 128 ms. C: Pacing with AV delay set at 80 ms resulted in normalization of QRSd to 120 ms. This is due to fusion between anterograde right bundle branch conduction and LBBA pacing. D: Follow-up ECG in the device clinic in 1 month during threshold testing showed QS in lead V1 during bipolar pacing with anodal capture threshold of 2.2 V at 0.4 ms. E: Final pacing configuration with AV delay set at 80 ms and output programmed at 2 V at 0.4 ms showing normalization of QRS complexes with QRSd of 120 ms. Threshold was 0.8 V at 0.4 ms. Of note, milrinone was discontinued the day after device implant. Follow-up echocardiogram 2 months later showed ejection fraction of 30%–35% (not shown). The patient required no heart failure hospitalizations and reported New York Heart Association functional class II symptoms 5 months after device implant.

      Determining LBBA capture

      Mafi-Rad et al
      • Mafi-Rad M.
      • Luermans J.G.L.M.
      • Blaauw Y.
      • et al.
      Feasibility and acute hemodynamic effect of left ventricular septal pacing by transvenous approach through the interventricular septum.
      demonstrated the feasibility of LV septal pacing using a custom-designed lead implanted in mid-distal septum. LV septal pacing resulted in a narrower QRS (144 ± 20 ms) and provided acute hemodynamic benefits over RV pacing. Both LV septal pacing and LBBAP can result in a relatively narrow QRS with RBB morphology. When CSP is intended, it is imperative to demonstrate LBBA capture. However, whether clinical outcomes differ between LV septal pacing and LBBAP remains to be determined.
      The criteria for determining LBBA capture are being defined and need to be validated in future studies. Huang et al
      • Huang W.
      • Chen X.
      • Su L.
      • Wu S.
      • Xia X.
      • Vijayaraman P.
      A beginner’s guide to permanent left bundle branch pacing.
      proposed criteria to demonstrate LBBA capture. Successful LBBAP is considered when ≥3 of the following criteria are met:
      • 1.
        Paced morphology of RBBB pattern
      • 2.
        Presence of LBB potential
      • 3.
        Left ventricular activation time measured from stimulus to peak of R wave in lead V5/V6
      • 4.
        Determination of selective (S) and nonselective (NS) LBB pacing (Figures 1J and 1K)
        • S-LBB: Stim-QRS latency and discrete local EGM separate from stimulus artifact seen
        • NS-LBB: No stim-QRS latency; no discrete local EGM separate from stimulus artifact
      • 5.
        Evidence for direct LBB capture
      Unlike HBP, LBBAP almost always results in simultaneous capture of the LBB and the surrounding myocardium due to its anatomic location in the muscular septum. Recently Jastrzębski et al
      • Jastrzębski M.
      • Moskal P.
      • Bednarek A.
      • et al.
      Programmed deep septal stimulation: a novel maneuver for the diagnosis of left bundle branch capture during permanent pacing.
      elegantly described programmed extrastimulus to differentiate LBB capture vs LV septal myocardial capture based on their differential effective refractory periods. Premature beats were delivered during sinus rhythm or after an 8-beat drive train at 600 ms with a 450-ms coupling interval, which was further stepwise decreased by 10-ms intervals. Response to premature beats was categorized as myocardial when the paced QRS morphology changed to myocardial-only capture (broader QRS, with slur/notch/plateau and/or with change in amplitude/polarity in several leads) or selective LBB when the paced QRS morphology changed to a typical RBB morphology preceded by a latency. Either myocardial or selective LBB was considered diagnostic of LBBA capture and was noted in 80% of the patients with LBBAP.
      • Jastrzębski M.
      • Moskal P.
      • Bednarek A.
      • et al.
      Programmed deep septal stimulation: a novel maneuver for the diagnosis of left bundle branch capture during permanent pacing.

      Does LBBAP preserve electrical and mechanical synchrony?

