Better responses by combination of left bundle branch area pacing and cardiac resynchronization therapy in heart failure patients

Better responses by combination of left bundle branch area pacing and cardiac resynchronization therapy in heart failure patients | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Better responses by combination of left bundle branch area pacing and cardiac resynchronization therapy in heart failure patients Jing Tan, Ting Liu, Xiaoyong Li, Yu Kang, Yang Zhang, Ke Feng, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8183133/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 15 You are reading this latest preprint version Abstract Background Left bundle branch-optimized CRT (LOT-CRT), combining left bundle branch area pacing (LBBAP) with coronary venous pacing, may enhance resynchronization.WE aimed to compare LOT-CRT efficacy versus conventional biventricular CRT (BiV-CRT) or LBBAP-only. Methods This prospective study included 70 patients (66 ± 9 years, 68.6% male) (30 LOT-CRT, 40 BiV-CRT). Apart from QRS duration (QRSd), interventricular mechanical delay (IVMD), peak strain dispersion (PSD), global longitudinal strain (GLS) and myocardial work (MW) as global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE) were assessed by speckle-tracking echocardiography. LOT-CRT responders were switched to LBBAP-only mode for one month. Results During 6-month follow-up, the LOT-CRT group had a more profound reduction in QRSd (42.0 [23.3, 74.5] vs. 17.0 [16.3, 23.8]ms, P < 0.001) and PSD (72.0 [43.0, 114.3] vs. 35.5 [4.3, 82.0]ms, P = 0.001). Similar improvement was achieved in left ventricular ejection fraction (LVEF) (16.5 [3.8, 24.0] vs. 15.5 [5.3, 20.8]%) and GLS (-4.5 [-6.0, -3.0] vs. -3 [-6.0, -1.3]%) but the LOT-CRT group displayed better increase in GWE (24.0 [11.0, 29.3] vs. 10.0 [6.3, 14.8] %, P < 0.001). Both echocardiographic and clinical responses were achieved in 66.7% patients receiving LOT-CRT and 72.5% receiving BiV-CRT (P = 0.598). After switching to LBBAP, LOT-CRT responders (n = 20) showed QRSd widening (131.5 ± 26.4 vs. 142.2 ± 29.4ms, P < 0.001) accompanied by worsening LVEF (55.6 ± 7.7 vs 51.1 ± 7.7%, P = 0.002) and GLS (-10.9 ± 2.8 vs. -10.0 ± 2.3%, P = 0.006). Conclusions LOT-CRT represented as a viable alternative to BiV-CRT with superior intraventricular resynchronization, whereas LBBAP alone failed to maintain the benefits in cardiac synchrony and function of LOT-CRT. Trial registration: This study was registered with the Chinese Clinical Trial Registry (ChiCTR) at http://www.chictr.org.cn/ (registration number: ChiCTR2500110771). cardiac resynchronization therapy heart failure left bundle branch pacing intraventricular dyssynchrony Figures Figure 1 Figure 2 Figure 3 Introduction Cardiac resynchronization therapy (CRT) via biventricular pacing (BiV-CRT) has long been promoted as an effective therapy for heart failure (HF) with reduced ejection fraction (HFrEF) and conduction disturbances [ 1 ][ 2 ][ 3 ] . It can correct electromechanical dyssynchrony of the failing heart and has been proved to not only improve quality of life and exercise capacity but also reduce HF hospitalization and all-cause mortality [ 4 ][ 5 ] . However, even though patients are strictly selected according to current guidelines, nearly one third of them would be non-responders in which nonphysiological epicardial stimulation by conventional BiV-CRT could be one reason [ 6 ] . First applied in patients with HFrEF and left bundle branch block (LBBB), left bundle branch area pacing (LBBAP) is a novel pacing modality of which the electrical activation and conduction sequence is more physiological [ 7 ] . A few studies have shown its superiority to BiV-CRT in achieving a narrower QRS duration (QRSd) [ 8 ] with shorter implant time and lower pacing threshold [ 9 ][ 10 ] . Nevertheless, its inability in restoring physiological activation of the left ventricular (LV) lateral wall in patients with distal conduction delay and the difficulty in differentiating left bundle branch capture from LV septal capture are two main limitations of the technique [ 11 ] . Therefore, left bundle branch-optimized cardiac resynchronization therapy (LOT-CRT) was suggested to be a better solution, which could be achieved by replacing the RV lead with LBBAP for BiV-CRT or adding a LV coronary venous lead to LBBAP [ 11 ][ 12 ] . Due to very limited studies that demonstrated the feasibility and efficacy of this novel technique, the aim of our study was to compare LOT-CRT head-to-head to BiV-CRT and LBBAP in CRT candidates. Methods Study population and design This was a prospective cohort study that enrolled a consecutive series of patients at a tertiary referral hospital from March 2020 to March 2022, who met the following inclusion criteria: (1) New York Heart Association class II to IV HF with a LV ejection fraction (LVEF) ≤ 35% after at least 3 months of optimal medication therapy; (2) QRSd \(\:\ge\:\) 120ms. Patients who had advanced malignancy, a life expectancy less than 6 months, unwillingness to participate in the study, or poor image quality of echocardiography were excluded. Written informed consent was obtained from all participants, and this study was approved by the ethics committee of the hospital and registered with the Chinese Clinical Trial Registry (ChiCTR) at http://www.chictr.org.cn/ (registration number: ChiCTR2500110771). Procedure of implantation The decision for either LOT-CRT or traditional BiV-CRT was made by the individual implantation doctor according to the condition of each individual patient. Namely, all patients who consented to CRT-D implantation were assigned to BiV-CRT, since the Medtronic special 3830 lead (designed for left bundle branch capture) could not serve as a defibrillation electrode. All patients with atrial fibrillation/flutter (AF) were given LOT-CRT. BiV-CRT implantation was performed in accordance with established clinical guidelines, utilizing commercially available pacing leads. With a standard right atrial (RA) lead positioned at auricula dextra to maintain constant atrial rate, the right ventricular (RV) lead was systematically placed at the ventricular mid-septum equipped with defibrillation capability if needed, while the LV pacing lead was deployed through the posterolateral or lateral branches of the coronary sinus. In LOT-CRT, LBBAP was firstly performed according to the established method described elsewhere [ 13 ] . In brief, LBBAP was implemented through the insertion of a pre-selected Secure lead (model 3830, Medtronic Inc; Minneapolis, MN) equipped with a C315 delivery sheath (Medtronic Inc; Minneapolis, MN) into the His bundle region, facilitated by the assistance of an electrophysiology recording system. Subsequently, the lead was positioned approximately 1.5 to 2 centimeters distal to the tricuspid annulus, situated between the His bundle and the apex of the right ventricle at the right anterior oblique 30°. The lead was then securely anchored and deeply screwed into the interventricular septum with clockwise rotations until the paced QRS morphology in lead V1 displayed Qr or QR pattern. Successful LBBP capture was concluded with a paced right bundle branch block (RBBB) morphology in lead V1, accompanied by at least one of the following critria: (1) an abrupt shortening of V6RWPT by ≥ 10 ms during lead advancement with subsequent stabilization at low output or paced V6RWPT ≤ 80 ms; (2) transition from nonselective to selective LBBP; (3) V6–V1 interpeak interval exceeding 44 ms. LVSP was diagnosed by the presence of a paced RBBB pattern in lead V1 in the absence of all the aforementioned criteria. The LV pacing lead was placed in posterolateral or lateral coronary sinus branch same as in BiV-CRT, adjusting to the anatomical location that exhibited maximal QLV. For patients without AF, another lead was placed at RA port to sense atrial depolarization and triggering synchronized ventricular pacing (Lead configuration: LBBAP lead + LV lead + RA lead). For patients with persistent AF, considering ineffectiveness in atrial pacing, the lead was implanted at RV port for biventricular synchronous contraction (Lead configuration: LBBAP lead + LV lead + RV lead). If left bundle branch could not be successfully captured after five attempts of lead positioning, BiV-CRT was performed as an alternative option (Fig. 1 ). ECG-guided interventricular delay optimization was performed to minimize QRSd and AV interval was programmed to the shortest value (25–30ms).. Data acquisition Patient characteristics including age, sex, blood pressure (BP), heart rate (HR), body surface area (BSA), and comorbidities were recorded at baseline. Electrocardiographic (ECG) parameters, echocardiographic parameters, B-type natriuretic peptide (BNP) level, New York heart association (NYHA) functional class and distance of 6-minute walk test distance (6-MWT) were collected before the operation and at 3-day and 6-month follow-up. QRSd was calculated as the mean duration of the three widest QRS complexes on lead II, V1 or V2. V6 R-wave peak time (V6RWPT), defined as the interval from QRS onset to the R-wave peak in lead V6, was assessed to confirm left bundle branch capture and to exclude lead microdislodgement post-implantation. Routine transthoracic echocardiography was performed using commercial Vivid E95 scanners (GE 12 Vingmed Ultrasound AS, Horten Norway) equipped with a M5Sc probe. Prior to each echocardiographic assessment, brachial artery BP measurements were acquired for the purpose of analyzing myocardial work (MW). Images encompassing parasternal long-axis view, apical three-chamber view, apical four-chamber view, and apical two-chamber view were captured over 3 consecutive cardiac cycles for sinus rhythm and 5 or more cycles for AF at a frame rate of 40–70 frames per second which were offline analyzed utilizing EchoPAC software (version 204, GE Vingmed). The left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV) and left ventricular ejection fraction (LVEF) were measured using the biplane Simpson’s method. Interventricular mechanical dyssynchrony was expressed by interventricular mechanical delay (IVMD) as the difference between the pre-ejection intervals from QRS onset to the beginning of ventricular ejection at the pulmonary and aortic valve levels using pulsed-wave Doppler. Two-dimensional speckle tracking echocardiography (2D-STE) was utilized to assess LV global longitudinal strain (GLS) and peak strain dispersion (PSD). PSD was employed as a quantitative measure to evaluate LV intraventricular synchrony. The LV pressure-strain loop and MW indices were automatically produced by inputting non-invasive BP, including global work index (GWI), global constructive work (GCW), global wasted work (GWW) and global work efficiency (GWE). All echocardiographic online scans and subsequent offline analyses were conducted by a single operator who was unaware of the study group assignment. All parameters were measured across 3 consecutive cardiac cycles for patients in sinus rhythm and 5 cycles for AF patients, followed by calculation of the mean values. At 6-month follow up, echocardiographic response was defined as a ≥ 5% increase in LVEF and clinical response was defined as at least 1 grade improvement in NYHA functional class. LOT-CRT switched to LBBAP Mode Those patients in the LOT-CRT group who showed both echocardiographic response and clinical response at 6-month follow up were included in the second phase as the only LBBAP period. In patients with AF, the RV lead and the LV lead were both programmed ‘OFF’, leaving only the LBBAP lead on. In patients with sinus rhythm, the LV lead was turned off, leaving the RA and LBBAP lead to work. Electrocardiography and echocardiography were performed 1 month later to assess the change in cardiac systolic synchrony and LV function. Statistical analysis Values are expressed as frequencies and percentages