| 1. |
- Bothe, Wolfgang, et al.
(författare)
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Effects of acute ischemic mitral regurgitation on three-dimensional mitral leaflet edge geometry
- 2008
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Ingår i: European Journal of Cardio-Thoracic Surgery. - : Oxford University Press (OUP). - 1010-7940 .- 1873-734X. ; 33, s. 191-197
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Tidskriftsartikel (refereegranskat)abstract
- Background: Improved quantitative understanding of in vivo leaflet geometry in ischemic mitral regurgitation (IMR) is needed to improve reparative techniques, yet few data are available due to current imaging limitations. Using marker technology we tested the hypotheses that IMR (1) occurs chiefly during early systole; (2) affects primarily the valve region contiguous with the myocardial ischemic insult; and (3) results in systolic leaflet edge restriction. Methods: Eleven sheep had radiopaque markers sutured as five opposing pairs along the anterior (A1–E1) and posterior (A2–E2) mitral leaflet free edges from the anterior commissure (A1–A2) to the posterior commissure (E1–E2). Immediately postoperatively, biplane videofluoroscopy was used to obtain 4D marker coordinates before and during acute proximal left circumflex artery occlusion. Regional mitral orifice area (MOA) was calculated in the anterior (Ant-MOA), middle (Mid-MOA), and posterior (Post-MOA) mitral orifice segments during early systole (EarlyS), mid systole (MidS), and end systole (EndS). MOA was normalized to zero (minimum orifice opening) at baseline EndS. Tenting height was the distance of the midpoint of paired markers to the mitral annular plane at EndS. Results: Acute ischemia increased echocardiographic MR grade (0.5 ± 0.3 vs 2.3 ± 0.7, p < 0.01) and MOA in all regions at EarlyS, MidS, and EndS: Ant-MOA (7 ± 10 vs 22 ± 19 mm2, 1 ± 2 vs18 ± 16 mm2, 0 vs 17 ± 15 mm2); Mid-MOA (9 ± 13 vs 25 ± 17 mm2, 3 ± 6 vs 21 ± 19 mm2, 0 vs 25 ± 17 mm2); and Post-MOA (8 ± 10 vs 25 ± 16, 2 ± 4 vs 22 ± 13 mm2, 0 vs 23 ± 13 mm2), all p < 0.05. There was no change in MOA throughout systole (EarlyS vs MidS vs EndS) during baseline conditions or ischemia. Tenting height increased with ischemia near the central and the anterior commissure leaflet edges (B1–B2: 7.1 ± 1.8 mm vs 7.9 ± 1.7 mm, C1–C2: 6.9 ± 1.3 mm vs 8.0 ± 1.5 mm, both p < 0.05). Conclusions: MOA during ischemia was larger throughout systole, indicating that acute IMR in this setting is a holosystolic phenomenon. Despite discrete postero-lateral myocardial ischemia, Post-MOA was not disproportionately larger. Acute ovine IMR was associated with leaflet restriction near the central and the anterior commissure leaflet edges. This entire constellation of annular, valvular, and subvalvular ischemic alterations should be considered in the approach to mitral repair for IMR.
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| 2. |
- Bothe, Wolfgang, et al.
(författare)
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Regional Mitral Leaflet Opening During Acute Ischemic Mitral Regurgitation
- 2009
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Ingår i: Journal of Heart Valve Disease. - : I C R Publishers. - 0966-8519 .- 2053-2644. ; 18:6, s. 586-597
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Tidskriftsartikel (refereegranskat)abstract
- Background and aim of the studyDiastolic mitral valve (MV) opening characteristics during ischemic mitral regurgitation (IMR) are poorly characterized. The diastolic MV opening dynamics was quantified along the entire valvular coaptation line in an ovine model of acute IMR.MethodsTen radiopaque markers were sutured in pairs on the anterior (A1-E1) and corresponding posterior (A2-E2) leaflet edges from the anterior (A1/A2) to the posterior (E1/E2) commissure in 11 adult sheep. Immediately after surgery, 4-D marker coordinates were obtained before and during occlusion of the proximal left circumflex coronary artery. Distances between marker pairs were calculated throughout the cardiac cycle every 16.7 ms. Leaflet opening was defined as the time after end-systole (ES) when the first derivative of the distance between marker pairs was greater than a threshold value of 3 cm/s. Valve opening velocity was defined as the maximum slope of marker pair tracings.ResultsHemodynamics were consistent with acute ischemia, as reflected by increased MR grade (0.5 ± 0.3 versus 2.3 ± 0.7, p <0.05), decreased contractility (dP/dtmax: 1,948 ± 598 versus 1,119 ± 293 mmHg/s, p <0.05), and slower left ventricular relaxation rate (dP/dtmin: −1,079 ± 188 versus −538 ± 147 mmHg/s, p <0.05). During ischemia, valve opening occurred earlier (A1/A2: 112 ± 28 versus 83 ± 43 ms, B1/B2: 105 ± 32 versus 68 ± 35 ms, C1/C2: 126 ± 25 versus 74 ± 37 