The Effect of CRT on the Hypercapnic Ventilatory Response

Heart Failure Clinical Trial

Official title:

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

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT02203383
• Other study ID #: 14/LO/0078
• Status: Suspended
• Phase: N/A
• First received: July 28, 2014
• Last updated: November 8, 2016
• Start date: June 2014
• Est. completion date: October 2017

Study information

• Verified date: November 2016
• Source: Royal Brompton & Harefield NHS Foundation Trust
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Research Ethics Committee
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 40
• Est. completion date: October 2017
• Est. primary completion date: October 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Observational Model: Case Control, Time Perspective: Prospective

Related Conditions & MeSH terms

• Heart Failure
• Respiratory Aspiration
• Sleep Disordered Breathing

Intervention

Device:
• CRT Implantation
Implantation of a biventricular pacemaker or defibrillator.

Locations

Country	Name	City	State
United Kingdom	Royal Brompton and Harefield NHS Foundation Trust	London

Sponsors (2)

Lead Sponsor	Collaborator
Royal Brompton & Harefield NHS Foundation Trust	Boston Scientific Corporation

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The change in gradient of minute ventilation vs end tidal CO2 before and after CRT (the hypercapnic ventilatory response).		6 weeks and 6 months	No
Secondary	6 minute walk distance		6 weeks and 6 months	No
Secondary	Change in resting PaCO2		6 weeks and 6 months	No
Secondary	Change in left ventricular ejection fraction		6 weeks and 6 months	No
Secondary	Change in plasma B-Type Natriuretic Peptide level		6 weeks and 6 months	No