Muralidhar Padala

Saddle Shape of the Mitral Annulus Reduces Systolic Strains on the P2 Segment of the Posterior Mitral Leaflet

BACKGROUND The three-dimensional saddle shape of the mitral annulus is well characterized in animals and humans, but the impact of annular nonplanarity on valve function or mechanics is poorly understood. In this study, we investigated the impact of the saddle shaped mitral annulus on the mechanics of the P2 segment of the posterior mitral leaflet. METHODS Eight porcine mitral valves (n = 8) were studied in an in-vitro left heart simulator with an adjustable annulus that could be changed from flat to different degrees of saddle. Miniature markers were placed on the atrial face of the posterior leaflet, and leaflet strains at 0%, 10%, and 20% saddle were measured using dual-camera stereophotogrammetry. Averaged areal strain and the principal strain components are reported. RESULTS Peak areal strain magnitude decreased significantly from flat to 20% saddle annulus, with a 78% reduction in the measured strain over the entire P2 region. In the radial direction (annulus free edge), a 44.4% reduction in strain was measured, whereas in the circumferential direction (commissure-commissure), a 34% reduction was measured from flat to 20% saddle. CONCLUSIONS Nonplanar shape of the mitral annulus significantly reduced the mechanical strains on the posterior leaflet during systolic valve closure. Reduction in strain in both the radial and circumferential directions may reduce loading on the suture lines and potentially improve repair durability, and also inhibit progression of valve degeneration in patients with myxomatous valve disease.

Mitral valve hemodynamics after repair of acute posterior leaflet prolapse: Quadrangular resection versus triangular resection versus neochordoplasty

OBJECTIVE Leaflet prolapse resulting from acute chordal rupture is one presentation of fibroelastic deficiency that is associated with minimal leaflet changes in the prolapsing segment. Minimizing resection and preserving leaflet tissue may be an optimal surgical strategy. We examined the importance of the leaflet preservation concept by comparing resective and nonresective surgical procedures in practice today. METHODS Eight porcine mitral valves were evaluated in an in vitro heart simulator before surgical manipulation. Mitral regurgitation was created in these valves by transecting the posterior marginal chordae resulting in severe P2 prolapse. After confirmation of mitral regurgiation via regurgitant flow measurement (mL/beat), regurgitation was corrected by three repairs: neochordoplasty with polytetrafluoroethylene sutures (Gore-Tex; W. L. Gore & Associates, Inc, Flagstaff, Ariz), triangular resection, and quadrangular resection with annular compression. Postrepair valve hemodynamics were quantified under pulsatile conditions of 120 mm Hg peak transmitral pressure and 5 L/min cardiac output at 70 beats/min. Furthermore, hemodynamic, geometric, and echocardiographic indices were measured. RESULTS Transecting the marginal chordae resulted in severe P2 prolapse and significant mitral regurgiation (19.3 +/- 4.3 mL/beat). Regurgitant volume was significantly reduced after any of the three surgical approaches (quadrangular, 4.38 +/- 1.6 mL/beat; triangular, 2.56 +/- 1.0 mL/beat; neochordal, 2.86 +/- 1.24 mL/beat). In comparison with the baseline normal valves, leaflet coaptation length and posterior leaflet mobility were significantly reduced in the quadrangular resection group, whereas they were partially restored in the triangular resection and fully preserved in the neochordoplasty group. CONCLUSIONS Although the three repair procedures are hemodynamically comparable, valve function and leaflet kinematics were significantly better after a nonresection or limited resective correction of leaflet prolapse in this experimental model of acute chordal rupture with otherwise normal leaflet geometry.

Design of an ex vivo culture system to investigate the effects of shear stress on cardiovascular tissue.

