An interventional study of Cardiac Resynchronization Therapy Devices with Defibrillator Function (CRT-D) or CRT-D Leads Replacement and CRT-D or CRT-D Leads Replacement with New Lead Implantation to Left Bundle Branch and Inactivation of Conventional Right and Left Ventricular Pacing in Heart Failure, Left Bundle-Branch Block and Ischemic Cardiomyopathy, sponsored by Tomsk National Research Medical Center of the Russian Academy of Sciences. Recruiting at 1 site in Russian Federation. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2024-11-22.
Sponsored by Tomsk National Research Medical Center of the Russian Academy of Sciences · Not applicable, Interventional, and Treatment
Heart failure (HF) is the most common nosology encountered in clinical practice. Its incidence and prevalence increase exponentially with increasing age and it is associated with the increased mortality, more frequent hospitalization and decreased quality of life. An initial approach to the treatment of HF patients with reduced left ventricular (LV) systolic function and left bundle branch block (LBBB) was implantation of device for cardiac resynchronization therapy using biventricular pacing. This has resulted in long-term clinical benefits such as improved quality of life, increased functional capacity, reduced HF hospitalizations and overall mortality. However, conventional cardiac resynchronization therapy (CRT) is effective in only 70% of patients. And the remaining 30% of patients are non-responders to conventional CRT. Cardiac conduction system pacing is currently a promising technique for these patients. Particularly, His bundle pacing (HBP) has been developed to achieve the same results. According to other studies HBP has shown greater improvement in hemodynamic parameters comparing with conventional biventricular CRT. But, nevertheless, there are significant clinical troubles with HBP, especially high pacing threshold. In this regard, in 2017, the left bundle branch pacing (LBBP) was developed, which demonstrated clinical advantages compared to conventional biventricular CRT. Also, since 2019, left bundle branch pacing-optimized CRT (LBBPO CRT) has been used in clinical practice. These methods have become an alternative to HBP due to the stimulation of LBB outside the blocking site, a stable pacing threshold and a narrow QRS complex duration on electrocardiogram. A series of case reports and observational studies have demonstrated the efficacy and safety of LBBP and LBBPO CRT in patients with CRT indications. However, it is not enough data about impact of CRT with LBBP and combined CRT with LBBP and LV pacing on myocardial remodeling, reducing mortality and complications. According to our hypothesis, CRT with LBBP and combined CRT with LBBP and LV pacing compared with conventional biventricular pacing will significantly improve the clinical outcomes and reverse myocardial remodeling in patients who are non-responders to biventricular CRT with HF, reduced LV ejection fraction and with indications to CRT devices with defibrillator function (CRT-D) or one of the CRT-D leads replacement.
Recent advances in the cardiovascular pharmacological and cardiac device-based therapy have led to many benefits which improve the clinical condition, reduce morbidity, and increase survival in patients with heart failure (HF). Cardiac resynchronization therapy (CRT) with biventricular pacing is a well-established method for the treatment of patients with the left bundle branch block (LBBB), cardiomyopathy of difference etiologies and HF with the reduced left ventricular ejection fraction (LVEF). Several prospective randomized trials have shown that biventricular CRT improves quality of life, improves exercise tolerance, reduces HF hospitalizations, and reduces all-cause mortality. The enthusiasm for this remarkable efficacy of CRT is limited by the fact that a proportion of patients have no benefits from this treatment. This category of patients is called nonresponder. These patients have no clinical and echocardiographic improvement with CRT. According to some studies, 30-50% of patients with biventricular CRT are non-responders.
The left bundle branch pacing (LBBP) was proposed in 2017 and demonstrated clinical benefits in patients with HF and LBBB, aiming to pace the proximal left bundle branch (LBB) along with LV myocardial capture. During selective pacing, only LBB is captured without the nearby myocardium, while with non-selective LBBP the septal myocardium is captured. LBBP with lead implanted slightly distal to the His bundle and screwed deep into the left ventricular (LV) septum is ideal for LBB capture. LBBP has emerged as an alternative to HBP due to pacing outside the blocking site, a stable pacing threshold, and a narrow QRS complex duration on electrocardiogram in patients with the bradycardia. In some clinical cases for the first time was demonstrated that LBBP could lead to complete correction of LBBB and improvement in cardiac function in patients with LBBB and HF. In another observational study it was shown that LBBP could be a new method of CRT. Subsequently, several case reports and observational studies have demonstrated the efficacy and safety of LBBP in patients with indications for CRT device implantation.
