Clinical trial NCT02203383: The Effect of CRT on the Hypercapnic Ventilatory Response
Official title: Sleep Disordered Breathing in Patients With Implanted Cardiac Devices: Assessment of the Change in Sensitivity to Carbon Dioxide With Cardiac Resynchronization Therapy.
Study type: OBSERVATIONAL
Overall status: SUSPENDED
Conditions: Sleep Disordered Breathing
Heart Failure
Keywords: Cardiac Resynchronization Therapy
Central Sleep Apnoea
Sleep Disordered Breathing
Heart Failure
Hypercapnic Ventilatory Response
Lead sponsor: Royal Brompton & Harefield NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: Boston Scientific Corporation
First posted: 2014-07-29
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with heart failure with reduced ejection fraction (\<40% on echocardiography) due to undergo implantation of a biventricular pacemaker, with either no significant sleep disordered breathing or moderate to severe CSA.

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.

Eligibility criteria: 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

Primary outcomes:
measure: The change in gradient of minute ventilation vs end tidal CO2 before and after CRT (the hypercapnic ventilatory response).
timeFrame: 6 weeks and 6 months
Secondary outcomes:
measure: 6 minute walk distance
timeFrame: 6 weeks and 6 months
measure: Change in resting PaCO2
timeFrame: 6 weeks and 6 months
measure: Change in left ventricular ejection fraction
timeFrame: 6 weeks and 6 months
measure: Change in plasma B-Type Natriuretic Peptide level
timeFrame: 6 weeks and 6 months
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Royal Brompton and Harefield NHS Foundation Trust
Study officials:
affiliation: Imperial College. Royal Brompton Hospital
name: Ali Vazir, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Imperial College London
name: Martin Cowie, MD
role: STUDY_CHAIR
References: