Atorvastatin Effect on Aortic Dilatation and Valvular Calcification Progression in Bicuspid Aortic Valve (BICATOR): A Randomized Clinical Trial.

BACKGROUND: Ascending aorta dilation and aortic valve degeneration are common complications in patients with bicuspid aortic valve. Several retrospective studies have suggested the benefit of statins in reducing these complications. This study aimed to determine whether atorvastatin treatment is effective in reducing the growth of aortic diameters in bicuspid aortic valve and if it slows the progression of valve calcification. METHODS: In a randomized clinical trial, 220 patients with bicuspid aortic valve (43 women; 46±13 years of age) were included and treated with either 20 mg of atorvastatin per day or placebo for 3 years. Inclusion criteria were ≥18 years of age, nonsevere valvular dysfunction, nonsevere valve calcification, and ascending aorta diameter ≤50 mm. Computed tomography and echocardiography studies were performed at baseline and after 3 years of treatment. RESULTS: During follow-up, 28 patients (12.7%) discontinued medical treatment (15 on atorvastatin and 13 taking placebo). Thus, 192 patients completed the 36 months of treatment. Low-density lipoprotein cholesterol levels decreased significantly in the atorvastatin group (median [interquartile range], -30 mg/dL [-51.65 to -1.75 mg/dL] versus 6 mg/dL [-4, 22.5 mg/dL]; P<0.001). The maximum ascending aorta diameter increased with no differences between groups: 0.65 mm (95% CI, 0.45-0.85) in the atorvastatin group and 0.74 mm (95% CI, 0.45-1.04) in the placebo group (P=0.613). Similarly, no significant differences were found for the progression of the aortic valve calcium score (P=0.167) or valvular dysfunction. CONCLUSIONS: Among patients with bicuspid aortic valve without severe valvular dysfunction, atorvastatin treatment was not effective in reducing the progression of ascending aorta dilation and aortic valve calcification during 3 years of treatment despite a significant reduction in low-density lipoprotein cholesterol levels. REGISTRATION: URL: https://www.clinicaltrialsregister.eu; Unique identifier: 2015-001808-57. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02679261.

False lumen hemodynamics and partial thrombosis in chronic aortic dissection of the descending aorta.

OBJECTIVES: Partial thrombosis of the false lumen (FL) in patients with chronic aortic dissection (AD) of the descending aorta has been associated with poor outcomes. Meanwhile, the fluid dynamic and biomechanical characteristics associated with partial thrombosis remain to be elucidated. This retrospective, single-center study tested the association between FL fluid dynamics and biomechanics and the presence and extent of FL thrombus. METHODS: Patients with chronic non-thrombosed or partially thrombosed FLs in the descending aorta after an aortic dissection underwent computed tomography angiography, cardiovascular magnetic resonance (CMR) angiography, and a 4D flow CMR study. A comprehensive quantitative analysis was performed to test the association between FL thrombus presence and extent (percentage of FL with thrombus) and FL anatomy (diameter, entry tear location and size), fluid dynamics (inflow, rotational flow, wall shear stress, kinetic energy, and flow acceleration and stasis), and biomechanics (pulse wave velocity). RESULTS: Sixty-eight patients were included. In multivariate logistic regression FL kinetic energy (p = 0.038) discriminated the 33 patients with partial FL thrombosis from the 35 patients with no thrombosis. Similarly, in separated multivariate linear correlations kinetic energy (p = 0.006) and FL inflow (p = 0.002) were independently related to the extent of the thrombus. FL vortexes, flow acceleration and stasis, wall shear stress, and pulse wave velocity showed limited associations with thrombus presence and extent. CONCLUSION: In patients with chronic descending aorta dissection, false lumen kinetic energy is related to the presence and extent of false lumen thrombus. CLINICAL RELEVANCE STATEMENT: In patients with chronic aortic dissection of the descending aorta, false lumen hemodynamic parameters are closely linked with the presence and extent of false lumen thrombosis, and these non-invasive measures might be important in patient management. KEY POINTS: • Partial false lumen thrombosis has been associated with aortic growth in patients with chronic descending aortic dissection; therefore, the identification of prothrombotic flow conditions is desirable. • The presence of partial false lumen thrombosis as well as its extent was related with false lumen kinetic energy. • The assessment of false lumen hemodynamics may be important in the management of patients with chronic aortic dissection of the descending aorta.

