the prevalence of as ranges from 2% to 9% of aged population over 65 years old , and it is increasingly diagnosed in the contemporary era of aging society.1 ) given no established medical treatment to improve prognosis of as patients , decision to proceed with corrective surgery is crucial . progression of as is usually longitudinally followed using transthoracic echocardiography , and the estimation of effective orifice area of aortic valve ( eoaav ) is considered the most important parameter to monitor as patients.2 ) eoaav is calculated by the transvalvular pressure gradient ( tpg ) and transvalvar flow , and tpg is associated with systemic vascular resistance ( svr).3 ) in the presence of systemic hypertension or peripheral arterial disease , svr increases and this svr alteration might possibly change the parameters that are frequently used to determine as severity . this hypothesis is corroborated by notion that high left ventricular ( lv ) afterload can result in paradoxical low - flow , low - gradient severe as , highlighting the notion that lv afterload should be considered in terms of assessing severe as.4 ) furthermore , in contrast to traditional belief that blood pressure was thought to be decreased in case of severe as , recent studies reported that hypertension is common even in severe as patients and one of the important risk factors of significant as.1 ) therefore , consideration of hypertension is a commonly encountered clinical situation in estimating as severity.5 ) the aim of this study was to investigate the impact of lv afterload on the assessment of as severity . patients diagnosed as moderate or severe as ( eoaav calculated from continuity equation of less than 1.5 cm ) were consecutively enrolled from march 2008 to february 2009 . exclusion criteria were as follows ; patients with inadequate image quality due to poor echo window , any valvular regurgitation more than mild degree , any valvular stenosis other than aortic valve , severe systemic hypertension [ systolic blood pressure ( bp ) of > 180 mmhg , and/or diastolic bp of > 110 mmhg ] , severe lv dysfunction defined as lv ejection fraction ( ef ) of less than 30% , and diagnosis of acute coronary syndrome within a month . patients with peripheral artery disease with claudication transthoracic echocardiography was performed using commercially available echocardiography machine ( vivid 7 , ge medical systems , milwaukee , wi , usa ) . if the patient was confirmed to be eligible , baseline echocardiography was performed after 20 minutes of rest . non - invasive bp and heart rate ( hr ) were measured just before echocardiography examination . peak early ( e ) and late ( a ) diastolic velocities of the mitral inflow were measured using a pulsed - wave doppler at the tip of mitral valve leaflets , and peak early ( e ' ) and late ( a ' ) diastolic mitral annular velocities were acquired at the septal side in the apical 4 chamber view . recording of aortic valve maximal systolic velocity ( av vmax ) was acquired from multiple views including suprasternal , right parasternal , apical and subcostal transducer positions with a continuous - wave doppler echocardiographic technique , among which only the highest peak velocity was chosen for subsequent analyses . pulsed - wave doppler at lv outflow tract ( lvot ) was also obtained at the apical 5-chamber view . lv end - systolic wall stress was calculated as follows ; ( lv end - systolic wall stress is in g / cm , pes , which stands for lv end - systolic pressure plus maximal pressure gradient of aortic valve , is in mmhg , des and he s are in cm , and 0.34 is the factor for converting pes from mmhg to g / cm . ) specially designed pneumatic trousers without the bladder for compression of the lower abdomen were put on the patients as previously described.6 ) after baseline echocardiography data acquisition , a specially designed compressor inflated the pneumatic trousers up to a pressure of 100 mmhg on both lower extremities and this pressure was maintained throughout the examination . echocardiography was performed including doppler parameters 3 minutes after pneumatic compression of the lower extremities ( pcom ) . doppler measurements of av vmax , transvalvular peak and mean pressure gradient ( av peak pg and av mean pg ) , and time - velocity integral of lv outflow tract ( tvilvot ) and aortic valve ( tviav ) were also made . eoaav was calculated by continuity equation as previously described.7 ) doppler velocity index ( tvilvot / tviav ) was calculated , as well . lvot area ( csalvot ) was calculated from the diameter obtained at the level of the aortic annulus during systole with the assumption of a circular shape of lvot . lv stroke volume was calculated by multiplying csalvot by tvilvot as previously described.8 ) cardiac output ( co ) was calculated by multiplying sv and hr . systemic vascular resistance ( svr ) was estimated as : svr = 80  mean bp / co and systemic arterial compliance ( sac ) was calculated as : sac = sv / ( sbp - dbp ) numerical data are expressed as means  sd or median ( interquartile range ) where appropriate . paired t - test was adopted for comparison of echocardiographic parameters between before and after application of pcom . all statistical analyses were performed using pasw 18.0 ( spss inc . , chicago , il , usa ) , and p - values of < 0.05 were considered statistically significant . patients diagnosed as moderate or severe as ( eoaav calculated from continuity equation of less than 1.5 cm ) were consecutively enrolled from march 2008 to february 2009 . exclusion criteria were as follows ; patients with inadequate image quality due to poor echo window , any valvular regurgitation more than mild degree , any valvular stenosis other than aortic valve , severe systemic hypertension [ systolic blood pressure ( bp ) of > 180 mmhg , and/or diastolic bp of > 110 mmhg ] , severe lv dysfunction defined as lv ejection fraction ( ef ) of less than 30% , and diagnosis of acute coronary syndrome within a month . patients with peripheral artery disease with claudication were also excluded . transthoracic echocardiography was performed using commercially available echocardiography machine ( vivid 7 , ge medical systems , milwaukee , wi , usa ) . if the patient was confirmed to be eligible , baseline echocardiography was performed after 20 minutes of rest . non - invasive bp and heart rate ( hr ) were measured just before echocardiography examination . peak early ( e ) and late ( a ) diastolic velocities of the mitral inflow were measured using a pulsed - wave doppler at the tip of mitral valve leaflets , and peak early ( e ' ) and late ( a ' ) diastolic mitral annular velocities were acquired at the septal side in the apical 4 chamber view . recording of aortic valve maximal systolic velocity ( av vmax ) was acquired from multiple views including suprasternal , right parasternal , apical and subcostal transducer positions with a continuous - wave doppler echocardiographic technique , among which only the highest peak velocity was chosen for subsequent analyses . pulsed - wave doppler at lv outflow tract ( lvot ) was also obtained at the apical 5-chamber view . lv end - systolic wall stress was calculated as follows ; ( lv end - systolic wall stress is in g / cm , pes , which stands for lv end - systolic pressure plus maximal pressure gradient of aortic valve , is in mmhg , des and he s are in cm , and 0.34 is the factor for converting pes from mmhg to g / cm . ) specially designed pneumatic trousers without the bladder for compression of the lower abdomen were put on the patients as previously described.6 ) after baseline echocardiography data acquisition , a specially designed compressor inflated the pneumatic trousers up to a pressure of 100 mmhg on both lower extremities and this pressure was maintained throughout the examination . echocardiography was performed including doppler parameters 3 minutes after pneumatic compression of the lower extremities ( pcom ) . doppler measurements of av vmax , transvalvular peak and mean pressure gradient ( av peak pg and av mean pg ) , and time - velocity integral of lv outflow tract ( tvilvot ) and aortic valve ( tviav ) were also made . eoaav was calculated by continuity equation as previously described.7 ) doppler velocity index ( tvilvot / tviav ) was calculated , as well . lvot area ( csalvot ) was calculated from the diameter obtained at the level of the aortic annulus during systole with the assumption of a circular shape of lvot . lv stroke volume was calculated by multiplying csalvot by tvilvot as previously described.8 ) cardiac output ( co ) was calculated by multiplying sv and hr . systemic vascular resistance ( svr ) was estimated as : svr = 80  mean bp / co and systemic arterial compliance ( sac ) was calculated as : sac = sv / ( sbp - dbp ) numerical data are expressed as means  sd or median ( interquartile range ) where appropriate . paired t - test was adopted for comparison of echocardiographic parameters between before and after application of pcom . all statistical analyses were performed using pasw 18.0 ( spss inc . , chicago , il , usa ) , and p - values of < 0.05 were considered statistically significant . mean bp was significantly increased from 92  13 to 98  14 mmhg ( p svr significantly increased from 1351.0  370.2 to 1450.3  476.0 dyns / cm ( p = 0.004 ) and accordingly , sac was decreased from 1.57  0.53 to 1.49  0.55 ml / mmhg ( p = 0.07 ) . however , hr remained unchanged ( 67.23  13.4 bpm at baseline vs. 67.1  12.8 bpm under pcom , p = 0.69 ) . pcom application exerted no significant effect on lv end - systolic dimension and lv ef ( table 2 ) . likewise , lv sv and co under pcom were comparable to those measured at baseline . in contrast , lv end - diastolic