Central Aortic Stiffness and Its Association with Ascending Aorta Dilation in Subjects with a Bicuspid Aortic Valve


Reduced elasticity and dilatation of the proximal aorta are highly prevalent in patients with bicuspid aortic valves (BAVs), even in the absence of valvular dysfunction. The aim of this study was to examine central aortic stiffness and its association with ascending aortic dilation in subjects with BAVs compared with controls.


Fifty subjects with BAVs (39 men; mean age, 52 ± 14 years) without significant valve dysfunction and 50 age-matched and gender-matched controls with normal trileaflet aortic valves were studied. Aortic diameter was measured using two-dimensional echocardiography, and central hemodynamics were assessed simultaneously using radial artery tonometry. Subjects with BAVs were divided into two groups on the basis of the median value of the aortic diameter.


Subjects with BAVs had larger ascending aortic diameters (20.6 ± 4.0 vs 17.9 ± 2.4 mm/m 2 , P < .001), higher augmentation indexes normalized for a heart rate of 75 beats/min (25.3 ± 9.7% vs 16.7 ± 8.6%, P < .001), higher pulse-wave velocities (7.8 ± 1.5 vs 7.2 ± 1.0 m/sec, P = .013), and lower pulse pressure amplification (1.24 ± 0.27 vs 1.35 ± 0.18, P = .022) than control subjects. The higher augmentation indexes were significant even in subjects with BAVs with relatively normal sized aortas. The diameter of the ascending aorta was correlated with augmentation index ( r = 0.48, P < .001), pulse-wave velocity ( r = 0.27, P = .063), and pulse pressure amplification ( r = −0.46, P = .001) in subjects with BAVs.


Subjects with BAVs had stiffer central hemodynamics than controls with tricuspid aortic valves, even in the absence of significant aortic dilation. Central aortic stiffness was positively correlated with the degree of aortic dilation in subjects with BAV. Thus, the evaluation of central aortic stiffness could be useful for the early detection and risk stratification of aortopathy in subjects with BAVs.

A bicuspid aortic valve (BAV) is the most common congenital cardiac malformation, occurring in 1% to 2% of the population. BAV is frequently associated with significant abnormalities of the aorta, and the risk for dissection is higher in subjects with BAVs than in those with normal trileaflet valves. Interestingly, the degree of aortic dilation is not directly related to valve hemodynamics. Increased aortic wall stiffness has been reported in subjects with normally functioning or mildly dysfunctional BAVs, and abnormal aortic elastic properties are not based solely on aortic size. The exact mechanisms leading to dilation are not fully understood, but pulsatile stress probably plays an important role. The characteristics of central hemodynamics and their association with the aortic dimension in subjects with BAVs are still unknown.

Central aortic stiffness is a hallmark of the aging process and a surrogate for vascular disease. Arterial stiffness increases as elastic fibers in the lamina media of the aorta are destroyed and replaced by collagen fibers, causing a substantial increase in aortic impedance and resultant changes in the central pulse wave. Pulse-wave analysis is a valid, noninvasive, reproducible method with which to measure central pressure and the two indices of arterial stiffness, the augmentation index (AIx) and the pulse-wave velocity (PWV).

Our aims in the present study were to evaluate central hemodynamics using pulse-wave analysis in subjects with BAVs without significant aortic valve dysfunction compared with controls and to determine the association between central aortic stiffness and ascending aortic dilation.


Study Subjects

We prospectively identified 50 subjects with BAVs (mean age, 52 ± 14 years) without aortic valve dysfunction, defined as less than mild aortic stenosis or regurgitation, who underwent echocardiography at Severance Cardiovascular Hospital (Seoul, Korea) between June 1, 2009, and May 31, 2010. The control group, matched for sex and age, comprised 50 subjects who were referred for echocardiography to evaluate cardiac function. All subjects in both groups were in sinus rhythm and had normal left ventricular (LV) ejection fractions (≥55%). Subjects were excluded if they had significant mitral, aortic, or tricuspid valvular dysfunction; Marfan syndrome or other connective tissue diseases; peripheral artery disease; cardiomyopathies; peripheral systolic blood pressure (BP) > 140 mm Hg; or renal insufficiency (serum creatinine level ≥ 1.4 mg/dL). This study was approved by the institutional review board of our institution, and informed consent was obtained from all study subjects.


