In vitro dynamic strain behavior of the mitral valve posterior leaflet

Knowledge of mitral valve (MV) mechanics is essential for the understanding of normal MV function, and the design and evaluation of new surgical repair procedures. In the present study, we extended our investigation of MV dynamic strain behavior to quantify the dynamic strain on the central region of the posterior leaflet. Native porcine MVs were mounted in an in-vitro physiologic flow loop. The papillary muscle (PM) positions were set to the normal, taut, and slack states to simulate physiological and pathological PM positions. Leaflet deformation was measured by tracking the displacements of 16 small markers placed in the central region of the posterior leaflet. Local leaflet tissue strain and strain rates were calculated from the measured displacements under dynamic loading conditions. A total of 18 mitral valves were studied. Our findings indicated the following: (1) There was a rapid rise in posterior leaflet strain during valve closure followed by a plateau where no additional strain (i.e., no creep) occurred. (2) The strain field was highly anisotropic with larger stretches and stretch rates in the radial direction. There were negligible stretches, or even compression (stretch < 1) in the circumferential direction at the beginning of valve closure. (3) The areal strain curves were similar to the stretches in the trends. The posterior leaflet showed no significant differences in either peak stretches or stretch rates during valve closure between the normal, taut, and slack PM positions. (4) As compared with the anterior leaflet, the posterior leaflet demonstrated overall lower stretch rates in the normal PM position. However, the slack and taut PM positions did not demonstrate the significant difference in the stretch rates and areal strain rates between the posterior leaflet and the anterior leaflet. The MV posterior leaflet exhibited pronounced mechanically anisotropic behavior Loading rates of the MV posterior leaflet were very high. The PM positions influenced neither peak stretch nor stretch rates in the central area of the posterior leaflet. The stretch rates and areal strain rates were significantly lower in the posterior leaflet than those measured in the anterior leaflet in the normal PM position. However, the slack and taut PM positions did not demonstrate the significant differences between the posterior leaflet and the anterior leaflet. We conclude that PM positions may influence the posterior strain in a different way as compared to the anterior leaflet.     

Annulus tension of the prolapsed mitral valve corrected by edge-to-edge repair

BackgroundMitral valve (MV) performance after edge-to-edge repair (ETER) without ring annuloplasty is suboptimal. ETER efficacy needs to be evaluated from annulus tension (AT) of a prolapsed MV corrected by ETER to understand annular dilatation.MethodsTen porcine MVs were harvested and mounted on a MV closure test rig. The MV annulus tissue rested on top of a saddle-shaped plastic ring on which the annulus could slide freely. The annulus was held by strings in the periphery during MV closure under a hydrostatic trans-mitral pressure. String tensions were measured and further divided by string spacing to obtain AT. The MVs were then prolapsed by shifting split papillary muscles to simulate mono-leaflet prolapse due to elongation of chords, which insert into a single leaflet. Last, MV prolapse was corrected by ETER applied in the central leaflet region and AT was measured.ResultsAT in both anterior and posterior leaflet prolapse corrected by ETER was less than that of normal MVs. AT in the anterior leaflet prolapse corrected by ETER was less than that in the posterior leaflet prolapse corrected by ETER.ConclusionETER does not restore the normal AT and therefore leads potential of annular dilatation. The anterior leaflet prolapse has a greater potential of annular dilatation than the posterior leaflet prolapse after ETER. Annuloplasty is recommended to maintain long-term ETER efficacy.     

