Clinical Efficacy and Safety of Left Bundle Branch Area Pacing Using Quantitative Guidance of Multimodal Data in the Treatment of Heart Failure

Clinical Efficacy and Safety of Left Bundle Branch Area Pacing Using Quantitative Guidance of Multimodal Data in the Treatment of Heart Failure: A Multicenter, Randomized Controlled Study

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.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure; Left Bundle Branch Block; Non-ischemic Cardiomyopathy
• Intervention / Treatment: Procedure: Apply multimodal data fusion for quantitative guidance of left bundle branch region pacing; Procedure: Conventional Biventricular Pacing

Detailed Description

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.

1. Study Design and Overall Framework This study is a multicenter, prospective, randomized controlled clinical trial led by the Second Affiliated Hospital of Nanchang University, with the participation of three other tertiary general hospitals including the People's Hospital of Inner Mongolia Autonomous Region, Hohhot First Hospital and Chifeng Hospital. The study will continuously screen eligible patients from March 2024 to March 2025. The entire study will be conducted in strict compliance with the Declaration of Helsinki, and the protocol will be reviewed and approved by the ethics committees of all participating institutions. All enrolled patients must sign a paper informed consent form before enrollment, and all original clinical data will be transmitted to the Second Affiliated Hospital of Nanchang University for unified statistical analysis. The study adopts a 1:1 parallel group design with a preset crossover rule, to ensure that patients who fail the initially assigned pacing strategy can still receive appropriate treatment without compromising clinical safety.
2. Study Population and Eligibility Criteria The study enrolls patients diagnosed with non-ischemic cardiomyopathy complicated by complete left bundle branch block and heart failure. The inclusion criteria are as follows. First, patients aged between 18 and 80 years old. Second, patients with sinus rhythm and complete left bundle branch block meeting the Strauss criteria, defined as QRS duration > 140 ms for male patients and > 130 ms for female patients. Third, patients with non-ischemic cardiomyopathy, left ventricular ejection fraction ≤ 40%, and New York Heart Association functional class II to IV. Fourth, patients who voluntarily sign the written informed consent form. All enrolled patients must have received at least 3 months of guideline-recommended standard anti-heart failure drug therapy before enrollment. The exclusion criteria are as follows. First, patients with ischemic cardiomyopathy confirmed by coronary CT. Second, patients with wide QRS waves of non-left bundle branch block morphology, including right bundle branch block and non-specific intraventricular conduction block. Third, patients with persistent atrial fibrillation. Fourth, patients undergoing pacemaker replacement who do not need reimplantation of ventricular leads. Fifth, patients with special conditions such as pregnancy and advanced malignant tumor.
3. Group Assignment and Crossover Rules Eligible patients will be randomly assigned to the left bundle branch area pacing group and the biventricular pacing group at a 1:1 ratio through a central randomization system. A crossover mechanism is set in the study to guarantee clinical safety and treatment effect. For patients assigned to the left bundle branch area pacing group, if no evidence of left bundle branch capture is observed after standard attempts intraoperatively, the procedure will be judged as failed, and the patient will cross over to the biventricular pacing group. For patients assigned to the biventricular pacing group, if left ventricular lead implantation fails due to anatomical reasons such as no accessible target vein, excessively high pacing threshold or intolerable phrenic nerve stimulation, the patient will cross over to the left bundle branch area pacing group. All crossover cases will be recorded in detail and included in the final statistical analysis according to the intention-to-treat principle.

4. 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.

5. 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.

