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.

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.

Changes in echocardiographic parameters over time in paradoxical low-flow low-gradient aortic stenosis.

AIMS: To assess the progression of the disease and evolution of the main echocardiographic variables for quantifying AS in patients with severe low-flow low-gradient (LFLG) AS compared to other severe AS subtypes. METHODS AND RESULTS: Longitudinal, observational, multicenter study including consecutive asymptomatic patients with severe AS (aortic valve area, AVA < 1.0 cm²) and normal left ventricle ejection fraction (LVEF ≥ 50%). Patients were classified according to baseline echocardiography into: HG (high gradient; mean gradient ≥ 40 mmHg), NFLG (normal-flow low-gradient; mean gradient < 40 mmHg, indexed systolic volume (SVi) > 35mL/m2), or LFLG (mean gradient < 40 mmHg, SVi ≤ 35 mL/m²). AS progression was analyzed by comparing patients' baseline measurements and their last follow-up measurements or those taken prior to aortic valve replacement (AVR). Of the 903 included patients, 401 (44.4%) were HG, 405 (44.9%) NFLG, and 97 (10.7%) LFLG. Progression of the mean gradient in a linear mixed regression model was greater in low-gradient groups: LFLG vs. HG (regression coefficient 0.124, P = 0.005) and NFLG vs. HG (regression coefficient 0.068, P = 0.018). No differences were observed between the LFLG and NFLG groups (regression coefficient 0.056, P = 0.195). However, AVA reduction was slower in the LFLG group compared to the NFLG (P < 0.001). During follow-up, in conservatively-managed patients, 19.1% (n = 9) of LFLG patients evolved to having NFLG AS and 44.7% (n = 21) to having HG AS. In patients undergoing AVR, 58.0% (n = 29) of LFLG baseline patients received AVR with a HG AS. CONCLUSION: LFLG AS shows an intermediate AVA and gradient progression compared to NFLG and HG AS. The majority of patients initially classified as having LFLG AS changed over time to having other severe forms of AS, and most of them received AVR with a HG AS.

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.

Fully Three-Dimensional Hemodynamic Characterization of Altered Blood Flow in Bicuspid Aortic Valve Patients With Respect to Aortic Dilatation: A Finite Element Approach.

Background and Purpose: Prognostic models based on cardiovascular hemodynamic parameters may bring new information for an early assessment of patients with bicuspid aortic valve (BAV), playing a key role in reducing the long-term risk of cardiovascular events. This work quantifies several three-dimensional hemodynamic parameters in different patients with BAV and ranks their relationships with aortic diameter. Materials and Methods: Using 4D-flow CMR data of 74 patients with BAV (49 right-left and 25 right-non-coronary) and 48 healthy volunteers, aortic 3D maps of seventeen 17 different hemodynamic parameters were quantified along the thoracic aorta. Patients with BAV were divided into two morphotype categories, BAV-Non-AAoD (where we include 18 non-dilated patients and 7 root-dilated patients) and BAV-AAoD (where we include the 49 patients with dilatation of the ascending aorta). Differences between volunteers and patients were evaluated using MANOVA with Pillai's trace statistic, Mann-Whitney U test, ROC curves, and minimum redundancy maximum relevance algorithm. Spearman's correlation was used to correlate the dilation with each hemodynamic parameter. Results: The flow eccentricity, backward velocity, velocity angle, regurgitation fraction, circumferential wall shear stress, axial vorticity, and axial circulation allowed to discriminate between volunteers and patients with BAV, even in the absence of dilation. In patients with BAV, the diameter presented a strong correlation (> |+/-0.7|) with the forward velocity and velocity angle, and a good correlation (> |+/-0.5|) with regurgitation fraction, wall shear stress, wall shear stress axial, and vorticity, also for morphotypes and phenotypes, some of them are correlated with the diameter. The velocity angle proved to be an excellent biomarker in the differentiation between volunteers and patients with BAV, BAV morphotypes, and BAV phenotypes, with an area under the curve bigger than 0.90, and higher predictor important scores. Conclusions: Through the application of a novel 3D quantification method, hemodynamic parameters related to flow direction, such as flow eccentricity, velocity angle, and regurgitation fraction, presented the best relationships with a local diameter and effectively differentiated patients with BAV from healthy volunteers.

Prognosis of Paradoxical Low-Flow Low-Gradient Aortic Stenosis: A Severe, Non-critical Form, With Surgical Treatment Benefits.

