ORIGINAL ARTICLE

Subtypes of bicuspid aortic valves in coarctation of the aorta

Daniel Rinnstrom • Karl Gunnar Engstrom •

Bengt Johansson

Received: 30 October 2012 / Accepted: 17 May 2013

� Springer Japan 2013

Abstract Bicuspid aortic valves (BAVs) represent a wide

morphologic and functional spectrum. In coarctation of the

aorta, BAVs are common, but the proportion of BAV

subtypes and their relation to aortic dimensions and

development of late valve dysfunction are unknown. Sixty-

two cardiovascular magnetic resonance investigations of

patients with coarctation of the aorta were reviewed with

respect to aortic valve morphology, aortic valve function,

and aortic dimensions. BAVs were identified in 45 patients

(72.6 %), of which 13 (20.9 %) were type-0 (two com-

missures), 28 (45.1 %) type-1 (three commissures but

fusion of one commissure with a raphe) and 4 (6.5 %)

valves were bicuspid but not possible to classify further.

Patients with BAVs type-0 had larger dimensions in their

sinus of Valsalva (35.5 ± 6.8 vs. 29.7 ± 2.7 mm, p =

0.002), ascending aorta (33.1 ± 6.2 vs. 26.0 ± 4.3 mm,

p = 0.005) and sino-tubular junction (29.3 ± 7.4 vs.

24.2 ± 3.5 mm, p = 0.040) compared with tricuspid aortic

valves (TAVs). Moderate and severe aortic valve disease

was more common in BAV type-0 compared with BAV

type-1 (p = 0.030) and TAV (p = 0.016). In a multivariate

linear regression model BAV type-0 (p = 0.005), BAV

type-1 (p = 0.011), age (p \ 0.001), patient height

(p = 0.009), and aortic valve disease (p = 0.035) were

independently associated with increased diameter of the

ascending aorta (R2 of the model 0.54, p \ 0.001). BAV

type-0 is relatively common in coarctation of the aorta.

Both BAV type-0 and type-1 are associated with increased

diameter of the ascending aorta but this association is

stronger for BAV type-0. Development of aortic valve

disease is more common in BAV type-0 than in BAV type-

1. Discrimination between BAV subtypes may potentially

provide clinical and prognostic information in patients with

coarctation of the aorta.

Keywords Coarctation of the aorta � Bicuspid aortic

valves � Congenital heart disease � Cardiovascular magnetic

resonance � Cardiovascular imaging

Introduction

Bicuspid aortic valve (BAV) is the most common congenital

heart lesion occurring in 1–2 % of the general population [1]

and is associated with increased risk of later development of

aortic valve complications [2]. In recent years, more atten-

tion has been drawn to BAVs and associated complications

[3]. Subtypes of BAVs have been described [4–7], and while

several classification systems have been proposed [8, 9], we

have chosen to apply the system suggested by Sievers and

Schmidtke [9], which classifies valves primarily by the

number of leaflets and location of raphes expressed, rather

than the angle of the commissural line.

Approximately 60–85 % of the patients with coarctation

of the aorta also have BAVs [10, 11]. These patients are at

risk for different long-term complications including aortic

valve disease and dilatation of the ascending aorta [12, 13].

The distribution of BAV subtypes in conjunction with

aortic coarctation has not been described. Moreover, it

remains unknown if these conditions are related to late

morbidity, such as dilatation of the ascending aorta and

aortic valve disease, though genetic risk profile and

D. Rinnstrom � B. Johansson (&)

Cardiology, Heart Centre and Department of Public Health and

Clinical Medicine, Umea University, 90187 Umea, Sweden

e-mail: bengt.johansson@medicin.umu.se

K. G. Engstrom

Cardiothoracic Surgery, Heart Centre and Department of

Perioperative Sciences, Umea University, 90187 Umea, Sweden

123

Heart Vessels

DOI 10.1007/s00380-013-0370-x

histological features of the ascending aorta seem to affect

the development of aortic aneurysms [14].

