The Study Of Echocardiographic Notch Formation At High Altitude And Its Clinical Significances

Background:Acute mountain sickness（AMS）is a complex clinical syndrome and the most common high altitude illnesses.With acclimatization to high altitude hypoxia,mild AMS symptoms are gradually alleviated,however severe AMS may progress to life-threatening high altitude illnesses such as high altitude cerebral edema and high altitude pulmonary edema.After high altitude exposure,the cardiopulmonary system altered the most at the earliest time in response to hypoxia.Hypoxia in the whole lung induces global hypoxic pulmonary vasoconstriction（HPV）,which leads to an increase in pulmonary artery pressure,pulmonary vascular resistance（PVR）and right ventricular afterload.With excessive cardiopulmonary response to hypoxia,exaggerated HPV leads to a highly increased pulmonary artery pressure,which may develop high altitude pulmonary edema and even right ventricular failure.Echocardiographic Notch refers to the Notching of the right ventricular outflow tract systolic flow velocity Doppler envelope,while the profile in a healthy individual is parabolic or triangular.The formation of echocardiographic Notch is due to the rapid conduction of pulmonary artery reflection wave,which reaches the pulmonary valve before it’s closed,causing deceleration of the right ventricular outflow tract flow.Previous studies reported that right ventricular outflow tract Notch mainly exists in various types of pulmonary hypertension,which is an echocardiographic indicator of poor prognosis and is related to higher pulmonary artery pressure,higher PVR and worse right ventricular function.As pulmonary artery pressure increases in varying degrees upon acute high altitude exposure,the presence of echocardiographic Notch at high altitude is not reported.This study aims to explore the occurrence,formation mechanism and clinical significances of echocardiographic Notch at high altitude.Objectives:1.To explore the incidence,morphological characteristics and significances of right ventricular outflow tract Notch at high altitude and reveal its related factors;2.To explore the association between echocardiographic Notch and AMS upon acute high altitude exposure;3.To explore the impact of echocardiographic Notch on cardiac function in subjects upon acute high altitude exposure.Methods:1.This part of study consisted of two cohorts.In June 2013,130 subjects（Cohort 1）were enrolled in Yanggongqiao（400 m,Chongqing）,and then ascended to 4100 m（Litang,Sichuan）by bus within 7 days.Demographic,Physiological and echocardiographic data were collected before ascending and after arriving at 4100 m high altitude.In June 2019,99subjects（Cohort 2）were enrolled in Chengdu（500 m,Sichuan）,and then ascended to 4100 m（Litang,Sichuan）by bus over a 2-day period.Demographic,Physiological and echocardiographic data were collected before ascending and after arriving at 4100 m high altitude.Spectral Doppler images were employed to identify the right ventricular outflow tract Notch at high altitude and determine the morphologic characteristics,incidence and sex difference of echocardiographic Notch at high altitude.Logistic regression analysis was used to analyze the relationship between echocardiographic Notch and demographic,physiological and cardiac function parameters,in order to identify the related factors associated with echocardiographic Notch formation at high altitude.2.The subjects and conventional data collection in this part are the same as in Cohort 1.Moreover,the incidence of AMS,the AMS（-）and AMS（+）subjects were determined according to the 2018 Lake Louise AMS diagnostic criteria.The Notch（-）and Notch（+）subjects were determined by echocardiographic data.The differences between AMS（-）and AMS（+）subjects and between Notch（-）and Notch（+）subjects in demographic data,physiological and echocardiographic parameters were compared.Logistic regression analysis was used to analyze the relationship between AMS and demographic data,physiological and echocardiographic parameters,in order to determine the risk factors of AMS.The occurrences of clinical symptoms in Notch（-）and Notch（+）subjects were compared,in order to explore the reason that subjects with echocardiographic Notch had higher AMS occurrence.Linear regression was used to investigate the relationship between systolic pulmonary artery pressure and AMS score,in order to unravel that the increased pulmonary artery pressure potentially underlies the association between echocardiographic Notch and AMS at high altitude.3.The subjects and conventional data collection in