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aIaIaIZ�Z�gjaIaIaIQ��]�]�]�],,,�'�C�,,,�C��bt	����������Echocardiographic investigation of sojourner�s right heart hypertrophy in highland

Wei Yao, MD, Ultrasonic Examination Department of Yangpu District Central Hospital, 450, Tengyue Road, Shanghai, 200090 P. R. China. 

Total word count: 4448
The brief title: Sojourner�s right heart hypertrophy in highland
The manuscript has no relationship with any industry.

Address for correspondence: Wei Yao, Ultrasonic Examination Department of Yangpu Hospital, 450, Tengyue Road, Shanghai, 200092 P. R. China. Telephone number: 86-021-65690520-298, fax:86-021-55227387, e-mail:  HYPERLINK "mailto:da2004m@163.com" da2004m@163.comEchocardiographic investigation of sojourner�s right heart hypertrophy in highland
ABSTRACT  
Background The hypertrophy of right ventricle in association with high altitude hypoxia has seldom been detected or measured successfully by X-ray, electrocardiogram or other techniques except for echocardiography. The investigation was designed to prove the existence of the highland sojourner�s right heart hypertrophy by echocardiography and make clear the features of it.
Methods In the investigation, the Echocardiographic measurements of 312 healthy highland sojourners, 184 healthy highland residents, 51 high altitude heart disease patients and 50 healthy sea-level residents were selected and attributed to corresponding groups. Both of the highland sojourner and highland resident groups were divided into ethnic subgroups, but only the highland sojourner group was re-divided into age and high altitude duration subgroups. Parameters were analyzed by analysis of variance, Student�s t test and correlation analysis. 
Results The investigation showed that highland sojourner�s right atrium was significantly bigger than that of highland and sea-level residents. However, the right atrium and right ventricle of highland sojourner were significantly smaller than those of high altitude heart disease patient. And it was found that the factors like ethnicity, age and duration at high altitude act little in sojourner�s hypertrophy. 
Conclusion The investigation proved that right heart hypertrophy exists among healthy highland sojourners, found that the hypertrophy is different from the general saying right heart hypertrophy among highland disease patients and has its own features, and confirmed that the hypertrophy is not the early stage of high altitude heart disease, but only an adaptive response to high altitude hypoxia.
KEYWORDS highland sojourner; right heart hypertrophy; high altitude adaptation; echocardiography
Abbreviations:

