Long QT Syndrome and Sleep Apnea
Condition: Long QT Syndrome; Sleep Apnea
MeSH terms: Apnea; Sleep Apnea Syndromes; Long QT Syndrome; Syndrome
Study type: Interventional

Summary: 
      Obstructive sleep apnea (OSA) has been associated with cardiac repolarization abnormalities
      and implicated in sudden cardiac death. A biologically plausible mechanism by which OSA
      exerts this lethality is by QT interval prolongation, a known marker of ventricular
      tachyarrhythmias (VTA) leading to cardiac death. Congenital long QT syndrome (LQTS) is a
      familial arrhythmogenic disorder characterized by prolonged QT interval on the
      electrocardiogram and increased propensity for VTA. Preliminary data identify an association
      of the extent of severity of OSA and progressive prolongation of the corrected QT interval in
      LQTS.
    

Detailed description: 
      Potential participants will come to the Cleveland Clinic Clinical Research Unit (CRU) for
      informed consent, eligible participants will undergo a 12 lead electrocardiogram. If the
      participants is found to have long QT syndrome (QTc ≥ 450 in men ad ≥ 470 in women) the
      participant will continue on in the study. If the participant is found to not have long QT
      syndrome the participant will exit the study. If continuing on in the study the participant
      will undergo a fasting venipuncture and blood pressure measurements. The participant will
      then be shown how to use the portable sleep study hook-up and continuous 12-lead ECG
      monitoring to be monitored in the home setting. The sleep study and ECG monitors will be
      returned by a courier service the next morning.

      Those participants who are identified to have OSA (apnea hypopnea index>5, estimate 50% of
      those recruited) on the portable sleep monitoring will be invited to wear CPAP for 2-3 months
      with a follow up visit with repeat portable polysomnographic and continuous
      electrophysiologic assessments and CRU visit for bloodwork and blood pressure.

      DATA COLLECTION Portable Polysomnography The Embletta Gold ® is a battery-operated device
      that can sample data at a 1000 Hz sampling rate and store data at 200 Hz, with 1 GB of
      storage capacity allowing storage of data from up to 20-24 hrs of recording. The device
      contains the critical sensors which are recommended by the American Academy of Sleep Medicine
      as validated sensors for measuring OSA: nasal pressure/flow; thoracic and abdominal
      inductance plethysmography (effort); and finger pulse oximetry (oxygen saturation).

      Relevant PSG Variables: A registered polysomnologist will score the sleep study data. Apneas
      will be classified as "central" or "obstructive" according to the absence or presence of
      respiratory effort respectively. Hypopneas will be scored as a 50% amplitude reduction in
      inductance or flow and associated 3% oxygen desaturation or arousal. Periodic breathing will
      be defined as airflow or inductance channels increasing and decreasing at least 50% from the
      maximum, in a cyclic waxing and waning or "sinusoidal" manner for a consecutive period of >10
      min.

      Continuous Overnight 12-lead ECG Monitoring CardioDay Holter (GE) monitoring reads SEER 12
      data and exports Holter data as individual 10 second, 12 lead reports up to six per minute,
      i.e. all recorded data. The monitor is capable of continuous 12-lead ECG monitoring with the
      ability to record up to 10 days with Bluetooth ® technology and 12-bit signal resolution with
      up to 1024 sampling rate.

      ECG Sensor Application. This will be performed by a trained research coordinator at the visit
      in tandem with sleep monitor lead hook-up. Participants will be asked to remove clothing from
      the waist up to attach the sensors to the chest. Staff will ensure privacy by covering the
      participant with a sheet or gown. The staff will shave necessary areas on the chest prior to
      sensor application to ensure that the sensors stick closely to the skin and will provide the
      participant with the ECG monitor/holster/clip, leads, communicator and charger, electrodes
      and a handbook with simple pictorial/written educational instructions. A research coordinator
      will be available by phone 24-7 to address issues with device malfunction, lead placement and
      replacement of equipment. ECG quality grade data will be collected: (excellent: >90% of ECG
      data without artifact, good: 70-90% without artifact, fair: 50-70% without artifact, poor
      <50% artifact free).

      Relevant ECG Variables. Standard average QT interval measures will be obtained with eventual
      ability to examine peri-apneic and peri-hypopneic alterations in QT interval. Novel QT
      morphologic assessments will be made with the GE compatible platform described below.

      Novel QT analysis platform An analysis system which enables biopharmaceutical companies to
      analyze detailed morphology of the electrocardiography (ECG) T-wave (QT Guard Plus™,
      eResearchTechnology, Inc.). The system identifies and quantifies characteristic changes in
      the shape of the T-wave found in drugs that produce Torsades de Pointes (TdP), the latter a
      potentially lethal tachyarrhythmia. QT Guard Plus imports individual 10 second, 12 lead
      reports for analysis and parameter extraction, i.e. T wave shape measures with the capability
      to extract other electrophysiologic signatures as well.

      Resting Blood Pressure BP will be measured after the participant has been sitting quietly for
      at least 5 minutes following standardized guidelines using a calibrated sphygmomanometer.
      Cuff size will be determined by measuring the circumference of the upper arm, measured at the
      midpoint and identifying the appropriate bladder size from a standard chart. Measurements
      will be repeated three times and recorded.

      Fasting Venipuncture Phlebotomy (40cc) will be performed the morning of the baseline and
      follow-up visits using standard techniques by trained research staff following written
      procedures (e.g., pre-labeled bar coded tubes, minimizing trauma, etc.). The sample will be
      divided into tubes for the varied analyses (20 mL clot for serum, 20 mL EDTA). Clots will be
      centrifuged and the serum removed within 1 hr of venipuncture. Plasma from EDTA samples will
      be stored for future DNA analysis. Assays will be stored in dedicated, alarmed freezers at
      -80°C in the CRU Core Lab and transferred to designated space in the Pathology and Laboratory
      Medicine Institute.

      Morning blood work to examine the association of electrolytes in relation to QT interval
      duration and stability upon follow up after use of CPAP. With collateral funding, bloodwork
      will allow for examination of markers of systemic inflammation which may serve as
      intermediary pathways for cardiac electrophysiologic biomarkers of VTA in OSA.

      Continuous Positive Airway Pressure Intervention Participants randomized to CPAP will be
      provided with an Autopap REMstar device (Philips-Respironics, Inc, Murrysville, PA) with
      integrated humidifier, set at a pressure range of 4-20 cm H2O, with auto-titration according
      to the device's algorithm for detecting airflow limitation which provided wireless
      transmission of usage information to our research team.
    

Intervention name(s): Continuous Positive Airway Pressure (CPAP)
Intervention type(s): Device
Intervention description(s): If diagnosed with Long QT Syndrome and have Sleep Apnea index >5 pauses per hour then given CPAP to wear for approximately 3 months.
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment