Alumina as a Computed Tomography Soft Material and Tissue Fiducial Marker.

Background: The use of 3D imaging is becoming increasingly common, so too is the use of fiducial markers to identify/track regions of interest and assess material deformation. While many different materials have been used as fiducials, they are often used in isolation, with little comparison to one another. Objective: In the current study, we aim to directly compare different Computed Tomography (CT and µCT) fiducial materials, both metallic and nonmetallic. Methods: µCT imaging was performed on a soft-tissue structure, in this case heart valve tissue, with various markers attached. Additionally, we evaluated the same markers with DiceCT stained tissue in a fluid medium. Eight marker materials were tested in all. Results: All of the metallic markers generated significant artifacts and were found unsuitable for soft-tissue µCT imaging, whereas alumina markers were found to perform the best, with excellent contrast and consistency. Conclusions: These findings support the further use of alumina as fiducial markers for soft material and tissue studies that utilize CT and µCT imaging.

MicroCT Imaging of Heart Valve Tissue in Fluid.

BACKGROUND: Heart valve computational models require high quality geometric input data, commonly obtained using micro-computed tomography. Whether in the open or closed configuration, most studies utilize dry valves, which poses significant challenges including gravitational and surface tension effects along with desiccation induced mechanical changes. OBJECTIVE: These challenges are overcome by scanning in a stress-free configuration in fluid. Utilizing fluid backgrounds however reduces overall contrast due to the similar density of fluid and tissue. METHODS: The work presented here demonstrates imaging of the mitral valve by utilizing an iodine-based staining solution to improve the contrast of valve tissue against a fluid background and investigates the role of stain time and concentration. RESULTS: It is determined that an Olea europaea oil bath with a relatively high concentration, short stain time approach produces high quality imagery suitable for creating accurate 3D renderings. CONCLUSIONS: Micro-CT scanning of heart valves in fluid is shown to be feasible using iodine staining techniques.

Anterior mitral leaflet curvature in the beating ovine heart: a case study using videofluoroscopic markers and subdivision surfaces.

The implantation of annuloplasty rings is a common surgical treatment targeted to re-establish mitral valve competence in patients with mitral regurgitation. It is hypothesized that annuloplasty ring implantation influences leaflet curvature, which in turn may considerably impair repair durability. This research is driven by the vision to design repair devices that optimize leaflet curvature to reduce valvular stress. In pursuit of this goal, the objective of this manuscript is to quantify leaflet curvature in ovine models with and without annuloplasty ring using in vivo animal data from videofluoroscopic marker analysis. We represent the surface of the anterior mitral leaflet based on 23 radiopaque markers using subdivision surfaces techniques. Quartic box-spline functions are applied to determine leaflet curvature on overlapping subdivision patches. We illustrate the virtual reconstruction of the leaflet surface for both interpolating and approximating algorithms. Different scalar-valued metrics are introduced to quantify leaflet curvature in the beating heart using the approximating subdivision scheme. To explore the impact of annuloplasty ring implantation, we analyze ring-induced curvature changes at characteristic instances throughout the cardiac cycle. The presented results demonstrate that the fully automated subdivision surface procedure can successfully reconstruct a smooth representation of the anterior mitral valve from a limited number of markers at a high temporal resolution of approximately 60 frames per minute.

Transmural strains in the ovine left ventricular lateral wall during diastolic filling.

Rapid early diastolic left ventricular (LV) filling requires a highly compliant chamber immediately after systole, allowing inflow at low driving pressures. The transmural LV deformations associated with such filling are not completely understood. We sought to characterize regional transmural LV strains during diastole, with focus on early filling, in ovine hearts at 1 week and 8 weeks after myocardial marker implantation. In seven normal sheep hearts, 13 radiopaque markers were inserted to silhouette the LV chamber and a transmural beadset was implanted into the lateral equatorial LV wall to measure transmural strains. Four-dimensional marker dynamics were obtained 1 week and 8 weeks thereafter with biplane videofluoroscopy in closed-chest, anesthetized animals. LV transmural strains in both cardiac and fiber-sheet coordinates were studied from filling onset to the end of early filling (EOEF, 100 ms after filling onset) and at end diastole. At the 8 week study, subepicardial circumferential strain (ECC) had reached its final value already at EOEF, while longitudinal and radial strains were nearly zero at this time. Subepicardial ECC and fiber relengthening (Eff) at EOEF were reduced to 1 compared with 8 weeks after surgery (ECC:0.02+/-0.01 to 0.08+/-0.02 and Eff:0.00+/-0.01 to 0.03+/-0.01, respectively, both P<0.05). Subepicardial ECC during early LV filling was associated primarily with fiber-normal and sheet-normal shears at the 1 week study, but to all three fiber-sheet shears and fiber relengthening at the 8 week study. These changes in LV subepicardial mechanics provide a possible mechanistic basis for regional myocardial lusitropic function, and may add to our understanding of LV myocardial diastolic dysfunction.

