Abnormal aortic elastic properties in adults with congenital valvular aortic stenosis

doi:10.1016/j.ijcard.2007.06.065

International Journal of Cardiology

Volume 128, Issue 3, 29 August 2008, Pages 336-341

https://doi.org/10.1016/j.ijcard.2007.06.065 Get rights and content

Abstract

Background

Abnormalities of the aortic root are common in patients with a bicuspid aortic valve. Our aim was to investigate the elastic properties of the aortic root in patients with congenital aortic valvular stenosis (AS) in comparison with age- and gender-matched controls, and to investigate the influence of stenosis severity and aortic size on aortic root elasticity.

Methods

Thirty-two adults (mean age 30.4 ± 7.5 years, 22 men) with congenital AS without previous cardiovascular surgery were prospectively studied. Aortic root elasticity indices such as aortic stiffness index (ASI), aortic root distensibility (ARD), and aortic strain were calculated with the use of M-mode echocardiography.

Results

ASI was significantly higher in patients compared to controls, 8.5 ± 8.4 versus 4.0 ± 1.4, respectively (P < 0.01). Other indices of aortic root elasticity were similar between patients and controls: ARD was 4.2 ± 3.6 versus 4.3 ± 1.9 × 10^− 6 cm²/dynes, respectively, and aortic strain was 12.4 ± 9.6 versus 13.5 ± 5.0%, respectively (P = NS for all). Correlations were found between aortic size and indices of aortic elasticity (i.e., aortic strain and ARD), denoting that an increased aortic dimension is associated with a stiffer aorta. Interestingly, no correlations were found between indices of severity of AS and aortic elasticity, suggesting that an abnormal aortic elasticity is independent of stenosis severity.

Conclusions

Congenital AS results in abnormal aortic elastic properties, independent of stenosis severity. Furthermore, there seems to be a relationship between aortic dimensions and aortic stiffness.

Introduction

Abnormalities of the thoracic aorta are common in patients with a bicuspid aortic valve (BAV). Approximately 50% of patients with BAV have a dilated aortic root regardless of the presence or absence of hemodynamically significant valve dysfunction [1], [2], [3], which is probably due to aortic medial disease (i.e., fragmentation of elastin, abnormal collagen and smooth muscle cell, increased ground substance) [4], [5], [6], [7], [8]. These abnormalities within the aortic media results in BAV being responsible for 6–10% of all aortic dissections [9]. It has been estimated that approximately 5% of BAV patients will develop aortic dissection during their lifetime [9]. Besides aortic dilatation and dissections, a clear correlation with the presence of aortic coarctation has been found. BAV occurs in 25–85% of patients with coarctation of the aorta [10].

Once thought to be the consequence of post-stenotic dilatation, currently aortic medial disease (“cystic medial degeneration”) has been found to be the underlying cause of aortic dilatation and possibly abnormal aortic elastic properties [4], [5], [6], [7], [8]. Patients with normally functioning BAV have been shown to have abnormal elastic properties of the aortic root compared to controls, expressed by an increased aortic stiffness and a decreased aortic distensibility assessed by M-mode echocardiography [11]. Moreover, a recent MRI study has shown that the aortic stiffness in BAV patients is comparable to those of Marfan patients [12]. However, the effect of a stenotic BAV on the elastic properties of a structurally deficient aortic wall has not been investigated. Local flow perturbations above the stenotic valve could have an influence on the aortic elasticity. The aim of the present study was to compare the elastic properties of the aortic root in a homogenous population of patients with congenital valvular aortic stenosis (AS) to age- and gender-matched controls. In addition, we investigated whether stenosis severity or aortic dimensions influenced aortic elasticity.

Section snippets

Study population

Thirty-two young adults with congenital valvular AS (aortic jet velocity ≥ 2.5 m/s, all BAV) were prospectively examined from May 2005 till November 2006. Exclusion criteria were: 1) previous cardiovascular surgery; 2) the presence of moderate-to-severe aortic regurgitation; 3) aortic coarctation. All results were compared with those of 32 age- and gender-matched controls. All patients underwent transthoracic echocardiography. The study was approved by the local ethics committee, and informed

Results

Clinical, echocardiographic, hemodynamic, and aortic elasticity data are presented in Table 1. Patients and controls were similar with regard to age, body surface area, systolic blood pressure, and pulse pressure. As expected, patients with congenital AS had a higher LV mass and larger aortic roots compared to controls. Furthermore, there was a small but significant difference in the DBP between groups (73.5 ± 7.8 in patients versus 78.7 ± 11.7 mm Hg in controls, P = 0.04). When comparing indices of

Discussion

Although numerous studies have demonstrated abnormalities of the aortic wall in BAV patients [1], [2], [3], [4], [5], [6], [7], [8], the number of studies evaluating the effect of BAV on the vascular function of the aorta is limited [11], [12], [16], [17]. In the present study, we demonstrated that these patients have an abnormal aortic elasticity, which seems to be related to the dimensions of the aorta, but is independent of stenosis severity.

