Abbreviations and Acronyms

AI

aortic insufficiency

AS

aortic stenosis

AVR

aortic valve replacement

BAV

bicuspid aortic valve

CPB

cardiopulmonary bypass

R/L

right-light

R/N

right-noncoronary

TAV

tricuspid aortic valve

Introduction

Bicuspid aortic valve (BAV) is a common congenital valvular malformation found in 1% to 2% of the general population, and it is responsible for a significant proportion of aortic valve replacement (AVR) in adults.^1,2 Patients with BAV are at increased risk for aortic stenosis (AS) and aortic insufficiency (AI), which may require catheter or surgical intervention, such that up to one-third of patients undergoing aortic valve surgery in the United States has BAV.³ Ascending aortopathy is a less-recognized association with BAV despite the fact that it can result in significant dilation of the ascending aorta at an earlier age than in patients with aortopathy from other etiologies.^4,5 Because aortic complications in patients with BAV are more frequent than in the general population (accounting for up to 15% of aortic dissections), identifying risk factors for aortic root dilation is an important endeavor.⁶

Currently, there is limited information regarding whether the type of leaflet morphology in BAV is associated with abnormalities of valve function and the aortic size in a young adult population.^5,7,8 The aim of this study was to analyze the impact of leaflet fusion pattern on aortopathy severity and the differences in aortic root diameter in patients undergoing AVR surgery for different morphologies of BAV vs tricuspid aortic valve (TAV) disease.

Patients and Methods

Results

There were 2 early deaths (2.2%) and 3 late deaths (3.3%) out of 90 patients. The early deaths occurred in TAV (n = 1) and BAV (n = 1) groups, and the late deaths occurred in BAV (n = 2) and TAV (n = 1) groups. The 5-year survival rate was 94.4%. Six patients required extracorporeal membrane oxygenation or intra-aortic balloon pumping for postoperative low cardiac output (TAV, n = 3 vs BAV, n = 3; P = .40), all of which were successfully weaned from extracorporeal membrane oxygenation. Additional morbidity included reexploration for bleeding in 5 patients (TAV, n = 2 and BAV, n = 3) and complete heart block that required permanent pacemaker insertion in 2 patients (both from the BAV group). Overall, freedom from postoperative morbidity at 7 years was 83% for the TAV group and 87% for the BAV group (P = .75).

The demographic and preoperative patient characteristics are displayed in Table I.¹³ There were no significant differences between the BAV and TAV groups with respect to age, weight, height, grade of AI, size of implanted prostheses, and presence of concomitant Bentall procedure. Longer CPB time (mean [SD]: TAV, 142 [84] min vs BAV, 107 [56] min; P = .04) and cross-clamp time (mean [SD]: TAV, 113 [61] min vs BAV, 81 [33] min; P = .01) as well as high percentages of any concomitant heart procedures except Bentall procedure (TAV, 47% vs BAV, 10%; P < .001), were significantly more common in the TAV group (Table I). Conversely, a higher peak preoperative gradient on the aortic valve was significantly associated with the BAV group (mean [SD]: BAV, 62 [38] mm Hg vs TAV, 41.5 [40.5] mm Hg; P = .03). Preoperative aortic measurements (diameter at 4 levels and Z value) of patients in BAV and TAV groups before AVR are shown in Table II.

TABLE I. Preoperative and Intraoperative Characteristics of Patients With Aortic Valve Replacement

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TABLE II. Preoperative Aortic Measurements in Patients With Aortic Valve Replacement

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In the subanalysis for all 3 groups, the preoperative peak gradient on aortic valves was significantly higher in patients in the R/L group than in the TAV group (mean [SD]: R/L, 63.5 [33.5] mm Hg vs TAV, 41.5 [40.5] mm Hg; P = .02) but was not significantly different than in the R/N group (R/N, mean [SD], 58.3 [50.6] mm Hg; P = .72). The CPB and cross-clamp times were significantly longer for patients in the TAV group than for those in the R/L group (P < .05 and P = .02, respectively). Conversely, the CPB time was not significantly different between patients in the TAV and R/N groups (R/N, mean [SD], 111 [45] min; P = .11). Finally, there was no significant difference in preoperative and intraoperative measurements between the R/L and R/N subgroups (Table I).

Patients with R/L fusion were more likely to have AS than were those in the TAV group (R/L, 51% vs TAV, 27%; P < .05), but the presence of AS was not significantly different between either R/L and R/N subgroups (R/N, 38%; P = .56) or between patients with R/N and TAV (P = .50). The size of the ascending aorta was significantly larger in patients with R/N fusion than in the TAV group (mean [SD]: R/N, 46.5 [7.6] mm vs TAV, 37.7 [10.1] mm; P = .002) and in the R/L subgroup (R/L, mean [SD], 38.5 [9.5] mm; P = .003). Nevertheless, there were no significant preoperative differences in the levels of aortic annulus, sinotubular junction, or sinus of Valsalva among all 3 groups (Fig. 1).

