Cardiac Resynchronisation Therapy in Combination With Overdrive Pacing in the Treatment of Central Sleep Apnea in CHF (Morpheus)

The primary objective of this study is to compare the Apnea- Hypopnea Index in HF patients with concomitant CSA, after 12 weeks of CRT alone to CRT in combination with one night of overdrive pacing. Secondary objectives are to evaluate the effects of a single night of overdrive pacing applied after 12 weeks of CRT vs. CRT alone on breathing events, sleeping events, and neurohormonal markers. An additional secondary objective of the study is to compare the efficacy of CRT in HF patients with concomitant CSA to HF patients without concomitant CSA.

Study Overview

• Status: Completed
• Conditions: Heart Failure; Central Sleep Apnea
• Intervention / Treatment: Device: CRT + AOP

Detailed Description

Sleep apnea is a common and often undiagnosed disorder associated with substantial cardiovascular morbidity and mortality. In recent years studies have been published presenting the relationship between heart failure (HF) and central sleep apnea (CSA). CSA associated with Cheyne-Stokes respiration is a form of periodic breathing in which central apneas and hypopnea alternate with periods of hyperventilation, characterized by a regular crescendo-decrescendo oscillation of tidal volume, which is thought to be caused by dysfunction of central respiratory control. Unlike, obstructive sleep apnea (OSA), CSA likely arises as a consequence of HF.Since 2002, several results have reported on the benefit of atrial overdrive (AOP) pacing in patients suffering from sleep apnea. These results could not be confirmed for obstructive sleep apnea in several subsequent studies. Cardiac resynchronization therapy (CRT) has been proposed as another potential therapeutic pacing approach for CSA by two recently published investigations.The combined therapeutic impact of AOP and CRT (CRT+AOP) so far has not been investigated.We aimed to evaluate the effect of CRT alone and CRT+AOP on CSA in patients with CHF.

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • Bonn, Germany, 53105
    • Medizinische Klinik und Poliklinik II Universitätsklinikum, University of Bonn
  • Göttingen, Germany, D-37075
    • Georg-August-Universität, Department of Cardiology and Pneumology

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients with documented clinical history of symptomatic but stable congestive heart failure, NYHA III or NYHA IV, of at least six weeks duration.
• Patient has an indication for a CRT device, or patients with previous pacemaker indication, except Sick Sinus Syndrome, and currently in need for an upgrade to a CRT device
• Patient is scheduled for the implantation of a CRT device
• Patient is over 18 years of age
• Patient provides Informed Consent

Exclusion Criteria:

• Inability to complete overnight sleep study as specified by the protocol
• Myocardial infarction or coronary revascularization procedure within 2 calendar months prior to enrollment
• Planned or strong likelihood of cardiac surgery within 4 months following enrollment
• A spirometric confirmation of obstructive lung disease
• Evidence of obstructive sleep apnea at baseline polysomnography
• Body mass index >30 kg/m²
• Pregnant women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: CRT for patients with CSA; Patients suffering from HF with central Sleep Apnea (CSA) programmed to DDD/45 (CRT) for 12 weeks. Intervention is CRT.
Active Comparator: CRT + AOP for patients with CSA; Patients suffering from HF with central Sleep Apnea programmed to DDD/+15 bpm nocturnal rate (CRT + AOP) for 12 weeks. Intervention is the AOP in addition to CRT.	Device: CRT + AOP; The CSA group will undergo 2 sleep evaluation on two consecutive nights, during which the device will be programmed according to the randomization scheme (one night CRT, DDD/45 and the other CRT, DDD/15 bpm over mean nocturnal heart rate). The mean nocturnal heart rate over the last week is derived from the device memory.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AHI	To demonstrate that a single night of overdrive pacing applied after 12 weeks of cardiac resynchronization therapy in comparison to cardiac resynchronization alone will improve sleep apnea as measured by Apnea- hypopnea- index (AHI)	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NYHA class	To evaluate the effects of nocturnal overdrive pacing applied after 12 weeks of CRT vs. CRT alone on NYHA	12 weeks
Echocardiographic parameter	To evaluate the effects of nocturnal overdrive pacing applied after 12 weeks of CRT vs. CRT alone on LVEF	12 weeks
Neurohormonal parameter	To evaluate the effects of nocturnal overdrive pacing applied after 12 weeks of CRT vs. CRT alone on neurohormonal marker NT pro-BNP	12 weeks
Clinical parameter	To evaluate the effects of nocturnal overdrive pacing applied after 12 weeks of CRT vs. CRT alone on the clinical parameter VO2max	12 weeks
Quality of Life	To evaluate the effects of nocturnal overdrive pacing applied after 12 weeks of CRT vs. CRT alone on Quality of life	12 weeks

Collaborators and Investigators

• Sponsor: Medtronic Cardiac Rhythm and Heart Failure
• Investigators: Principal Investigator: S Andreas, Prof. Dr, Georg-August-Universität, Göttingen, Department of Cardiology and Pneumology, Robert-Koch Str. 40, 37075 Göttingen, Germany

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2005
• Primary Completion (Actual): December 1, 2006
• Study Completion (Actual): December 1, 2006

Study Registration Dates

• First Submitted: October 30, 2007
• First Submitted That Met QC Criteria: October 30, 2007
• First Posted (Estimated): October 31, 2007

Study Record Updates

• Last Update Posted (Actual): July 3, 2025
• Last Update Submitted That Met QC Criteria: June 30, 2025
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Sleep Apnea, CRT
• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Wake Disorders; Signs and Symptoms, Respiratory; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Apnea Syndromes; Apnea; Sleep Apnea, Central
• Other Study ID Numbers: 113 (Shenzhen Universisty general hospital)