      HBP is the most physiological mode of pacing that preserves or restores electrical and mechanical synchrony by simultaneous activation of both ventricles.
      • Arnold A.D.
      • Shun-Shin M.J.
      • Keene D.
      • et al.
      his resynchronization versus biventricular pacing in patients with heart failure and left bundle branch block.
      In contrast, LBBAP by direct capture of the LBB preserves or restores physiological activation of the LV. Electrocardiographically, one would expect complete RBBB morphology, but often incomplete RBBB/RBB conduction delay pattern is noted with a relatively narrow QRS duration <130 ms. The mechanism of incomplete RBBB during LBBAP is intriguing, and possible hypotheses include transverse connections between LBB and RBB,
      • James T.N.
      • Sherf L.
      Fine structure of the His bundle.
      ,
      • Lazzara R.
      • Yeh B.K.
      • Samet P.
      Functional transverse interconnections within the His bundle and the bundle branches.
      retrograde activation of His and RBB during LBBAP, and virtual electrode effect.
      • Zhang S.
      • Zhou X.
      • Gold M.R.
      Left bundle branch pacing: JACC review topic of the week.
      Whether the delayed RV activation from LBBAP could result in clinically significant interventricular dyssynchrony and pacing-induced cardiomyopathy is unknown. Limited studies have shown LV mechanical synchrony with LBBAP similar to that of HBP based on phase analysis of gated single photon emission computed tomography myocardial perfusion imaging,
      • Hou X.
      • Qian Z.
      • Wang Y.
      • et al.
      Feasibility and cardiac synchrony of permanent left bundle branch pacing through the interventricular septum.
      to that of native conduction based on echocardiographic imaging,
      • Cai B.
      • Huang X.
      • Li L.
      • et al.
      Evaluation of cardiac synchrony in left bundle branch pacing: insights from echocardiographic research.
      and improved LV mechanical synchrony in patients with LBBB and heart failure based on echocardiographic imaging.
      • Huang 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.
      ,
      • Zhang W.
      • Huang J.
      • Qi Y.
      • et al.
      Cardiac resynchronization therapy by left bundle branch area pacing in patients with heart failure and left bundle branch block.

      Acute clinical and safety outcomes with LBBAP

      The initial results of small prospective observational studies on LBBAP are encouraging (Table 1). The overall success rate varied from 80%–94%. High success rates were achieved in patients with advanced conduction system disease. Lead parameters specifically capture thresholds remained stable during short-term follow-up. Furthermore, LBBAP holds tremendous promise in achieving cardiac resynchronization therapy in patients with heart failure and LBBB.
      • Huang 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.
      ,
      • Zhang W.
      • Huang J.
      • Qi Y.
      • et al.
      Cardiac resynchronization therapy by left bundle branch area pacing in patients with heart failure and left bundle branch block.
      In a study of 11 patients with heart failure and LBBB, LBBAP resulted in LBB correction with significant narrowing of QRS from a mean of 180 ± 16 ms to 129 ± 16 ms.
      • Zhang W.
      • Huang J.
      • Qi Y.
      • et al.
      Cardiac resynchronization therapy by left bundle branch area pacing in patients with heart failure and left bundle branch block.
      Notably, the lead parameters remained stable, and there was significant improvement in left ventricular ejection fraction and dyssynchrony on echocardiographic imaging at mean follow-up of 6.7 months.
      • Zhang W.
      • Huang J.
      • Qi Y.
      • et al.
      Cardiac resynchronization therapy by left bundle branch area pacing in patients with heart failure and left bundle branch block.
      LBBAP is an emerging pacing technique, and only the short-term safety profile is currently known. Of the 530 published cases (Table 1), 6 (1%) lead dislodgments (1 intraoperative, 3 within 24 hours, 1 at 2 months, and 1 at 4 months) and 9 (1.7%) septal perforations (8 intraoperative and 1 at 1 month) have been reported.
      • Hou X.
      • Qian Z.
      • Wang Y.
      • et al.
      Feasibility and cardiac synchrony of permanent left bundle branch pacing through the interventricular septum.
      ,
      • Li X.
      • Li H.
      • Ma W.
      • et al.
      Permanent left bundle branch area pacing for atrioventricular block: feasibility, safety, and acute effect.
      ,
      • Vijayaraman P.
      • Subzposh F.A.
      • Naperkowski A.
      • et al.
      Prospective evaluation of feasibility and electrophysiologic and echocardiographic characteristics of left bundle branch area pacing.
      ,
      • Jiang Z.
      • Chang Q.
      • Wu Y.
      • Ji L.
      • Zhou X.
      • Shan Q.
      Typical BBB morphology and implantation depth of 3830 electrode predict QRS correction by left bundle branch area pacing.
      ,
      • Wang J.
      • Liang Y.
      • Wang W.
      • et al.
      Left bundle branch area pacing is superior to right ventricular septum pacing concerning depolarization-repolarization reserve.
      No major complications associated with perforation, including transient ischemic attack/stroke and pericardial effusion have been described. Lead-related complications, such as infection, sensing issues, and delayed threshold rise, have not been reported. Other potential complications, such as intramural hematoma, coronary artery injury, tricuspid regurgitation, risk of septal contractile stress fracture of the lead, and risk of lead extraction, need to be investigated in future clinical studies.

      Is LBBAP the “holy grail” of physiological pacing?