for categorical variables and as mean ± SD for continuous variables. For continuous variables, differences between the LOT-CRT group and BiV-CRT group were assessed using Student’s t-test and Mann-Whitney test, or χ2 test and Fisher exact test when appropriate. Paired data were compared using t-test if normally distributed or Mann-Whitney test if non-parametric. A P value of < 0.05 was considered significant. Statistical analysis was performed using SPSS version 27.0 (SPSS, Chicago, Illinois). Intra- and inter-observer variability Intraobserver and interobserver variability were evaluated through intraclass correlation coefficient (ICC) analysis complemented by standard error of measurement (SEM) calculations. To assess intraobserver consistency, a randomly selected subset of 15 measurements underwent blinded reanalysis by the original observer following a two-week washout period. The ICC values of intraobserver reliability reached 0.925 (P < 0.001) for GLS and 0.914 (P < 0.001) for PSD, establishing excellent measurement consistency. Interobserver variability was assessed through independent measurements conducted by a second blinded observer using the identical image cohort. The interobserver analysis also revealed comparably strong reliability, with ICC values of 0.931 (P < 0.001) for GLS and 0.894 (P < 0.001) for PSD. Results Baseline characteristics A total of 70 patients were included in the study (68.6% male, 66 ± 9 years). LOT-CRT was attempted in 33 patients primarily but 3 of them were transferred to the BiV-CRT group due to unfavorable capture of left bundle branch (Fig. 2). Eventually, 30 patients had LOT-CRT and 40 had BiV-CRT. The success rate was 90.9% for LOT-CRT. Baseline characteristics are summarized in Table 1. Two groups had comparable age, gender, BNP level, NYHA functional class and 6-MWT distance (all P > 0.05). LBBB was present in 20 patients (66.7%) in the LOT-CRT group and 19 patients (47.5%) in the BiV-CRT group (P = 0.110). Table 1 Baseline Patients Characteristics Characteristic LOT-CRT (n = 30) BiV-CRT (n = 40) P value Age 64.4 ± 9.5 66.5 ± 9.4 0.369 Male 21 (70.0%) 27 (67.5%) 0.517 SBP (mmHg) 104.3 ± 7.7 102.7 ± 7.8 0.396 DBP (mmHg) 68.5 ± 6.7 68.7 ± 4.5 0.856 BSA (m 2 ) 1.65 ± 0.17 1.58 ± 0.14 0.067 QRSd 0.364 120-129ms 2 (6.7%) 7 (17.5%) 130-150ms 6 (20.0%) 6 (15.0%) > 150ms 22 (73.3%) 27 (67.5%) Medical history LBBB 20 (66.7%) 19 (47.5%) 0.110 IVCD 10 (33.3%) 21 (52.5%) 0.110 Atrial fibrillation 13 (43.3%) 0 < 0.001 Ischemic cardiomyopathy 6 (20.0%) 9 (22.5%) 0.520 Diabetes mellitus 7 (23.3%) 8 (20.0%) 0.775 Hypertension 9 (30.0%) 11 (27.5%) 0.573 Chronic kidney disease 7 (23.3%) 9 (22.5%) 0.578 Clinical assessment BNP (pg/L) 668.8 ± 547.5 676.5 ± 504.1 0.951 NYHA functional class 3.4 ± 0.6 3.45 ± 0.5 0.697 6-MWT (m) 226.0 ± 41.0 223.9 ± 46.9 0.842 Values are presented as mean±SD or n (%) . BiV−CRT, biventricular pacing cardiac resynchronization therapy; BNP, B−type natriuretic peptide; BSA, body surface area; DBP, diastolic blood pressure; IVCD, intraventricular conduction delay; LBBB, left bundle branch block; LOT−CRT, left bundle branch−optimized cardiac resynchronization therapy; NYHA, New York Heart Association; QRSd, QRS duration; SBP, systolic blood pressure; and 6−MWT, 6−minute walk test . Maintenance of LBBAP In patients receiving LOT-CRT, the V6RWPT significantly decreased after lead implantation and maintained stable from 3 days to 6 months (75.2 ± 7.9 vs. 54.9 ± 6.0 vs. 54.3 ± 5.7, P < 0.001). None of the patients exhibited an increase in V6RWPT of 10 ms or more at 6 months compared to 3 days. Systolic synchrony At baseline, no significant difference was found in QRSd and IVMD between the LOT-CRT and the BiV-CRT group, while the LOT-CRT group had higher PSD and PSD% (Table 2). After implantation, the LOT-CRT group showed abrupt decrease in QRSd at 3-day follow-up and tended to be stable afterwards, yet the BiV-CRT group showed gradual shortening of QRSd. The absolute reduction of QRSd was significantly more profound in the LOT-CRT group which had an evidently narrower QRSd at 3-day and 6-month follow-up. Similar acute and further shortening of IMVD was observed in the two groups with no intergroup difference at 3-day and 6-month follow-up (Table 2). Both groups exhibited significantly decreased PSD shortly after the procedure with a further decrease at 6-month follow-up, but the absolute change of PSD was significantly higher in the LOT-CRT group. Table 2 Electrical and mechanical synchrony Parameters Group Baseline 3-Day 6-Month P value 3-day vs. Baseline 6-month vs. Baseline 3-day vs. 6-month QRSd (ms) LOT-CRT 173.5 ± 26.7 134.4 ± 28.3 △ 133.9 ± 25.3 △ < 0.001 < 0.001 0.888 BiV-CRT 168.7 ± 30.7 152.0 ± 27.5 149.5 ± 29.3 < 0.001 < 0.001 0.007 IVMD (ms) LOT-CRT 47.5 ± 17.3 24.6 ± 10.8 15.5 ± 9.7 < 0.001 < 0.001 0.005 BiV-CRT 45.5 ± 15.8 22.5 ± 10.8 13.8 ± 8.0 < 0.001 < 0.001 < 0.001 PSD (ms) LOT-CRT 172.5 ± 60.0 △ 141.2 ± 43.6 89.2 ± 39.9 0.005 < 0.001 < 0.001 BiV-CRT 141.3 ± 42.3 123.0 ± 31.8 102.7 ± 55.1 0.011 < 0.001 0.004 △P<0.05 vs. BiV−CRT group; ★Change refers to change of parameters from baseline to 6 months after implantation . IMVD, interventricular mechanical delay; PSD, peak strain dispersion; and other abbreviations as in Table 1 . LV response After implantation, both groups exhibited an equivalent immediate reduction in LVESV and LVEDV at 3-day follow-up, with a further decrease in both LVESV and LVEDV observed at 6-month follow-up. Although LVEDD did not decrease significantly from baseline at 3-day in the two groups, noticeable reduction was documented after 6 months. No statistical difference was reported between two groups from baseline to 6-month follow-up (Table 3). Table 3 LV reverse remodeling and improvement of systolic function Parameters Group Baseline 3 Days 6 Months P value 3-day vs. Baseline 6-month vs. Baseline 3-day vs. 6-month LVEDD (mm) LOT-CRT 66.6 ± 9.0 65.3 ± 9.2 57.7 ± 11.4 0.051 < 0.001 < 0.001 BiV-CRT 67.2 ± 6.7 67.3 ± 6.7 58.7 ± 9.1 0.061 < 0.001 < 0.001 LVEDV (mL) LOT-CRT 234.7 ± 76.2 216.2 ± 76.3 174.7 ± 80.8 < 0.001 < 0.001 < 0.001 BiV-CRT 235.1 ± 54.3 221.3 ± 47.8 177.6 ± 67.2 < 0.001 < 0.001 < 0.001 LVESV (mL) LOT-CRT 164.6 ± 64.5 143.1 ± 62.9 101.7 ± 66.6 < 0.001 < 0.001 < 0.001 BiV-CRT 166.1 ± 44.7 150.2 ± 38.5 104.9 ± 57.8 0.003 < 0.001 < 0.001 LVEF (%) LOT-CRT 30.9 ± 3.9 32.7 ± 5.0 46.6 ± 13.1 < 0.001 < 0.001 < 0.001 BiV-CRT 29.0 ± 4.1 31.0 ± 3.8 43.9 ± 10.4 < 0.001 < 0.001 < 0.001 GLS (%) LOT-CRT -6.3 ± 2.2 -7.5 ± 2.9 -10.8 ± 3.0 < 0.001 < 0.001 < 0.001 BiV-CRT -7.7 ± 3.1 -8.4 ± 3.4 -10.5 ± 4.0 0.012 < 0.001 < 0.001 GWI (mmHg%) LOT-CRT 458.3 ± 222.2 579.9 ± 303.2 791.0 ± 292.3 0.002 < 0.001 < 0.001 BiV-CRT 516.5 ± 308.9 640.6 ± 334.2 867.2 ± 390.6 0.004 < 0.001 < 0.001 GCW (mmHg%) LOT-CRT 834.7 ± 283.0 963.1 ± 311.8 1126.7 ± 344.9 0.004 < 0.001 0.003 BiV-CRT 849.8 ± 325.4 984.4 ± 320.9 1242.1 ± 412.5 < 0.001 < 0.001 < 0.001 GWW (mmHg%) LOT-CRT 413.2 ± 131.9 △ 352.0 ± 110.0 262.7 ± 89.5 0.041 < 0.001 0.002 BiV-CRT 350.2 ± 164.6 301.8 ± 130.7 257.2 ± 134.1 0.090 < 0.001 0.003 GWE (%) LOT-CRT 63.9 ± 10.8 △ 66.0 ± 10.3 △ 84.8 ± 7.7 0.186 < 0.001 < 0.001 BiV-CRT 69.2 ± 10.6 70.9 ± 9.3 80.8 ± 10.0 0.172 < 0.001 < 0.001 △P<0.05 vs. BiV−CRT group . GCW, global constructive work; GLS, global longitudinal strain; GWE, global work efficiency; GWI, global work index; GWW global wasted work; LVEDD, left ventricular end−diastolic diameter; LVEDV, left ventricular end−diastolic volume; LVEF, left ventricular ejection fraction; LVESV, left ventricular end−systolic volume; and other abbreviations as in Table 1 . Both groups demonstrated comparable improvements in LVEF and GLS at 3 days post-implantation, with further significant gains sustained over 6 months. From baseline to 6-month follow-up, consistent improvements were observed for LVEF (16.5 [3.8, 24.0] vs. 15.5 [5.3, 20.8]; P = 0.565) and GLS (-4.5 [-6.0, -3.0] vs. -3.0 [-6.0, -1.3]; P = 0.096). Similar trends towards better GWI, GCW and GWE with progressive reduction of GWW were reported in both groups in the following 6 months after implantation (Table 3). At baseline, the LOT-CRT group demonstrated significantly higher GWW and lower GWE compared to the BiV-CRT group. However, these differences were no longer statistically significant at the 6-month follow-up (Table 3), indicating a substantially greater improvement in GWE from baseline to 6 months in the LOT-CRT group (21.0 ± 10.4% vs. 11.6 ± 8.9%, P < 0.001). Echocardiographic response rate did not differ significantly between the LOT-CRT group and the BiV-CRT group (76.7% vs. 77.5%, P = 0.935). Clinical response The trend towards lower BNP levels (LOT-CRT: 668.8 ± 547.5 vs. 359.9 ± 277.6, P < 0.001; BiV-CRT: 676.5 ± 504.1 vs. 351.2 ± 250.8, P < 0.001) and NYHA functional class (3.4 ± 0.6 vs. 2.0 ± 1.0, P < 0.001; 3.5 ± 0.5 vs. 2.0 ± 1.0, P < 0.001) as well as longer distance of 6-MWT (226.0 ± 41.0 vs. 356.8 ± 108.0, P < 0.001; 223.9 ± 46.9 vs. 320.8 ± 68.7, P < 0.001) reached statistical significance at 6-month follow-up compared with baseline in both groups. Clinical performance was not statistically different between the two groups from baseline to 6 months. A higher proportion of patients in the LOT-CRT group achieved improvement in NYHA functional class ≥ 1 (86.7% vs. 75.0%, P = 0.227), although it did not reach a statistical significance. BiV-CRT versus LOT-CRT without AF After excluding patients with AF (N = 17), the LOT-CRT group consistently demonstrated significantly greater improvements in QRSd (36.8 ± 20.7ms, P < 0.001 vs. BiV-CRT), PSD (84.3 ± 47.2ms, P = 0.005 vs. BiV-CRT; Supplementary table 1) and GWE (21.7 ± 10.3%, P < 0.001 vs. BiV-CRT; Supplementary table 2) at 6-month follow-up. Changes in only LBBAP mode Compared to the BiV-CRT group, the LOT-CRT group demonstrated a numerically higher rate of achieving either echocardiographic or clinical response (93.3% vs. 80.0%; P = 0.218) while the proportion achieving both responses was 66.7% (20/30) with LOT-CRT and 72.5% (29/40) with BiV-CRT (P = 0.598). The 20 responders achieving both responses in the LOT-CRT group were switched to LBBAP mode. One month following the transition, all patients reported V6RWPT < 75ms (58.2 ± 8.4) and only one patient (5%) had over 10ms increase compared to 6 months after LOT-CRT. A notable widening of the QRS wave was observed (Fig. 3) with a prolongation in PSD. Furthermore, a significant enlargement of both LVEDD and LVESD was recorded, accompanied by a marked decrease in LVEF and the absolute value of GLS (Fig. 3). When compared to the 29 responders in the BiV-CRT group, the patients in LBBAP mode had significantly higher PSD and more impaired GLS (Fig. 3). Discussion This prospective study revealed three key findings: 1) LOT-CRT showed superior electrical and mechanical resynchronization compared to BiV-CRT; 2) both LOT-CRT and BiV-CRT reached equivalent echocardiographic and clinical improvement at 6 months; 3) LBBAP alone was less effective than LOT-CRT in improving systolic synchrony and LV function in HF patients indicated for CRT. Superiority of LOT-CRT in restoring intraventricular synchronicity Consistent with previous studies [ 11 ][ 14 ][ 15 ] , LOT-CRT achieved greater QRSd reduction than BiV-CRT. However, although QRSd has been introduced as a possible predictor for response to CRT [ 16 ][ 17 ] , there is no direct correlation between QRSd and mechanical dyssynchrony [ 18 ] , the latter of which remains a critical determinant of CRT responses [ 19 ][ 20 ] . A more pronounced reduction in PSD but not in IVMD by LOT-CRT suggested that a better resynchronization observed with LOT-CRT should stem primarily from its ability to ameliorate LV intraventricular dyssynchrony. Peix et al. reported that improvements in PSD (assessed via gated-SPECT imaging) correlated with better patient outcomes, underscoring the importance of LV intraventricular synchronization [ 21 ] . Furthermore, Maffessanti