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Timek T.A.,West Michigan Cardiothoracic Surgeons and Spectrum Health | Lai D.T.,Stanford University | Liang D.,Stanford University | Daughters G.T.,Stanford University | And 3 more authors.
Journal of Heart Valve Disease | Year: 2010

Background and aim of the study: The optimal treatment of moderate ischemic mitral regurgitation (IMR) remains contested. Thus, radiopaque markers were implanted on valvular structures to investigate the geometric and hemodynamic variables associated with the evolution and progression of acute ovine IMR. Methods: Eight adult sheep underwent implantation of five radiopaque markers on the edge of the posterior mitral leaflet (PML), and five on the edge of the anterior mitral leaflet (AML). Eight additional markers were sewn around the mitral annulus (MA). The animals were studied immediately after surgery, using biplane videofluoroscopy and transesophageal echocardiography. Data were acquired at Baseline and at two time points (IMR1 and IMR2) during acute snare occlusion of the proximal left circumflex coronary artery and progressive IMR. The orthogonal distance of each leaflet edge marker to the least-squares annular plane, mitral annular area (MAA), and septal-lateral diameter (SL) were calculated at end-systole. The leaflet tenting area (TA) was calculated at valve center (CENT) and near the anterior (ACOM) and posterior (PCOM) commissures. Results: The degree of MR was 0.6 ± 0.4, 1.8 ± 0.7, and 2.8 ± 0.7 for Baseline, IMR1, and IMR2, respectively (p <0.005). IMR1 was associated with annular dilatation and leaflet restriction near the valve center, and prolapse near the PCOM versus Baseline. Although both left ventricular pressure (LVP) and left ventricular dP/dt decreased significantly from IMR1 to IMR 2, there were no differences in leaflet or annular geometry. Conclusion: The initiation of moderate IMR was associated with significant alterations in annular and leaflet geometry, but only a small decrease in LV systolic function, was needed for IMR progression. These data suggest that the surgical repair and optimization of LV function may be important in combination to treat moderate IMR, as only small hemodynamic deterioration and perturbations in valvular geometry are necessary for significant IMR progression. © Copyright by ICR Publishers 2010.


Stevanella M.,Polytechnic of Milan | Krishnamurthy G.,Stanford University | Krishnamurthy G.,Research Institute of the Palo Alto Medical Foundation | Votta E.,Polytechnic of Milan | And 4 more authors.
Journal of Biomechanics | Year: 2011

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. © 2011 Elsevier Ltd.


Kindberg K.,Linköping University | Oom C.,Linköping University | Ingels N.B.,Stanford University | Ingels N.B.,Research Institute of the Palo Alto Medical Foundation | Karlsson M.,Linköping University
Biomechanics and Modeling in Mechanobiology | Year: 2011

Left ventricular myofibers are connected by an extensive extracellular collagen matrix to form myolaminar sheets. Histological cardiac tissue studies have previously observed a pleated transmural distribution of sheets in the ovine heart, alternating sign of the sheet angle from epicardium to endocardium. The present study investigated temporal variations in myocardial fiber and sheet architecture during the cardiac cycle. End-diastolic histological measurements made at subepicardium, midwall, and subendocardium at an anterior-basal and a lateral-equatorial region of the ovine heart, combined with transmural myocardial Lagrangian strains, showed that the sheet angle but not the fiber angle varied temporally throughout the cardiac cycle. The magnitude of the sheet angle decreased during systole at all transmural depths at the anterior-basal site and at midwall and subendocardium depths at the lateral-equatorial site, making the sheets more parallel to the radial axis. These results support a previously suggested accordion-like wall-thickening mechanism of the myocardial sheets. © Springer-Verlag 2010.


Dimasi A.,Polytechnic of Milan | Cattarinuzzi E.,Polytechnic of Milan | Stevanella M.,Polytechnic of Milan | Conti C.A.,Polytechnic of Milan | And 6 more authors.
Cardiovascular Engineering and Technology | Year: 2012