Nonhomogeneous strain from sparse marker arrays for analysis of transmural myocardial mechanics.

BACKGROUND: Knowledge of normal cardiac kinematics is important when attempting to understand the mechanisms that impair the contractile function of the heart during disease. The complex kinematics of the heart can be studied by inserting radiopaque markers in the cardiac wall and study the pumping heart with biplane cineradiography. In order to study the local strain, the bead array was developed where small radiopaque beads are inserted along three columns transmurally in the left ventricle. METHOD: This paper suggests a straightforward method for strain computation, based on polynomial least-squares fitting and tailored for combined marker and bead array analyses. RESULTS: This polynomial method gives small errors for a realistic bead array on an analytical test case. The method delivers an explicit expression of the Lagrangian strain tensor as a polynomial function of the coordinates of material points in the reference configuration. The method suggested in this paper is validated with analytical strains on a deforming cylinder resembling the heart, compared to a previously suggested finite element method, and applied to in vivo ovine data. The errors in the estimated strain components are shown to remain unchanged on an analytical test case when evaluating the effects of one missing bead. In conclusion, the proposed strain computation method is accurate and robust, with errors smaller or comparable to the current gold standard when applied on an analytical test case.

Contribution of mitral annular dynamics to LV diastolic filling with alteration in preload and inotropic state.

Mitral annular (MA) excursion during diastole encompasses a volume that is part of total left ventricular (LV) filling volume (LVFV). Altered excursion or area variation of the MA due to changes in preload or inotropic state could affect LV filling. We hypothesized that changes in LV preload and inotropic state would not alter the contribution of MA dynamics to LVFV. Six sheep underwent marker implantation in the LV wall and around the MA. After 7-10 days, biplane fluoroscopy was used to obtain three-dimensional marker dynamics from sedated, closed-chest animals during control conditions, inotropic augmentation with calcium (Ca), preload reduction with nitroprusside (N), and vena caval occlusion (VCO). The contribution of MA dynamics to total LVFV was assessed using volume estimates based on multiple tetrahedra defined by the three-dimensional marker positions. Neither the absolute nor the relative contribution of MA dynamics to LVFV changed with Ca or N, although MA area decreased (Ca, P < 0.01; and N, P < 0.05) and excursion increased (Ca, P < 0.01). During VCO, the absolute contribution of MA dynamics to LVFV decreased (P < 0.001), based on a reduction in both area (P < 0.001) and excursion (P < 0.01), but the relative contribution to LVFV increased from 18 +/- 4 to 45 +/- 13% (P < 0.001). Thus MA dynamics contribute substantially to LV diastolic filling. Although MA excursion and mean area change with moderate preload reduction and inotropic augmentation, the contribution of MA dynamics to total LVFV is constant with sizeable magnitude. With marked preload reduction (VCO), the contribution of MA dynamics to LVFV becomes even more important.

Three-dimensional geometric comparison of partial and complete flexible mitral annuloplasty rings.

