Tom C Nguyen

Stanford University, Palo Alto, California, United States

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Publications (24)139.03 Total impact

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    ABSTRACT: Progressive growth and remodeling of the left ventricle are part of the natural history of chronic heart failure and strong clinical indicators for survival. Accompanied by changes in cardiac form and function, they manifest themselves in alterations of cardiac strains, fiber stretches, and muscle volume. Recent attempts to shed light on the mechanistic origin of heart failure utilize continuum theories of growth to predict the maladaptation of the heart in response to pressure or volume overload. However, despite a general consensus on the representation of growth through a second order tensor, the precise format of this growth tensor remains unknown. Here we show that infarct-induced cardiac dilation is associated with a chronic longitudinal growth, accompanied by a chronic thinning of the ventricular wall. In controlled in vivo experiments throughout a period of seven weeks, we found that the lateral left ventricular wall adjacent to the infarct grows longitudinally by more than 10%, thins by more than 25%, lengthens in fiber direction by more than 5%, and decreases its volume by more than 15%. Our results illustrate how a local loss of blood supply induces chronic alterations in structure and function in adjacent regions of the ventricular wall. We anticipate our findings to be the starting point for a series of in vivo studies to calibrate and validate constitutive models for cardiac growth. Ultimately, these models could be useful to guide the design of novel therapies, which allow us to control the progression of heart failure.
    Journal of the mechanical behavior of biomedical materials. 04/2012; 8:165-77.
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    ABSTRACT: 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.
    AJP Heart and Circulatory Physiology 01/2012; 302(1):H180-7. · 4.01 Impact Factor
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    ABSTRACT: To establish the correspondence between the two histologically observable and diffusion tensor MRI (DTMRI) measurements of myolaminae orientation for the first time and show that single myolaminar orientations observed in local histology may result from histological artifact. DTMRI was performed on six sheep left ventricles (LV), then corresponding direct histological transmural measurements were made within the anterobasal and lateral-equatorial LV. Secondary and tertiary eigenvectors of the diffusion tensor were compared with each of the two locally observable sheet orientations from histology. Diffusion tensor invariants were calculated to compare differences in microstructural diffusive properties between histological locations with one observable sheet population and two observable sheet populations. Mean difference ± 1SD between DTMRI and histology measured sheet angles was 8° ± 27°. Diffusion tensor invariants showed no significant differences between histological locations with one observable sheet population and locations with two observable sheet populations. DTMRI measurements of myolaminae orientations derived from the secondary and tertiary eigenvectors correspond to each of the two local myolaminae orientations observed in histology. Two local sheet populations may exist throughout LV myocardium, and one local sheet population observed in histology may be a result of preparation artifact.
    Journal of Magnetic Resonance Imaging 09/2011; 34(5):1080-91. · 2.57 Impact Factor
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    ABSTRACT: Diastolic mitral valve (MV) opening characteristics during ischemic mitral regurgitation (IMR) are poorly characterized. The diastolic MV opening dynamics were quantified along the entire valvular coaptation line in an ovine model of acute IMR. Ten 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. Hemodynamics 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/dt(max): 1,948 +/- 598 versus 1,119 +/- 293 mmHg/s, p < 0.05), and slower left ventricular relaxation rate (dP/dt(min): -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. Acute 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.
    The Journal of heart valve disease 11/2009; 18(6):586-96; discussion 597. · 1.07 Impact Factor
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    ABSTRACT: The mitral annulus is a dynamic, saddle-shaped structure consisting of fibrous and muscular regions. Normal physiologic mechanisms of annular motion are incompletely understood, and more complete characterization is needed to provide rational basis for annuloplasty ring design and to enhance clinical outcomes. Seventeen sheep had radiopaque markers implanted; 16 around the annulus and 2 on middle anterior and posterior leaflet edges. Four-dimensional marker coordinates were acquired with biplanar videofluoroscopy at 60 Hz. Hinge angle was quantified between fibrous and muscular annular planes, with 0 degrees defined at end diastole, to characterize its contribution to alterations in mitral septal-lateral dimension and 2-dimensional total annular area throughout the cardiac cycle. During isovolumic contraction (pre-ejection), hinge angle abruptly increased, reaching maximum (steepest saddle shape, change 18 degrees +/- 13 degrees ) at peak left ventricular pressure. During ejection, hinge angle did not change; it then decreased during early filling (change 2 degrees +/- 2 degrees ). Septal-lateral dimension and total area paralleled hinge angle dynamics and leaflet distance (anterior to posterior marker). Pre-ejection septal-lateral reduction was 13% +/- 7% (3.3 +/- 1.5 mm) from 9% muscular dimension fall and 18 degrees +/- 13 degrees hinge angle increase. Pre-ejection increase in hinge angle contributes substantially to septal-lateral and total area reduction, facilitating leaflet coaptation. Semirigid annuloplasty rings or partial bands may preserve hinge motion, but possible recurrent annular dilatation could result in recurrent mitral regurgitation. Long-term clinical studies are required to determine who might benefit most from preserving intrinsic hinge motion without compromising repair durability.