In the present study we have reviewed cardiovascular

magnetic resonance (CMR) investigations in patients with

coarctation of the aorta in order to classify the different

BAVs and relate them to aortic dimensions and aortic valve

disease.

Materials and methods

Patients

In this retrospective, cross-sectional study, all adult patients

with coarctation of the aorta that had been evaluated by a

previous CMR at our institution, between January of 2006

and September of 2011, were identified. In general, adult

patients followed at our institution have undergone at least

one MRI-examination. The indication for CMR is wide and

aims to elucidate the result of the previous intervention, and

exclude complications such as postoperative aneurysms. The

routine protocol for coarctation involved imaging of the

aortic valve. All included patients were above 15 years of

age. Investigations without sufficient CMR image data and

patients who had received any kind of prosthetic aortic valve

implant were excluded, to allow 62 patients remaining for

analysis. Clinical data and echocardiography reports were

reviewed. The study complies with the Declaration of Hel-

sinki, and was approved by the Regional Ethical Review

Board in Umea (Dnr 09-194 M).

Cardiovascular magnetic resonance

The investigations were performed on a Philips 1.5-T In-

tera or Achieva scanner (Philips, Best, The Netherlands).

All patients had a transaxial stack of T2-weighted ‘‘black-

blood’’ images covering the heart and the great vessels.

The cine (steady-state free-precession—SSFP) images

included two-chamber, three-chamber and a plane per-

pendicular to this through the left ventricular outflow tract

and the aorta, four-chamber, oblique-coronal, and a stack

of three image planes perpendicular to the aortic root

covering the aortic valve and sinus of Valsalva.

Measurements of aortic dimensions

The diameter of the ascending and descending aorta was

measured in a transaxial plane at the level of the pulmonary

artery bifurcation on T2-weighed black-blood images. The

sinus of Valsalva was measured in two positions. (I): In

SSFP cross sections of the sinus of Valsalva in diastole.

The image with the largest dimensions was selected, out of

three possible levels. In type-1 BAVs and in tricuspid

aortic valves (TAVs), three measurements were obtained,

each perpendicular to the respective sinus and across to the

opposite side, i.e., from the left (coronary) sinus, right

coronary sinus, and the right non-coronary sinus. In type-0

valves, only the dimension across the commissural line was

measured. (II): In a plane through the LVOT perpendicular

to the SSFP 3-chamber view.

The subvalvular LVOT diameter was measured in the

three-chamber view and in a plane through the LVOT but

perpendicular to the SSFP three-chamber view. The sino-

tubular junction was measured in diastole, in a plane

through the LVOT but perpendicular to the SSFP three-

chamber view.

Classification of BAVs

There is no generally accepted classification of bicuspid

valves. We have chosen to apply the strict logic approach

suggested by Sievers and Schmidtke [9]. The classification

considered [1]; the number of raphes and commissures [2],

the spatial position of cusps or raphes, and if applicable [3],

the functional status, i.e., presence of stenosis or regurgi-

tation. Accordingly, we applied the following terminology;

type-0 (no raphe, two commissures), type-1 (one raphe,

three commissures), and type 2 (two raphes, three com-

missures). Information on spatial position between left (L),

right coronary (R) or the non-coronary (N) cusps or, in

type-0, the orientation of the sinuses were also considered.

The functional status of the valve was here disregarded in

terms of classification in the descriptive part, as this study

focuses primarily on valve morphology. For illustration of

the classification system, see Fig. 1.

The classification was performed simultaneously by two

of the investigators (DR and BJ) and based on consensus.

For a valve to be classified as bicuspid, it needed to exhibit

an opening pattern consistent with bicuspid anatomy (i.e.,

‘‘fish-mouth’’ opening in contrast to ‘‘triangular’’ opening

typical for tricuspid valves). To be classified as type-0

(‘‘anatomically bicuspid’’), it also needed to exhibit two

clearly defined sinuses of Valsalva rather than three, and no

visible raphe in either leaflet. If the images suggested the

presence of a raphe, the valve was instead classified as

type-1 (‘‘functionally’’ bicuspid). Valves with bicuspid

opening pattern but with too poor image detail to evaluate

them further, were classified as bicuspid, but without dis-

cernible subtype (n = 4).