Recent studies have demonstrated that, due to the active involvement of leaflet contractile elements, the anterior mitral leaflet (AML) is very stiff and maintains a compound curvature during ventricular systole. Studies based on structural mechanics have shown that both leaflet stiffness and compound curvature are key factors limiting AML deformation in the presence of high left ventricular (LV) systolic pressures. In the present study, we tested the hypothesis that maintenance of this physiological AML compound curvature also plays a role in the optimization of LV outflow during ejection. The LV cavity, mitral valve and aortic root of a healthy human were reconstructed from cardiac magnetic resonance images on 18 evenly rotated long-axis cut-planes at peak systole. Computational fluid dynamics was used to assess hemodynamics within the ventricular outflow tract in the presence of three different AML profiles: (i) physiologically compound as measured in vivo, (ii) flat, (iii) concave (i. e., prolapsed) towards the ventricle. Relative to the physiologic profile, AML flat and concave profiles induced progressively increasing hemodynamic alterations at the LV outflow and immediately downstream to the aortic valve, characterized at peak systole by flow detachment, a mean vorticity increase of 15.6 and 53.1% and an instantaneous power loss increase of 12 and 46%, respectively. These results support the hypothesis that the physiological AML shape plays an important role in optimizing LV ejection. This implies that AML profile alterations associated with valvular disease or surgical repair procedures can significantly reduce LV ejection efficiency. © 2012 Biomedical Engineering Society.


Itoh A.,Stanford University | Stephens E.H.,Rice University | Ennis D.B.,University of California at Los Angeles | Carlhall C.-J.,Linköping University | And 6 more authors.
American Journal of Physiology - Heart and Circulatory Physiology | Year: 2012

Previous studies of transmural left ventricular (LV) strains suggested that the myocardium overlying the papillary muscle displays decreased deformation relative to the anterior LV free wall or significant regional heterogeneity. These comparisons, however, were made using different hearts. We sought to extend these studies by examining three equatorial LV regions in the same heart during the same heartbeat. Therefore, deformation was analyzed from transmural beadsets placed in the equatorial LV myocardium overlying the anterolateral papillary muscle (PAP), as well as adjacent equatorial LV regions located more anteriorly (ANT) and laterally (LAT). We found that the magnitudes of LAT normal longitudinal and radial strains, as well as major principal strains, were less than ANT, while those of PAP were intermediate. Subepicardial and midwall myofiber angles of LAT, PAP, and ANT were not significantly different, but PAP subendocardial myofiber angles were significantly higher (more longitudinal as opposed to circumferential orientation). Subepicardial and midwall myofiber strains of ANT, PAP, and LAT were not significantly different, but PAP subendocardial myofiber strains were less. Transmural gradients in circumferential and radial normal strains, and major principal strains, were observed in each region. The two main findings of this study were as follows: 1) PAP strains are largely consistent with adjacent LV equatorial free wall regions, and 2) there is a gradient of strains across the anterolateral equatorial left ventricle despite similarities in myofiber angles and strains. These findings point to graduated equatorial LV heterogeneity and suggest that regional differences in myofiber coupling may constitute the basis for such heterogeneity. © 2012 the American H180 Physiological Society.


Kindberg K.,Linköping University | Haraldsson H.,Linköping University | Sigfridsson A.,Linköping University | Engvall J.,Linköping University | And 4 more authors.
BMC Medical Imaging | Year: 2012

Background: The ability to measure and quantify myocardial motion and deformation provides a useful tool to assist in the diagnosis, prognosis and management of heart disease. The recent development of magnetic resonance imaging methods, such as harmonic phase analysis of tagging and displacement encoding with stimulated echoes (DENSE), make detailed non-invasive 3D kinematic analyses of human myocardium possible in the clinic and for research purposes. A robust analysis method is required, however.Methods: We propose to estimate strain using a polynomial function which produces local models of the displacement field obtained with DENSE. Given a specific polynomial order, the model is obtained as the least squares fit of the acquired displacement field. These local models are subsequently used to produce estimates of the full strain tensor.Results: The proposed method is evaluated on a numerical phantom as well as in vivo on a healthy human heart. The evaluation showed that the proposed method produced accurate results and showed low sensitivity to noise in the numerical phantom. The method was also demonstrated in vivo by assessment of the full strain tensor and to resolve transmural strain variations.Conclusions: Strain estimation within a 3D myocardial volume based on polynomial functions yields accurate and robust results when validated on an analytical model. The polynomial field is capable of resolving the measured material positions from the in vivo data, and the obtained in vivo strains values agree with previously reported myocardial strains in normal human hearts. © 2012 Kindberg et al; licensee BioMed Central Ltd.


