- Email: [email protected]
History of His bundle pacing
Available online at www.sciencedirect.com
ScienceDirect Journal of Electrocardiology xx (2016) xxx – xxx www.jecgonline.com
Review
History of His bundle pacing☆ Gopi Dandamudi, MD, a,⁎ Pugazhendhi Vijayaraman, MD b a
Indiana University School of Medicine, Indianapolis, IN b Geisinger Heart Institute, Wilkes-Barre, PA
Abstract
Chronic right ventricular (RV) pacing has been shown over the years to exert detrimental physiological changes including increased risk for heart failure and atrial fibrillation. His bundle pacing offers the promise of physiological activation of the ventricular tissue, with the potential for reducing the detrimental effects of RV pacing. We describe His bundle pacing in a historical context and briefly highlight several clinical trials that have helped shape the landscape of permanent His bundle pacing. © 2016 Elsevier Inc. All rights reserved.
Keywords:
His bundle pacing; Chronic RV pacing; Heart failure; QRS complex
Introduction Permanent His bundle pacing (PHBP) offers a very attractive option to pace the ventricles. It is by far the most physiological form of pacing and its theoretical benefits are unquestioned. Limited studies have shown the potential clinical benefits that can be derived from this form of pacing [1–5]. Other forms of pacing currently employed in clinical practice have their limitations. Chronic RV pacing has been shown to increase heart failure (HF) and atrial fibrillation (AF) [6,7]. Biventricular pacing (BiV) has limited benefits in patients with a non-LBBB ECG and significantly reduced ejection fraction (EF) [8]. In mildly reduced EF patients, BiV pacing benefits are equivocal at best [9,10]. We discuss the anatomy and physiology of the His bundle (HB) in a historical context and briefly discuss some clinical trials that have demonstrated safety and efficacy of PHBP.
First anatomical descriptions As a practicing anatomist and physiologist, Johann Evangelist Purkinje first described the existence of Purkinje fibers in 1839. The first descriptions of the HB were made in 1893 by Wilhelm His Jr., a Swiss cardiologist and anatomist. He was the first to coin the term “heart block” and described the significance of the HB as a conduit to conduction from the auricles to the ventricular septal walls. In 1903, Sunao Tawara, a Japanese pathologist, published his monograph on the ☆ COI: Dr. Dandamudi and Dr. Vijayaraman serve as consultants to Medtronic, Inc. ⁎ Corresponding author at: Indiana University Health Cardiac Electrophysiology, Indiana University School of Medicine, 1801 N. Senate Boulevard, Indianapolis, IN 46202. E-mail addresses: [email protected], [email protected]
http://dx.doi.org/10.1016/j.jelectrocard.2016.09.011 0022-0736/© 2016 Elsevier Inc. All rights reserved.
cardiac conduction system and made several seminal observations including the existence of the AV node, detailed descriptions of the bundle branches and the Purkinje system, and histology of the cardiac conduction system [11].
Physiological recordings It was not until 1958 when Alanis and colleagues demonstrated the first HB recordings in Mexico City [12]. Using isolated perfused hearts of dog and cats, steel needles were used to record physiological signals that were identified as HB recordings for the first time. They described the HB as a “zone” with changing HV intervals, as the HB was mapped from a proximal to distal location. They also demonstrated that decremental conduction occurred in the AV node and HB conduction was non-decremental in nature. The first known human recordings of the HB were carried out by Giraud et al. in 1959 in a patient with tetralogy of Fallot [13]. Ten years later, Benjamin Scherlag and colleagues used intravascular catheters to record HB recordings in humans [14]. Over the next several years, numerous observations were made about the HB that would increase our understanding of the anatomy and physiology of this complex cardiac structure.