ms, D1/D2: 114 ± 28 versus 71 ± 34 ms, E1/E2: 125 ± 29 versus 105 ± 33 ms; all p <0.05) and was slower (A1/A2: 16.8 ± 9.6 versus 14.2 ± 9.4 cm/s, B1/B2: 40.4 ± 9.9 versus 32.2 ± 10.0 cm/s, C1/C2: 59.0 ± 14.9 versus 50.4 ± 18.1 cm/s, D1/D2: 34.4 ± 10.4 versus 25.5 ± 10.9 cm/s; all p <0.05), except at the posterior edge (E1/E2: 13.3 ± 8.7 versus 10.6 ± 7.2 cm/s). The sequence of regional mitral leaflet separation along the line of coaptation did not change with ischemia.ConclusionAcute posterolateral left ventricular ischemia causes earlier leaflet opening, probably due to a MR-related elevation in left-atrial pressure; reduces leaflet opening velocity, potentially reflecting an impaired left ventricular relaxation rate; and does not perturb the homogeneous temporal pattern of regional valve opening along the line of coaptation. Future studies will confirm whether these findings are apparent in patients with chronic IMR, and may help to refine the current strategies used to treat IMR.
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| 3. |
- Carlhäll, Carljohan, et al.
(författare)
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Alterations in transmural myocardial strain - An early marker of left ventricular dysfunction in mitral regurgitation?
- 2008
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 118:14, s. S256-S262
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Tidskriftsartikel (refereegranskat)abstract
- Background-In asymptomatic patients with severe isolated mitral regurgitation (MR), identifying the onset of early left ventricular (LV) dysfunction can guide the timing of surgical intervention. We hypothesized that changes in LV transmural myocardial strain represent an early marker of LV dysfunction in an ovine chronic MR model. Methods and Results-Sheep were randomized to control (CTRL, n = 8) or experimental (EXP, n = 12) groups. In EXP, a 3.5-or 4.8-mm hole was created in the posterior mitral leaflet to generate "pure" MR. Transmural beadsets were inserted into the lateral and anterior LV wall to radiographically measure 3-dimensional transmural strains during systole and diastolic filling, at 1 and 12 weeks postoperatively. MR grade was higher in EXP than CTRL at 1 and 12 weeks (3.0 [2-4] versus 0.5 [0-2], 3.0 [1-4] versus 0.5 [0-1], respectively, both P < 0.001). At 12 weeks, LV mass index was greater in EXP than CTRL (201 +/- 18 versus 173 +/- 17 g/m(2), P < 0.01). LVEDVI increased in EXP from 1 to 12 weeks (P = 0.015). Between the 1 and 12 week values, the change in BNP (-4.5 +/- 4.4 versus-3.0 +/- 3.6 pmol/L), PRSW (9 +/- 13 versus 23 +/- 18 mm Hg), tau (-3 +/- 11 versus-4 +/- 7 ms), and systolic strains was similar between EXP and CTRL. The changes in longitudinal diastolic filling strains between 1 and 12 weeks, however, were greater in EXP versus CTRL in the subendocardium (lateral:-0.08 +/- 0.05 versus 0.02 +/- 0.14, anterior:-0.10 +/- 0.05 versus-0.02 +/- 0.07, both P < 0.01). Conclusions-Twelve weeks of ovine "pure" MR caused LV remodeling with early changes in LV function detected by alterations in transmural myocardial strain, but not by changes in BNP, PRSW, or tau.
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| 4. |
- Itoh, Akinobu, et al.
(författare)
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Active stiffening of mitral valve leaflets in the beating heart
- 2009
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Ingår i: AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY. - : American Physiological Society. - 0363-6135 .- 1522-1539. ; 296:6, s. H1766-H1773
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Tidskriftsartikel (refereegranskat)abstract
- The anterior leaflet of the mitral valve (MV), viewed traditionally as a passive membrane, is shown to be a highly active structure in the beating heart. Two types of leaflet contractile activity are demonstrated: 1) a brief twitch at the beginning of each beat (reflecting contraction of myocytes in the leaflet in communication with and excited by left atrial muscle) that is relaxed by midsystole and whose contractile activity is eliminated with beta-receptor blockade and 2) sustained tone during isovolumic relaxation, insensitive to beta-blockade, but doubled by stimulation of the neurally rich region of aortic-mitral continuity. These findings raise the possibility that these leaflets are neurally controlled tissues, with potentially adaptive capabilities to meet the changing physiological demands on the heart. They also provide a basis for a permanent paradigm shift from one viewing the leaflets as passive flaps to one viewing them as active tissues whose complex function and dysfunction must be taken into account when considering not only therapeutic approaches to MV disease, but even the definitions of MV disease itself.