BACKGROUND: It has previously been shown in sheep that mitral annular physiologic dynamics during the cardiac cycle are abolished by complete ring annuloplasty, but recent clinical studies suggest that flexible partial ring annuloplasty preserves normal mitral annular dynamics. METHODS: Eight radiopaque markers were sutured equidistantly around the mitral anulus in 3 groups of sheep: no-ring control animals (n = 16); animals with a flexible Tailor partial ring annuloplasty (n = 6; St Jude Medical, Inc, St Paul, Minn); and animals with a flexible Duran ring annuloplasty (n = 7; Medtronic, Inc, Minneapolis, Minn). After 7 to 10 days' recovery, 3-dimensional marker coordinates were measured by biplane cinefluoroscopy. Mitral annular area and folding (defined as displacement of the mitral anulus from a least-squares plane) and mitral annular septal-lateral and commissure-commissure dimensions were calculated from the 3-dimensional marker coordinates throughout the cardiac cycle every 17 ms. RESULTS: In the no-ring control group mitral annular area varied from 8.0 +/- 0.2 to 7.2 +/- 0.2 cm(2) (10% +/- 2%), and the septal-lateral and commissure-commissure dimensions varied from 27.7 +/- 0.4 to 25.9 +/- 0.4 mm (7% +/- 1%) and from 38.2 +/- 0.8 to 36.4 +/- 0.8 mm (5% +/- 1%), respectively (mean +/- standard error of the mean, P <.001 for all comparisons). In the Duran ring annuloplasty and Tailor partial ring annuloplasty groups, the anulus was fixed in size throughout the cardiac cycle (area = 4.8 +/- 0.1 and 5.3 +/- 0.3 cm(2), septal-lateral = 21.8 +/- 0.7 and 22.0 +/- 0.8 mm, and commissure-commissure = 27.7 +/- 0.7 and 31.2 +/- 1.7 mm). Mitral annular folding did not differ significantly between the control and Tailor partial ring annuloplasty groups but was dampened in the Duran ring annuloplasty group. CONCLUSIONS: Partial Tailor flexible ring annuloplasty fixed mitral annular area and dimensions throughout the cardiac cycle in sheep; however, it preserved physiologic mitral annular folding dynamics, which might be important in terms of long-term valve function and prevention of left ventricular outflow tract obstruction.

Edge-to-edge mitral repair: tension on the approximating suture and leaflet deformation during acute ischemic mitral regurgitation in the ovine heart.

BACKGROUND: Edge-to-edge approximation of the mitral valve leaflets (Alfieri procedure) is a novel surgical treatment for patients with ischemic mitral regurgitation (IMR). Long-term durability may be limited if abnormal mitral leaflet stresses result from this procedure. The aim of the current study was to measure Alfieri stitch tension (F(A)) and to explore its geometric determinants in an ovine model of acute IMR as a reflection of the mitral leaflet stresses imposed by the procedure. METHODS AND RESULTS: Eight sheep were studied immediately after surgical placement of (1) a force transducer interposed between sutures approximating the central leaflet edges and (2) radiopaque markers around the mitral annulus and leaflet edges. Computer-aided analysis of videofluorograms was used to obtained 3D marker coordinates. Simultaneous measurements of F(A), septal-lateral annular dimension (L(S-L)), leaflet edge separation (L(SEP)), anterior (L(AL)) and posterior (L(PL)) leaflet length, and hemodynamic variables were obtained at baseline (CTL) and during acute IMR (circumflex artery occlusion). F(A) was significantly elevated throughout the cardiac cycle during IMR compared with CTL, with maximum F(A) in diastole (0.26+/-0.05 versus 0.46+/-0.08 N, CTL versus IMR; P<0.05). Multivariable analysis revealed L(S-L) as the single independent predictor of maximum F(A) (P<0.001). Positive linear correlations were shown between values of F(A) and L(AL) and L(PL) (dependent variables). CONCLUSIONS: These experimental data demonstrate higher F(A) during IMR and cyclic changes in F(A) closely paralleling changes in L(S-L), eg, being greatest in diastole when the annulus is largest. Increased F(A) during IMR is probably indicative of successful therapeutic intent, but higher diastolic leaflet stresses resulting from persistent or progressive mitral annular dilatation may adversely affect repair durability. This indirectly implies that concomitant mitral ring annuloplasty should be added to the Alfieri repair.

Pathogenesis of mitral regurgitation in tachycardia-induced cardiomyopathy.