Earlier observations As mentioned before, Scherlag and colleagues published their technique for recording HB activity in humans in 1969 [14]. This led to the rapid growth of cardiac electrophysiology and is considered one of the pivotal events in this field. They were able to place bipolar catheters percutaneously and demonstrate HB physiology in humans that was first reported by Alanis et al. in animals. Over the next decade, this group
2
G. Dandamudi, P. Vijayaraman / Journal of Electrocardiology xx (2016) xxx–xxx
published several studies assessing the physiology of the HB. Specifically, they reported their findings on complete heart block patients and bundle branch block patients as detailed below. Narula and colleagues published an elegant series on patients with Wenckebach and Mobitz II heart block [15]. They were able to demonstrate that Mobitz II heart block could occur either with bilateral bundle branch blocks or due to intra-Hisian heart blocks (i.e. more proximal in the common bundle). They also suggested that intra-Hisian block was not uncommon and that heart block could be intra-Hisian in location even in patients with abnormal QRS durations. James and Sherf published a detailed anatomical description of the HB in humans using light and electron microscopy in 1971 [16]. They demonstrated the architecture of the HB, including their longitudinal orientation with collagen interspersed between the cells. They also described sparse transverse connections between these bundles. In 1973, Lazzara et al. demonstrated that in partially transected (80–90%) right and left bundle branches in canine hearts, conduction could resume with no significant delay [17]. They also demonstrated that the transverse conduction velocity was significantly less than the longitudinal conduction velocity in the common bundle. The concept of functional longitudinal dissociation of the HB was first proposed by Kaufman and Rothberger in 1919 [18]. Predestined fibers within the His bundle conducted selectively to each fascicle and these fibers originated within the proximal portions of the common bundle. This concept was very elegantly demonstrated by Narula in 1977 [19]. Patients with LBBB and baseline prolonged HV intervals were studied and pacing slightly distal to the proximal His bundle resulted in narrowing of the QRS. El-Sherif et al. published both clinical and experimental evidence for longitudinal dissociation in the diseased His bundle in humans in 1978 [20]. They evaluated patients with both RBBB and LBBB, and prolonged HV intervals. With distal HB pacing, they were able to normalize the QRS duration. They demonstrated this in canine models with ligated septal arteries that resulted in intra-His conduction delay and bundle branch blocks. Once again, with slightly distal pacing within the common bundle, they were able to normalize QRS complexes and conduction times. Even though there was mounting evidence that heart blocks and bundle branch blocks could be manifestations of proximal HB disease and that pacing from the common bundle can result in resumption of conduction with recruitment of the bundle branches as described earlier, further clinical studies were not undertaken at that time. With the advent of biventricular pacing a few years later, there was a stalemate in further development of PHBP.
Clinical evidence for PHBP In the year 2000, Deshmukh et al. published the seminal paper demonstrating the safety and feasibility of PHBP in humans [1]. They attempted PHBP in 18 patients with chronic AF, EF b40%, QRS b120 ms, and NYHA class III–IV HF symptoms who underwent AV nodal ablation. They were successful in achieving PHBP in two thirds of their patients.
They were able to demonstrate positive LV remodeling in this cohort, with an improvement in LV EF from 20 ± 9% to 31 ± 11% (P b 0.01). This set the stage for clinicians around the world to pursue PHBP as an alternative to RV pacing. Selected PHBP clinical trials and related observations are outlined below. Dyssynchronous RV pacing vs. physiological PHBP It has been demonstrated that PHBP does not induce ventricular dyssynchrony unlike RV apical pacing [2]. In this study, intra-patient acute comparisons were made between both forms of pacing and it showed that indices of ventricular dyssynchrony were significantly reduced, including the degree of mitral regurgitation and improvement in LV systolic function Tei index with PHBP. There was no difference in these indices whether pure His bundle pacing (termed selective His bundle pacing) or His bundle pacing plus local septal myocardial capture (termed non-selective His bundle pacing) occurred. LV ejection fraction significantly decreased in the RV paced group compared to that in the PHBP group (50.1 ± 8.8% vs. 57.3 ± 8.5%, P b 0.001). In another study, patients underwent implantation of an HB lead as well as an RV apical pacing lead [3]. During long-term follow-up, pacing was temporarily switched in patients with HB pacing to RV apical pacing. Acutely, LV EF decreased significantly along with worsening mitral regurgitation and inter-ventricular delay. Clinical benefits of His bundle pacing In a small study of 12 consecutive patients who underwent PHBP along with RV apical pacing, coronary perfusion was significantly better with PHBP compared to that with RV apical pacing [21]. Also, there was a significant reduction in mitral regurgitation and ventricular dyssynchrony in PHBP. In another study, PHBP outcomes were compared to RV pacing outcomes in an unselected patient population who had indications for