Aortic valve function

Information concerning aortic valve function (degree of

stenosis or regurgitation) was obtained from CMR (aortic

regurgitation) or echocardiography (aortic stenosis). In

CMR, phase velocity sequences were applied and placed

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perpendicular to the ascending aorta approximately 2–3 cm

above the aortic valve. The regurgitant fraction was cal-

culated using the software ViewForum (Philips, Best, The

Netherlands). The valve function was determined using the

definitions and graded as listed in Table 1. In the statistical

analysis, moderate and severe lesions were classed as one

group and mild lesions together with normal valve function

as one group.

Statistics

All calculations were performed using SPSS 19 (IBM,

Armonk, NY, USA). Differences in means and ratios were

tested by one-way ANOVA or multifrequency cross tables,

respectively. In post hoc mode, Student’s t test, Chi-square,

or Fisher’s exact test were used as appropriate. For multi-

ple-group comparisons, the Bonferroni correction was

applied. Variables were tested by univariate linear regres-

sion versus the diameter of the ascending aorta. Outliers

and co-linear dependencies between variables were

reviewed. For the three-level variable describing valvular

subtype (i.e., BAV type-0, BAV type-1, and TAV), TAV

served as a reference. The effect of variables was tested by

multivariable linear regression, run in a manual backward

mode. The distribution of residuals was continuously

reviewed, and correlations and multi-colinearity were

evaluated and considered during the analysis. The null-

hypothesis was rejected for p values \0.05.

Results

Patients

The demographics are shown in Table 2 with subdivision

according to the three major aortic valve morphologies.

Patients with BAV more frequently had previous surgery

for coarctation than those in the TAV group. Except for

this finding, there were no differences between the

groups.

Types of aortic valves

Images of the three major types of aortic valve morphology

are shown in Fig. 2. The distribution of theses morpholo-

gies is shown in Fig. 3. Among the 45 patients with BAV,

13 were of type-0 (two commissures) and 28 were of type-

1 (three commissures but fusion of one commissure with a

raphe). In four of these patients, the morphology was not

possible to classify into these subtypes.

Most patients with BAV type-0 had an anteroposterior

orientation of the commissural line, whereas only two had

Fig. 1 Schematic presentation

of the classification system of

bicuspid aortic valves, adapted

from the system suggested by

Sievers and Schmidtke [9].

Other configurations are

possible, but those have been

omitted since no such valves

were found in this particular

study

Table 1 Grading of aortic stenosis and aortic regurgitation, defined

by peak systolic velocity across the aortic valve and regurgitant

fraction, respectively

Degree of stenosis Peak systolic velocity

across the aortic valve (m/s)

0 (none) \2

1 (mild) 2–3

2 (moderate) 3–4

3 (severe) [4

Degree of regurgitation Regurgitant fraction (%)

0 (none) \5

1 (mild) \20

2 (moderate) 20–40

3 (severe) [40

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lateral orientation. In type-1, the raphe was most com-

monly located between the two coronary cusps. In two

patients, the raphe was located between the right coronary

and the non-coronary cusps (Fig. 1), thus qualifying their

aortic valves as BAV type-1 R-N.

Dimensions of the aorta

The dimensions of the ascending aorta are shown in

Table 3. At the level of the pulmonary artery bifurcation,

the ascending aorta was wider in patients with all types

of BAV versus those with TAV (p = 0.009). Patients

classified as BAV type-0 had a larger diameter of their

ascending aorta compared with TAV (p = 0.005,

Table 3; Fig. 4).

The sinus of Valsalva (cross-sectional SSFP) was wider

in type-0 BAV compared with type-1 BAV (p = 0.010)

and compared with TAV (p = 0.002, Table 3; Fig. 4).

Similarly, the sino-tubular junction (measured in a plane

through the LVOT perpendicular to the SSFP 3-chamber

view resembling the ‘‘LAO’’ projection) was wider in

patients with BAV compared with TAV (p = 0.033).

There were no differences in the diameter of the

descending aorta between different types of aortic valves.