dimension was slightly increased under pcom ( 47.4  5.9 mm vs. 48.9  4.9 mm , p < 0.02 ) . e wave velocity was also significantly increased after pneumatic compression ( 0.74  0.21 m / s vs. 0.82  0.26 m / s , p < 0.001 ) , and e / e ' tended to be slightly increased with a borderline statistical significance ( 16.9  7.6 vs. 17.8  8.6 , p = 0.06 ) . neither s ' nor calculated end - systolic wall stress under pcom showed significant changes . doppler velocity index ( tvilvot / tviav ) was not changed under pcom ( p = 0.48 ) ( table 3 ) . however , av vmax and av peak pg displayed a small , but significant decline under pcom however absolute difference between the two different afterload status was only 0.10  0.24 m / s and 1.73  6.08 mmhg , respectively ( table 3 ) . mean bp was significantly increased from 92  13 to 98  14 mmhg ( p < 0.001 ) ( fig . svr significantly increased from 1351.0  370.2 to 1450.3  476.0 dyns / cm ( p = 0.004 ) and accordingly , sac was decreased from 1.57  0.53 to 1.49  0.55 ml / mmhg ( p = 0.07 ) . however , hr remained unchanged ( 67.23  13.4 bpm at baseline vs. 67.1  12.8 bpm under pcom , p = 0.69 ) . pcom application exerted no significant effect on lv end - systolic dimension and lv ef ( table 2 ) . likewise , lv sv and co under pcom were comparable to those measured at baseline . in contrast , lv end - diastolic dimension was slightly increased under pcom ( 47.4  5.9 mm vs. 48.9  4.9 mm , p < 0.02 ) . e wave velocity was also significantly increased after pneumatic compression ( 0.74  0.21 m / s vs. 0.82  0.26 m / s , p < 0.001 ) , and e / e ' tended to be slightly increased with a borderline statistical significance ( 16.9  7.6 vs. 17.8  8.6 , p = 0.06 ) . neither s ' nor calculated end - systolic wall stress under pcom showed significant changes . doppler velocity index ( tvilvot / tviav ) was not changed under pcom ( p = 0.48 ) ( table 3 ) . however , av vmax and av peak pg displayed a small , but significant decline under pcom however absolute difference between the two different afterload status was only 0.10  0.24 m / s and 1.73  6.08 mmhg , respectively ( table 3 ) . in the present study , we modulated lv afterload using specially designed pneumatic compression trousers without any significant effect on hr to evaluate the impact of lv afterload modification on the assessment of as severity . pcom successfully increased lv afterload , as evidenced by increased svr as well as decreased sac without any change of hr . although tpg of aortic valve slightly decreased with lv afterload rise , this was not translated into significant changes in eoaav and doppler velocity index obtained with routine echocardiography . increased afterload may have a potential to affect the accuracy of assessment of as severity . increased afterload increases svr , which subsequently elevates the ascending aortic pressure . in case of significant as , the effect of increased systemic central bp on intraventricular pressure might be minimal , and thus , tpg between lv and ascending aorta might be decreased because of relatively increased central aortic pressure in comparison with intra - lv pressure . however , if the transmission of increased afterload into lv cavity per se were considerable , lv systolic wall stress would rise and lead to a decrease in lv systolic performance . in addition , increased lv afterload along with a decrease in sac can attenuate lv co,9 ) and finally result in a decrease in av mean pg , av vmax , and av peak pg . it may be possible that aortic root expansion also can increase csalvot during systole , and subsequently lead to commissural separation and finally stretch the free edge of the aortic valve leaflets . although the effect of aortic root expansion was previously reported in normal aortic valve,10)11 ) it appears to be unclear whether thickened and less mobile aortic valve and annulus can change their shape during lv afterload changes as normal aortic valve does . in this study , we found that lv ef , lv sv and co did not change significantly with a maneuver leading to a rise in lv afterload . in order to achieve effective lv afterload increment without any influence of hr although we could did not directly measure intracardiac pressure , pcom was considered very effective in modifying lv afterload , as demonstrated by a significant increase in svr . as shown in our representative cases in fig . 