    The Journal of thoracic and cardiovascular surgery 09/2009; 138(5):1090-9. · 3.41 Impact Factor
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    ABSTRACT: The mitral annulus (MA) is a dynamic structure that joins the left atrium (LA) and left ventricle (LV), but it is unknown whether MA motion is coupled to the LA or the LV or neither of the two. Since a well orchestrated coordination of LA, MA and LV septal-lateral (S-L) dynamics is essential for efficient valve closure, we assessed their functional coupling in an experimental ovine model. To assess the coupling under a wide range of physiological conditions, data were acquired in normal and acutely volume depleted hearts. In 10 sheep, radiopaque markers were placed in LA, MA and LV base (LVbase). Twelve weeks postoperatively, 4-D marker coordinates were obtained by stereo videofluoroscopy (60 frames/s) before (CTRL) and during acute inferior vena caval occlusion (VCO). Septal-lateral dimensions were calculated as distances between corresponding marker pairs in the LA, MA and LVbase 5 frames before end-diastole (ED-84 ms) and at end-diastole. Dynamics during late diastole are described as changes from ED-84 ms versus end-diastole. To study the functional coupling between LA, MA and LVbase we calculated slopes during late diastole from simple linear regressions on an animal-by-animal basis. During late diastole in CTRL, the LA and MA both shortened along the S-L dimension (32.9 +/- 6.6 mm vs 31.0 +/- 5.5 mm, p = 0.026 and 27.3 +/- 3.7 mm vs 24.6 +/- 4.1 mm, p = 0.005, respectively) whereas the LVbase lengthened (56.2 +/- 9.3 mm vs 57.3 +/- 9.3 mm, p = 0.012). VCO abolished septal-lateral dynamics of LA and LVbase during late diastole (27.8 +/- 4.3 mm vs 27.4 +/- 3.9 mm, p = 0.155 and 49.4 +/- 7.7 mm vs 49.5 +/- 7.5 mm, p = 0.752, respectively) while the MA still shortened (19.0 +/- 2.9 vs 18.0 +/- 2.8, p = 0.042). Under CTRL conditions LA dynamics were linearly dependent from MA dynamics (average coefficient 0.57, p = 0.001), suggesting that LA and MA are functionally coupled. With acute volume depletion, MA dynamics were linearly independent from both, LA and LV (average coefficient 0.28, p = 0.159 and 0.58, p = 0.192, respectively). Whereas MA and LA dynamics are coupled during late diastole in hearts with normal LV volumes, presystolic mitral annular septal-lateral shortening is independent from LA and LV dynamics with acute volume depletion. A better understanding of mitral annular dynamics and their functional coupling may help improve mitral valve repair strategies.
