4D flow cardiovascular magnetic resonance for monitoring of aortic valve repair in bicuspid aortic valve disease

This prospective study was approved by the local ethics board. Written informed consent was obtained from all patients.

Patients with adult congenital heart disease (BAV or UAV) and symptomatic, predominant aortic regurgitation who were referred for minimally invasive aortic valve repair between April 2017 and February 2019 were included in the study. Patients with contraindications for CMR or younger than 18 years were excluded.

Diagnosis of aortic regurgitation was based on transthoracic echocardiography. Echocardiography was also used to assess the quality of aortic cusp tissue and absence of severe calcifications prior to surgery. In case of intraoperative findings like severe cusp calcifications or fenestrations, aortic valve repair was not performed and patients were not included in this study. The procedure of aortic valve repair has been previously described [2].

All patients underwent non-contrast 4D flow CMR of the thoracic aorta on a 3 T system (Ingenia, Philips Healthcare, Best, The Netherlands) with a 32-channel body-phased array coil before and after surgery. Respiratory gated and cardiac triggered 4D flow CMR data were acquired over the entire cardiac cycle with full volumetric coverage of the thoracic aorta. Scan parameters included: velocity encoding 200 cm/s, temporal resolution 24–38 ms, acquired spatial resolution 2.5 × 2.5 × 2.5 mm³, field of view (280–330) x (280–330) x (50–66) mm³, flip angle = 8°. Parallel imaging (k-t BLAST) with an acceleration factor of 4 was used. Scan time for each acquisition was 13.9 ± 3.0 min, depending on heart rate, respiratory pattern, and efficiency of respiratory gating.

Electrocardiogram (ECG)-gated CMR imaging was performed for assessment of left ventricular (LV) volumes and function by using balanced steady-state free-precession (bSSFP) cine CMR [32]. ECG-gated bSSFP imaging of the thoracic aorta was performed for assessment of aortic diameters [33, 34].

4D flow data were corrected for Maxwell terms, eddy currents and phase aliasing in accordance with current consensus recommendations [35]. All data sets were automatically reconstructed to 24 time frames per cardiac cycle and used to render three-dimensional phase-contrast CMR angiograms in a 3D visualization software (GTFlow, GyroTools LLC, Zurich, Switzerland).

One radiologist with 4 years of experience in the assessment of 4D flow data manually placed analysis planes at six defined anatomic landmarks in the thoracic aorta at the level of the aortic valve, the sinotubular junction, the mid-ascending aorta, the aortic arch proximal to the brachiocephalic trunc, the aortic arch distal to the left subclavian artery and the proximal descending aorta [36].

The same radiologist quantified peak velocity as well as forward and backward flow volumes at the aortic valve level and the regurgitant fraction (%) was calculated [37, 38].

Helical and vortical blood flow patterns in the ascending aorta (AAo), the aortic arch (AA), and the descending aorta (DAo) were semiquantitatively evaluated according to a 3-point scale: 0 (none), 1 (< 360°), and 2 (> 360°). A helical flow pattern was defined as a regional spiral movement along the blood flow direction and a vortical flow pattern as a regional circular movement deviating from the physiological flow-direction by > 90° [39, 40].

Flow displacement, a marker to quantify outflow asymmetry, was automatically quantified by exporting defined analyses planes into MATLAB (The MathWorks, Natick, Massachusetts, USA). Flow displacement was defined as the distance from the vessel centroid to the velocity-weighted centroid of the upper 15% of peak systolic forward flow velocity normalized to the vessel diameter, similar to the strategy reported by Sigovan et al. and Mahadevia et al [24, 26]

WSS, a time-resolved three-dimensional force, was quantified in GTFlow (Gyrotools). Magnitudinal WSS, which is the resulting net vector along the entire vascular wall, was derived from each analysis plane at peak systole [23, 41]. Values for peak systolic WSS were averaged over the five cardiac time frames centered on peak systole to reduce measurement noise [39]. Averaged circumferential WSS was assessed for each plane as well as segmental WSS at 8 standardized local anatomic orientations of the vessel wall: anterior (A), left-anterior (LA), left (L), left-posterior (LP), posterior (P), right-posterior (RP), right (R), and right-anterior (RA) [21, 26, 40].

4D flow CMR before and after aortic valve repair was successfully completed in 20 patients with adult congenital heart disease and symptomatic aortic valve regurgitation. Three other patients had to be excluded from the main analyses. In one patient, the dilated aortic root was only partially covered by the 3D volume of the 4D flow sequence. Two patients required aortic valve replacement instead of repair and therefore did not undergo the second CMR examination.

Median age of the 20 included patients at the time of surgery was 35 years (IQR 29–47). Median time between CMR examinations was 9 days (IQR 6–38). There were no relevant medications changed between CMR imaging examinations.

