587 ORIGINAL SCIENTIFIC ARTICLE His bundle pacing: initial Slovenian single-centre experience Copyright (c) 2021 Slovenian Medical Journal. This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. His bundle pacing: initial Slovenian single-centre experience Spodbujanje Hisovega snopa: prve izkušnje v Sloveniji Maja Ivanovski,1 Anja Zupan Mežnar,1 Jernej Štublar,1 David Žižek1,2 Abstract Background: High right ventricular (RV) pacing burden may promote left ventricular dysfunction. Recently, His bundle pacing (HBP) has emerged as an alternative method to RV pacing that provides physiological ventricular activation by directly stimulating the conduction system. Methods: Consecutive 75 patients (male 61.3%, age 65 ± 14 yrs, preserved ejection fraction 53.8%, atrial fibrillation (AF) 56%) in whom HBP was attempted at our centre between May 2018 and September 2020 were included. Acute implant success rate, complications and mid-term outcomes were assessed. Results: Permanent HBP was acutely successful in 69 patients (92%). There were no acute procedure-related complica- tions. Most common indication was AF with rapid ventricular response (38.7%) where HBP was performed in conjunction with atrioventricular node ablation. Median fluoroscopy time was lower during the second half of implants (6.35 (2.7 – 47) vs. 5.4 (1.3 – 13.6) minutes; p = 0.004). His capture parameters remained stable during the median follow-up of 193 (59 – 342) days. Eleven patients (11/69, 15.9%) with initially successful procedure experienced a significant rise in HBP threshold. Three patients (3/69, 4.3%) needed HBP lead revision or deactivation. Conclusion: Our initial experience indicates that HBP is feasible and safe in various pacing indications. Further random- ized clinical trials with long-term follow-up are needed to provide the grounds for wider clinical application of this prom- ising physiological pacing technique. Slovenian Medical Journallovenian Medical Journal 1 Department of Cardiology, Division of Internal Medicine, University Medical Centre Ljubljana, Ljubljana, Slovenia 2 Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia Correspondence / Korespondenca: Maja Ivanovski, e: majaivanovski94@gmail.com Key words: His bundle pacing; conduction system pacing; physiological pacing; pacemaker; initial experience Ključne besede: spodbujanje Hisovega snopa; spodbujanje prevodnega sistema; fiziološko spodbujanje; srčni spodbujevalnik; prve izkušnje Received / Prispelo: 29. 11. 2020 | Accepted / Sprejeto: 8. 3. 2021 Cite as / Citirajte kot: Ivanovski M, Zupan Mežnar A, Štublar J, Žižek D. His bundle pacing: initial Slovenian single-centre experience. Zdrav Vestn. 2021;90(11–12):587–95. DOI: https://doi.org/10.6016/ZdravVestn.3196 eng slo element en article-lang 10.6016/ZdravVestn.3196 doi 29.11.2020 date-received 8.3.2021 date-accepted Cardiovascular system Srce in obtočila discipline Original scientific article Izvirni znanstveni članek article-type His bundle pacing: initial Slovenian single-cen- tre experience Spodbujanje Hisovega snopa: prve izkušnje v Sloveniji article-title His bundle pacing Spodbujanje Hisovega snopa: prve izkušnje v Sloveniji alt-title His bundle pacing, conduction system pacing, physiological pacing, pacemaker, initial expe- rience spodbujanje Hisovega snopa, spodbujanje prevodnega sistema, fiziološko spodbujanje, srčni spodbujevalnik, prve izkušnje kwd-group The authors declare that there are no conflicts of interest present. Avtorji so izjavili, da ne obstajajo nobeni konkurenčni interesi. conflict year volume first month last month first page last page 2021 90 11 12 587 595 name surname aff email Maja Ivanovski 1 majaivanovski94@gmail.com name surname aff Anja Zupan Mežnar 1 Jernej Štublar 1 David Žižek 1 eng slo aff-id Department of Cardiology, Division of Internal Medicine, University Medical Centre Ljubljana, Ljubljana, Slovenia Klinični oddelek za kardiologijo, Interna klinika, Univerzitetni klinični center Ljubljana, Ljubljana, Slovenija 1 Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia Medicinska fakulteta, Univerza v Ljubljani, Ljubljana, Slovenija 2 588 CARDIOVASCULAR SYSTEM Zdrav Vestn | November – December 2021 | Volume 90 | https://doi.org/10.6016/ZdravVestn.3196 1 Introduction Right ventricular (RV) pacing-induced electrome- chanical dyssynchrony which results in an increased risk of heart failure (HF) and atrial fibrillation (AF) is well established (1-2). The pursuit of alternate pacing sites in- cluding RV septum and RV outflow tract produced only modest or no clinical benefits (3). Furthermore, several device programming algorithms to minimize ventricu- lar pacing were developed which are ineffective with ad- vanced atrioventricular (AV) block and mainly function at the expense of AV dyssynchrony further increasing the risk of AF (4). Compared to RV pacing, biventric- ular (BiV) pacing derived better results in patients with AV