Impact of valve-sparing aortic root replacement on aortic fluid dynamics and biomechanics in patients with syndromic heritable thoracic aortic disease.

OBJECTIVES: Patients with syndromic heritable thoracic aortic diseases (sHTAD) who underwent prophylactic aortic root replacement are at high risk of distal aortic events, but the underlying mechanisms are poorly understood. This prospective, longitudinal study aims to assess the impact of valve-sparing aortic root replacement (VSARR) on aortic fluid dynamics and biomechanics in these patients, and to examine whether they present altered haemodynamics or biomechanics prior to surgery compared to sHTAD patients with no indication for surgery (sHTAD-NSx) and healthy volunteers (HV). METHODS: Sixteen patients with Marfan or Loeys-Dietz syndrome underwent two 4D flow CMR studies before (sHTAD-preSx) and after VSARR (sHTAD-postSx). Two age, sex and BSA matched cohorts of 40 HV and 16 sHTAD-NSx patients with available 4D flow CMR, were selected for comparison. In-plane rotational flow (IRF), systolic flow reversal ratio (SFRR), wall shear stress (WSS), pulse wave velocity (PWV) and aortic strain were analysed in the ascending (AscAo) and descending aorta (DescAo). RESULTS: All patients with sHTAD presented altered haemodynamics and increased aortic stiffness (p<0.05) compared to HV, both in the AscAo (median PWV 7.4 in sHTAD-NSx; 6.8 in sHTAD-preSx; 4.9m/s in HV) and DescAo (median PWV 9.1 in sHTAD-NSx; 8.1 in sHTAD-preSx; 6.3m/s in HV). Patients awaiting VSARR had markedly reduced in-plane (median IRF -2.2 vs 10.4 cm2/s in HV, p=0.001), but increased through-plane flow rotation (median SFRR 7.8 vs 3.8% in HV, p=0.002), and decreased WSS (0.36 vs 0.47N/m2 in HV, p=0.004) in the proximal DescAo. After VSARR, proximal DescAo in-plane rotational flow (p=0.010) and circumferential WSS increased (p=0.011), no longer differing from HV, but through-plane rotational flow, axial WSS and stiffness remained altered. Patients in which aortic tortuosity was reduced after surgery showed greater post-surgical increase in IRF compared to those in which tortuosity increased (median IRF increase 18.1 vs 3.3cm²/s, p=0.047). Most AscAo flow alterations were restored to physiological values after VSARR. CONCLUSIONS: In patients with sHTAD, VSARR partially restores downstream fluid dynamics to physiological levels. However, some flow disturbances and increased stiffness persist in the proximal DescAo. Further longitudinal studies are needed to evaluate whether persistent alterations contribute to post-surgical risk.

Three-dimensional aortic geometry mapping via registration of non-gated contrast-enhanced or gated and respiratory-navigated MR angiographies.

BACKGROUND: The measurement of aortic dimensions and their evolution are key in the management of patients with aortic diseases. Manual assessment, the current guideline-recommended method and clinical standard, is subjective, poorly reproducible, and time-consuming, limiting the capacity to track aortic growth in everyday practice. Aortic geometry mapping (AGM) via image registration of serial computed tomography angiograms outperforms manual assessment, providing accurate and reproducible 3D maps of aortic diameter and growth rate. This observational study aimed to evaluate the accuracy and reproducibility of AGM on non-gated contrast-enhanced (CE-) and cardiac- and respiratory-gated (GN-) magnetic resonance angiographies (MRA). METHODS: Patients with thoracic aortic disease followed with serial CE-MRA (n = 30) or GN-MRA (n = 15) acquired at least 1 year apart were retrospectively and consecutively identified. Two independent observers measured aortic diameters and growth rates (GR) manually at several thoracic aorta reference levels and with AGM. Agreement between manual and AGM measurements and their inter-observer reproducibility were compared. Reproducibility for aortic diameter and GR maps assessed with AGM was obtained. RESULTS: Mean follow-up was 3.8 ± 2.3 years for CE- and 2.7 ± 1.6 years for GN-MRA. AGM was feasible in the 93% of CE-MRA pairs and in the 100% of GN-MRA pairs. Manual and AGM diameters showed excellent agreement and inter-observer reproducibility (ICC>0.9) at all anatomical levels. Agreement between manual and AGM GR was more limited, both in the aortic root by GN-MRA (ICC=0.47) and in the thoracic aorta, where higher accuracy was obtained with GN- than with CE-MRA (ICC=0.55 vs 0.43). The inter-observer reproducibility of GR by AGM was superior compared to manual assessment, both with CE- (thoracic: ICC= 0.91 vs 0.51) and GN-MRA (root: ICC=0.84 vs 0.52; thoracic: ICC=0.93 vs 0.60). AGM-based 3D aortic size and growth maps were highly reproducible (median ICC >0.9 for diameters and >0.80 for GR). CONCLUSION: Mapping aortic diameter and growth on MRA via 3D image registration is feasible, accurate and outperforms the current manual clinical standard. This technique could broaden the possibilities of clinical and research evaluation of patients with aortic thoracic diseases.