BACKGROUND: Dilated cardiomyopathy is often associated with mitral regurgitation (MR), or so-called functional MR, the mechanism of which continues to be debated. We studied the valvular and ventricular 3D geometric perturbations associated with MR in an ovine model of tachycardia-induced cardiomyopathy (TIC). METHODS AND RESULTS: Nine sheep underwent myocardial marker implantation in the left ventricle (LV), mitral annulus, and mitral leaflets. After 5 to 8 days, the animals were studied with biplane videofluoroscopy (baseline), and mitral competence was assessed by transesophageal echocardiography. Rapid ventricular pacing (180 to 230 bpm) was subsequently initiated for 15+/-6 days until the development of TIC and MR, whereupon biplane videofluoroscopy and transesophageal echocardiography studies were repeated. LV volume was calculated from the epicardial marker array. Valve closure time was defined as the time after end diastole when the distance between leaflet edge markers reached its minimal plateau. TIC resulted in increased LV end-diastolic volume (P=0.001) and LV end-systolic volume (P=0.0001) and greater LV sphericity (P=0.02). MR increased significantly (grade 0.2+/-0.3 versus 2.2+/-0.9, P=0.0001), as did mitral annulus area (817+/-146 versus 1100+/-161 mm(2), P=0.0001) and mitral annulus septal-lateral diameter (28.2+/-3.5 versus 35.1+/-2.6 mm, P=0.0001). Time of valve closure (70+/-18 versus 87+/-14 ms, P=0.23) and angular displacement of both the anterior (29+/-5 degrees versus 27+/-3 degrees, P=0.3) and posterior (55+/-15 degrees versus 44+/-11 degrees, P=0.13) leaflet edges relative to the mitral annulus after valve closure did not change, but leaflet edge separation after closure increased (5.2+/-0.9 versus 6.8+/-1.2 mm, P=0.019). CONCLUSIONS: MR in TIC resulted from decreased leaflet coaptation secondary to annular dilatation in the septal-lateral direction. These data support the use of annular reduction procedures, such as rigid, complete ring annuloplasty, to address functional MR in patients with dilated cardiomyopathy.

Influence of anterior mitral leaflet second-order chordae on leaflet dynamics and valve competence.

BACKGROUND: Chordal transposition is used in mitral valve repair, yet the effects of second-order chord transection on valve function have not been extensively studied. We evaluated leaflet coaptation, three-dimensional anterior mitral valve leaflet shape, and valve competence after cutting anterior second-order chordae. METHODS: In 8 sheep radiopaque markers were affixed to the left ventricle, mitral annulus, and leaflets. Animals were studied immediately with biplane videofluoroscopy and echocardiography before (Control) and after (Cut2) severing two anterior second-order "strut" chordae. Leaflet coaptation was assessed as separation between leaflet edge markers in the midleaflet and near each commissure (anterior commissure, posterior commissure). Anterior leaflet geometry was determined 100 milliseconds after end-diastole from three-dimensional coordinates of 13 markers. RESULTS: Anterior leaflet geometry changed only slightly after chordal transection without inducing mitral regurgitation. Leaflet coaptation times were 79+/-17 and 87+/-22 milliseconds at the anterior commissure; 72+/-21, 72+/-19 milliseconds at midleaflet, and 71+/-12 and 75+/-8 milliseconds at the posterior commissure (p = NS) for Control and Cut2, respectively. CONCLUSIONS: Cutting anterior second-order chordae did not cause delayed leaflet coaptation, alter leaflet shape, or create mitral regurgitation. These data indicate that transposition of second-order anterior chordae ("strut" chordae) is not deleterious to anterior leaflet motion per se.

The role of atrial contraction in mitral valve closure.

BACKGROUND AND AIM OF THE STUDY: Ovine mitral valve closure is associated with presystolic mitral annular reduction coincident with atrial contraction, which is abolished with ventricular pacing. Whether lack of properly timed atrial contraction influences mitral valve closure or competence, however, is not known. METHODS: Eight sheep underwent myocardial marker implantation on the left ventricle, mitral annulus (MA), and mitral leaflets. After 7-10 days, the animals were studied with biplane videofluoroscopy at baseline and during ventricular or atrioventricular (AV) sequential pacing. Valve closure was timed from end-diastole (ED) and defined as minimum distance between two leaflet edge markers. ED was defined as peak of ECG R wave, end-systole as peak negative left ventricular (LV) dP/dt, and end-isovolumic contraction (EIVC) as 83.5 ms after ED. Septal-lateral (S-L) annular diameter was defined as distance between two markers at the middle of the anterior and posterior annulus. Regurgitant volume (RV) was calculated as relative volume change between ED and EIVC. RESULTS: V-pacing was associated with delayed leaflet closure (65 +/- 5 versus 29 +/- 10 ms, p = 0.008); moreover, RV (4.1 +/- 0.5 versus 1.4 +/- 0.5 ml, p = 0.02), end-diastolic S-L diameter (2.87 +/- 0.10 versus 2.67 +/- 0.09 cm, p = 0.0005), and MA area (8.12 +/- 0.37 versus 7.26 +/- 0.31 cm2, p = 0.009) all increased. RV and leaflet and annular dynamics during AV-pacing were similar to baseline. CONCLUSION: V-pacing increased S-L MA diameter by only 8 +/- 1%, but this change was associated with delayed leaflet coaptation and a 16 +/- 1% regurgitant fraction. These findings provide direct evidence that a properly timed atrial contraction is functionally important for effective mitral leaflet closure.