BAV is associated with aortic root dilatation [1],

Acknowledgements

The Netherlands Organisation for Health Research and Development provided funding for Dr. Yap (920-03-405, The Hague, The Netherlands). Dr. Nemes is a visiting fellow from the University of Szeged (Szeged, Hungary) and is supported by the “Research Fellowship of the European Society of Cardiology”.

References (27)

R.T. Hahn et al.
Association of aortic dilation with regurgitant, stenotic and functionally normal bicuspid aortic valves
J Am Coll Cardiol
(1992)
E.W. Larson et al.
Risk factors for aortic dissection: a necropsy study of 161 cases
Am J Cardiol
(1984)
T. Oosterhof et al.
Comparison of aortic stiffness in patients with juvenile forms of ascending aortic dilatation with versus without Marfan's syndrome
Am J Cardiol
(2005)
K. Hirata et al.
The Marfan syndrome: abnormal aortic elastic properties
J Am Coll Cardiol
(1991)
E.A. Karpanou et al.
Effects of menopause on aortic root function in hypertensive women
J Am Coll Cardiol
(1996)
R.M. Lang et al.
Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology
J Am Soc Echocardiogr
(2005)
B.M. Schaefer et al.
Usefulness of bicuspid aortic valve phenotype to predict elastic properties of the ascending aorta
Am J Cardiol
(2007)
H.B. Grotenhuis et al.
Reduced aortic elasticity and dilatation are associated with aortic regurgitation and left ventricular hypertrophy in nonstenotic bicuspid aortic valve patients
J Am Coll Cardiol
(2007)
M. Ferencik et al.
Changes in size of ascending aorta and aortic valve function with time in patients with congenitally bicuspid aortic valves
Am J Cardiol
(2003)
K. Hayashi et al.
Stiffness and elastic behavior of human intracranial and extracranial arteries
J Biomech
(1980)

M. Briand et al.

Reduced systemic arterial compliance impacts significantly on left ventricular afterload and function in aortic stenosis: implications for diagnosis and treatment

J Am Coll Cardiol

(2005)

A. Nemes et al.

Aortic valve replacement for aortic stenosis is associated with improved aortic distensibility at long-term follow-up

Am Heart J

(2007)

S. Nistri et al.

Aortic root dilatation in young men with normally functioning bicuspid aortic valves

Heart

(1999)

Cited by (24)

