Obstructive Sleep Apnea Destabilizes Myocardial Repolarization Homogeneity

Literature shows that patients with obesity and Obstructive Sleep Apnea (OSA), both occurring independently, are more likely to develop cardiovascular diseases and sudden cardiac death (SCD). Assuming that ventricular depolarization is more stable than repolarization then QT interval parameters may be used for heart muscle repolarization assessment for those groups of patients.

There were 121 patients included in the study, both - women and men, aging from 35-65 with visceral obesity. Only healthy patients were included - the ones who were not treated for any chronic disease, taking QT elongating drugs, or were not treated with Continuous Positive Airway Pressure (CPAP) therapy at that time.

The current study was a prospective, observational clinical trial performed between September 2016 and August 2019 at a single-center institution specializing in treatment of patients with obstructive sleep apnea. The inclusion criteria were as follows: (1) gender: female or male, (2) age 35-65 years old, (3) visceral obesity, (4) lack of acute or chronic diseases that may have an influence on rhythm or conduction disorders, (5) not undergoing Continuous Positive Airway Pressure therapy (CPAP) or taking drugs that have or may have an influence on QT interval duration \[according to Credible Meds list (Woosley et al, 2019)\], (6) not consuming grapefruits or grapefruit juice for at least 2 weeks before Holter-ECG examination. Patients, who met all inclusion criteria, underwent subject and physical examination, an over-night Holter-ECG, polygraphy and laboratory biochemical tests (sodium, potassium, calcium, magnesium concentration and fasting glyceamia.

Enrolled patients were asked questions about general frame of mind, daytime and nighttime symptoms that may suggest OSA \[according to Epworth Sleepiness Scale (https://epworthsleepinessscale.com/about-the-ess/ access date 08 May 2020)\]. All patients were fully physically examined. Neck and waist circumference were measured according to STEPwise Approach to Surveillance (STEPS) by WHO (https://www.who.int/ncds/surveillance/steps/en/. \[access date 23 April.2019\]. Upon subject examination (snoring and choking feeling during the sleep) a corrected neck circumference was calculated.

Polygraphy was conducted using MED Recorder device by Infoscan company according to AASM guidelines (American Academy of Sleep Medicine, International classification of sleep disorders, 2016). The device registered blood saturation, heart rate, airflow, chest and abdomen movements, body position, snoring and single lead ECG. OSA was diagnosed according to AASM definition (American Academy of Sleep Medicine, Sleep-related breathing disorders in adults, 1999): in every patient with Respiratory Disturbance Index (RDI) ≥ 5/hour and with concomitant OSA sings (Epworth Sleepiness Scale ≥ 11 pts) or with RDI ≥ 15/hour. The minimum time of analyzed data without artifacts had to last at least 6 h.

A Holter-ECG examination was conducted using DMS 300-3A device by Oxford company suitable for Cardioscan 10 system. Registration was made simultaneously with polygraphy, during the night. Chosen QT interval assessment parameters were evaluated upon partially automatically analyzed fragments of ECG records. Only nighttime ECG records were analyzed due to maximum comparability (similar patient's physical activity and minimized, because of limited body movements, artifacts). Moreover, the study aimed to assess a heart's activity simultaneous to sleep breathing disorders. Only ECG strips with constant heart rate, optimally within 50-70/min limits, were chosen due to the minimum impact of such heart rate on QT interval correction formula. QTc data was calculated upon Bazett's formula. QTV and QTVi were calculated upon Berger's formula.

After getting all results they were checked against the following exclusion criteria: 1) revealing that information about patient's chronic illness or drugs therapy was obfuscated, revealing increased fasting serum glucose concentration or ionic disturbances. It was strongly recommended to every patient to visit their GP for further diagnostics, 2) revealing any important deviation in physical examination i.a. blood pressure taken twice at the visit ≥140/ ≥90 mmHg, 3) revealing, upon Holter ECG examination, tachycardia or too numerous artifacts making QT interval assessment incredible, 4) too short total sleep time (\< 6 hours) registered on polygraphy.

Out of 187 consecutive patients meeting the inclusion criteria, 66 patients met at least one exclusion criterion, leaving 121 patients for the study analyses.

Eligibility Criteria:
Inclusion Criteria:

* gender: female or male,
* age 35-65 years old,
* visceral obesity,
* lack of acute or chronic diseases that may have an influence on rhythm or conduction disorders,
* not undergoing Continuous Positive Airway Pressure therapy (CPAP) or taking drugs that have or may have an influence on QT interval duration \[according to Credible Meds list (Woosley et al, 2019)\],
* not consuming grapefruits or grapefruit juice for at least 2 weeks before Holter-ECG examination.

Exclusion Criteria:

* revealing that information about patient's chronic illness or drugs therapy was obfuscated, revealing increased fasting serum glucose concentration or ionic disturbances. It was strongly recommended to every patient to visit their GP for further diagnostics,
* revealing any important deviation in physical examination i.a. blood pressure taken twice at the visit ≥140/ ≥90 mmHg,
* revealing, upon Holter ECG examination, tachycardia or too numerous artifacts making QT interval assessment incredible,
* too short total sleep time (\< 6 hours) registered on polygraphy.