block and systolic dysfunction, however, the benefit was much less distinct in patients with preserved ejec- tion fraction (5-6). Recently, permanent His bundle pacing (HBP) has emerged as a physiological alternative to convention- al RV and BiV pacing. By capturing the His-Purkinje conduction system, HBP provides normal synchronous activation and preserves left ventricular (LV) function in patients who require a pacemaker due to bradycardia (7). In addition, several studies have shown the poten- tial of HBP to correct underlying bundle branch block (BBB), improving the ventricular activation time and narrowing the QRS (8). However, due to the anatomic location and surrounding fibrous tissue, lead position- ing in the His bundle area could be technically chal- lenging, consequently extending procedural and fluo- roscopy times compared to standard pacing methods. Izvleček Izhodišča: Visok delež stimulacije desnega prekata lahko vpliva na poslabšanje delovanja levega prekata. Spodbujanje Hisovega snopa je alternativa običajni stimulaciji srca, saj z neposredno stimulacijo prevodnega sistema omogoča fiziolo- ško aktiviranje srca. Metode: V analizo smo vključili 75 zaporednih bolnikov (moški 61,3 %, starost 65 ± 14 let, ohranjen iztisni delež levega pre- kata 53, 8 %, atrijska fibrilacija (AF) 56 %), pri katerih smo v našem centru, med majem 2018 in septembrom 2020, poizku- sili spodbujati Hisov snop. Pregledali smo uspešnost posega, zaplete in parametre stimulacije po srednjeročnem sledenju. Rezultati: Uspešno spodbujanje Hisovega snopa smo dosegli pri 69 bolnikih (92 %). Akutnih zapletov nismo zaznali. Najpogostejša indikacija je bila AF s tahikardnim odgovorom prekatov (38, 7 %). Pri teh bolnikih smo hkrati z vstavitvijo srčnega spodbujevalnika s stimulacijo Hisovega snopa opravili tudi ablacijo preddvorno-prekatnega vozla. Srednji čas trajanja diaskopije je bil statistično krajši pri drugi polovici posegov: 6,35 (2, 7–47) vs. 5, 4 (1,3–13,6) minut; p = 0.004. V času spremljanja pri 193 (59–342) bolnikih ni prišlo do pomembnih sprememb praga stimulacije. Pomemben porast praga spodbujanja Hisovega snopa smo zaznali pri 11 bolnikih (11/69, 15,9 %) že po uspešnem posegu. Trije bolniki (3/69, 4, 3 %) so potrebovali popravilo ali izklop elektrode. Zaključek: Naše prve izkušnje kažejo, da je metoda spodbujanja Hisovega snopa izvedljiva in varna pri različnih indikaci- jah za trajno stimulacijo srca. Za širšo klinično uporabo te obetavne metode, ki omogoča fiziološko spodbujanje srca, so potrebne nadaljnje randomizirane klinične študije z daljšim sledenjem. In addition, there is concern about maintaining chronic pacing due to higher initial pacing thresholds, exit block and risk of progressive electrical block distal to the HBP lead. These uncertainties hinder wider clinical adoption of this physiological technique, although technical ad- vancements and specialized delivery tools substantially improved recently reported success rates in experienced centres (9). The aim of our study was to evaluate the feasibility, safety and mid-term outcomes during the implementa- tion of the HBP programme in our centre. 2 Methods 2.1 Study design We implemented HBP programme at the Universi- ty Medical Centre Ljubljana in May 2018, and all con- secutive patients in whom the procedure was attempted were included in this single-centre, observational, ret- rospective study. All HBP procedures were performed by a single operator (200 device implantations per year) without previous exposure to the technique or electro- physiology procedures. Implant success rate, specific im- plant characteristics, procedural complications and elec- trical HBP parameters during follow-up were analysed. The study complies with the Declaration of Helsinki and was approved by the institutional review board. The study design was approved by the Republic of Slovenia 589 ORIGINAL SCIENTIFIC ARTICLE His bundle pacing: initial Slovenian single-centre experience National Medical Ethics Committee (decision no. 0120- 95/2019/18 on 28. 10. 2019). 2.2 Patient population All consecutive patients who underwent an attempt at permanent HBP from May 2018 to September 2020 in our centre were included. There were no pre-speci- fied inclusion criteria, however, HBP was initially pre- ferred in AF patients with bradycardia, in AF patients in whom AV node ablation was also scheduled, and in patients with prolonged AV intervals where high burden of ventricular pacing was expected. As our experience deepened, HBP was expanded to patients with advanced AV block, BBB and complete AV block with stable es- cape rhythms. In advanced AV block pacing indications, nonselective HBP was preferentially targeted to enhance safety by ensuring the capture of ventricular myocardi- um. In patients who required temporary pacing, HBP was not attempted. 