this part are the same as in Cohort 2.The Notch（-）and Notch（+）subjects were determined by right ventricular outflow tract Doppler inspection.Additionally,mid systolic DT（mid systolic deceleration time）,the parameter of right ventricular outflow tract Notch,was recorded.The differences between Notch（-）and Notch（+）subjects in demographic data,physiological and echocardiographic parameters at sea level/high altitude were compared,in order to explore the impact of echocardiographic Notch on cardiac function upon acute high altitude exposure.Notch（+）subjects were categorized into mid systolic DT<120 mm group and mid systolic DT>120mm group,echocardiographic parameters were compared between two groups to investigate the impact of mid systolic DT on cardiac function in Notch（+）subjects at high altitude.Results:1.Cohort 1 consisted of 130 Chinese young men and Cohort 2 consisted of 99 adult Chinese subjects,including 69 males and 30 females.None of the echocardiographic Notch formation was found at sea level.In Cohort 1,right ventricular outflow tract Notch formation was detected in 26 subjects（20.0%）at high altitude.In the Notch（+）,18 subjects（69.2%）with late systolic Notch（LSN）and 8 subjects（30.8%）with mid systolic Notch（MSN）were found.The incidence of LSN was higher than that of MSN.In Cohort 2,right ventricular outflow tract Notch was found in 20 subjects（20.0%）at high altitude.The Notch（+）subjects consisted of 12 males（60.0%）and 8 females（40.0%）.There was no sex difference in the occurrence of echocardiographic Notch at high altitude.Both in Cohort 1 and Cohort 2,multivariate logistic regression analysis revealed that SPAP was an independent risk factor of right ventricular outflow tract Notch at high altitude.2.Of all the 130 subjects in Cohort 1,the median age was 20 years.After acute altitude exposure,37 in 130 subjects（28.5%）were diagnosed as AMS in Cohort 1.The proportions of smokers and echocardiographic Notch cases in AMS（+）subjects are higher than those in the AMS（-）subjects.Multivariate logistic regression analysis showed that the formation of Notch at high altitude（OR=5.48,p=0.001）and HR（OR=1.05,p=0.007）were independent risk factors for AMS.Compared with Notch（-）subjects.Linear regression analysis showed that SPAP was positively correlated with AMS score（r=0.20,p=0.020）,which is profound in Notch（+）subjects（r=0.44,p=0.023）.3.Of all the 99 subjects in Cohort 2,the median age was 25 years.After ascending to high altitude rapidly,Sp O₂ in all groups decreased,and the Sp O₂ in Notch（+）group was lower than that in Notch（-）group.In left ventricular function,the mitral s’in the total and Notch（-）subjects increased,but the mitral s’in Notch（+）subjects did not change.In right ventricular function,TRV,SPAP,m PAP and PVR in all groups increased,and the increase in Notch（+）subjects is higher than that in Notch（-）subjects.In total and Notch（-）subjects,tricuspid s’and ICV increased after high altitude exposure,but tricuspid s’and ICV in Notch（+）subjects did not change.The RV FAC,TAPSE,TAPSE/SPAP and RV GLS in Notch（-）and Notch（+）subjects decreased,and the decreases of TAPSE/SPAP and RV GLS were more profound in Notch（+）subjects.The decrease in RV GLS was mainly attributed to 2DS RVFW mid and 2DS RVFW base.The RVSD4 in all groups increased,and was more significant in Notch（+）group.In the Notch（+）subgroup analysis,RVD base and RVD mid in the mid systolic DT<120mm group were longer than those in the mid systolic DT>120mm group at high altitude.Conclusion:1.The incidence of echocardiographic Notch formation in subjects upon high altitude exposure was about 20%,with no sex difference.Moreover,the incidence of LSN was higher than that of MSN.The formation of echocardiographic Notch at high altitude is associated with the increase of pulmonary artery pressure.2.The formation of echocardiographic Notch is an independent risk factor of AMS in subjects upon high altitude exposure,with a 5.48 times higher risk to develop AMS in subjects with echocardiographic Notch.Compare with subjects without echocardiographic Notch,the higher incidence of AMS in subjects with echocardiographic Notch was attributed to the higher incidence of headache and fatigue.3.Upon acute high altitude exposure,the left ventricular function in subjects with echocardiographic Notch is well preserved.However,the presence of an RVOT Notch was associated with impaired RV function,including blunted right ventricular myocardial velocity,deteriorated right ventricular-pulmonary artery coupling,reduction of right ventricular deformation,and increase of right ventricular intraventricular dyssynchrony.