Mechanical forces are known to affect the biomechanical properties of native and engineered cardiovascular tissue. In particular, shear stress that results from the relative motion of heart valve leaflets with respect to the blood flow is one important component of their mechanical environment in vivo. Although different types of bioreactors have been designed to subject cells to shear stress, devices to expose biological tissue are few. In an effort to address this issue, the aim of this study was to design an ex vivo tissue culture system to characterize the biological response of heart valve leaflets subjected to a well-defined steady or time-varying shear stress environment. The novel apparatus was designed based on a cone-and-plate viscometer. The device characteristics were defined to limit the secondary flow effects inherent to this particular geometry. The determination of the operating conditions producing the desired shear stress profile was streamlined using a computational fluid dynamic (CFD) model validated with laser Doppler velocimetry. The novel ex vivo tissue culture system was validated in terms of its capability to reproduce a desired cone rotation and to maintain sterile conditions. The CFD results demonstrated that a cone angle of 0.5 deg, a cone radius of 40 mm, and a gap of 0.2 mm between the cone apex and the plate could limit radial secondary flow effects. The novel cone-and-plate permits to expose nine tissue specimens to an identical shear stress waveform. The whole setup is capable of accommodating four cone-and-plate systems, thus concomitantly subjecting 36 tissue samples to desired shear stress condition. The innovative design enables the tissue specimens to be flush mounted in the plate in order to limit flow perturbations caused by the tissue thickness. The device is capable of producing shear stress rates of up to 650 dyn cm(-2) s(-1) (i.e., maximum shear stress rate experienced by the ventricular surface of an aortic valve leaflet) and was shown to maintain tissue under sterile conditions for 120 h. The novel ex vivo tissue culture system constitutes a valuable tool toward elucidating heart valve mechanobiology. Ultimately, this knowledge will permit the production of functional tissue engineered heart valves, and a better understanding of heart valve biology and disease progression.

Temporal Changes in Interpapillary Muscle Dynamics as an Active Indicator of Mitral Valve and Left Ventricular Interaction in Ischemic Mitral Regurgitation

BACKGROUND Regional subpapillary myocardial hypokinesis may impair lateral reduction in the interpapillary muscle distance (IPMD) from diastole to systole, and adversely affect mitral valve geometry and tethering. OBJECTIVES The goal of this study was to investigate the impact of impaired lateral shortening in the interpapillary muscle distance on mitral valve geometry and function in ischemic heart disease. METHODS To quantify ventricular size/shape, regional myocardial contraction, lateral shortening of the IPMD, mitral valve geometry, and severity of mitral regurgitation, 67 patients with ischemic heart disease underwent cardiac magnetic resonance imaging, and a correlation analysis of measured parameters was performed. The impact of reduced IPMD shortening on mitral valve (dys)function was confirmed in swine and in a physiological computational mitral valve model. RESULTS Lateral shortening of the IPMD from diastole to systole was severely reduced in patients with moderate/severe ischemic mitral regurgitation (9.6 ± 2.8 mm), but preserved in mild IMR (11.5 ± 3.4 mm). Left ventricular size and ejection fraction did not differ between the groups. In swine with subpapillary infarction and impaired IPMD, mitral regurgitation was evident within 1 week, compared to those pigs with a nonpapillary infarction and preserved IPMD. In the controlled computational valve model, IPMD had the maximal impact on regurgitation, and was exacerbated with additional annular dilation. CONCLUSIONS By using cardiac magnetic resonance imaging in humans, we demonstrated that it is the impairment of lateral shortening between the papillary muscles, and not passive ventricular size, that governs the severity of mitral regurgitation. Loss of lateral shortening of IPMD tethers the leaflet edges and impairs their systolic closure, resulting in mitral regurgitation, even in small ventricles. Understanding the lateral dynamics of ventricular-valve interactions could aid the development of new repair techniques for ischemic mitral regurgitation.

Mechanics of the Mitral Valve Strut Chordae Insertion Region

Interest in developing durable mitral valve repair methods is growing, underscoring the need to better understand the native mitral valve mechanics. In this study, the authors investigate the dynamic deformation of the mitral valve strut chordae-to-anterior leaflet transition zone using a novel stretch mapping method and report the complex mechanics of this region for the first time. Eight structurally normal porcine mitral valves were studied in a pulsatile left heart simulator under physiological hemodynamic conditions -120 mm peak transvalvular pressure, 5 l/min cardiac output at 70 bpm. The chordal insertion region was marked with a structured array of 31 miniature markers, and their motions throughout the cardiac cycle were tracked using two high speed cameras. 3D marker coordinates were calculated using direct linear transformation, and a second order continuous surface was fit to the marker cloud at each time frame. Average areal stretch, principal stretch magnitudes and directions, and stretch rates were computed, and temporal changes in each parameter were mapped over the insertion region. Stretch distribution was heterogeneous over the entire strut chordae insertion region, with the highest magnitudes along the edges of the chordal insertion region and the least along the axis of the strut chordae. At early systole, radial stretch was predominant, but by mid systole, significant stretch was observed in both radial and circumferential directions. The compressive stretches measured during systole indicate a strong coupling between the two principal directions, explaining the small magnitude of the systolic areal stretch. This study for the first time provides the dynamic kinematics of the strut chordae insertion region in the functioning mitral valve. A heterogeneous stretch pattern was measured, with the mechanics of this region governed by the complex underlying collagen architecture. The insertion region seemed to be under stretch during both systole and diastole, indicating a transfer of forces from the leaflets to the chordae and vice versa throughout the cardiac cycle, and demonstrating its role in optimal valve function.