2.3 Implantation techniques and tools The procedure was performed as previously de- scribed (8-12). In short, a 4.1 Fr bipolar active fixation lead (SelectSecure 3830, Medtronic, Minneapolis, MN, USA) and dedicated delivery sheath (C315His or C304, Medtronic, Minneapolis, MN, USA) were used for His bundle area mapping under fluoroscopy (Figure 1A). His bundle potential mapping was performed in a unipolar setting with the use of the electrophysiological system LAB system Pro, BARD (Boston Scientific, Lowell, MA, USA) or EP-TRACER 2 Portable (CardioTek B.V., Sit- tard, The Netherlands) at a sweep speed of 100 mm/s. Additional visualization of the tricuspid valve annulus via contrast injection through delivery sheath was usual- ly performed before mapping to delineate the anatomical landmark of His bundle area (Figure 1B) (11). After lo- calizing the His bundle potential (Figure 1C), preferably the most distal His deflection with ventricular to atri- al electrogram ratio >3:1, pacing was attempted before the lead fixation to confirm HB capture. The lead then screwed into position with 4 or 5 clockwise rotations and acute HBP threshold ≤ 2.5V at 1ms was considered ac- ceptable. Selective or non-selective HBP was categorized according to the recently proposed definitions (13). Ad- ditional backup RV lead was implanted only in few ini- tial cases and in all patients undergoing concomitant AV node ablation. In latter cases, HBP lead was connected to the atrial port of the dual-chamber device. Figure 1: His bundle pacing procedure. (A) Dedicated implantation tools: fixed dual-plane curve C315 His sheath and 4.1 Fr bipolar active fixation SelectSecure 3830 His pacing lead. (B) Fluoroscopic image with contrast injection through the C315 His sheath to show the tricuspid valve annulus and potential site for His bundle pacing (HBP) with schematic representation of the conduction system - atrioventricular (AV) node, bundle of His (HB), right bundle branch (RBB), and left bundle branch (LBB). Final HBP lead position after the sheath is withdrawn to the high right atrium until an adequate loop is formed (bellow). Right ventricular (RV) lead was used as a backup. (C) Distal His bundle potential (arrows) followed by a large ventricular signal in the unipolar setting after HBP lead fixation. Image is from authors’ own archive. 590 CARDIOVASCULAR SYSTEM Zdrav Vestn | November – December 2021 | Volume 90 | https://doi.org/10.6016/ZdravVestn.3196 2.4 Procedural outcome definitions and follow-up The procedure was considered successful when ven- tricular activation occurring over the conduction system was proven. Selective or non-selective HBP was cate- gorized according to the recently proposed definitions (13). Briefly, selective HB capture ventricular activation occurs solely over the His-Purkinje system (Figure 2A), while non-selective HB capture results in a fusion cap- ture of HB and adjacent ventricular tissue that could be recognized by the absence of isoelectric interval between pacing stimulus and QRS. The capture of the local myo- cardium beside His-Purkinje system produces a pseu- do-delta wave on the 12-lead ECG (Figure 2B). Assess- ment of selective or nonselective HB capture was made by increasing or decreasing pacing output and the simul- taneous observation of QRS morphology changes in the standard 12-lead ECG. Patients with selective HBP with an output near HB capture threshold values but non- selective at the final programmed pacing output were classified as nonselective (Figure 3). If HBP could not be achieved, the lead was inserted in the RV mid-sep- tum. Procedure duration was defined as the time from subcutaneous injection of local anaesthetic until the last skin suture. Fluoroscopy time was generally limited to 25 minutes. His bundle and myocardial capture thresh- old, R waves, lead impedance, intrinsic and paced QRS duration were measured at implant for each patient. HBP threshold testing was performed at a pulse width of 1ms (13). In cases with underlying BBB, the output necessary to correct the BBB was noted as a final thresh- old. Patients were evaluated in the device clinic 1 month after implantation, at 6 months, and every 6 months thereafter. During each follow-up, device interrogation and 12-lead ECG were performed. An increase in HBP capture threshold of >1V at 1ms compared to the im- plant measurement was considered significant. The im- pact of the learning curve on acute procedure success rate, fluoroscopy time and HBP thresholds was assessed by comparison of the initial half of the cases with the remaining cases. 