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Background The effect of FBN1 mutation type on the severity of cardiovascular manifestations in patients with Marfan syndrome (MFS) has been reported with disparity results. Objectives This study aims to determine the impact of the FBN1 mutation type on aortic diameters, aortic dilation rates and on cardiovascular events (ie, aortic dissection and cardiovascular mortality). Methods MFS patients with a pathogenic FBN1 mutation followed at two specialised units were included. FBN1 mutations were classified as being dominant negative (DN; incorporation of non-mutated and mutated fibrillin-1 in the extracellular matrix) or having haploinsufficiency (HI; only incorporation of non-mutated fibrillin-1, thus a decreased amount of fibrillin-1 protein). Aortic diameters and the aortic dilation rate at the level of the aortic root, ascending aorta, arch, descending thoracic aorta and abdominal aorta by echocardiography and clinical endpoints comprising dissection and death were compared between HI and DN patients. Results Two hundred and ninety patients with MFS were included: 113 (39%) with an HI- FBN1 mutation and 177 (61%) with a DN- FBN1 . At baseline, patients with HI- FBN1 had a larger aortic root diameter than patients with DN- FBN1 (HI: 39.3±7.2 mm vs DN: 37.3±6.8 mm, p=0.022), with no differences in age or body surface area. After a mean follow-up of 4.9±2.0 years, aortic root and ascending dilation rates were increased in patients with HI- FBN1 (HI: 0.57±0.8 vs DN: 0.28±0.5 mm/year, p=0.004 and HI: 0.59±0.9 vs DN: 0.30±0.7 mm/year, p=0.032, respectively). Furthermore, patients with HI- FBN1 tended to be at increased risk for the combined endpoint of dissection and death compared with patients with DN- FBN1 (HR: 3.3, 95% CI 1.0 to 11.4, p=0.060). Conclusions Patients with an HI mutation had a more severely affected aortic phenotype, with larger aortic root diameters and a more rapid dilation rate, and tended to have an increased risk of death and dissections compared with patients with a DN mutation.

Acute aortic syndromes include a variety of overlapping clinical and anatomic diseases. Intramural hematoma (IMH), penetrating atherosclerotic ulcer (PAU), and aortic dissection can occur as isolated processes or can be found in association. All these entities are potentially life threatening, so prompt diagnosis and treatment is of paramount importance. IMH and PAU affect patients with atherosclerotic risk factors and are located in the descending aorta in 60–70% of cases. IMH diagnosis can be correctly made in most cases. Aortic ulcer is a morphologic entity which comprises several entities—the differential diagnosis includes PAU, focal intimal disruptions (FID) in the context of IMH evolution and ulcerated atherosclerotic plaque. The pathophysiologic mechanism, evolution and prognosis differ somewhat between these entities. However, most PAU are diagnosed incidentally outside the acute phase. Persistent pain despite medical treatment, hemodynamic instability, maximum aortic diameter (MAD) >55 mm, significant periaortic hemorrhage and FID in acute phase of IMH are predictors of acute-phase mortality. In these cases, TEVAR or open surgery should be considered. In non-complicated IMH or PAU, without significant aortic enlargement, strict control of cardiovascular risk factors and frequent follow-up imaging appears to be a safe management strategy.

Purpose To determine the normal size and wall thickness of the ascending thoracic aorta (AA) and its relationship with cardiovascular risk factors in a large population-based study. Materials and Methods The mean AA luminal diameter was measured in 3573 Multi-Ethnic Study of Atherosclerosis (MESA) participants (age: 45–84 years), using gradient echo phase contrast cine MRI. Multiple linear regression models were used to evaluate the associations between risk factors and AA diameter. The median and upper normal limit (95th percentile) was defined in a “healthy” subgroup as well as AA wall thickness. Results The upper limits of body surface area indexed AA luminal diameter for age categories of 45–54, 55–64, 65–74, and 75–84 years are 21, 22, 22, and 28 mm/m2 in women and 20, 21, 22, 23 mm/m2 in men, respectively. The mean AA wall thickness was 2.8 mm. Age, gender, and body surface area were major determinants of AA luminal diameter (∼+1 mm/10 years; ∼+1.9 mm in men than women; ∼+1 mm/ 0.23 m2; P