Comprehensive transthoracic echocardiography was performed using commercially available equipment (Vivid 7, GE Vingmed Ultrasound AS, Horten, Norway; or Sonos 5500, Philips Medical Systems, Andover, MA). Aortic valve morphology was evaluated in the parasternal long-axis and short-axis views, and only those subjects with clearly identified aortic valve orifices and leaflets were included. A congenital BAV was diagnosed when only two cusps were unequivocally identified in systole and diastole in the short-axis view, with a clear “fish mouth” appearance during systole. We classified BAV phenotypes into three types according to raphe orientation in relation to the sinuses and cusp fusion pattern: (1) fusion of the left coronary and right coronary cusps, (2) fusion of the right coronary and noncoronary cusps, and (3) fusion of the left coronary and noncoronary cusps. The presence and severity of aortic regurgitation were assessed using an integrated approach. Color Doppler imaging was performed to measure the proximal jet width or cross-sectional area obtained from the long-axis view immediately below the aortic valve (within 1 cm of the valve), and the ratio of the proximal jet width to the LV outflow tract diameter was calculated. Other specific and supportive signs of severity were also assessed. Peak aortic velocity was assessed by continuous-wave Doppler, and aortic stenosis was considered to be present when the peak aortic velocity was > 2.5 m/sec. Measurements of the four aortic segments, including the aortic annulus, sinus of Valsalva, sinotubular junction, and proximal ascending aorta 1 cm above the sinotubular junction, were obtained at end-diastole by two-dimensional echocardiography. A dilated ascending aorta was defined as an aorta with a diameter ≥ 40 mm. Aortic dimensions were normalized to body surface area.

LV internal diameter, septal thickness, and LV posterior wall thickness were measured at end-diastole. LV mass was calculated using the formula developed by Devereux et al. and indexed to body surface area. Left atrial volume was calculated from the parasternal long-axis view and apical four-chamber view using the prolate ellipse method and indexed to body surface area. Mitral inflow velocities were obtained by pulsed-wave Doppler in the apical four-chamber view. Mitral early diastolic velocity (E) and the deceleration time of the E velocity were measured. Peak early diastolic mitral annular velocity (Ea) was measured from the septal mitral annulus, and the E/Ea ratio, a measure of LV filling pressure, was calculated. For each quantitative parameter, three consecutive beats were averaged. Echocardiographic data were gathered and analyzed by two independent investigators who were unaware of subjects’ clinical data.

Measurement of Central Hemodynamics

Central hemodynamics and parameters of arterial stiffness were assessed by pulse-wave analysis of the radial artery using a commercially available radial artery tonometry system (SphygmoCor; AtCor Medical, Sydney, Australia). Measurements were taken with subjects in the supine position after ≥5 min of rest immediately before echocardiography. As reported previously, peripheral pressure waveforms were recorded from the radial artery at the wrist using applanation tonometry with a high-fidelity micromanometer (Millar Instruments, Houston, TX). After 20 sequential waveforms were acquired, a validated generalized transfer function was used to generate the corresponding central aortic pressures and pressure waveforms. Central systolic and diastolic BP, pulse pressure (PP), augmentation pressure, and the AIx were derived by pulse waveform analysis ( Figure 1 ). PP was calculated as the difference between the respective systolic and diastolic pressures. Augmentation pressure was calculated as the difference between the second (reflected wave) and first systolic (ejection wave) peaks, and AIx was defined as the ratio of the augmentation pressure to the aortic PP and is expressed as a percentage. In addition, given that AIx is influenced by heart rate, an index normalized for a heart rate of 75 beats/min (AIx@75) was used in accordance with Wilkinson et al. PP amplification (PPA) was calculated as the ratio of the peripheral to the central PP. PWV was assessed using the quotient of the carotid-femoral path length and carotid-femoral pressure pulse transit time. High-quality recordings, which were defined as those with in-device quality indexes > 90%, were derived from an algorithm that included average pulse height, pulse height variation, diastolic variation, and the maximum rate of rise of the peripheral waveform. Peripheral BP was measured with subjects in the supine position at the brachial artery of the dominant arm after 15 min of rest in the laboratory using the validated Omron HEM-705 CP oscillometric sphygmomanometer (Omron Corporation, Kyoto, Japan). These hemodynamic data were measured and analyzed by an independent investigator who was unaware of subjects’ clinical data.

