Malenka M. Bissell

Aortic Dilation in Bicuspid Aortic Valve Disease Flow Pattern Is a Major Contributor and Differs With Valve Fusion Type

Background— Ascending aortic dilation is important in bicuspid aortic valve (BAV) disease, with increased risk of aortic dissection. We used cardiovascular MR to understand the pathophysiology better by examining the links between 3-dimensional flow abnormalities, aortic function, and aortic dilation. Methods and Results— A total of 142 subjects underwent cardiovascular MR (mean age, 40 years; 95 with BAV, 47 healthy volunteers). Patients with BAV had predominantly abnormal right-handed helical flow in the ascending aorta, larger ascending aortas (18.3±3.3 versus 15.2±2.2 mm/m2; P <0.001), and higher rotational (helical) flow (31.7±15.8 versus 2.9±3.9 mm2/s; P <0.001), systolic flow angle (23.1°±12.5° versus 7.0°±4.6°; P <0.001), and systolic wall shear stress (0.85±0.28 versus 0.59±0.17 N/m2; P <0.001) compared with healthy volunteers. BAV with right-handed flow and right-non coronary cusp fusion (n=31) showed more severe flow abnormalities (rotational flow, 38.5±16.5 versus 27.8±12.4 mm2/s; P <0.001; systolic flow angle, 29.4°±10.9° versus 19.4°±11.4°; P <0.001; in-plane wall shear stress, 0.64±0.23 versus 0.47±0.22 N/m2; P <0.001) and larger aortas (19.5±3.4 versus 17.5±3.1 mm/m2; P <0.05) than right–left cusp fusion (n=55). Patients with BAV with normal flow patterns had similar aortic dimensions and wall shear stress to healthy volunteers and younger patients with BAV showed abnormal flow patterns but no aortic dilation, both further supporting the importance of flow pattern in the pathogenesis of aortic dilation. Aortic function measures (distensibility, aortic strain, and pulse wave velocity) were similar across all groups. Conclusions— Flow abnormalities may be a major contributor to aortic dilation in BAV. Fusion type affects the severity of flow abnormalities and may allow better risk prediction and selection of patients for earlier surgical intervention.Background—Ascending aortic dilation is important in bicuspid aortic valve (BAV) disease, with increased risk of aortic dissection. We used cardiovascular MR to understand the pathophysiology better by examining the links between 3-dimensional flow abnormalities, aortic function, and aortic dilation. Methods and Results—A total of 142 subjects underwent cardiovascular MR (mean age, 40 years; 95 with BAV, 47 healthy volunteers). Patients with BAV had predominantly abnormal right-handed helical flow in the ascending aorta, larger ascending aortas (18.3±3.3 versus 15.2±2.2 mm/m2; P<0.001), and higher rotational (helical) flow (31.7±15.8 versus 2.9±3.9 mm2/s; P<0.001), systolic flow angle (23.1°±12.5° versus 7.0°±4.6°; P<0.001), and systolic wall shear stress (0.85±0.28 versus 0.59±0.17 N/m2; P<0.001) compared with healthy volunteers. BAV with right-handed flow and right-non coronary cusp fusion (n=31) showed more severe flow abnormalities (rotational flow, 38.5±16.5 versus 27.8±12.4 mm2/s; P<0.001; systolic flow angle, 29.4°±10.9° versus 19.4°±11.4°; P<0.001; in-plane wall shear stress, 0.64±0.23 versus 0.47±0.22 N/m2; P<0.001) and larger aortas (19.5±3.4 versus 17.5±3.1 mm/m2; P<0.05) than right–left cusp fusion (n=55). Patients with BAV with normal flow patterns had similar aortic dimensions and wall shear stress to healthy volunteers and younger patients with BAV showed abnormal flow patterns but no aortic dilation, both further supporting the importance of flow pattern in the pathogenesis of aortic dilation. Aortic function measures (distensibility, aortic strain, and pulse wave velocity) were similar across all groups. Conclusions—Flow abnormalities may be a major contributor to aortic dilation in BAV. Fusion type affects the severity of flow abnormalities and may allow better risk prediction and selection of patients for earlier surgical intervention.