Structural effects of an innovative surgical technique to repair heart valve defects

The structural and functional effects of the “edge-to-edge” technique on the human mitral valve have been investigated, paying particular attention to the diastolic phase. An advanced finite element model of the valve has been developed, using a hyperelastic material schematization, suitable geometry and constraint conditions, and an effective fluidodynamic analysis. The edge-to-edge suture has been applied on this model and the diastolic phase has been simulated. The results of this calculation show that the operation increases the transvalvular pressure and the maximum stress in the leaflets, which reaches a level similar to that of the systolic phase. The influence of suture position and extension, and the mitral annulus dimension has also been investigated. The results indicate that a lateral location of the stitch is better than a central one, both regarding valve functionality (pressure level and mobility) and internal stresses level, that a longer suture worsens the valve functionality but reduces the stresses level, finally, that the dilatation of the mitral annulus does not affect the valve functionality but increases the stresses level.     

Material properties of the ovine mitral valve anterior leaflet in vivo from inverse finite element analysis

We measured leaflet displacements and used inverse finite-element analysis to define, for the first time, the material properties of mitral valve (MV) leaflets in vivo. Sixteen miniature radiopaque markers were sewn to the MV annulus, 16 to the anterior MV leaflet, and 1 on each papillary muscle tip in 17 sheep. Four-dimensional coordinates were obtained from biplane videofluoroscopic marker images (60 frames/s) during three complete cardiac cycles. A finite-element model of the anterior MV leaflet was developed using marker coordinates at the end of isovolumic relaxation (IVR; when the pressure difference across the valve is approximately 0), as the minimum stress reference state. Leaflet displacements were simulated during IVR using measured left ventricular and atrial pressures. The leaflet shear modulus (G(circ-rad)) and elastic moduli in both the commisure-commisure (E(circ)) and radial (E(rad)) directions were obtained using the method of feasible directions to minimize the difference between simulated and measured displacements. Group mean (+/-SD) values (17 animals, 3 heartbeats each, i.e., 51 cardiac cycles) were as follows: G(circ-rad) = 121 +/- 22 N/mm2, E(circ) = 43 +/- 18 N/mm2, and E(rad) = 11 +/- 3 N/mm2 (E(circ) > E(rad), P < 0.01). These values, much greater than those previously reported from in vitro studies, may result from activated neurally controlled contractile tissue within the leaflet that is inactive in excised tissues. This could have important implications, not only to our understanding of mitral valve physiology in the beating heart but for providing additional information to aid the development of more durable tissue-engineered bioprosthetic valves.     

Can isolated annular dilatation cause significant ischemic mitral regurgitation? Another look at the causative mechanisms

This study was to investigate the mechanisms of ischemic mitral regurgitation (IMR) by using a finite element (FE) approach. IMR is a common complication of coronary artery disease; and it usually occurs due to myocardial infarction. The pathophysiological mechanisms of IMR have not been fully understood, much debate remains about the exact contribution of each mechanism to IMR. Two patient-specific FE models of normal mitral valves (MV) were reconstructed from multi-slice computed tomography scans. Different grades of IMR during its pathogenesis were created by perturbation of the normal MV geometry. Effects of annular dilatation and papillary muscle (PM) displacement (both isolated and combined) on the severity of IMR were examined. We observed greater increase in IMR (in terms of regurgitant area and coaptation length) in response to isolated annular dilatation than that caused by isolated PM displacement, while a larger PM displacement resulted in higher PM forces. Annular dilation, combined with PM displacement, was able to significantly increase the severity of IMR and PM forces. Our simulations demonstrated that isolated annular dilatation might be a more important determinant of IMR than isolated PM displacement, which could help explain the clinical observation that annular size reduction by restrictive annuloplasty is generally effective in treating IMR.     