permanent pacemaker placement [4]. PHBP could be achieved in 80% of patients without the use of a separate mapping catheter in this cohort. More importantly, in patients with N40% ventricular pacing, heart failure hospitalizations were significantly reduced (2% vs. 15%) in the PHBP pacing group compared to those in the RV pacing group. In six of the nine patients in the RV pacing group, there was a significant reduction in LV EF (from a mean of 58% to 33%). Recently, it was also shown that direct HB pacing can improve acute hemodynamic function in patients with heart failure and PR interval prolongation without LBBB [22]. AV optimization was performed acutely with both HB pacing and BiV pacing. There was improvement in systolic BP in both groups but the QRS duration was lengthened in the BiV pacing group (change = +22 ms [95% CI: +18 to +25 ms]) but not in the His pacing group (change = +0.5 ms [95% CI: −2.6 to +3.6 ms). His bundle pacing in patients with heart block In one small study, PHBP was able to be achieved in 5 patients with infra-Hisian heart block [23]. Ventricular dyssynchrony (as measured by 2D echo) that was present in patients
G. Dandamudi, P. Vijayaraman / Journal of Electrocardiology xx (2016) xxx–xxx
3
Fig. 1. ECG example of permanent His bundle pacing in a 42-year-old male with history of high grade AV block (1A) who underwent permanent non-selective His bundle pacing (fusion between local myocardial capture and His bundle capture) (1B).
prior to implant had improved during follow-up. In another study, permanent para-Hisian pacing (i.e. non-selective HBP) was shown to be better than RV apical pacing in a double-blinded cross over study in patients who underwent PHBP in the setting of advanced AV block and narrow QRS complex [24]. There was improvement in NYHA class, exercise tolerance, QoL scores, valvular regurgitation and interventricular mechanical delay. In a study with a larger patient
population, it was demonstrated that PHBP could be achieved in patients regardless of the type of heart block [25]. Acutely, 73% of all patients presenting for permanent pacemaker implantation had HB recruitment. In the end, PHBP was successful in 44% of these patients. In another study, 38 patients with second- or third-degree AV block with QRS b120 ms and EF N40% underwent PHBP along with placement of an RV lead in the mid-septal region [26]. The
Fig. 2. Example of a 12-lead ECG demonstrating recruitment of left bundle branch block with permanent His bundle pacing in a 56-year-old male who presented for CRT pacing. The red asterisks demonstrate fusion beats between native conduction with LBBB and His bundle pacing due to VVI pacing during threshold testing.
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authors were able to achieve an 85% success rate in permanently recruiting the His bundle, although vast majority of patients had non-selective His bundle pacing. In a large series of patients with advanced heart block, a recent study highlighted that PHBP can be achieved successfully in these patients [27]. In this study, PHBP was successful in 84% of the patients (93% in AV nodal block patients and 76% in infra-nodal block patients) (Fig. 1). It is noteworthy that the majority of patients did not receive a back-up RV pacing lead. Acute HB current of injury was demonstrated at the time of lead affixation during PHBP in close to 40% of patients [28]. HB current of injury resulted in lower pacing thresholds when compared to patients where HB current of injury could not be demonstrated at the time of implantation. His bundle pacing in patients with LBBB PHBP has been compared to BiV pacing in CRT-indicated patients (LBBB) in a cross over fashion [5] (Fig. 2). In this study, both HB leads and LV leads were placed and connected to a Y-adaptor. 72% of patients demonstrated narrowing of QRS complex at the time of implant. At 6 months, patients were crossed over to the other group. There was no significant difference between both groups, suggesting that PHBP was at least as effective as CRT pacing in this cohort. There was improvement in the baseline EF from 26% to 32% and 31% in the PHBP and CRT groups, respectively, at 6 months. Additional echocardiographic parameters (end-systolic and diastolic volumes, mitral regurgitation jet area, and LV outflow tract velocity time integrals) showed improvement in both groups, with a trend toward more improvement in the PHBP group. Conclusion Over the past few years, PHBP has been gaining ground as an alternative form of permanent ventricular pacing. Added benefits include limited hardware use (compared to CRT therapy), AV and VV synchronization by utilizing the native conduction system, and the lead tip possibly resting in the right atrium resulting in less incidence of tricuspid valve injury or regurgitation [29–31]. Compared to other ventricular pacing therapies in practice today, PHBP offers true physiological pacing by utilizing the native conduction system. As outlined in this paper, current data exist to support its safety and efficacy in clinical practice. Long-term studies and randomized trials are needed to confirm its broad applicability as the preferred form of permanent ventricular pacing. References [1] Deshmukh P, Casavant DA, 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(8):869–77. [2] Catanzariti D, Maines M, Cemin C, Broso G, Marotta T, Vergara G. Permanent direct His bundle pacing does not induce ventricular dyssynchrony unlike conventional right ventricular apical pacing. J Interv Card Electrophysiol 2006;16(2):81–92.