      Based on the early clinical experience, LBBAP seems to be the best approach to physiological pacing and circumvents many of the limitations noted with HBP (Table 2). The large anatomic target site, technically less challenging procedure, easier lead fixation, shorter procedural and fluoroscopic times,
      • Li Y.
      • Chen K.
      • Dai Y.
      • et al.
      Left bundle branch pacing for symptomatic bradycardia: implant success rate, safety, and pacing characteristics.
      higher success rates, ability to preserve or improve LV synchrony,
      • Hou X.
      • Qian Z.
      • Wang Y.
      • et al.
      Feasibility and cardiac synchrony of permanent left bundle branch pacing through the interventricular septum.
      ,
      • Zhang W.
      • Huang J.
      • Qi Y.
      • et al.
      Cardiac resynchronization therapy by left bundle branch area pacing in patients with heart failure and left bundle branch block.
      ,
      • Cai B.
      • Huang X.
      • Li L.
      • et al.
      Evaluation of cardiac synchrony in left bundle branch pacing: insights from echocardiographic research.
      and, most importantly, stable lead parameters with LBBAP argue strongly for LBBAP to be the holy grail of physiological pacing.
      Table 2Differences between HBP and LBBAP
      HBPLBBAP
      AnatomyNarrow target zone (20 mm length, 4-mm diameter)Wider target zone
      HistologySurrounding electrically inert fibrous milieuSurrounding muscular tissue
      PhysiologyPreserves or restores RV and LV synchronyPreserves or restores LV synchrony
      ImplantationTechnically challenging

      High precision

      Long learning curve
      Relatively easier

      Less precision

      Short learning curve
      Success rates in AV nodal and infranodal diseaseLower due to high thresholds or inability to correct the underlying conduction system diseaseHigher as pacing beyond the site of block
      Pacing morphologiesSelective His

      Nonselective His

      Myocardial capture
      Selective LBB

      Nonselective LBB

      RV septum + LBB (anodal capture)

      Myocardial capture
      Sensing R wavesLow amplitude
      • Risk of oversensing atrial or His signals
      • Risk of undersensing ventricular signals
      High amplitude

      No sensing issues
      Thresholds (acute)Relatively higher as stimulating ventricles through a fibrous sheathLower
      Thresholds (chronic)Can be unstable, unpredictable, with a delayed rise; thresholds ≥2.5 V @1 ms seen in 25%–30% of patients

      Possible hypothesis:
      • Anatomic characteristics
      • Local fibrosis leading to exit block
      • Micro-dislodgment
      • Progression of disease
      Stable
      RV backup leadMay be necessary in dependent patientsNot necessary
      Lead complications
      • Septal perforation
      • Dislodgments
      • Loss of conduction system capture
      • Lead revision rate
      • Not reported
      • Possible
      • Up to 10%
      • High (8%–10%)
      • Possible
      • Possible
      • To be determined
      • Low (1%)
      Device programmingComplex
      • Selective HBP: shorten AV delays
      • Automatic capture thresholds turned off
      • Ventricular safety pacing turned off
      • High thresholds: unipolar or extended bipolar
      Simple
      • AV delays adjusted in patients with LBBB to allow fusion
      • Autocapture turned on
      • Ventricular safety pacing turned on
      Battery longevityShorter

      Frequent generator replacements, associated risks
      Longer
      AV nodal ablationChallenging

      Risk of damaging His lead
      Relatively easy

      No risk of damaging LBBAP lead
      AV = atrioventricular; HBP = His-bundle pacing; LBB = left bundle branch; LBBAP = left bundle branch area pacing; LBBB = left bundle branch block; LV = left ventricle; RV = right ventricle.
      The rate of LBBAP technique adoption in clinical practice is fascinating. In China, 80% of 5000 CSP cases performed in 2018 were LBBAP.
      • Zhang S.
      • Zhou X.
      • Gold M.R.
      Left bundle branch pacing: JACC review topic of the week.
      In a recently published Polish experience, 40% of patients referred to an experienced center for CSP in 1 year received LBBAP leads after they failed to obtain an adequate result with HBP.
      • Jastrzębski M.
      • Moskal P.
      • Bednarek A.
      • et al.
      Programmed deep septal stimulation: a novel maneuver for the diagnosis of left bundle branch capture during permanent pacing.
      Our experience at Virginia Commonwealth University (VCU) also reflects a paradigm shift regarding the site of CSP. Approximately 300 HBP leads were implanted at VCU over a 5-year period (2014–2019). This is in striking contrast to 150 LBBAP leads implanted over a 1-year period (2019–2020). Similar to the published data, our experience with LBBAP has been incredibly positive, with high success rates, stable thresholds, and no major complications to date.

      Future directions

      LBBAP is currently performed using the 3830 lead and C315-HIS or C304-HIS sheath, none of which were designed for LBBAP. Further refinements in technique and tools are needed for improvement of overall success rates. The criteria for LBBA capture need to be further refined and validated. The long-term safety profile, lead integrity, and risk of extraction of deep septal LBBAP leads need to be determined. The role of LBBAP in patients requiring cardiac resynchronization therapy needs to be investigated in prospective randomized clinical trials.

      Acknowledgment

      The authors are grateful to Dr Pugazhendhi Vijayaraman for teaching us the left bundle branch area pacing technique.

      Appendix. Supplementary data

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