Figure 1

A central aortic pressure waveform and parameters from radial artery tonometry.

Statistical Analysis

Data are expressed as mean ± SD for continuous variables. Pairwise comparisons between patients with BAVs and controls were performed using standard χ 2 tests for categorical variables and paired t tests for continuous variables.

To compare continuous variables related to central aortic stiffness in different BAV phenotypes, analysis of variance was performed. To determine independent correlates of AIx@75 and PPA, linear relations were verified using simple linear regression analysis. Variables that were statistically significant in the univariate analysis were included in the multiple linear regression model. Subgroup analysis was performed using unpaired t tests among controls and those with aortic diameter values above and below the median for subjects with BAVs. P values < .05 were considered statistically significant.


The baseline characteristics of the two groups were largely comparable ( Table 1 ). The echocardiographic parameters are summarized in Table 2 . Aortic diameters were significantly larger in subjects with BAVs than in controls at the site of the annulus (12.1 ± 1.2 vs 13.4 ± 2.3 mm/m 2 ), sinus of Valsalva (18.0 ± 2.3 vs 20.5 ± 4.0 mm/m 2 ), sinotubular junction (16.8 ± 2.0 vs 18.4 ± 3.4 mm/m 2 ), and ascending aorta (17.9 ± 2.4 vs 20.6 ± 4.0 mm/m 2 ) ( P < .05 for all). Of the subjects with BAVs, 62% showed the phenotype of fusion of the left coronary and right coronary cusps. LV end-diastolic diameters were significantly larger in subjects with BAVs. LV ejection fraction, LV mass index, LA volume index, E velocity, and deceleration time of the E velocity were not significantly different between the two groups. However, Ea velocity, which reflects LV longitudinal relaxation, was significantly lower, and the E/Ea ratio, which reflects LV filling pressure, was significantly higher in subjects with BAVs than in controls.

Table 1

Clinical characteristics of subjects with BAVs and controls

Variable Controls ( n = 50) Subjects with BAVs ( n = 50) P
Age (y) 52 ± 14 52 ± 14 1.000
Men 39 (78.0%) 39 (78.0%) 1.000
Height (cm) 168 ± 8 167 ± 8 .486
Weight (kg) 69.6 ± 10.5 68.1 ± 11.0 .185
BMI (kg/m 2 ) 25.2 ± 2.7 24.7 ± 2.9 .742
Hypertension 25 (52.1%) 20 (40.0%) .230
Diabetes mellitus 4 (8.3%) 6 (12.0%) .549
Dyslipidemia 14 (28.0%) 10 (20.0%) .349
CAD 2 (4.0%) 4 (8.0%) .400
Smoking 21 (44.7%) 16 (32.0%) .199
Diuretics 4 (8.5%) 10 (20.0%) .108
β-blockers 6 (12.8%) 10 (20.0%) .284
ACE inhibitors or ARBs 12 (25.5%) 19 (38.0%) .188
CCBs 15 (30.0%) 11 (23.4%) .464

Data are expressed as mean ± SD or as number (percentage).

ACE , Angiotensin-converting enzyme; ARB , angiotensin receptor blocker; BMI , body mass index; CAD , coronary artery disease; CCB , calcium channel blockers.