[3] Catanzariti D, Maines M, Manica A, Angheben C, Varbaro A, Vergara G. Permanent His-bundle pacing maintains long-term ventricular synchrony and left ventricular performance, unlike conventional right ventricular apical pacing. Europace 2013;15(4):546–53. [4] Sharma PS, Dandamudi G, Naperkowski A, Oren JW, Storm RH, Ellenbogen KA, et al. Permanent His-bundle pacing is feasible, safe, and superior to right ventricular pacing in routine clinical practice. Heart Rhythm 2015;12(2):305–12. [5] Lustgarten DL, Crespo EM, Arkhipova-Jenkins I, Lobel R, Winget J, Koehler J, et al. His-bundle pacing versus biventricular pacing in cardiac resynchronization therapy patients: a crossover design comparison. Heart Rhythm 2015;12(7):1548–57. [6] Sweeney MO, Hellkamp AS, Ellenbogen KA, Greenspon AJ, Freedman RA, Lee KL, et al. Adverse effect of ventricular pacing on heart failure and atrial fibrillation among patients with normal baseline QRS duration in a clinical trial of pacemaker therapy for sinus node dysfunction. Circulation 2003;107(23):2932–7. [7] Wilkoff BL, Cook JR, Epstein AE, Greene HL, Hallstrom AP, Hsia H, et al. Dual-chamber pacing or ventricular backup pacing in patients with an implantable defibrillator: the Dual Chamber and VVI Implantable Defibrillator (DAVID) Trial. JAMA 2002;288(24):3115–23. [8] Egoavil CA, Ho RT, Greenspon AJ, Pavri BB. Cardiac resynchronization therapy in patients with right bundle branch block: analysis of pooled data from the MIRACLE and Contak CD trials. Heart Rhythm 2005;2(6):611–5. [9] Curtis AB, Worley SJ, Adamson PB, Chung ES, Niazi I, Sherfesee L, et al. Biventricular pacing for atrioventricular block and systolic dysfunction. Med 2013;368(17):1585–93. [10] Funck RC, Blanc JJ, Mueller HH, Schade-Brittinger C, Bailleul C, Maisch B. Biventricular stimulation to prevent cardiac desynchronization: rationale, design, and endpoints of the ‘Biventricular Pacing for Atrioventricular Block to Prevent Cardiac Desynchronization (BioPace)’study. Europace 2006;8(8):629–35. [11] Tawara S. Das reizleitungssystem des Säugetierherzens. Fischer; 1906. [12] Alanís J, González H, López E. The electrical activity of the bundle of His. J Physiol 1958;142(1):127. [13] Giraud G, Puech P, Latour H, Hertault J. Variations de potentiel liees a l’activite du systeme de conduction auriculo-ventriculaire chez l’homme. Arch Mal Coeur 1960;53:757–76. [14] Scherlag BJ, Lau SH, Helfant RH, Berkowitz WD, Stein E, Damato AN. Catheter technique for recording His bundle activity in man. Circulation 1969;39(1):13–8. [15] Narula OS, Samet P. Wenckebach and Mobitz type II AV block due to block within the His bundle and bundle branches. Circulation 1970;41(6):947–65. [16] James TN, Sherf L. Fine structure of the His bundle. Circulation 1971;44(1):9–28. [17] Lazzara R, Yeh BK, Samet P. Functional transverse interconnections within the His bundle and the bundle branches. Circ Res 1973;32(4):509–15. [18] Kaufmann R, Rothberger CJ. Beiträge zur entstehungsweise extrasystolischer allorhythmien. Z Gesamte Exp Med 1919;9(1):104–22. [19] Narula OS. Longitudinal dissociation in the His bundle. Bundle branch block due to asynchronous conduction within the His bundle in man. Circulation 1977;56(6):996–1006. [20] El-Sherif N, Amay-Y-Leon F, Schonfield CL, Scherlag BJ, Rosen KE, Lazzara RA, et al. Normalization of bundle branch block patterns by