Relationship Between Left Ventricular Geometry And Atrial Phasic Function And Epicardial Adipose Tissue In Patients With Obstructive Sleep Apnea:An Observational Clinical Study

Objective:Obstructive sleep apnea syndrome（OSAS）as a risk factor for the initiation and progression of cardiovascular diseases,which is primarily related to its influence on cardiac and vascular subclinical structural changes.Left ventricular hypertrophy,atrial enlargement and endothelial dysfunction are common manifestations of cardiovascular damage in patients with OSAS.However,in the majority of studies which assessed the influence of OSAS on the cardiac structure,especially focused on the independent changes of left ventricular hypertrophy and atrial enlargement,as well as the application of single echocardiography,disregarding the changes of atrial structure and function based on left ventricular geometry（LVG）.In addition,obesity,especially visceral obesity,is a common sign in patients with OSAS,which is closely associated with the pathological changes of the target organs.Epicardial adipose tissue（EAT）,a new important parameter of visceral obesity,has the dual effects that are providing myocardial energy under physiological conditions and lipotoxicity under pathological conditions in the etiopathogenesis and development of cardiovascular diseases.However,there was a lack of research data on the relationship between epicardial adipose tissue and left ventricular geometry.Therefore,from the point of view of left ventricular geometry,the purpose of this study was to explore the effect of left ventricular geometry on atrial phasic function and the correlation between left ventricular geometry and epicardial adipose tissue thickness in patients with OSAS.Methods:This study was a cross-sectional observation study.A total of 330 patients with OSAS were collected from the Sleep Units of the Respiratory Department of the First Hospital of Shanxi Medical University from January to December 2019.According to the inclusion and exclusion criteria,221 patients with OSAS were enrolled eventually in the study.All subjects were divided into four groups:normal geometry group（NG）,concentric remodeling group（CR）,eccentric hypertrophy group（EH）and concentric hypertrophy group（CH）based on the left ventricular mass index（LVMI）and relative wall thickness（RWT）.The specific research methods are as follows:1.Clinical characteristicsThe past and present medical history,as well as physical examination（height,weight,waist circumference,and blood pressure）were conducted on all OSAS patients.2.PolysomnographyAll patients underwent overnight（more than 7 hours）polysomnography（PSG）in the Sleep Units.The sleep recordings including the apnea-hypopnea index（AHI）,mean oxygen saturation（Mean-Sa O₂）,lowest oxygen saturation（Lowest-Sa O₂）,and percentage of total sleep time when blood oxygen saturation is less than 90%（T90）were taken by a skilled technician based on the clinical practice guide of the American Association of Sleep Medicine（AASM）.3.Blood biochemical testBlood samples from a peripheral vein were drawn in the morning after PSG.Total cholesterol（TC）,triglycerides（TG）,high-density lipoprotein（HDL）,low-density lipoprotein（LDL）,and fasting blood glucose（Glu）were measured.4.Echocardiography examination（1）Left ventricular structure and function parametersThe left ventricular end-diastolic diameter（LVEDD）,inter-ventricular septum thickness（IVST）,left ventricular posterior wall thickness（LVPWT）,transmitral peak velocities during early diastolic（E）,Transmitral peak velocities during late diastolic（A）,average of the peak myocardial velocities during early diastolic of the septal and lateral mitral annulus（E’）,and left ventricular ejection fraction（LVEF）were measured.Further,LVMI and RWT were calculated.（2）Right ventricular structural and functional parametersThe right ventricular free wall thickness（RV-fwt）,right ventricular outflow tract diameter（RVOT）,peak myocardial velocities during early diastolic of tricuspid annulus（Et）,peak myocardial velocities during late diastolic of tricuspid annulus（At）,tricuspid annular plane systolic excursion（TAPSE）,right ventricular fractional area changes（RV-FAC）and systolic pressure in pulmonary artery（SPAP）were measured.