et al. used invasive electromechanical mapping to show that prolonged total LV activation time (TLVAT), a marker of impaired conduction within LV, predicted suboptimal reverse remodeling after BiV-CRT [ 22 ] . Both studies emphasized the importance of correcting intraventricular dyssynchrony. Non-inferiority of LOT-CRT in reaching CRT response Both LOT-CRT and BiV-CRT comparably facilitated LV reverse remodeling and functional recovery, sustained at 6-month follow-up. In a recent single-arm study conducted by Jastrzębski et al., LOT-CRT and BiV-CRT similarly enhanced hemodynamics immediately following implantation, as assessed invasively via LV pressure maximal first derivative (LV dP/dt max ) [ 15 ] . However, acute improvements in dP/dt max were not correlated with either long-term response or clinical outcomes. Likely due to relatively high proportion of female and non-ischemic cardiomyopathy patients, our study displayed favorable and comparable echocardiographic response between LOT-CRT and BiV-CRT at mid-term follow-up, slightly exceeding the average response rate of CRT among all CRT recipients observed in prior large-scale randomized controlled clinical trials (approximately 70%). In contrast, two recent observational studies demonstrated superior echocardiographic response rates with LOT-CRT versus BiV-CRT [ 14 ][ 23 ] . This discrepancy may stem from differences in patient populations between the studies (since those investigations included subjects with intraventricular conduction delay [IVCD]), or because the current study’s limited sample size may have rendered it underpowered to detect potential superiority of LOT-CRT in LV reverse remodeling and LV functional recovery. Interestingly, our study reinforced their findings by validating the heightened efficacy of LOT-CRT in correcting intraventricular dyssynchrony. Both LOT-CRT and BiV-CRT presented ideal clinical benefit for patients including reducuction in BNP levels, improvement in NYHA functional class and enhancement in 6-MWT distance on the basis of guideline-directed medical therapy [ 24 ] . The clinical response rate of LOT-CRT in our study which was in line with previous prospective observational studies [ 12 ][ 25 ] . Inadequacy of LBBAP in CRT candidates Despite procedural advantages (cost, radiation exposure), LBBAP alone failed to match LOT-CRT/ in QRSd reduction and restoration of cardiac structure/ function. Similarly, Jastrzębski et al. also observed that LBBAP offered less hemodynamic benefit than LOT-CRT [ 15 ] , underscoring concerns about its clinical utility for CRT. After comparing the status of the 20 patients in LBBAP mode with that of the 29 responders in the BiV-CRT group, we identified a longer PSD and a lower absolute value of GLS in the former group. The suboptimal efficacy of LBBAP in CRT candidates may be attributed to its limited ability to correct the delayed activation of the LV lateral wall, which is likely caused by factors other than the damage of left bundle branch, such as myocardial fibrosis, electrical uncoupling, functional conduction block, and conduction delays within the cardiac conduction system [ 11 ][ 26 ] . Therefore, although it has been advocated by some studies as a viable alternative for CRT candidates [ 9 ][ 27 ][ 28 ] , the results of our study continued to corroborate the necessity of pacing both ventricles. Limitations This was a cohort study that limited to its non-randomized design with, because stability of patients during the procedure was given the first priority of decision-making. Relatively small sample size, short follow-up and inadequate hard endpoints in the pilot study counted as other limitations, which would hopefully be overcome in future clinical studies. Conclusions LOT-CRT is a feasible alternative to BiV-CRT, offering superior electrical/mechanical resynchronization, particularly in correcting intraventricular dyssynchrony. LBBAP alone remains suboptimal for CRT candidates compared to LOT-CRT, necessitating biventricular pacing for comprehensive resynchronization. Declarations Ethics approval and consent to participate The study study was performed according to the principles of the Declaration of Helsinki and was approved by the Ethics Committee of Guizhou Provincial People’s Hospital (No. 202123). All patients provided written informed consent. Consent for publication Not applicable. Availability of data and materials The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Competing interests Not applicable. Funding The study was supported financially by grants from “0 to 1” Innovative research project of Sichuan University (Grant number 2023SCUH0063) and Key Advantageous Discipline Construction Project of Guizhou Provincial Health Commission in 2023 (Grant number LC[2022]011). Authors' contributions Jing Tan: Conceptualization, Writing – original draft, Formal analysis, Data curation. Ting Liu: Methodology, Investigation, Project administration, Validation. Xiaoyong Li: Software, Visualization, Resources. Yu Kang: Supervision, Writing – review & editing. Yang Zhang: Investigation, Data collection. Ke Feng: Resources, Data collection. Zixuan Yang: Resources, Data collection. Yujia Pan: Resources, Visualization. Xin Wei: Data interpretation. Jie Bu: Investigation, Software. Yaning Chen: Methodology. Qing Zhang: Supervision, Funding acquisition, Conceptualization. Sha Yu: Conceptualization, Funding acquisition, Project administration. Acknowledgments The author(s) have no acknowledgments to declare. References Bristow MR, Saxon LA, Boehmer J, et al. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med. 2004;350(21):2140–50. McDonagh TA, Metra M, Adamo M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure [published correction appears in. Eur Heart J. 2021;42(48):4901. Chung MK, Patton KK, Lau CP, et al. 2023 HRS/APHRS/LAHRS guideline on cardiac physiologic pacing for the avoidance and mitigation of heart failure. Heart Rhythm. 2023;20(9):e17–91. Moss AJ, Hall WJ, Cannom DS, et al. Cardiac-resynchronization therapy for the prevention of heart-failure events. N Engl J Med. 2009;361(14):1329–38. Cleland JG, Daubert JC, Erdmann E, et al. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med. 2005;352(15):1539–49. 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Cardiol Plus. 2024;9(1):6–8. Zhang D, Lang M, Prakash Earnest BS, Ali Abdou IEM. Application and Research of Left Bundle Branch-Optimized Cardiac Resynchronization Therapy in Ischemic Cardiomyopathy. Rev Cardiovasc Med. 2025;26(3):26240. Jastrzębski M, Kiełbasa G, Curila K, et al. Physiology-based electrocardiographic criteria for left bundle branch capture. Heart Rhythm. 2021;18(6):935–43. Vijayaraman P, Sharma PS, Cano Ó, et al. Comparison of Left Bundle Branch Area Pacing and Biventricular Pacing in Candidates for Resynchronization Therapy. J Am Coll Cardiol. 2023;82(3):228–41. Wang Y, Zhu H, Hou X, et al. Randomized Trial of Left Bundle Branch vs Biventricular Pacing for Cardiac Resynchronization Therapy. J Am Coll Cardiol. 2022;80(13):1205–16. Additional Declarations No competing interests reported. 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16:43:36","extension":"html","order_by":17,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":122920,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8183133/v1/d2d57f0d67f6126074770251.html"},{"id":98430042,"identity":"f0eb40e2-bcdc-4c5d-abde-bf340fc3e95e","added_by":"auto","created_at":"2025-12-17 16:44:40","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":728891,"visible":true,"origin":"","legend":"\u003cp\u003eFluoroscopic imaging of LOT-CRT and BiV-CRT lead implantation.\u003c/p\u003e\n\u003cp\u003eLead location of LOT-CRT in PA (A), RAO 30° (B), and LAO 30°(C) fluoroscopic views respectively for a patient with AF in the upper panel, lead location of LOT-CRT in PA (D), RAO 30° (E), and LAO 30° (F) fluoroscopic views respectively for a patient with SR in the middle panel and lead location of BiV-CRT in PA (G), RAO 30° (H), and LAO 30° (I) fluoroscopic views respectively. AF, atrial fibrillation; BiV-CRT, biventricular pacing cardiac resynchronization therapy; LAO, left anterior oblique; LOT-CRT, left bundle branch-optimized cardiac resynchronization therapy; PA, postero-anterior; RAO, right anterior oblique; SR, sinus rhythm.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8183133/v1/78b8d2217801828897a54f72.png"},{"id":98106710,"identity":"56b711cf-343b-477a-94fb-a223889f7e84","added_by":"auto","created_at":"2025-12-13 00:18:04","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":98173,"visible":true,"origin":"","legend":"\u003cp\u003eFlow chart of the study.\u003c/p\u003e\n\u003cp\u003eBiV-CRT, cardiac resynchronization therapy via biventricular pacing; CRT, cardiac resynchronization therapy; and LOT-CRT, left bundle branch pacing-optimized cardiac resynchronization therapy.\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8183133/v1/95a7eb670463bda996315f81.jpeg"},{"id":98431047,"identity":"e5ea6b89-d5f6-477e-8a21-93c8620d62d4","added_by":"auto","created_at":"2025-12-17 16:46:51","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":236281,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of synchronicity and LV function among three pacing modes in responders.\u003c/p\u003e\n\u003cp\u003eQRS duration (QRSd). (B) peak strain dispersion (PSD). (C) left ventricular end-diastolic diameter (LVEDD). (D) left ventricular end-systolic diameter (LVESD). (E) left ventricular ejection fraction (LVEF). (F) global longitudinal strain (GLS).\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-8183133/v1/086d2b90788d3773f568c861.png"},{"id":98444815,"identity":"1a8b0db6-625f-4d04-bf42-5bc380094694","added_by":"auto","created_at":"2025-12-17 17:17:40","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2054678,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8183133/v1/3137ea72-cb0b-4521-b048-26c9ce184ddc.pdf"},{"id":98106709,"identity":"b1280c6a-5c97-4c9c-8e21-6ea8a6334382","added_by":"auto","created_at":"2025-12-13 00:18:04","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":22081,"visible":true,"origin":"","legend":"","description":"","filename":"SUPPLEMENTARY.docx","url":"https://assets-eu.researchsquare.com/files/rs-8183133/v1/a04a9324b78e09b686471b5b.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Better responses by combination of left bundle branch area pacing and cardiac resynchronization therapy in heart failure patients","fulltext":[{"header":"Introduction","content":"\u003cp\u003eCardiac resynchronization therapy (CRT) via biventricular pacing (BiV-CRT) has long been promoted as an effective therapy for heart failure (HF) with reduced ejection fraction (HFrEF) and conduction disturbances\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e][\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e][\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. It can correct electromechanical dyssynchrony of the failing heart and has been proved to not only improve quality of life and exercise capacity but also reduce HF hospitalization and all-cause mortality \u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e][\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. However, even though patients are strictly selected according to current guidelines, nearly one third of them would be non-responders in which nonphysiological epicardial stimulation by conventional BiV-CRT could be one reason\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eFirst applied in patients with HFrEF and left bundle branch block (LBBB), left bundle branch area pacing (LBBAP) is a novel pacing modality of which the electrical activation and conduction sequence is more physiological\u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e. A few studies have shown its superiority to BiV-CRT in achieving a narrower QRS duration (QRSd) \u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e with shorter implant time and lower pacing threshold\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e][\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e. Nevertheless, its inability in restoring physiological activation of the left ventricular (LV) lateral wall in patients with distal conduction delay and the difficulty in differentiating left bundle branch capture from LV septal capture are two main limitations of the technique\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eTherefore, left bundle branch-optimized cardiac resynchronization therapy (LOT-CRT) was suggested to be a better solution, which could be achieved by replacing the RV lead with LBBAP for BiV-CRT or adding a LV coronary venous lead to LBBAP\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e][\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e. Due to very limited studies that demonstrated the feasibility and efficacy of this novel technique, the aim of our study was to compare LOT-CRT head-to-head to BiV-CRT and LBBAP in CRT candidates.