2.5 Statistical analysis Categorical variables were presented as counts and percentages, continuous variables were reported as mean ± standard deviation or median (interquartile range), according to the distribution. Regression models were constructed to assess the correlation between procedure Figure 2: Forms of His bundle pacing. (A) During selective His bundle (HB) capture, ventricular activation occurs directly over the His-Purkinje system. There is an isoelectric line between the pacing stimulus and the QRS which is identical to the native QRS. (B) In nonselective HB pacing there is fusion capture of HB and adjacent myocardial tissue resulting in the presence of pseudo-delta wave. Although paced QRS duration is slightly increased (by the H-QRS interval), the overall electrical axis of the paced QRS is concordant with the electrical axis of the intrinsic QRS. Image is from authors’ own archive. Figure 3: Output dependence of His bundle capture. Nonselective His bundle pacing (HBP) with fusion of ventricular and HB capture can be seen in lead II and electrogram (EGM) at higher pacing output. As the output decreases to 0.25V at 1ms, there is a transition to selective HBP with the presence of isoelectric interval between pacing stimulus and QRS. QRS morphology in lead II and EGM during selective HBP is identical to the native QRS (bellow). His bundle lead is connected to the atrial port of a dual-chamber device and right ventricular lead was used as a backup. After successful HBP procedure, atrioventricular node ablation was performed due to refractory atrial fibrillation with high ventricular rate. Image is from authors’ own archive. 591 ORIGINAL SCIENTIFIC ARTICLE His bundle pacing: initial Slovenian single-centre experience or diascopy time and operator’s experience. The differ- ences in mean values of the continuous variables were compared using paired or unpaired t-test if the data were normally distributed, otherwise Mann – Whitney U test or Wilcoxon Sign test were adopted. All hypotheses were two-tailed and p-value ≤ 0.05 was considered sig- nificant. The analysis was performed using SPSS version 22.0 (SPSS, Chicago, IL, USA). 3 Results 3.1 Clinical characteristics and pacing indications Seventy-five consecutive patients in whom HBP was attempted were included in the study. Baseline charac- teristics are presented in Table 1. Mean age of the study population was 65 ± 14 years, 46 (61.3%) of the patients were male and 30 (46.2%) had reduced EF before the procedure. The youngest patient who received perma- nent HBP was a 5-year-old child. Most of the procedures were de-novo implantations. There were only 2 upgrade procedures: in one case with complete AV block where previous epicardial leads were replaced with endocardial leads and in an HF patient with implantable cardiovert- er-defibrillator (ICD) in whom pace and ablate strategy was indicated. His bundle pacing was mainly performed in AF patients with a rapid ventricular response in con- junction with AV node ablation (29; 38.7%). Pacing in- dications are presented in Table 2. Age [years] 65 ± 14 Gender male 46 (61.3%) Comorbidities diabetes mellitus 20 (26.7%) hypertension 49 (65.3%) valvular disease 13 (17.3%) ischaemic heart disease 25 (33.3%) atrial fibrillation 42 (56%) Left ventricular function, n = 65 preserved (EF > 50 %) 35 (53.8%) impaired (EF < 50 %) 30 (46.2%) Intrinsic QRS [ms], n = 68 114 ± 27 > 120ms 17 (22.7%) LBBB 11 (14.7%) RBBB 6 (8%) Table 1: Baseline characteristics. Legend: EF – ejection fraction, LBBB – left bundle branch block, RBBB – right bundle branch block. skin suture. Fluoroscopy time was generally limited to 25 minutes. His bundle and myocardial capture thresh- old, R waves, lead impedance, intrinsic and paced QRS duration were measured at implant for each patient. HBP threshold testing was performed at a pulse width of 1ms (13). In cases with underlying BBB, the output necessary to correct the BBB was noted as a final thresh- old. Patients were evaluated in the device clinic 1 month after implantation, at 6 months, and every 6 months thereafter. During each follow-up, device interrogation and 12-lead ECG were performed. An increase in HBP capture threshold of >1V at 1ms compared to the im- plant measurement was considered significant. The im- pact of the learning curve on acute procedure success rate, fluoroscopy time and HBP thresholds was assessed by comparison of the initial half of the cases with the remaining cases. 2.5 Statistical analysis Categorical variables were presented as counts and percentages, continuous variables were reported as mean ± standard deviation or median (interquartile range), according to the distribution. Regression models were constructed to assess the correlation between procedure Figure 2: Forms of His bundle pacing. (A) During selective His bundle (HB) capture, ventricular activation occurs directly over the His-Purkinje system. There is an isoelectric line between the pacing stimulus and the QRS which is identical to the native QRS. (B) In nonselective HB pacing there is fusion capture of HB and adjacent myocardial tissue resulting in the presence of pseudo-delta wave. Although paced QRS duration is slightly increased (by the H-QRS interval), the overall electrical axis of the paced QRS is concordant with the electrical axis of the intrinsic QRS. Image is from