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| 5. |
- Itoh, Akinobu, et al.
(författare)
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Contribution of myocardium overlying the anterolateral papillary muscle to left ventricular deformation
- 2012
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Ingår i: American Journal of Physiology. Heart and Circulatory Physiology. - : American Physiological Society. - 0363-6135 .- 1522-1539. ; 302:1, s. H180-H187
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Tidskriftsartikel (refereegranskat)abstract
- Itoh A, Stephens EH, Ennis DB, Carlhall CJ, Bothe W, Nguyen TC, Swanson JC, Miller DC, Ingels NB Jr. Contribution of myocardium overlying the anterolateral papillary muscle to left ventricular deformation. Am J Physiol Heart Circ Physiol 302: H180-H187, 2012. First published October 28, 2011; doi:10.1152/ajpheart.00687.2011.-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.
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| 6. |
- Krishnamurthy, Gaurav, et al.
(författare)
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Stress-strain behavior of mitral valve leaflets in the beating ovine heart
- 2009
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Ingår i: JOURNAL OF BIOMECHANICS. - : Elsevier BV. - 0021-9290. ; 42:12, s. 1909-1916
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Tidskriftsartikel (refereegranskat)abstract
- Excised anterior mitral leaflets exhibit anisotropic, non-linear material behavior with pre-transitional stiffness ranging from 0.06 to 0.09 N/mm(2) and post-transitional stiffness from 2 to 9 N/mm(2). We used inverse finite element (FE) analysis to test, for the first time, whether the anterior mitral leaflet (AML), in vivo, exhibits similar non-linear behavior during isovolumic relaxation (IVR). Miniature radiopaque markers were sewn to the mitral annulus, AML, and papillary muscles in 8 sheep. Four-dimensional marker coordinates were obtained using biplane videofluoroscopic imaging during three consecutive cardiac cycles. A FE model of the AML was developed using marker coordinates at the end of isovolumic relaxation (when pressure difference across the valve is approximately zero), as the reference state. AML displacements were simulated during IVR using measured left ventricular and atrial pressures. AML elastic moduli in the radial and circumferential directions were obtained for each heartbeat by inverse FEA, minimizing the difference between simulated and measured displacements. Stress-strain curves for each beat were obtained from the FE model at incrementally increasing transmittal pressure intervals during IVR. Linear regression of 24 individual stress-strain curves (8 hearts, 3 beats each) yielded a mean (+/- SD) linear correlation coefficient (r(2)) of 0.994 +/- 0.003 for the circumferential direction and 0.995 +/- 0.003 for the radial direction. Thus, unlike isolated leaflets, the AML, in vivo, operates linearly over a physiologic range of pressures in the closed mitral valve.
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| 7. |
- Nguyen, Tom c., et al.
(författare)
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The effect of pure mitral regurgitation on mitral annular geometry and three-dimensional saddle shape
- 2008
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Ingår i: Journal of Thoracic and Cardiovascular Surgery. - : Elsevier BV. - 0022-5223 .- 1097-685X. ; 136:3, s. 557-565
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Chronic ischemic mitral regurgitation is associated with mitral annular dilatation in the septal-lateral dimension and flattening of the annular 3-dimensional saddle shape. To examine whether these perturbations are caused by the ischemic insult, mitral regurgitation, or both, we investigated the effects of pure mitral regurgitation (low pressure volume overload) on annular geometry and shape. Methods: Eight radiopaque markers were sutured evenly around the mitral annulus in sheep randomized to control (CTRL, n = 8) or experimental (HOLE, n = 12) groups. In HOLE, a 3.5- to 4.8-mm hole was punched in the posterior leaflet to generate pure mitral regurgitation. Four-dimensional marker coordinates were obtained radiographically 1 and 12 weeks postoperatively. Mitral annular area, annular septal-lateral and commissure-commissure dimensions, and annular height were calculated every 16.7 ms. Results: Mitral regurgitation grade was 0.4 ± 0.4 in CTRL and 3.0 ± 0.8 in HOLE (P < .001) at 12 weeks. End-diastolic left ventricular volume index was greater in HOLE at both 1 and 12 weeks, end-systolic volume index was larger in HOLE at 12 weeks. Mitral annular area increased in HOLE predominantly in the commissure-commissure dimension, with no difference in annular height between HOLE versus CTRL at 1 or 12 weeks, respectively. Conclusion: In contrast with annular septal-lateral dilatation and flattening of the annular saddle shape observed with chronic ischemic mitral regurgitation, pure mitral regurgitation was associated with commissure-commissure dimension annular dilatation and no change in annular shape. Thus, infarction is a more important determinant of septal-lateral dilatation and annular shape than mitral regurgitation, which reinforces the need for disease-specific designs of annuloplasty rings. © 2008 The American Association for Thoracic Surgery.
