The Effect of CRT on the Hypercapnic Ventilatory Response

Study Overview
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Brief Summary
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Central Sleep Apnoea (CSA) affects up to half of patients with severe heart failure and is associated with a poor prognosis. CSA is manifest as episodes of deep breathing interspersed with very shallow or absent breathing and is largely due to an exaggerated response to rising carbon dioxide in the blood, which normally drives how hard we breathe. Cardiac Resynchronization therapy (CRT), in which a pacemaker is implanted to improve co-ordinated contraction of the heart, has been shown to reduce the severity of CSA in some patient groups. We aim to determine whether this improvement is due to normalization of the body's response to carbon dioxide in the blood. Our hypothesis is that CRT improves CSA by normalizing the brain's response to carbon dioxide.

Detailed Description
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Sleep disordered Breathing is common in heart failure, affecting around half of patients. This may be Obstructive Sleep Apnoea due to loss of pharyngeal muscle tone (OSA, associated with obesity and snoring and predisposing to hypertension, heart attack and stroke) or Central Sleep Apnoea (CSA). CSA is particularly prevalent in severe heart failure and associated with an adverse prognosis. The mechanism involves reflex hyperventilation due to pulmonary oedema, exaggerated chemosensor response to hypercapnoea associated with increased sympathetic nervous system activation and a prolonged circulation time. It is known that CRT improved CSA in 'responders' but the mechanism is unknown. We hypothesis that CRT normalizes the respiratory response to carbon dioxide (the hypercapnic ventilatory response - HCVR). We will screen patients undergoing CRT with an Embletta sleep study to identify a group with moderate to severe CSA and a group with no sleep apnoea (controls). Patients will undergo assessment of the hypercapnic ventilatory response with a Read Re-Breathe test prior to device implantation and 6 weeks and 6 months afterwards. The gradient of minute ventilation vs PaCO2 will be compared.

Official Title
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Sleep Disordered Breathing in Patients With Implanted Cardiac Devices: Assessment of the Change in Sensitivity to Carbon Dioxide With Cardiac Resynchronization Therapy.

Conditions
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Sleep Disordered Breathing, Heart Failure

Intervention / Treatment
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* Device: CRT Implantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Heart failure with reduced ejection fraction (<40%) Either no significant sleep disordered breathing or moderate to severe CSA Able to consent to the study Ambulatory Aged 18-100 years Exclusion Criteria: Patients on Non-Invasive Ventilation Predominant OSA Unable to consent or attend for the study

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Pts with CSA for CRT implantation<br>Patients with heart failure (EF<40%) and moderate to severe CSA (>15 events per hour, >50% Central) | Device: CRT Implantation<br>* Implantation of a biventricular pacemaker or defibrillator.<br>* Other names: AUTOGEN;|
| No Sleep Apnoea for CRT implantation<br>Heart failure (EF < 40%) but no significant sleep apnoea (<5 events per hour). | Device: CRT Implantation<br>* Implantation of a biventricular pacemaker or defibrillator.<br>* Other names: AUTOGEN;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change in gradient of minute ventilation vs end tidal CO2 before and after CRT (the hypercapnic ventilatory response). |  | 6 weeks and 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6 minute walk distance |  | 6 weeks and 6 months | 
| Change in resting PaCO2 |  | 6 weeks and 6 months | 
| Change in left ventricular ejection fraction |  | 6 weeks and 6 months | 
| Change in plasma B-Type Natriuretic Peptide level |  | 6 weeks and 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiac Resynchronization Therapy, Central Sleep Apnoea, Sleep Disordered Breathing, Heart Failure, Hypercapnic Ventilatory Response