authors’ own archive. Figure 3: Output dependence of His bundle capture. Nonselective His bundle pacing (HBP) with fusion of ventricular and HB capture can be seen in lead II and electrogram (EGM) at higher pacing output. As the output decreases to 0.25V at 1ms, there is a transition to selective HBP with the presence of isoelectric interval between pacing stimulus and QRS. QRS morphology in lead II and EGM during selective HBP is identical to the native QRS (bellow). His bundle lead is connected to the atrial port of a dual-chamber device and right ventricular lead was used as a backup. After successful HBP procedure, atrioventricular node ablation was performed due to refractory atrial fibrillation with high ventricular rate. Image is from authors’ own archive. 592 CARDIOVASCULAR SYSTEM Zdrav Vestn | November – December 2021 | Volume 90 | https://doi.org/10.6016/ZdravVestn.3196 (66/69, 95.7%) with initially successful HBP procedure. During the follow-up of 193 (59 – 342) days His cap- ture thresholds remained stable (Figure 5) regardless of whether selective or nonselective pacing was achieved (Table 3). However, 11 out of 69 patients (15.9%) ex- perienced a significant rise in HBP capture threshold. Loss of capture necessitating lead revision or repro- gramming occurred in 3 patients (3/69, 4.3%). In 2 patients, HBP threshold rose from initial 2.3V to 6.5V at 1ms and from 3.5V to 5.5V at 1ms after AV node ablation. In both cases HBP lead was deactivated and switched to back-up RV lead pacing. In 1 patient, HBP lead revision was required due to dislocation and only RV septal pacing was obtained after repositioning. Two patients died during follow-up; the cause of death was unrelated to the procedure. One patient un- derwent heart transplantation. 4 Discussion The findings of our study demonstrate that estab- lishing HBP was feasible and safe in various pacing indications. We had a high acute implant success rate of 92% and His capture parameters remained stable during mid-term follow-up. A modest proportion of patients (15.9%) did experience a significant rise (more than 1V) in HBP threshold. In the published literature, HBP implant success rates range from 75% to 99% (9,11,15-20). Our acute HBP success rate is in accordance with a recent me- ta-analysis which showed 92% implant success when catheter-delivered systems were used (14). Howev- er, pacing indication might have an impact on HBP procedure while studies reporting outcomes of HBP in patients with complete AV blocks and BBB record- ed significantly lower success rates (17,19) compared to the studies that mostly included patients with AF, less advanced AV blocks and narrow QRS (9,10,18). Therefore, the fact that most of our patient population had less advanced conduction disorders could have Figure 5: His bundle pacing capture thresholds during follow-up. Mid-term follow-upShort-term follow-upImplantation H BP c ap tu re th re sh ol d [V ] 6 5 4 3 2 1 0 1.50 1.0 1.0p = 0.082 p = 0.197 All (n=66) Nonselective pacing (n=35) Selective pacing (n=31) Initial threshold [V] 1.50 (1 – 2.25) 1.50 (1 – 2.50) 1.25 (1 – 2) Short-term follow-up threshold [V] 1 (0.75 – 2.25) p = 0.082 1.25 (0.75 – 2.50) p = 0.013 1 (0.75 – 2.25) p = 0.903 Mid-term follow-up threshold [V] 1 (0.75 – 2.50) p = 0.197 1.25 (0.75 – 2.75) p = 0.092 1 (0.75 – 2.50) p = 0.937 Table 3: Acute and chronic His bundle pacing thresholds. 3.2 Implant success rate and procedure characteristics Acute HBP was successful in 69 of the 75 patients (92%). Among 6 unsuccessful procedures, in 3 HB po- tential could not be located, high His capture threshold was considered unacceptable in 1 case, and in 2 cases LBBB correction could not be obtained. Acute success rate was higher (36/37, 97.2 %) in the second half of the implant attempts compared to the initial cases (33/38, 86.8%). There were no acute procedural complica- tions. Median procedure time was 60 (50 – 80) min- utes and median fluoroscopy time was 6 (4.5 – 10.1) minutes. Negative correlation was found between pro- cedure time (r = -0.246, p = 0.040) or fluoroscopy time (r = -0.325, p = 0.005) and number of cases performed. There was also a statistically significant difference between median fluoroscopy time in the first half of the implantations (success rate 86.1 %) and the subsequent procedures (success rate 97.2%) [6.35 (2.7 – 47) vs. 5.4 (1.3 – 13.6) minutes, p = 0.004] (Figure 4), indicating a learning curve. Defibrillator lead or back-up RV pac- ing lead implantation (n=36) did not affect the pro- cedure [60 (50 - 72) minutes vs. 60 (50 - 83) minutes, p = 0.767] or fluoroscopy time [6.1 (4.5 – 9.8) minutes vs. 5.5 (3.8 – 9.7) minutes, p= 0.626]. 