Isolated effect of geometry on mitral valve function for in silico model development

Computational models for the heart's mitral valve (MV) exhibit several uncertainties that may be reduced by further developing these models using ground-truth data-sets. This study generated a ground-truth data-set by quantifying the effects of isolated mitral annular flattening, symmetric annular dilatation, symmetric papillary muscle (PM) displacement and asymmetric PM displacement on leaflet coaptation, mitral regurgitation (MR) and anterior leaflet strain. MVs were mounted in an in vitro left heart simulator and tested under pulsatile haemodynamics. Mitral leaflet coaptation length, coaptation depth, tenting area, MR volume, MR jet direction and anterior leaflet strain in the radial and circumferential directions were successfully quantified at increasing levels of geometric distortion. From these data, increase in the levels of isolated PM displacement resulted in the greatest mean change in coaptation depth (70% increase), tenting area (150% increase) and radial leaflet strain (37% increase) while annular dilatation resulted in the largest mean change in coaptation length (50% decrease) and regurgitation volume (134% increase). Regurgitant jets were centrally located for symmetric annular dilatation and symmetric PM displacement. Asymmetric PM displacement resulted in asymmetrically directed jets. Peak changes in anterior leaflet strain in the circumferential direction were smaller and exhibited non-significant differences across the tested conditions. When used together, this ground-truth data-set may be used to parametrically evaluate and develop modelling assumptions for both the MV leaflets and subvalvular apparatus. This novel data may improve MV computational models and provide a platform for the development of future surgical planning tools.     

Effects of exercise training on plasma catecholamines and blood pressure in labile hypertensive subjects

Plasma catecholamine concentrations (norepinephrine, NE; epinephrine, E) were measured along with heart rate (HR) and blood pressure (BP) at rest in supine (20 min) and standing (10 min) positions and in response to cycle ergometer exercise (5 min; 60% estimated maximal aerobic power) in 12 hypertensive patients before and after 20 weeks of aerobic training on cycle ergometer (six males, one female) or by jogging (five males). In a control group of labile hypertensive patients (five males, two females), estimated maximal aerobic power as well as HR and BP at rest in the supine and standing positions and in response to exercise were not modified from the first to the second evaluation (43 +/- 4 vs 43 +/- 5 ml.kg-1.min-1). In comparison estimated maximal aerobic power significantly increased in both training groups (cycle: 38 +/- 4 to 43 +/- 4; jogging: 38 +/- 3 to 46 +/- 4 ml.kg-1.min-1). However HR and BP were not modified following training, except for small reductions in systolic (18.9 to 18 kPa: 142 to 135 mmHg) and diastolic pressures (13.3 to 12 kPa: 100 to 90 mmHg) (p less than 0.05) at standing rest in the cycle group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Determination of the tensile mechanical properties of the segmented mitral valve annulus

The mitral valve annulus is a complex and irregular component of the mitral valve apparatus, serving both a structural and sphincteric role. We have sought to determine the mechanical properties of the mitral valve annulus segmentally. Twenty porcine hearts were dissected to isolate the annulus. The annulus was segmented into four sections: anterior, posterior, and left and right commissural sections. Ten of these were tensile tested to failure as control samples. The remaining ten were digested in order to fully isolate the annulus from the myocardium, and subsequently tensile tested to failure. Histological samples of each segment were analysed to determine collagen/annular content. Whole segments of muscular annulus were tensile tested to failure; the stress and strain at failure and location of failure were determined in these larger specimens. Our results demonstrated that the anterior annulus is stiffer than the posterior segment by a factor of approximately 27 at a 2% strain level, and approximately 13 at a 6% strain. There is a trend in the results that identifies that the muscular annulus is stiffest at the right commissural segment, while the posterior segment tends to be the least stiff. The stiffness of the samples can be correlated with the area associated with the dense collagen annulus using histological analysis. Finally, the weakest section of the mitral valve annulus was identified as the intersection of the right commissural segment and the posterior segment.     

Identification of a sperm nuclear annulus: a sperm DNA anchor

We report the isolation and characterization of a new nuclear structure from spermatozoa of the golden Syrian hamster which we term the nuclear annulus. The nuclear annulus was located at the implantation fossa, the point at which the tail is joined to the sperm head, inside the nucleus adjacent to the inner nuclear envelope. Extraction of sperm nuclei with 2 M NaCl and 10 mM dithiothreitol caused the solubilization of the protamines and DNA decondensation. This released the DNA from its structural constraints except that the DNA remained anchored to the nuclear annulus, which survived the extraction procedure. Nuclear annuli were isolated and examined by scanning electron microscopy. The nuclear annulus was a double-crescent, ring-shaped structure, 2.10 +/- 0.16 micron long and 1.36 +/- 0.13 micron wide. We believe that the nuclear annulus may play an important role in the organization of sperm DNA.     