Edge-to-edge mitral repair: gradients and three-dimensional annular dynamics in vivo during inotropic stimulation.

OBJECTIVE: The edge-to-edge (Alfieri) mitral repair technique appears to be clinically promising, but the potential for functional mitral stenosis, especially with exercise, remains a concern. We used the myocardial marker method combined with Doppler echocardiography to evaluate mitral annular (MA) three-dimensional (3-D) dynamics and transvalvular gradients after leaflet approximation before and during dobutamine infusion. METHODS: Eight adult sheep underwent implantation of eight myocardial markers around the MA and nine in the left ventricle. Mitral leaflet edges were approximated at the valve center and micromanometers were placed in the left ventricle and atrium. The animals were studied with biplane videofluoroscopy to determine 3-D marker coordinates for computation of precise 3-D MA area and left ventricular (LV) volume. Epicardial Doppler echocardiography measured peak and mean diastolic mitral valve gradients at baseline and during dobutamine infusion (10 microg/kg per min). RESULTS: During dobutamine stimulation, left ventricular dP/dt increased from 1776+/-712 to 3390+/-618 mmHg/s (P=0.002), and cardiac output (CO) increased from 2.7+/-1.1 to 5.1+/-1.2 l/min (P=0.009). Mitral annular area (MAA) at end-diastole (ED) fell from 8.6+/-1.4 to 7.0+/-1.8 cm(2) (P=0.001) with inotropic stimulation, but only a modest increase was observed in mean (1.4+/-0.4 vs. 2.4+/-1.0 mmHg, P=0.046) and peak (2.7+/-0.8 vs. 4.9+/-2.5 mmHg, P=0.03) diastolic mitral valve gradients. MAA changed dynamically throughout the cardiac cycle, reflecting normal physiology, but the magnitude of MAA change was augmented during inotropic stimulation (18+/-5% and 27+/-4% for control and dobutamine, respectively; P=0.004). CONCLUSION: Dobutamine increased CO by 89% and decreased ED annular area by 19% after edge-to-edge repair, yet only a small increase in valve gradient occurred. Marker analysis showed enhanced dynamic motion of the mitral annulus. Thus, the edge-to-edge mitral valve repair was not associated with substantial transvalvular obstruction during high flow conditions and did not perturb normal MA 3-D dynamics in normal ovine hearts.

Three-dimensional in-vivo dimensions of 'He's triangle' during acute left ventricular ischemia.

BACKGROUND AND AIM OF THE STUDY: Changes in the dimensions of 'He's triangle' (formed by mitral leaflet segments subtending two associated chordae tendineae) derived from data obtained in in-vitro mitral valve models have been proposed to provide a mechanistic explanation for mitral leaflet malcoaptation. The in-vivo dynamics of He's triangle, however, have not been hitherto determined. METHODS: Radio-opaque markers were placed in 13 sheep to delineate the mitral annulus and four (of an infinite number of possible) He's triangles formed by: (i) the anterior mitral leaflet (AML), first- (CT1) and second-order (CT2) chordae tendineae emanating from the anterior papillary tip (APT1) as well as from the posterior papillary tip (PPT1), respectively; and (ii) the posterior mitral leaflet (PML), CT1 and CT2 emanating from other loci on the anterior as well as the posterior papillary tips (APT2 and PPT2), respectively. Immediately postoperatively (anesthetized, open-chest), three-dimensional end-systolic marker positions were measured before and during circumflex coronary artery occlusion sufficient to produce mitral regurgitation, as verified by echocardiography. RESULTS: During ischemia, three leaflet segments constituting one side of three He's triangles elongated: The AML attached to APT1 and to PPT1 by 1.5+/-1.2 mm (p <0.001) and 1.3+/-0.8 mm (p <0.001), respectively, and the posterior leaflet attached to APT2 by 1.4+/-1.9 mm (p = 0.02). Apart from a 0.9+/-1.1 mm (p = 0.02) increase in the length of CT2 attached to APT2, the length of the seven other CT1 and CT2 remained relatively unchanged during acute left ventricular ischemia. CONCLUSION: With acute posterolateral ischemia, the lengths of CT1 and CT2 remained relatively constant, but the AML and PML lengths were not constant as the AML and PML 'unfurled' during acute left ventricular ischemia. These geometric changes may provide further insight into the mechanisms of acute ischemic mitral regurgitation, though it is not clear how they will be clinically helpful.