（3）Atrial phasic functionThe atrial maximum volume（AVmax）,atrial minimum volume（AVmin）and atrial pre-contraction volume（AVpre）were collected by volumetric methods（two-dimensional“area-length”method and three-dimensional“full volume”method）,and the atrial total emptying fraction（A-Tot EF）,atrial passive emptying fraction（A-Pass EF）and atrial active emptying fraction（A-Act EF）were calculated.The atrial strain during systolic（AS-S）,atrial strain during early diastolic（AS-E）and atrial strain during late diastolic（AS-A）were measured by strain method（two-dimensional speckle tracking echocardiography）.Atrial phasic function was divided into three phases:reservoir function（represented by A-Tot EF and AS-S）,conduit function（represented by A-Pass EF and AS-E）and booster pump function（represented by A-Act EF and AS-A）.（4）Epicardial adipose tissue thicknessMaking measurement by taking the aortic root as the reference,the epicardial adipose tissue（EAT）thickness was measured vertically on the anterior wall of the right ventricle at end-systolic period.Results:1.Comparison of clinical characteristics,polysomnography and blood biochemical parameters in patients with OSAS with four left ventricular geometric patterns.（1）Patients with CH and EH were older than patients with NG and CR（P<0.05）.Then,and had higher values of systolic blood pressure（SBP）and diastolic blood pressure（DBP）（P<0.05）.（2）AHI and T90 in OSAS patients with CH and EH were higher than those in NG group,while Mean-Sa O₂was lower than that in NG（P<0.05）.（3）There were no significant difference in gender distribution,BMI,Lowest-Sa O₂,waist circumference,heart rate and blood biochemical parameters among four left ventricular geometric patterns.2.Comparison of structural and functional parameters of left ventricle and right ventricle in patients with OSAS with four left ventricular geometric patterns.（1）There were significant differences in left ventricular structural parameters（LVEDD,IVST,LVPWT,LVMI and RWT）in patients with four left ventricular geometric patterns（P<0.05）;Left ventricular diastolic function decreased gradually from NG→CR→EH to CH,and the diastolic function was the worst in patients with CH（P<0.05）.（2）RVOT and SPAP in OSAS patients with CH were higher than those in patients with NG（P<0.05）;Patients with CR,EH and CH had thicker RV-fwt than patients with NG（P<0.05）;The right ventricular diastolic function also decreased gradually from NG→CR→EH to CH,and the right diastolic function was worse in patients with CH than NG and CR,and was worse in patients with EH than NG（P<0.05）.（3）There was no significant difference in left ventricular and right ventricular systolic function among four left ventricular geometric patterns.3.Impact of left ventricular geometry on left atrial phasic function.（1）The left atrial volume and volume index progressively increased from NG→CR→EH to CH group by using 2DE“area-length”method and 3DE“full volume”method;Patients with CH and EH had higher LAVImax,LAVImin and LAVIpre than those in NG and CR,and also higher in patients with CH than those in patients with EH.（2）The left atrial reservoir function decreased gradually from NG→CR→EH to CH group;Patients with CH had lower 2DE-LA Tot EF than patients with NG,however,patients with CH had lower 3DE-LA Tot EF than patients with NG and CR;Also,patients with CH and EH groups had lower LAS-S than patients with NG and CR.（3）The left atrial conduit function also decreased gradually from NG→CR→EH to CH;Patients with CH and EH had lower 2DE-and 3DE-LA Pass EF and LAS-E than patients with NG and CR;（4）On the contrary,the left atrial booster pump function increased gradually from NG→CR→EH and CH;Patients with CH had higher 3DE-LA Act EF than patients with NG,and had higher LAS-A than patients with NG,CR and EH.（5）Correlation analysis showed that2DE-and 3DE-LAVImax,LA Tot EF and LA Pass EF were negatively associated with left ventricular geometry,while 3DE-Act EF was positively associated with left ventricular geometry.