Bicuspid Aortic Valve Identifying Knowledge Gaps and Rising to the Challenge From the International Bicuspid Aortic Valve Consortium (BAVCon)

> Everything should be kept as simple as possible, but no simpler. > > —Albert Einstein1 Since its estimated first description >500 years ago by Leonardo da Vinci,2 the bicuspid aortic valve (BAV) has progressively built a reputation; initially, as a curious valvular phenotype with a tendency to develop obstruction and insufficiency. In more contemporary times, however, the BAV is recognized as underlying almost 50% of isolated severe aortic stenosis cases requiring surgery,3 and has been extensively associated with ominous outcomes such as bacterial endocarditis and aortic dissection.4 These associations, coupled with the high prevalence of BAV in humans,5 have prompted investigative efforts into the condition, which although insightful, have generated more questions than answers. This review describes our current knowledge of BAV, but, more importantly, it highlights knowledge gaps and areas where basic and clinical research is warranted. Our review has 2 sections. The first section outlines the multifaceted challenge of BAV, our current understanding of the condition, and barriers that may hamper the advancement of the science. The second section proposes a roadmap to discovery based on current imaging, molecular biology, and genetic tools, recognizing their advantages and limitations. ### A Condition Characterized by Variable Clinical Presentation The clinical presentation and consequences of BAV in humans are exceedingly heterogeneous, with few clinical or molecular markers to predict associated complications.4,6 BAV can be diagnosed at any stage during a lifetime, from newborns7 to the elderly,8 and in the setting of variable clinical circumstances. Some are benign circumstances such as auscultatory abnormalities or incidental echocardiographic findings in otherwise healthy patients8; other circumstances are morbid, such as early severe aortic valve dysfunction, premature congestive heart failure, and thoracic aortic aneurysms (TAAs).8,9 Life-threatening circumstances include bacterial endocarditis and acute aortic dissection.8–11 These complications may present …

4D flow magnetic resonance imaging in bicuspid aortic valve disease demonstrates altered distribution of aortic blood flow helicity.

Changes in aortic geometry or presence of aortic valve (AoV) disease can result in substantially altered aortic hemodynamics. Dilatation of the ascending aorta or AoV abnormalities can result in an increase in helical flow.

Aortic relative pressure components derived from four-dimensional flow cardiovascular magnetic resonance.

To describe the assessment of the spatiotemporal distribution of relative aortic pressure quantifying the magnitude of its three major components.

Aortic 4D flow: Quantification of signal-to-noise ratio as a function of field strength and contrast enhancement for 1.5T, 3T, and 7T

To investigate for the first time the feasibility of aortic four‐dimensional (4D) flow at 7T, both contrast enhanced (CE) and non‐CE. To quantify the signal‐to‐noise ratio (SNR) in aortic 4D flow as a function of field strength and CE with gadobenate dimeglumine (MultiHance).

Towards the improved quantification of in vivo abnormal wall shear stresses in BAV-affected patients from 4D-flow imaging: Benchmarking and application to real data

Bicuspid aortic valve (BAV), i.e. the fusion of two aortic valve cusps, is the most frequent congenital cardiac malformation. Its progression is often characterized by accelerated leaflet calcification and aortic wall dilation. These processes are likely enhanced by altered biomechanical stimuli, including fluid-dynamic wall shear stresses (WSS) acting on both the aortic wall and the aortic valve. Several studies have proposed the exploitation of 4D-flow magnetic resonance imaging sequences to characterize abnormal in vivo WSS in BAV-affected patients, to support prognosis and timing of intervention. However, current methods fail to quantify WSS peak values. On this basis, we developed two new methods for the improved quantification of in vivo WSS acting on the aortic wall based on 4D-flow data. We tested both methods separately and in combination on synthetic datasets obtained by two computational fluid-dynamics (CFD) models of the aorta with healthy and bicuspid aortic valve. Tests highlighted the need for data spatial resolution at least comparable to current clinical guidelines, the low sensitivity of the methods to data noise, and their capability, when used jointly, to compute more realistic peak WSS values as compared to state-of-the-art methods. The integrated application of the two methods on the real 4D-flow data from a preliminary cohort of three healthy volunteers and three BAV-affected patients confirmed these indications. In particular, quantified WSS peak values were one order of magnitude higher than those reported in previous 4D-flow studies, and much closer to those computed by highly time- and space-resolved CFD simulations.

