Background
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.
Methods
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).
Results
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.
Conclusions
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.
A bicuspid aortic valve (BAV) is the most common congenital cardiac malformation, occurring in 1% to 2% of the general population, and is associated with accelerated development of (AS) and/or aortic regurgitation (AR). Among patients aged >50 years requiring aortic valve replacement, 50% have BAVs. BAV is also associated with dilation, aneurysm, and dissection of the ascending aorta. A number of studies have demonstrated abnormalities in the aortic wall in patients with BAVs, including histopathologic changes and alterations in the metabolism, biology, and gene expression in smooth muscle cells. Our group recently reported on changes in the structure of the extracellular matrix and differences in gene expression in the wall of the ascending aorta between patients with BAVs and those with tricuspid aortic valves (TAVs).
Impaired elastic properties of the aorta in patients with BAVs include abnormalities in aortic dimensions, stiffness, distensibility, aortic strain, and systolic distension rates. A dilated and functionally abnormal aortic root has been shown in first-degree relatives of people with BAVs. Reports in the literature on the elastic properties of the aorta refer almost exclusively to the aortic root and/or the ascending aorta, whereas less is known about the dimensions and regional elastic properties of the descending aorta in patients with BAVs. However because coarctation of the aorta and patent ductus arteriosus are associated with BAV, the involvement of the descending aorta in BAV aortopathy seems conceivable. Furthermore, reported increased frequency of intracranial aneurysms and increased global aortic stiffness in patients with asymptomatic BAVs suggest a generalized connective tissue disorder with a more diffuse arteriopathy involving descending aorta and other vascular territories in the BAV population.
The use of magnetic resonance imaging and different ultrasound-based methods in the regional assessment of elasticity in the descending aorta has been described recently; these methods include M-mode echocardiography, Doppler tissue imaging, and Velocity Vector Imaging (VVI; Siemens Healthcare, Erlangen, Germany). VVI is a semiautomatic speckle-tracking-based method that permits automatic registration of the area change, frame by frame, along the entire circumference of the descending aorta. This method has been shown to be feasible for evaluating the functional characteristics of the aorta.
The aim of the present study was to explore the differences in the elastic properties of the descending aorta between patients with BAVs and those with TAVs undergoing valvular surgery for isolated severe AS or AR. We aimed to analyze the influence of different cardiovascular risk factors on the aortic properties.
Methods
Study Population
The initial population comprised 312 patients included in the Advanced Study of Aortic Pathology, a prospective single-center study performed at the Karolinska University Hospital (Stockholm, Sweden) from 2007 to 2010. Consecutive patients with aortic valve disease and/or aneurysms of the ascending aorta who required surgery were recruited if they did not have any significant coronary artery disease according to coronary angiography. None of the patients had aortic coarctation. Twelve patients were excluded before surgery. Transesophageal echocardiography (TEE) was performed in 288 patients in the operating room according to the study design. The aortic root morphology of all patients has been described in a previous report, and some of the patients have also been described in a VVI feasibility study. VVI could be analyzed in 259 patients, constituting 90% of the TEE sample ( n = 288). On inclusion, all patients underwent evaluation of cardiovascular risk, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured, and blood samples were drawn for blood analyses. Classification of the valve morphology as tricuspid or bicuspid was made intraoperatively by the surgeon. Three cusps and three commissures denoted a tricuspid valve, while two cusps and two commissures denoted a bicuspid valve; a single cusp and a single commissure denoted a unicuspid aortic valve (UAV).
According to our aims, we included only patients with severe isolated AS and isolated AR, yielding 192 patients as the final population of this study; 140 patients had isolated AS, and 52 had isolated AR. The classification criteria are described below.
Each subject gave written consent for participation in the study, which was approved by the Regional Ethical Review Board, Stockholm, Sweden.
