Luca Del Viscovo

Biomechanical implications of the congenital bicuspid aortic valve: A finite element study of aortic root function from in vivo data

OBJECTIVE Congenital bicuspid aortic valves frequently cause aortic stenosis or regurgitation. Improved understanding of valve and root biomechanics is needed to achieve advancements in surgical repair techniques. By using imaging-derived data, finite element models were developed to quantify aortic valve and root biomechanical alterations associated with bicuspid geometry. METHODS A dynamic 3-dimensional finite element model of the aortic root with a bicuspid aortic valve (type 1 right/left) was developed. The models geometry was based on measurements from 2-dimensional magnetic resonance images acquired in 8 normotensive and otherwise healthy subjects with echocardiographically normal function of their bicuspid aortic valves. Numeric results were compared with those obtained from our previous model representing the normal root with a tricuspid aortic valve. The effects of raphe thickening on valve kinematics and stresses were also evaluated. RESULTS During systole, the bicuspid valve opened asymmetrically compared with the normal valve, resulting in an elliptic shape of its orifice. During diastole, the conjoint cusp occluded a larger proportion of the valve orifice and leaflet bending was altered, although competence was preserved. The bicuspid model presented higher stresses compared with the tricuspid model, particularly in the central basal region of the conjoint cusp (+800%). The presence of a raphe partially reduced stress in this region but increased stress in the other cusp. CONCLUSIONS Aortic valve function is altered in clinically normally functioning bicuspid aortic valves. Bicuspid geometry per se entails abnormal leaflet stress. The stress location suggests that leaflet stress may play a role in tissue remodeling at the raphe region and in early leaflet degeneration.

Association between left atrial myocardial function and exercise capacity in patients with either idiopathic or ischemic dilated cardiomyopathy: A two-dimensional speckle strain study

BACKGROUND In patients with idiopathic dilated cardiomyopathy (DCM) a more depressed left atrial (LA) booster pump function has been observed compared to ischemic patients although under similar loading conditions, and attributed both to altered LA overload and to LA larger involvement in the myopathic process. AIM OF THE STUDY To detect by speckle-tracking two-dimensional strain (2DSE) LA systolic dysfunction in patients with either idiopathic or ischemic DCM, and to assess in these patients possible correlation between LA myocardial function and exercise capacity during cardiopulmonary test. METHODS Three-hundred-fourteen patients (52.4+/-11.2 years) with either idiopathic (160 patients) or ischemic (154 patients) DCM underwent cardiopulmonary stress test, standard Doppler echo and 2DSE analysis of atrial longitudinal strain in the basal segments of LA septum and LA lateral wall, and in LA roof. RESULTS The two groups were comparable for most of clinical variables. LV volumes, ejection fraction, stroke volume, and mitral valve effective regurgitant orifice were similar between the two groups. No significant differences were evidenced in Doppler transmitral inflow measurements. Also LA diameter and maximal volume were similar between the two groups. Conversely, LA active empting volume and fraction were both lower in patients with idiopathic DCM (<0.001). Peak systolic myocardial atrial strain was significantly reduced in patients with idiopathic DCM compared with ischemic DCM at the level of all the analyzed atrial segments (p<0.0001). By multivariable analysis, in the overall population, ischemic aetiology of DCM (p<0.0001) and LA volume (p<0.001) were the only independent determinants of LA lateral wall systolic strain. On the other hand, LA lateral wall systolic strain (p<0.0001) and LA volume (p<0.001) were powerful independent predictors of peak oxygen consumption during cardiopulmonary exercise testing. CONCLUSIONS Two-dimensional strain represents a promising non-invasive technique to assess LA atrial myocardial function in patients with DCM. LA systolic deformation is more depressed in idiopathic compared with ischemic DCM, and is closely associated with functional capacity during effort. Future longitudinal studies are warranted to further our understanding of the natural history of LA myocardial function, the extent of reversibility of LA dysfunction with therapy, and the possible prognostic impact of such indexes in patients with congestive heart failure.

Effects of global longitudinal strain and total scar burden on response to cardiac resynchronization therapy in patients with ischaemic dilated cardiomyopathy.

To evaluate whether quantification of the extent of scarred left ventricular (LV) tissue by speckle‐tracking strain echo (2DSE) can predict response to cardiac resynchronization therapy (CRT) in patients with ischaemic dilated cardiomyopathy (DCM).

Distinct disease phenotypes linked to different combinations of GAA mutations in a large late-onset GSDII sibship.

BackgroundGlycogenosis type II (GSDII or Pompe disease) is an autosomal recessive disease, often characterized by a progressive accumulation of glycogen within lysosomes caused by a deficiency of α-1,4-glucosidase (GAA; acid maltase), a key enzyme of the glycogen degradation pathway. To date, more than 326 different mutations in the GAA gene have been identified in patients with GSDII but the course of the disease is difficult to be predicted on the basis of molecular genetic changes. Studies on large informative families are advisable to better define how genetics and non genetics factors like exercise and diet may influence the clinical phenotype.Methods and resultsIn this study, we report on clinical, instrumental, and pathological features as well as on molecular analysis of a family with 10 out of 13 siblings affected by late-onset Pompe disease. Three mutations segregated in the family, two of which are novel mutations. Siblings showing a more severe phenotype were compound heterozygous for c.118C > T [p.R40X] and c.2647-7G > A [p.N882fs] on GAA, whereas, two patients showing a mild phenotype were compound heterozygous c.2647-7G > A [p.N882fs] and c.2276G > C [p.G759A] mutations. Quantitative expression analysis showed, in the patients carrying p.R40X/ p.N882fs, a significant (p 0.01) correlation between the levels of expression of the mutated allele and the age at onset of the disease.ConclusionsAs far as we know, this is the largest informative family with late-onset Pompe disease described in the literature showing a peculiar complex set of mutations of GAA gene that may partially elucidate the clinical heterogeneity of this family.