Machine learning for the automatic assessment of aortic rotational flow and wall shear stress from 4D flow cardiac magnetic resonance imaging.

OBJECTIVE: Three-dimensional (3D) time-resolved phase-contrast cardiac magnetic resonance (4D flow CMR) allows for unparalleled quantification of blood velocity. Despite established potential in aortic diseases, the analysis is time-consuming and requires expert knowledge, hindering clinical application. The present research aimed to develop and test a fully automatic machine learning-based pipeline for aortic 4D flow CMR analysis. METHODS: Four hundred and four subjects were prospectively included. Ground-truth to train the algorithms was generated by experts. The cohort was divided into training (323 patients) and testing (81) sets and used to train and test a 3D nnU-Net for segmentation and a Deep Q-Network algorithm for landmark detection. In-plane (IRF) and through-plane (SFRR) rotational flow descriptors and axial and circumferential wall shear stress (WSS) were computed at ten planes covering the ascending aorta and arch. RESULTS: Automatic aortic segmentation resulted in a median Dice score (DS) of 0.949 and average symmetric surface distance of 0.839 (0.632-1.071) mm, comparable with the state of the art. Aortic landmarks were located with a precision comparable with experts in the sinotubular junction and first and third supra-aortic vessels (p = 0.513, 0.592 and 0.905, respectively) but with lower precision in the pulmonary bifurcation (p = 0.028), resulting in precise localisation of analysis planes. Automatic flow assessment showed excellent (ICC > 0.9) agreement with manual quantification of SFRR and good-to-excellent agreement (ICC > 0.75) in the measurement of IRF and axial and circumferential WSS. CONCLUSION: Fully automatic analysis of complex aortic flow dynamics from 4D flow CMR is feasible. Its implementation could foster the clinical use of 4D flow CMR. KEY POINTS: • 4D flow CMR allows for unparalleled aortic blood flow analysis but requires aortic segmentation and anatomical landmark identification, which are time-consuming, limiting 4D flow CMR widespread use. • A fully automatic machine learning pipeline for aortic 4D flow CMR analysis was trained with data of 323 patients and tested in 81 patients, ensuring a balanced distribution of aneurysm aetiologies. • Automatic assessment of complex flow characteristics such as rotational flow and wall shear stress showed good-to-excellent agreement with manual quantification.

Registration-based semi-automatic assessment of aortic diameter growth rate from contrast-enhanced computed tomography outperforms manual quantification.