Coordinate-free analysis of mitral valve dynamics in normal and ischemic hearts.

BACKGROUND: The purpose of this investigation was to study mitral valve 3D geometry and dynamics by using a coordinate-free system in normal and ischemic hearts to gain mechanistic insight into normal valve function, valve dysfunction during ischemic mitral regurgitation (IMR), and the treatment effects of ring annuloplasty. METHODS AND RESULTS: Radiopaque markers were implanted in sheep: 9 in the ventricle, 1 on each papillary tip, 8 around the mitral annulus, and 1 on each leaflet edge midpoint. One group served as a control (n=7); all others underwent flexible Tailor partial (n=5) or Duran complete (n=6) ring annuloplasty. After an 8+/-2-day recovery, 3D marker coordinates were measured with biplane videofluoroscopy before and during posterolateral left ventricular ischemia, and MR was assessed by color Doppler echocardiography. Papillary to annular distances remained constant throughout the cardiac cycle in normal hearts, during ischemia, and after ring annuloplasty with either type of ring. Papillary to leaflet edge distances similarly remained constant throughout ejection. During ischemia, however, the absolute distances from the papillary tips to the annulus changed in a manner consistent with leaflet tethering, and IMR was observed. In contrast, during ischemia in either ring group, those distances did not change from preischemia, and no IMR was observed. CONCLUSIONS: This analysis uncovered a simple pattern of relatively constant intracardiac distances that describes the 3D geometry and dynamics of the papillary tips and leaflet edges from the dynamic mitral annulus. Ischemia perturbed the papillary-annular distances, and IMR occurred. Either type of ring annuloplasty prevented such changes, preserved papillary-annular distances, and prevented IMR.

The effects of ring annuloplasty on mitral leaflet geometry during acute left ventricular ischemia.

BACKGROUND: The perturbed mitral leaflet geometry that leads to acute ischemic mitral regurgitation during acute left ventricular ischemia has not been quantified, nor is it known whether annuloplasty rings affect these detrimental changes in leaflet geometry. METHODS: Radiopaque markers were implanted on both mitral leaflets and around the anulus in 3 groups of sheep: one group without rings served as the control group (n = 7); the others underwent Duran (n = 6; Medtronic Heart Valve Division, Minneapolis, Minn) or Carpentier-Edwards Physio (n = 5; Baxter Cardiovascular Division, Santa Ana, Calif) ring annuloplasty. After recovery, 3-dimensional marker coordinates were obtained by means of biplane videofluoroscopy before and during acute posterolateral left ventricular ischemia. Leaflet geometry was defined by measuring distances between annular and leaflet markers and perpendicular distances to the leaflet markers from a best-fit annular plane. RESULTS: In all control animals, left ventricular ischemia was associated with acute ischemic mitral regurgitation and apical displacement (away from the annular plane) of the posterior leaflet edge and base markers by 0.6 +/- 0.4 mm (P =.01) and 0.7 +/- 0.2 mm (P <.001), respectively. The distance between the posterior leaflet markers and the mid-posterior anulus did not change significantly during ischemia. The anterior leaflet edge marker extended 1.0 +/- 0. 5 mm (P =.01) away from the mid-anterior anulus during ischemia, but compared with its nonischemic position, the anterior leaflet was not displaced apically away from the annular plane. In all animals in the Duran and Physio groups, leaflet geometry was unchanged during ischemia, and acute ischemic mitral regurgitation was not detected. CONCLUSION: Acute ischemic mitral regurgitation was associated with restricted motion of the posterior leaflet and extension of the anterior leaflet. Annuloplasty rings prevented these geometric perturbations of the mitral leaflets during acute left ventricular ischemia and preserved valvular competence.

Mitral annular dynamics during rapid atrial pacing.