Background— This study sought to assess cross-sectional associations of aortic stiffness assessed by magnetic resonance imaging with left ventricular (LV) remodeling and myocardial deformation in the Multi-Ethnic Study of Atherosclerosis (MESA). Methods and Results— Aortic arch pulse wave velocity (PWV) was measured with phase contrast cine magnetic resonance imaging. LV circumferential strain (Ecc), torsion, and early diastolic strain rate were determined by tagged magnetic resonance imaging. Multivariable linear regression models were used to adjust for demographics and cardiovascular risk factors. Of 2093 participants, multivariable linear regression models demonstrated that higher arch PWV was associated with higher LV mass index ( B =0.53 per 1 SD increase for log-transformed PWV, P B =0.015, P B =−0.84; P B =0.55; P B =−0.11; P B =−0.003; P B =0.02; P B =0.60; P B =−0.45; P B =0.49; P B =−1.21; P B =−0.17; P Conclusions— Higher arch PWV is associated with LV remodeling, and reduced LV systolic and diastolic function in a large multiethnic population. Greater aortic arch stiffness is associated with concentric LV remodeling and relatively preserved LVEF with maintained torsion in women, whereas greater aortic arch stiffness is associated with greater LV dysfunction demonstrated as impaired Ecc, torsion, and LVEF, with less concentric LV remodeling in men.

Background: Aortic root dilation and type A aortic dissection are the most common cardiovascular complications of Marfan syndrome (MFS). Current clinical management of MFS patients relies on a close follow-up of aortic root diameter and preventive aortic root surgery in case of severe or fast-progressing dilation. However, as the capacity of aortic diameter to predict type A aortic dissection is limited, new non-invasive biomarkers to improve risk stratification are needed. We investigated the capacity of proximal aorta circumferential and longitudinal strain and ascending aorta distensibility to predict aortic root diameter dilation and occurrence of major cardiovascular events in Marfan patients. Methods: Eighty-seven Marfan patients without previous cardiac/aortic surgery or dissection were prospectively included in a multicenter follow-up. Proximal aorta longitudinal and circumferential strain and distensibility were computed from baseline CMR. Results: During a follow-up of 81.6 ± 17 months, 11 patients underwent elective aortic root replacement, and 2 experienced type A aortic dissections. Mean dilation rate was 0.65 ± 0.67 mm/year and z-score growth rate 0.07 ± 0.13 1/year. In multivariable analysis, proximal aorta longitudinal strain but not circumferential strain and distensibility were independent predictors of diameter growth-rate (p = 0.001, p = 0.385 and p = 0.381, respectively), z-score growth-rate (p = 0.018, p = 0.515 and p = 0.484, respectively) and major cardiovascular events (p = 0.018, p = 0.064 and p = 0.205, respectively) corrected for demographic and clinical characteristics and baseline aortic root diameter. Conclusions: In Marfan syndrome, proximal aorta longitudinal strain is an independent predictor of aortic root dilation and major cardiovascular events beyond aortic root diameter and established risk factors.

We are pleased to learn of the interest demonstrated in our recent work published in JACC by Drs. Galderisi and Trimarco who raise a very important issue related to the mechanisms underlying cumulative hypertension–related myocardial dysfunction demonstrated by our group on behalf of the

Background: Major aortic remodeling processes ensue with aging. Information on the patterns of the longitudinal changes in aortic geometry is essential to understand the dramatic hemodynamic changes observed with aging. Methods: Data from 1396 MESA participants who had aortic magnetic resonance imaging in 2000-02 and 2010-12 were analyzed. Ascending aorta diastolic diameter (Add), strain (Astr), arch length (Alen) and their rates of change (Δ) were determined using the validated automated software (ARTFUN, INSERM LIB). Multivariate analysis was performed to examine the correlates of the changes of these parameters. Least square means of Add and Alen adjusted for body surface area were plotted against age for those not on anti-HTN drugs on either visit (n=590). Results: The main correlates of increased ΔAdd, and ΔAlen were male gender, smaller baseline Add, and Alen, lower PP, greater MAP and ΔMAP. Increased ΔAdd was also associated with greater baseline Astr and with not being on anti-HTN drugs, while greater ΔAlen, was associated with smaller ΔPP in women only (P Conclusion: Gender, baseline blood pressure parameters and baseline aortic geometry and elasticity are the main determinants of aortic remodeling. Aortic elongation and dilatation follow different trajectories and vary by gender. In contrast to men, aortic dilation in women was minimal beyond the 7th decade and aortic elongation was the main remodeling process and was inversely associated with changes in PP. Gender differences in aortic remodeling might explain the increased pulsatility observed in women with advancing aging.