3.3 Electrical parameters and clinical outcomes during follow-up Compared to intrinsic QRS duration, HBP did not result in significant prolongation (114 ± 26ms vs. 115 ± 20ms, p = 0.662) of paced QRS duration. In 15 patients with underlying BBB, there was a significant reduction of paced QRS duration (153 ± 18ms vs. 122 ± 20ms, p < 0.001) compared to intrinsic QRS. Median acute HBP threshold was 1.5 (1 – 2.25) V at 1ms. Nonselective HB capture was achieved in 36 patients (52.2%) with a median threshold of 1.5 (1 – 2.4) V at 1ms. Selective HB capture was observed in 33 patients (47.8%) with a median threshold of 1.5 (1 – 2) V at 1ms. Median threshold for bundle recruit- ment in patients with a baseline left (n=9) or right (n=6) BBB was 1.25 (1 – 2) V at 1ms. In addition, acute HBP thresholds were lower in the second half of the implants 1.75 (1.25 – 2.4) V vs. 1.1 (0.8 – 2) V, p = 0.013, again demonstrating a learning curve with increasing HBP experience. Permanent HBP was maintained in 66 patients Indications Number (%) Symptomatic 1st degree AV block 7 (9.3%) AV block 2nd degree Mobitz II 9 (12.0%) Complete AV block 13 (17.3%) BBB 4 (5.3%) AF with slow conduction 13 (17.3%) AF with rapid ventricular response 29 (38.7%) Table 2: Pacing indications. Legend: AV – atrioventricular, BBB – bundle branch block, AF – atrial fibrillation. Figure 4: Comparison of fluoroscopy time between the initial half and the subsequent half of procedures. Second half of proceduresFirst half of procedures Fl uo ro sc op y tim e [m in ] 50 40 30 20 10 0 6.35 5.40p = 0.004 593 ORIGINAL SCIENTIFIC ARTICLE His bundle pacing: initial Slovenian single-centre experience (66/69, 95.7%) with initially successful HBP procedure. During the follow-up of 193 (59 – 342) days His cap- ture thresholds remained stable (Figure 5) regardless of whether selective or nonselective pacing was achieved (Table 3). However, 11 out of 69 patients (15.9%) ex- perienced a significant rise in HBP capture threshold. Loss of capture necessitating lead revision or repro- gramming occurred in 3 patients (3/69, 4.3%). In 2 patients, HBP threshold rose from initial 2.3V to 6.5V at 1ms and from 3.5V to 5.5V at 1ms after AV node ablation. In both cases HBP lead was deactivated and switched to back-up RV lead pacing. In 1 patient, HBP lead revision was required due to dislocation and only RV septal pacing was obtained after repositioning. Two patients died during follow-up; the cause of death was unrelated to the procedure. One patient un- derwent heart transplantation. 4 Discussion The findings of our study demonstrate that estab- lishing HBP was feasible and safe in various pacing indications. We had a high acute implant success rate of 92% and His capture parameters remained stable during mid-term follow-up. A modest proportion of patients (15.9%) did experience a significant rise (more than 1V) in HBP threshold. In the published literature, HBP implant success rates range from 75% to 99% (9,11,15-20). Our acute HBP success rate is in accordance with a recent me- ta-analysis which showed 92% implant success when catheter-delivered systems were used (14). Howev- er, pacing indication might have an impact on HBP procedure while studies reporting outcomes of HBP in patients with complete AV blocks and BBB record- ed significantly lower success rates (17,19) compared to the studies that mostly included patients with AF, less advanced AV blocks and narrow QRS (9,10,18). Therefore, the fact that most of our patient population had less advanced conduction disorders could have Figure 5: His bundle pacing capture thresholds during follow-up. Mid-term follow-upShort-term follow-upImplantation H BP c ap tu re th re sh ol d [V ] 6 5 4 3 2 1 0 1.50 1.0 1.0p = 0.082 p = 0.197 All (n=66) Nonselective pacing (n=35) Selective pacing (n=31) Initial threshold [V] 1.50 (1 – 2.25) 1.50 (1 – 2.50) 1.25 (1 – 2) Short-term follow-up threshold [V] 1 (0.75 – 2.25) p = 0.082 1.25 (0.75 – 2.50) p = 0.013 1 (0.75 – 2.25) p = 0.903 Mid-term follow-up threshold [V] 1 (0.75 – 2.50) p = 0.197 1.25 (0.75 – 2.75) p = 0.092 1 (0.75 – 2.50) p = 0.937 Table 3: Acute and chronic His bundle pacing thresholds. contributed to higher acute success rate compared to some reported in literature in more experienced cen- tres (17,19). His bundle pacing is associated with higher ini- tial and chronic pacing thresholds compared to stan- dard RV pacing (9,10,20). Acute median HBP capture threshold in our study population was 1.50 (1 – 2.25) V at 1ms, which is comparable with the results in sever- al published studies (9,14,16,19). Moreover, our acute HBP thresholds were lower in more recent procedures, which is in line with Keene et al. (9) who acknowl- edged a learning curve of approximately 30-50 cases in HBP capture reduction. During mid-term median follow-up, no significant deterioration in the capture threshold was recorded in the majority of cases. How- ever, 11 patients (15.9%) did experience a significant rise in HBP threshold that mainly required an increase in pacing output and potentially increased battery drain. Only 4.3% of the patients in our cohort required HBP lead intervention, which is comparable