LEft VEntricuLar Activation Time Shortening With Physiological Pacing vs Biventricular Resynchronization Therapy

Study Overview
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Brief Summary
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The LEVEL-AT Trial (LEft VEntricuLar Activation Time Shortening with Physiological Pacing vs Biventricular Resynchronization therapy: a randomized study) is a non-inferiority study that aims to determine if physiological pacing could decrease the left ventricular activation time compared with biventricular therapy.

Detailed Description
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To date studies have showed that physiological pacing could get similar clinical and echocardiographic response to that obtained with biventricular therapy. Activation time shortening with permanent physiological pacing has not been studied. This study will randomize 70 patients to a strategy of: biventricular pacing versus physiological pacing. LEVEL-AT study will analyze the following parameters in the 2 groups: shortening of the QRS, activation time with electrocardiographic imaging, echocardiographic asynchrony and ventricular function and clinical parameters (NYHA functional class, mortality and heart failure hospitalization). Clinical, electrocardiographic, echocardiographic and electrocardiographic imaging follow-up will be performed for 1 year.

Official Title
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LEft VEntricuLar Activation Time Shortening With Physiological Pacing vs Biventricular Resynchronization Therapy: a Randomized Study (LEVEL-AT)

Conditions
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Physiological Pacing, Resynchronization Therapy

Intervention / Treatment
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* Device: Lead placed in the His-Purkinje system in order to achieve QRS shortening.
* Device: Lead is placed in a tributary of the coronary sinus.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient must indicate their acceptance to participate in the study by signing an informed consent document. The patient must be ≥ 18 years of age. Left bundle branch block, QRS ≥130 and FEVI <=35% (Indication of cardiac resynchronization IA or IB ESC Guidelines). No indication of stimulation for AV block. Patients with indication of resynchronization therapy for ventricular dysfunction and indication of cardiac stimulation for AV block according to ESC Guidelines (IA ESC Guidelines). Non-left bundle branch block, QRS ≥150 and FEVI <=35% (Indication of cardiac resynchronization IIaB ESC Guidelines). Exclusion Criteria: Myocardial infarction, unstable angina or cardiac revascularization during the previous 3 months. Pregnancy. Participating currently in a clinical investigation that includes an active treatment.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, unicentric, simple blind.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Physiological pacing<br>Pacing the his-purkinje system. Crossover to biventricular CRT will be allowed in the following situations: failed physiological pacing lead implantation; high thresholds (>3.5V / 1ms); no shortening of QRS (shortening <20%) or failure to meet non-selective HBP criteria [Europace. 2019 Oct 9. doi: 10.1093/europace/euz275]. | Device: Lead placed in the His-Purkinje system in order to achieve QRS shortening.<br>* Physiologic pacing to achieve QRS shortening. If the patient has indication of stimulation (AV block), a backup lead will be implanted in the right ventricle. All patients will have a lead placed in the right atrium (except those that have permanent atrial fibrillation).<br>|
| Active Comparator: Biventricular resynchronization therapy<br>Pacing from the right ventricular and coronary sinus leads. Electrocardiographic optimization with fusion-optimized intervals. Crossover from biventricular CRT to physiological pacing will be allowed in the following situations: coronary sinus cannot be cannulated; no lateral or posterolateral branches; or phrenic stimulation. | Device: Lead is placed in a tributary of the coronary sinus.<br>* Biventricular Resynchronization Therapy is the use of a pacemaker with two endocardial leads placed in the right atrium and right ventricle. The third lead is placed in a tributary of the coronary sinus.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Left ventricular activation time. | Left ventricular activation time measured by eletrocardiographic imaging. | 45 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| QRS duration. | QRS duration (milliseconds) measured with a 12-lead ECG. | Implant, 6 months and 12 months. | 
| Left ventricular activation time. | Left ventricular activation time measured by eletrocardiographic imaging | 6 months and 12 months. | 
| Change in left ventricular function. | Left ventricular ejection fraction measured with Simpson method with echocardiography. | 6 months and 12 months. | 
| Change in end-systolic volume. | End-systolic volume measured with echocardiography. | 6 months and 12 months. | 
| Change in NYHA functional class. | NYHA functional class I, II, III, IV. | 6 months and 12 months. | 
| Hospitalization due to heart failure or mortality (combined endpoint). | Hospitalization: patient hospitalization (yes/no) Mortality: mortality (yes/no) | 1 year. | 
| Correction of septal flash | Correction of septal flash determined with echocardiography (M mode) | 15 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Physiological pacing, Resynchronization therapy, Electrocardiographic imaging