OBJECTIVES: Manual assessment of aortic diameters on double-oblique reformatted computed tomography angiograms (CTA) is considered the current standard, although the reproducibility for growth rates has not been reported. Deformable registration of CTA has been proposed to provide 3D aortic diameters and growth maps, but validation is lacking. This study aimed to quantify accuracy and inter-observer reproducibility of registration-based and manual assessment of aortic diameters and growth rates. METHODS: Forty patients with ≥ 2 CTA acquired at least 6 months apart were included. Aortic diameters and growth rate were obtained in the aortic root and the entire thoracic aorta using deformable image registration by two independent observers, and compared with the current standard at typical anatomical landmarks. RESULTS: Compared with manual assessment, the registration-based technique presented low bias (0.46 mm), excellent agreement (ICC = 0.99), and similar inter-observer reproducibility (ICC = 0.99 for both) for aortic diameters; and low bias (0.10 mm/year), good agreement (ICC = 0.82), and much higher inter-observer reproducibility for growth rates (root: ICC = 0.96 vs 0.68; thoracic aorta: ICC = 0.96 vs 0.80). Registration-based growth rate reproducibility over a 6-month-long follow-up was similar to that obtained by manual assessment after 2.7 years (LoA = [- 0.01, 0.33] vs [- 0.13, 0.21] mm/year, respectively). Mapping of diameter and growth rate was highly reproducible (ICC > 0.9) in the whole thoracic aorta. CONCLUSIONS: Registration-based assessment of aortic dilation on CTA is accurate and substantially more reproducible than the current standard, even at follow-up as short as 6 months, and provides robust 3D mapping of aortic diameters and growth rates beyond the pre-established anatomic landmarks. KEY POINTS: • Registration-based semi-automatic assessment of progressive aortic dilation on CTA is accurate and substantially more reproducible than the current standard. • The registration-based technique allows robust growth rate assessment at follow-up as short as 6 months, with a similar reproducibility to that obtained by manual assessment at around 3 years. • The use of image registration provides robust 3D mapping of aortic diameters and growth rates beyond the pre-established anatomic landmarks.

False lumen rotational flow and aortic stiffness are associated with aortic growth rate in patients with chronic aortic dissection of the descending aorta: a 4D flow cardiovascular magnetic resonance study.

BACKGROUND: Patency of the false lumen in chronic aortic dissection (AD) is associated with aortic dilation and long-term aortic events. However, predictors of adverse outcomes in this population are limited. The aim of this study was to evaluate the relationship between aortic growth rate and false lumen flow dynamics and biomechanics in patients with chronic, patent AD. METHODS: Patients with a chronic AD with patent false lumen in the descending aorta and no genetic connective tissue disorder underwent an imaging follow-up including a contrast-enhanced 4D flow cardiovascular magnetic resonance (CMR) protocol and two consecutive computed tomography angiograms (CTA) acquired at least 1 year apart. A comprehensive analysis of anatomical features (including thrombus quantification), and false lumen flow dynamics and biomechanics (pulse wave velocity) was performed. RESULTS: Fifty-four consecutive patients with a chronic, patent false lumen in the descending aorta were included (35 surgically-treated type A AD with residual tear and 19 medically-treated type B AD). Median follow-up was 40 months. The in-plane rotational flow, pulse wave velocity and the percentage of thrombus in the false lumen were positively related to aortic growth rate (p = 0.006, 0.017, and 0.037, respectively), whereas wall shear stress showed a trend for a positive association (p = 0.060). These results were found irrespectively of the type of AD. CONCLUSIONS: In patients with chronic AD and patent false lumen of the descending aorta, rotational flow, pulse wave velocity and wall shear stress are positively related to aortic growth rate, and should be implemented in the follow-up algorithm of these patients. Further prospective studies are needed to confirm if the assessment of these parameters helps to identify patients at higher risk of adverse clinical events.

Leaflet fusion length is associated with aortic dilation and flow alterations in non-dysfunctional bicuspid aortic valve.

OBJECTIVE: Bicuspid aortic valve (BAV), the most common congenital valve defect, is associated with increased risk of aortic dilation and related complications; however, current risk assessment is not effective. Most of BAV have three leaflets with a fusion between two of them of variable length. This study aimed to ascertain whether the extent of leaflet fusion (often called raphe) is related to aortic dilation and flow abnormalities in BAV with no significant valvular dysfunction. METHODS: One hundred and twenty BAV patients with no significant valvular dysfunction or history of surgical repair or aortic valve replacement were consecutively and prospectively enrolled (September 2014-October 2018). Cardiac magnetic resonance protocol included a 4D flow sequence for haemodynamic assessment. Moreover, a stack of double-oblique cine images of the aortic valve were used to quantify fusion length (in systole) and leaflet length (diastole). Inter- and intra-observer reproducibility was tested in 30 randomly selected patients. RESULTS: Aortic valve leaflet fusion was measurable in 112 of 120 (93%) cases with good reproducibility (ICC = 0.826). Fusion length varied greatly (range: 2.3-15.4 mm; mean: 7.8 ± 3.2 mm). After correction for demographic and clinical conditions, fusion length was independently associated with diameter and z-score at the sinus of Valsalva (p = 0.002 and p = 0.002, respectively) and ascending aorta (p = 0.028 and p = 0.046). Fusion length was positively related to flow asymmetry, vortices and circumferential wall shear stress, thereby possibly providing a pathophysiological link with aortic dilation. CONCLUSIONS: Aortic valve fusion length is related to aortic dilation and flow abnormalities in BAV patients. KEY POINTS: • The length of the fusion between leaflets in non-dysfunctional bicuspid aortic valves varies substantially and can be reliably measured by cine CMR. • Aortic valve leaflet fusion length is independently related to aortic sinus and ascending aorta diameter. • Increased flow asymmetry, circumferential wall shear stress and presence of vortices are positively related to aortic valve leaflet fusion length.