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy population and design\u003c/h2\u003e\u003cp\u003eThis was a prospective cohort study that enrolled a consecutive series of patients at a tertiary referral hospital from March 2020 to March 2022, who met the following inclusion criteria: (1) New York Heart Association class II to IV HF with a LV ejection fraction (LVEF)\u0026thinsp;\u0026le;\u0026thinsp;35% after at least 3 months of optimal medication therapy; (2) QRSd \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\ge\\:\\)\u003c/span\u003e\u003c/span\u003e120ms. Patients who had advanced malignancy, a life expectancy less than 6 months, unwillingness to participate in the study, or poor image quality of echocardiography were excluded. Written informed consent was obtained from all participants, and this study was approved by the ethics committee of the hospital and registered with the Chinese Clinical Trial Registry (ChiCTR) at \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.chictr.org.cn/\u003c/span\u003e\u003cspan address=\"http://www.chictr.org.cn/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (registration number: ChiCTR2500110771).\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eProcedure of implantation\u003c/h3\u003e\n\u003cp\u003eThe decision for either LOT-CRT or traditional BiV-CRT was made by the individual implantation doctor according to the condition of each individual patient. Namely, all patients who consented to CRT-D implantation were assigned to BiV-CRT, since the Medtronic special 3830 lead (designed for left bundle branch capture) could not serve as a defibrillation electrode. All patients with atrial fibrillation/flutter (AF) were given LOT-CRT.\u003c/p\u003e\u003cp\u003e BiV-CRT implantation was performed in accordance with established clinical guidelines, utilizing commercially available pacing leads. With a standard right\u003c/p\u003e\u003cp\u003eatrial (RA) lead positioned at auricula dextra to maintain constant atrial rate, the right ventricular (RV) lead was systematically placed at the ventricular mid-septum equipped with defibrillation capability if needed, while the LV pacing lead was deployed through the posterolateral or lateral branches of the coronary sinus.\u003c/p\u003e\u003cp\u003eIn LOT-CRT, LBBAP was firstly performed according to the established method described elsewhere\u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e. In brief, LBBAP was implemented through the insertion of a pre-selected Secure lead (model 3830, Medtronic Inc; Minneapolis, MN) equipped with a C315 delivery sheath (Medtronic Inc; Minneapolis, MN) into the His bundle region, facilitated by the assistance of an electrophysiology recording system. Subsequently, the lead was positioned approximately 1.5 to 2 centimeters distal to the tricuspid annulus, situated between the His bundle and the apex of the right ventricle at the right anterior oblique 30\u0026deg;. The lead was then securely anchored and deeply screwed into the interventricular septum with clockwise rotations until the paced QRS morphology in lead V1 displayed Qr or QR pattern. Successful LBBP capture was concluded with a paced right bundle branch block (RBBB) morphology in lead V1, accompanied by at least one of the following critria: (1) an abrupt shortening of V6RWPT by \u0026ge;\u0026thinsp;10 ms during lead advancement with subsequent stabilization at low output or paced V6RWPT\u0026thinsp;\u0026le;\u0026thinsp;80 ms; (2) transition from nonselective to selective LBBP; (3) V6\u0026ndash;V1 interpeak interval exceeding 44 ms. LVSP was diagnosed by the presence of a paced RBBB pattern in lead V1 in the absence of all the aforementioned criteria. The LV pacing lead was placed in posterolateral or lateral coronary sinus branch same as in BiV-CRT, adjusting to the anatomical location that exhibited maximal QLV. For patients without AF, another lead was placed at RA port to sense atrial depolarization and triggering synchronized ventricular pacing (Lead configuration: LBBAP lead\u0026thinsp;+\u0026thinsp;LV lead\u0026thinsp;+\u0026thinsp;RA lead). For patients with persistent AF, considering ineffectiveness in atrial pacing, the lead was implanted at RV port for biventricular synchronous contraction (Lead configuration: LBBAP lead\u0026thinsp;+\u0026thinsp;LV lead\u0026thinsp;+\u0026thinsp;RV lead). If left bundle branch could not be successfully captured after five attempts of lead positioning, BiV-CRT was performed as an alternative option (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). ECG-guided interventricular delay optimization was performed to minimize QRSd and AV interval was programmed to the shortest value (25\u0026ndash;30ms)..\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\n\u003ch3\u003eData acquisition\u003c/h3\u003e\n\u003cp\u003ePatient characteristics including age, sex, blood pressure (BP), heart rate (HR), body surface area (BSA), and comorbidities were recorded at baseline. Electrocardiographic (ECG) parameters, echocardiographic parameters, B-type natriuretic peptide (BNP) level, New York heart association (NYHA) functional class and distance of 6-minute walk test distance (6-MWT) were collected before the operation and at 3-day and 6-month follow-up. QRSd was calculated as the mean duration of the three widest QRS complexes on lead II, V1 or V2. V6 R-wave peak time (V6RWPT), defined as the interval from QRS onset to the R-wave peak in lead V6, was assessed to confirm left bundle branch capture and to exclude lead microdislodgement post-implantation.\u003c/p\u003e\u003cp\u003eRoutine transthoracic echocardiography was performed using commercial Vivid E95 scanners (GE 12 Vingmed Ultrasound AS, Horten Norway) equipped with a M5Sc probe. Prior to each echocardiographic assessment, brachial artery BP measurements were acquired for the purpose of analyzing myocardial work (MW). Images encompassing parasternal long-axis view, apical three-chamber view, apical four-chamber view, and apical two-chamber view were captured over 3 consecutive cardiac cycles for sinus rhythm and 5 or more cycles for AF at a frame rate of 40\u0026ndash;70 frames per second which were offline analyzed utilizing EchoPAC software (version 204, GE Vingmed). The left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV) and left ventricular ejection fraction (LVEF) were measured using the biplane Simpson\u0026rsquo;s method. Interventricular mechanical dyssynchrony was expressed by interventricular mechanical delay (IVMD) as the difference between the pre-ejection intervals from QRS onset to the beginning of ventricular ejection at the pulmonary and aortic valve levels using pulsed-wave Doppler.\u003c/p\u003e\u003cp\u003eTwo-dimensional speckle tracking echocardiography (2D-STE) was utilized to assess LV global longitudinal strain (GLS) and peak strain dispersion (PSD). PSD was employed as a quantitative measure to evaluate LV intraventricular synchrony. The LV pressure-strain loop and MW indices were automatically produced by inputting non-invasive BP, including global work index (GWI), global constructive work (GCW), global wasted work (GWW) and global work efficiency (GWE).\u003c/p\u003e\u003cp\u003eAll echocardiographic online scans and subsequent offline analyses were conducted by a single operator who was unaware of the study group assignment. All parameters were measured across 3 consecutive cardiac cycles for patients in sinus rhythm and 5 cycles for AF patients, followed by calculation of the mean values.\u003c/p\u003e\u003cp\u003eAt 6-month follow up, echocardiographic response was defined as a\u0026thinsp;\u0026ge;\u0026thinsp;5% increase in LVEF and clinical response was defined as at least 1 grade improvement in NYHA functional class.\u003c/p\u003e\n\u003ch3\u003eLOT-CRT switched to LBBAP Mode\u003c/h3\u003e\n\u003cp\u003eThose patients in the LOT-CRT group who showed both echocardiographic response and clinical response at 6-month follow up were included in the second phase as the only LBBAP period. In patients with AF, the RV lead and the LV lead were both programmed \u0026lsquo;OFF\u0026rsquo;, leaving only the LBBAP lead on. In patients with sinus rhythm, the LV lead was turned off, leaving the RA and LBBAP lead to work. Electrocardiography and echocardiography were performed 1 month later to assess the change in cardiac systolic synchrony and LV function.\u003c/p\u003e\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eValues are expressed as frequencies and percentages for categorical variables and as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD for continuous variables. For continuous variables, differences between the LOT-CRT group and BiV-CRT group were assessed using Student\u0026rsquo;s t-test and Mann-Whitney test, or χ2 test and Fisher exact test when appropriate. Paired data were compared using t-test if normally distributed or Mann-Whitney test if non-parametric. A P value of \u0026lt;\u0026thinsp;0.05 was considered significant. Statistical analysis was performed using SPSS version 27.0 (SPSS, Chicago, Illinois).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eIntra- and inter-observer variability\u003c/h2\u003e\u003cp\u003eIntraobserver and interobserver variability were evaluated through intraclass correlation coefficient (ICC) analysis complemented by standard error of measurement (SEM) calculations. To assess intraobserver consistency, a randomly selected subset of 15 measurements underwent blinded reanalysis by the original observer following a two-week washout period. The ICC values of intraobserver reliability reached 0.925 (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) for GLS and 0.914 (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) for PSD, establishing excellent measurement consistency. Interobserver variability was assessed through independent measurements conducted by a second blinded observer using the identical image cohort. The interobserver analysis also revealed comparably strong reliability, with ICC values of 0.931 (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) for GLS and 0.894 (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) for PSD.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec10\"\u003e\n \u003ch2\u003eBaseline characteristics\u003c/h2\u003e\n \u003cp\u003eA total of 70 patients were included in the study (68.6% male, 66\u0026thinsp;\u0026plusmn;\u0026thinsp;9 years). LOT-CRT was attempted in 33 patients primarily but 3 of them were transferred to the BiV-CRT group due to unfavorable capture of left bundle branch (Fig.\u0026nbsp;2). Eventually, 30 patients had LOT-CRT and 40 had BiV-CRT. The success rate was 90.9% for LOT-CRT. Baseline characteristics are summarized in Table\u0026nbsp;1. Two groups had comparable age, gender, BNP level, NYHA functional class and 6-MWT distance (all P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). LBBB was present in 20 patients (66.7%) in the LOT-CRT group and 19 patients (47.5%) in the BiV-CRT group (P\u0026thinsp;=\u0026thinsp;0.110).