    European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 05/2009; 36(2):236-42; discussion 242-3. · 2.40 Impact Factor
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    ABSTRACT: Global left ventricular (LV) torsion declines with chronic ischemic mitral regurgitation (MR), which may accelerate the LV remodeling spiral toward global cardiomyopathy; however, it has not been definitively established whether this torsional decline is attributable to the infarct, the MR, or their combined effect. We tested the hypothesis that chronic "pure" MR alone reduces global LV torsion. Chronic "pure" MR was created in 13 sheep by surgically punching a 3.5- to 4.8-mm hole (HOLE) in the mitral valve posterior leaflet. Nine control (CNTL) sheep were operated on concurrently. At 1 (WK-01) and 12 weeks (WK-12) postoperatively, the 4D motion of implanted radiopaque markers was used to calculate global LV torsion. MR-grade in HOLE was greater than CNTL at WK-01 and WK-12 (2.5+/-1.1 versus 0.6+/-0.5, P<0.001 at WK-12). HOLE LV mass index was larger at WK-12 compared with CNTL (195+/-14 versus 170+/-17 g/m(2), P<0.01), indicating LV remodeling. Global LV systolic torsion decreased in HOLE from WK-01 to WK-12 (4.1+/-2.8 degrees versus 1.7+/-1.7 degrees , P<0.01), but did not change in CNTL (5.5+/-1.8 degrees versus 4.2+/-2.7 degrees , P=NS). Global LV torsion was lower in HOLE relative to CNTL at WK-12 (P<0.05) but not at WK-01 (P=NS). Twelve weeks of chronic "pure" MR resulting in mild global LV remodeling is associated with significantly increased LV mass index and reduced global LV systolic torsion, but no other significant changes in hemodynamics. MR alone is a major component of torsional deterioration in "pure" MR and may be an important factor in chronic ischemic mitral regurgitation.
    Circulation Cardiovascular Imaging 03/2009; 2(2):85-92. · 5.80 Impact Factor
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    ABSTRACT: Recent computational models of optimized left ventricular (LV) myofiber geometry that minimize the spatial variance in sarcomere length, stress, and ATP consumption have predicted that a midwall myofiber angle of 20 degrees and transmural myofiber angle gradient of 140 degrees from epicardium to endocardium is a functionally optimal LV myofiber geometry. In order to test the extent to which actual fiber angle distributions conform to this prediction, we measured local myofiber angles at an average of nine transmural depths in each of 32 sites (4 short-axis levels, 8 circumferentially distributed blocks in each level) in five normal ovine LVs. We found: (1) a mean midwall myofiber angle of -7 degrees (SD 9), but with spatial heterogeneity (averaging 0 degrees in the posterolateral and anterolateral wall near the papillary muscles, and -9 degrees in all other regions); and (2) an average transmural gradient of 93 degrees (SD 21), but with spatial heterogeneity (averaging a low of 51 degrees in the basal posterior sector and a high of 130 degrees in the mid-equatorial anterolateral sector). We conclude that midwall myofiber angles and transmural myofiber angle gradients in the ovine heart are regionally non-uniform and differ significantly from the predictions of present-day computationally optimized LV myofiber models. Myofiber geometry in the ovine heart may differ from other species, but model assumptions also underlie the discrepancy between experimental and computational results. To test the predictive capability of the current computational model would we propose using an ovine specific LV geometry and comparing the computed myofiber orientations to those we report herein.
    Journal of Biomechanics 10/2008; 41(15):3219-24. · 2.72 Impact Factor
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    ABSTRACT: Although chronic mitral regurgitation results in adverse left ventricular remodeling, its effect on the mitral valve leaflets per se is unknown. In a chronic ovine model, we tested whether isolated mitral regurgitation alone was sufficient to remodel the anterior mitral leaflet. Twenty-nine sheep were randomized to either control (CTRL, n=11) or experimental (HOLE, n=18) groups. In HOLE, a 2.8- to 4.8-mm diameter hole was punched in the middle scallop of the posterior mitral leaflet to create "pure" mitral regurgitation. At 12 weeks, the anterior mitral leaflet was analyzed immunohistochemically to assess markers of collagen and elastin synthesis as well as matrix metalloproteinases and proteoglycans. A semiquantitative grading scale for characteristics such as intensity and delineation of stain between layers was used to quantify differences between HOLE and CTRL specimens across the heterogeneous leaflet structure. At 12 weeks, mitral regurgitation grade was greater in HOLE versus CTRL (3.0+/-0.8 versus 0.4+/-0.4, P<0.001). In HOLE anterior mitral leaflet, saffron-staining collagen (Movat) decreased, consistent with an increase in matrix metalloproteases throughout the leaflet. Type III collagen expression was increased in the midleaflet and free edge and expression of prolyl-4-hydroxylase (indicating collagen synthesis) was increased in the spongiosa layer. The proteoglycan decorin, also involved in collagen fibrillogenesis, was increased compared with CTRL (all P</=0.05). In HOLE anterior mitral leaflet, the increased expression of proteins related to collagen synthesis and matrix degradation suggests active matrix turnover. These are the first observations showing that regurgitation alone can stimulate mitral leaflet remodeling. Such leaflet remodeling needs to be considered in reparative surgical techniques.