Low and Oscillatory Wall Shear Stress Is Not Related to Aortic Dilation in Patients With Bicuspid Aortic Valve: A Time-Resolved 3-Dimensional Phase-Contrast Magnetic Resonance Imaging Study.

OBJECTIVE: To assess the relationship between regional wall shear stress (WSS) and oscillatory shear index (OSI) and aortic dilation in patients with bicuspid aortic valve (BAV). Approach and Results: Forty-six consecutive patients with BAV (63% with right-left-coronary-cusp fusion, aortic diameter ≤ 45 mm and no severe valvular disease) and 44 healthy volunteers were studied by time-resolved 3-dimensional phase-contrast magnetic resonance imaging. WSS and OSI were quantified at different levels of the ascending aorta and the aortic arch, and regional WSS and OSI maps were obtained. Seventy percent of BAV had ascending aorta dilation. Compared with healthy volunteers, patients with BAV had increased WSS and decreased OSI in most of the ascending aorta and the aortic arch. In both BAV and healthy volunteers, regions of high WSS matched regions of low OSI and vice versa. No regions of both low WSS and high OSI were identified in BAV compared with healthy volunteers. Patients with BAV with dilated compared with nondilated aorta presented low and oscillatory WSS in the aortic arch, but not in the ascending aorta where dilation is more prevalent. Furthermore, no regions of concomitant low WSS and high OSI were identified when BAV were compared according to leaflet fusion pattern, despite the well-known differences in regional dilation prevalence. CONCLUSIONS: Regions with low WSS and high OSI do not match those with the highest prevalence of dilation in patients with BAV, thus providing no evidence to support the low and oscillatory shear stress theory in the pathogenesis of proximal aorta dilation in the presence of BAV.

Geometric, Biomechanic and Haemodynamic Aortic Abnormalities Assessed by 4D Flow Cardiovascular Magnetic Resonance in Patients Treated by TEVAR Following Blunt Traumatic Thoracic Aortic Injury.

OBJECTIVE: Thoracic endovascular aortic repair (TEVAR) is widely used for the treatment of patients with blunt traumatic thoracic aortic injury (BTAI). However, aortic haemodynamic and biomechanical implications of this intervention are poorly investigated. This study aimed to assess whether patients treated by TEVAR following BTAI have thoracic aortic abnormalities in geometry, stiffness, and haemodynamics. METHODS: Patients with BTAI treated by TEVAR at Vall d'Hebron Hospital between 1999 and 2019 were compared with propensity score matched healthy volunteers (HVs). All subjects underwent cardiovascular magnetic resonance (CMR) comprising a 4D flow CMR sequence. Spatially resolved aortic diameter, length, volume, and curvature were assessed. Pulse wave velocity, distensibility, and longitudinal strain (all measurements of aortic stiffness) were determined regionally. Moreover, advanced haemodynamic descriptors were quantified: systolic flow reversal ratio (SFRR), quantifying backward flow during systole, and in plane rotational flow (IRF), measuring in plane strength of helical flow. RESULTS: Twenty-six BTAI patients treated by TEVAR were included and matched with 26 HVs. They did not differ in terms of age, sex, and body surface area. Patients with TEVAR had a larger and longer ascending aorta (AAo) and marked abnormalities in local curvature. Aortic stiffness was greater in the aortic segments proximal and distal to TEVAR compared with controls. Moreover, TEVAR patients presented strongly altered flow dynamics compared with controls: a reduced IRF from the distal AAo to the proximal descending aorta and an increased SFRR in the whole thoracic aorta. These differences persisted adjusting for cardiovascular risk factors and were independent of time elapsed since TEVAR implantation. CONCLUSION: At long term follow up, previously healthy patients who underwent TEVAR implantation following BTAI had increased diameter, length and volume of the ascending aorta, and increased aortic stiffness and abnormal flow patterns in the whole thoracic aorta compared with matched controls. Further studies should address whether these alterations have clinical implications.