The diameter of the ascending aorta increased signifi-

cantly with age, diameter of coarctation, moderate or

severe aortic valve disease, and presence of BAV type-0

(Table 4). BAV type-1 was found borderline significant

with p = 0.065. Both bicuspid valve subtypes used only

TAV as reference in these analyses, as this valve anatomy

may reasonably be considered the normal state.

Based on the findings in the univariate analyses, a

multivariate linear regression model was generated

including the above-mentioned factors but with both

bicuspid valve subtypes using TAV and the other main

bicuspid subtype together as a reference group. Height was

also included as this factor has previously been shown to be

associated with ascending aortic diameter [15]. The gen-

erated model was associated with an adjusted R2 value of

0.488 and a significance of \0.001 (Table 5).

We also generated a multivariate linear regression model

that included hypertension. This factor was found to be

significant, however; the relationship between hypertension

and aortic diameter was not as intuitively expected, showing

a negative coefficient to suggest an inverse relationship

against the aortic diameter. It was found that hypertension

was confounded by age, with an inverse interaction in the

model to explain an increased aortic diameter.

Table 2 Overview of the demographic data for patients with different types of aortic valves

Demographic

variables

All patients

(n = 62)

BAV type-0

(n = 13)

BAV type-1

(n = 28)

All BAVs

(including those

without

discernable

subtype)

(n = 45)

TAV (n = 17) Comparison

between

BAV type-0,

BAV type-1,

and TAV

(ANOVA)

Comparison

between all

BAVs and

TAV (t test

or Chi-

square)

n Mean ± SD n Mean ± SD n Mean ± SD n Mean ± SD n Mean ± SD p value p value

Age (years) 62 33.2 ± 15.5 13 37.3 ± 17.0 28 31.9 ± 14.8 45 33.0 ± 15.4 17 33.6 ± 16.4 0.61 0.90

Length (cm) 60 174 ± 9.5 13 173 ± 11.9 27 173 ± 8.1 43 174 ± 9.3 17 174 ± 10.2 0.98 0.99

Weight (kg) 60 73.8 ± 1.4 13 76.1 ± 13.2 27 70.0 ± 13.4 43 72.5 ± 13.7 17 76.9 ± 14.6 0.20 0.27

n # Positive n # Positive n # Positive n # Positive n # Positive p value p value

Cardiac medication 56 30 (54 %) 11 7 (64 %) 26 14 (54 %) 41 22 (54 %) 15 8 (53 %) 0.84 0.61

Females 62 25 (40 %) 13 7 (54 %) 28 10 (36 %) 45 18 (40 %) 17 7 (41 %) 0.55 0.58

Hypertension 58 24 (41 %) 12 7 (58 %) 27 11 (41 %) 43 18 (42 %) 15 6 (40 %) 0.55 0.57

Smoking 27 – 4 – 14 – 20 – 7 – 0.65 0.44

Never – 20 (74 %) – 3 (75 %) – 11 (79 %) – 16 (80 %) – 4 (57 %) – –

Previously – 4 (15 %) – 1 (25 %) – 1 (7 %) – 2 (10 %) – 2 (29 %) – –

Currently – 3 (11 %) – 0 (0 %) – 2 (14 %) – 2 (10 %) – 1 (14 %) – –

Surgical intervention 62 47 (76 %) 13 10 (77 %) 28 24 (86 %) 45 38 (84 %) 17 9 (53 %) 0.05 0.014*

Surgical reintervention 58 6 (10 %) 12 2 (17 %) 28 3 (11 %) 44 5 (11 %) 14 1 (7 %) 0.74 0.55

Possible differences between the different types of valves were tested with ANOVA and if significant, multiple comparisons between groups

were performed with t tests or Chi-square tests, as appropriate, and with post hoc Bonferroni correction of p values

