An interventional study of Apply multimodal data fusion for quantitative guidance of left bundle branch region pacing and Conventional Biventricular Pacing in Heart Failure, Left Bundle Branch Block and Non-ischemic Cardiomyopathy, sponsored by Second Affiliated Hospital of Nanchang University. Recruiting at 1 site in China. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2026-09-11.
Sponsored by Second Affiliated Hospital of Nanchang University · Not applicable, Interventional, and Treatment
Heart failure is a common chronic cardiovascular disease that seriously impairs patients' quality of life and long-term prognosis. When heart failure is complicated by complete left bundle branch block, the electrical signals that regulate orderly heart contraction cannot be transmitted normally along the left conduction pathway, causing the left and right ventricles to contract out of sync. This will gradually weaken the heart's pumping capacity, leading to symptoms such as exertional shortness of breath, persistent fatigue and body edema, and significantly increasing the risk of repeated hospital admissions and premature death.
Traditional biventricular pacing is the standard treatment recommended by international clinical guidelines for this condition. By implanting pacing leads in both ventricles to deliver synchronized electrical stimulation, it restores cardiac synchrony, improves cardiac function and reduces mortality in most eligible patients. However, the placement of left ventricular leads is entirely dependent on the anatomy of the coronary venous system. Due to wide individual differences in venous structure, many patients encounter intraoperative difficulties such as failed coronary sinus intubation, absence of suitable target veins, phrenic nerve stimulation, high pacing thresholds and postoperative lead displacement. More importantly, approximately 30% to 40% of patients still show no significant improvement in cardiac function or symptoms even after optimized device programming, a condition known as non-response to cardiac resynchronization therapy.
Left bundle branch area pacing is an innovative physiological pacing technique originally developed in China. It advances a pacing lead through the ventricular septum to directly activate the heart's intrinsic conduction bundle, allowing electrical impulses to spread along the natural conduction pathway and restore ventricular synchrony. Previous single-center observational studies have shown that this technique features stable long-term pacing parameters, relatively low operative difficulty and a favorable safety profile, and can achieve satisfactory cardiac resynchronization effects. Nevertheless, there is still a lack of high-quality multicenter randomized controlled evidence to confirm its long-term clinical hard endpoint benefits. In addition, current implantation operations largely rely on the personal experience of operators, without a unified quantitative positioning standard.
This multicenter prospective randomized controlled study is led by the Second Affiliated Hospital of Nanchang University, with three other tertiary general hospitals participating. A total of 100 eligible heart failure patients with left bundle branch block and left ventricular ejection fraction ≤ 40% will be enrolled. All participants have received at least 3 months of standardized guideline-directed anti-heart failure drug therapy before enrollment, and will be randomly assigned to two groups at a 1:1 ratio. One group will receive left bundle branch area pacing guided by multimodal quantitative data, and the other will receive traditional biventricular pacing. If the initially assigned pacing strategy cannot be successfully implemented during surgery, the patient will cross over to the alternative approach to ensure clinical safety and therapeutic effect.
After the implantation procedure, all patients will receive regular follow-up every 3 months for at least 1 year. During follow-up, the research team will perform examinations including 12-lead electrocardiogram, echocardiogram, 6-minute walk test and pacemaker device interrogation, and systematically record clinical events such as all-cause death, heart failure rehospitalization, malignant arrhythmia and procedure-related complications. The core goal of this study is to compare the incidence of the composite endpoint of all-cause death and heart failure rehospitalization between the two groups, and verify whether multimodal quantitative-guided left bundle branch area pacing can bring superior long-term clinical benefits to heart failure patients. The findings are expected to provide reliable evidence for the clinical application of this technique, help establish standardized quantitative implantation standards, and offer a more optimized treatment option for more heart failure patients.
Cardiac resynchronization therapy is a standard treatment for heart failure patients with complete left bundle branch block, and traditional biventricular pacing is the most widely used approach to achieve resynchronization. However, biventricular pacing is restricted by the variable anatomy of the coronary venous system, with common intraoperative complications and a 30% to 40% rate of non-response. His bundle pacing, as the most physiological pacing modality, is limited by high operation difficulty, gradually increasing pacing thresholds and unstable long-term capture. Left bundle branch area pacing is an emerging physiological pacing technique originating in China, which can correct conduction block and restore ventricular synchrony with stable pacing parameters. Existing studies are mostly single-center observational research with short follow-up periods, lacking high-quality multicenter randomized controlled evidence on long-term hard clinical endpoints. In addition, there is no unified quantitative standard for intraoperative lead positioning, and the procedure relies heavily on operator experience. Based on the previously established multimodal quantitative positioning system, this study conducts a multicenter randomized controlled trial to compare the long-term efficacy and safety of multimodal-guided left bundle branch area pacing and traditional biventricular pacing in heart failure patients.