2 , tpg of av , as represented by 2 parameters of av vmax and av peak pg , was decreased under pcom , suggesting the fact that an increase of aortic pressure was even greater than an increase of intra - lv pressure during systolic phase in the setting of lv afterload increment . on the other hand , eoaav and doppler velocity index did not change , indirectly highlighting that increased afterload did not modulate aortic root size or commissural opening of stenotic aortic valve in this special as population . in this study , we used pcom for experimental change in afterload . pcom successfully increased lv afterload without a significant change in hr ; however , pcom possibly increases the venous return from lower extremities , which could explain , to some extent , increased e velocity , and slightly increased lv end - diastolic dimension . increased preload can increase the stroke volume and possibly increase the av vmax of aortic valve . our data showed no significant change of stroke volume , av peak pg and av vmax before and after pcom ; thus the effects of pcom on lv preload and stroke volume , and furthermore as severity assessment appears negligible . a previous study by little et al.12 ) showed decreased ava by acute bp elevation induced by phenylephrine infusion and hand grip exercise . they suggested that the impact of bp change is associated with transvalvular flow rate through aortic valve without relation to svr or sac . in this study , we adopted pcom instead of hand grip exercise or phenylephrine infusion because these methods augment heart rate and induce a significant change in ejection time , as previously described . because our study was free from changes in hr and lv ejection time under pcom , an impact of lv afterload change on ava assessment can be exclusively assessed , which is , we believe , a significant advantage of the current study . pcom is a useful method to increase lv afterload without change of preload or hr when compared to other methods , such as hand grip exercise or phenylephrine infusion.12 ) however , pcom possibly increases the venous return from lower extremities , which could explain , to some extent , increased e velocity , and slightly increased lv end - diastolic dimension . however , a previous study clearly demonstrated that the primary mechanism whereby pcom induced changes in hemodynamics is through an acute increase in lv afterload.13 ) in addition , a change in lv co was minimal , highlighting the impression that hemodynamic effect by venous return for cardiac performance was , if any , negligible . simulation of arterial bp elevation by pcom also has a limitation for svr increase alone , and can not increase aortic stiffness which is more important in essential hypertension in elderly patients . we also can not directly measure lv systolic wall stress and central bp , because we did not perform invasive monitoring of intra - lv pressure and central bp , however , svr and sac that were employed in the current study were previously validated against invasively obtained hemodynamic data as indirect indexes for lv afterload.14)15 ) assessment of as severity by routine transthoracic echocardiography was not significantly influenced by a change in lv afterload . av vmax could be slightly decreased when lv afterload rises , but these changes did not seem to exert a significant influence on clinical decision making in managing as patients . eoaav and doppler velocity index is more stable method for evaluation of as severity than av vmax , and therefore these 2 indexes should be used in the determination of as severity , rather than av vmax or tpg of av . pcom is a useful method to increase lv afterload without change of preload or hr when compared to other methods , such as hand grip exercise or phenylephrine infusion.12 ) however , pcom possibly increases the venous return from lower extremities , which could explain , to some extent , increased e velocity , and slightly increased lv end - diastolic dimension . however , a previous study clearly demonstrated that the primary mechanism whereby pcom induced changes in hemodynamics is through an acute increase in lv afterload.13 ) in addition , a change in lv co was minimal , highlighting the impression that hemodynamic effect by venous return for cardiac performance was , if any , negligible . simulation of arterial bp elevation by pcom also has a limitation for svr increase alone , and can not increase aortic stiffness which is more important in essential hypertension in elderly patients . we also can not directly measure lv systolic wall stress and central bp , because we did not perform invasive monitoring of intra - lv pressure and central bp , however , svr and sac that were employed in the current study were previously validated against invasively obtained hemodynamic data as indirect indexes for lv afterload.14)15 ) assessment of as severity by routine transthoracic echocardiography was not significantly influenced by a change in lv afterload . av vmax could be slightly decreased when lv afterload rises , but these changes did not seem to exert a significant influence on clinical decision making in managing as patients . eoaav and doppler velocity index is more stable method for evaluation of as severity than av vmax , and therefore these 2 indexes should be used in the determination of as severity , rather than av vmax or tpg of av .