\u003c/p\u003e\n \u003cdiv\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 1\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eBaseline Patients Characteristics\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCharacteristic\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eLOT-CRT\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;30)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eBiV-CRT\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;40)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e64.4\u0026thinsp;\u0026plusmn;\u0026thinsp;9.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e66.5\u0026thinsp;\u0026plusmn;\u0026thinsp;9.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.369\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21 (70.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27 (67.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.517\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSBP (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e104.3\u0026thinsp;\u0026plusmn;\u0026thinsp;7.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e102.7\u0026thinsp;\u0026plusmn;\u0026thinsp;7.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.396\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDBP (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e68.5\u0026thinsp;\u0026plusmn;\u0026thinsp;6.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e68.7\u0026thinsp;\u0026plusmn;\u0026thinsp;4.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.856\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBSA (m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.65\u0026thinsp;\u0026plusmn;\u0026thinsp;0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.58\u0026thinsp;\u0026plusmn;\u0026thinsp;0.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.067\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eQRSd\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.364\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e120-129ms\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (6.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7 (17.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e130-150ms\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (20.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (15.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;150ms\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22 (73.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27 (67.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedical history\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLBBB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20 (66.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19 (47.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.110\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIVCD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10 (33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21 (52.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.110\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAtrial fibrillation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13 (43.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIschemic cardiomyopathy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (20.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9 (22.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.520\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDiabetes mellitus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7 (23.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8 (20.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.775\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHypertension\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9 (30.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11 (27.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.573\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChronic kidney disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7 (23.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9 (22.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.578\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eClinical assessment\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBNP (pg/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e668.8\u0026thinsp;\u0026plusmn;\u0026thinsp;547.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e676.5\u0026thinsp;\u0026plusmn;\u0026thinsp;504.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.951\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNYHA functional class\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.45\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.697\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6-MWT (m)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e226.0\u0026thinsp;\u0026plusmn;\u0026thinsp;41.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e223.9\u0026thinsp;\u0026plusmn;\u0026thinsp;46.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.842\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\"\u003e\u003csup\u003eValues are presented as mean\u0026plusmn;SD or n (%)\u003c/sup\u003e.\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\"\u003e\u003csup\u003eBiV\u0026minus;CRT, biventricular pacing cardiac resynchronization therapy; BNP, B\u0026minus;type natriuretic peptide; BSA, body surface area; DBP, diastolic blood pressure; IVCD, intraventricular conduction delay; LBBB, left bundle branch block; LOT\u0026minus;CRT, left bundle branch\u0026minus;optimized cardiac resynchronization therapy; NYHA, New York Heart Association; QRSd, QRS duration; SBP, systolic blood pressure; and 6\u0026minus;MWT, 6\u0026minus;minute walk test\u003c/sup\u003e.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec11\"\u003e\n \u003ch2\u003eMaintenance of LBBAP\u003c/h2\u003e\n \u003cp\u003eIn patients receiving LOT-CRT, the V6RWPT significantly decreased after lead implantation and maintained stable from 3 days to 6 months (75.2\u0026thinsp;\u0026plusmn;\u0026thinsp;7.9 vs. 54.9\u0026thinsp;\u0026plusmn;\u0026thinsp;6.0 vs. 54.3\u0026thinsp;\u0026plusmn;\u0026thinsp;5.7, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). None of the patients exhibited an increase in V6RWPT of 10 ms or more at 6 months compared to 3 days.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec12\"\u003e\n \u003ch2\u003eSystolic synchrony\u003c/h2\u003e\n \u003cp\u003eAt baseline, no significant difference was found in QRSd and IVMD between the LOT-CRT and the BiV-CRT group, while the LOT-CRT group had higher PSD and PSD% (Table\u0026nbsp;2). After implantation, the LOT-CRT group showed abrupt decrease in QRSd at 3-day follow-up and tended to be stable afterwards, yet the BiV-CRT group showed gradual shortening of QRSd. The absolute reduction of QRSd was significantly more profound in the LOT-CRT group which had an evidently narrower QRSd at 3-day and 6-month follow-up. Similar acute and further shortening of IMVD was observed in the two groups with no intergroup difference at 3-day and 6-month follow-up (Table\u0026nbsp;2). Both groups exhibited significantly decreased PSD shortly after the procedure with a further decrease at 6-month follow-up, but the absolute change of PSD was significantly higher in the LOT-CRT group.\u003c/p\u003e\n \u003cdiv\u003e\n \u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 2\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eElectrical and mechanical synchrony\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eParameters\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eGroup\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eBaseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e3-Day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e6-Month\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"4\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3-day vs. Baseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6-month vs. Baseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3-day vs.\u003c/p\u003e\n \u003cp\u003e6-month\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eQRSd (ms)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLOT-CRT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e173.5\u0026thinsp;\u0026plusmn;\u0026thinsp;26.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e134.4\u0026thinsp;\u0026plusmn;\u0026thinsp;28.3\u003csup\u003e△\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e133.9\u0026thinsp;\u0026plusmn;\u0026thinsp;25.3\u003csup\u003e△\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.888\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBiV-CRT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e168.7\u0026thinsp;\u0026plusmn;\u0026thinsp;30.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e152.0\u0026thinsp;\u0026plusmn;\u0026thinsp;27.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e149.5\u0026thinsp;\u0026plusmn;\u0026thinsp;29.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.007\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eIVMD (ms)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLOT-CRT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e47.5\u0026thinsp;\u0026plusmn;\u0026thinsp;17.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24.6\u0026thinsp;\u0026plusmn;\u0026thinsp;10.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15.5\u0026thinsp;\u0026plusmn;\u0026thinsp;9.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.005\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBiV-CRT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e45.5\u0026thinsp;\u0026plusmn;\u0026thinsp;15.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22.5\u0026thinsp;\u0026plusmn;\u0026thinsp;10.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13.8\u0026thinsp;\u0026plusmn;\u0026thinsp;8.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003ePSD (ms)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLOT-CRT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e172.5\u0026thinsp;\u0026plusmn;\u0026thinsp;60.0\u003csup\u003e△\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e141.2\u0026thinsp;\u0026plusmn;\u0026thinsp;43.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e89.2\u0026thinsp;\u0026plusmn;\u0026thinsp;39.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.005\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBiV-CRT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e141.3\u0026thinsp;\u0026plusmn;\u0026thinsp;42.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e123.0\u0026thinsp;\u0026plusmn;\u0026thinsp;31.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e102.7\u0026thinsp;\u0026plusmn;\u0026thinsp;55.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.011\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.004\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"9\"\u003e\u003csup\u003e△P\u0026lt;0.05 vs. BiV\u0026minus;CRT group; ★Change refers to change of parameters from baseline to 6 months after implantation\u003c/sup\u003e.\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"9\"\u003e\u003csup\u003eIMVD, interventricular mechanical delay; PSD, peak strain dispersion; and other abbreviations as in Table 1\u003c/sup\u003e.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec13\"\u003e\n \u003ch2\u003eLV response\u003c/h2\u003e\n \u003cp\u003eAfter implantation, both groups exhibited an equivalent immediate reduction in LVESV and LVEDV at 3-day follow-up, with a further decrease in both LVESV and LVEDV observed at 6-month follow-up. Although LVEDD did not decrease significantly from baseline at 3-day in the two groups, noticeable reduction was documented after 6 months. No statistical difference was reported between two groups from baseline to 6-month follow-up (Table\u0026nbsp;3).