    Circulation 10/2008; 118(14 Suppl):S243-9. · 15.20 Impact Factor
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    ABSTRACT: 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. 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). 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.
    Circulation 10/2008; 118(14 Suppl):S256-62. · 15.20 Impact Factor
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    ABSTRACT: 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. 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. 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. 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.
    The Journal of thoracic and cardiovascular surgery 09/2008; 136(3):557-65. · 3.41 Impact Factor
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    ABSTRACT: Myocardial fibers are grouped into lamina (or sheets) 3 to 4 cells thick. Fiber shortening produces systolic left ventricular (LV) wall thickening primarily by laminar extension, thickening, and shear, but the regional variability and transmural distribution of these 3 mechanisms are incompletely understood. Nine sheep had transmural radiopaque markers inserted into the anterior basal and lateral equatorial LV. Four-dimensional marker dynamics were studied with biplane videofluoroscopy to measure circumferential, longitudinal, and radial systolic strains in the epicardium, midwall, and endocardium. Fiber and sheet angles from quantitative histology allowed transformation of these strains into transmural contributions of sheet extension, thickening, and shear to systolic wall thickening. At all depths, systolic wall thickening in the anterior basal region was 1.6 to 1.9 times that in the lateral equatorial region. Interestingly, however, systolic fiber shortening was identical at each transmural depth in these regions. Endocardial anterior basal sheet thickening was >2 times greater than in the lateral equatorial region (epicardium, 0.16+/-0.15 versus 0.03+/-0.06; endocardium, 0.45+/-0.40 versus 0.17+/-0.09). Midwall sheet extension was >2 times that in the lateral wall (0.22+/-0.12 versus 0.09+/-0.06). Epicardial and midwall sheet shears in the anterior wall were approximately 2 times higher than in the lateral wall (epicardium, 0.14+/-0.07 versus 0.05+/-0.03; midwall, 0.21+/-0.12 versus 0.12+/-0.06). These data demonstrate fundamentally different regional contributions of laminar mechanisms for amplifying fiber shortening to systolic wall thickening. Systolic fiber shortening was identical at each transmural depth in both the anterior and lateral LV sites. However, systolic wall thickening of the anterior site was much greater than that of the lateral site. Fiber shortening drives systolic wall thickening, but sheet dynamics and orientations are of great importance to systolic wall thickening. LV wall thickening and its clinical implications pivot on different wall thickening mechanisms in various LV regions. Attempts to implant healthy contractile cells into diseased hearts or to surgically manipulate LV geometry need to take into account not only cardiomyocyte contraction but also transmural LV intercellular architecture and geometry.
    Circulation 09/2008; 118(7):713-21. · 15.20 Impact Factor
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    ABSTRACT: 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. 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. 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. 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.
    The Journal of heart valve disease 04/2008; 17(2):168-77; discussion 178. · 1.07 Impact Factor
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    ABSTRACT: 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. Eleven sheep had radiopaque markers sutured as five opposing pairs along the anterior (A(1)-E(1)) and posterior (A(2)-E(2)) mitral leaflet free edges from the anterior commissure (A(1)-A(2)) to the posterior commissure (E(1)-E(2)). 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. 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 mm(2), 1+/-2 vs 18+/-16 mm(2), 0 vs 17+/-15 mm(2)); Mid-MOA (9+/-13 vs 25+/-17 mm(2), 3+/-6 vs 21+/-19 mm(2), 0 vs 25+/-17 mm(2)); and Post-MOA (8+/-10 vs 25+/-16, 2+/-4 vs 22+/-13 mm(2), 0 vs 23+/-13 mm(2)), 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 (B(1)-B(2): 7.1+/-1.8mm vs 7.9+/-1.7 mm, C(1)-C(2): 6.9+/-1.3mm vs 8.0+/-1.5mm, both p<0.05). 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.