INTRODUCTION: Ovine mitral annular area (MAA) reduction predominantly occurs before ventricular systole. We used the myocardial marker methods to investigate left atrial and MAA dynamics during rapid atrial pacing. METHODS: Seven sheep underwent implantation of 21 myocardial markers around the mitral annulus, the left ventricle and left atrium. After 7 to 10 days, animals were studied with biplane videofluoroscopy to determine 3-dimensional marker coordinates unpaced and during rapid atrial pacing at 140 minutes(-1). Left ventricle volume, left atrial volume (LAV), and MAA were calculated from marker coordinates. End diastole (ED) was defined at peak of the electrocardiogram R wave; times of minimum MAA and minimum LAV were expressed relative to ED (t = 0). Percent reduction in MAA and LAV were calculated from maximum and minimum values between diastole and early systole. RESULTS: The time of minimum MAA occurred earlier relative to ED during rapid pacing compared with control (-48 +/- 21 vs 19 +/- 14 msec; P <.001), as did the time of minimum LAV (-47 +/- 18 vs 4 +/- 16 msec; P <.001). Minimum MAA and LAV were significantly smaller with rapid pacing (6. 8 +/- 0.6 vs 6.5 +/- 0.5 cm(2); P <.05, respectively; and 15.4 +/- 2. 4 vs 16.5 +/- 2.3 mL; P <.01, respectively), and a relatively greater fractional reduction in MAA and LAV was observed during presystole. CONCLUSIONS: Rapid atrial pacing resulted in greater MAA and LAV reduction, both of which occurred entirely during diastole. This study supports the notion that MAA reduction is closely linked to LA dynamics.

Ring annuloplasty prevents delayed leaflet coaptation and mitral regurgitation during acute left ventricular ischemia.

OBJECTIVE: Incomplete mitral leaflet coaptation during acute left ventricular ischemia is associated with end-diastolic mitral annular dilatation and ischemic mitral regurgitation. Annular rings were implanted in sheep to investigate whether annular reduction alone is sufficient to prevent mitral regurgitation during acute posterolateral left ventricular ischemia. METHODS: Radiopaque markers were inserted around the mitral anulus, on papillary muscle tips, and on the central meridian of both mitral leaflets in three groups of sheep: control (n = 5), Physio ring (n = 5) (Baxter Cardiovascular Div, Santa Ana, Calif), and Duran ring (n = 6) (Medtronic Heart Valve Div, Minneapolis, Minn). After 8 +/- 1 days, animals were studied with biplane videofluoroscopy before and during left ventricular ischemia. Annular area was calculated from 3-dimensional marker coordinates and coaptation defined as minimal distance between leaflet edge markers. RESULTS: Before ischemia, leaflet coaptation occurred just after end-diastole in all groups (control 17 +/- 41, Duran 33 +/- 30, Physio 33 +/- 24 ms, mean +/- SD, P >.2 by analysis of variance). During ischemia, regurgitation was detected in all control animals, and leaflet coaptation was delayed to 88 +/- 8 ms after end-diastole (P =.02 vs preischemia). This was associated with increased end-diastolic annular area (8.0 +/- 0.9 vs 6.7 +/- 0.6 cm(2), P =.004) and septal-lateral annular diameter (2.9 +/- 0.1 vs 2.5 +/- 0.1 cm, P =.02). Mitral regurgitation did not develop in Duran or Physio sheep, time to coaptation was unchanged (Duran 25 +/- 25 ms, Physio 30 +/- 48 ms [both P >.2 vs preischemia]), and annular area remained fixed. CONCLUSION: Mitral annular area reduction and fixation with an annuloplasty ring eliminated delayed leaflet coaptation and prevented mitral regurgitation during acute left ventricular ischemia after ring implantation.

Deformational dynamics of the aortic root: modes and physiologic determinants.

BACKGROUND: Current surgical methods for treating aortic valve and aortic root pathology vary widely, and the basis for selecting one repair or replacement alternative over another continues to evolve. More precise knowledge of the interaction between normal aortic root dynamics and aortic valve mechanics may clarify the implications of various surgical procedures on long-term valve function and durability. METHODS AND RESULTS: To investigate the role of aortic root dynamics on valve function, we studied the deformation modes of the left, right, and noncoronary aortic root regions during isovolumic contraction, ejection, isovolumic relaxation, and diastole. Radiopaque markers were implanted at the top of the 3 commissures (sinotubular ridge) and at the annular base of the 3 sinuses in 6 adult sheep. After a 1-week recovery, ECG and left ventricular and aortic pressures were recorded in conscious, sedated animals, and the 3D marker coordinates were computed from biplane videofluorograms (60 Hz). Left ventricular preload, contractility, and afterload were independently manipulated to assess the effects of changing hemodynamics on aortic root 3D dynamic deformation. The ovine aortic root undergoes complex, asymmetric deformations during the various phases of the cardiac cycle, including aortoventricular and sinotubular junction strain and aortic root elongation, compression, shear, and torsional deformation. These deformations were not homogeneous among the left, right, and noncoronary regions. Furthermore, changes in left ventricular volume, pressure, and contractility affected the degree of deformation in a nonuniform manner in the 3 regions studied, and these effects varied during isovolumic contraction, ejection, isovolumic relaxation, and diastole. CONCLUSIONS: These complex 3D aortic root deformations probably minimize aortic cusp stresses by creating optimal cusp loading conditions and minimizing transvalvular turbulence. Aortic valve repair techniques or methods of replacement using unstented autograft, allograft, or xenograft tissue valves that best preserve this normal pattern of aortic root dynamics should translate into a lower risk of long-term cusp deterioration.