to 4.8% published in the recent meta-analysis (14) and lower compared to 6.7% (16) and 8% (17) reported in two studies with long-term follow-up. Although a relatively short follow-up in our study might have affected lower rate of HBP lead interventions, most revisions due to His capture threshold rising usually occur during the first 90 days (17). The target area of His bundle is relatively small making HBP lead positioning and fixation technical- ly challenging, consequently extending procedure and fluoroscopy times compared to standard pacing meth- ods. Recent introduction of dedicated tools in form of specific pre-shaped or steerable His catheters improved success rates and reduced fluoroscopy times (7-14). Our median fluoroscopy time of 6 minutes was consid- erably lower compared to the published studies ranging from 10 to 12 minutes (10,14,19). This divergence is potentially associated with the utilization of additional radiation exposure-reducing implantation techniques in most of our procedures. First, visualization of the 594 CARDIOVASCULAR SYSTEM Zdrav Vestn | November – December 2021 | Volume 90 | https://doi.org/10.6016/ZdravVestn.3196 References 1. Sharma AD, Rizo-Patron C, Hallstrom AP, O’Neill GP, Rothbart S, Martins JB, et al.; DAVID Investigators. Percent right ventricular pacing predicts outcomes in the DAVID trial. Heart Rhythm. 2005;2(8):830-4. DOI: 10.1016/j.hrthm.2005.05.015 PMID: 16051118 2. Steinberg JS, Fischer A, Wang P, Schuger C, Daubert J, McNitt S, et al.; MADIT II Investigators. The clinical implications of cumulative right ventricular pacing in the multicenter automatic defibrillator trial II. J Cardiovasc Electrophysiol. 2005;16(4):359-65. DOI: 10.1046/j.1540- 8167.2005.50038.x PMID: 15828875 3. Vijayaraman P, Bordachar P, Ellenbogen KA. The Continued Search for Physiological Pacing: Where Are We Now? J Am Coll Cardiol. 2017;69(25):3099-114. DOI: 10.1016/j.jacc.2017.05.005 PMID: 28641799 4. Boriani G, Pieragnoli P, Botto GL, Puererfellner H, Mont L, Ziacchi M, et al. Effect of PR interval and pacing mode on persistent atrial fibrillation incidence in dual chamber pacemaker patients: a sub-study of the international randomized MINERVA trial. Europace. 2019;21(4):636-44. DOI: 10.1093/europace/euy286 PMID: 30649270 5. Curtis AB, Worley SJ, Chung ES, Li P, Christman SA, St John Sutton M. Improvement in Clinical Outcomes With Biventricular Versus Right Ventricular Pacing: the BLOCK HF Study. J Am Coll Cardiol. 2016;67(18):2148-57. DOI: 10.1016/j.jacc.2016.02.051 PMID: 27151347 6. Beck H, Curtis AB. Right Ventricular Versus Biventricular Pacing for Heart Failure and Atrioventricular Block. Curr Heart Fail Rep. 2016;13(5):230-6. DOI: 10.1007/s11897-016-0299-3 PMID: 27553893 7. Sharma PS, Vijayaraman P, Ellenbogen KA. Permanent His bundle pacing: shaping the future of physiological ventricular pacing. Nat Rev Cardiol. 2020;17(1):22-36. DOI: 10.1038/s41569-019-0224-z PMID: 31249403 8. Vijayaraman P, Chung MK, Dandamudi G, Upadhyay GA, Krishnan K, Crossley G, et al.; ACC’s Electrophysiology Council. His bundle pacing. J Am Coll Cardiol. 2018;72(8):927-47. DOI: 10.1016/j.jacc.2018.06.017 PMID: 30115232 tricuspid valve annulus via contrast injection through the delivery sheath enabled prompt identification of the target zone for His bundle area (11,21). Secondly, after the identification of the anatomical landmark, target- ing His potential was mainly electrogram-guided, thus reducing fluoroscopy time (22). Thirdly, three-dimen- sional electro-anatomical mapping system was used in few cases, including in a small child (23), to facilitate the procedure and reduce the fluoroscopy time (24). Finally, further reduction was achieved with opera- tors’ experience as fluoroscopy times were significantly shorter in the second period of the procedures. 4.1 Clinical implications Our initial experience indicates that HBP proce- dure is feasible and safe in various pacing indications. It can be readily learned in the hands of an experienced device specialist without previous exposure to the technique or electrophysiology procedures. There is a learning curve which not only affects procedure success rate but also the progressive reduction of fluoroscopy time and HBP capture threshold. The challenges with rising thresholds require close monitoring during the implementation of this pacing method. Still, current limitations of HBP compared to standard RV pacing might also reflect the early stage of new technology. Therefore, improvement of delivery tools, leads, battery capacity, implantation technique, and further random- ized clinical trials with long-term follow-up are needed to provide the grounds for wider clinical adoption of this promising physiological pacing technique. 