Transthoracic echocardiography (TTE), multidetector computed tomography (MDCT), and magnetic resonance imaging (MRI) have been widely used to monitor aortic diameters, with no consensus as to the best measurement approach. Thus, the aim of this study was to establish the best measurement methods by two-dimensional (2D) TTE, MDCT, and MRI to achieve comparable aortic diameters.One hundred forty patients with severe aortic valvular disease or aortic dilatation were prospectively evaluated using 2D TTE and MDCT (n = 70) or MRI (n = 70). The aorta was measured at three different levels: sinuses of Valsalva, sinotubular junction, and ascending aorta. Three different measurements were made by 2D TTE-inner edge to inner edge, leading edge to leading edge (L-L), and outer edge to outer edge-and then compared with the inner edge-to-inner edge and outer edge-to-outer edge measurements of cusp-to-cusp and cusp-to-commissure diameters by MDCT or MRI. Inter- and intraobserver variability was analyzed.Aortic diameters by 2D TTE, MDCT, and MRI showed excellent inter- and intraobserver variability using all conventions. Significant underestimation was observed of all aortic diameters assessed by 2D TTE using the inner edge-to-inner edge convention compared with those obtained by MDCT or MRI (P .0001). However, excellent accuracy was observed by 2D TTE when the L-L convention was used and compared with the internal diameter by MDCT and MRI (mean differences, 0.6 ± 2.6 mm [P = .158] for MDCT and 0.4 ± 3.5 mm [P = .852] for MRI). Cusp-to-cusp diameters were slightly larger than cusp-to-commissure diameters. The diameter by 2D TTE using the L-L convention correlated best with the noncoronary cusp-to-right coronary cusp diameter determined by both MDCT and MRI.Aortic root and ascending aortic diameters measured by 2D TTE using the L-L convention showed accurate and reproducible values compared with internal diameters assessed by MDCT or MRI. This approach permits a multimodality follow-up of patients with aortic diseases and avoids disparities in measurements obtained by different conventions.

Background: The carotid-femoral pulse wave velocity (PWV) assessed by tonometry is predictive of future cardiovascular disease (CVD) events. However, the predictive value of aortic arch PWV assessed by MRI for mortality and CVD events has not been established in the general population. The aim of this study was to evaluate the association of arch PWV with all-cause mortality and incident CVD events over 10 years in the Multi-Ethnic Study of Atherosclerosis (MESA). Method: Aortic arch PWV was measured using phase contrast (PC) cine MRI at the level of the pulmonary artery bifurcation for transit time and black blood sagittal image for transit length at baseline in 3537 MESA participants free of overt CVD. Cox regression was used to evaluate the risk of death and incident CVD in relation to arch PWV adjusted for age, gender, race, and CV risk factors. Results: At baseline, participants were aged 62 ± 10 years; 53% women; 36% White, 15% Chinese, 29% African American, 20% Hispanic; 45% hypertension. The mean value of arch PWV was 9.0 ± 6.3 m/s. There were 418 deaths and 236 CVD events over 10-year follow-up. There was significant interaction between arch PWV and mean age for both outcomes, so we stratified by age; below 60 years (n=1503) and above 60 years (n=2034). Increased PWV had a trend with increased risk of all-cause mortality with a hazard ratio for the 4th vs 1st quartile of PWV of 2.1 (95%CI: 1.0-4.6, p=0.05) independent of risk factors in age below 60 years group. There was no significant association of PWV with incident CVD in age below 60 years after adjustment for risk factors. In age above 60 years group, increased PWV was not associated with either all-cause mortality or incident CVD events in univariate or multivariate analysis (Table). Conclusion: Arch PWV assessed by MRI is not a significant predictor of all-cause mortality and incident CVD events among individuals without overt CVD.

Purpose: Different altered flow dynamics may influence ascending aorta (AAo) dilation morphotypes in bicuspid aortic valve (BAV) (1). Using 4D-flow CMR, we aimed to identify flow variables related to root or ascending dilation in BAV. Methods: One-hundred and one BAV patients (no severe valvular disease, aortic diameters 2. Univariate and multivariate linear regression were used to identify factors related to dilation. ROC curves were performed to assess the relationship between variables obtained in the multivariate analysis and dilation morphotypes. Results: Fusion phenotype was right-left (RL) in 78 patients, and right-non coronary (RN) in 23. Dilation morphotype was non-dilated in 24 patients, root in 11 and ascending in 66. On univariate analysis, BAV phenotype (RN), displacement and circumferential WSS presented the highest odds ratios (Table). On multivariate analysis, sex (male), proximal velocity and axial WSS were related to root morphotype (AUC 0.91, P < 0.001), while RN-BAV, distal IRF, and mid-AAo SFRR and circumferential WSS were related to ascending morphotype (AUC 0.81, P < 0.001) (Table and Figure). Univariate analysis of aortic dilation Multivariate analysis of aortic dilation Root morphotype Ascending morphotype Odds Ratio P-value Odds Ratio P-value Odds Ratio P-value BAV phenotype (RL/RN) 3.23 0.02 1.33 0.008 Sex (Male) 1.10 0.02 4.67 0.005 Prox Peak velocity 1.02 0.028 1.10 0.043 Jet angle 1.05 0.037 Displacement 3.56 0.001 1.11 0.021 IRF 1.01 0.002 WSSaxial 1.20 0.003 7.64 0.008 WSSCireumf 1.65 0.05 Mid Jet angle 1.07 0.006 Displacement 2.46 0.002 IRF 1.01 0.007 SFRR (%) 1.20 0.001 1.2

