Persistent Shift in Laminar Planes Contribute to Post-Surgical Decline in LVEF in Patients with Primary Mitral Regurgitation

Persistent Shift in Laminar Planes Contribute to Post-Surgical Decline in LVEF in Patients with Primary Mitral Regurgitation | medRxiv /* */ /* */ <!-- <!-- /*! * yepnope1.5.4 * (c) WTFPL, GPLv2 */ (function(a,b,c){function d(a){return"[object Function]"==o.call(a)}function e(a){return"string"==typeof a}function f(){}function g(a){return!a||"loaded"==a||"complete"==a||"uninitialized"==a}function h(){var a=p.shift();q=1,a?a.t?m(function(){("c"==a.t?B.injectCss:B.injectJs)(a.s,0,a.a,a.x,a.e,1)},0):(a(),h()):q=0}function i(a,c,d,e,f,i,j){function k(b){if(!o&&g(l.readyState)&&(u.r=o=1,!q&&h(),l.onload=l.onreadystatechange=null,b)){"img"!=a&&m(function(){t.removeChild(l)},50);for(var d in y[c])y[c].hasOwnProperty(d)&&y[c][d].onload()}}var j=j||B.errorTimeout,l=b.createElement(a),o=0,r=0,u={t:d,s:c,e:f,a:i,x:j};1===y[c]&&(r=1,y[c]=[]),"object"==a?l.data=c:(l.src=c,l.type=a),l.width=l.height="0",l.onerror=l.onload=l.onreadystatechange=function(){k.call(this,r)},p.splice(e,0,u),"img"!=a&&(r||2===y[c]?(t.insertBefore(l,s?null:n),m(k,j)):y[c].push(l))}function j(a,b,c,d,f){return q=0,b=b||"j",e(a)?i("c"==b?v:u,a,b,this.i++,c,d,f):(p.splice(this.i++,0,a),1==p.length&&h()),this}function k(){var a=B;return a.loader={load:j,i:0},a}var l=b.documentElement,m=a.setTimeout,n=b.getElementsByTagName("script")[0],o={}.toString,p=[],q=0,r="MozAppearance"in l.style,s=r&&!!b.createRange().compareNode,t=s?l:n.parentNode,l=a.opera&&"[object Opera]"==o.call(a.opera),l=!!b.attachEvent&&!l,u=r?"object":l?"script":"img",v=l?"script":u,w=Array.isArray||function(a){return"[object Array]"==o.call(a)},x=[],y={},z={timeout:function(a,b){return b.length&&(a.timeout=b[0]),a}},A,B;B=function(a){function b(a){var a=a.split("!"),b=x.length,c=a.pop(),d=a.length,c={url:c,origUrl:c,prefixes:a},e,f,g;for(f=0;f<d;f++)g=a[f].split("="),(e=z[g.shift()])&&(c=e(c,g));for(f=0;f<b;f++)c=x[f](c);return c}function g(a,e,f,g,h){var i=b(a),j=i.autoCallback;i.url.split(".").pop().split("?").shift(),i.bypass||(e&&(e=d(e)?e:e[a]||e[g]||e[a.split("/").pop().split("?")[0]]),i.instead?i.instead(a,e,f,g,h):(y[i.url]?i.noexec=!0:y[i.url]=1,f.load(i.url,i.forceCSS||!i.forceJS&&"css"==i.url.split(".").pop().split("?").shift()?"c":c,i.noexec,i.attrs,i.timeout),(d(e)||d(j))&&f.load(function(){k(),e&&e(i.origUrl,h,g),j&&j(i.origUrl,h,g),y[i.url]=2})))}function h(a,b){function c(a,c){if(a){if(e(a))c||(j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}),g(a,j,b,0,h);else if(Object(a)===a)for(n in m=function(){var b=0,c;for(c in a)a.hasOwnProperty(c)&&b++;return b}(),a)a.hasOwnProperty(n)&&(!c&&!--m&&(d(j)?j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}:j[n]=function(a){return function(){var b=[].slice.call(arguments);a&&a.apply(this,b),l()}}(k[n])),g(a[n],j,b,n,h))}else!c&&l()}var h=!!a.test,i=a.load||a.both,j=a.callback||f,k=j,l=a.complete||f,m,n;c(h?a.yep:a.nope,!!i),i&&c(i)}var i,j,l=this.yepnope.loader;if(e(a))g(a,0,l,0);else if(w(a))for(i=0;i (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0];var j=d.createElement(s);var dl=l!='dataLayer'?'&l='+l:'';j.src='//www.googletagmanager.com/gtm.js?id='+i+dl;j.type='text/javascript';j.async=true;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-P4HH5NV'); Skip to main content Home About Submit ALERTS / RSS Search for this keyword Advanced Search Persistent Shift in Laminar Planes Contribute to Post-Surgical Decline in LVEF in Patients with Primary Mitral Regurgitation View ORCID Profile Louis J. Dell’Italia , Mariame Selma Kane , Jingyi Zheng , Shao-Wei Huang , Betty Pat , View ORCID Profile Thomas S. Denney Jr doi: https://doi.org/10.1101/2025.04.10.25325619 Louis J. Dell’Italia 1 Birmingham Veterans Affairs Health Care System , Birmingham, AL, USA 2 Division of Cardiovascular Disease, University of Alabama at Birmingham , Birmingham, AL, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Louis J. Dell’Italia For correspondence: louis.dellitalia{at}va.gov Mariame Selma Kane 1 Birmingham Veterans Affairs Health Care System , Birmingham, AL, USA 2 Division of Cardiovascular Disease, University of Alabama at Birmingham , Birmingham, AL, USA PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Jingyi Zheng 3 Department of Mathematics and Statistics, Auburn University , Auburn, AL, USA PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Shao-Wei Huang 3 Department of Mathematics and Statistics, Auburn University , Auburn, AL, USA Find this author on Google Scholar Find this author on PubMed Search for this author on this site Betty Pat 1 Birmingham Veterans Affairs Health Care System , Birmingham, AL, USA 2 Division of Cardiovascular Disease, University of Alabama at Birmingham , Birmingham, AL, USA PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Thomas S. Denney Jr 4 Samuel Ginn College of Engineering, Auburn University , Auburn, AL, USA PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Thomas S. Denney Jr Abstract Full Text Info/History Metrics Data/Code Preview PDF Abstract Background The double helical direction of LV laminar sheets from endocardium to epicardium allows for wringing motion or LV twist. This provides a major component to LV wall thickening, stroke volume, and ejection fraction (EF). When this laminar sheet arrangement changes in Primary Mitral Regurgitation (PMR) and whether it reverts to normal after mitral valve repair is unknown. Methods Normal subjects (n=55) PMR patients had cardiac magnetic resonance imaging (CMR) with tissue tagging and 3-dimensional (3-D) analysis. They were grouped as asymptomatic moderate (n=23) and severe PMR (n=25) by regurgitant volume (RV) and pre-surgery (n=54) with post-surgery follow up at six, 12, and 24 months. Amplitude and directional vector of longitudinal (Ell), circumferential (Ecc), and maximal shortening were computed along with principle strain angles (Ecc°, Ell°, and Err°) at basal, mid, and distal LV levels. Results Asymptomatic moderate (RV 35 ± 16 ml; LVEF 62 ± 6%) and severe (RV 55 ±16 ml; LVEF 63 ± 6%) and symptomatic pre-surgery (RV 61 ± 29 ml; LVEF 63 ± 8%) had similar increases in mid LV 3-D radius to wall thickness (R/T), decrease in LV mass to volume (M/V) and sphericity index (SI) vs. normal. Radial longitudinal shear strain and mid LV Ecc° and EII° angles increased in all PMR groups, consistent with a shift in LV laminar plane direction and decreased LV SI. Post-surgery, LV end-diastolic (ED) volume, LVED M/V and 3-D R/T returned to normal within two years; however, mid LV circumferential, longitudinal, and maximal shortening decrease below normal. LV Ecc° and Ell° angles, and SI are unchanged from pre-surgery. LVEF decreased post-surgery and had a negative correlation with LV twist at six (r 2 = 0.30, p < 0.001), 12, (r 2 = 0.33, p < 0.001) and 24 months (r 2 = 0.38, p < 0.001) post-surgery. Conclusion Early changes in Ecc° and Ell° angles, radial longitudinal shear strain, and LV spherical dilatation are consistent with a shift of LV laminar planes that persists after surgery. The extent to which this affects LV twist may underlie a heretofore explanation underlying the decrease in LVEF after surgery for PMR. Introduction Normal left ventricular (LV) geometry is ellipsoidal and becomes spherical as the heart dilates and fails. 1 We and others have reported that the LV of primary mitral regurgitation (PMR) undergoes spherical remodeling accompanied by an increase in 3-dimensional radius to wall thickness (3D R/T) ratio from base to apex and a decrease in LV end-diastolic (LVED) mass/volume ratio. 2 – 7 Dogma of LV eccentric remodeling espouses a series replication of cardiomyocyte sarcomeres as opposed to in parallel in pressure overload. 8 However, breakdown in the endomysial interstitial collagen scaffolding between cardiomyocytes is an important component in the eccentric remodeling of myofibers sheets in volume overload. 9 . 10 This also includes the perimysial collagen connecting myofibers, or bundles of four to six cardiomyocytes, and epimysial collagen connecting myocardial laminae, or myofiber sheets that are oriented in a double helical arrangement from endocardium to epicardium. 11 – 14 Fifty years ago Spotnitz and Streeter described extracellular gaps between laminar bundles of myocytes connected by an extracellular matrix. 15 , 16 The double helical orientation of these laminar layers from endocardium to epicardial allows for sliding of these laminar layers in a wringing motion that provides a major component to wall thickening, stroke volume and ejection fraction. 1 , 15 , 16 A decrease in LV twist in PMR has been reported with Echo speckle tracking 17 – 19 and cardiac magnetic resonance (CMR) tissue tagging in human subjects, 2 , 6 and with implanted radiopaque markers in animal studies. 