4.2 Study limitations The retrospective design of the study and a low num- ber of patients limits the strength of our findings. Only mid-term follow-up may underestimate the concern of unpredictable increase in HBP thresholds, loss of HB capture, and lead interventions. We did not include any follow-up data on ejection fraction or clinical outcomes since this was beyond the scope of the present study that mainly focused on crucial procedure-related pa- rameters that are important for the implementation of a new pacing strategy in routine clinical practice. 5 Conclusion Our initial experience indicates that HBP procedure is feasible and safe in various pacing indications. There is a learning curve which not only affects procedure suc- cess rate but also the progressive reduction of fluoros- copy time and HBP capture threshold. The challenges with rising thresholds require close monitoring during the implementation of this pacing method. Further ran- domized clinical trials with long-term follow-up are needed to provide the grounds for wider clinical adop- tion of this promising physiological pacing technique. Conflict of interest None declared. 595 ORIGINAL SCIENTIFIC ARTICLE His bundle pacing: initial Slovenian single-centre experience 9. Keene D, Arnold AD, Jastrzębski M, Burri H, Zweibel S, Crespo E, et al. His bundle pacing, learning curve, procedure characteristics, safety, and feasibility: insights from a large international observational study. J Cardiovasc Electrophysiol. 2019;30(10):1984-93. DOI: 10.1111/jce.14064 PMID: 31310403 10. Jastrzębski M, Moskal P, Bednarek A, Kiełbasa G, Czarnecka D. His- bundle pacing as a standard approach in patients with permanent atrial fibrillation and bradycardia. Pacing Clin Electrophysiol. 2018;41(11):1508- 12. DOI: 10.1111/pace.13490 PMID: 30192005 11. Gu M, Hu Y, Hua W, Niu H, Chen X, Cai M, et al. Visualization of tricuspid valve annulus for implantation of His bundle pacing in patients with symptomatic bradycardia. J Cardiovasc Electrophysiol. 2019;30(10):2164- 9. DOI: 10.1111/jce.14140 PMID: 31456266 12. Vijayaraman P, Dandamudi G. Anatomical approach to permanent His bundle pacing: optimizing His bundle capture. J Electrocardiol. 2016;49(5):649-57. DOI: 10.1016/j.jelectrocard.2016.07.003 PMID: 27457727 13. Vijayaraman P, Dandamudi G, Zanon F, Sharma PS, Tung R, Huang W, et al. Permanent His bundle pacing: Recommendations from a Multicenter His Bundle Pacing Collaborative Working Group for standardization of definitions, implant measurements, and follow-up. Heart Rhythm. 2018;15(3):460-8. DOI: 10.1016/j.hrthm.2017.10.039 PMID: 29107697 14. Zanon F, Ellenbogen KA, Dandamudi G, Sharma PS, Huang W, Lustgarten DL, et al. Permanent His-bundle pacing: a systematic literature review and meta-analysis. Europace. 2018;20(11):1819-26. DOI: 10.1093/ europace/euy058 PMID: 29701822 15. Su L, Wu S, Wang S, Wang Z, Xiao F, Shan P, et al. Pacing parameters and success rates of permanent His-bundle pacing in patients with narrow QRS: a single-centre experience. Europace. 2019;21(5):763-70. DOI: 10.1093/europace/euy281 PMID: 30561576 16. 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. DOI: 10.1016/j.hrthm.2014.10.021 PMID: 25446158 17. Bhatt AG, Musat DL, Milstein N, Pimienta J, Flynn L, Sichrovsky T, et al. The efficacy of His bundle pacing: lessons learned from implementation for the first time at an experienced electrophysiology center. JACC Clin Electrophysiol. 2018;4(11):1397-406. DOI: 10.1016/j.jacep.2018.07.013 PMID: 30466843 18. Vijayaraman P, Subzposh FA, Naperkowski A. Atrioventricular node ablation and His bundle pacing. Europace. 2017;19:iv10-6. DOI: 10.1093/ europace/eux263 PMID: 29220422 19. 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. DOI: 10.1016/j.jacep.2015.09.012 PMID: 29759411 20. Abdelrahman M, Subzposh FA, Beer D, Durr B, Naperkowski A, Sun H, et al. Clinical outcomes of his bundle pacing compared to right ventricular pacing: results from the HBP registry. J Am Coll Cardiol. 2018;71(20):2319- 30. DOI: 10.1016/j.jacc.2018.02.048 PMID: 29535066 21. Gu M, Niu H, Hu Y, Liu X, Zhang N, Cai M, et al. Permanent His Bundle Pacing Implantation Facilitated by Visualization of the Tricuspid Valve Annulus. Circ Arrhythm Electrophysiol. 2020;13(10):e008370. DOI: 10.1161/CIRCEP.120.008370 PMID: 32911981 22. Zanon F, Marcantoni L, Zuin M, Pastore G, Baracca E, Tiribello A, et al. Electrogram-only guided approach to His bundle pacing with minimal fluoroscopy: A single-center experience. J Cardiovasc Electrophysiol. 2020;31(4):805-12. DOI: 10.1111/jce.14366 PMID: 31976602 23. Žižek D, Štublar J, Weiss M, Jan M. His bundle pacing in a young child guided by electroanatomical mapping. Pacing Clin Electrophysiol. 2021;44(1):199-202. DOI: 10.1111/pace.14112 PMID: 33118169 24. Orlov MV, Koulouridis I, Monin AJ, Casavant D, Maslov M, Erez A, et al. Direct Visualization of the His Bundle Pacing Lead Placement by 3-Dimensional Electroanatomic Mapping: Technique, Anatomy, and Practical Considerations. Circ Arrhythm Electrophysiol. 2019;12(2):e006801. DOI: 10.1161/CIRCEP.118.006801 PMID: 30739495