Intervention Procedures For patients in the left bundle branch area pacing group, the trans-septal approach is adopted for implantation. All procedures are performed by three experienced clinicians with rich pacemaker implantation experience from the research team. A 3830 active fixation lead is delivered through a C315 delivery sheath under 30-degree right anterior oblique fluoroscopy guidance. The lead implantation site is selected under the guidance of the multimodal quantitative system established in previous research. The 12-lead surface electrocardiogram and intracardiac electrogram are synchronously displayed and recorded on the Bard LabSystem Pro electrophysiology recording system during the whole procedure.
The quantitative guidance system includes two core parts: imaging distance indicators and electrocardiographic indicators. For imaging indicators, a quantitative coordinate system is established with the contraction line as the reference axis under fluoroscopy. The longitudinal distance and lateral distance from the lead tip to the reference axis are measured, and corrected values are calculated to eliminate the influence of individual differences in heart size. The conversion between measured distance and real anatomical distance is calibrated by the known true diameter of the pacing lead, and all imaging distance measurements are performed on LibreCAD software with three repeated measurements to take the average value. For electrocardiographic indicators, positioning pacing is performed at 2.0V/0.5ms output, and parameters including local left ventricular activation time, local paced QRS duration and their ratio are measured, along with the waveform amplitude and direction of lead II and III. The optimal implantation site must meet the comprehensive quantitative criteria: corrected longitudinal distance ≥ 26.9 mm, local paced QRS duration ≤ 141 ms, local left ventricular activation time ≤ 92 ms, local left ventricular activation time / QRS duration ratio ≤ 63.9%, and negative QRS waveform in lead II/III during positioning pacing.
After confirming the target site, the lead is screwed clockwise into the deep septum until left bundle branch capture is achieved. During the screwing process, unipolar sensing, pacing electrocardiogram and pacing impedance are tested continuously, with simultaneous monitoring of surface electrocardiogram, intracardiac electrogram and fluoroscopic images. Left bundle branch capture is defined by the following criteria. First, the paced QRS waveform in lead V1 presents typical or atypical right bundle branch block morphology. Second, left ventricular activation time ≤ 90 ms under low voltage pacing. Third, at least one of the following evidences is met: sudden shortening of left ventricular activation time by more than 10 ms during lead screwing with no further change with deeper screwing; QRS morphology changes from non-selective to selective pacing with stable left ventricular activation time when reducing pacing voltage; left ventricular activation time prolongs by more than 10 ms when pacing mode changes from non-selective left bundle branch pacing to left ventricular septal pacing. If left bundle branch capture cannot be achieved after attempts at 5 sites, the procedure will be converted to biventricular pacing. After surgery, the pacemaker is programmed to DDD mode, and the atrioventricular interval is optimized to achieve the narrowest paced QRS width.
For patients in the biventricular pacing group, retrograde coronary venography is routinely performed during surgery to display the main coronary sinus trunk and all branch vessels. The lateral vein or posterolateral vein is usually selected as the target vein for coronary sinus lead implantation. The defibrillation lead is placed in the right ventricular outflow tract septum or right ventricular apex. If there is no suitable target vessel, or the lead cannot be implanted successfully, or the pacing threshold is too high, or phrenic nerve stimulation occurs, the patient will cross over to the left bundle branch area pacing group. After surgery, the pacemaker is programmed to DDD mode, and the atrioventricular interval and interventricular interval are optimized to ensure a biventricular pacing ratio higher than 92%. For patients with quadripolar left ventricular leads, the optimal pacing vector is selected according to pacing threshold and paced QRS width. All patients receive atrioventricular and interventricular interval optimization before discharge to achieve the best atrioventricular synchrony and maximum aortic flow velocity.
Outcome Measures The primary endpoint of the study is the composite endpoint of all-cause death and/or heart failure rehospitalization. Heart failure rehospitalization is defined as worsening of heart failure symptoms and signs in outpatient, emergency or inpatient settings, requiring oral or intravenous diuretics to relieve clinical symptoms.