Heterogeneity of the myocardium. Function of the left and right ventricle under normal and pathological conditions

A number of important differences can be found between the left ventricle (LV) and right ventricle (RV) of the heart under physiological conditions. In anatomy, the most important is probably the architecture of the atrioventricular valve and its annulus. The LV has a mitral valve (with two cusps) and a firm annulus, while the RV has a tricuspid valve with a greater total area, but relatively small cuspid areas, and an elastic annulus. The difference in the blood supply is important. Owing to high intramural pressure, the coronary flow in the wall of the LV occurs only during the diastole; in the RV it is limited only in the presence of a significant increase in intracavitary pressure. The LV myocardium is functionally "accustomed" to short-term marked changes in the systolic load (in extreme static exercise the arterial pressure rises for a short time to three times the normal value), while the RV is adapted to changes in the diastolic load (marked filling changes associated with deep breathing, for instance). The difference in the response to a long-term volume load is difficult to evaluate: between a defect of the interatrial septum and aortic insufficiency there are too many differences. A long-term pressure load seems to be tolerated better by the right ventricle: patients with severe pulmonary stenosis and a pressure six times higher than the physiological value have lived 25 years and patients with isolated corrected L-transposition of the great arteries can reach 35 years without any signs of impaired RV function.(ABSTRACT TRUNCATED AT 250 WORDS)     

Atomic force microscope elastography reveals phenotypic differences in alveolar cell stiffness.

To understand the connection between alveolar mechanics and key biochemical events such as surfactant secretion, one first needs to characterize the underlying mechanical properties of the lung parenchyma and its cellular constituents. In this study, the mechanics of three major cell types from the neonatal rat lung were studied; primary alveolar type I (AT1) and type II (AT2) epithelial cells and lung fibroblasts were isolated using enzymatic digestion. Atomic force microscopy indentation was used to map the three-dimensional distribution of apparent depth-dependent pointwise elastic modulus. Histograms of apparent modulus data from all three cell types indicated non-Gaussian distributions that were highly skewed and appeared multimodal for AT2 cells and fibroblasts. Nuclear stiffness in all three cell types was similar (2.5+/-1.0 kPa in AT1 vs. 3.1+/-1.5 kPa in AT2 vs. 3.3+/-0.8 kPa in fibroblasts; n=10 each), whereas cytoplasmic moduli were significantly higher in fibroblasts and AT2 cells (6.0+/-2.3 and 4.7+/-2.9 kPa vs. 2.5+/-1.2 kPa). In both epithelial cell types, actin was arranged in sparse clusters, whereas prominent actin stress fibers were observed in lung fibroblasts. No systematic difference in actin or microtubule organization was noted between AT1 and AT2 cells. Atomic force microscope elastography, combined with live-cell fluorescence imaging, revealed that the stiffer measurements in AT2 cells often colocalized with lamellar bodies. These findings partially explain reported heterogeneity of alveolar cell deformation during in situ lung inflation and provide needed data for better understanding of how mechanical stretch influences surfactant release.     