Proximal aorta longitudinal strain predicts aortic root dilation rate and aortic events in Marfan syndrome.

AIMS: Life expectancy in Marfan syndrome patients has improved thanks to the early detection of aortic dilation and prophylactic aortic root surgery. Current international clinical guidelines support the use of aortic root diameter as a predictor of complications. However, other imaging markers are needed to improve risk stratification. This study aim to ascertain whether proximal aorta longitudinal and circumferential strain and distensibility assessed by cardiac magnetic resonance (CMR) predict the aortic root dilation rate and aortic events in Marfan syndrome. METHODS AND RESULTS: One hundred and seventeen Marfan patients with no previous aortic dissection, cardiac/aortic surgery, or moderate/severe aortic regurgitation were prospectively included in a multicentre protocol of clinical and imaging follow-up. At baseline, CMR was performed and proximal aorta longitudinal strain and ascending aorta circumferential strain and distensibility were obtained. During follow-up (85.7 [75.0-93.2] months), the annual growth rate of aortic root diameter was 0.62 ± 0.65 mm/year. Fifteen patients underwent elective surgical aortic root replacement and four presented aortic dissection. Once corrected for baseline clinical and demographic characteristics and aortic root diameter, proximal aorta longitudinal strain, but not circumferential strain and distensibility, was an independent predictor of the aortic root diameter growth rate (P = 0.001, P = 0.823, and P = 0.997, respectively), z-score growth rate (P = 0.013, P = 0.672, and P = 0.680, respectively), and aortic events (P = 0.023, P = 0.096, and P = 0.237, respectively). CONCLUSION: Proximal aorta longitudinal strain is independently related to the aortic root dilation rate and aortic events in addition to aortic root diameter, clinical risk factors, and demographic characteristics in Marfan syndrome patients.

3D axial and circumferential wall shear stress from 4D flow MRI data using a finite element method and a laplacian approach.

PURPOSE: To decompose the 3D wall shear stress (WSS) vector field into its axial (WSSA ) and circumferential (WSSC ) components using a Laplacian finite element approach. METHODS: We validated our method with in silico experiments involving different geometries and a modified Poiseuille flow. We computed 3D maps of the WSS, WSSA , and WSSC using 4D flow MRI data obtained from 10 volunteers and 10 patients with bicuspid aortic valve (BAV). We compared our method with the centerline method. The mean value, standard deviation, root mean-squared error, and Wilcoxon signed rank test are reported. RESULTS: We obtained an error <0.05% processing analytical geometries. We found good agreement between our method and the modified Poiseuille flow for the WSS, WSSA , and WSSC . We found statistically significance differences between our method and a 3D centerline method. In BAV patients, we found a 220% significant increase in the WSSC in the ascending aorta with respect to volunteers. CONCLUSION: We developed a novel methodology to decompose the WSS vector in WSSA and WSSC in 3D domains, using 4D flow MRI data. Our method provides a more robust quantification of WSSA and WSSC in comparison with other reported methods. Magn Reson Med 79:2816-2823, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Aortic flow patterns and wall shear stress maps by 4D-flow cardiovascular magnetic resonance in the assessment of aortic dilatation in bicuspid aortic valve disease.