Transthoracic Echocardiography
All patients were examined using transthoracic echocardiography before surgery, using an iE33 ultrasound scanner (Philips Medical Systems, Bothell, WA). Two-dimensional echocardiography and Doppler measurements were performed according to the standards of the American Society of Echocardiography. In patients with AS, transvalvular velocity was measured using continuous-wave Doppler. The peak transvalvular pressure gradient was calculated by applying the Bernoulli equation, whereas the mean transvalvular pressure gradient (P mean ) was calculated by averaging the instantaneous gradients over the ejection period. Stroke volume and aortic valve area were calculated according to the continuity equation. AR was evaluated using the pressure half-time, jet density, diastolic flow reversal in the descending aorta, AR color flow jet area, and vena contracta. AR was classified into grades 0 to 3 (0 = none, 1 = mild, 2 = moderate, and 3 = severe) according to American Society of Echocardiography guidelines ; the proximal isovelocity surface area method was not used. Isolated AS was defined as P mean > 40 mm Hg and/or aortic valve area < 1 cm 2 and AR grade ≤ 1; isolated AR was defined as AR grade 3 and P mean < 20 mm Hg. Total systemic arterial compliance (SAC) was calculated as stroke volume index on echocardiography divided by pulse pressure and valvuloarterial impedance (Z va ) as (P mean + SBP)/stroke volume index.
TEE
TEE was performed in the operating room under general anesthesia before surgery using a Sequoia c512 ultrasound scanner (Siemens Medical Solutions USA, Inc, Mountain View, CA) with a transducer frequency of 6 or 7 MHz. The electrocardiogram was recorded and displayed on the ultrasound images.
The descending aorta was scanned in the short-axis view at three predefined distances from the teeth (30, 35, and 40 cm), the 35-cm level representing approximately at the level of the left atrium in the majority of patients. Segments with aortic plaque were excluded from the analysis. The descending aortic diameter was measured from leading edge to leading edge on short-axis M-mode recordings in diastole. The maximum diameter of the ascending aorta was measured according to the standards of the American Society of Echocardiography. The diameters of the ascending and descending aorta are reported in absolute dimensions and relative to body surface area. Blood pressure was measured invasively in the radial artery simultaneously with the acquisition of the transesophageal echocardiographic images.
The morphologic phenotype of the BAV was also classified using TEE according to the cusps fused: fusion of the right and left coronary cusps (RL), fusion of the right and noncoronary cusps (RN), fusion of the left and noncoronary cusps, or “true bicuspid” valve if two cusps but no raphe were present. A small number of patients ( n = 5) were classified by the surgeon as having UAVs. Distinguishing between a BAV and a UAV can be difficult, especially for calcified valves. All of the valves classified as unicuspid by the surgeon were categorized as BAVs on TEE. On a close transesophageal echocardiographic image, these valves all were type 2 BAVs according to the classification of Sievers and Schmidtke (e.g., two raphes extending toward the aortic wall were seen). There were no UAVs with one commissure and no raphe on TEE. Therefore, we included these patients in the BAV group.
VVI Analyses
All analyses were performed offline using a syngo US WP 30 VVI system (Siemens Medical Solutions USA, Inc), as described previously. In brief, the best loops were chosen, and the blood-intima border was traced manually. If the subsequent tracking was unsatisfactory, a new tracing was performed or another loop (at the same level) was chosen. Maximal systolic circumferential strain (VVI strain), maximal systolic area (DesSA), and minimum diastolic area (DesDA) of the descending aorta were calculated automatically, and the relevant values of each variable were recorded from the respective curves ( Figure 1 ). The results shown are the means of two to four cardiac cycles from the two levels with the best image quality (except in 35 patients in whom only one level had adequate image quality). Variables of aortic elasticity were calculated as described by Schaefer et al . as follows:
VVI stiffness = ln ( SBP VVI / DBP VVI ) / { [ ( 4 DesSA / π ) − ( 4 DesDA / π ) ] / ( 4 DesDA / π ) }
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