This prospective, randomized study was conducted at the People’s Hospital affiliated with Chengdu University of Traditional Chinese Medicine from March 2020 to March 2022. Patients with ICM who met the following criteria were eligible for inclusion: age range of 18 to 65 years; conformity with CRT criteria: New York Heart Association (NYHA) functional classes III–IV, electrocardiogram showing complete LBBB, QRS interval $>$120 ms, and left ventricular ejection fraction (LVEF) $\le$35%. All enrolled patients received at least three months of guideline-directed drug therapy [9]. The exclusion criteria were as follows: patients who did not meet the diagnostic criteria for ICM; patients requiring an upgrade from the common pacemaker to CRT; severe liver and kidney insufficiency; life expectancy 1 year [10, 11]; patients unwilling to participate in the study.

During the study period, 78 patients who met the inclusion criteria were randomly assigned to the LOT-CRT (n = 39) and BVP (n = 39) groups using a random number table. Overall, from the originally assigned 39 patients in the BVP group, two patients were reassigned to the LOT-CRT group; one abandoned surgery, and another experienced a surgical failure; thus, 35 patients were included in the BVP group. Comparatively, for the LOT-CRT group, two patients experienced surgical failure and were excluded; however, since two patients were reassigned from the BVP group, the number of patients in the LOT-CRT group remained at 39. This study was approved by the Medical Ethics Committee of the Fifth People’s Hospital, Affiliated with the Chengdu University of Traditional Chinese Medicine (Ethics Number: Ethical review 2022-009 (Section) -01). Written informed consent was obtained from all patients before their enrolment. This study was conducted in accordance with the guidelines of the Declaration of Helsinki. Data were anonymized during analysis and reporting to protect the privacy of participants.

Patients were randomly assigned to either the LOT-CRT or BVP groups using a computer-generated random number table. The allocation was performed in a 1:1 ratio. To ensure anonymity, the randomization process was managed by an independent coordinator not involved in patient care or the follow-up assessment. The assignment was sealed in opaque envelopes and opened after the patient met the inclusion criteria and provided informed consent. This randomization method was implemented to minimize selection bias and ensure comparable baseline characteristics between the two groups.

All patients were treated for chronic HF using angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor antagonists (angiotensin receptor blocker, ARB) and $\beta$ receptor blockers as per the clinical guidelines. Diuretics were administered depending on the state of fluid retention. All patients received standard medication for at least three months [12, 13, 14]. All surgeons involved in the procedure had prior experience with CRT implants, having completed a minimum of 50 LBBP implants. The LBBP procedure was carried out using the SelectSecure system (Model 3830 Lead, 69 cm; C315 His sheath, Medtronic, Minneapolis, MN, USA).

The 3830 pacing lead was positioned in the right anterior oblique 30° fluoroscopic view via the C315 His sheath. Unipolar pacing was conducted at 2.0 V/0.4 ms to identify the optimal pacing site based on the following criteria: (1) The pacing QRS duration in lead V1 with the 3830 lead tip should exceed 120 ms and display a “W” morphology, with a notch observed at either the nadir or upstroke; (2) The R-wave amplitude at the tip electrode should be at least 5.0 mV. The 3830 lead was then rotated clockwise, approximately five to six turns, with unipolar pacing applied at each rotation to dynamically assess QRS morphology, QRS duration (QRSd), pacing impedance, and R-wave amplitude. As the lead approached the left bundle branch (LBB) region, a marked reduction in QRSd was observed. The left ventricular peak time was assessed in leads V5 to V6. Rotation was stopped once the left ventricular peak time significantly shortened and stabilized across different pacing outputs ($>$5.0 V/0.4 ms and 2.0 V/0.4 ms). Pacing and fluoroscopic assessments were performed at a 45° left anterior oblique position to gauge the depth of septal penetration. Both unipolar and bipolar pacing tests were conducted, and the LBB potential was evaluated using the intracardiac electrogram. Fluoroscopy was set to 4 frames per second, with cine imaging recorded at 7.5 frames per second.