ANOVA = analysis of variance 
HHD = high altitude heart disease 
HHDG = high altitude heart disease group 
HRG = highland resident group 
HRGh = Han highland resident subgroup 
HRGt = Tibetan highland resident subgroup 
HSG = highland sojourner group 
HSGh = Han highland sojourner subgroup 
HSGt = Tibetan highland sojourner subgroup 
RDA = the transverse dimension ratio between right atrium and left atrium 
RDAPT = the diameter ratio between aorta at valve and pulmonary artery at trunk 
RDAPV = the diameter ratio between aorta at valve and pulmonary artery at valve 
RDV = the transverse dimension ratio between right ventricle and left ventricle 
RTWPA = the thickness ratio between left ventricular posterior wall and right ventricular anterior wall 
RTWPL = the thickness ratio between left ventricular posterior wall and right ventricular lateral wall 
RTWPO = the thickness ratio between left ventricular posterior wall and right ventricular outlet wall 
RVA = the volume ratio between right atrium and left atrium 
RVV = the volume ratio between right ventricle and left ventricle 
SRG = sea-level resident group 
Introduction 
The hypertrophy of right ventricle in association with high altitude hypoxia was first noted in 1912. But since then it has seldom been detected or measured successfully by X-ray, electrocardiogram or other techniques except for echocardiography [1]. Since the existence of right heart hypertrophy among highland sojourners has never been proved, it is thought that the right heart hypertrophy of healthy highland sojourners is so slight that it can even be negligible, just like that of highland residents, who live at high altitude for lifelong. The generally saying right heart hypertrophy, which consists of thickened right ventricular wall, thickened pulmonary artery and enlarged right atrium and right ventricle, is thought to exist only among the patients of sub-acute and chronic altitude illness, such as high altitude heart disease (HHD), a form of cor pulmonale in children and adults due to chronic hypoxia at altitudes higher than 3000m characterized by pulmonary hypertension, right heart hypertrophy and failure [2]. 
When talking about the right heart hypertrophy at high altitude, there are two other facts which are necessary to mention. One fact is that the concern of the hypertrophy has always been given to right ventricle. Nothing has ever been mentioned about right atrium in all the studies of right heart hypertrophy at high altitude [3]. The other fact is that lifelong highland residents are reported different from newcomers in high altitude adaptation [4] and high altitude heart disease is reported rare in Tibetan natives [2]. Some literature even suggests that the researches of this domain should continue to search for the genetic basis of high altitude illnesses [5].
Recently the author of the paper had an opportunity to work in Lhasa (3658m above sea level), the capital of Tibet, China, for about one year. During that year, he surprisingly found in some cases that healthy highland sojourners had a kind of right heart hypertrophy, which could be easily detected by echocardiography. He called it sojourner�s hypertrophy. But the hypertrophy was quite different from the general saying right heart hypertrophy which exists among the patients of sub-acute and chronic altitude illness. Highland sojourners were so afraid when they heard they had right heart hypertrophy. They doubted it was an early stage of HHD. Therefore, the author of the paper made an investigation to study the sojourner�s hypertrophy. 
This investigation was designed to answer the following questions. Did the sojourner�s hypertrophy exist extensively among healthy highland sojourners? What were the echocardiographic features of the hypertrophy, which made it so different from the hypertrophy among altitude disease patients? Was there any factor which could make some influence on the hypertrophy? Was the sojourner�s hypertrophy an early stage of HHD or could a sojourner experience the hypertrophy? 
Materials and Methods
Groups 
The investigation was a retrospective study. The main data of the investigation were selected from the medical data storage of the hospital in Lhasa (3658m above sea-level), which the author worked in. The subjects involved in the investigation and the doctors doing the echocardiographic examination or treating the patients were all blinded to the investigation. This investigation was approved by the institutions related. Because nothing more than routine examination was performed in the investigation, informed consent was not required; patient anonymity was maintained. 
The investigation consisted of four data groups which were highland sojourner group (HSG), highland resident group (HRG), high altitude heart disease group (HHDG) and sea-level resident group (SRG). The data of HSG and HRG were selected from the health checkup cohort of the hospital in Lhasa. The health checkup cohort were free living people who went to the hospital only to have periodical health checkup. Altogether, 531 highland subjects� data were recruited for HSG and HRG. But the data of 496 subjects, who hadn�t any known systemic disease, were selected, of which 312 subjects� data were attributed to the HSG, and the rest 184 subjects� data were attributed to the HRG. The HSG subjects were born under 3600m and then came to Lhasa after their respective stay down there, including 223 men and 89 women, age 0.7~70 years. The HRG subjects were born above 3600m (including 3600m) and lived there afterwards, including 90 men and 94 women, age 0.1~82 years. As Han usually lives at sea-level and Tibetan is regarded as lifelong highland resident, there might be some genetic difference between the two races in high altitude right heart hypertrophy. In order to seek the supposed difference, both the HSG and HRG were divided into Han and Tibetan sub-groups according to the ethnicity of the subjects, which were Han highland sojourner subgroup (HSGh), Tibetan highland sojourner subgroup (HSGt), Han highland resident subgroup (HRGh) and Tibetan highland resident subgroup (HRGt). HSGh was made by 280 healthy Han subjects� data, 205 men and 75 women, age 0.7~69 years. HSGt was made by 32 healthy Tibetan subjects� data, 18 men and 14 women, age 17~70 years. HRGh was made by 19 healthy Han subjects� data, 11 men and 8 women, age 0.1~62 years. HRGt was made by 165 healthy Tibetan subjects� data, 79 men and 86 women, age 0.25~82 years. The Tibetan subjects of the HSGt were from the area in Tibet lower than Lhasa. 