Comprehensive assessment of local and regional aortic stiffness in patients with tricuspid or bicuspid aortic valve aortopathy using magnetic resonance imaging
2021, International Journal of Cardiology
We aimed to provide a comprehensive aortic stiffness description using magnetic resonance imaging (MRI) in patients with ascending thoracic aorta aneurysm and tricuspid (TAV-ATAA) or bicuspid (BAV) aortic valve.
This case-control study included 18 TAV-ATAA and 19 BAV patients, with no aortic valve stenosis/severe regurgitation, who were 1:1 age-, gender- and central blood pressures (BP)-matched to healthy volunteers. Each underwent simultaneous aortic MRI and BP measurements. 3D anatomical MRI provided aortic diameters. Stiffness indices included: regional ascending (AA) and descending (DA) aorta pulse wave velocity (PWV) from 4D flow MRI; local AA and DA strain, distensibility and theoretical Bramwell-Hill (BH) model-based PWV, as well as regional arch PWV from 2D flow MRI.
Patient groups had significantly higher maximal AA diameter (median[interquartile range], TAV-ATAA: 47.5[42.0–51.3]mm, BAV: 45.0[41.0–47.0]mm) than their respective controls (29.1[26.8–31.8] and 28.1[26.0–32.0]mm, p < 0.0001), while BP were similar (p ≥ 0.25). Stiffness indices were significantly associated with age (ρ ≥ 0.33), mean BP (arch PWV: ρ = 0.25, p = 0.05; DA distensibility: ρ = −0.30, p = 0.02) or AA diameter (arch PWV: ρ = 0.28, p = 0.03; DA PWV: ρ = 0.32, p = 0.009). None of them, however, was significantly different between TAV-ATAA or BAV patients and their matched controls. Finally, while direct PWV measures were significantly correlated to BH-PWV estimates in controls (ρ ≥ 0.40), associations were non-significant in TAV-ATAA and BAV groups (p ≥ 0.18).
The overlap of MRI-derived aortic stiffness indices between patients with TAV or BAV aortopathy and matched controls highlights another heterogeneous feature of aortopathy, and suggests the urgent need for more sensitive indices which might help better discriminate such diseases.
Circulating Lp-PLA2 is associated with high valvuloarterial impedance and low arterial compliance in patients with aortic valve bioprostheses
2016, Clinica Chimica Acta
Citation Excerpt :
However, whether the Zva has a predictive value for the mortality risk after an AVR is presently unknown. Patients with CAVS have an elevated prevalence of a reduced arterial compliance [27]. In the present study, the mean Zva was high (5.7 ± 1.2 mm Hg·ml− 1·m2) in this group of patients followed-up on average 8 years post-AVR.
We previously reported that plasma Lp-PLA2 was associated with aortic valve disease progression and degeneration of bioprostheses. Low systemic arterial compliance and high valvuloarterial impedance (Z_va) are predictors of poor survival in patients with aortic valve disease. However, the prevalence of high Z_va after AVR is largely unknown and whether Lp-PLA2 could predict Z_va has not been documented. We investigated the relationships between plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) mass and activity and valvuloarterial impedance (Z_va), an index of global LV hemodynamic load, in patients that underwent aortic valve replacement (AVR).
A total of 195 patients with aortic bioprostheses underwent echocardiographic assessment of the prosthetic aortic valve function 8 ± 3.4 years after AVR. Lp-PLA2 mass and activity were measured.
In this group of patients, the mean Z_va was elevated (5.73 ± 1.21 mm Hg·ml^− 1·m²). In univariate analyses, Lp-PLA2 mass (p = 0.003) and Lp-PLA2 activity (p = 0.046) were associated with Z_va. After adjustment for covariates including age, gender, clinical risk factors, anti-hypertensive medications, body mass index and prosthesis size, Lp-PLA2 mass was associated with high Z_va (≥ 4.5 mm Hg·ml^− 1·m²) (OR: 1.29, 95%CI: 1.10–1.53; p = 0.005) and was inversely related with the systemic arterial compliance (β = − 0.01, SEM = 0.003; p = 0.003).
An increased Z_va, an index of excessive hemodynamic load, was highly prevalent 8-year post-AVR and was independently related to circulating Lp-PLA2.
Aortic valve replacement reduces valvuloarterial impedance but does not affect systemic arterial compliance in elderly men with degenerative calcific trileaflet aortic valve stenosis
2014, Journal of Cardiothoracic and Vascular Anesthesia
Standard methods of quantifying aortic valve stenosis (AS), which focus entirely on the valve itself, do not adequately characterize the magnitude, predict the onset, progression, and severity of symptoms, or identify the incidence of subsequent adverse events. Valvuloarterial impedance (Z_va) is an index of global left ventricular (LV) afterload that incorporates valvular and arterial loads. The authors tested the hypothesis that aortic valve replacement (AVR) reduces Z_va but does not affect the arterial component of LV afterload in elderly patients with degenerative calcific trileaflet AS.
Observational study.
Veterans affairs medical center.