Traditional CRT was performed via the axillary vein approach. A balloon catheter was inserted, and after retrograde venography delineated the course of the coronary vein, the left ventricular lead was advanced through the coronary sinus sheath to the distal lateral or posterolateral branch of the coronary sinus. After obtaining a satisfactory threshold and sensing parameters, the pacing was performed at 10 V, with a pulse width of 1.0 ms to prevent diaphragmatic stimulation. The right ventricular apical and right atrial leads were then implanted sequentially using conventional methods. Finally, the pacemaker generator was connected to the leads and placed into a preformed subcutaneous pocket. The incision was then sutured in layers. The pocket was closed and covered with a sterile dressing, and local pressure was applied for six to eight hours using a sandbag (Fig. 1). All patients underwent transvenous implantation of a biventricular pacemaker, with no cases requiring open-chest implantation for the left ventricular lead. Postoperative CRT programming was optimized to the dual-chamber demand (DDD) pacing or dual-chamber demand rate-adaptive (DDDR) pacing mode, with an atrioventricular (AV) sensing interval of 100 ms and an AV pacing interval of 130 ms. The lower pacing rate was adjusted to achieve a BVP ratio of $>$90%, while the upper rate was set between 120 and 130 bpm. In cases where the LBBP successfully corrected the LBBB, the LBBP was applied independently, with a maximum V–V delay of 80 ms. The right ventricle (RV) or left ventricle (LV) lead output was set to 0.5 V for 0.1 ms to avoid RV or LV pacing. In instances where only LBBP was used intraoperatively, and the QRS duration exceeded 140 ms, sequential pacing, including LBBP and coronary sinus left ventricular (CS-LV) pacing, was employed, with programmed LV–RV (V–V) intervals to shorten the QRS duration further. For patients in sinus rhythm, the atrioventricular (A–V) delays were adjusted to optimize the electrocardiographic performance. The operating surgeon regularly modified the A–V and V–V intervals in patients receiving BVP to reduce the QRS duration. When QRS shortening was insufficient, echocardiographic optimization was utilized to refine the A–V and V–V intervals.

Fig. 1.

Representative chest X-rays from the first postoperative day are shown for both groups.

To ensure consistency in surgical techniques across patients, we implemented a comprehensive CRT implantation protocol in this study. All procedures were performed by experienced surgeons who had completed at least 50 LOT-CRT implantations. The surgical team held regular meetings to ensure strict adherence to the established protocol by all participating surgeons. Key steps in the procedure, including accurate positioning of the left bundle branch, control of implantation depth, and intraoperative monitoring and adjustment of QRS duration, were standardized using real-time imaging and electrophysiological evaluation during surgery. Additionally, pacing parameters during follow-up, including pacing threshold, impedance, and QRS duration, were uniformly recorded and analyzed to maintain consistency in postoperative outcomes.

All patients were monitored through follow-up visits at the arrhythmia outpatient clinic every three months. Diuretics and digitalis were gradually reduced during these visits if the patient’s HF symptoms significantly improved. The dosages of $\beta$-blockers, spironolactone, ACEIs/ARBs, or angiotensin receptor-neprilysin inhibitors (ARNIs) were maintained unchanged during the first six months of follow-up. Data on R-wave amplitude, capture threshold, impedance, ventricular pacing percentage, and 12-lead electrocardiogram (ECG) were recorded at baseline and subsequent follow-up visits. Regular follow-ups were also performed to monitor for any electrode-related complications. QRSd was measured in the lead V1 at both the time of implantation and during follow-up visits. Echocardiography, conducted by an experienced sonographer, was performed at baseline and again at six months post-surgery. Left ventricular ejection fraction (LVEF) was calculated using the biplanar Simpson method from two-dimensional transthoracic echocardiography, with the sonographer blinded to all clinical data. Functional status was assessed using the NYHA classification, and plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were measured at each follow-up visit. The incidence of rehospitalization for HF and mortality were documented throughout the follow-up period. A positive response to CRT was defined as an improvement to NYHA grade 1 and an increase in echocardiographic LVEF of 5%.