The data of HHDG were selected from that of indoor patients of the same hospital in Lhasa, and their reason for admission was heart disease. 234 patients were recruited but only 51 patients were selected according to the inclusion criteria, which were 1, right heart failure, 2, peak pulmonary pressure > 40 mmHg, 3, right ventricular hypertrophy and enlargement, 4, 1~3 were induced by no other reason but high altitude and 5, no other heart disease was accompanied. According to these criteria, the subjects selected were definitely HHD patients [6] with no other heart disease accompanied. The patients with other heart diseases, like valvular heart disease, congenital heart disease, coronary heart disease etc, were carefully excluded. HHDG included the data of 24 men and 27 women, age 0.1~71 years.
The data of SRG were selected from the health checkup cohort of a hospital in Shanghai (sea-level), China. The data of 50 normal subjects in Shanghai were selected by the inclusion criteria that the subject hadn�t any known systemic disease and had never been to any high altitude area. SRG included the data of 28 men and 22 women, age 11~76 years. 
The general data, the inclusion criteria and the duration at high altitude of all the above groups are listed in Table 1. 
Age and high altitude duration were two generally recognized important factors in high altitude right heart hypertrophy. Difference was expected from highland sojourners of different age or duration. Therefore, the HSG was divided into three subgroups (children (age d"14y), adolescents (14y < age d" 21y) and adults (age > 21y)) according to the subject s age. And according to the subject s duration at high altitude, the HSG was also divided into three other subgroups (duration above 3600m d" 1 month, 1 month < duration above 3600md" 1 year and duration above 3600m > 1 year). 
Ultrasound Systems
The echocardiographic measurements of the HSG, HRG and HHDG subjects were collected by an ATL Ultramark 7 echocardiographic system (ATL advanced technology laboratoriesTM, Bothell, WA) with a 2.5Mhz probe in Lhasa, while the measurements of the SRG subjects were collected using an Agilent Sonos 5500 (Agilent technologies, Andover, MA) with a S4 probe in Shanghai. 
Echocardiographic parameters
While replaying the images of the selected subjects on the machine, the echocardiographic measurements concerning the right heart hypertrophy at high altitude were measured by the author and made up the echocardiographic data of all the groups in the investigation. These measurements could be divided into three sections, which were (1) the diameter and volume of right atrium and ventricle, and the diameter and volume of left atrium and ventricle; (2) the thickness of three parts of right ventricular wall (right ventricular lateral wall, right ventricular outlet wall and right ventricular anterior wall), and the thickness of left ventricular posterior wall; (3) the diameter of pulmonary artery at valve and trunk, and the diameter of aorta at valve. The measuring methods of these measurements were recommended by Liu and Xiong [7] and are shown in the corresponding figures. These measurements were:
The transverse dimension of right atrium (Figure 1),
The transverse dimension of left atrium (Figure 1),
The volume of right atrium (Figure 2),
The volume of left atrium (Figure 2),
The transverse dimension of right ventricle (Figure 3),
The transverse dimension of left ventricle (Figure 3),
The volume of right ventricle (Figure 4),
The volume of left ventricle (Figure 4),
The thickness of right ventricular lateral wall (Figure 3),
The thickness of right ventricular outlet wall (Figure 5),
The thickness of right ventricular anterior wall (Figure 6), 
The thickness of left ventricular posterior wall (Figure 6), 
The diameter of aorta at valve (Figure 6), 
The diameter of pulmonary artery at valve (Figure 7), 
The diameter of pulmonary artery at trunk (Figure 7). 
Then, the normalization by the corresponding left heart measurements was selected, which was commonly used in echocardiographic researches [8-10]. That meant all the above echocardiographic measurements were used to calculate ratios between right heart measurements and their left heart corresponding measurements, thus forming 9 parameters which were used to study the right heart hypertrophy at high altitude. These exact parameters were 
I. the transverse dimension ratio between right atrium and left atrium (RDA),  EMBED Equation.3  �which was a one-dimensional size parameter of right atrium compared with that of left atrium, 
II. the volume ratio between right atrium and left atrium (RVA),  EMBED Equation.3  , which was a two-dimensional-area inducing volume parameter of right atrium compared with that of left atrium,
III. the transverse dimension ratio between right ventricle and left ventricle (RDV),  EMBED Equation.3  , which was a one-dimensional size parameter of right ventricle compared with that of left ventricle,
IV. the volume ratio between right ventricle and left ventricle (RVV),  EMBED Equation.3  , which was a two-dimensional-area inducing volume parameter of right ventricle compared with that of left ventricle,
V. the thickness ratio between left ventricular posterior wall and right ventricular lateral wall (RTWPL),  EMBED Equation.3  , which was a one-dimensional thickness parameter of right ventricular lateral wall compared with that of left ventricular posterior wall,
VI. the thickness ratio between left ventricular posterior wall and right ventricular outlet wall (RTWPO),  EMBED Equation.3  , which was a one-dimensional thickness parameter of right ventricular outlet wall compared with that of left ventricular posterior wall,
VII. the thickness ratio between left ventricular posterior wall and right ventricular anterior wall (RTWPA), EMBED Equation.3  , which was a one-dimensional thickness parameter of right ventricular anterior wall compared with that of left ventricular posterior wall,
