The Role of ECG-Gated CT in Patients with Bicuspid Aortic Valve Replacement: New Perspectives in Short- and Long-Term Followup

The aim of our study was to compare the results of the TTE (transthoracic echocardiography) with the results obtained by the ECG-gated 64 slices CT during the followup of patients with bicuspid aortic valve (BAV), after aortic valve replacement; in particular we evaluated the aortic root and the ascending aorta looking for a new algorithm in the followup of these patients. From January 1999 to December 2009 our attention was focused on 67 patients with isolated surgical substitution of aortic valve; after dismissal they were strictly observed. During the period between May and September 2010, these patients underwent their last evaluation, and clinical exams, ECG, TTE, and an ECG-gated-MDCT were performed. At followup TTE results showed an aortic root of 36.7 ± 4 mm and an ascending aorta of 39.6 ± 4.8 mm. ECG- gated CT showed an aortic root of 37.9 ± 5.5 mm and an ascending aorta of 43.1 ± 5.2. The comparison between preoperative and postoperative TTE shows a significant long-term dilatation of the ascending aorta while the aortic root diameter seems to be stable. ECG-gated CT confirms the stability of the aortic root diameter (38.2 ± 5.3 mm versus 37.9 ± 5.5  mm; <0.0001) and the increasing diameter value of the ascending aorta (40.2 ± 3.9 mm versus 43.1 ± 5.2 mm; P = 0.0156). Due to the different findings between CT and TTE studies, ECG-gated CT should no longer be considered as a complementary exam in the followup of patients with BAV, but as a fundamental role since it is a real necessity.


Introduction
Bicuspid aortic valve is an autosomal dominant hereditary disease with incomplete penetrance and represents the most common congenital disease that can be found in the general population, with prevalence between 1% and 2%. However, a threefold higher male predominance one was observed, suggesting that this disease may be related to an X-linked hereditary [1].
Patients with bicuspid aortic valve have a higher morbidity and mortality owing to the associated cardiovascular complications.
Aortic coarctation, dilatation, and consequent aneurysm or dissections of the ascending aorta are very common in this group of patients.
Aortic stenosis/insufficient valve is very common in these patients and it is related to gradual calci�cation of the valve. In these patients a valve replacement is necessary and the surgical rational is similar to the valve replacement of the tricuspid one. It is generally accepted that replacement of the ascending aorta should be performed, at the time of  [10]. In fact a dilatation of the ascending aorta could occur, even aer the valve replacement, so the followup of the aorta in these patients is needed. Echocardiography is considered the �rst standard examination for the diagnosis and the followup of this disease, especially if performed via transthoracic approach, with sensibility of 87% and speci�city of 91%.
ECG-gated CT has been shown to provide accurate information about the aortic valve and root and may be considered as an alternative imaging technique [11][12][13].
e aim of our study is to compare the results of the TEE (transthoracic echocardiography) with the results obtained by the ECG-gated 64 slices CT during the followup of patients with BAV, aer aortic valve replacement; in particular we evaluated the aortic root and the ascending aorta looking for a new algorithm in the followup of these patients. surgical treatment by Cardiac Surgery Division of Tor Vergata University Foundation. In particular our attention was focused on 67 patients with isolated surgical substitution of aortic valve (48 male, 19 female; mild age of 61 ± 15, min age 21, max age 88), selected for clinical and instrumental preoperative and postoperative studies with echo-cardiac and MDCT exams, on the bases of ascending aortic diameters <45 mm at the moment of surgical treatment, absence of genetic disease (e.g., Marfan syndrome), general CT exam contraindications, and also for geographical territory distribution.

Materials and Methods
Preoperatory characteristics of this selected population of patients are shown in Table 1.
e study was approved by the local ethics committee and all the patients provided informed consent to the examination.
An echo-cardiac transthoracic exam (Table 2) and MDCT (Table 3) were performed before surgical treatment.
A preoperative coronary study was also performed by means of a conventional coronarographic study in 60 patients and a MDCT in 7 patients.
All these patients underwent surgical implanted valves; in particular, 30 of them received a biological prosthesis (Lifesciences Edwards C-E Perimount) and 37 of them a mechanical prosthesis (24 Sorin Bicarbon, 12 CarboMedics, 1 St.Jude Medical).
Aer dismissal, all of these patients were strictly observed with clinical exams, ECG, transthoracic echocardiography, and in selected cases with MDCT.

Followup.
During the period between May to September 2010, these patients underwent their last evaluation, and clinical exams, ECG, transthoracic echocardiography and an ECG-gated-MDCT were performed.