distal His bundle pacing. Clinical and experimental evidence of longitudinal dissociation in the pathologic His bundle. Circulation 1978;57(3):473–83. [21] Zanon F, Bacchiega E, Rampin L, Aggio S, Baracca E, Pastore G, et al. Direct His bundle pacing preserves coronary perfusion compared with right ventricular apical pacing: a prospective, cross-over mid-term study. Europace 2008;10(5):580–7. [22] Sohaib SA, Wright I, Lim E, Moore P, Lim PB, Koawing M, et al. Atrioventricular optimized direct His bundle pacing improves acute hemodynamic function in patients with heart failure and PR interval prolongation without left bundle branch block. JACC: Clin Electrophysiol 2015;1(6):582–91. [23] Barba-Pichardo R, Moriña-Vázquez P, Venegas-Gamero J, MarotoMonserrat F, Cid-Cumplido M, Herrera-Carranzaa M. Permanent Hisbundle pacing in patients with infra-Hisian atrioventricular block. Rev Esp Cardiol (English Edition) 2006;59(6):553–8.
G. Dandamudi, P. Vijayaraman / Journal of Electrocardiology xx (2016) xxx–xxx [24] Occhetta E, Bortnik M, Marino P. Permanent parahisian pacing. Indian Pacing Electrophysiol J 2006;7(2):110–25. [25] Barba-Pichardo R, Moriña-Vázquez P, Fernández-Gómez JM, VenegasGamero J, Herrera-Carranza M. Permanent His-bundle pacing: seeking physiological ventricular pacing. Europace 2010;12(4):527–33. [26] Kronborg MB, Mortensen PT, Gerdes JC, Jensen HK, Nielsen JC. His and para-His pacing in AV block: feasibility and electrocardiographic findings. J Interv Card Electrophysiol 2011;31(3):255–62. [27] Vijayaraman P, Naperkowski A, Ellenbogen KA, Dandamudi G. Electrophysiologic insights into site of atrioventricular block: lessons from permanent His bundle pacing. JACC: Clin Electrophysiol 2015;1(6):571–81.
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[28] Vijayaraman P, Dandamudi G, Worsnick S, Ellenbogen KA. Acute Hisbundle injury current during permanent His-bundle pacing predicts excellent pacing outcomes. Pacing Clin Electrophysiol 2015;38(5):540–6. [29] de Sa DD, Hardin NJ, Crespo EM, Nicholas KB, Lustgarten DL. Autopsy analysis of the implantation site of a permanent selective direct His bundle pacing lead. Circ Arrhythm Electrophysiol 2012;5(1):244–6. [30] Vijayaraman P, Dandamudi G, Bauch T, Ellenbogen KA. Imaging evaluation of implantation site of permanent direct His bundle pacing lead. Heart Rhythm 2014;11(3):529–30. [31] Bauch T, Vijayaraman P, Dandamudi G, Ellenbogen K. Threedimensional printing for in vivo visualization of His bundle pacing leads. Cardiol 2015;116(3):485–6.
ScienceDirect Journal of Electrocardiology xx (2016) xxx – xxx www.jecgonline.com
Review
History of His bundle pacing☆ Gopi Dandamudi, MD, a,⁎ Pugazhendhi Vijayaraman, MD b a
Indiana University School of Medicine, Indianapolis, IN b Geisinger Heart Institute, Wilkes-Barre, PA
Abstract
Chronic right ventricular (RV) pacing has been shown over the years to exert detrimental physiological changes including increased risk for heart failure and atrial fibrillation. His bundle pacing offers the promise of physiological activation of the ventricular tissue, with the potential for reducing the detrimental effects of RV pacing. We describe His bundle pacing in a historical context and briefly highlight several clinical trials that have helped shape the landscape of permanent His bundle pacing. © 2016 Elsevier Inc. All rights reserved.