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The Z values of the ascending aorta and sinotubular junction diameters were significantly higher in patients with R/N fusion (mean [SD], 7.0 [1.6] and 3.4 [1.9], respectively) than in the R/L (mean [SD], 4.6 [2.5] and 2.2 [1.6]; P < .001 and P = .04, respectively) and TAV (mean [SD], 4.2 [2.7] and 2.1 [2.4]; P < .001 and P = .05, respectively) groups, whereas the Z values of sinus of Valsalva or aortic annulus junction diameters were similar among all groups (Fig. 2).¹³ In addition, there were no significant differences in Z values at all 4 levels between TAV and R/L fusion subgroups.

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In the subanalysis between patients with preoperative AS and AI, AI is associated with diffuse, significant enlargement at all 4 levels (both diameter and Z score; see Table III). Importantly, the Z score of the ascending aorta in patients with AS also is enlarged (AS subgroup, mean [SD], 3.8 [2.2]); however, it was significantly lower than Z score of ascending aorta with patients with AI (AI subgroup, mean [SD], 6.4 [2.7]; P < .001). In the subanalysis between patients with a Bentall procedure (n = 19) and those with a non-Bentall procedure (n = 71), the Bentall procedure was associated with diffuse, significant enlargement of the aorta (at all 4 levels, both diameter and Z score). Importantly, the size of the ascending aorta is significantly larger in patients with Bentall procedure (Bentall: mean [SD], 54.6 [5.0] mm; vs non-Bentall: mean [SD], 35.4 [16.1] mm; P < .001). Furthermore, the diameter of implanted prostheses is significantly larger in the Bentall subgroup of patients (Bentall: mean [SD], 25.2 [2.3] mm vs non-Bentall: mean [SD], 23.1 [2.3] mm; P = .002).

TABLE III. Preoperative Aortic Measurements in Patients With AS and AI

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Follow-up data were available for all patients. The mean (SD) follow-up was 2.7 (1.8) years (range, 2 months-7 years; total, 248 patient-years). During the follow-up period, 3 patients underwent a redo intervention (1 from each group) at a mean (SD) interval of 2.8 (1.9) years (median, 2 years; range, 1.5–5 years). Overall freedom from aortic valve redo procedure at 7 years was 97% and was not significantly different between the groups. At the last follow-up, according to echocardiograms, the sizes of ascending aorta were similar between all groups (mean [SD]: BAV, 30.5 [5.9] mm vs TAV, 31.8 [5.3] mm; P = .50) and among the 3 subgroups (mean [SD]: TAV vs R/L, 29.8 [6.1] mm vs R/N, 33.2 [4.3] mm; P = .59). Moreover, there were no significant differences in the levels of aortic annulus, sinotubular junction, or sinus of Valsalva among the 3 groups (the diameters and Z values) at last follow-up. Finally, there were no significant differences in the ascending aorta diameter and Z score between Bentall and non-Bentall patients at last follow-up (P = .64).

Discussion

Bicuspid aortic valve disease is a common congenital valve disorder that affects 1% to 2% of the population. The condition may be associated with significant valvular dysfunction and can lead to AS or AI at an early age. It also places patients at increased risk for infective endocarditis. In addition, BAV has been associated with aortic wall abnormalities, including coarctation of the aorta, supravalvular AS, and ascending aortic dilatation and aneurysm formation. All of these disorders can have serious clinical consequences, such as potential aortic dissection and rupture.

The contribution of BAV leaflet anatomy to the associated aortic wall dilatation has attracted considerable interest more recently, but the association remains unclear, and contradictory data exist. One such example is the speculation that certain BAV phenotypes are associated with a higher risk of dissection and thus predispose patients to aortic root dilatation and aortic regurgitation, but this remains to be shown.^14,15

The relative distribution of morphologically distinct cusp fusion patterns in BAV (ie, R/L and R/N) observed in this study is similar to those demonstrated in earlier reports.^8,16 Previous series have described that 70% to 75% of patients with BAV have fused R/L coronary cusps, whereas R/N cusp fusion is less prominent and found in only 20% of patients with BAV. The series in this study revealed the prevalence of R/L fusion to be very similar (R/L, 75% vs R/N, 25%). Regarding the geometry of the outflow tract, patients with BAV have consistently demonstrated larger annulus and left ventricular outflow tract dimensions than do patients with TAV, regardless of the presence of an aneurysm or ectasia.^14,15,17 The relationship between leaflet morphology and aortic features has not been so consistent. Jackson et al¹⁵ found no relationship between BAV leaflet morphology and the frequency of aneurysm or ectasia, which stands in contrast to earlier reports where BAV R/L or R/N configuration was reported to be more frequently associated with dilatation of the aorta.¹⁴