2.3.
Echocardiography. An echo-cardiac transthoracic exam was performed in order to measure the diameter of the aortic root, sinotubular junction, and ascending aorta.
A measurement of parietal thickness, telediastolic and telesystolic le ventricular diameter and le ventricular ejection fraction was also obtained.
As regards the prosthesis aortic valve, we evaluated transvalvular maximum and medium gradients and the presence of re�ux; we also studied the other valves and systolic pulmonary arterial pressure.

CT.
MDCT was also performed before surgical treatment to measure the aortic root diameter, sinotubular junction, and ascending aorta (at the bifurcation of pulmonary trunk) and proximal aortic arch. An evaluation of the aortic valve was also made.
Cardiac frequency <75 bpm was required for the execution of the examination; in the case of higher frequency a beta blocker was administrated (5 mg propranolol ev.).

Acquisition
Protocol. CT exams were performed with a 64-slice CT scanner (LightSpeed VCT, General Electric Medical System, Milwaukee, WI, USA), and by a retrospective synchronization technique.
A preliminary unenhanced scan was done in order to determine the scan extent and calculate the calcium score (SmartScore protocol). e acquisition stack extended from the pulmonary apex to the diaphragm inferiorly. A second image stack was then acquired aer intravenous administration of iodinated contrast material using a dualhead automated injector (Stellant, MEDRAD, Pittsburgh, PA, USA). A dose of 90 mL of nonionic iodinated contrast material (Iomeron 400, Bracco, Milan, Italy) was administered through an 18-gauge needle cannula placed in an antecubital vein, followed by a 40 mL saline solution injection, both at a rate of 5 mL/s. To synchronize the acquisition start with the arrival of the contrast agent in the aortic root, the bolustracking technique was used. Parameters for the contrastenhanced scan were beam collimation 64 × 0.625 mm, slice thickness 0.625 mm, reconstruction increment 0.625 mm, table feed 2.9 mm/rotation, tube rotation 0.35 s, tube voltage 120 kV, dose modulation protocol (intensity 140-750 mA), and craniocaudal scan direction. Scan duration was 10-12 s. Image reconstruction was carried out using 75% of the cardiac cycle, corresponding to the R-R interval or end diastole.

Statistical Analysis.
All the data was entered into a database for statistical processing. e data was expressed as means plus one standard deviation (SD) or as percentages. e comparison between groups was obtained using the 2 test and the Student's -test, as appropriate. Statistical signi�cant was set at < . .

Results
During the period between May to September 2010, these patients underwent their last evaluation; clinical exams, ECG, transthoracic echocardiography, and an ECG-gated-MDCT were performed.
e average time of the followup was ± 3 months (range 9-137 months, median 44 months). Table 4 shows all the clinical characteristics of the population during the followup.
TTE results show an aortic root of 36.7 ± 4 mm and an ascending aorta of 39.6 ± 4.8 mm (Table 5).
All the patients underwent ECG-gated CT and none of them were excluded during the examination.
ECG-gated CT con�rms the stability of the aortic root diameter (38.2 ± .3 mm versus 37.9 ± . mm; <0.0001) and the increasing diameter value of the ascending aorta (4 .2 ± 3.9 mm versus 43.1 ± .2 mm; . 1 6). In particular, we noticed that in 7 (10.4%) patients, the diameter of the ascending aorta was ≥50 mm (Figure 1). Comparing this group of patients with the rest of the population we discovered that the only statistical difference was in the period of followup; in fact these 7 patients have been observed for a period longer than 60 months. ECG-gated CT acquisition allowed us an evaluation of the coronary tree in all patients: 43 (64.1%) patients did not show coronary stenosis, while 21 (31.3%) of them had a nonsigni�cant coronary stenosis (<50%) and 3 (4.4%) had a signi�cant coronary stenosis (≥50%).