However, proximal LBBP is inherently limited in its ability to restore the physiological activation of LV lateral wall in patients with the conduction delay in the distal segment of LBB, Purkinje fibers or LV myocardium. Moreover, it is possible that in many patients with LBBP, only LV septal myocardial capture has been obtained, resulting in a small but potentially important non-physiological delay in LV lateral wall activation.
Conventional biventricular CRT based on right ventricular (RV) and LV pacing is also limited in its ability to fully restore physiological LV activation. Limitations of biventricular CRT may also include the potential desynchronizing effect of RV pacing , non-physiological epicardial LV pacing, latency and suboptimal position of LV lead (paraseptal or apical) due to anatomical features of the target vein, and the presence of LV myocardial scar. The inability of biventricular CRT to restore physiological activation may be expressed in QRS complex widening, rather than in its narrowing. That is observed in a third of patients with biventricular CRT and associated with a poor prognosis.
The combination of LBB and LV pacing may overcome some of the aforementioned limitations of both methods, providing a narrower QRS complex and more effective CRT, especially in difficult cases and in patients with more severe HF. Several studies have shown that combined CRT with LBB and LV pacing is feasible and safe and provides greater electrical resynchronization compared to biventricular CRT.
The above studies demonstrate that LBBP is clinically feasible in patients with HF and LBBB. However, there are still few data about CRT using LBBP in patients with HF and reduced LVEF. There are also only few studies on direct comparison of changes in clinical, speckle tracking echocardiography and other laboratory and instrumental parameters between patients with conventional biventricular CRT and CRT with LBBP.
CRT induces reverse remodeling of the affected heart, improves LV systolic and diastolic function and left heart filling pressure. The measurement of fibrosis and remodeling biomarkers representing the pattern of active processes in HF may be useful.
The relationship between changes in the biomarkers level and reverse remodeling process in patients with LBBP is currently poorly understood. And there are no publications regarding the correlation of the level of such biomarkers as mid-regional pro atrial natriuretic peptide (MR-proANP), growth differentiation factor (GDF)-15, galectin-3, suppression of tumorigenicity 2 (ST2), mid-regional pro adrenomedullin (MR-proADM) and aminoterminal propeptide of type I procollagen (PINP) with clinical and instrumental indicators of patients with LBBP in the available literature. This creates all the prerequisites for studying the association of the above biomarkers with the reverse remodeling process in patients with CRT using LBBP.
6,331 studies on the registry are indexed under Heart Failure; 1,396 are open to participants now.
This study's planned enrollment of 30 is below the median of 76 across 4,049 interventional studies indexed under Heart Failure.
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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.
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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.
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.
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.
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A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
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.
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.
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.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Patients who are non-responders to biventricular cardiac resynchronization therapy (CRT) with indications to CRT devices with defibrillator function (CRT-D) or CRT-D leads replacement. CRT-D or CRT-D leads replacement will be performed in this group of patients.
Device: Cardiac Resynchronization Therapy Devices with Defibrillator Function (CRT-D) or CRT-D Leads Replacement
Patients who are non-responders to biventricular cardiac resynchronization therapy (CRT) with indications to CRT devices with defibrillator function (CRT-D) or CRT-D leads replacement. CRT-D or CRT-D leads replacement with the new lead implantation to the left bundle branch and inactivation of conventional right and left ventricular pacing will be performed in this group of patients.
Device: CRT-D or CRT-D Leads Replacement with New Lead Implantation to Left Bundle Branch and Inactivation of Conventional Right and Left Ventricular Pacing
Patients who are non-responders to biventricular cardiac resynchronization therapy (CRT) with indications to CRT devices with defibrillator function (CRT-D) or CRT-D leads replacement. CRT-D or CRT-D leads replacement with the new lead implantation to the left bundle branch and inactivation of conventional right ventricular pacing will be performed in this group of patients.
Device: CRT-D or CRT-D Leads Replacement with New Lead Implantation to Left Bundle Branch and Inactivation of Conventional Right Ventricular Pacing
The local anesthesia will be performed on the left/right subclavian area after prepping the skin. The device pocket will be opened, the old CRT-D will be removed and disconnected from the leads. The pacing threshold, intracardiac signal amplitude and impedance (pacing and shock) on the atrial, defibrillation and left ventricular leads will be performed. If there is a lead dysfunction, the new lead will be implanted. The new CRT-D will be connected with leads and placed back into the pocket. The pocket will be closed by separate stitches (2-4 suffice) using the resorbable braided suture.