VIII. the diameter ratio between aorta at valve and pulmonary artery at valve (RDAPV),  EMBED Equation.3  , which was a one-dimensional diameter parameter of pulmonary artery at valve compared with that of aorta at valve,
IX. the diameter ratio between aorta at valve and pulmonary artery at trunk (RDAPT),  EMBED Equation.3  , which was a one-dimensional diameter parameter of pulmonary artery at trunk compared with that of aorta at valve. 
Statistical Analysis
The parameters of HSG were compared with the corresponding parameters of HHDG, HRG and SRG by analysis of variance (ANOVA) and post hoc testing. 
The parameters of age subgroups and highland duration subgroups of HSG were compared with each other respectively by ANOVA and post hoc testing. Then, the relationships between the parameters of HSG and the corresponding subject�s duration at high altitude were studied by correlation analysis. Finally, the parameters in subgroups of the same ethnicity of HSG and HRG (HSGh vs HRGh, HSGt vs HRGt) were compared by Student�s t test. As the sizes of the ethnic subgroups were not similar, subjects were selected from HSGh and HRGt by the criterion of matched age and gender with the subjects in HRGh and HSGt, and made a matched pair design.
Results
The results of ANOVA showed that both the two parameters of highland sojourner s right atrium�RDA and RVA	� were significantly bigger than those of highland and sea-level resident (p<0.01) (Table 2: I, III). But only one parameter of highland sojourner s right ventricle (RDV) was significantly bigger than that of sea-level resident alone (p<0.01) (Table 2: II). That meant, comparing with those of highland and sea-level resident, right atrium of highland sojourner enlarged significantly, but the enlargement of right ventricle was not so definite. However, the enlarged right atrium and right ventricle of highland sojourner were significantly smaller than those of high altitude heart disease patient (p<0.01) (Table 2: I~IV). The results also showed that the thickness of right ventricular wall and the diameter of pulmonary artery of highland sojourner had no significant difference from those of highland and sea-level resident (p>0.05), and were significantly thinner than those of high altitude heart disease patient (p<0.01) (Table 2: V~IX). 
No definite difference was found in the parameters among the duration subgroups and the age subgroups of HSG, which means the two factors, duration at high altitude and age, act weakly in the highland sojourner�s right heart hypertrophy.
The results of correlation analysis showed that all the parameters of HSG subjects had no significant correlation (p>0.05) with the subjects� duration at high altitude except for one parameter (RDA), of which the positive correlation was only significant at 0.05 level. That also means duration at high altitude has little influence to sojourner�s hypertrophy. 
The results of Student�s t test showed that, among the people of same ethnicity, the situation between highland sojourner and highland resident was the same as that between highland sojourner and highland resident which had no ethnic limitation. No obvious ethnic difference was found in the statistical analysis.
Discussion 
The investigation proves the existence of right heart hypertrophy among healthy sojourners at high altitude. But the hypertrophy has its own features which include that the size of right atrium enlarges much more obviously than the right ventricle does, the enlargement of right ventricle has been proved uncertain, and the thickness of right ventricular wall and the diameter of pulmonary artery have no obvious enhancement. That means sojourner�s right heart hypertrophy at high altitude is very slight. It is quite different from the generally saying right heart hypertrophy which consists of thickened right ventricular wall, thickened pulmonary artery and enlarged right atrium and right ventricle. This is the most important finding of the investigation.
 The cause of sojourner�s right heart hypertrophy relates to the increase of pulmonary artery pressure. A lot of studies have proved that a prompt but variable increase in pulmonary vascular resistance occurs on ascent to high altitude [1,11,12]. Therefore, sojourner�s hypertrophy is most likely due to the increased afterload because of a higher pulmonary artery pressure. As atrial wall is much thinner than ventricular wall, the right atrium enlarges much more obviously than the right ventricle does. And mostly the right atrium can be bigger than the left atrium, thus forming the echocardiographic features of sojourner�s hypertrophy, which can be described as a special heart shape situates between the heart shapes of highland resident and HHD patient. It is common sense that right heart hypertrophy of highland resident is not obvious. So highland resident has a similar heart shape to that of sea-level resident, of which both the right atrium and ventricle are slightly smaller than the corresponding left atrium and ventricle, and all the echocardiographic measurements keep in the normal range. But HHD patient has a very big right heart with thick right ventricular wall and thick pulmonary artery, both the right atrium and ventricle are obviously bigger than those in the left. Highland sojourner has an obviously enlarged right atrium, which is the same as or slightly bigger than the left atrium, but which is not so big as that of HHD patient. However, the enlargement of highland sojourner�s right ventricle is not definite and the right ventricle is still slightly smaller than the left ventricle, which is like those of highland resident and sea-level resident. This kind of special heart shape of highland sojourner can be easily recognized by an experienced echocardiographist (Figure 8). As another echocardiographic feature of highland sojourner�s right heart hypertrophy, the right ventricular wall thickness and pulmonary artery diameter of highland sojourner, which are normal as those of highland resident and sea-level resident, are also significantly smaller than those of HHD patient, respectively. 