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| 8. |
- Nguyen, Tom, et al.
(författare)
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Functional uncoupling of the mitral annulus and left ventricle with mitral regurgitation and dopamine
- 2008
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Ingår i: Journal of Heart Valve Disease. - 0966-8519 .- 2053-2644. ; 17, s. 168-178
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The mitral annulus and left ventricle are generally thought to be functionally coupled, in the sense that increases in left ventricular (LV) size, as seen in ischemic mitral regurgitation (MR), or decreases in LV size, as seen with inotropic stimulation, are thought to increase or decrease annular dimensions in similar manner. The study aim was to elucidate the functional relationship between the mitral annulus and left ventricle during acute MR and inotrope-induced MR reduction.METHODS: Radiopaque markers were implanted on the left ventricle and mitral annulus of five adult sheep. A suture was placed on the central scallop of the posterior mitral leaflet and exteriorized through the atrial-ventricular groove. Open-chest animals were studied at baseline (CTRL), at seconds after pulling on the suture to create moderate-severe 'pure' MR (PULL), and after titration of dopamine until the MR grade was maximally reduced (PULL+DOPA). This process was repeated two to three times for each animal.RESULTS: The MR grade was increased with PULL (from 0.5 +/- 0.01 to 3.4 +/- 0.4, p < 0.01) and decreased after PULL+DOPA (from 3.4 +/- 0.4 to 1.5 +/- 0.9, p < 0.001). PULL resulted in an increase in mitral annular (MA) area, predominantly by an increase in the muscular mitral annulus. PULL+DOPA caused a decrease in MA area, but the LV volume and dimensions were not altered with either PULL or PULL+DOPA.CONCLUSION: The acute geometric response to 'pure' MR and inotrope-induced MR reduction was limited to the mitral annulus. Surprisingly, the LV volume and dimensions did not change with acute MR or with inotrope-induced MR reduction. This suggests that, under these two conditions in an ovine model, the mitral annulus and left ventricle are functionally uncoupled.
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| 9. |
- Swanson, Julia C., et al.
(författare)
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Multiple mitral leaflet contractile systems in the beating heart
- 2011
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Ingår i: Journal of Biomechanics. - : Elsevier BV. - 0021-9290 .- 1873-2380. ; 44:7, s. 1328-1333
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Tidskriftsartikel (refereegranskat)abstract
- Mitral valve closure may be aided by contraction of anterior leaflet (AL) cardiac myocytes located in the annular third of the leaflet. This contraction, observed as a stiffening of the annular region of the AL during isovolumic contraction (IVC), is abolished by beta-blockade (βB). Sub-threshold rapid pacing in the region of aorto-mitral continuity (STIM) also causes AL stiffening, although this increases the stiffness of the entire leaflet during both IVC and isovolumic relaxation (IVR). We investigated whether these contractile events share a common pathway or whether multiple AL contractile mechanisms may be present. Ten sheep had radiopaque-markers implanted: 13 silhouetting the LV, 16 on the mitral annulus, an array of 16 on the AL, and one on each papillary muscle tip. 4-D marker coordinates were obtained from biplane videofluoroscopy during control (C), βB (esmolol) and during βB+STIM. Circumferential and radial stiffness values for three AL regions (Annular, Belly, and free-Edge), were obtained from inverse finite element analysis of AL displacements in response to trans-leaflet pressure changes during IVC and IVR. βB+STIM increased stiffness values in all regions at both IVC and IVR by 35 ± 7% relative to βB (p<0.001). Thus, even when AL myocyte contraction was blocked by βB, STIM stiffened all regions of the AL during both IVC and IVR. This demonstrates the presence of at least two contractile systems in the AL; one being the AL annular cardiac muscle, involving a β-dependent pathway, others via a β-independent pathway, likely involving valvular interstitial cells and/or AL smooth muscle cells.
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