Right ventricular papillary muscle approximation as a novel technique of valve repair for functional tricuspid regurgitation in an ex vivo porcine model

OBJECTIVES Annuloplasty for functional tricuspid regurgitation may sometimes be ineffective because of chamber dilation and valve tethering. This study compared a novel technique, right ventricle (RV)-papillary muscle approximation, with annuloplasty in experimentally-produced tricuspid regurgitation. METHODS RVs of isolated porcine hearts (n = 10) were statically pressurized, which led to RV dilation and central tricuspid regurgitation. Regurgitant flow was measured with a saline solution-filled column. The head of the anterior papillary muscle was approximated to 4 points on the ventricular septum. Next, a prosthetic ring was implanted, and then RV-papillary muscle approximation was combined. Tricuspid annular dimension, RV geometry, and tricuspid valve tethering were analyzed with 3-dimensional echocardiography. RESULTS Tricuspid regurgitation (2270 ± 186 mL/min) was reduced by RV-papillary muscle approximation alone (214 ± 45 mL/min; P < .05) more than by annuloplasty alone (724 ± 166 mL/min; P < .05). Combined RV-papillary muscle approximation and annuloplasty resulted in the least regurgitation (80 ± 39 mL/min). RV-papillary muscle approximation reduced tricuspid septolateral diameter (25%; P < .05), and annular area (23%; P < .05), as did annuloplasty. RV-papillary muscle approximation also reduced RV sphericity index (33%; P < .05) and tricuspid tethering height (54%; P < .05), whereas annuloplasty did not. Direction of RV-papillary muscle approximation did not independently affect outcomes. CONCLUSIONS This ex vivo study suggests that RV-papillary muscle approximation potentially repairs tricuspid regurgitation better than annuloplasty by improving ventricular sphericity and valve tethering as well as annular dimension.

Regional analysis of dynamic deformation characteristics of native aortic valve leaflets.

BACKGROUND The mechanical environment of the aortic valve (AV) has a significant impact on valve cellular biology and disease progression, but the regional variation in stretch across the AV leaflet is not well understood. This study, therefore, sought to quantify the regional variation in dynamic deformation characteristics of AV leaflets in the native mechanical environment in order to link leaflet stretch variation to reported AV calcification patterns. METHODS Whole porcine AVs (n=6) were sutured into a physiological left heart simulator and subjected to pulsatile and physiologically normal hemodynamic conditions. A grid of ink dots was marked on the entire ventricular surface of the AV leaflet. Dual camera stereo photogrammetry was used to determine the stretch magnitudes across the entire ventricular surface over the entire diastolic duration. RESULTS Elevated stretch magnitudes were observed along the leaflet base and coaptation line consistent with previously reported calcification patterns suggesting the higher mechanical stretch experienced by the leaflets in these regions may contribute to increased disease propensity. Transient stretch overloads were observed during diastolic closing, predominantly along the leaflet base, indicating the presence of a dynamic fluid hammer effect resulting from retrograde blood flow impacting the leaflet. We speculate the function of the leaflet base to act in cooperation with the sinuses of Valsalva to dampen the fluid hammer effect and reduce stress levels imparted on the rest of the leaflet.