BACKGROUND: In patients with bicuspid valve (BAV), ascending aorta (AAo) dilatation may be caused by altered flow patterns and wall shear stress (WSS). These differences may explain different aortic dilatation morphotypes. Using 4D-flow cardiovascular magnetic resonance (CMR), we aimed to analyze differences in flow patterns and regional axial and circumferential WSS maps between BAV phenotypes and their correlation with ascending aorta dilatation morphotype. METHODS: One hundred and one BAV patients (aortic diameter ≤ 45 mm, no severe valvular disease) and 20 healthy subjects were studied by 4D-flow CMR. Peak velocity, flow jet angle, flow displacement, in-plane rotational flow (IRF) and systolic flow reversal ratio (SFRR) were assessed at different levels of the AAo. Peak-systolic axial and circumferential regional WSS maps were also estimated. Unadjusted and multivariable adjusted linear regression analyses were used to identify independent correlates of aortic root or ascending dilatation. Age, sex, valve morphotype, body surface area, flow derived variables and WSS components were included in the multivariable models. RESULTS: The AAo was non-dilated in 24 BAV patients and dilated in 77 (root morphotype in 11 and ascending in 66). BAV phenotype was right-left (RL-) in 78 patients and right-non-coronary (RN-) in 23. Both BAV phenotypes presented different outflow jet direction and velocity profiles that matched the location of maximum systolic axial WSS. RL-BAV velocity profiles and maximum axial WSS were homogeneously distributed right-anteriorly, however, RN-BAV showed higher variable profiles with a main proximal-posterior distribution shifting anteriorly at mid-distal AAo. Compared to controls, BAV patients presented similar WSS magnitude at proximal, mid and distal AAo (p = 0.764, 0.516 and 0.053, respectively) but lower axial and higher circumferential WSS components (p < 0.001 for both, at all aortic levels). Among BAV patients, RN-BAV presented higher IRF at all levels (p = 0.024 proximal, 0.046 mid and 0.002 distal AAo) and higher circumferential WSS at mid and distal AAo (p = 0.038 and 0.046, respectively) than RL-BAV. However, axial WSS was higher in RL-BAV compared to RN-BAV at proximal and mid AAo (p = 0.046, 0.019, respectively). Displacement and axial WSS were independently associated with the root-morphotype, and circumferential WSS and SFRR with the ascending-morphotype. CONCLUSIONS: Different BAV-phenotypes present different flow patterns with an anterior distribution in RL-BAV, whereas, RN-BAV patients present a predominant posterior outflow jet at the sinotubular junction that shifts to anterior or right anterior in mid and distal AAo. Thus, RL-BAV patients present a higher axial WSS at the aortic root while RN-BAV present a higher circumferential WSS in mid and distal AAo. These results may explain different AAo dilatation morphotypes in the BAV population.

Pathophysiology of the ascending aorta: Impact of dilation and valve phenotype on large-scale blood flow coherence detected by 4D flow MRI.

BACKGROUND AND OBJECTIVE: The evidence on the role of hemodynamics in aorta pathophysiology has yet to be robustly translated into clinical applications, to improve risk stratification of aortic diseases. Motivated by the need to enrich the current understanding of the pathophysiology of the ascending aorta (AAo), this study evaluates in vivo how large-scale aortic flow coherence is affected by AAo dilation and aortic valve phenotype. METHODS: A complex networks-based approach is applied to 4D flow MRI data to quantify subject-specific AAo flow coherence in terms of correlation between axial velocity waveforms and the aortic flow rate waveform along the cardiac cycle. The anatomical length of persistence of such correlation is quantified using the recently proposed network metric average weighted curvilinear distance (AWCD). The analysis considers 107 subjects selected to allow an ample stratification in terms of aortic valve morphology, absence/presence of AAo dilation and of aortic valve stenosis. RESULTS: The analysis highlights that the presence of AAo dilation as well as of bicuspid aortic valve phenotype breaks the physiological AAo flow coherence, quantified in terms of AWCD. Of notice, it emerges that cycle-average blood flow rate and relative AAo dilation are main determinants of AWCD, playing opposite roles in promoting and hampering the persistence of large-scale flow coherence in AAo, respectively. CONCLUSIONS: The findings of this study can contribute to broaden the current mechanistic link between large-scale blood flow coherence and aortic pathophysiology, with the prospect of enriching the existing tools for the in vivo non-invasive hemodynamic risk assessment for aortic diseases onset and progression.

Quantitative Computed Tomography Angiography for the Evaluation of Valvular Fibrocalcific Volume in Aortic Stenosis.