Methods 423 studies by 1.5-T whole-body MRI were analyzed. CMRI protocol included cardiac function and late gadolinium enhancement. Only participants with no findings of myocardial scar were included. AWT images were obtained using a double inversion recovery black-blood fast spin-echo sequence and phase contrast cine gradient echo sequence was used to evaluate aortic stiffness. Aortic sagittal oblique plane with black blood sequence was acquired to position the aortic imaging and allowed for the measurement of the distance between the ascending and descending aorta. Images of the ascending and descending aorta were obtained in the transverse plane at the level of the right pulmonary artery perpendicular to the vessel lumen. The thickness of the midthoracic descending aortic wall was measured using electronic calipers at 4 standard positions: 12, 3, 6, and 9 o’clock (QMASS 7.2). The average value of these 4 measurements was calculated. Distensibiliy of the ascending aorta and PWV were performed using validated automated software (ARTFUN. INSERM U678). Results Table 1 lists demographics, AWT, distensibility and PWV stratified by hypertension status. AWT was not different (p = 0.35) but distensibility was lower (p < 0.001) and PWV was higher (p = 0.012) in hypertension. Linear regression analyses (Table 2) demonstrate distensibility was significantly correlated to AWT in the cohort without hypertension. AWT was a predictor for PWV with the basic adjustment (Model 1) in the hypertension group, but this correlation diminished after adjusting for more variables (Model 2, only systolic blood pressure and black race were positively correlated to PWV significantly).

To determine the normal size and wall thickness of the ascending thoracic aorta (AA) and its relationship with cardiovascular risk factors in a large population-based study.The mean AA luminal diameter was measured in 3573 Multi-Ethnic Study of Atherosclerosis (MESA) participants (age: 45-84 years), using gradient echo phase contrast cine MRI. Multiple linear regression models were used to evaluate the associations between risk factors and AA diameter. The median and upper normal limit (95th percentile) was defined in a "healthy" subgroup as well as AA wall thickness.The upper limits of body surface area indexed AA luminal diameter for age categories of 45-54, 55-64, 65-74, and 75-84 years are 21, 22, 22, and 28 mm/m(2) in women and 20, 21, 22, 23 mm/m(2) in men, respectively. The mean AA wall thickness was 2.8 mm. Age, gender, and body surface area were major determinants of AA luminal diameter (∼+1 mm/10 years; ∼+1.9 mm in men than women; ∼+1 mm/ 0.23 m(2) ; P 0.001). The AA diameter in hypertensive subjects was +0.9 mm larger than in normotensives (P 0.001).AA diameter increases gradually with aging for both genders among all race/ethnicities. The normal value of AA diameter is provided.

La valvula aortica bicuspide (VAB) es la anomalia cardiaca congenita mas comun, con una incidencia de un 0,5-1,4% de la poblacion. De forma esporadica, esta anomalia se transmite geneticamente segun un patron de herencia autosomico dominante, con un predominio en varones de 3:1. La VAB es una entidad clinicamente relevante, no solo por las complicaciones relacionadas con la valvula (disfuncion valvular, endocarditis infecciosa), sino tambien por su asociacion con muchas anomalias vasculares como la dilatacion aortica (fig. 1A). La prevalencia registrada de dilatacion aortica asociada a VAB oscila entre el 33 y el 80%. Esta variacion se atribuye a diferencias en los umbrales utilizados para definir la dilatacion, los valores normales para edad y superficie corporal y la region de aorta analizada. Se han descrito diferentes tipos de aneurisma aortico en funcion de la region afectada, y la dilatacion de la aorta ascendente media (dilatacion aislada de la porcion tubular de la aorta ascendente) es el patron observado mas frecuentemente. Se ha relacionado la edad y la morfologia valvular con las dimensiones de la aorta ascendente (AoAsc), aunque el papel de la morfologia no esta claramente definido.