    European Journal of Cardio-Thoracic Surgery 03/2008; 33(2):191-7. · 2.67 Impact Factor
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    ABSTRACT: Previous single-institution studies have documented a 0.6% to 2.4% incidence of gastrointestinal (GI) complications after coronary artery bypass grafting (CABG), with an associated 14% to 63% mortality rate. To better determine the incidence and impact of GI complications after CABG, national outcomes for CABG were examined from 1998 to 2002. The Nationwide Inpatient Sample was queried for all patients undergoing CABG (ICD9 procedure codes 36.10 to 36.16). Two cohorts were compared: CABGs with and without GI complications. Both demographic and outcomes variables were compared by either t-test or chi-square analysis. Logistic regression analyses indicated potential predictors of CABG inpatient mortality and GI complications after CABG. The incidence of GI complications among 2.7 million CABGs identified was 4.1%. Total hospital length of stay (19.3 versus 8.8 days) and inpatient mortality (12.0% versus 2.5%, both p < 0.0001) were increased in CABG patients having GI complications. Factors associated with increased risk of GI complications included: age greater than 65 years (odds ratio [OR], 2.1); hemodialysis (OR, 3.4); intraaortic balloon pump (OR, 1.6); concomitant valve procedure (OR, 1.5); and procedure urgency (OR, 1.22). Use of an internal mammary graft was protective (OR, 0.5), but GI complications increased inpatient mortality risk (OR, 2.6). This national population-based study indicates that GI complications after CABG occur at a higher rate than previously described, leading to increased hospital length of stay and mortality.
    Journal of the American College of Surgeons 12/2007; 205(6):741-7. · 4.50 Impact Factor
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    ABSTRACT: Undersized mitral annuloplasty has been widely employed for patients with ischemic mitral regurgitation. Beyond correction of mitral regurgitation, ring annuloplasty is postulated to normalize global left ventricular (LV) shape, thereby decreasing LV wall stress and promoting reverse LV remodeling. The effect of undersized annuloplasty on regional transmural LV wall thickening and strain patterns, however, has not been examined. In nine sheep, transmural radiopaque beadsets were inserted into the anterobasal and equatorial lateral LV walls, with additional markers silhouetting the left ventricle and mitral annulus. Four-dimensional marker dynamics were studied with biplane videofluoroscopy (open-chest) before and after tightening a Paneth-type mitral annuloplasty suture. LV volumes, mitral dimensions, transmural circumferential, longitudinal, and radial systolic strains, and end-diastolic (ED) and end-systolic (ES) remodeling strains in the two LV regions were computed. In the anterobasal LV wall close to the mitral annulus, annuloplasty increased ED wall thickness and surprisingly reduced systolic radial strain (wall thickening) at all transmural depths. Radial subepicardial, midwall, and subendocardial wall-thickening strains at ES in the anterobasal LV site were 0.25 +/- 0.15, 0.33 +/- 0.16, and 0.47 +/- 0.29, respectively, before tightening the suture annuloplasty, compared to 0.13 +/- 0.12, 0.15 +/- 0.18, and 0.20 +/- 0.26 after tightening. In the equatorial lateral LV wall further away from the annulus, most LV transmural systolic and remodeling strains did not change. Simulated undersized annuloplasty acutely decreased transmural systolic LV wall thickening in the anterobasal region, without substantially affecting transmural deformations in the lateral LV wall. These acute effects of undersized annuloplasty require a better understanding as they may potentially be deleterious, and a direct ventricular approach may be needed as an adjunct to promote reverse LV remodeling.