BAV bicuspid aortic valve, TAV tricuspid aortic valve

* p \ 0.05

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Aortic valve function in relation to type and subtype

of aortic valve

Evaluating all bicuspid aortic valves, regardless of subtype,

there was no significant difference in functional status

between this group and the group with tricuspid valves in

terms of aortic valve dysfunction. However, when the

bicuspid valves were sorted according to subtype, a sig-

nificant increase in aortic valve dysfunction was observed

in patients with BAV type-0 in comparison to both those

with BAV type-1 (p = 0.036), and those with TAV

(p = 0.027) (Table 6). As isolated regurgitation was very

rare in this material (0 cases in BAV type-0, and 1 case in

TAV), this suggests that the difference is generated by

differences in moderate to severe aortic stenosis, a condi-

tion more common in BAV type-0 than in TAV (no dif-

ference in functional status was found when comparing

patients with BAV type-1 to those with TAV; p [ 0.999

after Bonferroni correction).

Discussion

Our results suggest that BAV type-0, as defined by Sievers

and Schmidtke [9], represents the more severe spectrum of

BAV disease with high prevalence in coarctation of the

aorta, and that this type of valve is associated with both

increased diameter of the ascending aorta, and with

increased risk of moderate to severe aortic stenosis—the

latter connection was not found for BAV type-1. Further-

more, the association with increased diameter of the

ascending aorta was independent of presence of aortic

valve disease. It might therefore be prudent to make a clear

distinction between the BAV subtypes and treat these as

two separate conditions rather than just different expres-

sions of the same basic pathology, at least for patients with

coarctation of the aorta.

Bicuspid aortic valve is a spectrum of morphologies

with subdivision into different subtypes as yet not applied

in clinical practice. There are several reasons for this, but

Fig. 2 Steady-state free precession images of the aortic valve in

diastole (a–c) and systole (d–f). a, d Bicuspid aortic valve type-0. b,

e Bicuspid valve type-1. c, f Tricuspid valve. Note the raphe between

left (L) and right (R) coronary cusp in b and e (arrow), perpendicular

to the non-coronary cusp (N)

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the limited ability of non-invasive imaging modalities to

differentiate between different valves is perhaps the most

important. Here we apply CMR and use the classification

system suggested by Sievers and Schmidke, originally used

in cardiac surgery where the valves were inspected and

classified during intervention. In this study, we found that

type-0 aortic valves accounted for 28.9 % of BAVs in our

patient group with coarctation of the aorta, in contrast to

6.9 % in an unselected population with BAVs [9]. Fur-

thermore, we found that type-0 ap made up 84.6 % of the

total number of type-0 valves, in contrast to 25.0 % in the

same unselected population [9]. These numbers are derived

from different investigations but still our data indicate that

a relatively high proportion of type-0 BAVs may be a

feature of coarctation of the aorta.

The location of the raphe in type-1 BAVs is not random

and was in our material most prevalent between the right and

left coronary cusps. This is in line with previously reported

data [9]. In bicommissural valves, the commissural line is

most often located in the anteroposterior position. Thus, the

subdivision in different types of BAVs clearly do not follow

a random pattern and the spectrum of different BAVs seems

to differ between BAV in coarctation of the aorta and in

unselected populations of BAVs [9]. The factors regulating

these processes are unknown. In is known that BAVs are

inherited in some families [16] and associated mutations

have been reported [17–19] but at present there is no estab-

lished genetic association with BAV subtype.

Besides surgical and autopsy studies, most previous

investigations on BAVs have been performed with

echocardiography which, at least in older studies, may have

been less sensitive than CMR in identifying BAV subtypes.

Most patients included in this study had relatively unaf-

fected valves, but reliable morphologic evaluation may be

difficult in severely affected valves, as is often the case

when surgery is indicated. It is therefore difficult to com-

pare these surgical and non-invasive imaging methods.

There is no golden standard for evaluating aortic valve

morphology using non-invasive imaging techniques. As far

as we know, there is no study comparing echocardiography

and CMR. CMR is not dependent on good imaging win-

dows, and provides detailed images of the moving aortic

valve. In contrast to echocardiography, the imaging planes

can always be planned perpendicular to the aortic root. We

therefore consider CMR a useful tool in assessing BAV,

both in the clinical setting and in research.

