Right Ventricular Resynchronization Therapy

Study Overview
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Brief Summary
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The purpose of this study is to determine whether cardiac resynchronization therapy with the use of an implanted electronic pacemaker reduces morbidity associated with chronic thromboembolic pulmonary hypertension

Detailed Description
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Rationale: The clinical severity of right ventricular disease is largely determined by right-to-left ventricular dyssynchrony, i.e., delay of electrical activity between the right and left ventricles. Moreover, in patients with chronic thromboembolic pulmonary hypertension (CTEPH), we found that acute correction of this dyssynchrony by temporary pacing (prior to pulmonary endarterectomy, presently the therapy of choice for CTEPH) results in significant improvement in cardiac output. In this study, we aim to establish whether chronic pacing with the use of implanted pacemakers confers long-lasting improvements in cardiac output and functional class. Objective: To study whether chronic pacing with implanted pacemakers confers long-lasting improvements in cardiac output and functional class in severely symptomatic CTEPH patients who are not eligible for pulmonary endarterectomy, or those in whom pulmonary endarterectomy has failed. Study design: Chronic intervention study, double-blinded, randomized, cross-over. Study population: Adult CTEPH patients who are not eligible for pulmonary endarterectomy, or those in whom pulmonary endarterectomy has failed. Intervention (if applicable): chronic right ventricular resynchronization therapy (RVRT), i.e., chronic right atrial, right ventricular, and left ventricular pacing with the use of implanted pacemakers. Main study parameters/endpoints: (Duration of) improvements (in l/min) in cardiac output as measured using Doppler echocardiography, and functional class as measured using 6-minute walking distance (6-MWD), right and left ventricular dimensions and ejection fractions (99mTechnetium scintigraphy), biomarkers for heart failure (serum NT-proBNP levels), and quality of life (SF-36) questionnaire. Design: Randomized, double-blind, cross-over study with 2 arms of 10 patients each (arms 1 and 2). In arm 1, RVRT is switched on immediately after pacemaker implant, is switched of in week 5, and switched on at the start of week 6 until study end (32 weeks). In arm 2, RVRT is switched at the start of week 5 after pacemaker implant until study end (32 weeks). At various follow-up visits at weeks 1, 4, 5, 6, 8, 12, 16, the main study parameters/endpoints (see previous paragraph) will be assessed.

Official Title
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Long-term Right Ventricular Resynchronization Therapy for Chronic Thromboembolic Pulmonary Hypertension

Conditions
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Right Ventricular Failure, Chronic Thromboembolic Pulmonary Hypertension, Pulmonary Hypertension

Intervention / Treatment
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* Device: Implantation of 3-chamber pacemaker


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients with chronic thromboembolic pulmonary hypertension (CTEPH) who are ineligible for pulmonary endarterectomy, and those in whom pulmonary endarterectomy has failed Exclusion Criteria: None

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: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Immediate RVRT<br>RVRT switched on immediately after pacemaker implant | Device: Implantation of 3-chamber pacemaker<br>* Implantation of pacemaker with leads in right atrium, right ventricle, and coronary sinus (left ventricle) with the aim of providing right ventricular resynchronization therapy (RVRT); this is accomplished by pacing the right ventricle ahead of the left ventricle, e.g., by setting (shortening) the A-V delay between right atrium and right ventricle to an optimal level.<br>* Other names: Medtronic CRT pacemaker systems will be implanted;|
| Placebo Comparator: Delayed RVRT<br>RVRT switched on 4 weeks after pacemaker implant | Device: Implantation of 3-chamber pacemaker<br>* Implantation of pacemaker with leads in right atrium, right ventricle, and coronary sinus (left ventricle) with the aim of providing right ventricular resynchronization therapy (RVRT); this is accomplished by pacing the right ventricle ahead of the left ventricle, e.g., by setting (shortening) the A-V delay between right atrium and right ventricle to an optimal level.<br>* Other names: Medtronic CRT pacemaker systems will be implanted;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in right/left ventricular synchrony measured using tissue Doppler echocardiography |  | within 8 months after pacemaker implantation | 
| Increase in cardiac output measured using Doppler echocardiography and scintigraphy |  | within 8 months after pacemaker implantation | 
| Increase in functional capacity measured with six-minute walking distance |  | within 8 months after pacemaker implantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Increase in well-being assessed with questionnaire |  | within 8 months after pacemaker implantation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Right ventricular failure, Pacemaker, Cardiac resynchronization therapy, Pulmonary hypertension