Keywords:
His bundle pacing; Chronic RV pacing; Heart failure; QRS complex
Introduction Permanent His bundle pacing (PHBP) offers a very attractive option to pace the ventricles. It is by far the most physiological form of pacing and its theoretical benefits are unquestioned. Limited studies have shown the potential clinical benefits that can be derived from this form of pacing [1–5]. Other forms of pacing currently employed in clinical practice have their limitations. Chronic RV pacing has been shown to increase heart failure (HF) and atrial fibrillation (AF) [6,7]. Biventricular pacing (BiV) has limited benefits in patients with a non-LBBB ECG and significantly reduced ejection fraction (EF) [8]. In mildly reduced EF patients, BiV pacing benefits are equivocal at best [9,10]. We discuss the anatomy and physiology of the His bundle (HB) in a historical context and briefly discuss some clinical trials that have demonstrated safety and efficacy of PHBP.
First anatomical descriptions As a practicing anatomist and physiologist, Johann Evangelist Purkinje first described the existence of Purkinje fibers in 1839. The first descriptions of the HB were made in 1893 by Wilhelm His Jr., a Swiss cardiologist and anatomist. He was the first to coin the term “heart block” and described the significance of the HB as a conduit to conduction from the auricles to the ventricular septal walls. In 1903, Sunao Tawara, a Japanese pathologist, published his monograph on the ☆ COI: Dr. Dandamudi and Dr. Vijayaraman serve as consultants to Medtronic, Inc. ⁎ Corresponding author at: Indiana University Health Cardiac Electrophysiology, Indiana University School of Medicine, 1801 N. Senate Boulevard, Indianapolis, IN 46202. E-mail addresses: [email protected], [email protected]
http://dx.doi.org/10.1016/j.jelectrocard.2016.09.011 0022-0736/© 2016 Elsevier Inc. All rights reserved.
cardiac conduction system and made several seminal observations including the existence of the AV node, detailed descriptions of the bundle branches and the Purkinje system, and histology of the cardiac conduction system [11].
Physiological recordings It was not until 1958 when Alanis and colleagues demonstrated the first HB recordings in Mexico City [12]. Using isolated perfused hearts of dog and cats, steel needles were used to record physiological signals that were identified as HB recordings for the first time. They described the HB as a “zone” with changing HV intervals, as the HB was mapped from a proximal to distal location. They also demonstrated that decremental conduction occurred in the AV node and HB conduction was non-decremental in nature. The first known human recordings of the HB were carried out by Giraud et al. in 1959 in a patient with tetralogy of Fallot [13]. Ten years later, Benjamin Scherlag and colleagues used intravascular catheters to record HB recordings in humans [14]. Over the next several years, numerous observations were made about the HB that would increase our understanding of the anatomy and physiology of this complex cardiac structure.
Earlier observations As mentioned before, Scherlag and colleagues published their technique for recording HB activity in humans in 1969 [14]. This led to the rapid growth of cardiac electrophysiology and is considered one of the pivotal events in this field. They were able to place bipolar catheters percutaneously and demonstrate HB physiology in humans that was first reported by Alanis et al. in animals. Over the next decade, this group
2
G. Dandamudi, P. Vijayaraman / Journal of Electrocardiology xx (2016) xxx–xxx
published several studies assessing the physiology of the HB. Specifically, they reported their findings on complete heart block patients and bundle branch block patients as detailed below. Narula and colleagues published an elegant series on patients with Wenckebach and Mobitz II heart block [15]. They were able to demonstrate that Mobitz II heart block could occur either with bilateral bundle branch blocks or due to intra-Hisian heart blocks (i.e. more proximal in the common bundle). They also suggested that intra-Hisian block was not uncommon and that heart block could be intra-Hisian in location even in patients with abnormal QRS durations. James and Sherf published a detailed anatomical description of the HB in humans using light and electron microscopy in 1971 [16]. They demonstrated the architecture of the HB, including their longitudinal orientation with collagen interspersed between the cells. They also described sparse transverse connections between these bundles. In 1973, Lazzara et al. demonstrated that in partially transected (80–90%) right and left bundle branches in canine hearts, conduction could resume with no significant delay [17]. They also demonstrated that the transverse conduction velocity was significantly less than the longitudinal conduction velocity in the common bundle. The concept of functional longitudinal dissociation of the HB was first proposed by Kaufman and Rothberger in 1919 [18]. Predestined fibers within the His bundle