Table 2

Echocardiographic parameters of subjects with BAVs and controls

Variable Controls ( n = 50) Subjects with BAVs ( n = 50) P
Dilated ascending aorta 0 (0%) 14 (28%) <.001
Indexed aortic diameter
Annulus (mm/m 2 ) 12.1 ± 1.2 13.4 ± 2.3 .001
Sinus of Valsalva (mm/m 2 ) 18.0 ± 2.3 20.5 ± 4.0 <.001
Sinotubular junction (mm/m 2 ) 16.8 ± 2.0 18.4 ± 3.4 .006
Ascending aorta (mm/m 2 ) 17.9 ± 2.4 20.6 ± 4.0 <.001
BAV phenotypes
LC-RC fusion 31 (62%)
RC-NC fusion 12 (24%)
LC-NC fusion 7 (14%)
LVEDD (mm) 48.9 ± 4.0 51.0 ± 4.2 .012
LVESD (mm) 32.3 ± 4.9 34.0 ± 4.6 .088
LVEF (%) 66.3 ± 7.7 65.7 ± 7.5 .712
LV mass index (g/m 2 ) 92.5 ± 15.7 99.5 ± 17.1 .197
LA volume index (mL/m 2 ) 24.4 ± 7.1 25.6 ± 9.5 .465
E velocity (cm/sec) 66.6 ± 16.3 70.8 ± 18.4 .234
Deceleration time (msec) 195.9 ± 34.2 204.0 ± 48.4 .338
Ea velocity (cm/sec) 8.4 ± 1.6 6.7 ± 2.3 <.001
E/Ea ratio 9.8 ± 4.1 11.5 ± 4.3 .043

Data are expressed as mean ± SD or as number (percentage).

LA , Left atrial; LC , left coronary cusp; LVEDD , LV end-diastolic diameter; LVEF , LV ejection fraction; LVESD , LV end-systolic diameter; NC , noncoronary cusp; RC , right coronary cusp.

The central and peripheral hemodynamic variables of the two groups are presented in Table 3 . Peripheral systolic and diastolic BP and PP were not significantly different between groups. Similarly, central systolic and diastolic BP were also not significantly different between the two groups. However, central PP (36.0 ± 7.7 vs 39.6 ± 8.1 mm Hg, P = .042), augmentation pressure (8.8 ± 5.6 vs 11.7 ± 6.4 mm Hg, P = .017), AIx (22.6 ± 11.0% vs 30.2 ± 10.4%, P = .001), and AIx@75 (17.6 ± 9.8% vs 25.8 ± 9.0%, P < .001) were significantly higher, and PPA (1.36 ± 0.17 vs 1.28 ± 0.19, P = .024) was significantly lower in subjects with BAVs. Table 4 shows hemodynamic parameters reflecting central aortic stiffness in the different BAV phenotypes. Subjects with BAVs with fusion of the left coronary and right coronary cusps showed higher PWVs and lower PPA than subjects with fusion of the left coronary and noncoronary cusps. However, there were no significant differences in parameters of central aortic stiffness among the groups of three different phenotypes.

Table 3

Peripheral and central hemodynamics of subjects with BAVs and controls

Variable Controls
( n = 50)
Subjects with BAVs
( n = 50)
Peripheral SBP (mm Hg) 120.1 ± 10.0 121.1 ± 16.1 .674
Peripheral DBP (mm Hg) 75.0 ± 8.0 74.8 ± 11.8 .318
Peripheral PP (mm Hg) 45.3 ± 10.0 46.5 ± 11.0 .366
Central SBP (mm Hg) 109.3 ± 10.3 111.7 ± 15.0 .480
Central DBP (mm Hg) 73.9 ± 8.0 71.8 ± 9.2 .321
Central PP (mm Hg) 36.0 ± 7.7 39.6 ± 8.1 .042
Heart rate (beats/min) 64.3 ± 9.9 62.5 ± 14.5 .471
AP (mm Hg) 8.8 ± 5.6 11.7 ± 6.4 .017
AIx (%) 22.6 ± 11.0 30.2 ± 10.4 .001
AIx@75 (%) 17.6 ± 9.8 25.8 ± 9.0 <.001
PPA 1.36 ± 0.17 1.28 ± 0.19 .024
PWV (m/sec) 7.3 ± 1.1 7.7 ± 1.5 .156

Data are expressed as mean ± SD.

AP , Augmentation pressure; DBP , diastolic BP; SBP , systolic BP.

Jun 11, 2018 | Posted by in CARDIOLOGY | Comments Off on Central Aortic Stiffness and Its Association with Ascending Aorta Dilation in Subjects with a Bicuspid Aortic Valve

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