Long QT Syndrome and Sleep Apnea

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.