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.

Sport PRactice and its Effects on aortic size and valve function in bicuspid Aortic valve Disease: a cross-sectional report from the SPREAD study.

OBJECTIVE: Concerns exist about the possible detrimental effects of exercise training on aortic size and valve function in individuals with bicuspid aortic valve (BAV). This multicentre international study aimed to determine the characteristics of aortic size and valve function in athletes versus non-athletes with BAV and athletes with tricuspid aortic valve (TAV). METHODS: We enrolled competitive athletes with BAV and age- and sex-matched athletes with TAV and non-athletes with BAV. We assessed valve function, aortic size and biventricular measures using echocardiography. Individuals with established moderate-severe AV stenosis, regurgitation or significant aortic dilation were excluded from the study. RESULTS: The study population comprised 504 participants: 186 competitive athletes with BAV (84% males; age 30±11 years), 193 competitive athletes with TAV and 125 non-athletes with BAV. The aortic annulus was greater in athletes with BAV than athletes with TAV and non-athletes with BAV (p<0.001). Both athletic and non-athletic individuals with BAV had greater sinuses of Valsalva, sino-tubular junction and ascending aorta diameters than athletes with TAV (p<0.001). However, no significant differences were found between athletes and non-athletes with BAV. Left ventricular index volumes and mass were greater in athletes with BAV than in the other two groups (p<0.001). Individuals with BAV (athletes and non-athletes) had greater mean gradients than TAV athletes. CONCLUSION: This multicentre international study demonstrates no differences between athletes with BAV and non-athletes with BAV regarding aortic valve function or aortic dimensions. However, athletes with BAV have larger aortic diameters and a relatively worse valvular function than athletes with TAV.

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.

Echocardiographic findings on aortic stenosis: an observational, prospective, and multi-center registry.

BACKGROUND: The aim of this aortic stenosis registry was to investigate the changes of routine echocardiographic indices and strain in patients with moderate-to-severe aortic stenosis over a 6-month follow-up period. METHODS: Our aortic stenosis registry is observational, prospective, multicenter registry of nine countries, with 197 patients with aortic valve area less than 1.5 cm2. The enrolment took place from January to August 2017. We excluded patients with uncontrolled atrial arrhythmias, pulmonary hypertension or cardiomyopathies, as well as those with hemodynamically significant valvular disease other than aortic stenosis. We included patients who did not require intervention and who had a complete follow-up study. RESULTS: In patients with preserved ejection fraction, left ventricular mass has significantly increased between baseline and follow-up studies (218 ± 34 grams vs 253 ± 29 grams, p = 0.02). However, when indexed to body surface area, there was no significant difference. Left ventricular global longitudinal strain significantly decreased (-19.7 ± -4.8 vs (-16.4 vs -3.8, p = 0.01). Left atrial volume was significantly higher at follow-up (p = 0.035). Right ventricular basal diameter and mid-cavity diameter were greater at the follow-up (p = 0.04 and p = 0.035, respectively). Patients with low-flow low-gradient aortic stenosis had significantly lower global longitudinal strain (-12.3% ± -3.9% vs -19.7% ± -4.8%, p = 0.01). CONCLUSION: Left atrial dilatation is one of the first changes to take place in low-flow low-gradient aortic stenosis patients even when left ventricular dimensions and function remains intact. Global longitudinal strain is an important determinant of left ventricular systolic and diastolic dysfunction and right ventricular function is an important parameter of aortic stenosis assessment. Accordingly, our registry has further shed the light on these indices role as multisite follow-up of aortic stenosis.