    The Journal of heart valve disease 08/2007; 16(4):349-58. · 1.07 Impact Factor
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    ABSTRACT: Septal-lateral annular cinching ('SLAC') corrects both acute and chronic ischemic mitral regurgitation in animal experiments, which has led to the development of therapeutic surgical and interventional strategies incorporating this concept (e.g., Edwards GeoForm ring, Myocor Coapsys, Ample Medical PS3). Changes in left ventricular (LV) transmural cardiac and fiber-sheet strains after SLAC, however, remain unknown. Eight normal sheep hearts had two triads of transmural radiopaque bead columns inserted adjacent to (anterobasal) and remote from (midlateral equatorial) the mitral annulus. Under acute, open chest conditions, 4D bead coordinates were obtained using videofluoroscopy before and after SLAC. Transmural systolic strains were calculated from bead displacements relative to local circumferential, longitudinal, and radial cardiac axes. Transmural cardiac strains were transformed into fiber-sheet coordinates (X(f), X(s), X(n)) oriented along the fiber (f), sheet (s), and sheet-normal (n) axes using fiber (alpha) and sheet (beta) angle measurements. Results: SLAC markedly reduced (approximately 60%) septal-lateral annular diameter at both end-diastole (ED) (2.5+/-0.3 to 1.0+/-0.3 cm, p=0.001) and end-systole (ES) (2.4+/-0.4 to 1.0+/-0.3 cm, p=0.001). In the LV wall remote from the mitral annulus, transmural systolic strains did not change. In the anterobasal region adjacent to the mitral annulus, ED wall thickness increased (p=0.01) and systolic wall thickening was less in the epicardial (0.28+/-0.12 vs 0.20+/-0.06, p=0.05) and midwall (0.36+/-0.24 vs 0.19+/-0.11, p=0.04) LV layers. This impaired wall thickening was due to decreased systolic sheet thickening (0.20+/-0.8 to 0.12+/-0.07, p=0.01) and sheet shear (-0.15+/-0.07 to -0.11+/-0.04, p=0.02) in the epicardium and sheet extension (0.21+/-0.11 to 0.10+/-0.04, p=0.03) in the midwall. Transmural systolic and remodeling strains in the lateral midwall (remote from the annulus) were unaffected. Although SLAC is an alluring concept to correct ischemic mitral regurgitation, these data suggest that extreme SLAC adversely effects systolic wall thickening adjacent to the mitral annulus by inhibiting systolic sheet thickening, sheet shear, and sheet extension. Such alterations in LV strains could result in unanticipated deleterious remodeling and warrant further investigation.
    European Journal of Cardio-Thoracic Surgery 04/2007; 31(3):423-9. · 2.67 Impact Factor
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    ABSTRACT: Ischemic mitral regurgitation (IMR) limits life expectancy and can lead to postinfarction global left ventricular (LV) dilatation and remodeling, the pathogenesis of which is not completely known. We tested the hypothesis that IMR perturbs adjacent myocardial LV systolic strains. Thirteen sheep had three columns of miniature beads inserted across the lateral LV wall, with additional epicardial markers silhouetting the ventricle. One week later posterolateral infarction was created. Seven weeks thereafter, the animals were divided into two groups according to severity of IMR (< or = 1+, n = 7, IMR[-] vs > or = 2+, n = 6, IMR[+]). Four dimensional marker coordinates and quantitative histology were used to calculate ventricular volumes, transmural myocardial systolic strains, and systolic fiber shortening. Seven weeks after infarction, end-diastolic (ED) volume increased similarly in both groups, end-systolic (ES) E13 (circumferential-radial) shear increased in both groups, but more so in IMR(+) than IMR(-) (+0.12 vs 0.04, p < 0.005), and E12 (circumferential-longitudinal) shear increased in IMR(-) but not IMR(+) (+0.04 vs -0.01, p < 0.005). There were no significant differences in ED or ES remodeling strains or systolic fiber shortening between IMR(-) and IMR(+). An equivalent increase in LV end-diastolic (ED) volume in both groups, coupled with unchanged ED and end-systolic remodeling strains as well as systolic circumferential, longitudinal, and radial strains, argue against a global LV or regional myocardial geometric basis for the cardiomyopathy associated with IMR. Further, similar systolic fiber shortening in both groups militates against an intracellular (cardiomyocyte) mechanism. The differences in subepicardial E12 and E13 shears, however, suggest a causal role of altered interfiber (cytoskeleton and extracellular-matrix) interactions.