Many researchers think age and duration would have significant effect on high altitude associated right heart hypertrophy. But, surprisingly, it has been found from the ANOVA results of age subgroups of HSG that there is no definite difference among the parameters of children, adolescents and adults immigrating to highland, which means that age acts little in sojourner�s hypertrophy. It is also quite surprising to find that the duration at high altitude has no significant effect on the right heart hypertrophy process of highland sojourner. Thus, it is believed that sojourner�s hypertrophy is not a pathological process which can be divided into acute, sub-acute and chronic period like altitude illness. 
A healthy sojourner can keep the heart shape features of his right heart hypertrophy at high altitude as time goes along. This has been proved by correlation analysis that most of the highland sojourner�s parameters show no significant correlation with his duration at high altitude (The significant correlation of one size parameter of right atrium at only 0.05 level is not thought reliable while other eight parameters, including the other size parameter of right atrium, show no significant correlation). The fact can also be proved by the ANOVA results of highland duration subgroups of HSG that no significant difference was found among the parameters of the subgroups, which means that the heart shape of highland sojourner keeps unchanged as time goes along at high altitude. In fact, the author found some highland sojourners kept their heart shapes for 30, even more than 40 years as they stayed at high altitude and never had HHD. That is because highland sojourner�s right heart hypertrophy balances the enhanced pulmonary artery pressure, therefore the pulmonary artery pressure doesn�t go up further. So, sojourner�s right heart hypertrophy is not an early stage of high altitude heart disease, but only an adaptive response to high altitude hypoxia, and a healthy sojourner can experience it.
The last feature of the hypertrophy found in the investigation is that Tibetan acts the same as Han does in sojourner�s hypertrophy. It is found by the Student�s t test between highland sojourner subgroups and highland resident subgroups of the same ethnicity that the Tibetan, who are regarded as lifelong highland resident, can also have sojourner�s hypertrophy if they have been born at sea level or low altitude, then come back to high altitude, and the Han, who usually live at sea level, can have highland resident�s heart shapes at high altitude if they have been born at high altitude and live there afterwards. Moreover, it can not be regarded as rare that 24 Tibetan HHD patients were found in the HHDG which consisted of altogether 51 subjects. The above findings show no different response was found between a high altitude living race and a sea-level living race in sojourner�s hypertrophy. Therefore, the existence of genetic basis in high altitude adaptation is doubted. The various differences between highland resident and sojourner [4,13] are believed only to be a kind of adaptation which can be changed if the living altitude is changed long enough. 
As right atrium enlarges more obviously than right ventricle does, measuring right atrium is better than measuring right ventricle in detecting highland sojourner�s right heart hypertrophy. Since chest radiograph can not show a clear boundary between right atrium and left atrium, echocardiography, using the proper parameters of right atrium, like RDA and RVA, is a better method to evaluate sojourner�s hypertrophy. It is noninvasive, accurate, convenient and cheap. Therefore, it is believed useful to monitor the hypertrophy using echocardiography in predicting some of altitude illnesses. For example, both HHD and high altitude pulmonary edema have excessive pulmonary hypertension [2,11]. The pathologically high pulmonary artery pressure of the two diseases must induce a bigger right atrium than that induced by lightly enhanced pulmonary artery pressure of a healthy highland sojourner. In this case, the size parameters of right atrium may be used as indicators to differentiate an early stage of HHD or high altitude pulmonary edema from a healthy right heart hypertrophy.
Two limitations should be acknowledged for this study. First, as the only echocardiographic machine in that hospital at Lhasa (ATL Ultramark 7 echocardiographic system) was a very old one and was in poor condition, tricuspid or pulmonary regurgitation was not found in most of the healthy subjects investigated. Therefore, it couldn�t have the pulmonary artery pressure values of healthy highland sojourners and highland residents, because, on that machine, pulmonary artery pressure could only be accurately estimated by measuring the velocity of tricuspid or pulmonary regurgitation flow [7,8,14,15]. The second limitation was that HSG had a predominance of men. The reason was that most of highland sojourners were men, and husbands left their wives and children at home in lowland. So the gender distribution of HSG was not similar as that in other groups. 
The conclusion of the paper is that right heart hypertrophy takes place in healthy asymptomatic sojourners in high altitude regions and the hypertrophy can now be easily non-invasively detected and accurately measured by echocardiography. On the contrary of the previous understanding, sojourner�s hypertrophy is found quite different from the right heart hypertrophy among high altitude disease patients. Sojourner�s hypertrophy has several features, which are that the right atrium enlarges much more obviously than the right ventricle does, the enlargement of right ventricle is uncertain and the right ventricular wall thickness and pulmonary artery diameter keep normal. It is also proved that sojourner�s hypertrophy, upon which the factors like ethnicity, age and duration at high altitude are of little effect, is not an early stage of HHD, but only an adaptive response to high altitude hypoxia and a healthy sojourner can experience it. Further study of the hypertrophy may be useful in the prevention of altitude illnesses and may benefit millions of people who go to high altitude area from low places.
Acknowledgments