4D Flow Analysis of BAV-Related Fluid-Dynamic Alterations: Evidences of Wall Shear Stress Alterations in Absence of Clinically-Relevant Aortic Anatomical Remodeling

Bicuspid aortic valve (BAV) is the most common congenital cardiac disease and is a foremost risk factor for aortopathies. Despite the genetic basis of BAV and of the associated aortopathies, BAV-related alterations in aortic fluid-dynamics, and particularly in wall shear stresses (WSSs), likely play a role in the progression of aortopathy, and may contribute to its pathogenesis. To test whether WSS may trigger aortopathy, in this study we used 4D Flow sequences of phase-contrast cardiac magnetic resonance imaging (CMR) to quantitatively compare the in vivo fluid dynamics in the thoracic aorta of two groups of subjects: (i) five prospectively enrolled young patients with normo-functional BAV and with no aortic dilation and (ii) ten age-matched healthy volunteers. Through the semi-automated processing of 4D Flow data, the aortic bulk flow at peak systole was quantified, and WSSs acting on the endothelium of the ascending aorta were characterized throughout the systolic phase in terms of magnitude and time-dependency through a method recently developed by our group. Variables computed for each BAV patient were compared vs. the corresponding distribution of values obtained for healthy controls. In BAV patients, ascending aorta diameter was measured on cine-CMR images at baseline and at 3-year follow-up. As compared to controls, normo-functional BAV patients were characterized by minor bulk flow disturbances at peak systole. However, they were characterized by evident alterations of WSS distribution and peak values in the ascending aorta. In particular, in four BAV patients, who were characterized by right-left leaflet fusion, WSS peak values exceeded by 27–46% the 90th percentile of the distribution obtained for healthy volunteers. Only in the BAV patient with right-non-coronary leaflet fusion the same threshold was exceeded by 132%. Also, evident alterations in the time-dependency of WSS magnitude and direction were observed. Despite, these fluid-dynamic alterations, no clinically relevant anatomical remodeling was observed in the BAV patients at 3-year follow-up. In light of previous evidence from the literature, our results suggest that WSS alterations may precede the onset of aortopathy and may contribute to its triggering, but WSS-driven anatomical remodeling, if any, is a very slow process.

Flow vortices in the aortic root: in vivo 4D-MRI confirms predictions of Leonardo da Vinci

Leonardo da Vinci described (∼1512–13) multiply ‘layered’ vortices that he postulated occurred in the proximal aorta. To demonstrate these, he constructed a glass model in which blood flow was simulated by grass seeds suspended in water. However, neither Leonardo nor twentieth century investigators could study these events in vivo . Here, 500 years after Leonardos original observation, we use time-resolved magnetic resonance techniques to map aortic root blood flow using encoded three-dimensional vector fields in a human subject. Leonardo proposed that vortices, effecting …

Evaluation of Circulation, Γ, as a quantifying metric in 4D flow MRI

Background 4D flow MRI provide a wonderfully rich set of data for diagnosis and understanding of cardiac disease. Interpretation of this wealth of data can be challenging and it may be desirable to simplify it to make analysis manageable. We have observed interesting rotational behavior of blood in the aorta in a number of cardiac diseases. Circulation (Γ) is a metric used in fluid dynamics to quantify the rotational components of flow. This metric has not been reported before for 4D flow MRI and may provide a measurement that can be used diagnostically. The purpose of this work is to define the normal range of Γ in the ascending aorta and investigate its reproducibility.

Congenital aortopulmonary window; an unusual cause of breathlessness

Having recently moved to the UK, a 27-year-old woman with known uncorrected congenital heart disease was referred for cardiovascular MRI (CMRI) due to increased shortness of breath. CMRI revealed a large (40 mm) aortopulmonary window (figure 1) with complete mixing of the pulmonary and systemic circulations (SaO2 73%), moderate mixed aortic valve disease and mild-moderate pulmonary valve regurgitation. Left and right ventricular …