The secondary endpoints include the following items. First, all-cause death. Second, heart failure rehospitalization. Third, malignant ventricular arrhythmia. The definition of malignant ventricular arrhythmia is consistent with the previously published VANIS study, meeting any of the following criteria: three or more episodes of ventricular tachycardia all terminated by anti-bradycardia pacing, with at least one episode accompanied by clinical symptoms; one or more appropriate implantable cardioverter defibrillator shocks; three or more episodes of ventricular tachycardia within 24 hours; sustained ventricular tachycardia with frequency not reaching the implantable cardioverter defibrillator treatment standard. Fourth, the occurrence of procedure-related complications, including lead perforation, lead dislodgement, excessively high pacing threshold, phrenic nerve stimulation, hemothorax, pneumothorax, pocket hematoma, pocket infection and pericardial effusion. During follow-up, if a patient experiences any of the above clinical endpoints or is lost to follow-up, the follow-up for that patient will be terminated. The electrocardiogram morphological diagnosis criteria in this study refer to the 2009 AHA/ACC/HRS standard for electrocardiogram standardization and interpretation.
In addition to clinical endpoints, the study also collects multiple evaluation indicators during follow-up, including 12-lead electrocardiogram parameters, echocardiographic parameters such as left ventricular ejection fraction, left ventricular end-diastolic diameter, left ventricular end-diastolic volume and left ventricular end-systolic volume, N-terminal pro-B-type natriuretic peptide level, 6-minute walk distance, New York Heart Association functional class, and pacing parameters including pacing threshold, impedance and sensing at intraoperative, 3-month, 6-month and 12-month time points. Baseline clinical data including age, gender, comorbidities, medication use and baseline electrocardiogram characteristics are also collected completely.
Data Management and Quality Control A unified case report form is used for data collection across all centers. To ensure data accuracy, two data administrators independently perform double data entry and conduct consistency verification of the data files. For questions in the case report form, the data administrator will issue a data query form through clinical research associates, and the researchers will answer and correct the data in a timely manner. The query and correction process is repeated until all data queries are completely resolved.
Data verification includes manual verification and computerized program verification. For data problems such as missing values, abnormal values and logical errors found during verification, the data administrator will promptly issue queries to the researchers for resolution. After data entry and query cleaning are completed, the sponsor, principal investigator, data manager and statistician will jointly conduct a final review of the data, define the analysis datasets including the full analysis set, per-protocol set and safety set, and confirm the handling rules of missing values and outliers. After confirming that the data are correct, the database will be locked with the joint approval of relevant personnel, and the locked data will be exported for subsequent statistical analysis.
Before the start of the study, all participating centers receive unified training on the study protocol, operation specifications and data recording standards. Regular on-site monitoring is conducted during the study period to ensure that all centers implement the protocol in a standardized manner and that the research data are authentic, complete and reliable.
Statistical Analysis Plan For baseline demographic and clinical characteristics, normally distributed measurement data are expressed as mean and standard deviation, and the difference between the two groups is compared by independent sample t-test. Measurement data that do not follow normal distribution are expressed as median and interquartile range, and the difference between the two groups is compared by independent sample Wilcoxon rank sum test. Categorical data are expressed as frequency and proportion, and the difference between the two groups is compared by chi-square test; if the conditions for chi-square test are not met, Fisher's exact test is used instead.
To maximize the retention of randomization information, the primary endpoint analysis follows the intention-to-treat principle, and per-protocol analysis is used as the sensitivity analysis result. Secondary endpoints also adopt intention-to-treat analysis. Finally, multivariate Cox proportional hazards regression analysis is performed with the primary and secondary endpoints as dependent variables, to explore independent influencing factors of long-term clinical outcomes. The study sets P \< 0.05 as the threshold for statistically significant difference.
6,331 studies on the registry are indexed under Heart Failure; 1,396 are open to participants now.
This study's planned enrollment of 100 is above the median of 76 across 4,049 interventional studies indexed under Heart Failure.
Browse Heart Failure studies →Second Affiliated Hospital of Nanchang University is the lead sponsor of 85 studies on the registry; 52 are open to participants now.
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Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants are randomly assigned to this arm at a 1:1 ratio. Eligible subjects are patients aged 18-80 years with sinus rhythm, complete left bundle branch block (Strauss criteria: QRS \>140 ms in males, QRS \>130 ms in females), non-ischemic cardiomyopathy, left ventricular ejection fraction ≤40%, NYHA functional class Ⅱ-Ⅳ, and who have received at least 3 months of guideline-directed medical therapy for heart failure. Subjects in this arm receive left bundle branch area pacing quantitatively guided by multimodal data fusion. If no evidence of left bundle branch capture is achieved intraoperatively, LBBP is defined as failed and participants will cross over to the biventricular pacing arm. All subjects undergo follow-up every 3 months after surgery for at least 1 year.