    The Annals of thoracic surgery 01/2007; 83(1):47-54. · 3.45 Impact Factor
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    ABSTRACT: Passive ventricular constraint provides external cardiac support to reduce left ventricular (LV) wall stress and myocardial stretch, which are primary determinants of LV remodeling. Altered wall strain results in cytokine and reactive oxygen species production, which, in turn, stimulates apoptosis and extracellular matrix disruption and could be an important trigger for adverse global LV dilatation and remodeling. The effects of the Acorn cardiac support device (CSD) on regional transmural LV wall strains, however, remain unknown. Thirty-three sheep had transmural radiopaque beadsets surgically inserted into the anterior basal and lateral equatorial LV walls, with additional markers silhouetting the left ventricle. Eight animals had CSD implanted (myocardial infarction [MI]+CSD). One week thereafter, the MI+CSD group and 10 animals without CSD (MI) underwent posterior LV infarction by snaring obtuse marginal coronary arteries. Fifteen animals (Sham) had no infarction or CSD. 4D marker dynamics were measured with biplane videofluoroscopy 1 and 8 weeks postoperatively. LV volumes, sphericity index, and transmural circumferential, longitudinal, and radial systolic strains were analyzed. Compared with Sham, infarction (MI) dilated the heart, reduced sphericity index (LV length/width), and increased longitudinal-radial shear strains in the inner half of both the anterior and lateral LV walls. CSD prevented this shear strain perturbation, minimized LV end diastolic volume increase, and augmented the LV sphericity index. Prophylactic CSD prevented infarct-induced shear strain progression not only in myocardium adjacent to, but also remote from, the infarct. CSD also prevented LV dilatation and sphericalization. By attenuating shear strain abnormalities, CSD could prevent the heart from entering into a positive feedback loop of further LV dilatation and exaggeration of LV wall stress and may reduce biochemical triggers portending adverse LV remodeling.
    Circulation 08/2006; 114(1 Suppl):I79-86. · 15.20 Impact Factor
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    ABSTRACT: Undersized mitral annuloplasty, widely used for ischemic and functional mitral regurgitation (MR), has been proposed as an "annular solution to a ventricular problem." Beyond relief of MR, it is thought to improve global left ventricular (LV) shape, hence potentially reducing myocardial stress and promoting beneficial reverse LV remodeling. We previously observed that undersized annuloplasty inhibited systolic wall thickening at the LV base near the mitral annulus. In this study, we measured the effects of undersized annuloplasty on regional transmural LV wall fiber and sheet strains and wall thickening mechanisms. Nine sheep had transmural radiopaque beadsets surgically inserted into anterobasal and lateral equatorial LV regions, with additional markers silhouetting the LV and mitral annulus. 4-Dimensional marker dynamics were studied with biplane videofluoroscopy before and after tightening an adjustable Paneth-type mitral annuloplasty suture. Transmural circumferential, longitudinal, and radial systolic and remodeling strains in the subepicardium (20% depth), midwall (50%), and subendocardium (80%) in both regions were computed. Fiber and sheet angles from quantitative regional histology allowed transformation of these strains into local fiber (f), sheet (s), and sheet-normal (n) coordinates. Further analysis calculated the transmural contributions of sheet extension (E(ssc)), sheet thickening (E(nnc)), and sheet shear (E(snc)) to systolic wall thickening (E(33)). In the anterobasal region, undersized annuloplasty reduced systolic wall thickening (E33) by &50% at all transmural depths by inhibiting: (1) subendocardial systolic fiber shortening (-0.10+/-0.05 versus -0.04+/-0.05; P<0.05); (2) subepicardial (0.16+/-0.15 versus 0.09+/-0.08; P<0.05) and subendocardial (0.45+/-0.40 versus 0.19+/-0.18; P<0.05) systolic sheet thickening; (3) midwall sheet extension (0.22+/-0.12 versus 0.11+/-0.06; P<0.05); and (4) transmural sheet shear (subepicardium, -0.14+/-0.07 versus -0.08+/-0.07; midwall, 0.21+/-0.12 versus 0.10+/-0.11; subendocardium, -0.19+/-0.23 versus -0.11+/-0.16; P<0.05). In the remote lateral equatorial region, fiber-sheet strains and E33 were unchanged. In this acute animal study, undersized annuloplasty inhibited systolic wall thickening in the anterobasal region by reducing subendocardial systolic fiber shortening and laminar sheet wall thickening, but had no effects in a more distant LV region. This suggests that undersized mitral annuloplasty may have potentially deleterious effects on local myocardial mechanics.
    Circulation 07/2006; 114(1 Suppl):I600-9. · 15.20 Impact Factor

Publication Stats

239 Citations
139.03 Total Impact Points

Institutions

  • 2005–2011
    • Stanford University
      • Department of Cardiothoracic Surgery
      Palo Alto, California, United States
  • 2006–2009
    • Stanford Medicine
      • • Department of Cardiothoracic Surgery
      • • Division of General Surgery
      Stanford, California, United States
  • 2006–2008
    • Palo Alto Medical Foundation
      Palo Alto, California, United States