6. Follow-up Schedule and Assessments All patients will receive regular outpatient or telephone follow-up every 3 months after surgery, with a minimum follow-up period of 1 year. At each follow-up visit, the research team will complete a series of standardized assessments. First, clinical evaluation including symptom assessment, New York Heart Association functional classification, and medication adherence review. Second, 12-lead electrocardiogram examination to evaluate paced QRS duration and morphology. Third, pacemaker device interrogation to record pacing threshold, impedance, sensing performance, pacing percentage and arrhythmia events recorded by the device. Fourth, echocardiographic examination at 3 months, 6 months and 12 months after surgery to evaluate cardiac structure and systolic function. Fifth, 6-minute walk test and N-terminal pro-B-type natriuretic peptide detection at specified follow-up time points. Sixth, systematic recording of all clinical endpoint events and adverse events, with detailed documentation of occurrence time, severity, treatment measures and final outcome. All follow-up data are recorded in a unified case report form to ensure data standardization and consistency across all participating centers.
7. Sample Size Calculation The sample size is calculated based on the primary composite endpoint of all-cause death and heart failure rehospitalization. According to the previous small-sample clinical study of the research team and the results of related published studies, the incidence of the primary endpoint is 24% in the left bundle branch area pacing group and 52% in the biventricular pacing group. PASS software is used for sample size calculation. Under the conditions of 80% statistical power and two-sided α = 0.05, a total of 88 subjects are required, with 44 cases in each group, to detect the statistical difference between the two groups. Considering a loss to follow-up rate of no more than 15%, the final sample size is determined to be 100 cases, with 50 cases in each group.

8. 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.

9. 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.

10. Expected Value and Feasibility Support This study is expected to provide high-level evidence-based medical evidence for the clinical application of left bundle branch area pacing, establish a set of quantitative and operable implantation standards, and promote the standardized popularization of physiological pacing technology. The Second Affiliated Hospital of Nanchang University has a strong cardiovascular department with complete medical equipment and rich experience in multicenter clinical trials. The principal investigator and the research team have long been engaged in arrhythmia and cardiac electrophysiology research, and have completed multiple relevant clinical studies, laying a solid methodological foundation for the smooth implementation of this study.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Zhenyu Zhai, PHD; Phone Number: +86 15079109953; Email: 13337107502@163.com

Study Locations

• China
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • Recruiting
      • Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
      • Contact: Zhenyu Zhai, PHD; Phone Number: +86 15079109953; Email: 13337107502@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 18-80 years;
• Sinus rhythm, complete left bundle branch block (LBBB) fulfilling the Strauss criteria (QRS duration >140 ms in men or >130 ms in women);
• Non-ischemic cardiomyopathy, left ventricular ejection fraction (LVEF) ≤40%, and New York Heart Association (NYHA) functional class II-IV;
• Signed informed consent.
• All enrolled patients received guideline-recommended pharmacological therapy for heart failure for at least 3 months.

Exclusion Criteria:

• Coronary CT-confirmed ischemic cardiomyopathy;
• wide QRS complex with non-LBBB morphology, including right bundle branch block and nonspecific intraventricular conduction block;
• persistent atrial fibrillation;
• pacemaker replacement without reimplantation of ventricular leads;
• patients with special conditions, such as pregnancy, gestation, and advanced malignancy.
• All patients underwent detailed recording of electrophysiological pacing parameters intraoperatively and postoperatively, and monitoring for surgical complications.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Left bundle branch area pacing (LBBAP) group; 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; 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.
Active Comparator: Biventricular pacing (BiVP) group; 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 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%.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Postoperative follow-up is conducted every 3 months for a total of one year.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	Postoperative follow-up is conducted every 3 months for a total of one year.

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital of Nanchang University
• Collaborators: The Affiliated Hospital of Inner Mongolia Medical University; Hohhot First Hospital, Hohhot, Inner Mongolia, China; Chifeng Municipal Hospital