No.References
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2. Sutton JR, Houston CS, Jones NL (1983) Hypoxia, exercise and altitude. (1st edtn), Alan R. Liss, Inc, New York, USA.
3. Milledge JS (2006) Altitude medicine and physiology including heat and cold: A review. Travel Medicine and Infectious Disease 4: 223-237.
4. Moore LG (2000) Comparative human ventilatory adaptation to high altitude. Respir physiol 121: 257-276.
5. Basnyat B, Murdoch DR (2003) High-altitude illness. Lancet 361: 1967-1974.
6. Anand IS, Malhotra RM, Chandrashekhar Y, et al (1990) Adult subacute mountain sickness�a syndrome of congestive heart failure in man at very high altitude. Lancet 335: 561-565.
7. Liu YL, Xiong JR (2001) Clinical echocardiography. (1st edtn), Science press, Beijing, China.
8. Bouhemad B, Ferrari F, Leleu K, Arbelot C, Lu Q, Rouby JJ (2008) Echocardiographic doppler estimation of pulmonary artery pressure in critically ill patients with severe hypoxemia. Anesthesiology 108: 55-62.
9. Huez S, Vachiery JL, Unger P, Brimioulle S, Naeije R (2007) Tissue Doppler imaging evaluation of cardiac adaptation to severe pulmonary hypertension. Am J Cardiol 10: 1473-1478.
10. Huez S, Faoro V, Gu�nard H, Martinot JB, Naeije R (2009) Echocardiographic and tissue Doppler imaging of cardiac adaptation to high altitude in native highlanders versus acclimatized lowlanders. Am J Cardiol 103: 1605-1609.
11. Auerbach, P.S. (2001) Wilderness Medicine. (4st edtn), Moshy, Inc, St. Louis, Missouri 63146.
12. Lieve EJV, Stickney JC (1963) Hypoxia. (1st edtn), The university of Chicago press, Chicago and London.
13. Wilkins MR, Aldashev A, Morrell NW �2002	�Nitric oxide, phosphodiesterase inhibition, and adaption to hypoxic conditions. Lancet 359: 1539-1540.
14. Bidart CM, Abbas AE, Parish JM, Chaliki HP, Moreno CA, Lester SJ�2007	�The noninvasive evaluation of exercise-induced changes in pulmonary artery pressure and pulmonary vascular resistance. J Am Soc Echocardiogr 20: 270-275.
15. Gurudevan SV, Malouf PJ, Kahn AM, et al. (2007	�Noninvasive assessment of pulmonary vascular resistance using doppler tissue imaging of the tricupid annulus. J Am Soc Echocardiogr 20: 1167-1171.