Maladaptive matrix remodeling and regional biomechanical dysfunction in a mouse model of aortic valve disease

Aortic valve disease (AVD) occurs in 2.5% of the general population and often requires surgical intervention. Aortic valve malformation (AVM) underlies the majority of cases, suggesting a developmental etiology. Elastin haploinsufficiency results in complex cardiovascular problems, and 20-45% of patients have AVM and/or AVD. Elastin insufficient (Eln+/-) mice demonstrate AVM and latent AVD due to abnormalities in the valve annulus region. The objective of this study was to examine extracellular matrix (ECM) remodeling and biomechanical properties in regional aortic valve tissue and determine the impact of early AVM on late AVD in the Eln+/- mouse model. Aortic valve ECM composition and remodeling from juvenile, adult, and aged stages were evaluated in Eln+/- mice using histology, ELISA, immunohistochemistry and gelatin zymography. Aortic valve tissue biomechanical properties were determined using micropipette aspiration. Cartilage-like nodules were demonstrated within the valve annulus region at all stages identifying a developmental abnormality preceding AVD. Interestingly, maladaptive ECM remodeling was observed in early AVM without AVD and worsened with late AVD, as evidenced by increased MMP-2 and MMP-9 expression and activity, as well as abnormalities in ADAMTS-mediated versican processing. Cleaved versican was increased in the valve annulus region of aged Eln+/- mice, and this abnormality correlated temporally with adverse alterations in valve tissue biomechanical properties and the manifestation of AVD. These findings identify maladaptive ECM remodeling in functional AVM as an early disease process with a progressive natural history, similar to that seen in human AVD, emphasizing the importance of the annulus region in pathogenesis. Combining molecular and engineering approaches provides complementary mechanistic insights that may be informative in the search for new therapeutic targets and durable valve bioprostheses.     

Fate of the autologous tri-cusp-valved pericardial conduit in the right ventricular outflow tract of growing pigs.

No perfect valve or valved conduit is currently available to reconstruct the right ventricular outflow tract (RVOT) in pediatric patients. To investigate the fate of autologous pericardial valved conduit, twenty piglets weighing 12.2 +/- 1.4 kg were divided into two groups. In 10 of them, the pericardium was immersed in 0.6% glutaraldehyde for 5 minutes (Gr PG) and then washed with normal saline. In the other 10 pigs, the pericardium was immersed in normal saline only (Gr PN) after procurement. Afterwards the autologous pericardium was tailored as designed to build a tri-cusp-valve inside the pericardial conduit with reconstruction of the sinus of Valsalva. This conduit was connected to the pulmonary trunk (PT) distally and RVOT proximally without a pump. The PT was then doubly ligated just above the annulus. The pigs survived 114 +/- 92 days in Gr PG and 82 +/- 50 days in Gr PN. The body weight increased to 42 +/- 29 kg in Gr PG and 30 +/- 9 kg in Gr PN. No cusps adhered to the conduit wall in either group. In Gr PN, the valve became retracted; in 7 of them an aneurysm developed proximal to the stenotic pulmonary valve, while only one pig in Gr PG developed an aneurysm. In Gr PG, the leaflet and conduit showed evidence of growth. In contrast, no evidence of valve growth was found in Gr PN. Calcification was evident more in Gr PG than in Gr PN either on the leaflet (9/10 vs. 5/10) or in the wall of conduit (8/10 vs. 6/10), but the differences were not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of testosterone on the apneic threshold in women during NREM sleep.

The hypocapnic apneic threshold (AT) is lower in women relative to men. To test the hypothesis that the gender difference in AT was due to testosterone, we determined the AT during non-rapid eye movement sleep in eight healthy, nonsnoring, premenopausal women before and after 10-12 days of transdermal testosterone. Hypocapnia was induced via nasal mechanical ventilation (MV) for 3 min with tidal volumes ranging from 175 to 215% above eupneic tidal volume and respiratory frequency matched to eupneic frequency. Cessation of MV resulted in hypocapnic central apnea or hypopnea depending on the magnitude of hypocapnia. Nadir minute ventilation as a percentage of control (%Ve) was plotted against the change in end-tidal CO(2) (Pet(CO(2))); %Ve was given a value of zero during central apnea. The AT was defined as the Pet(CO(2)) at which the apnea closest to the last hypopnea occurred; hypocapnic ventilatory response (HPVR) was defined as the slope of the linear regression Ve vs. Pet(CO(2)). Both the AT (39.5 +/- 2.9 vs. 42.1 +/- 3.0 Torr; P = 0.002) and HPVR (0.20 +/- 0.05 vs. 0.33 +/- 0.11%Ve/Torr; P = 0.016) increased with testosterone administration. We conclude that testosterone administration increases AT in premenopausal women, suggesting that the increased breathing instability during sleep in men is related to the presence of testosterone.     