\u003c/p\u003e\n \u003cdiv\u003e\n \u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 3\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eLV reverse remodeling and improvement of systolic function\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eParameters\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eGroup\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eBaseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e3 Days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e6 Months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3-day vs. Baseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6-month vs. Baseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3-day vs.\u003c/p\u003e\n \u003cp\u003e6-month\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eLVEDD (mm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLOT-CRT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e66.6\u0026thinsp;\u0026plusmn;\u0026thinsp;9.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e65.3\u0026thinsp;\u0026plusmn;\u0026thinsp;9.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e57.7\u0026thinsp;\u0026plusmn;\u0026thinsp;11.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.051\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBiV-CRT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e67.2\u0026thinsp;\u0026plusmn;\u0026thinsp;6.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e67.3\u0026thinsp;\u0026plusmn;\u0026thinsp;6.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e58.7\u0026thinsp;\u0026plusmn;\u0026thinsp;9.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.061\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eLVEDV (mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLOT-CRT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e234.7\u0026thinsp;\u0026plusmn;\u0026thinsp;76.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e216.2\u0026thinsp;\u0026plusmn;\u0026thinsp;76.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e174.7\u0026thinsp;\u0026plusmn;\u0026thinsp;80.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBiV-CRT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e235.1\u0026thinsp;\u0026plusmn;\u0026thinsp;54.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e221.3\u0026thinsp;\u0026plusmn;\u0026thinsp;47.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e177.6\u0026thinsp;\u0026plusmn;\u0026thinsp;67.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eLVESV (mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLOT-CRT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e164.6\u0026thinsp;\u0026plusmn;\u0026thinsp;64.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e143.1\u0026thinsp;\u0026plusmn;\u0026thinsp;62.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e101.7\u0026thinsp;\u0026plusmn;\u0026thinsp;66.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBiV-CRT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e166.1\u0026thinsp;\u0026plusmn;\u0026thinsp;44.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e150.2\u0026thinsp;\u0026plusmn;\u0026thinsp;38.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e104.9\u0026thinsp;\u0026plusmn;\u0026thinsp;57.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eLVEF (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLOT-CRT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e32.7\u0026thinsp;\u0026plusmn;\u0026thinsp;5.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e46.6\u0026thinsp;\u0026plusmn;\u0026thinsp;13.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBiV-CRT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29.0\u0026thinsp;\u0026plusmn;\u0026thinsp;4.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31.0\u0026thinsp;\u0026plusmn;\u0026thinsp;3.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e43.9\u0026thinsp;\u0026plusmn;\u0026thinsp;10.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eGLS (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLOT-CRT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-6.3\u0026thinsp;\u0026plusmn;\u0026thinsp;2.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-7.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-10.8\u0026thinsp;\u0026plusmn;\u0026thinsp;3.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBiV-CRT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-7.7\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-8.4\u0026thinsp;\u0026plusmn;\u0026thinsp;3.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-10.5\u0026thinsp;\u0026plusmn;\u0026thinsp;4.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.012\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eGWI (mmHg%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLOT-CRT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e458.3\u0026thinsp;\u0026plusmn;\u0026thinsp;222.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e579.9\u0026thinsp;\u0026plusmn;\u0026thinsp;303.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e791.0\u0026thinsp;\u0026plusmn;\u0026thinsp;292.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBiV-CRT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e516.5\u0026thinsp;\u0026plusmn;\u0026thinsp;308.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e640.6\u0026thinsp;\u0026plusmn;\u0026thinsp;334.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e867.2\u0026thinsp;\u0026plusmn;\u0026thinsp;390.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.004\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eGCW (mmHg%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLOT-CRT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e834.7\u0026thinsp;\u0026plusmn;\u0026thinsp;283.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e963.1\u0026thinsp;\u0026plusmn;\u0026thinsp;311.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1126.7\u0026thinsp;\u0026plusmn;\u0026thinsp;344.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.004\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBiV-CRT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e849.8\u0026thinsp;\u0026plusmn;\u0026thinsp;325.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e984.4\u0026thinsp;\u0026plusmn;\u0026thinsp;320.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1242.1\u0026thinsp;\u0026plusmn;\u0026thinsp;412.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eGWW (mmHg%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLOT-CRT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e413.2\u0026thinsp;\u0026plusmn;\u0026thinsp;131.9\u003csup\u003e△\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e352.0\u0026thinsp;\u0026plusmn;\u0026thinsp;110.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e262.7\u0026thinsp;\u0026plusmn;\u0026thinsp;89.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.041\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBiV-CRT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e350.2\u0026thinsp;\u0026plusmn;\u0026thinsp;164.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e301.8\u0026thinsp;\u0026plusmn;\u0026thinsp;130.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e257.2\u0026thinsp;\u0026plusmn;\u0026thinsp;134.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.090\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eGWE (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLOT-CRT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e63.9\u0026thinsp;\u0026plusmn;\u0026thinsp;10.8\u003csup\u003e△\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e66.0\u0026thinsp;\u0026plusmn;\u0026thinsp;10.3\u003csup\u003e△\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e84.8\u0026thinsp;\u0026plusmn;\u0026thinsp;7.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.186\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBiV-CRT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e69.2\u0026thinsp;\u0026plusmn;\u0026thinsp;10.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e70.9\u0026thinsp;\u0026plusmn;\u0026thinsp;9.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e80.8\u0026thinsp;\u0026plusmn;\u0026thinsp;10.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.172\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"8\"\u003e\u003csup\u003e△P\u0026lt;0.05 vs. BiV\u0026minus;CRT group\u003c/sup\u003e.\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"8\"\u003e\u003csup\u003eGCW, global constructive work; GLS, global longitudinal strain; GWE, global work efficiency; GWI, global work index; GWW global wasted work; LVEDD, left ventricular end\u0026minus;diastolic diameter; LVEDV, left ventricular end\u0026minus;diastolic volume; LVEF, left ventricular ejection fraction; LVESV, left ventricular end\u0026minus;systolic volume; and other abbreviations as in Table 1\u003c/sup\u003e.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003eBoth groups demonstrated comparable improvements in LVEF and GLS at 3 days post-implantation, with further significant gains sustained over 6 months. From baseline to 6-month follow-up, consistent improvements were observed for LVEF (16.5 [3.8, 24.0] vs. 15.5 [5.3, 20.8]; P\u0026thinsp;=\u0026thinsp;0.565) and GLS (-4.5 [-6.0, -3.0] vs. -3.0 [-6.0, -1.3]; P\u0026thinsp;=\u0026thinsp;0.096). Similar trends towards better GWI, GCW and GWE with progressive reduction of GWW were reported in both groups in the following 6 months after implantation (Table\u0026nbsp;3). At baseline, the LOT-CRT group demonstrated significantly higher GWW and lower GWE compared to the BiV-CRT group. However, these differences were no longer statistically significant at the 6-month follow-up (Table\u0026nbsp;3), indicating a substantially greater improvement in GWE from baseline to 6 months in the LOT-CRT group (21.0\u0026thinsp;\u0026plusmn;\u0026thinsp;10.4% vs. 11.6\u0026thinsp;\u0026plusmn;\u0026thinsp;8.9%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Echocardiographic response rate did not differ significantly between the LOT-CRT group and the BiV-CRT group (76.7% vs. 77.5%, P\u0026thinsp;=\u0026thinsp;0.935).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec14\"\u003e\n \u003ch2\u003eClinical response\u003c/h2\u003e\n \u003cp\u003eThe trend towards lower BNP levels (LOT-CRT: 668.8\u0026thinsp;\u0026plusmn;\u0026thinsp;547.5 vs. 359.9\u0026thinsp;\u0026plusmn;\u0026thinsp;277.6, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001; BiV-CRT: 676.5\u0026thinsp;\u0026plusmn;\u0026thinsp;504.1 vs. 351.2\u0026thinsp;\u0026plusmn;\u0026thinsp;250.8, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and NYHA functional class (3.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6 vs. 2.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001; 3.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5 vs. 2.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) as well as longer distance of 6-MWT (226.0\u0026thinsp;\u0026plusmn;\u0026thinsp;41.0 vs. 356.8\u0026thinsp;\u0026plusmn;\u0026thinsp;108.0, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001; 223.9\u0026thinsp;\u0026plusmn;\u0026thinsp;46.9 vs. 320.8\u0026thinsp;\u0026plusmn;\u0026thinsp;68.7, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) reached statistical significance at 6-month follow-up compared with baseline in both groups. Clinical performance was not statistically different between the two groups from baseline to 6 months. A higher proportion of patients in the LOT-CRT group achieved improvement in NYHA functional class\u0026thinsp;\u0026ge;\u0026thinsp;1 (86.7% vs. 75.0%, P\u0026thinsp;=\u0026thinsp;0.227), although it did not reach a statistical significance.