Effect of anterior strut chordal transection on the force distribution on the marginal chordae of the mitral valve

OBJECTIVES Transection of the secondary chordae on the anterior leaflet of the mitral valve to relieve leaflet tethering and reduce regurgitation is an experimentally proven procedure to correct functional mitral regurgitation. In the present study, we sought to investigate whether transecting the secondary chordae would have an effect on the marginal chordal force on the same leaflet. METHODS Adult porcine mitral valves (n = 8) were studied in a pulsatile heart simulator, in which the papillary muscle positions can be precisely positioned. Miniature transducers were inserted into the anterior marginal chordae to measure the chordal forces. Each valve was studied under baseline conditions, 3 different tethering conditions (apical, apical-lateral, and apical-lateral-posterior), and after chordal cutting in the 3 tethering conditions. The temporal changes and peak and average marginal chordal forces under each condition are reported. RESULTS Apical tethering increased the marginal chordal force by an average of 96% but remained unchanged after chordal cutting. With apical-lateral tethering, the marginal chordal force increased by 210% from baseline and increased further to 350% of baseline after chordal cutting. After apical-lateral-posterior tethering, the marginal chordal force increased to 335% of baseline before transection and by 548% after transection. CONCLUSIONS The increase in the marginal chordal force after secondary chordal cutting depends on the location of the papillary muscles and the extent of leaflet tethering. Although chordal cutting might not alter the valve mechanics under minimal leaflet tethering, it significantly affects the mechanics when the leaflet tethering is more pronounced, which is typically seen in patients with functional mitral regurgitation.

Elevated cyclic stretch and serotonin result in altered aortic valve remodeling via a mechanosensitive 5-HT2A receptor-dependent pathway

INTRODUCTION Serotonin/5-hydroxytryptamine (5-HT) has been implicated in valve disease and in the modulation of valve mechanical properties. Several 5-HT receptor subtypes are also known to be mechanosensitive in other cell types, but this has not been studied in the context of the valve. In this study, we sought to understand the effects of elevated 5-HT levels and stretch overload on aortic valve remodeling and the dominant 5-HT receptor subtype that regulates these processes. METHODS AND RESULTS Collagen biosynthesis and tissue mechanical properties of porcine aortic valve cusps were evaluated after 10% (physiologic) and 15% (pathologic) dynamic stretch. These studies were performed in normal medium or medium supplemented with 5-HT (1, 10, 100 μM) in the absence and presence of 5-HT(2A) or 5-HT(2B) receptor antagonists. Fresh valves served as controls. Valve collagen content was maximal at the 10-μM 5-HT concentration for both 10% and 15% stretch. The 5-HT(2A) receptor antagonist reduced collagen synthesis, cell proliferation, and hsp47 expression under elevated and normal stretch, whereas the 5-HT(2B) receptor antagonist was effective only at normal stretch. The pretransition stiffness of the valve cusps was also increased in response to 5-HT via a stretch-sensitive 5-HT(2A) mechanism, with the post-transition stiffness unaltered. CONCLUSIONS Combined elevated stretch and 5-HT resulted in increased valve collagen biosynthesis, cell proliferation, and tissue stiffness. These responses were inhibited by a 5-HT(2A) antagonist. This strongly suggests that the 5-HT(2A) receptor subtype is sensitive to elevated stretch.

Cleft closure and undersizing annuloplasty improve mitral repair in atrioventricular canal defects

OBJECTIVE Reoperation rates to correct left atrioventricular valve regurgitation after primary repair of atrioventricular canal defects remain relatively high. The causes of valvular regurgitation are likely multifactorial, and simple cleft closure is often insufficient to prevent recurrence. METHODS To elucidate the mechanisms leading to regurgitation, we conducted hemodynamic studies using isolated native mitral valves. Anatomy of these valves was altered to mimic atrioventricular canal type valves and studied under pediatric hemodynamic conditions. The impact of subvalvular geometry, cleft closure, annular dilatation, and annular undersizing on regurgitation were investigated. RESULTS Papillary muscle position did not have a significant effect on regurgitation. Cleft closure had a significant impact on valvular competence, with reduction in regurgitation volume with increased cleft closure. Regurgitation volume decreased from 12.5 +/- 2.4 mL/beat for an open cleft to 4.9 +/- 1.9 mL/beat for a partially closed cleft and to 1.4 +/- 1.6 mL/beat when the cleft was completely closed. Annular dilatation had a significant impact on regurgitation even after cleft closure. A 40% increase in annular size increased regurgitation by 59% for a partially closed cleft and by 84% for a fully closed cleft. Reducing the annular size by 20% from the physiologic level decreased the regurgitation volume by 12% for a fully open cleft and by 58% for the partially closed cleft case. CONCLUSIONS Annular dilatation after primary repair has a potentially significant role in the recurrence of atrioventricular valve regurgitation. Reducing the annular size and restricting dilatation as an adjunct to cleft closure is a promising surgical approach in such valve anatomies.