Procedure: Apply multimodal data fusion for quantitative guidance of left bundle branch region pacing
Participants are randomly assigned to this arm at a 1:1 ratio. Eligible subjects are patients aged 18-80 years with sinus rhythm, complete left bundle branch block (Strauss criteria), non-ischemic cardiomyopathy, LVEF ≤40%, NYHA class Ⅱ-Ⅳ, and at least 3 months of guideline-directed heart failure medical therapy. Subjects receive conventional biventricular pacing via coronary sinus lead implantation, with retrograde venography to select lateral or posterolateral target veins. If left ventricular lead implantation fails or phrenic nerve stimulation occurs, participants will cross over to the LBBAP arm. Postoperatively, devices are programmed to DDD mode with optimized intervals, and all subjects undergo standardized follow-up every 3 months for at least 1 year.
Procedure: Conventional Biventricular Pacing
This intervention adopts the trans-septal approach. A 3830 active fixation lead is delivered via a C315 delivery sheath under 30° right anterior oblique fluoroscopy to the right ventricular septal side. The implantation site is guided by multimodal data fusion, including imaging distance parameters and intraoperative pacing electrocardiographic indicators. The lead is screwed into the deep interventricular septum to reach the left ventricular subendocardial region, with paced QRS in lead V1 presenting right bundle branch block morphology to correct baseline left bundle branch block. Sensing function, pacing thresholds and pacing impedance are tested intraoperatively, and left ventricular activation time is measured to confirm left bundle branch capture. If LBBP is not achieved after 5 site attempts, participants will cross over to the biventricular pacing arm. Postoperatively, devices are programmed to DDD mode with optimized AV intervals to achieve the narrowest paced QRS duration.
This intervention delivers standard cardiac resynchronization therapy via the coronary sinus approach to correct left bundle branch block and restore biventricular electromechanical synchrony. Retrograde coronary venography is performed intraoperatively to visualize the coronary sinus trunk and its branch vessels, and the lateral or posterolateral vein is selected as the target for left ventricular lead implantation. For defibrillator devices, the defibrillation lead is implanted in the right ventricular outflow tract septum or apex. If no target vein is available, implantation fails, pacing threshold is excessively high, or phrenic nerve stimulation occurs, participants will cross over to the LBBAP arm. For patients with quadripolar left ventricular leads, pacing vectors are selected based on pacing threshold and paced QRS width. Postoperatively, devices are programmed to DDD mode with optimized AV and VV intervals to maintain a biventricular pacing proportion above 92%.
Incidence of composite endpoint of all-cause mortality and/or heart failure rehospitalization
This is the primary endpoint of the study. The composite endpoint consists of all-cause mortality and/or heart failure rehospitalization (HFH). HFH is defined as worsening of heart failure symptoms and signs in outpatient, emergency or inpatient settings, requiring oral or intravenous diuretics to relieve clinical symptoms. The incidence of the composite endpoint during follow-up is compared between the two study arms to evaluate the difference in clinical efficacy.
Time frame: Postoperative follow-up is conducted every 3 months for a total of one year.
Incidence of all-cause mortality during study follow-up
This secondary endpoint records the occurrence of all-cause death during the follow-up period. The incidence of all-cause mortality is compared between the left bundle branch area pacing group and the conventional biventricular pacing group.
Time frame: Postoperative follow-up is conducted every 3 months for a total of one year.
Incidence of heart failure rehospitalization during study follow-up
This secondary endpoint records the occurrence of heart failure rehospitalization, which is defined as rehospitalization due to exacerbated heart failure requiring diuretic therapy. The incidence is compared between the two study groups.
Time frame: Postoperative follow-up is conducted every 3 months for a total of one year.
Incidence of malignant ventricular arrhythmia during study follow-up
This secondary endpoint records the occurrence of malignant ventricular arrhythmia, whose definition is consistent with the previously published VANIS study. The incidence is compared between the two study arms.
Time frame: Postoperative follow-up is conducted every 3 months for a total of one year.
Incidence of procedure-related complications
This secondary safety endpoint records all procedure- and device-related complications. The incidence of complications is compared between the two groups to evaluate the safety profile of each pacing strategy.
Time frame: Postoperative follow-up is conducted every 3 months for a total of one year.
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Second Affiliated Hospital of Nanchang University