Rationale and methods for quantifying ascending aortic flow eccentricity: Back to the underlying mechanism?

We read with interest the article by Dr. Sigovan et al (1) claiming superiority of a ‘‘flow displacement’’ versus ‘‘jet angle’’ method for quantification of eccentric systolic flow in the ascending aorta of bicuspid aortic valve (BAV) patients. The rationale for the need to measure flow eccentricity is that it may play an important pathogenetic role in asymmetric aortic dilatation development (2), likely by increasing local wall shear stress (WSS) at the right-anterior wall (3). Although issued by an authoritative institution, the article arouses some criticisms. Flow displacement reflected the eccentricity degree better than jet angle (1); however, another study from the same institution (3) demonstrated that increasing eccentricity was not associated with any significant increase of rightanterior WSS. In the present study, WSS was not measured in patients, and only a monodimensional mathematical simulation was performed (1): flow displacement might fail to be confirmed as a good surrogate metric for WSS in vivo. Second, both title and abstract advert ‘‘4D Flow Parameters,’’ and the equation term i 1⁄4 x,y,z in the formula for the ‘‘center of velocity’’ suggests 3D computation of pixel position; nevertheless, the figures and text clarify that 2D data, ie, distance between center of velocity and center of lumen in a cross-sectional plane, were handled (1). This makes the method simpler than others (4), but can also weaken the reproducibility of flow displacement measurement, as the level of the cross-section was not precisely defined (‘‘just distal to the sinotubular junction’’ is quite subjective). Finally, the inclusion in the study, particularly in the group with marked eccentric flow, of aortic dilatation patients (1), in which greater flow displacement may be secondary to dilatation itself (5), eventually prevents the authors from reaching the target, stated in the Discussion (1), of identifying a metric for patient risk-stratification. A prognostic parameter should be capable of quantifying flow misdirection in a preclinical stage of the aortopathy, allowing to risk-stratify patients based on the exposure of their aorta to abnormal hemodynamic cues before dilatation development. Table 1 summarizes the methods and results of four recent studies searching for imaging tools potentially useful to the above prognostic purpose (1,4–6). Recently, the degree of BAV conjoint cusp opening restriction, which is the mechanism underlying BAVrelated flow eccentricity (6), was measured through a TrueFISP cine-MRI protocol in nonstenotic BAV subjects without aortic dilatation, and quantified by the ‘‘cusp opening angle’’ parameter (6). By PC-MRI and computational fluid dynamics models, cusp opening restriction was confirmed to be sufficient as a cause for the deflection of systolic flow jet, independent of the presence of aortopathy. Our anglebased measurement also proved an independent predictor of the annual growth rate of the aorta, assessed over a mean follow-up of 4 years (Table 1). Others even demonstrated a correlation between flow jet angle and plasma matrix metalloproteinase2 (4). We agree with Dr. Sigovan et al’s conclusion ‘‘[. . .] an agreed upon quantitative measure of eccentricity is needed for standardization’’: we believe that such agreement should be based on the demonstration of clinical meaningfulness of this quantitative measure.

Presence of transmural posterolateral scar by LGE MRI is associated with non-response to CRT

Background Several recent single center studies have used late Gadolinium enhancement (LGE) MRI to predict which patients would likely not respond to cardiac resynchronization therapy (CRT). Results from these studies have varied on the importance of scar location, transmurality, and burden on response to CRT. We analyzed cardiac MRI in patients undergoing CRT from 4 centers (two in Europe and two in the US), and hypothesized that the presence of transmural scar in the posterolateral wall (the most frequent site of left ventricular lead placement in CRT) would preclude positive response to CRT.

Biomechanical Implications of the Bicuspid Aortic Valve: A Finite Element Study From In Vivo Data

The bicuspid aortic valve (BAV) is the second most common congenital cardiac malformation, with an estimated prevalence of 0.9% to 2% in the general population [1]. BAV is widely recognized as a frequent cause of aortic stenosis and/or aortic regurgitation and as a risk factor for the early development of aortic aneurysms [2].Copyright

Aortic Root Finite Element Modeling From MR Imaging

The aortic root is the portion of the outflow tract of the left ventricle that includes the aortic leaflets, the aortic annulus, the sinuses of Valsalva and the sinotubular junction. The impairment of one or more of these structures can lead not only to dysfunctions of the root, but also to alterations of the adjacent anatomical sites, such as the ascending aorta. The raise and the progress of the alterations are often related to more concomitant factors, whose separated effect can be difficult to assess. At this purpose computational finite element (FE) models can be a useful tool, given their capability the recreate different scenarios by varying one or more parameters of the model in a controlled fashion.Copyright