Background Aortic stiffness parameters have been studied as a risk marker corollary to traditional risk markers used in Framingham risk stratification. Differences in risk prediction ability have been noted between pulse wave velocity (PWV) and other parameters. Here, the relationship of PWV and aortic distensibility with left ventricular deformational measurements (e.g. radial strain, circumferential strain, ejection fraction and torsion) are explored. Methods

Methods Twenty-five participants underwent aortic MRI twice over 13 ± 7 days. All aortic variables (ascending aortic area, descending aortic area, ascending and descending aortic strain [maximum area minus minimum area divided by minimum area], aortic arch transit time and pulse wave velocity [PWV]) from baseline and repeat MR were analyzed using a semi-automated method by the ARTFUN software. Phase contrast (PC) cine at the level of the pulmonary artery bifurcation was used for assessment of aortic area, aortic strain, and PWV. Steady State Free Precession (SSFP) sagittal images were used to measure aortic arch transit distance. To assess the inter-study reproducibility of aortic variables, we calculated intraclass correlation coefficient (ICC) for individual aortic measurements. Intraand inter-observer variability was also assessed using the baseline MR data.

Background A number of studies have been published over the years concerning the relationship between the thickened intima of human arteries and atherogenesis. Increased arterial wall thickness is associated with the prevalence and incidence of cardiovascular disease. Age-related increases of aortic wall thickness have been reported in several crosssectional community-based studies. However, longitudinal changes of these measurements have not yet been documented. The purpose of this study is to characterize ageand sex-specific aortic wall thickness (AWT) distributions and yearly rates of change in older adults. Methods 371 longitudinal and 426 cross sectional studies with AWT images by MRI were analyzed. MRI was performed at first in MESA1 (baseline, 2000-2001), and then in MESA5 (ten-year follow-up, 2010-2011). Both exams used 1.5-T whole-body MRI systems. Images were obtained using a double inversion recovery blackblood fast spin-echo sequence with ECG gating. Axial images of the descending thoracic aorta were obtained at the level of the right pulmonary artery. The thickness of the midthoracic descending aortic wall was measured using electronic calipers at 4 standard positions: 12, 3, 6

Background: Subclinical cardiovascular disease is prevalent in patients with Metabolic Syndrome (MetSyn). Left ventricular (LV) circumferential strain (eCC) and longitudinal strain (eLL), assessed by Speckle Tracking Echocardiography (STE), are indices of systolic function: shortening is indicated by negative strain, and thus, the more negative the strain, the better the LV systolic function. They have been used to demonstrate subclinical ventricular dysfunction in several clinical disorders. Objective: We hypothesized that MetSyn is associated with impaired myocardial function, as assessed by STE. Methods: We analyzed Multi-Ethnic Study of Atherosclerosis (MESA) participants who underwent STE and were evaluated for all MetSyn components. Results: Among the 133 participants included [women: 63%; age: 65 ± 9 years (mean ± SD)], the prevalence of MetSyn was 31% (41/133). Individuals with MetSyn had lower eCC and lower eLL than those without MetSyn (-16.3% ± 3.5% vs. -18.4% ± 3.7%, p < 0.01; and -12.1% ± 2.5% vs. -13.9% ± 2.3%, p < 0.01, respectively). The LV ejection fraction (LVEF) was similar in both groups (p = 0.09). In multivariate analysis, MetSyn was associated with less circumferential myocardial shortening as indicated by less negative eCC (B = 2.1%, 95%CI:0.6 3.5, p < 0.01) even after adjusting for age, ethnicity, LV mass, and LVEF). Likewise, presence of MetSyn (B = 1.3%, 95%CI:0.3 2.2, p < 0.01) and LV mass (B = 0.02%, 95% CI: 0.01-0.03, p = 0.02) were significantly associated with less longitudinal myocardial shortening as indicated by less negative eLL after adjustment for ethnicity, LVEF, and creatinine. Conclusion: Left ventricular eCC and eLL, markers of subclinical cardiovascular disease, are impaired in asymptomatic individuals with MetSyn and no history of myocardial infarction, heart failure, and/or LVEF < 50%.

International audience; Arterial stiffening is related to an intricate interplay between aging and other cardiovascular risk factors. The aortic arch accounts for most of the vascular buffering function and is primarily involved in arterial stiffening. MRI has been used to noninvasively measure strain, distensibility, and pulse wave velocity of the ascending aorta. We report aortic size and stiffness changes over mid to late adulthood in longitudinal comparisons with MRI over a 10-year period in the MESA cohort.