Objectives: To determine the risk of mortality and need for aortic valve replacement (AVR) in patients with low-flow low-gradient (LFLG) aortic stenosis (AS). Methods: A longitudinal multicentre study including consecutive patients with severe AS (aortic valve area [AVA] < 1.0 cm2) and normal left ventricular ejection fraction (LVEF). Patients were classified as: high-gradient (HG, mean gradient ≥ 40 mmHg), normal-flow low-gradient (NFLG, mean gradient < 40 mmHg, indexed systolic volume (SVi) > 35 ml/m2) and LFLG (mean gradient < 40 mmHg, SVi ≤ 35 ml/m2). Results: Of 1,391 patients, 147 (10.5%) had LFLG, 752 (54.1%) HG, and 492 (35.4%) NFLG. Echocardiographic parameters of the LFLG group showed similar AVA to the HG group but with less severity in the dimensionless index, calcification, and hypertrophy. The HG group required AVR earlier than NFLG (p < 0.001) and LFLG (p < 0.001), with no differences between LFLG and NFLG groups (p = 0.358). Overall mortality was 27.7% (CI 95% 25.3-30.1) with no differences among groups (p = 0.319). The impact of AVR in terms of overall mortality reduction was observed the most in patients with HG (hazard ratio [HR]: 0.17; 95% CI: 0.12-0.23; p < 0.001), followed by patients with LFLG (HR: 0.25; 95% CI: 0.13-0.49; p < 0.001), and finally patients with NFLG (HR: 0.29; 95% CI: 0.20-0.44; p < 0.001), with a risk reduction of 84, 75, and 71%, respectively. Conclusions: Paradoxical LFLG AS affects 10.5% of severe AS, and has a lower need for AVR than the HG group and similar to the NFLG group, with no differences in mortality. AVR had a lower impact on LFLG AS compared with HG AS. Therefore, the findings of the present study showed LFLG AS to have an intermediate clinical risk profile between the HG and NFHG groups.

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.

Unraveling Bicuspid Aortic Valve Enigmas by Multimodality Imaging: Clinical Implications.

Multimodality imaging is the basis of the diagnosis, follow-up, and surgical management of bicuspid aortic valve (BAV) patients. Transthoracic echocardiography (TTE) is used in our clinical routine practice as a first line imaging for BAV diagnosis, valvular phenotyping and function, measurement of thoracic aorta, exclusion of other aortic malformations, and for the assessment of complications such are infective endocarditis and aortic. Nevertheless, TTE is less useful if we want to assess accurately other aortic segments such as mid-distal ascending aorta, where computed tomography (CT) and magnetic resonance (CMR) could improve the precision of aorta size measurement by multiplanar reconstructions. A major advantage of CT is its superior spatial resolution, which affords a better definition of valve morphology and calcification, accuracy, and reproducibility of ascending aorta size, and allows for coronary artery assessment. Moreover, CMR offers the opportunity of being able to evaluate aortic functional properties and blood flow patterns. In this setting, new developed sequences such as 4D-flow may provide new parameters to predict events during follow up. The integration of all multimodality information facilitates a comprehensive evaluation of morphologic and dynamic features, stratification of the risk, and therapy guidance of this cohort of patients.

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.

Aortic flow dynamics and stiffness in Loeys-Dietz syndrome patients: a comparison with healthy volunteers and Marfan syndrome patients.

AIMS: To assess aortic flow and stiffness in patients with Loeys-Dietz syndrome (LDS) by 4D flow and cine cardiovascular magnetic resonance (CMR) and compare the results with those of healthy volunteers (HV) and Marfan syndrome (MFS) patients. METHODS AND RESULTS: Twenty-one LDS and 44 MFS patients with no previous aortic dissection or surgery and 35 HV underwent non-contrast-enhanced 4D flow CMR. In-plane rotational flow (IRF), systolic flow reversal ratio (SFRR), and aortic diameters were obtained at 20 planes from the ascending (AAo) to the proximal descending aorta (DAo). IRF and SFRR were also quantified for aortic regions (proximal and distal AAo, arch and proximal DAo). Peak-systolic wall shear stress (WSS) maps were also estimated. Aortic stiffness was quantified using pulse wave velocity (PWV) and proximal AAo longitudinal strain. Compared to HV, LDS patients had lower rotational flow at the distal AAo (P = 0.002), arch (P = 0.002), and proximal DAo (P < 0.001) even after adjustment for age, stroke volume, and local diameter. LDS patients had higher SFRR in the proximal DAo compared to both HV (P = 0.024) and MFS patients (P = 0.015), even after adjustment for age and local diameter. Axial and circumferential WSS in LDS patients were lower than in HV. AAo circumferential WSS was lower in LDS compared to MFS patients. AAo and DAo PWV and proximal AAo longitudinal strain revealed stiffer aortas in LDS patients compared to HV (P = 0.007, 0.005, and 0.029, respectively) but no differences vs. MFS patients. CONCLUSION: Greater aortic stiffness as well as impaired IRF and WSS were present in LDS patients compared to HV. Conversely, similar aortic stiffness and overlapping aortic flow features were found in Loeys-Dietz and Marfan patients.

Wall Shear Stress Predicts Aortic Dilation in Patients With Bicuspid Aortic Valve.

OBJECTIVES: This study sought to assess the predictive value of wall shear stress (WSS) for colocalized ascending aorta (AAo) growth rate (GR) in patients with bicuspid aortic valve (BAV). BACKGROUND: BAV is associated with AAo dilation, but there is limited knowledge about possible predictors of aortic dilation in patients with BAV. An increased WSS has been related to aortic wall damage in patients with BAV, but no previous prospective study tested its predictive value for dilation rate. Recently, a registration-based technique for the semiautomatic mapping of aortic GR has been presented and validated. METHODS: Forty-seven patients with BAV free from valvular dysfunction prospectively underwent 4-dimensional flow cardiac magnetic resonance to compute WSS and subsequent follow-up with 2 electrocardiogram-gated high-resolution contrast-enhanced computed tomography angiograms for GR assessment. RESULTS: During a median follow-up duration of 43 months, mid AAo GR was 0.24 mm/year. WSS and its circumferential component showed statistically significant association with mid AAo GR in bivariate (P = 0.049 and P = 0.014, respectively) and in multivariate analysis corrected for stroke volume and either baseline AAo diameter (P = 0.046 and P = 0.014, respectively) or z-score (P = 0.036 and P = 0.012, respectively). GR mapping further detailed that GR was heterogeneous in the AAo and that circumferential WSS, but not WSS magnitude, showed statistically significant positive associations with GR in the regions with the fastest growth. CONCLUSIONS: 4D flow cardiac magnetic resonance-derived WSS and, in particular, its circumferential component predict progressive dilation of the ascending aorta in patients with BAV. Thus, the assessment of WSS may be considered in the follow-up of these patients.

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.

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.

Diagnostic value of quantitative parameters for myocardial perfusion assessment in patients with suspected coronary artery disease by single- and dual-energy computed tomography myocardial perfusion imaging.

PURPOSE: To compare performance of visual and quantitative analyses for detecting myocardial ischaemia from single- and dual-energy computed tomography (CT) in patients with suspected coronary artery disease (CAD). METHODS: Eighty-four patients with suspected CAD were scheduled for dual-energy cardiac CT at rest (CTA) and pharmacological stress (CTP). Myocardial CT perfusion was analysed visually and using three parameters: mean attenuation density (MA), transmural perfusion ratio (TPR) and myocardial perfusion reserve index (MPRI), on both single-energy CT and CT-based iodine images. Significant CAD was defined in AHA-segments by concomitant myocardial hypoperfusion identified visually or quantitatively (parameter < threshold) and coronary stenosis detected by CTA. Single-photon emission CT and invasive coronary angiography were used as reference. Perfusion-parameter cut-off values were calculated in a randomly-selected subgroup of 30 patients. RESULTS: The best-performing thresholds for TPR, MPRI and MA were 0.96, 23 and 0.5 for single-energy CT and 0.97, 47 and 0.3 for iodine imaging. For both CT-imaging modalities, TPR yielded the highest area under receiver operating characteristic curve (AUC) (0.99 and 0.97 for single-energy CT and iodine imaging, respectively, in vessel-based analysis) compared to visual analysis, MA and MPRI. Visual interpretation on iodine imaging resulted in higher AUC compared to that on single-energy CT in per-vessel (AUC: 0.93 vs 0.86, respectively) and per-patient (0.94 vs 0.93) analyses. CONCLUSION: Transmural perfusion ratio on both CT-imaging modalities is the best-performing parameter for detecting myocardial ischaemia compared to visual method and other perfusion parameters. Visual analysis on CT-based iodine imaging outperforms that on single-energy CT.

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.

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.

Increased rotational flow in the proximal aortic arch is associated with its dilation in bicuspid aortic valve disease.

AIMS: Aortic dilation in bicuspid aortic valve (BAV) might extend to the proximal arch. Arch flow dynamics and their relationship with this segment dilation are still unexplored. Using 4D-flow cardiovascular magnetic resonance, we analysed flow dynamics in the arch for each BAV morphotype and their association with this segment dilation. METHODS AND RESULTS: One hundred and eleven BAV patients (aortic diameters ≤55 mm, non-severe valvular disease), 21 age-matched tricuspid aortic valve (TAV) patients with dilated arch and 24 healthy volunteers (HV) underwent 4D-flow. BAV were classified per fusion morphotype: 75% right-left (RL-BAV), and per arch dilation: 57% dilated, mainly affecting the right-noncoronary (RN) BAV (86% dilated vs. 47% in RL-BAV). Peak velocity, jet angle, normalized displacement, in-plane rotational flow (IRF), wall shear stress, and systolic flow reversal ratio (SFRR) were calculated along the thoracic aorta. ANCOVA and multivariate linear regression analyses were used to identify correlates of arch dilation. BAV had higher rotational flow and eccentricity than TAV in the proximal arch. Dilated compared with non-dilated BAV had higher IRF being more pronounced in the RN-morphotype. RN-BAV, IRF, and SFRR were independently associated with arch dilation. Aortic stenosis and male sex were independently associated with arch dilation in RL-BAV. Flow parameters associated with dilation converged to the values found in HV in the distal arch. CONCLUSION: Increased rotational flow could explain dilation of the proximal arch in RN-BAV and in RL-BAV patients of male sex and with valvular stenosis. These patients may benefit from a closer follow-up with cardiac magnetic resonance or computed tomography.