The local anesthesia will be performed on the left/right subclavian area after prepping the skin. The device pocket will be opened, the old CRT-D will be removed and disconnected from the leads. The pacing threshold, intracardiac signal amplitude and impedance (pacing and shock) on the atrial, defibrillation and left ventricular leads will be performed. If there is a lead dysfunction, the new lead will be implanted. The lead implantation to the left bundle branch (LBB) will be performed by transvenous approach and special delivery system. The new CRT-D will be connected with the leads (LBB pacing lead will be connected to defibrillation lead (DL) IS-1 connector of CRT-D and IS-1 tip of DL will be capped) and placed back into pocket. The pocket will be closed by separate stitches (2-4 suffice) using the resorbable braided suture. RV and LV pacing will be inactivated and only LBB pacing will be switched on.
The local anesthesia will be performed on the left/right subclavian area after prepping the skin. The device pocket will be opened, the old CRT-D will be removed and disconnected from the leads. The pacing threshold, intracardiac signal amplitude and impedance (pacing and shock) on the atrial, defibrillation and left ventricular leads will be performed. If there is a lead dysfunction, the new lead will be implanted. The lead implantation to the left bundle branch (LBB) will be performed by transvenous approach and special delivery system. The new CRT-D will be connected with the leads (LBB pacing lead will be connected to defibrillation lead (DL) IS-1 connector of CRT-D and IS-1 tip of DL will be capped) and placed back into pocket. The pocket will be closed by separate stitches (2-4 suffice) using the resorbable braided suture. LBB and LV pacing will be switched on.
All-cause mortality or worsening of heart failure requiring unplanned hospitalization (%)
Definition of all-cause mortality All deaths and all heart transplants due to the terminal heart failure. Heart transplanted patients will be dropped out and followed in respect of their vital status for the duration of the study. Definition of worsening of heart failure requiring unplanned hospitalization Patients requiring intra-venous medication for heart failure (including diuretics, vasodilators or inotropic agents) or a substantial increase in oral diuretic therapy for heart failure (i. e. an increase of Furosemide ≥ 40 mg or equivalent, or the addition of a thiazide to a loop diuretic) will be deemed to have worsening of heart failure. Further, rales and/or S3 sound, chest x-ray, worsening of dyspnoea, worsening of peripheral edema and increase of class NYHA will be assessed for determination of worsening of heart failure. Unplanned hospitalization is defined as any in-hospital stay over one date change, and not planned by the Investigator
Time frame: 24 month
All-cause Mortality (%)
As defined for primary endpoint: all deaths and all heart transplants because of terminal heart failure.
Time frame: 24 month
Cardiovascular Mortality (%)
All deaths due to cardiovascular reasons and all heart transplants because of terminal HF. Deaths due to worsening of HF, acute coronary syndrome, cerebrovascular accidents, or other cardiovascular events will qualify for this secondary endpoint.
Time frame: 24 month
Worsening of Heart Failure Requiring Unplanned Hospitalization (%)
As defined for the primary end-point: patients requiring intra-venous medication for HF (including diuretics, vasodilators, or inotropic agents) or a substantial increase in oral diuretic therapy for HF (i. e. an increase of Furosemide ≥ 40 mg or equivalent, or the addition of a thiazide to a loop diuretic) will be deemed to have worsening of HF. Further, rales and/or S3 sound, chest x-ray, worsening of dyspnoea, worsening of peripheral edema, and increase of class NYHA will be assessed for determination of worsening of HF. Unplanned hospitalization is defined as any in-hospital stay over one date change, and not planned by the Investigator. Reasons for worsening of HF may include atrial fibrillation, acute coronary syndrome and hypertension.
Time frame: 24 month
Unplanned Hospitalization due to Cardiovascular Reason (%)
Any in-hospital stay over one date change due to cardiovascular reason, which includes worsening of HF, acute coronary syndrome, cerebrovascular accidents, or other cardiovascular events, and not planned by the Investigator. In case the hospitalization is classified as planned by the Investigator, and the time interval between the decision to hospitalize and the hospitalization is less than 24 hours.
Time frame: 24 month
All-cause Hospitalization (%)
Any in-hospital stay over one date change.
Time frame: 24 month
Number of Delivered CRT-D Shocks (n)
An CRT-D shock is an electrical treatment consisting of a high voltage capacitor discharge delivered upon detection of VT/VF episode. All implantable cardioverter-defibrillator (ICD) shocks will be collected and classified by the Investigator as successful or non successful in respect to the termination of the tachyarrhythmia.
Time frame: 24 month
Time to First CRT-D Shock (days)
It is the time interval between the end of the 12 weeks blanking after baseline and the first shock. The appropriateness of the therapy will be also assessed.
Time frame: 24 month
Number of Delivered CRT-D ATPs (n)
An CRT-D antitachycardia pacing therapy (ATP) is an electrical treatment consisting of timed stimuli delivered upon detection of ventricular tachycardia/ventricular fibrillation (VT/VF) episode. All CRT-D ATPs will be collected and classified by the Investigator as successful or non successful in respect to the termination of the tachyarrhythmia.