conducted selectively to each fascicle and these fibers originated within the proximal portions of the common bundle. This concept was very elegantly demonstrated by Narula in 1977 [19]. Patients with LBBB and baseline prolonged HV intervals were studied and pacing slightly distal to the proximal His bundle resulted in narrowing of the QRS. El-Sherif et al. published both clinical and experimental evidence for longitudinal dissociation in the diseased His bundle in humans in 1978 [20]. They evaluated patients with both RBBB and LBBB, and prolonged HV intervals. With distal HB pacing, they were able to normalize the QRS duration. They demonstrated this in canine models with ligated septal arteries that resulted in intra-His conduction delay and bundle branch blocks. Once again, with slightly distal pacing within the common bundle, they were able to normalize QRS complexes and conduction times. Even though there was mounting evidence that heart blocks and bundle branch blocks could be manifestations of proximal HB disease and that pacing from the common bundle can result in resumption of conduction with recruitment of the bundle branches as described earlier, further clinical studies were not undertaken at that time. With the advent of biventricular pacing a few years later, there was a stalemate in further development of PHBP.
Clinical evidence for PHBP In the year 2000, Deshmukh et al. published the seminal paper demonstrating the safety and feasibility of PHBP in humans [1]. They attempted PHBP in 18 patients with chronic AF, EF b40%, QRS b120 ms, and NYHA class III–IV HF symptoms who underwent AV nodal ablation. They were successful in achieving PHBP in two thirds of their patients.
They were able to demonstrate positive LV remodeling in this cohort, with an improvement in LV EF from 20 ± 9% to 31 ± 11% (P b 0.01). This set the stage for clinicians around the world to pursue PHBP as an alternative to RV pacing. Selected PHBP clinical trials and related observations are outlined below. Dyssynchronous RV pacing vs. physiological PHBP It has been demonstrated that PHBP does not induce ventricular dyssynchrony unlike RV apical pacing [2]. In this study, intra-patient acute comparisons were made between both forms of pacing and it showed that indices of ventricular dyssynchrony were significantly reduced, including the degree of mitral regurgitation and improvement in LV systolic function Tei index with PHBP. There was no difference in these indices whether pure His bundle pacing (termed selective His bundle pacing) or His bundle pacing plus local septal myocardial capture (termed non-selective His bundle pacing) occurred. LV ejection fraction significantly decreased in the RV paced group compared to that in the PHBP group (50.1 ± 8.8% vs. 57.3 ± 8.5%, P b 0.001). In another study, patients underwent implantation of an HB lead as well as an RV apical pacing lead [3]. During long-term follow-up, pacing was temporarily switched in patients with HB pacing to RV apical pacing. Acutely, LV EF decreased significantly along with worsening mitral regurgitation and inter-ventricular delay. Clinical benefits of His bundle pacing In a small study of 12 consecutive patients who underwent PHBP along with RV apical pacing, coronary perfusion was significantly better with PHBP compared to that with RV apical pacing [21]. Also, there was a significant reduction in mitral regurgitation and ventricular dyssynchrony in PHBP. In another study, PHBP outcomes were compared to RV pacing outcomes in an unselected patient population who had indications for permanent pacemaker placement [4]. PHBP could be achieved in 80% of patients without the use of a separate mapping catheter in this cohort. More importantly, in patients with N40% ventricular pacing, heart failure hospitalizations were significantly reduced (2% vs. 15%) in the PHBP pacing group compared to those in the RV pacing group. In six of the nine patients in the RV pacing group, there was a significant reduction in LV EF (from a mean of 58% to 33%). Recently, it was also shown that direct HB pacing can improve acute hemodynamic function in patients with heart failure and PR interval prolongation without LBBB [22]. AV optimization was performed acutely with both HB pacing and BiV pacing. There was improvement in systolic BP in both groups but the QRS duration was lengthened in the BiV pacing group (change = +22 ms [95% CI: +18 to +25 ms]) but not in the His pacing group (change = +0.5 ms [95% CI: −2.6 to +3.6 ms). His bundle pacing in patients with heart block In one small study, PHBP was able to be achieved in 5 patients with infra-Hisian heart block [23]. Ventricular dyssynchrony (as measured by 2D echo) that was present in patients
G. Dandamudi, P. Vijayaraman / Journal of Electrocardiology xx (2016) xxx–xxx
3
Fig. 1. ECG example of permanent His bundle pacing in a 42-year-old male with history of high grade AV block (1A) who underwent permanent non-selective His bundle pacing (fusion between local myocardial capture and His bundle capture) (1B).