We confirm the magnitude of the previously reported

prevalence of BAV in coarctation of the aorta. Inter-study

differences may be related to different classification crite-

ria, patient selection, and investigation methods. Never-

theless, the prevalence appears to be in the range of

60–85 % [10, 11] with our data in the middle of this span.

The prevalence of BAV in coarctation of the aorta is thus

30- to 50-fold higher than in the general population.

The mean aortic diameter was larger in patients with

BAV type-0, compared with patients with tricuspid valves.

The aortic diameter in patients with BAV type-1 did not

differ from the other two groups, which may be related to

low statistical power, but may also reflect a true interme-

diate position with mean ascending aortic diameters

Fig. 3 Distribution of aortic

valve types in the 62 patients,

sorted by main category and

primary subcategory, as defined

by Sievers and Schmidtke

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between type-0 BAVs and TAVs. The diameter in the

descending aorta did not differ across groups, in line with

the concept of BAV as a disease of the proximal aorta.

Also in coarctation of the aorta, the dimensions of the

ascending aorta increase with age, a feature that is well

known in the normal ascending aorta [15]. This is potentially

important information in the assessment of patients with

coarctation of the aorta and increased diameter in the

ascending aorta. In this cross-sectional study, it was not possible

to measure the rate of progression over time, which is consid-

ered a crucial variable in clinical decision-making [20].

It might seem counterintuitive that our analyses did not

show a correlation between blood pressure and ascending

aortic diameter. One might speculate that hypertension, in

coarctation of the aorta, may be more dependent on the

aorta’s mechanical properties than on metabolic factors,

and if that is the case, it does not necessarily follow that

higher blood pressure would correlate with an increased

aortic diameter. Worth noting is that we attempted to

include blood pressure in the multivariate analysis, but

discarded this variable due to strong interaction between

blood pressure and age—an interaction likely to have be

Table 3 Dimensions of the aorta and comparison between BAV type-0, type-1, and TAVs and comparison between all BAVs and TAVs

Dimensions All patients

(n = 62)

BAV type-0

(n = 13)

BAV type-1

(n = 28)

All BAVs

(including those

without

discernable

subtype)

TAV (n = 17) Comparison

between BAV

type-0, BAV

type-1, and

TAV

(ANOVA)

Comparison

between all

BAVs and

TAV (t test)

n Mean ± SD n Mean ± SD n Mean ± SD n Mean ± SD n Mean ± SD p value p value

Ascending

aorta

(mm)

57 29.2 ± 6.2 13 33.1 ± 6.2 26 29.4 ± 6.4 40 30.6 ± 6.4 17 26.0 ± 4.3 0.007**,a 0.009**

Descending

aorta

(mm)

56 21.2 ± 5.4 13 21.6 ± 4.9 25 20.7 ± 5.9 39 21.0 ± 5.5 17 21.7 ± 5.4 0.81 0.65

Sinus

Valsalva

dia 1

(mm)

58 31.7 ± 4.7 13 35.5 ± 6.8 27 31.1 ± 3.4 42 32.4 ± 5.0 16 29.7 ± 2.7 0.002**,b 0.043**

Sinus

Valsalva

dia 2

(mm)

43 29.7 ± 4.4 0 – 27 30.7 ± 4.9 27 30.7 ± 4.9 16 28.1 ± 2.9 – 0 064

Sinus

Valsalva

dia 3

(mm)

43 32.0 ± 4.2 0 – 27 33.2 ± 4.5 27 33.2 ± 4.5 16 30.0 ± 2.7 – 0.015*

Sinus

Valsalva

‘‘LAO’’

(mm)

61 32.6 ± 5.2 13 34.0 ± 7.2 27 33.0 ± 4.5 44 33.6 ± 5.4 17 29.9 ± 3.6 0.061 0.012*

ST-junction

‘‘LAO’’

(mm)

61 27.1 ± 5.6 13 29.3 ± 7.4 27 27.7 ± 5.3 44 28.2 ± 5.9 17 24.2 ± 3.5 0.033*,c 0.012*