Bothe W.,Stanford University | Escobar Kvitting J.-P.,Stanford University | Stephens E.H.,Rice University | Swanson J.C.,Stanford University | And 4 more authors.
Journal of Thoracic and Cardiovascular Surgery | Year: 2011

Objective: The study objective was to quantify the effects of different annuloplasty rings on mitral leaflet septal-lateral tenting areas during acute myocardial ischemia. Methods: Radiopaque markers were implanted along the central septal-lateral meridian of the mitral valve in 30 sheep: 1 each to the septal and lateral aspects of the mitral annulus and 4 and 2 along the anterior and posterior mitral leaflets, respectively. Ten true-sized Carpentier-Edwards Physio, Edwards IMR ETLogix, and GeoForm annuloplasty rings (Edwards Lifesciences, Irvine, Calif) were inserted in a releasable fashion. Marker coordinates were obtained using biplane videofluoroscopy with ring inserted at baseline (RING-BL) and after 90 seconds of left circumflex artery occlusion (RING-ISCH). After ring release, another dataset was acquired before (No-Ring-BL) and after left circumflex artery occlusion (No-Ring-ISCH). Anterior and posterior mitral leaflet tenting areas were computed at mid-systole from sums of marker triangles with the midpoint between the annular markers being the vertex for all triangles. Results: Compared with No-Ring-BL, mitral regurgitation grades and all tenting areas significantly increased with No-Ring-ISCH. Compared with No-Ring-ISCH, (1) all rings significantly prevented mitral regurgitation and reduced all tenting areas; (2) Edwards IMR ETLogix and GeoForm rings reduced posterior mitral leaflet area, but not anterior mitral leaflet tenting area, to a significantly greater extent than the Carpentier-Edwards Physio ring; and (3) Edwards IMR ETLogix and GeoForm rings affected tenting areas similarly. Conclusions: In response to acute left ventricular ischemia, disease-specific functional/ischemic mitral regurgitation rings (Edwards IMR ETLogix, GeoForm) more effectively reduced posterior mitral leaflet area, but not anterior mitral leaflet tenting area, compared with true-sized physiologic rings (Carpentier-Edwards Physio). Despite its radical 3-dimensional shape and greater amount of mitral annular septal-lateral downsizing, the GeoForm ring did not reduce tenting areas more than the Edwards IMR ETLogix ring, suggesting that further reduction in tenting areas in patients with FMR/IMR may not be effectively achieved on an annular level. Copyright © 2011 by The American Association for Thoracic Surgery.


Timek T.A.,Meijer | Lai D.T.,Stanford University | Bothe W.,Stanford University | Liang D.,Stanford University | And 5 more authors.
Journal of Thoracic and Cardiovascular Surgery | Year: 2015

Background Novel surgical approaches are focusing on the "ventricular disease" of ischemic mitral regurgitation (IMR), to correct altered papillary muscle (PM) tip positions (apical displacement) and ameliorate leaflet tethering. Due to the anatomic complexity of the subvalvular apparatus, however, the precise geometric perturbations of the multiheaded PM tips associated with IMR remain uncharacterized. Methods In 6 adult sheep, we implanted 3 markers on each PM. To specifically identify distinct PM tips, 1 marker was placed on the PM origin of the dominant chord to the anterior, posterior, and commissural leaflets. Nine markers were placed on the edge of the posterior mitral leaflet, and 5 on the edge of the anterior mitral leaflet. Eight markers were sewn around the mitral annulus. Animals were studied immediately postoperatively, with biplane videofluoroscopy and transesophageal echocardiography, before and during acute snare occlusion of the proximal left circumflex coronary artery, to induce IMR. Papillary muscle tip and leaflet edge geometry was expressed as the orthogonal distance of each respective marker to the least-squares mitral annulus plane at end-systole. In addition, the distance from each PM tip marker to the mitral annulus "saddle horn" was calculated. Results Acute left circumflex occlusion significantly increased mitral regurgitation from a baseline of 0.7 ± 0.3 to 2.5 ± 0.5 (P <.05). The IMR was associated with posterior leaflet restriction near the central leaflet edge, with simultaneous prolapse of both leaflets near the posterior commissure. No apical displacement of PM tips was observed during IMR, although the posterior PM moved farther away from the midseptal annulus. Conclusions During acute ischemia, no apical displacement of any PM tip was observed. Posterior PM movement away from the annular saddle horn, and toward the annulus, was associated with IMR and leaflet prolapse near the posterior commissure, and with restriction near the valve center. These data may help guide development of surgical interventions aimed at PM repositioning. © 2015 The American Association for Thoracic Surgery.