Figure legends 

Figure 1. The measuring method of the transverse dimension of right atrium and left atrium. They were measured in apical four chamber view at the early diastole before the atrioventricular valves opened.

Figure 2. The measuring method of the volume of right atrium and left atrium. They were measured in apical four chamber view at the early diastole before the atrioventricular valves opened. The volume was calculated by the machine after the inner border of the chamber was traced.

Figure 3. The measuring method of the transverse dimension of right ventricle, left ventricle  and the thickness of right ventricular lateral wall. They were measured in apical four chamber view at the end diastole when the atrioventricular valves closed.

Figure 4. The measuring method of the volume of right ventricle and left ventricle. They were measured in apical four chamber view at the end diastole when the atrioventricular valves closed. The volume was calculated by the machine after the inner border of the chamber was traced.

Figure 5. The measuring method of the thickness of right ventricular outlet wall. It was measured in aortic short axis view at the end diastole when the tricuspid valve closed.

Figure 6. The measuring method of the thickness of right ventricular anterior wall, the thickness of left ventricular posterior wall and the diameter of aorta at valve. They were measured in left ventricular long axis view at the end diastole when the mitral valve closed. AO: aorta; LA: left atrium; LV: left ventricle; RV: right ventricle.

Figure 7. The measuring method of the diameter of pulmonary artery at valve and at trunk. They were measured in pulmonary artery long axis view at the end diastole before the pulmonary artery valve opened.

Figure 8. The comparison of heart shapes (all in apical four chamber view). A, the heart shape of a highland resident. B, the heart shape of a highland sojourner. C, the heart shape of a high altitude heart disease patient. D, the heart shape of a sea-level resident. The heart shapes of highland resident and sea-level resident are similar. The right heart hypertrophy of high altitude heart disease patient is severe (The picture focuses on the right atrium.). The right heart hypertrophy of highland sojourner is obvious. The heart shape of highland sojourner situates between that of highland resident and high altitude heart disease patient. LA: left atrium; LV: left ventricle; RA: right atrium; RV: right ventricle.

Table 1  The general data of the four groups and ethnicity subgroups
GroupNumber of subjectsGenderAgeEthnicityInclusion criteriaAltitude of examinationFormer altitude of residenceDuration of stay above 3600 mHSG312male 223 
female 89 0.7~70Han   280
Tibetan 321, without any known systemic disease. 2,born below 3600 m and came above 3600 m afterwards.3658 m< 3600 m3 d ~ 58y
mean 11.2yHSGh280male 205 
female 750.7~69Han   2801, 2 the same as those for HSG. 3, Han.3658 m< 3600 m3 d ~ 45y
mean 10.4yHSGt32male 18 
female 14 17~70Tibetan 321, 2 the same as those for HSG. 3, Tibetan.3658 m< 3600 m~58y
mean 18.6yHRG184male 90 
female 94 0.1~82Han    19
Tibetan 1651, without any known systemic disease. 2, born above 3600 m (including 3600 m) and lived there afterwards.3658 me"3600 msame as the subject s age
mean 41.7yHRGh19male 11  
female 8 0.1~62Han    191, 2 the same as those for HRG. 3, Han.3658 me"3600 msame as the subject s age
mean 26.8yHRGt165male 79 
female 860.25~82Tibetan 1651, 2 the same as those for HRG. 3, Tibetan.3658 me"3600 msame as the subject s age
mean 43.4yHHDG51male 24  
female 27 0.1~71Han   27
Tibetan 241, right heart failure. 2, peak pulmonary pressure > 40 mmHg. 3, right ventricular hypertrophy and enlargement. 4, 1~3 were ind,-ST_`a��������������������				
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