Publications and helpful links

General Publications

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• Moscoso I, Cebro-Marquez M, Martinez-Gomez A, Abou-Jokh C, Martinez-Monzonis MA, Martinez-Sande JL, Gonzalez-Melchor L, Garcia-Seara J, Fernandez-Lopez XA, Morana-Fernandez S, Gonzalez-Juanatey JR, Rodriguez-Manero M, Lage R. Circulating miR-499a and miR-125b as Potential Predictors of Left Ventricular Ejection Fraction Improvement after Cardiac Resynchronization Therapy. Cells. 2022 Jan 13;11(2):271. doi: 10.3390/cells11020271.
• Kaddour M, Kozhuharov N, Burri H. Case report of hidden (yet visible) systolic fascicular potentials in a patient with left bundle branch block during conduction system pacing implantation. Eur Heart J Case Rep. 2023 Jan 14;7(1):ytad024. doi: 10.1093/ehjcr/ytad024. eCollection 2023 Jan.
• Zaidi SMJ, Sohail H, Satti DI, Sami A, Anwar M, Malik J, Mustafa B, Mustafa M, Mehmoodi A. Tricuspid regurgitation in His bundle pacing: A systematic review. Ann Noninvasive Electrocardiol. 2022 Nov;27(6):e12986. doi: 10.1111/anec.12986. Epub 2022 Jun 28.
• Samy M, Hamdy RM. A case report of balloon-assisted tracking to overcome coronary sinus competent valve: a novel technique in left ventricular lead implantation. Eur Heart J Case Rep. 2022 Feb 2;6(2):ytac056. doi: 10.1093/ehjcr/ytac056. eCollection 2022 Feb.
• Verzaal NJ, van Deursen CJM, Pezzuto S, Wecke L, van Everdingen WM, Vernooy K, Delhaas T, Auricchio A, Prinzen FW. Synchronization of repolarization after cardiac resynchronization therapy: A combined clinical and modeling study. J Cardiovasc Electrophysiol. 2022 Aug;33(8):1837-1846. doi: 10.1111/jce.15581. Epub 2022 Jun 11.
• Yamada S, Kaneshiro T, Yoshihisa A, Nodera M, Amami K, Nehashi T, Takeishi Y. Albumin-Bilirubin Score for Prediction of Outcomes in Heart Failure Patients Treated with Cardiac Resynchronization Therapy. J Clin Med. 2021 Nov 18;10(22):5378. doi: 10.3390/jcm10225378.
• Chen HC, Liu WH, Tseng CH, Chen YL, Lee WC, Fang YN, Chong SZ, Chen MC. Diabetes Increases Risk of Cardiovascular Events in Patients Receiving Permanent Pacemaker: A Propensity Score-Matched Cohort Study. J Diabetes Res. 2022 Mar 28;2022:6758297. doi: 10.1155/2022/6758297. eCollection 2022.
• Liang Y, Wang J, Gong X, Lu H, Yu Z, Zhang L, Li M, Pan L, Chen X, Cui J, Zhang W, Li R, Zhou X, Huang W, Su Y, Ge J. Left Bundle Branch Pacing Versus Biventricular Pacing for Acute Cardiac Resynchronization in Patients With Heart Failure. Circ Arrhythm Electrophysiol. 2022 Nov;15(11):e011181. doi: 10.1161/CIRCEP.122.011181. Epub 2022 Oct 28.
• Baumgartner T, Kaelin-Friedrich M, Makowski K, Noti F, Schaer B, Haeberlin A, Badertscher P, Kozhuharov N, Baldinger S, Seiler J, Osswald S, Kuhne M, Roten L, Tanner H, Sticherling C, Reichlin T. Sex-Related Differences in Patient Selection for and Outcomes after Pace and Ablate for Refractory Atrial Fibrillation: Insights from a Large Multicenter Cohort. J Clin Med. 2022 Aug 22;11(16):4927. doi: 10.3390/jcm11164927.
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• WRITING COMMITTEE MEMBERS; Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Drazner MH, Fonarow GC, Geraci SA, Horwich T, Januzzi JL, Johnson MR, Kasper EK, Levy WC, Masoudi FA, McBride PE, McMurray JJ, Mitchell JE, Peterson PN, Riegel B, Sam F, Stevenson LW, Tang WH, Tsai EJ, Wilkoff BL; American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2013 Oct 15;128(16):e240-327. doi: 10.1161/CIR.0b013e31829e8776. Epub 2013 Jun 5. No abstract available.

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Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: July 9, 2026
• First Submitted That Met QC Criteria: September 5, 2026
• First Posted (Actual): September 11, 2026

Study Record Updates

• Last Update Posted (Actual): September 11, 2026
• Last Update Submitted That Met QC Criteria: September 5, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Heart failure; Biventricular pacing; Left bundle branch area pacing; Multimodal data; Complete left bundle branch block
• Additional Relevant MeSH Terms: Cardiac Conduction System Disease; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Heart Block; Pathological Conditions, Signs and Symptoms; Heart Failure; Bundle-Branch Block
• Other Study ID Numbers: I-MRER[2024] No.(55)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No