prior to implant had improved during follow-up. In another study, permanent para-Hisian pacing (i.e. non-selective HBP) was shown to be better than RV apical pacing in a double-blinded cross over study in patients who underwent PHBP in the setting of advanced AV block and narrow QRS complex [24]. There was improvement in NYHA class, exercise tolerance, QoL scores, valvular regurgitation and interventricular mechanical delay. In a study with a larger patient
population, it was demonstrated that PHBP could be achieved in patients regardless of the type of heart block [25]. Acutely, 73% of all patients presenting for permanent pacemaker implantation had HB recruitment. In the end, PHBP was successful in 44% of these patients. In another study, 38 patients with second- or third-degree AV block with QRS b120 ms and EF N40% underwent PHBP along with placement of an RV lead in the mid-septal region [26]. The
Fig. 2. Example of a 12-lead ECG demonstrating recruitment of left bundle branch block with permanent His bundle pacing in a 56-year-old male who presented for CRT pacing. The red asterisks demonstrate fusion beats between native conduction with LBBB and His bundle pacing due to VVI pacing during threshold testing.
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authors were able to achieve an 85% success rate in permanently recruiting the His bundle, although vast majority of patients had non-selective His bundle pacing. In a large series of patients with advanced heart block, a recent study highlighted that PHBP can be achieved successfully in these patients [27]. In this study, PHBP was successful in 84% of the patients (93% in AV nodal block patients and 76% in infra-nodal block patients) (Fig. 1). It is noteworthy that the majority of patients did not receive a back-up RV pacing lead. Acute HB current of injury was demonstrated at the time of lead affixation during PHBP in close to 40% of patients [28]. HB current of injury resulted in lower pacing thresholds when compared to patients where HB current of injury could not be demonstrated at the time of implantation. His bundle pacing in patients with LBBB PHBP has been compared to BiV pacing in CRT-indicated patients (LBBB) in a cross over fashion [5] (Fig. 2). In this study, both HB leads and LV leads were placed and connected to a Y-adaptor. 72% of patients demonstrated narrowing of QRS complex at the time of implant. At 6 months, patients were crossed over to the other group. There was no significant difference between both groups, suggesting that PHBP was at least as effective as CRT pacing in this cohort. There was improvement in the baseline EF from 26% to 32% and 31% in the PHBP and CRT groups, respectively, at 6 months. Additional echocardiographic parameters (end-systolic and diastolic volumes, mitral regurgitation jet area, and LV outflow tract velocity time integrals) showed improvement in both groups, with a trend toward more improvement in the PHBP group. Conclusion Over the past few years, PHBP has been gaining ground as an alternative form of permanent ventricular pacing. Added benefits include limited hardware use (compared to CRT therapy), AV and VV synchronization by utilizing the native conduction system, and the lead tip possibly resting in the right atrium resulting in less incidence of tricuspid valve injury or regurgitation [29–31]. Compared to other ventricular pacing therapies in practice today, PHBP offers true physiological pacing by utilizing the native conduction system. As outlined in this paper, current data exist to support its safety and efficacy in clinical practice. Long-term studies and randomized trials are needed to confirm its broad applicability as the preferred form of permanent ventricular pacing. References [1] Deshmukh P, Casavant DA, 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(8):869–77. [2] Catanzariti D, Maines M, Cemin C, Broso G, Marotta T, Vergara G. Permanent direct His bundle pacing does not induce ventricular dyssynchrony unlike conventional right ventricular apical pacing. J Interv Card Electrophysiol 2006;16(2):81–92.
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