（6）After adjusting for gender,age,BMI,SBP,AHI,LVMI,Glu and lipid profiles,multiple linear regression showed that 2DE-LAVImax was associated with CH（β=0.449,P<0.001）,and 3DE-LAVImax was associated with CH（β=0.539,P<0.001）and EH（β=0.137,P=0.025）.2DE-and 3DE-LA-Tot EF were associated with CH（β=-0.219,P=0.046;β=-0.276,P=0.010）;2DE-and 3DE-LA Pass EF were associated with CH（β=-0.422,P<0.001;β=-0.589,P<0.001）and EH（β=-0.221,P=0.019;β=-0.382,P<0.001）.3DE-LA-Act EF was associated with CH（β=0.239,P=0.035）.LAS-S,LAS-E and LAS-A were all associated with CH（β=-0.546,P<0.001;β=-0.636,P<0.001;β=0.450,P<0.001）and EH（β=-0.403,P<0.001;β=-0.400,P<0.001;β=0.194,P=0.035）.4.Impact of left ventricular geometry on right atrial phasic function.（1）The right atrial volume and volume index progressively increased from NG→CR→EH to CH group used 2DE“area-length”method and 3DE“full volume”method;Patients with CH and EH had higher 2DE-LAVImax,2DE-LAVImin and 2DE-LAVIpre than patients with NG and CR,and also higher in patients with CH than EH;Patients with CH had higher 3DE-RAVImax,3DE-RAVImin and 3DE-RAVIpre than patients with NG,CR and EH,and also higher in patients with EH than patients with NG.（2）The right atrial reservoir function decreased gradually from NG→CR→EH to CH group;Patients with CH and EH had lower 2DE-and 3DE-RA Tot EF than patients with NG,and lower in patients with CH than CR;Also,patients with CH and EH had lower RAS-S than patients with NG and CR.（3）The right atrial conduit function also decreased gradually from NG→CR→EH to CH;Patients with CH and had lower 2DE-RA Pass EF than NG and CR,and had lower 3DE-RA Pass EF than patients with NG,CR and EH,and had lower in patients with EH than patients with NG;Also,patients with CH and EH had lower RAS-E than NG and CR,and had lower in patients with CH than EH.（4）On the contrary,the right atrial booster pump function increased gradually from NG→CR→EH to CH;patients with CH had higher 2DE-and 3DE-RA Act EF than patients with NG,and also patients with CH and EH had higher RAS-A than patients with NG and CR,and higher in patients with CH than patients with EH.（5）Correlation analysis showed that2DE-and 3DE-RA Tot EF,RA Pass EF were negatively associated with left ventricular geometry,while 2DE-and 3DE-RA Act EF were positively associated with left ventricular geometry.（6）After adjusting for gender,age,BMI,SBP,AHI,LVMI,SPAP,RV-fwt,Glu and lipid profiles,further multiple linear regression analysis showed that2DE-RA-Tot EF was associated with CH（β=-0.236,P=0.025）,3DE-RA Tot EF was associated with CH（β=-0.272,P=0.015）and EH（β=-0.209,P=0.033）.2DE-RA Pass EF was associated with CH（β=-0.365,P=0.002）,3DE-RA Pass EF was associated with CH（β=-0.456,P<0.001）and EH（β=-0.301,P=0.001）;2DE and 3DE-RA Act EF were associated with CH（β=0.218,P=0.004;β=0.374,P<0.001）;RAS-S and RAS-E were both associated with CH（β=-0.437,P<0.001;β=-0.443,P<0.001）and EH（β=-0.219,P<0.001;β=-0.185,P<0.001）,and RAS-A was associated with CH（β=0.366,P<0.001）.5.Correlation between left ventricular geometry and epicardial adipose tissue thickness.（1）The EAT thickness increased gradually from NG→CR→EH to CH group,and patients with CH and EH had the thicker EAT than NG and CR.（2）Correlation analysis showed that EAT was positively associated with age,BMI,SBP,DBP,AHI,T90,TC,TG,Glu,LVMI and RWT,and negatively associated with Mean-SaO₂,Lowest-Sa O₂and HDL.（3）After adjusting the gender,age,BMI,SBP,LVMI,PSG parameters,Glu and lipid factors,multiple linear regression analysis showed that there was an association between EAT thickness and abnormal left ventricular geometry（CR:β=0.114,95%CI:0.007-0.055,P=0.010;CH:β=0.439,95%CI:0.121-0.180,P<0.001;EH:β=0.296,95%CI:0.083-0.150,P<0.001）.Conclusion:1.The biatrial structure and phasic function varied with left ventricular geometry.Concentric hypertrophy had the most significant negative effect on biatrial structure and phasic function.It is suggested that we should pay more attention to the changes of atrial structure and function based on left ventricular geometry in clinical,which may have a certain value in predicting the occurrence of cardiovascular events.However,further prospective cohort studies are still needed.2.Epicardial adipose tissue thickness was different among left ventricular geometric patterns and was associated with left ventricular geometry.It is suggested that epicardial adipose tissue may be a risk factor for abnormal left ventricular geometry.However,further longitudinal and molecular mechanisms are needed.