LVOT 3-ch 62 23.3 ± 3.3 13 24.3 ± 4.3 28 23.3 ± 3.2 45 23.7 ± 3.5 17 22.4 ± 2.6 0.30 0.18

LVOT

‘‘LAO’’

(mm)

61 25.5 ± 3.4 13 25.4 ± 3.2 27 25.5 ± 3.4 44 25.8 ± 3.6 17 24.9 ± 2.8 0.82 0.37

Dia 1-3 denotes measurements in SSFP cross sections of the sinus of Valsalva in diastole perpendicular to: 1, the left sinus; 2, the right coronary

sinus; 3, the right non-coronary sinus. ‘‘LAO’’ denotes a plane resembling the left anterior oblique projection as described in ‘‘Materials and

methods’’. 3-ch denotes a three-chamber projection, BAV bicuspid aortic valve, TAV tricuspid aortic valve

* p \ 0.05, ** p \ 0.01, *** p \ 0.001a Difference in diameter of the ascending aorta between BAV type-0 and TAV: p = 0.005b Difference in diameter of sinus Valsalva dia 1 between BAV type-0 and BAV type-1: p = 0.01. Difference in diameter of sinus of Valsalva dia

1 between BAV type-0 and TAV: p = 0.002c Difference in diameter of ST-junction ‘‘LAO’’ between BAV type-0 and TAV: p = 0.040

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found, even had we not limited our study to individuals

with coarctation of the aorta.

It is known that BAV is associated with late develop-

ment of aortic stenosis [1]. Here we show that BAV type-0

appears to be more prone to develop aortic stenosis than

BAV type-1—a hitherto unknown connection. It is still

being debated whether aortopathies, such as aortic stenosis

and dilatation of the ascending aorta in BAV disease, are

best explained in terms of hemodynamic or genetic factors

[21], and as our data suggest that BAV is an independent

predictor of diameter of the ascending aorta, identifica-

tion of correct BAV morphology may have prognostic

implications.

In contrast to the classification system used here by us,

the alternative clinical classification system for BAV is

mainly based on the spatial orientation of the leaflets

irrespective of the presence and number of raphes. In this

system, bicuspid valves are classified as either R/L (cor-

responding to type-0 ap, and type-1 R-L) or R/N (corre-

sponding to type-0 lat, and type-1 R-N). In the present

study, we have not been able to use this classification

system, as the reclassified R/N-group would consist of only

four patients, and therefore be unfit for statistical analysis.

Instead, we have chosen to use the first subtype of BAV

classified by Sievers and Schmidtke [9] in the statistical

analyses, thus classifying the valves by the presence or

absence of raphe, regardless of the spatial orientation of the

leaflets. As the R/N phenotype (corresponding to type-1

R-N and type-0 lat) dominates among bicuspid valves in

our study, an analysis using the R/N-classification would

be very similar to comparing BAVs vs. TAVs. Here we

show that the number of morphological leaflets in BAVs is

important in addition to discrimination between tri-and

bicuspid valves.

When comparing our results with previously published

data, one must be aware that different methods have been

used to evaluate the aortic valves. Even so, we felt it

prudent to include this comparison. In patients with iso-

lated BAVs, Sievers and Schmidtke [9] reported 21 type-0

aortic valves among 304 patients (6.9 %), which in a

binomial test differed from our results based on patients

with coarctation. In our study, 13 of 34 patients had BAV

type-0 (28.9 %) which represents a significant difference

against that previously reported (p \ 0.001). Sievers and

Schmidtke [9] also found 14 patients defined as type 2,

meaning functionally bicuspid valves with two raphe

(‘‘unicuspid valves’’). No such valves were identified in the

present investigation. Furthermore, Sievers and Schmidtke

identified the secondary subtypes in 20 of the type-0 BAV

valves. Among these, 13 valves were of type-0 lat (65.0 %)

and 7 were of type-0 ap (25.0 %, for description of ter-

minology see Fig. 1). In our study, listing 13 type-0 BAV

valves, we found two type-0 lat (15.4 %) and 11 type-0 ap

(84.6 %) which differed from the previous report

(p \ 0.001). Thus, it appears that not only is type-0 BAV

the more common form of BAV in our patient group—

these valves are also dominated by the ap variety.

