Electrical Activation Mapping Guided Tailor Made Approach for Cardiac Resynchronization Therapy

Study Overview
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Brief Summary
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Background Cardiac Resynchronization Therapy (CRT) is proven to improve survival and heart function of patient with certain electrical conduction abnormality and heart failure. However, in patient with certain electrical conduction abnormality, a good response is observed in less than 40% in patient receiving CRT. Conventionally the surgical approach of CRT is to implant one pacing lead in the right heart and one in the left heart to resynchronize the contraction and the pacing lead in the left heart is usually placed in the posterior or lateral portion of the left heart. However, this single approach may not be optimal, especially for those patients with conduction abnormality known to have poor response to CRT. Purpose of the clinical investigation The purpose of the Electrical Activation Guided CRT Study is to study the effectiveness of a tailored made approach to CRT procedure by using a noninvasive globally mapping system studying the electrical conduction under different approaches to delivery CRT. The pacing approach that optimally corrects conduction abnormality will be determined before the actual implantation procedure. Conduct of the Investigation This study will include 93 patients with conduction abnormality that known to have a poor response to CRT from Prince of Wales Hospital, Hong Kong.Subjects will be followed up at 3 months and 6 months visit.

Detailed Description
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The purpose is to prospectively study the feasibility to optimize configuration of CRT delivery for acute correction of electrical dyssynchrony using a noninvasive mapping of global electrical activation. Study Hypothesis: Tailor-made configuration of CRT delivery is feasible and able to improve responder rate compare to single method of CRT delivery in candidates with known poor response to CRT. Primary outcome measure: Responder rate of greater than 10% of LV end systolic volume reduction in patients undergoing tailor-made approach of CRT delivery at 6 months. The responder rate is to compare with pre-defined level of 40% for single method of CRT delivery namely biventricular pacing with LV lead in coronary sinus. Sample Size: The total required sample size is 93 patients with device implanted.

Official Title
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Electrical Activation Mapping Guided Tailor Made Approach for Cardiac Resynchronization Therapy

Conditions
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Heart Failure

Intervention / Treatment
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* Procedure: Noninvasive electrical dyssynchrony study


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult (aged 18 or above) of both sexes Ischemic or non-ischemic cause of heart failure QRS duration > 120 ms, non -LBBB type of conduction disturbance NYHA class III or above Sinus rhythm Informed consent by the patient Already received stable dose of guideline directed medical therapy for at least 3 months Exclusion Criteria: LBBB* patients Pregnant women Participation in another study Patient with contraindication to left ventricle catheterization by a retrograde aortic approach (eg mechanical aortic valve, severe aortic stenosis and aortic dissection) *The definitions of LBBB (QRS duration ≥130 ms; QS or rS in lead V1; broad R waves in leads I, aVL, V5, or V6; and absent q waves in leads I, V5, and V6).

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tailor-made CRT delivery<br>Patient undergoes acute noninvasive electrical dyssynchrony study with various CRT configurations. CRT device is then implanted with optimal configuration. | Procedure: Noninvasive electrical dyssynchrony study<br>* Ventricular activation maps will be acquired simultaneously with hemodynamic measurements using noninvasive mapping system (ECVUE, Medtronic Inc, USA). A thoracic computed tomographic scan will be acquired with the electrodes attached to the patient. Local ventricular activation times will be defined as the onset of the QRS complex or the pacing spike to the maximal negative slope of each unipolar electrogram. Pacing leads will be placed in high right atrium, His-bundle region, right ventricular apex, high septal RV, coronary sinus posterior/lateral branch, coronary sinus anterior branch, lateral and septal region of endocardial LV in order to deliver CRT in 8 different configurations.<br>* Other names: ECVUE;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Responder rate of greater than 10% of LV end systolic volume reduction in patients undergoing tailor-made approach of CRT delivery at 6 months. | Responder rate of greater than 10% of LV end systolic volume reduction measured by echocardiogram comparing baseline and 6 months post implant in patients undergoing tailor-made approach of CRT delivery. Responder rate of greater than 10% of LV end systolic volume reduction measured by echocardiogram comparing baseline and 6 months post implant in patients undergoing tailor-made approach of CRT delivery. The responder rate is to compare with pre-defined level of 40% for single method of CRT delivery namely biventricular pacing with LV lead in coronary sinus. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The acute electrical dyssynchrony indices of different methods of CRT delivery. | The acute electrical dyssynchrony indices of different methods of CRT delivery. | during procedure | 
| The hemodynamic responses of different methods of CRT delivery. | The hemodynamic responses of different methods of CRT delivery. The hemodynamic response will be maximal dp/dt as measured by pressure wire introduced into the left ventricle during the procedure. | during procedure | 
| Procedure duration of the optimal CRT delivery method | Procedure duration of the optimal CRT delivery method as determined by the best improvement in electrical dyssynchrony indices. | during procedure | 
| Implantation success rate of the optimal CRT delivery method | Implantation success rate of the optimal CRT delivery method as determined by the best improvement in electrical dyssynchrony indices. | during procedure | 
| Cine images (PA, LAO 300, RAO 300) and Chest X ray (PA view) | Cine images (PA, LAO 300, RAO 300) and Chest X ray (PA view) | during procedure | 
| Peri-operative and 6 months follow-up complications rate: | Thromboembolic event Dislodgement and migration of pacing leads Phrenic nerve stimulation Others | Peri-operative and 6 months | 
| Left ventricular systolic and diastolic volume at baseline and 6 months: | Echocardiogram parameter of left ventricular systolic and diastolic volume at baseline and 6 months. | baseline and 6 months | 
| Left ventricular ejection fraction at baseline and 6 months: | Echocardiogram parameter of left ventricular ejection fraction at baseline and 6 months. | baseline and 6 months | 
| Degree of mitral regurgitation at baseline and 6 months: | Echocardiogram parameter of degree of mitral regurgitation at baseline and 6 months. | baseline and 6 months | 
| Strain imaging at baseline and 6 months: | Echocardiogram parameter of strain imaging at baseline and 6 months. | baseline and 6 months | 
| NYHA class | NYHA class at baseline and 6 months. | baseline and 6 months | 
| 6 minute hall walk test | 6 minute hall walk test at baseline and 6 months. | baseline and 6 months | 
| Quality of life using Minnesota's questionnaire | Quality of life using Minnesota's questionnaire at baseline and 6 months. | baseline and 6 months | 
| Electrical parameters including threshold, sensitivity and lead impedance of pacing leads at implant and 6 months follow-up. | Electrical parameters including threshold, sensitivity and lead impedance of pacing leads at implant and 6 months follow-up. | during procedure and 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Electrical dyssynchrony, Cardiac resynchronizaton therapy, Electrical activation mapping, Noninvasive