Dynamics of left ventricular wall and mitral valve mechanics--a model study

The relation between global left ventricular pumping characteristics and local cardiac muscle fiber mechanics is represented by a mathematical model of left ventricular mechanics in which the mitral valve papillary muscle system is incorporated. The wall of the left ventricle is simulated by a thick-walled cylinder. Transmural differences in fiber orientation are incorporated by changing the direction of material anisotropy across the wall. The cylinder is free to twist. The upper end of the cylinder is covered by a thin, flexible sheet, representing the base of the left ventricle. The mitral valve is incorporated in this sheet. The tips of the mitral leaflets are connected by chordae tendineae to the papillary muscles which are attached to the bottom of the cylinder. Canine cardiac cycles were simulated for various end-diastolic values of left ventricular volume (25-120 ml, control 60 ml), left atrial pressure (0-2.7 kPa, control 0.22 kPa) and aortic pressure (5-11 kPa, control 11 kPa). In this wide range of preload and afterload mechanical loading of the muscle fibers appeared to be distributed quite evenly (SD: +/- 5% of control value) over all muscular structures of the left ventricle, including the papillary muscles.     

Mutation study of antithrombin: the roles of disulfide bonds in intracellular accumulation and formation of russell body-like structures

Antithrombin (AT) is a major plasma protease inhibitor with three intramolecular disulfide bonds and a deficiency of it is associated with venous thrombosis. Recently, we prepared CHO cells overexpressing a novel mutant, AT(C95R), with a disulfide bond removed, and revealed that this mutant remained for a long time in the endoplasmic reticulum (ER) without being degraded and also accumulated in newly formed membrane structures that resembled Russell bodies (RB) [Tanaka, Y. et al. (2002) J. Biol. Chem. 277, 51058-51067]. In this study, we replaced each of the individual cysteine residues of AT with an arginine and also two paired cysteine residues with arginines. We stably expressed these mutant ATs in CHO cells, and examined the roles of each cysteine residue or disulfide bond in the accumulation of mutant ATs and the formation of RB-like structures. In pulse-chase experiments, the secretion of mutant ATs with single mutations decreased approximately 1/5-1/50 times compared to that of the wild type AT. All of the mutant ATs were retained in the ER and were also found to accumulate in the RB-like structures. On the other hand, the fates of mutant ATs with double mutations fell into two categories. Secretion of mutant AT(C8R,C128R) decreased only approximately 1/2 times and no RB-like structures appeared. Mutants AT(C21R,C95R) and AT(C247R,C430R) exhibited similar secretion kinetics to the mutant ATs with the single mutations and were found in RB-like structures. On a sucrose gradient, all of the mutant ATs that induced RB-like structures migrated as oligomeric structures, whereas wild type AT and AT(C8R,C128R) migrated as monomers. Further, to clarify the morphological pathway through which RB-like structures are formed, we prepared CHO cells in which the expression of AT(C95R) was controlled by the Tet-On system. During expression of AT(C95R), RB-like structures formed through expansion of the ER. These results suggest that the correct folding with each disulfide bond is essential for the secretion of AT and oligomerization of mutant ATs in the ER is involved in the formation of RB-like structures.     

Sudden interruption of leaflet opening by ventricular contractions: a mechanism of mitral regurgitation.