Fifteen patients (75%) had a BAV Sievers Type 1 phenotype with L/R cusp fusion (Fig. 2) and five patients (25%) presented with a UAV phenotype (Fig. 3) (Table 1). Seventeen patients (85%) underwent isolated aortic valve repair, while three patients (15%) needed additional aortic root remodeling [42]. After surgery, there was a significant reduction of mean aortic diameters at the level of the anulus (2.6 ± 0.4 vs. 2.3 ± 0.2 cm, p < 0.001), which is explained by suture annuloplasty aiming to reduce the basal ring diameter. The average diameter at the level of the bulbus aortae (3.8 ± 0.6 vs. 3.5 ± 0.4 cm, p = 0.03) and the mid-ascending aorta (3.3 ± 0.6 vs. 3.1 ± 0.4 cm, p = 0.03) was also significantly reduced, which is explained by the three patients with aortic root remodeling with Dacron prostheses. After surgery there was a significant reduction in stroke volume (120 ± 34 vs. 90 ± 28 ml, p < 0.001). There was no significant difference in LVEF after surgery (57.8 ± 7.8% vs. 58.7 ± 7.2%, p = 0.252). Patient characteristics of all patients and subgroup analyses of BAV and UAV patients including aortic diameters and cardiac function metrics before and after surgery are detailed in Table 1.

4D flow CMR-derived blood flow quantification revealed that aortic valve repair resulted in a significant reduction of forward flow, backward flow, and net flow volume at the aortic valve level (all p < 0.001) (Table 2). The improved aortic root geometry also resulted in a significantly reduced regurgitant fraction (17 ± 10% vs. 6 ± 4%, p < 0.001) (Fig. 2b and e, Fig. 3b and e) and systolic peak velocity (2.2 ± 0.9 vs. 1.9 ± 0.4 m/s, p = 0.014) (Table 2).

4D flow CMR allowed visualization of hemodynamic flow patterns such as helical and vortical flow in the thoracic aorta before (Fig. 2a and Fig. 3a) and after aortic valve repair (Fig. 2d and Fig. 3d).

All patients showed common global right-handed helical flow formation in the AAo before and after surgery. Pathologic, secondary local helical flow formations in the AAo were reduced after surgery in 13 of 20 patients (65%) (1.6 ± 0.6 vs. 0.9 ± 0.5, p < 0.001). Helical flow in the aortic arch and DAo was less pronounced, however, these differences where not statistically significant (Table 2).

Vortical flow patterns in the AAo were observed in 15 of 20 patients (75%) before surgery and in 9 of 20 patients (45%) after surgery, resulting in a significant decrease of the average vortical flow (1.2 ± 0.8 vs. 0.5 ± 0.6, p = 0.002). Although vortical flow was less pronounced in the aortic arch and DAo after surgery, these differences were not statistically significant (Table 2).

4D flow CMR revealed highly eccentric outflow jet patterns directed towards the right-anterior wall of the mid-ascending AAo before surgery (Fig. 2c and Fig. 3c) in all patients and a more centrally located flow profile after aortic valve repair (Fig. 2f and Fig. 3f) in twelve patients (60%) (Fig. 4). Flow displacement was significantly reduced after surgery in the mid-ascending AAo (0.3 ± 0.1 vs. 0.25 ± 0.1, p= 0.031) (Fig. 4). There was no significant change of flow displacement at the level of the sinotubular junction (0.19 ± 0.1 vs. 0.18 ± 0.1, p = 0.759) and the proximal aortic arch (0.3 ± 0.1 vs. 0.29 ± 0.1, p = 0.524).

Subgroup analyses of BAV and UAV patients are detailed in Table 3.

Circumferential WSS was significantly reduced after aortic valve repair in the mid-ascending AAo (0.8 ± 0.2 vs. 0.5 ± 0.2 N/m², p < 0.001), proximal aortic arch (0.8 ± 0.4 vs. 0.5 ± 0.2 N/m², p = 0.002), and distal aortic arch (0.6 ± 0.3 vs. 0.5 ± 0.2 N/m², P < 0.001) for all patients (Fig. 5a). There was no significant change at the level of the sinotubular junction (0.5 ± 0.2 vs. 0.4 ± 0.2 N/m², p = 0.233) and the DAo (0.6 ± 0.3 vs. 0.5 ± 0.2 N/m², p = 0.077). In the mid-ascending AAo, where circumferential WSS was highest, 4D flow CMR revealed decreased WSS postoperatively in 18 of 20 patients (90%) and an increased WSS in two patients (10%).

Subgroup analyses of BAV and UAV patients are detailed in Table 4.

Segmental WSS analyses along the aortic circumference are illustrated in Fig. 5b. The highest segmental WSS was observed in the mid-ascending AAo and the proximal aortic arch before aortic valve repair.

In the mid-ascending AAo, consistent with the regions of eccentric flow, segmental WSS before aortic valve repair was most pronounced at the anterior, right-anterior, and right aortic wall. After surgery, WSS was significantly reduced in the A, RA, R, P, L, and LA segments.

In the proximal aortic arch, segmental WSS magnitude and asymmetry was most pronounced before aortic valve repair at the anterior and left-anterior aortic wall. After aortic valve repair, WSS was significantly reduced in the A, R, RP, P, LP, L, and LA segments.

At the level of the distal aortic arch, aortic valve repair significantly reduced segmental WSS at the A, RA, and R segments. At the level of the DAo, aortic valve repair significantly reduced segmental WSS at the LA and A segments. At the level of the sinotubular junction, segmental WSS was lowest and without significant changes after aortic valve repair.