It is already recommended that all patients with coarc-

tation of the aorta should be monitored for late complica-

tions [20]. We show that for patients with coarctation of the

aorta, BAV subtype is associated with both the dimensions

of the ascending aorta and with the risk of developing

moderate to severe aortic stenosis. At present, existing

guidelines generally consider BAV a uniform identity [22,

23]. In dilatation of the aorta, surgery is recommended for

smaller aortic diameters if BAV is present, but with no

distinction between different BAV subtypes. Our data

indicates that BAV subtype may become an important

variable in clinical decision-making and that patients with

Fig. 4 Mean diameter of the ascending aorta by aortic valve type

(main category only). The error bars represent ±1 standard deviation

(a). Mean diameter of the left sinus of Valsalva measured from the

left sinus perpendicular to the commissural line, by aortic valve type

(main category only). The error bars represent ±1 standard deviation

(b)

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BAV type-0 potentially require more intense follow-up

strategies. Longitudinal studies are needed to clarify the

risk of developing complications over time related to BAV

subtype.

Acknowledgments This work was supported by the Swedish Heart-

Lung Foundation, the Heart Foundation of Northern Sweden,

Umea University, and Vasterbottens lans landsting (the County of

Vasterbotten).

Conflict of interest None.

Table 4 Univariate linear regression with the diameter of the ascending aorta as the dependent variable

Variable Coefficient 95 % CI Std. coefficient (b) p value

Lower Upper

Sex 0.631 -2.788 4.050 0.050 0.713

Age 0.219 0.125 0.313 0.538 \0.001**

Height 0.109 -0.069 0.287 0.166 0.225

Weight 0.045 -0.069 0.158 0.116 0.434

BAV type-1 3.369 -0.219 6.957 0.284 0.065*

BAV type-0 7.057 3.146 10.969 0.573 0.001**

Diameter of coarctation 0.468 0.044 0.891 0.288 0.031**

CoA ratio -0.683 -7.844 6.478 -0.026 0.849

Hypertension -0.103 -3.686 3.479 -0.008 0.954

Systolic blood pressure (right arm) -0.004 -0.089 0.081 -0.013 0.930

Blood pressure gradient between arm and leg -0.057 -0.179 0.065 -0.167 0.346

Other congenital heart defects -0.408 -4.299 3.483 -0.029 0.834

Cardiac medication 0.687 -2.956 4.329 0.055 0.706

Surgical intervention 3.361 -0.353 7.075 0.240 0.075*

Surgical reintervention -1.013 -6.565 4.539 -0.052 0.716

Increase in systolic blood pressure during stress test -0.028 -0.109 0.052 -0.127 0.480

Moderate or severe aortic valve disease 7.576 3.497 11.655 0.449 \0.001**

The group with tricuspid aortic valves has been used as a reference group among valve subtypes. CoA ratio is the ratio between the minimum

dimension at the level of coarctation and the distal descending aorta

* p \ 0.15, ** p \ 0.05

Table 5 Multivariate linear regression with dimension of the ascending aorta as dependent variable

Variable Coefficient 95 % CI coefficient Std. coefficient (b) p value

Lower Upper

Age 0.192 0.106 0.278 0.473 \0.001

Length 0.177 0.047 0.308 0.270 0.009

BAV type 0 5.141 1.601 8.681 0.349 0.005

BAV type-1 3.783 0.903 6.662 0.301 0.011

Moderate or severe aortic valve disease 4.091 0.309 7.874 0.242 0.035

Constant -11.529

Diameter of coarctation was also included in the regression, but did not turn out significant in the final model. Adjusted R2 for the model is 0.488,

n = 55, and its significance \0.001

Table 6 Cases of aortic valve dysfunction in the study population

Aortic valve function BAV

type-0

BAV

type-1

TAV

Normal valve function, or dysfunction

of degree B1

8 25 16

Aortic stenosis, degree C2 5 1 0

Isolated aortic regurgitation,

degree C2

0 2 1

All patients 13 28 17

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