The Effect of CRT on the Hypercapnic Ventilatory Response

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

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.

Study Overview

• Status: Suspended
• Conditions: Heart Failure; Sleep Disordered Breathing
• Intervention / Treatment: Device: CRT Implantation

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 Type: Observational
• Enrollment (Anticipated): 40

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, SW6 6NP
    • Royal Brompton and Harefield NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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.

Description

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 Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Royal Brompton & Harefield NHS Foundation Trust
• Collaborators: Boston Scientific Corporation
• Investigators: Principal Investigator: Ali Vazir, PhD, Imperial College. Royal Brompton Hospital; Study Chair: Martin Cowie, MD, Imperial College London

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Anticipated): October 1, 2017
• Study Completion (Anticipated): October 1, 2017

Study Registration Dates

• First Submitted: July 28, 2014
• First Submitted That Met QC Criteria: July 28, 2014
• First Posted (Estimate): July 29, 2014

Study Record Updates

• Last Update Posted (Estimate): November 9, 2016
• Last Update Submitted That Met QC Criteria: November 8, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: Heart Failure; Cardiac Resynchronization Therapy; Sleep Disordered Breathing; Central Sleep Apnoea; Hypercapnic Ventilatory Response
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Nervous System Diseases; Respiratory Tract Diseases; Apnea; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Heart Failure; Sleep Apnea Syndromes; Respiratory Aspiration
• Other Study ID Numbers: 14/LO/0078