The Effect of CRT on the Hypercapnic Ventilatory Response

Suspended

• Conditions: Heart Failure; Sleep Disordered Breathing
• Interventions: Device: CRT Implantation

• Registration Number: NCT02203383
• Lead Sponsor: Royal Brompton & Harefield NHS Foundation Trust

Brief Summary

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

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.

Study Timeline

• Study Start: 2014-06
• Study First Submitted: 2014-07-28
• Study First Submitted QC: 2014-07-28
• Study First Posted: 2014-07-29
• Status Verified: 2016-11
• Last Update Submitted: 2016-11-08
• Last Update Posted: 2016-11-09
• Primary Completion: 2017-10
• Study Completion: 2017-10

Recruitment & Eligibility

• Status: SUSPENDED
• Sex: All
• Target Recruitment: 40

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
No Sleep Apnoea for CRT implantation	CRT Implantation	Heart failure (EF \< 40%) but no significant sleep apnoea (\<5 events per hour).
Pts with CSA for CRT implantation	CRT Implantation	Patients with heart failure (EF\<40%) and moderate to severe CSA (\>15 events per hour, \>50% Central)

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Change in left ventricular ejection fraction	6 weeks and 6 months
Change in resting PaCO2	6 weeks and 6 months
6 minute walk distance	6 weeks and 6 months
Change in plasma B-Type Natriuretic Peptide level	6 weeks and 6 months

Trial Locations

Locations (1)

Royal Brompton and Harefield NHS Foundation Trust; 🇬🇧 London, United Kingdom