The motion of both mitral cusps and the presence of valvular regurgitation during ventricular contractions were investigated in seven experiments on dogs in which radiopaque markers had been sutured to the cusps and the valve annulus 1-32 wk before the studies. Cineangiograms of the left ventricle were obtained during ventricular ectopic beats, interposed throughout the cardiac cycle (20-99% of cycle length) and during induced variations in the P-R interval (0-200 ms). Mitral regurgitation was observed only during a) weak, early ectopic beats (peak pressure below 34 mmHg) which were incapable of closing the cusps and b) when ventricular contractions suddenly interrupted normal leaflet motion toward the ventricle, during three well-defined periods of diastole (diastolic valve opening, diastolic rebound, and atrial opening). Valve closure following sudden reversal of cusp opening was slow and the leaflets often did not arrive simultaneously at their closed positions. These findings suggest that sudden interruption of leaflet opening by ventricular contractions is an important mechanism of transient mitral regurgitation in the normal heart.     

Mitral leaflet modeling: Importance of in vivo shape and material properties

The anterior mitral leaflet (AML) is a thin membrane that withstands high left ventricular (LV) pressure pulses 100,000 times per day. The presence of contractile cells determines AML in vivo stiffness and complex geometry. Until recently, mitral valve finite element (FE) models have neglected both of these aspects. In this study we assess their effect on AML strains and stresses, hypothesizing that these will differ significantly from those reported in literature. Radiopaque markers were sewn on the LV, the mitral annulus, and AML in sheep hearts, and their four-dimensional coordinates obtained with biplane video fluoroscopy. Employing in vivo data from three representative hearts, AML FE models were created from the marker coordinates at the end of isovolumic relaxation assumed as the unloaded reference state. AML function was simulated backward through systole, applying the measured trans-mitral pressure on AML LV surface and marker displacements on AML boundaries. Simulated AML displacements and curvatures were consistent with in vivo measurements, confirming model accuracy. AML circumferential strains were mostly tensile (1-3%), despite being compressive (-1%) near the commissures. Radial strains were compressive in the belly (-1 to -0.2%), and tensile (2-8%) near the free edge. These results differ significantly from those of previous FE models. They reflect the synergy of high tissue stiffness, which limits tensile circumferential strains, and initial compound curvature, which forces LV pressure to compress AML radially. The obtained AML shape may play a role not only in preventing mitral regurgitation, but also in optimizing LV outflow fluid dynamics.     

In vitro assessment of the influence of aortic annulus ovality on the hydrodynamic performance of self-expanding transcatheter heart valve prostheses

Background

Although CT-studies as well as intraoperative analyses have described broad anatomic variations of the aortic annulus, which is predominantly found non-circular, commercially available transcatheter aortic heart valve prostheses are circular. In this study, we hypothesize that the in vitro hydrodynamic function of a self-expanding transcatheter heart valve (Medtronic CoreValve^®) assessed in an oval compartment representing the aortic annulus will differ from the conventionally used circular compartment.

Methods

Medtronic CoreValve^® prostheses were tested in specifically designed and fabricated silicone compartments with three degrees of defined ovalities. The measurements were performed in a left heart simulator at three different flow rates. In this setting, regurgitation flow, effective orifice area, and systolic pressure gradient across the valve were determined. In addition, high speed video recordings were taken to investigate leaflet kinematics.

Results

The pressure difference across the prosthesis increased with rising ovality. The effective orifice areas were only slightly impacted. The analyses of the regurgitation showed minor changes and partially lower regurgitation when switching from round to slightly oval settings, followed by strong increases for further ovalization. The high speed videos show minor central leakage and impaired leaflet apposition for strong ovalities, but no leaflet/stentframe contact in any setting.

Conclusion

This study quantifies the influence of oval expansion of transcatheter heart valve prostheses on their hydrodynamic performance. While slight ovalities were well tolerated by a self-expanding prosthesis, more significant ovality led to worsening of prosthesis function and regurgitation.