Sleep Apnea and CRT Upgrading

Study Overview
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Brief Summary
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Cardiac resynchronization therapy may reduce central sleep apnea, but there is no prospective randomized study so far demonstrating such an effect in patients with conventional pacemaker undergoing upgrading to CRT because of heart failure.

Detailed Description
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Within the last decade cardiac resynchronization therapy (CRT) has been proven to be an effective therapy to reduce morbidity and mortality in chronic heart failure patients with wide QRS complex, in particular complete left bundle branch block. New indications have recently been established, including patients with mild symptoms and patients in need of conventional pacing such as high-grade atrioventricular block. More than half - up to 80% - of patients with heart failure suffer from concomitant sleep apnea (SA), which further worsens symptoms and prognosis. Cardiac resynchronization therapy may ameliorate sleep apnea, but only the central form of sleep apnea (CSA). However, only very small uncontrolled studies with mainly less than 20 patients have been reported so far concerning the interactions between CRT and sleep apnea, and no data are available in patients with conventional right ventricular pacing undergoing upgrading to CRT. Therefore, we want to perform a study called UPGRADE which is characterized being the first randomized study comparing the effects of new-onset cardiac resynchronization therapy on moderate and severe central sleep apnea, defined by an AHI ≥ 15/h as assessed by polysomnography in patients with conventional right ventricular pacing which is known to decrease cardiac function, induce heart failure and atrial fibrillation using a new technology called AP Scan® which enables continuous and reliable monitoring of sleep-disordered breathing (SDB); this technology is further validated with polysomnography, the gold standard in the diagnosis and follow-up in patients with sleep apnea Unfortunately, one third of patients still do not benefit from CRT (so-called non-responders). On the other hand, up to 20% of patients greatly benefit and completely recover in terms of normalization of left ventricular ejection fraction and/or functional capacity (so-called super-responders). Research is urgently needed to decrease the number of non-responders and increase the number of super-responders. Patient selection is still based on QRS duration and its morphology. Echocardiography and other imaging techniques for mechanical dyssynchrony assessment have failed to be a useful predictor for adequate patient selection. Therefore, we further want to test whether CRT itself does not only improve concomitant sleep apnea, but also if preexisting sleep apnea predicts the response to CRT in patients with previously conventional right-ventricular pacing undergoing an upgrade to CRT by additional implantation of a left ventricular lead.

Official Title
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Central Sleep Apnea and New-onset Cardiac Resynchronization in Patients With Conventional Pacemaker or ICD Therapy: a Multicenter, Randomized Clinical Trial

Conditions
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Cardiomyopathy

Intervention / Treatment
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* Device: CRT
* Device: conventional right ventricular stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: left ventricular ejection fraction < 50% implanted conventional pacemaker or ICD with a right ventricular pacing rate > 40% or planned ablate and pace therapy age 40 - 85 years Exclusion Criteria: NYAH IV liver cirrhosis renal insufficiency (GFR < 30ml/min/1,73m²) expectancy of life < 1 year premenopausal woman drug or substance abuse hyperthyreosis custodianship CM allergy any condition that may compromise the compliance of the patient, or would preclude the patient from successful completion of the study plaster allergy enrollment in another clinical trial

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 85 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 |
| --- | --- |
| Other: CRT<br>After randomization and polysomnography the CRT will get activated. After 3-5 months cross over to conventional right ventricular stimulation. | Device: CRT<br>* The new device is the first CRT-P that relies on a physiological parameter, respiration, to allow the pacemaker to follow the patient's breath and help create an appropriate pacing rate.<br>* Other names: INCEPTA / AUTOGEN (Boston Scientific);|
| Other: Right Ventricular Stimulation<br>After randomization and polysomnography the conventional right ventricular stimulation will get activated. After 3-5 months cross over to CRT activation. | Device: conventional right ventricular stimulation<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of central sleep apnea | improvement of moderate / severe central sleep apnea (AHI ≥ 15/h) due to new onset CRT as compared to ongoing conventional right ventricular pacing | January 2014 - June 2021 | 
| Validation of the AP scan by the gold standard polysomnography |  | January 2014 - June 2021 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CRT response | secondary endpoints = CRT response according to pre-existing sleep apnea (RDI 0-14/h versus ≥ 15/h) improvement of left ventricular ejection fraction and reduction in left ventricular endsystolic volume as assessed by transthoracic echocardiography decrease in NTproBNP / BNP plasma concentration | January 2014 - June 2021 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Patients with pacemaker or ICD therapy