Time frame: 24 month
Time to First CRT-D ATP (days)
It is the time interval between the end of the 12 weeks blanking after baseline and the first ATP therapy.
Time frame: 24 month
Number of Device Detected VT/VF Episodes (n)
It is any ventricular tachyarrhythmia which fulfils the programmed detection criteria of the device in order to be classified as tachyarrhythmic ventricular episode. Device detected episodes will be classified by the Investigator as appropriately detected in presence of real tachyarrhythmia, or inappropriately detected in case of other reasons (oversensing, noise, fast ventricular rate due to supraventricular tachycardia).
Time frame: 24 month
Left Ventricular Function (LVEF, %)
The measurement of the left ventricular ejection fraction performed by echocardiography using the modified Simpson's rule.
Time frame: 24 month
Exercise Tolerance (m)
It is the measurement of the maximal distance that the patient is able to walk within 6 minutes.
Time frame: 24 month
Life Quality (MLWHFQ score)
The life quality is the patient's ability to enjoy normal life activities. For patients suffering from HF, improvement of quality of life is one of the most important goals of new treatments, sometimes as important as improved survival. Some medical treatments can seriously impair quality of life without providing appreciable benefit, while others greatly enhance it. To evaluate the effect of cardiac resynchronization therapy with left bundle branch pacing on the quality of life of patients, general and heart failure-related quality of life questionnaires, both filled in by each individual patient, will be used. The Minnesota Living with Heart Failure Questionnaire (MLWHFQ, scale from 0 to 5) will be used.
Time frame: 24 month
Life Quality (EuroQol 5-dimensional questionnaire score)
The life quality is the patient's ability to enjoy normal life activities. For patients suffering from HF, improvement of quality of life is one of the most important goals of new treatments, sometimes as important as improved survival. Some medical treatments can seriously impair quality of life without providing appreciable benefit, while others greatly enhance it. To evaluate the effect of cardiac resynchronization therapy with left bundle branch pacing on the quality of life of patients, general and heart failure-related quality of life questionnaires, both filled in by each individual patient, will be used. The European Quality of Life Questionnaire (EuroQol 5-dimensional questionnaire, scale from 0 to 100) will be used.
Time frame: 24 month
Echocardiography Left Ventricular Volume Improvement (%)
Echocardiographic measurements will be done at baseline, 6, 12, 18 and 24 month follow-up, to evaluate effect of CRT-D implantation on left ventricle (LV) volume. Improvements due to reverse remodelling of the heart will be evaluated by measuring left ventricular end-systolic volume (LVESV), which is supposed to decrease at follow-up. Further, LV volume improvement will be calculated using formula: ((A-B)/A) x 100% (A-baseline LVESV; B-follow-up LVESV).
Time frame: 24 month
Echocardiography Left Ventricular Ejection Fraction Improvement (%)
Echocardiographic measurements will be done at baseline, 6, 12, 18 and 24 month follow-up, to evaluate effect of CRT-D implantation on left ventricle (LV) contractility function. Improvements due to reverse remodelling of the heart will be evaluated by measuring left ventricular ejection fraction (LVEF), which is supposed to increase at follow-up. Further, LV contractility function improvement will be calculated using formula: ((A-B)/A) x 100% (A-baseline LVEF; B-follow-up LVEF).
Time frame: 24 month
NYHA Class
The NYHA functional classification provides a simple way of classifying the extent of HF. It is based on questions, related to the usual daily activities and symptoms posed to the patients, and it will be determined at enrollment, baseline and at each follow-up visit. In ablated patients an improvement of NYHA class is expected, the analysis of which will help to assess the efficacy of ablation therapy.
Time frame: 24 months]
Rate of Drug Support Requirements (%)
Beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, aldosterone antagonists, diuretics, and sodium-glucose transporter type 2 inhibitors, antiarrhythmics and diuretics are drugs commonly taken by patients suffering from HF. Those drugs may have the potential to induce arrhythmic events. In patients with left bundle branch pacing (LBBP) CRT-D a reduction in drug consumption is expected, with a consequent reduction of side effects. The evaluation of the drug regimen will help to assess the effectiveness of LBBP.
Time frame: 24 month
Plan to share: Yes — Next individual participant data will be shared with other researchers: gender, age, laboratory and instrumental data
Supporting information: Statistical analysis plan, Clinical study report, Analytic code
Time frame: Starting 12 months after publication
Access criteria: Principal investigator and study director will review requests and criteria for reviewing requests
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Tomsk National Research Medical Center of the Russian Academy of Sciences