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec15\"\u003e\n \u003ch2\u003eBiV-CRT versus LOT-CRT without AF\u003c/h2\u003e\n \u003cp\u003eAfter excluding patients with AF (N\u0026thinsp;=\u0026thinsp;17), the LOT-CRT group consistently demonstrated significantly greater improvements in QRSd (36.8\u0026thinsp;\u0026plusmn;\u0026thinsp;20.7ms, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001 vs. BiV-CRT), PSD (84.3\u0026thinsp;\u0026plusmn;\u0026thinsp;47.2ms, P\u0026thinsp;=\u0026thinsp;0.005 vs. BiV-CRT; Supplementary table 1) and GWE (21.7\u0026thinsp;\u0026plusmn;\u0026thinsp;10.3%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001 vs. BiV-CRT; Supplementary table 2) at 6-month follow-up.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec16\"\u003e\n \u003ch2\u003eChanges in only LBBAP mode\u003c/h2\u003e\n \u003cp\u003eCompared to the BiV-CRT group, the LOT-CRT group demonstrated a numerically higher rate of achieving either echocardiographic or clinical response (93.3% vs. 80.0%; P\u0026thinsp;=\u0026thinsp;0.218) while the proportion achieving both responses was 66.7% (20/30) with LOT-CRT and 72.5% (29/40) with BiV-CRT (P\u0026thinsp;=\u0026thinsp;0.598). The 20 responders achieving both responses in the LOT-CRT group were switched to LBBAP mode. One month following the transition, all patients reported V6RWPT\u0026thinsp;\u0026lt;\u0026thinsp;75ms (58.2\u0026thinsp;\u0026plusmn;\u0026thinsp;8.4) and only one patient (5%) had over 10ms increase compared to 6 months after LOT-CRT. A notable widening of the QRS wave was observed (Fig.\u0026nbsp;3) with a prolongation in PSD. Furthermore, a significant enlargement of both LVEDD and LVESD was recorded, accompanied by a marked decrease in LVEF and the absolute value of GLS (Fig.\u0026nbsp;3). When compared to the 29 responders in the BiV-CRT group, the patients in LBBAP mode had significantly higher PSD and more impaired GLS (Fig.\u0026nbsp;3).\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis prospective study revealed three key findings: 1) LOT-CRT showed superior electrical and mechanical resynchronization compared to BiV-CRT; 2) both LOT-CRT and BiV-CRT reached equivalent echocardiographic and clinical improvement at 6 months; 3) LBBAP alone was less effective than LOT-CRT in improving systolic synchrony and LV function in HF patients indicated for CRT.\u003c/p\u003e\u003cdiv id=\"Sec18\" class=\"Section2\"\u003e\u003ch2\u003eSuperiority of LOT-CRT in restoring intraventricular synchronicity\u003c/h2\u003e\u003cp\u003eConsistent with previous studies\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e][\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e][\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e, LOT-CRT achieved greater QRSd reduction than BiV-CRT. However, although QRSd has been introduced as a possible predictor for response to CRT\u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e][\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e, there is no direct correlation between QRSd and mechanical dyssynchrony\u003csup\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e, the latter of which remains a critical determinant of CRT responses\u003csup\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e][\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e. A more pronounced reduction in PSD but not in IVMD by LOT-CRT suggested that a better resynchronization observed with LOT-CRT should stem primarily from its ability to ameliorate LV intraventricular dyssynchrony. Peix et al. reported that improvements in PSD (assessed via gated-SPECT imaging) correlated with better patient outcomes, underscoring the importance of LV intraventricular synchronization\u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e. Furthermore, Maffessanti et al. used invasive electromechanical mapping to show that prolonged total LV activation time (TLVAT), a marker of impaired conduction within LV, predicted suboptimal reverse remodeling after BiV-CRT\u003csup\u003e[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e. Both studies emphasized the importance of correcting intraventricular dyssynchrony.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec19\" class=\"Section2\"\u003e\u003ch2\u003eNon-inferiority of LOT-CRT in reaching CRT response\u003c/h2\u003e\u003cp\u003eBoth LOT-CRT and BiV-CRT comparably facilitated LV reverse remodeling and functional recovery, sustained at 6-month follow-up. In a recent single-arm study conducted by Jastrzębski et al., LOT-CRT and BiV-CRT similarly enhanced hemodynamics immediately following implantation, as assessed invasively via LV pressure maximal first derivative (LV dP/dt\u003csub\u003emax\u003c/sub\u003e)\u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e. However, acute improvements in dP/dt\u003csub\u003emax\u003c/sub\u003e were not correlated with either long-term response or clinical outcomes. Likely due to relatively high proportion of female and non-ischemic cardiomyopathy patients, our study displayed favorable and comparable echocardiographic response between LOT-CRT and BiV-CRT at mid-term follow-up, slightly exceeding the average response rate of CRT among all CRT recipients observed in prior large-scale randomized controlled clinical trials (approximately 70%). In contrast, two recent observational studies demonstrated superior echocardiographic response rates with LOT-CRT versus BiV-CRT\u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e][\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e. This discrepancy may stem from differences in patient populations between the studies (since those investigations included subjects with intraventricular conduction delay [IVCD]), or because the current study\u0026rsquo;s limited sample size may have rendered it underpowered to detect potential superiority of LOT-CRT in LV reverse remodeling and LV functional recovery. Interestingly, our study reinforced their findings by validating the heightened efficacy of LOT-CRT in correcting intraventricular dyssynchrony.\u003c/p\u003e\u003cp\u003eBoth LOT-CRT and BiV-CRT presented ideal clinical benefit for patients including reducuction in BNP levels, improvement in NYHA functional class and enhancement in 6-MWT distance on the basis of guideline-directed medical therapy\u003csup\u003e[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e. The clinical response rate of LOT-CRT in our study which was in line with previous prospective observational studies\u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e][\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec20\" class=\"Section2\"\u003e\u003ch2\u003eInadequacy of LBBAP in CRT candidates\u003c/h2\u003e\u003cp\u003eDespite procedural advantages (cost, radiation exposure), LBBAP alone failed to match LOT-CRT/ in QRSd reduction and restoration of cardiac structure/ function. Similarly, Jastrzębski et al. also observed that LBBAP offered less hemodynamic benefit than LOT-CRT\u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e, underscoring concerns about its clinical utility for CRT. After comparing the status of the 20 patients in LBBAP mode with that of the 29 responders in the BiV-CRT group, we identified a longer PSD and a lower absolute value of GLS in the former group. The suboptimal efficacy of LBBAP in CRT candidates may be attributed to its limited ability to correct the delayed activation of the LV lateral wall, which is likely caused by factors other than the damage of left bundle branch, such as myocardial fibrosis, electrical uncoupling, functional conduction block, and conduction delays within the cardiac conduction system\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e][\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/sup\u003e. Therefore, although it has been advocated by some studies as a viable alternative for CRT candidates\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e][\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e][\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/sup\u003e, the results of our study continued to corroborate the necessity of pacing both ventricles.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec21\" class=\"Section2\"\u003e\u003ch2\u003eLimitations\u003c/h2\u003e\u003cp\u003eThis was a cohort study that limited to its non-randomized design with, because stability of patients during the procedure was given the first priority of decision-making. Relatively small sample size, short follow-up and inadequate hard endpoints in the pilot study counted as other limitations, which would hopefully be overcome in future clinical studies.\u003c/p\u003e\u003c/div\u003e"},{"header":"Conclusions","content":"\u003cp\u003eLOT-CRT is a feasible alternative to BiV-CRT, offering superior electrical/mechanical resynchronization, particularly in correcting intraventricular dyssynchrony. LBBAP alone remains suboptimal for CRT candidates compared to LOT-CRT, necessitating biventricular pacing for comprehensive resynchronization.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study study was performed according to the principles of the Declaration of Helsinki and was approved by the Ethics Committee of Guizhou Provincial People’s Hospital (No. 202123). All patients provided written informed consent.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was supported financially by grants from\u0026nbsp;“0 to 1” Innovative research project of Sichuan University (Grant number 2023SCUH0063) and Key Advantageous Discipline Construction Project of Guizhou Provincial Health Commission in 2023 (Grant number LC[2022]011).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eJing Tan:\u0026nbsp;\u003c/strong\u003eConceptualization, Writing\u0026nbsp;– original draft, Formal analysis, Data curation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTing Liu:\u0026nbsp;\u003c/strong\u003eMethodology, Investigation, Project administration, Validation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eXiaoyong Li:\u0026nbsp;\u003c/strong\u003eSoftware, Visualization, Resources.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eYu Kang:\u0026nbsp;\u003c/strong\u003eSupervision, Writing\u0026nbsp;– review \u0026amp; editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eYang Zhang:\u0026nbsp;\u003c/strong\u003eInvestigation, Data collection.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eKe Feng:\u003c/strong\u003e Resources, Data collection.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eZixuan Yang:\u003c/strong\u003e Resources, Data collection.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eYujia Pan:\u0026nbsp;\u003c/strong\u003eResources, Visualization.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eXin Wei:\u003c/strong\u003e Data interpretation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eJie Bu:\u003c/strong\u003e Investigation, Software.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eYaning Chen:\u0026nbsp;\u003c/strong\u003eMethodology.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eQing Zhang:\u003c/strong\u003e Supervision, Funding acquisition, Conceptualization.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSha Yu:\u003c/strong\u003e Conceptualization, Funding acquisition, Project administration.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe author(s) have no acknowledgments to declare.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBristow MR, Saxon LA, Boehmer J, et al. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med. 2004;350(21):2140\u0026ndash;50.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMcDonagh TA, Metra M, Adamo M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure [published correction appears in. Eur Heart J. 2021;42(48):4901.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChung MK, Patton KK, Lau CP, et al. 2023 HRS/APHRS/LAHRS guideline on cardiac physiologic pacing for the avoidance and mitigation of heart failure. Heart Rhythm. 2023;20(9):e17\u0026ndash;91.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMoss AJ, Hall WJ, Cannom DS, et al. Cardiac-resynchronization therapy for the prevention of heart-failure events. N Engl J Med. 2009;361(14):1329\u0026ndash;38.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCleland JG, Daubert JC, Erdmann E, et al. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med. 2005;352(15):1539\u0026ndash;49.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDaubert C, Behar N, Martins RP, Mabo P, Leclercq C. Avoiding non-responders to cardiac resynchronization therapy: a practical guide. Eur Heart J. 2017;38(19):1463\u0026ndash;72.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHuang W, Su L, Wu S, et al. A Novel Pacing Strategy With Low and Stable Output: Pacing the Left Bundle Branch Immediately Beyond the Conduction Block. Can J Cardiol. 2017;33(12):e17361\u0026ndash;1736.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eVijayaraman P, Sharma PS, Cano \u0026Oacute;, et al. Comparison of Left Bundle Branch Area Pacing and Biventricular Pacing in Candidates for Resynchronization Therapy. J Am Coll Cardiol. 2023;82(3):228\u0026ndash;41.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDiaz JC, Sauer WH, Duque M, et al. Left Bundle Branch Area Pacing Versus Biventricular Pacing as Initial Strategy for Cardiac Resynchronization. JACC Clin Electrophysiol. 2023;9(8 Pt 2):1568\u0026ndash;81.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eParlavecchio A, Vetta G, Caminiti R, et al. Left bundle branch pacing versus biventricular pacing for cardiac resynchronization therapy: A systematic review and meta-analysis. Pacing Clin Electrophysiol. 2023;46(5):432\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJastrzębski M, Moskal P, Huybrechts W, et al. Left bundle branch-optimized cardiac resynchronization therapy (LOT-CRT): Results from an international LBBAP collaborative study group. Heart Rhythm. 2022;19(1):13\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eVijayaraman P. Left Bundle Branch Pacing Optimized Cardiac Resynchronization Therapy: A Novel Approach. JACC Clin Electrophysiol. 2021;7(8):1076\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHuang W, Chen X, Su L, Wu S, Xia X, Vijayaraman P. A beginner\u0026rsquo;s guide to permanent left bundle branch pacing. Heart Rhythm. 2019;16:1791\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChen X, Li X, Bai Y, et al. Electrical Resynchronization and Clinical Outcomes During Long-Term Follow-Up in Intraventricular Conduction Delay Patients Applied Left Bundle Branch Pacing-Optimized Cardiac Resynchronization Therapy. Circ Arrhythm Electrophysiol. 2023;16(9):e011761.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJastrzębski M, Foley P, Chandrasekaran B, et al. Multicenter Hemodynamic Assessment of the LOT-CRT Strategy: When Does Combining Left Bundle Branch Pacing and Coronary Venous Pacing Enhance Resynchronization? Primary Results of the CSPOT Study. Circ Arrhythm Electrophysiol. 2024;17(11):e013059.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJastrzebski M, Baranchuk A, Fijorek K, et al. Cardiac resynchronization therapy-induced acute shortening of QRS duration predicts long-term mortality only in patients with left bundle branch block. Europace. 2019;21(2):281\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eShukla HH, Hellkamp AS, James EA, et al. Heart failure hospitalization is more common in pacemaker patients with sinus node dysfunction and a prolonged paced QRS duration. Heart Rhythm. 2005;2(3):245\u0026ndash;51.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFriedman DJ, Emerek K, S\u0026oslash;rensen PL, et al. Relationship Between Electrical and Mechanical Dyssynchrony and Outcomes Among Patients Undergoing Cardiac Resynchronization Therapy. Circ Arrhythm Electrophysiol. 2021;14(12):e010217.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWouters PC, van Everdingen WM, Vernooy K, et al. Does mechanical dyssynchrony in addition to QRS area ensure sustained response to cardiac resynchronization therapy? Eur Heart J Cardiovasc Imaging. 2022;23(12):1628\u0026ndash;35.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGorcsan J 3rd, Oyenuga O, Habib PJ, et al. Relationship of echocardiographic dyssynchrony to long-term survival after cardiac resynchronization therapy. Circulation. 2010;122(19):1910\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePeix A, Karthikeyan G, Massardo T, et al. Value of intraventricular dyssynchrony assessment by gated-SPECT myocardial perfusion imaging in the management of heart failure patients undergoing cardiac resynchronization therapy (VISION-CRT). J Nucl Cardiol. 2021;28(1):55\u0026ndash;64.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMaffessanti F, Jadczyk T, Wilczek J, et al. Electromechanical factors associated with favourable outcome in cardiac resynchronization therapy. Europace. 2023;25(2):546\u0026ndash;53.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eUpadhyay GA, Jastrzębski M, Foley P et al. Echocardiographic response from Left Bundle Branch Area Pacing Optimized Cardiac Resynchronization Therapy (LOT-CRT) versus traditional CRT. \u003cem\u003eHeart Rhythm\u003c/em\u003e. Published online April 18, 2025.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFu M, Swedberg K. Enhancing implementation of evidence-based heart failure therapies in clinical practice: vital to modern medicine. Cardiol Plus. 2024;9(1):6\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhang D, Lang M, Prakash Earnest BS, Ali Abdou IEM. Application and Research of Left Bundle Branch-Optimized Cardiac Resynchronization Therapy in Ischemic Cardiomyopathy. Rev Cardiovasc Med. 2025;26(3):26240.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJastrzębski M, Kiełbasa G, Curila K, et al. Physiology-based electrocardiographic criteria for left bundle branch capture. Heart Rhythm. 2021;18(6):935\u0026ndash;43.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eVijayaraman P, Sharma PS, Cano \u0026Oacute;, et al. Comparison of Left Bundle Branch Area Pacing and Biventricular Pacing in Candidates for Resynchronization Therapy. J Am Coll Cardiol. 2023;82(3):228\u0026ndash;41.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWang Y, Zhu H, Hou X, et al. Randomized Trial of Left Bundle Branch vs Biventricular Pacing for Cardiac Resynchronization Therapy. J Am Coll Cardiol. 2022;80(13):1205\u0026ndash;16.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-cardiovascular-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcar","sideBox":"Learn more about [BMC Cardiovascular Disorders](http://bmccardiovascdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcar/default.aspx","title":"BMC Cardiovascular Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"cardiac resynchronization therapy, heart failure, left bundle branch pacing, intraventricular dyssynchrony","lastPublishedDoi":"10.21203/rs.3.rs-8183133/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8183133/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eLeft bundle branch-optimized CRT (LOT-CRT), combining left bundle branch area pacing (LBBAP) with coronary venous pacing, may enhance resynchronization.WE aimed to compare LOT-CRT efficacy versus conventional biventricular CRT (BiV-CRT) or LBBAP-only.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eThis prospective study included 70 patients (66\u0026thinsp;\u0026plusmn;\u0026thinsp;9 years, 68.6% male) (30 LOT-CRT, 40 BiV-CRT). Apart from QRS duration (QRSd), interventricular mechanical delay (IVMD), peak strain dispersion (PSD), global longitudinal strain (GLS) and myocardial work (MW) as global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE) were assessed by speckle-tracking echocardiography. LOT-CRT responders were switched to LBBAP-only mode for one month.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eDuring 6-month follow-up, the LOT-CRT group had a more profound reduction in QRSd (42.0 [23.3, 74.5] vs. 17.0 [16.3, 23.8]ms, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and PSD (72.0 [43.0, 114.3] vs. 35.5 [4.3, 82.0]ms, P\u0026thinsp;=\u0026thinsp;0.001). Similar improvement was achieved in left ventricular ejection fraction (LVEF) (16.5 [3.8, 24.0] vs. 15.5 [5.3, 20.8]%) and GLS (-4.5 [-6.0, -3.0] vs. -3 [-6.0, -1.3]%) but the LOT-CRT group displayed better increase in GWE (24.0 [11.0, 29.3] vs. 10.0 [6.3, 14.8] %, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Both echocardiographic and clinical responses were achieved in 66.7% patients receiving LOT-CRT and 72.5% receiving BiV-CRT (P\u0026thinsp;=\u0026thinsp;0.598). After switching to LBBAP, LOT-CRT responders (n\u0026thinsp;=\u0026thinsp;20) showed QRSd widening (131.5\u0026thinsp;\u0026plusmn;\u0026thinsp;26.4 vs. 142.2\u0026thinsp;\u0026plusmn;\u0026thinsp;29.4ms, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) accompanied by worsening LVEF (55.6\u0026thinsp;\u0026plusmn;\u0026thinsp;7.7 vs 51.1\u0026thinsp;\u0026plusmn;\u0026thinsp;7.7%, P\u0026thinsp;=\u0026thinsp;0.002) and GLS (-10.9\u0026thinsp;\u0026plusmn;\u0026thinsp;2.8 vs. -10.0\u0026thinsp;\u0026plusmn;\u0026thinsp;2.3%, P\u0026thinsp;=\u0026thinsp;0.006).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eLOT-CRT represented as a viable alternative to BiV-CRT with superior intraventricular resynchronization, whereas LBBAP alone failed to maintain the benefits in cardiac synchrony and function of LOT-CRT.\u003c/p\u003e\u003ch2\u003eTrial registration:\u003c/h2\u003e\u003cp\u003eThis study was registered with the Chinese Clinical Trial Registry (ChiCTR) at \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.chictr.org.cn/\u003c/span\u003e\u003cspan address=\"http://www.chictr.org.cn/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (registration number: ChiCTR2500110771).\u003c/p\u003e","manuscriptTitle":"Better responses by combination of left bundle branch area pacing and cardiac resynchronization therapy in heart failure patients","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-13 00:18:00","doi":"10.21203/rs.3.rs-8183133/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-02-02T08:36:33+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-07T12:42:15+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-03T14:13:00+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-14T20:20:58+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"268525987920354784020950214247797787747","date":"2025-12-10T06:57:00+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"47839292896702934551856658747801312738","date":"2025-12-09T21:56:58+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"318923538825815780870425645198936347036","date":"2025-12-08T18:48:14+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"323104690162802914005193875099673567753","date":"2025-12-08T18:38:52+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"137985576620803449339787981267768252602","date":"2025-12-08T18:16:04+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"7451665309082233682758374510882608616","date":"2025-12-06T17:48:10+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-12-06T17:29:47+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-12-06T17:22:55+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-11-28T06:37:55+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-11-28T06:19:51+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Cardiovascular Disorders","date":"2025-11-28T06:12:10+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cardiovascular-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcar","sideBox":"Learn more about [BMC Cardiovascular Disorders](http://bmccardiovascdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcar/default.aspx","title":"BMC Cardiovascular Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"8a62e11c-3095-4a65-a078-44a91b3cd76b","owner":[],"postedDate":"December 13th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-15T10:23:09+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-13 00:18:00","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8183133","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8183133","identity":"rs-8183133","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}