Tricuspid valve leaflet strains in the beating ovine heart.

The tricuspid leaflets coapt during systole to facilitate proper valve function and, thus, ensure efficient transport of deoxygenated blood to the lungs. Between their open state and closed state, the leaflets undergo large deformations. Quantification of these deformations is important for our basic scientific understanding of tricuspid valve function and for diagnostic or prognostic purposes. To date, tricuspid valve leaflet strains have never been directly quantified in vivo. To fill this gap in our knowledge, we implanted four sonomicrometry crystals per tricuspid leaflet and six crystals along the tricuspid annulus in a total of five sheep. In the beating ovine hearts, we recorded crystal coordinates alongside hemodynamic data. Once recorded, we used a finite strain kinematic framework to compute the temporal evolutions of area strain, radial strain, and circumferential strain for each leaflet. We found that leaflet strains were larger in the anterior leaflet than the posterior and septal leaflets. Additionally, we found that radial strains were larger than circumferential strains. Area strains were as large as 97% in the anterior leaflet, 31% in the posterior leaflet, and 31% in the septal leaflet. These data suggest that tricuspid valve leaflet strains are significantly larger than those in the mitral valve. Should our findings be confirmed they could suggest either that the mechanobiological equilibrium of tricuspid valve resident cells is different than that of mitral valve resident cells or that the mechanotransductive apparatus between the two varies. Either phenomenon may have important implications for the development of tricuspid valve-specific surgical techniques and medical devices.

Experimental and clinical assessment of mitral annular area and dynamics: what are we actually measuring?

The mitral annulus is an essential, dynamic, and tightly coupled component of the mitral valve/left atrial/left ventricular complex that aids in effective and efficient valve closure and unimpeded left ventricular filling. Although the dynamic nature of mitral annular motion has been studied carefully for more than 30 years, accurate measurement of mitral annular area and motion continues to be a challenge for physiologists and clinicians alike. Roentgenographic ciné imaging of radiopaque markers, sonomicrometry, magnetic resonance imaging, and two-dimensional echocardiography have all been used to evaluate mitral annular area and dynamics, yet widely disparate measurements abound. Paradoxically, newer three-dimensional transesophageal echocardiographic findings may have added to this miasma. To explore the variability of these measurements, we reviewed our experimental data as well as clinical and experimental observations reported in the literature to clarify what we are actually measuring and perhaps explain the reported disagreement. The objective was to shed some light on the possible reasons for these discordant findings.

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.

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.

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.