The primary outcome of this study was to analyze the improvement in LVEF at six months post-procedure, chosen due to its strong association with long-term prognosis in heart failure patients.

The secondary outcomes included the following: QRS duration was measured at baseline, immediately after the procedure, and six months post-procedure. NYHA functional class: assessed at baseline and six months post-procedure. The left ventricular end-diastolic diameter (LVEDD) was measured by echocardiography at baseline and six months after the procedure. Plasma NT-proBNP levels were measured at baseline and six months as a marker of the severity of heart failure. The incidence of arrhythmic episodes was monitored throughout the follow-up period. Rehospitalization for heart failure and all-cause mortality were recorded as clinical outcomes at the follow-up.

Statistical analysis was performed using SPSS 19.0 software (IBM Corp., Armonk, NY, USA). Continuous variables with normal distribution are presented as the mean $\pm$ standard deviation, and between-group differences were assessed using the independent two-sample t-test. For non-normally distributed continuous variables, data are expressed as the median (interquartile range) and analyzed by the Wilcoxon rank sum test. Categorical variables are reported as the frequency (percentage) and compared using the $\chi$² test. A p-value of 0.05 was considered statistically significant. A multivariable regression analysis was conducted to address potential confounding variables. Meanwhile, variables such as age, gender, and baseline LVEF were included to adjust for their possible impact on the outcomes. This method helps reduce the influence of residual confounding, leading to more reliable conclusions. The regression model was utilized to examine the relationship between the pacing method (LOT-CRT vs. BVP) and key outcome measures, including changes in LVEF, NYHA class, and QRS duration.

The mean age in the LOT-CRT group was 55.8 $\pm$ 10.0 years, and the mean LVEF percentage was 26.00 $\pm$ 4.32%. The mean age in the BVP group was 56.5 $\pm$ 10.4 years, and the mean LVEF percentage was 26.83 $\pm$ 4.17. There were no significant differences between the groups regarding sex, age at pacemaker implantation, NYHA cardiac function classification, LVEF, LV end-diastolic diameter (LVEDD), left ventricular diastolic size (LVDS), mitral regurgitation area (MRA), LV end-systolic volume (LVESV), LV end-diastolic volume (LVEDV), usage of ACEIs/ARBs, $\beta$-blockers, and digoxin, and LV electrode target vein selection (p $>$ 0.05, Table 1). All patients received the prescribed medical treatment for at least three months.

At the time of implantation, the mean QRSd in the LOT-CRT group was significantly shorter than in the BVP group (p 0.001). Six months post-implantation, the QRSd in the LOT-CRT group remained notably shorter than in the BVP group (114.0 $\pm$ 13.0 vs. 151.0 $\pm$ 19.2 ms, p 0.001). Furthermore, significant differences were observed in the LBBP thresholds and pacing impedance between the two groups (p 0.001, Table 2).

The LOT-CRT group showed significantly greater LVEF (p 0.001), a higher rate of CRT over-response (p 0.001), significant improvement in NYHA cardiac grade (p 0.001), a substantial reduction in plasma NT-proBNP level (p 0.001), and higher CRT response rate (89.7% vs. 74.2%, p = 0.021). No events of HF rehospitalization or all-cause death were observed in either group at the six-month follow-up. Moreover, the differences in outcome measures between the LOT-CRT and BVP groups remained significant even after adjusting for potential confounders (age, gender, and baseline LVEF) using multivariable regression analysis. Specifically, the LOT-CRT group demonstrated a greater improvement in LVEF (adjusted p 0.001), a more significant reduction in QRS duration (adjusted p 0.001), and better NYHA class improvement (adjusted p 0.001) compared to the BVP group. These findings suggest that the observed benefits of LOT-CRT are independent of the baseline characteristics (Table 3).