Discussion
Bicuspid aortic valve (BAV) is the most common congenital cardiac malformation, affecting 1-2% of the population, with strong male predominance [14]. It has been recognized as a syndrome incorporating aortic valve disorders and aortic wall abnormalities. ese intrinsic defects in the aortic wall end up in late complications such as aortic root dilatation, ascending aortic aneurysm, oen asymmetric [15], and dissection.
Because these complications, with a potentially fatal outcome, will develop in approximately one third of all patients with a bicuspid aortic valve, it is of the utmost importance to correctly detect and treat this type of congenital malformation, and also to follow these possible complications over time [16]. For this reason, different surgical options have been developed for these patients, including not only aortic valve replacement but, in some cases, also concomitant prophylactic surgery of the aorta. According to the guidelines of the American College of Cardiology and of the American Heart Association, patients with BAV should undergo elective repair of the aortic root or replacement of the ascending aorta, at the time of aortic valve replacement, if the diameter of these structures exceeds 45 mm [17]. In fact, the risk of combined surgery on the aortic valve and ascending aorta is almost comparable to the risk of isolated valve replacement, but it is considerably lower than the risk of a possible resurgery in election, or even worse, in emergency.
In case of only aortic valve replacement, a close followup is required aer surgery, to evaluate aortic dilatation and to avoid late complications. Indeed, in patients with BAV without dilatation of the ascending aorta, even successful valve replacement is not able to prevent long-term dilatation of the ascending aorta. Transthoracic echocardiography (TTE) is the �rst standard examination during the followup of these patients [18]. Currently, in patients with previous BAV and aortic valve replacement, transthoracic echocardiographic followup is performed twice a year and it is integrated with angio-CT in the case of initial signs of aortic disease or of suspicious echocardiographic �ndings. Followup evaluation includes the state of the heart chambers, the functioning of prosthetic aortic valve, and the size of thoracic aorta. TEE is an excellent method for studying the aortic root, although this technique has some limitations: it is operator dependent and has a high incidence of artefacts in the evaluation of the upper ascending aorta. e interposition of the trachea and le main bronchus between the aorta and the oesophagus can cause a "blind spot" in this area, and also the presence of severe aortic wall calci�cations may lead to misdiagnosis because of the resulting "acoustic shadows". Additionally, the examination may be undetermined by the lack of a suitable acoustic window due to body habitus and artefacts related to the presence of prostheses. Furthermore, the use of TTE does not permit the visualization of the descending aorta.
e introduction of the latest generation of 64-slice CT scanners with short acquisition times and their high spatial and temporal resolution allows images to be acquired during a single short breath-hold and thus with a high level of anatomical detail of the whole thoracic aorta and of the other anatomic thoracic structures. Furthermore, ECG-gated synchronization with its reconstruction algorithms permits a correct evaluation of cardiovascular structures minimizing cardiac motion artefacts; the advantage of cardiac CT in these patients is that it allows a better visualization of the aortic root and aortic valve and that permits a simultaneous evaluation of the coronary arteries. A heart rate <70 bpm, whether spontaneous or induced by -blockers, is considered sufficient to increase diastolic time and duration of end-diastole, when the heart, the valves, the aortic root, and coronary arteries are nearly motionless. e volume of data acquired during scanning time can be subsequently reelaborated by a postprocessing procedure. Multiplanar reconstruction (MPR), Maximum intensity projection (MIP), and volume rendering (VR) techniques provide a comprehensive depiction of the prosthesis valve, the aortic root, the thoracic aorta, and coronary artery tree. All this information is achieved with values of an absorbed dose of between 8-10 mSv. However, when the heart rate is stable and lower than 65 bpm, a prospective ECG-gated CT protocol could be used with a signi�cant reduction in the adsorbed dose, up to �-5 mSv, without decreasing the image quality.
In our study we investigated the clinical applicability and image quality of retrospectively ECG-gated 64 slices CT for the followup of patients with aortic valve replacement due to BAV, in comparison with transthoracic echocardiography. In particular, our evaluation included thoracic aorta diameters at different levels: aortic root, sinotubular junction, ascending aorta, and aortic arch. In all patients the study was also extended to the descending aorta and completed with an evaluation of the coronary artery tree. We observed a statistically signi�cant difference between CT and TTE in the evaluation of ascending aorta diameters. In particular, in 7 patients, the ascending aortic diameter measured by CT exceeded 50 mm, while echocardiographic measurements were lower. ese results disagree with those of other studies, in particular the study by Tamborini et al. [19], in which there was a good correlation between CT and TTE measurements.
Moreover, it is important to notice that in these patients we observed the longest followup overall, 60 months. is evidence underlines the progression of ascending aorta dilatation and also enhances the importance of long-term evaluation, with an accurate imaging technique, in patients with a prosthesis substitution of BAV.
e most important issue emerging from our study is that ascending aorta shows a progressively long-term dilatation while aortic root's diameters seem to be more stable. Probably, this happens because in patients with BAV syndrome the defects of the valve had previously caused a hemodynamic stress of the ascending aorta wall associated with a congenital alteration of the structures of the aortic wall.

Conclusion
Due to the different �ndings between CT and TTE studies, angio-CT should no longer be considered as a complementary exam in the followup of these patients, but as a fundamental role since it is a real necessity. We think that should be necessary to perform two angio-CT exams in followup, respectively 12 months and 48 months aer aortic valve replacement. Indeed, if between these observation times there are changes in the clinical history of the patient, it is important to perform also one more angio-CT study. Our study demonstrated that angio-CT is a compulsory diagnostic step, in the followup of patients with previous BAV who have undergone aortic valve replacement, to avoid late complications. e information provided by angio-CT regarding the thoracic aorta is more complete and exhaustive than that obtained by TTE.