Different Loop Gain Phenotypes in Patients With Chronic Systolic Heart Failure and Periodic Breathing

December 14, 2023 updated by: Wissenschaftliches Institut Bethanien e.V

Central sleep apnoea (CSA) is common in patients with chronic systolic heart failure (HFrEF). Various trials have shown a prevalence of 21 - 37% in this group of people. Up to 66% of patients with CSA and HFrEF present with periodic breathing (PB), which is considered being a marker of HF severity and poor prognosis. Brack et al. summarized data from cohorts, longitudinal studies and retrospective analyses showing an independently increased risk of death in HF patients with PB (HR 2.1-5.7 in five of seven studies). Furthermore, PB in HF patients is known to reduce quality of life and exercise performance and to increase sympathetic nerve activity as well as the probability of malignant cardiac arrhythmias.

The pathogenesis of PB is characterized by an instability of ventilatory drive. The level of carbon dioxide (CO2) in blood and cerebrospinal fluid correlates linearly with minute ventilation. A high level of CO2 increases ventilation while hypocapnia dampens it. This control theory is based on the loop gain (LG), which represents the sensitivity and reactivity of the ventilatory system and comprises three components: The plant gain defines the capacity of the system to change PaCO2 in response to a change in ventilation (metabolic response). It is influenced by the lung volume as well as the anatomy of the thorax and the upper airways. The feedback gain is defined by the chemoreceptor responsiveness in reaction to blood gas changes. The controller gain is represented by the respiratory control center in the brain stem and defines the capacity of the system to change ventilation in response to a change in PaCO2 (ventilatory response).

Sands et al. proposed and validated a mathematical model based on the ventilatory cycle pattern that quantifies the feedback loop. The ratio of ventilatory and cycle duration within the PB pattern is defined as the duty ratio (DR), which is the basis to calculate the LG. Any temporary breathing disturbance causing a PB pattern with a LG < 1 stabilizes within a few breathing cycles. A LG > 1 represents an unstable ventilatory response and slight changes of CO2 are accompanied by overshooting and undershooting of the ventilation. In that case, the polysomnography shows the typical pattern of waxing and waning of the tidal volume and effort.

HF patients typically present with an increased LG due to an impaired left ventricular function and a hyperstimulation of pulmonary vagal receptors. Furthermore, Khoo showed an increased chemosensitivity (controller gain) as well as a decreased ventilatory capacity (plant gain) in this group of people.

Sands and colleagues characterized PB considering the mean LG derived from several ventilatory cycles during non-REM sleep. This retrospective study of PB in HFrEF patients addresses the following questions:

  1. Is a single LG value appropriate to characterize the individual PB?
  2. Does the LG depend on sleep stage and body position?
  3. Does the intraindividual LG variability allow for the discrimination of different PB phenotypes and, if so, do these phenotypes differ in further characteristics?

Study Overview

Status

Completed

Conditions

Study Type

Observational

Enrollment (Actual)

12

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Solingen, Germany, 42699
        • Wissenschaftliches Institut Bethanien für Pneumologie e.V.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

Patients admitted to the sleep lab for diagnostic polysomnography.

Description

Inclusion Criteria:

  • Systolic heart failure with left-ventricular ejection fraction <45%
  • Apnea-Hypopnea index >15 per hour as determined by diagnostic polysomnography
  • Predominant central sleep apnea as defined by >50% central respiratory events

Exclusion Criteria:

  • <50 evaluable respiratory events for loop gain analysis during diagnostic polysomnography

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
HF+CSA+PB
Systolic heart failure with predominant central sleep apnea and periodic breathing

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Loop Gain
Time Frame: During one day of diagnostic polysomnography
Mathematically determined loop gain of periodic breathing according to Sands et al. [10] based on diagnostic polysomnography
During one day of diagnostic polysomnography

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Wissenschaftliches Institut Bethanien e.V

Investigators

  • Principal Investigator: Winfried J Randerath, Prof. Dr., Director

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 28, 2016

Primary Completion (Actual)

November 14, 2016

Study Completion (Actual)

November 14, 2016

Study Registration Dates

First Submitted

May 9, 2018

First Submitted That Met QC Criteria

May 21, 2018

First Posted (Actual)

May 22, 2018

Study Record Updates

Last Update Posted (Estimated)

December 15, 2023

Last Update Submitted That Met QC Criteria

December 14, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • WI_LoopGain

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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