Functional evaluation of the medtronic stentless porcine xenograft mitral valve in sheep.

BACKGROUND: Recently, renewed interest in allograft and stentless "freehand" bileaflet xenograft mitral valve replacement has arisen. The variability of human papillary tip anatomy and scarcity of donors limit allograft availability, making xenograft mitral valves an attractive alternative; however, these valves require new surgical implantation techniques, and assessment of their hemodynamics and functional geometry is lacking. METHODS: Seven sheep underwent implantation of a new stentless, glutaraldehyde-preserved porcine mitral valve (Physiological Mitral Valve [PMV], Medtronic) and were studied acutely under open-chest conditions. A new method of retrograde cardioplegia was developed. Hemodynamic valve function was assessed by epicardial Doppler echocardiography. 3D motion of miniature radiopaque markers sutured to the valve leaflets, annulus, and papillary tips was measured. Six other sheep with implanted markers served as controls. RESULTS: Both papillary muscle tips avulsed in the first animal, leaving 6 other animals. Mitral regurgitation was not observed in any xenograft valve. The peak and mean transvalvular gradients were 4.6+/-1.8 mm Hg and 2.6+/-1.5 mm Hg, respectively. The average mitral valve area was 5.7+/-1.6 cm(2). Valve closure in the xenograft group occurred later (30+/-11 ms, P<0. 015) and at higher left-ventricular pressure (61+/-9 mm Hg, P<0.001) than in the control group; furthermore, leaflet coaptation was displaced more apically (5.6+/-2.2 mm, P<0.001) and septally (5. 8+/-1.5 mm, P<0.001), and the anterolateral papillary tip underwent greater septal-lateral displacement (2.7+/-1.5 mm, P<0.001). Annular contraction during the cardiac cycle was similar in the 2 groups (xenograft 9.2+/-4.5% versus control 10.6+/-4.5% [mean+/-SD; 2-factor ANOVA model]). CONCLUSIONS: Successful freehand stentless porcine mitral valve implantation is feasible in sheep and was associated with excellent early postoperative hemodynamics. Physiological mitral valve annular contraction and functional leaflet closure mechanics were preserved. Long-term valve durability, calcification, and hemodynamic performance remain to be determined in models.

Mitral annular dilatation and papillary muscle dislocation without mitral regurgitation in sheep.

BACKGROUND: Asymmetrical mitral annular (MA) dilatation and papillary muscle dislocation are implicated in the pathogenesis of functional mitral regurgitation (MR). METHODS AND RESULTS: To determine the mechanism by which annular and papillary muscle geometric alterations result in MR, we implanted radiopaque markers in the left ventricle, mitral annulus, anterior and posterior mitral leaflets, and papillary muscle tips and bases in 2 groups of sheep. One group served as controls (CTL, n=7); an experimental group (EXP, n=9) underwent topical phenol application to obliterate anterior annular and leaflet muscle (confirmed histologically ex vivo). After 1 week of recovery, markers were imaged with biplane videofluoroscopy, and hemodynamic data were recorded. MA area (computed from 3-dimensional marker coordinates) was 11% to 13% larger in the EXP group than in the CTL group (P<0.05 by ANOVA). This area increase resulted exclusively from intercommissural axis increase except in 1 heart with large (>1 cm) increases in both the intercommissural and septolateral annular axes. The anterior papillary muscle tip in EXP was displaced from CTL by 2.9+/-0.23 mm toward the anterolateral left ventricle and 2.5+/-0.12 mm toward the mitral annulus at end systole; the posterior papillary muscle geometry was unchanged. Transthoracic echocardiography revealed MR only in the heart exhibiting biaxial annular enlargement. CONCLUSIONS: MA dilatation in the intercommissural dimension with anterior papillary muscle tip displacement toward the annulus is insufficient to produce MR in sheep. Functional MR may require MA dilatation in the septolateral axis, as observed with proximal circumflex coronary occlusion.