Swanson J.C.,Stanford University | Krishnamurthy G.,Stanford University | Kvitting J.E.,Stanford University | Miller D.C.,Stanford University | And 2 more authors.
American Journal of Physiology - Heart and Circulatory Physiology | Year: 2011

Anterior leaflet (AL) stiffening during isovolumic contraction (IVC) may aid mitral valve closure. We tested the hypothesis that AL stiffening requires atrial depolarization. Ten sheep had radioopaque-marker arrays implanted in the left ventricle, mitral annulus, AL, and papillary muscle tips. Four-dimensional marker coordinates (x, y, z, and t) were obtained from biplane videofluoroscopy at baseline (control, CTRL) and during basal interventricular-septal pacing (no atrial contraction, NAC; 110-117 beats/min) to generate ventricular depolarization not preceded by atrial depolarization. Circumferential and radial stiffness values, reflecting force generation in three leaflet regions (annular, belly, and free-edge), were obtained from finite-element analysis of AL displacements in response to transleaflet pressure changes during both IVC and isovolumic relaxation (IVR). In CTRL, IVC circumferential and radial stiffness was 46 ± 6% greater than IVR stiffness in all regions (P < 0.001). In NAC, AL annular IVC stiffness decreased by 25% (P = 0.004) in the circumferential and 31% (P = 0.005) in the radial directions relative to CTRL, without affecting edge stiffness. Thus AL annular stiffening during IVC was abolished when atrial depolarization did not precede ventricular systole, in support of the hypothesis. The likely mechanism underlying AL annular stiffening during IVC is contraction of cardiac muscle that extends into the leaflet and requires atrial excitation. The AL edge has no cardiac muscle, and thus IVC AL edge stiffness was not affected by loss of atrial depolarization. These findings suggest one reason why heart block, atrial dysrhythmias, or ventricular pacing may be accompanied by mitral regurgitation or may worsen regurgitation when already present. © 2011 the American Physiological Society.


Bothe W.,Stanford University | Kvitting J.-P.E.,Stanford University | Swanson J.C.,Stanford University | Goktepe S.,Stanford University | And 4 more authors.
European Journal of Cardio-thoracic Surgery | Year: 2010

Objectives: To define the effects of annuloplasty rings (ARs) on the dynamic motion of anterior mitral leaflet (AML) and posterior mitral leaflet (PML). Methods: Fifty-eight adult, Dorsett-hybrid, male sheep (49±5kg) had radiopaque markers inserted: eight around the mitral annulus, four along the central meridian (from edge to annulus) of the AML (#A1-#A4) and one on the PML edge (#P1). True-sized Edwards Cosgrove (COS, n=12), St Jude RSAR (St. Jude Medical, St. Paul, MN, USA) (n=12), Carpentier-Edwards Physio (PHYSIO, n=12), Edwards IMR ETlogix (ETL, n=10) or Edwards GeoForm (GEO, n=12) ARs were implanted in a releasable fashion. Under acute open-chest conditions, 4D marker coordinates were obtained using biplane videofluoroscopy with the respective AR inserted (COS, RSAR, PHYSIO, ETL and GEO) and after release (COS-Control, RSAR-Control, PHYSIO-Control, ETL-Control and GEO-Control). AML and PML excursions were calculated as the difference between minimum and maximum angles between the central mitral annular septal-lateral chord and the AML edge markers (α1exc-α4exc) and PML edge marker (β1exc) during the cardiac cycle. Results: Relative to Control, (1) RSAR, PHYSIO, ETL and GEO increased excursion of the AML annular (α4exc: 13±6° vs 16±7°*, 16±7° vs 23±10°*, 12±4° vs 18±9°*, 15±1° vs 20±9°*, respectively) and belly region (α2exc: 41±10° vs 45±10°*, 42±8° vs 45±6°, n.s., 33±13° vs 42±14°*, 39±6° vs 44±6°*, respectively, α3exc: 24±9° vs 29±11°*, 28±10° vs 33±10°*, 16±9° vs 21±12°*, 25±7° vs 29±9°*, respectively), but not of the AML edge (α1exc: 42±8° vs 44±8°, 43±8° vs 41±6°, 42±11 vs 46±10°, 39±9° vs 38±8°, respectively, all n.s.). COS did not affect AML excursion (α1exc: 40±8° vs 37±8°, α2exc: 43±9° vs 41±9°, α3exc: 27±11° vs 27±10°, α4exc: 18±8° vs 17±7°, all n.s.). (2) PML excursion (β1exc) was reduced with GEO (53±5° vs 43±6°*), but unchanged with COS, RSAR, PHYSIO or ETL (53±13° vs 52±15°, 50±13° vs 49±10°, 55±5° vs 55±7°, 52±8° vs 58±6°, respectively, all n.s); *=p<0.05. Conclusions: RSAR, PHYSIO, ETL and GEO rings, but not COS, increase AML excursion of the AML annular and belly region, suggesting higher anterior mitral leaflet bending stresses with rigid rings, which potentially could be deleterious with respect to repair durability. The decreased PML excursion observed with GEO could impair left ventricular filling. Clinical studies are needed to validate these findings in patients. © 2010 European Association for Cardio-Thoracic Surgery.

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