BACKGROUND: Aortic stenosis (AS) is characterized by calcification and fibrosis. The ability to quantify these processes simultaneously has been limited with previous imaging methods. OBJECTIVES: The purpose of this study was to evaluate the aortic valve fibrocalcific volume by computed tomography (CT) angiography in patients with AS, in particular, to assess its reproducibility, association with histology and disease severity, and ability to predict/track progression. METHODS: In 136 patients with AS, fibrocalcific volume was calculated on CT angiograms at baseline and after 1 year. CT attenuation distributions were analyzed using Gaussian-mixture-modeling to derive thresholds for tissue types enabling the quantification of calcific, noncalcific, and fibrocalcific volumes. Scan-rescan reproducibility was assessed and validation provided against histology and in an external cohort. RESULTS: Fibrocalcific volume measurements took 5.8 ± 1.0 min/scan, demonstrating good correlation with ex vivo valve weight (r = 0.51; P < 0.001) and excellent scan-rescan reproducibility (mean difference -1%, limits of agreement -4.5% to 2.8%). Baseline fibrocalcific volumes correlated with mean gradient on echocardiography in both male and female participants (rho = 0.64 and 0.69, respectively; both P < 0.001) and in the external validation cohort (n = 66, rho = 0.58; P < 0.001). The relationship was driven principally by calcific volume in men and fibrotic volume in women. After 1 year, fibrocalcific volume increased by 17% and correlated with progression in mean gradient (rho = 0.32; P = 0.003). Baseline fibrocalcific volume was the strongest predictor of subsequent mean gradient progression, with a particularly strong association in female patients (rho = 0.75; P < 0.001). CONCLUSIONS: The aortic valve fibrocalcific volume provides an anatomic assessment of AS severity that can track disease progression precisely. It correlates with disease severity and hemodynamic progression in both male and female patients.

Mechanisms of Aortic Dilation in Patients With Bicuspid Aortic Valve: JACC State-of-the-Art Review.

Bicuspid aortic valve is the most common congenital heart disease and exposes patients to an increased risk of aortic dilation and dissection. Aortic dilation is a slow, silent process, leading to a greater risk of aortic dissection. The prevention of adverse events together with optimization of the frequency of the required lifelong imaging surveillance are important for both clinicians and patients and motivated extensive research to shed light on the physiopathologic processes involved in bicuspid aortic valve aortopathy. Two main research hypotheses have been consolidated in the last decade: one supports a genetic basis for the increased prevalence of dilation, in particular for the aortic root, and the second supports the damaging impact on the aortic wall of altered flow dynamics associated with these structurally abnormal valves, particularly significant in the ascending aorta. Current opinion tends to rule out mutually excluding causative mechanisms, recognizing both as important and potentially clinically relevant.

Network-Based Characterization of Blood Large-Scale Coherent Motion in the Healthy Human Aorta With 4D Flow MRI.

OBJECTIVE: The need for distilling the hemodynamic complexity of aortic flows into clinically relevant quantities resulted in a loss of the information hidden in 4D aortic fluid structures. To reduce information loss, this study proposes a network-based approach to identify and characterize in vivo the large-scale coherent motion of blood in the healthy human aorta. METHODS: The quantitative paradigm of the aortic flow as a "social network" was applied on 4D flow MRI acquisitions performed on forty-one healthy volunteers. Correlations between the aortic blood flow rate waveform at the proximal ascending aorta (AAo), assumed as one of the drivers of aortic hemodynamics, and the waveforms of the axial velocity in the whole aorta were used to build "one-to-all" networks. The impact of the driving flow rate waveform and of aortic geometric attributes on the transport of large-scale coherent fluid structures was investigated. RESULTS: The anatomical length of persistence of large-scale coherent motion was the 29.6% of the healthy thoracic aorta length (median value, IQR 23.1%-33.9%). Such length is significantly influenced by the average and peak-to-peak AAo blood flow rate values, suggesting a remarkable inertial effect of the AAo flow rate on the transport of large-scale fluid structures in the distal aorta. Aortic geometric attributes such as curvature, torsion and arch shape did not influence the anatomical length of persistence. CONCLUSION: The proposed in vivo approach allowed to quantitatively characterize the transport of large-scale fluid structures in the healthy aorta, strengthening the definition of coherent hemodynamic structures and identifying flow inertia rather than geometry as one of its main determinants. SIGNIFICANCE: The findings on healthy aortas may be used as reference values to investigate the impact of aortic disease or implanted devices in disrupting/restoring the physiological spatiotemporal coherence of large-scale aortic flow.