Eight elderly (age, 79±4 years) men with moderate-to-severe AS and normal preoperative LV function (ejection fraction, 61%±9%) scheduled for AVR with or without coronary artery bypass graft surgery were studied after institutional review board approval.
None.
A comprehensive TEE examination was performed during isoflurane-fentanyl-rocuronium anesthesia. Doppler echocardiography was used to measure pressure gradients across the aortic valve, stroke volume (continuity equation), and aortic valve area using standard techniques. Z_va was determined as (systolic arterial pressure+mean gradient)/stroke volume index. Energy loss index was calculated as (aortic area×aortic valve area)/([aortic area – aortic valve area]×body surface area). The stroke work loss was obtained as (mean gradient×100/[systolic arterial pressure+mean gradient]). The ratio of stroke volume index to pulse pressure was used to measure systemic arterial compliance. Z_va, energy loss index, stroke work loss, and systemic arterial compliance were assessed before and 15 minutes after cardiopulmonary bypass. Systemic and pulmonary hemodynamics (invasive catheters) were similar after versus before AVR. Aortic valve area increased significantly (p<0.05) with AVR (0.92±0.26 cm² to 1.94±0.35 cm²), concomitant with decreases in peak and mean gradients (60±17 mmHg to 15±8 mmHg and 38±11 mmHg to 8±5 mmHg, respectively) and peak blood flow velocity (3.9±0.5 m·s^-1 to 1.9±0.5 m·s^-1). AVR reduced Z_va (4.6±1.0 mmHg·mL^-1·m^-2 to 3.5±0.3 mmHg·mL^-1·m^-2) and improved energy loss index (0.55±0.16 cm²·m^-2 to 1.58±0.48 cm²·m^-2) concomitant with a decline in stroke work loss (25%±6% to 7%±4%), but systemic arterial compliance remained unchanged (0.63±0.13 compared with 0.70±0.12 mL·mmHg^-1·m^-2).
The current results showed that AVR acutely reduced Z_va, improved energy loss index, and decreased stroke work loss, but did not affect systemic arterial compliance in elderly men with degenerative calcific trileaflet AS.
A quinazoline-derivative compound with PARP inhibitory effect suppresses hypertension-induced vascular alterations in spontaneously hypertensive rats
2014, Biochimica et Biophysica Acta - Molecular Basis of Disease
Citation Excerpt :
Because of its high copy number, overactivation of the enzyme can induce NAD+ and thereby ATP depletion leading to necrotic cell death [18–20], or trigger apoptosis by promoting the release of mitochondrial pro-apoptotic proteins, such as AIF and endonuclease G [22,23]. In addition, PARP activation by promoting mitochondrial damage [21] can further induce ROS production, elevated intracellular Ca2 + and destabilize the mitochondrial membrane system leading to mitochondrial permeability transition and cell death [20,22,34]. Furthermore, PARP activation can activate NF-κB and AP-1 transcription factors [24–26], which can significantly contribute to cardiovascular remodeling [27,28].
Oxidative stress and neurohumoral factors play important role in the development of hypertension-induced vascular remodeling, likely by disregulating kinase cascades and transcription factors. Oxidative stress activates poly(ADP-ribose)-polymerase (PARP-1), which promotes inflammation and cell death. We assumed that inhibition of PARP-1 reduces the hypertension-induced adverse vascular changes. This hypothesis was tested in spontaneously hypertensive rats (SHR).
Ten-week-old male SHRs and wild-type rats received or not 5 mg/kg/day L-2286 (a water-soluble PARP-inhibitor) for 32 weeks, then morphological and functional parameters were determined in their aortas. L-2286 did not affect the blood pressure in any of the animal groups measured with tail-cuff method. Arterial stiffness index increased in untreated SHRs compared to untreated Wistar rats, which was attenuated by L-2286 treatment. Electron and light microscopy of aortas showed prominent collagen deposition, elevation of oxidative stress markers and increased PARP activity in SHR, which were attenuated by PARP-inhibition. L-2286 treatment decreased also the hypertension-activated mitochondrial cell death pathway, characterized by the nuclear translocation of AIF. Hypertension activated all three branches of MAP-kinases. L-2286 attenuated these changes by inducing the expression of MAPK phosphatase-1 and by activating the cytoprotective PI-3-kinase/Akt pathway. Hypertension activated nuclear factor-kappaB, which was prevented by PARP-inhibition via activating its nuclear export.
PARP-inhibition has significant vasoprotective effects against hypertension-induced vascular remodeling. Therefore, PARP-1 can be a novel therapeutic drug target for preventing hypertension-induced vascular remodeling in a group of patients, in whom lowering the blood pressure to optimal range is harmful or causes intolerable side effects.
Elastic properties of the descending aorta in patients with a bicuspid or tricuspid aortic valve and aortic valvular disease
2014, Journal of the American Society of Echocardiography
Citation Excerpt :