There are several theories of relationship between BAV and aortic root dilation.² In the authors' opinion, the hemodynamics theory deserves special attention. Recent studies using 4-dimensional flow magnetic resonance imaging have provided more insight into the different hemodynamic burden on the aortic wall caused by flow disturbances.^2,18,19 In TAV, the flow is directed along the curvature of the aorta. In BAV, the flow angle is disturbed, resulting in a different pattern of increased wall shear stress that is dependent on the orientation of the cusps. In BAV with fusion of the R/L cusps, the flow is directed anteriorly and toward the right, which increases the wall shear stress in this region and results in aortic root dilatation. In BAV with fusion of the R/N cusps, the flow is directed higher into the ascending aorta toward the posterior aortic wall, resulting in ascending aorta dilation.^2,18,19 In support of this theory, the current study found that the preoperative size of the ascending aorta (diameter) was significantly larger in patients with R/N fusion than in patients in the TAV group and those in the R/L subgroup.

Previous studies have demonstrated that aortic elastic properties change in patients with BAV.²⁰ This was further evaluated by Schaefer et al,¹⁴ who showed that the aortic root in an R/L fusion phenotype had a larger dimension and an increased wall stiffness than that with an R/N fusion phenotype. It was therefore speculated that differences in shear forces and pressure distribution within the aortic root had a direct effect on aortic root morphology. These findings support the idea of hemodynamics playing a major part in the pathogenesis of BAV-related aortic dilatation.^15,21 However, based on a similar classification and similar measurements, Jackson et al¹⁵ could not confirm these findings in their study, which is concordant with the findings of Cecconi et al.²² In contrast, the present study shows that although patients with R/N fusion had a significantly larger preoperative ascending aorta diameter, all other dimensions (sinus of Valsalva, sinotubular junction, and aortic annulus) were similar in the R/N and R/L fusion patient subgroups.

Before AVR, the preoperative ascending aortic dilatation rate in patients with BAV described in the present study was comparable to previously reported rates.^2,23,24 Detaint et al²³ showed a dilation rate of the sinus of Valsalva and ascending aorta of 0.21 mm/year and 0.42 mm/year, respectively. In the control group of patients with TAV, these dilation rates were significantly lower (0.09 mm/y and 0.20 mm/y, respectively).²³ In contrast, postoperative follow-up ascending aortic dilation rates were not significantly different between patients with BAV and TAV.²³ Abdulkareem et al²⁵ reported that all aortic root dimensions remained stable in patients with BAV and TAV after AVR. Moreover, Charitos et al²⁶ compared aortic dilation rates in patients with BAV and in patients with TAV and observed no significant difference directly postoperatively, although patients with BAV did have slightly larger ascending aortic dimensions than did those with TAV. No significant differences were found in this study between the 2 groups (and also among all 3 subgroups) in the dilation of the aortic root and ascending aorta at last follow-up. These findings would confirm the role of hemodynamics/flow direction theory in the dilation rate of the aortic root and ascending aorta when once the dysfunctional aortic valve has been replaced, the aortic dilation rate and risk of adverse aortic events at follow-up would be similar between BAV and TAV.^2,18

In the current study, it was determined that there was a comparably low risk of adverse aortic events 7 years after AVR in young adult patients with BAV vs TAV and concomitant mild to moderate dilation of the ascending aorta. There was no difference in the prevalences of proximal aortic surgery between the study groups with low hospital morbidity and mortality, low rate of redo procedure and aortic events, and survival at a mean (SD) follow-up period of 2.7 (1.8) years.

This study has several limitations. First, this study was a nonrandomized, observational, retrospective review. Second, only a relatively small cohort of patients was enrolled. To strengthen these findings, larger studies at this institution or a multi-institutional study will need to be performed in the future. The most important limitation to note is the time period during which this study took place. A longer follow-up time may be required to verify the outcomes of all 4 aortic measurements, and the findings presented herein may be different from those that result from a different time period of evaluation. More participants and a longer follow-up time may also help identify the risk factors of ascending aorta dilation. Finally, the number of patients in the TAV group was markedly lower than the number in the BAV group, as one would expect in this population. Increasing the number of patients in the TAV group might change the findings from this study.

In conclusion, the authors suggest from this study that aortic valve morphology may be a determinant of aortic dilation in patients with BAV. It was found that pre-operative dilation of the ascending aorta is more common in patients with R/N fusion, whereas there was no significant difference in R/L fusion between patients with BAVs and TAVs with respect to aortic dilation. Fusion of the R/L leaflets was associated with an increased likelihood of the presence of AS compared with R/N fusion and TAV. Finally, the presence of AI is similar in patients with R/N and TAV morphologies, and the degree of ascending aorta dilation at early follow-up is not significantly different between the groups.