In addition, increased global aortic stiffness (pulse wave velocity) has been demonstrated by magnetic resonance imaging in patients with asymptomatic BAVs.12 Regional elastic properties of the ascending aorta in patients with BAVs were examined in a few studies,24,28 and very little is known about the regional elastic function of the descending aorta in patients with BAVs, especially those with severe AS or AR. In our study, patients with BAV with AR showed altered elastic properties, suggesting that aortopathy may extend to the descending aorta.
The aim of this study was to explore possible differences in aortic strain, distensibility, and stiffness in the descending thoracic aorta between patients with bicuspid aortic valves (BAVs) and those with tricuspid aortic valves (TAVs) in relation to type of aortic valve disease and known cardiovascular risk factors.
Transesophageal echocardiography was used to examine 288 patients (mean age, 64 ± 13 years) in the operating room before surgery. The transesophageal echocardiographic images were analyzed offline using Velocity Vector Imaging software. One hundred forty patients had isolated severe aortic stenosis (AS) (89 of those with BAVs, 51 of those with TAVs), and 52 patients had isolated severe aortic regurgitation (AR) (24 of those with BAVs, 28 of those with TAVs).
In patients with AS, stiffness in the descending aorta was 10 (range, 7.3–16) in those with BAVs and 13 (range, 11–18) in those with TAVs (P < .001). Distensibility was 19 kPa⁻¹ 10⁻³ (range, 13–27 kPa⁻¹ 10⁻³) in patients with BAVs and 15 kPa⁻¹ 10⁻³ (range, 11–19 kPa⁻¹ 10⁻³) in those with TAVs (P < .01). In patients with AR, stiffness was 6.9 (range, 5.5–7.8) in those with BAVs and 8.0 (range, 6.6–11) in those with TAVs (P < .05). After correction for age, dimension of the ascending aorta, cholesterol, and stroke volume in a multivariate regression model, BAV was associated with lower strain and distensibility of the descending aorta in the AR group and higher distensibility in the AS group, whereas stiffness was no longer related to aortic valve morphology in either of the two groups.
The presence of BAVs in patients with severe AR is associated with lower strain and distensibility, suggesting that impairment of the elastic aortic properties may extend to the descending aorta. In patients with AS, BAVs correlate weakly with higher distensibility.
Morphology of the bicuspid aortic valve and elasticity of the adjacent aorta in children
2012, American Journal of Cardiology
Citation Excerpt :
Concerning AV function, we found the elasticity indexes to be superior in patients with congenital aortic stenosis than in patients with congenital aortic regurgitation. These findings are not in line with the data from adult studies.3,4 A possible explanation could be again that profound differences exists between the congenital and acquired forms of aortic stenosis.
Bicuspid aortic valve (BAV) is a common congenital malformation with the known sequela of ascending aortic dilation. The morphology of the BAV and the elasticity of the adjacent ascending aorta appear to influence the outcome. We prospectively examined 48 pediatric patients with an isolated, native BAV for the morphology and size of the aortic valve, aortic root, sinotubular junction, and ascending aorta and their elasticity indexes. A cohort of 48 matching subjects with tricuspid aortic valves was investigated as controls. A comparison of the aortic valve subtypes showed normal-size aortic dimensions in the tricuspid aortic valves. In contrast, in the BAVs, the ascending aorta and aortic valve itself tended to dilate with age and aortic elasticity deteriorated. In the BAVs, the stiffness was significantly greater (4.43 ± 1.82 vs 3.43 ± 0.81 in the tricuspid aortic valves; p = 0.001). The distensibility indexes decreased inversely in the BAVs (6.57 ± 2.83 vs 7.84 ± 2.04 cm² × dynes⁻¹ × 10⁻⁶, p = 0.013; and 53.5 ± 26.0 versus 64.3 ± 17.9 kPa⁻¹ × 10⁻³, p = 0.020). The anteroposterior-oriented phenotype of BAVs showed significantly stiffer and less distensible elasticity even after correction for congenital valve dysfunction, which was more frequent in the left–right-oriented phenotype. In conclusion, the morphology of the BAV seems to play a major role in the outcome of BAV disease, although the left–right phenotype is more prone to congenital valve dysfunction, the anteroposterior phenotype showed worse elasticity quality.

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Abnormal aortic elastic properties in adults with congenital valvular aortic stenosis

Abstract

Background

Methods

Results

Conclusions

Introduction

Section snippets

Study population

Results

Discussion

Acknowledgements

J Am Coll Cardiol

Am J Cardiol

Am J Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

J Am Soc Echocardiogr

Am J Cardiol

J Am Coll Cardiol

Am J Cardiol

J Biomech

J Am Coll Cardiol

Am Heart J

Aortic root dilatation in young men with normally functioning bicuspid aortic valves

Heart