20 – 23 In the volume overload model of aortocaval fistula in the dog, Covell and coworkers have demonstrated a time dependent progression of LV spherical remodeling coinciding with change in orientation of myocardial laminae, accounting for the decrease in LV twist in the spherically dilated LV. 24 , 25 There has been controversy regarding the mechanism of decrease in LVEF after surgical correction of PMR. Theories have shifted from a mechanical explanation related to a decrease in preload and increase in relative afterload due to correction of the low pressure leak 26 , 27 to a more recent myocardial focus related to severe cardiomyocyte ultrastructural damage masked by a normal LVEF 6 , 28 , 29 and increase in extracellular volume with gadolinium enhancement as a surrogate of fibrosis. 30 – 34 However, considering its importance to wall thickening, it is unknown whether shifts in myocardial laminar plane orientations return to normal after mitral valve surgery and how it may affect post-operative LVEF. Here we present serial CMR imaging with a 3-D analysis of tissue tagging in which we provide principle strain and shear angles demonstrating the shift of laminar planes in the process of spherical LV remodeling in PMR and its persistence after surgery. The subsequent negative effect on LV twist may explain a heretofore unexplained decrease in LVEF after surgery in PMR. Methods Patient Population The study population included 55 normal controls and PMR asymptomatic patients with moderate (n=23) and severe PMR (n=25) grouped by regurgitant volume (RV, moderate 30-40 ml and severe 40-60 ml); and symptomatic (pre-surgery, n=54) with follow up post-surgery at six, 12, and 24 months after mitral valve surgery. Patient recruitment occurred between 2006 and 2010 under National Heart, Lung, and Blood Institute Specialized Centers of Clinically Oriented Research Grant P50HL077100 in cardiac dysfunction. Patients with PMR had echo/Doppler severe isolated mitral regurgitation secondary to degenerative mitral valve disease referred for corrective mitral valve surgery. All pre-surgery patients had cardiac catheterization before surgery and were excluded for obstructive coronary artery disease (>50% stenosis), aortic valve disease, diabetes, or mitral stenosis. Asymptomatic PMR patients with moderate and severe MR had no evidence of coronary artery disease by history or maximal exercise stress test with nuclear perfusion. Normal patients (n = 48) had no prior history of cardiovascular disease or medical illness, no history of smoking, and were not taking any cardiovascular medications. The Institutional Review Boards of the University of Alabama at Birmingham and Auburn University approved the study protocol. All participants gave written informed consent. CMR Imaging Normal subjects and PMR patients underwent CMR on a 1.5-T scanner (Signa, GE) with standard cardiac cine slices in 2- and 4-chamber views, and a short-axis view covering both ventricles and atria. Parameters were set as follows: field-of-view, 360-400mm; 8-mm slice thickness; no gap; and 256*128 matrix. Tagged images were acquired using the same slice prescription as cine with the following parameters: repetition/echo times, 8/4.2 ms; tag spacing, 7 mm; trigger time, 10 ms from the R-wave; and flip angle 10 ° . 5 , 6 , 30 , 31 In short-axis views, endocardial contours were manually drawn at end-diastole (ED) and end-systole (ES). In all patients, intersections of the mitral and tricuspid valve leaflets with the LV and right ventricular (RV) wall were manually placed in left 2- and 4-chamber view and a right 2-chamber view at ED and ES. All intersections and endocardial contours were propagated to the remaining time frames using an automated algorithm with excellent reproducibility. Mitral regurgitant volume was derived from the difference between LV and RV stroke volumes (SV). The 3-dimensional endocardial circumferential curvature and wall thickness were computed from standard formulas at the wall segments as previously defined in our laboratory. 5 , 6 , 30 , 31 LA volumes were computed using biplane area length method with manual contours on 2- and 4-chamber long-axis views for each time frame. LA volumetric measurements were provided as maximum atrial volume (Vmax) when the mitral valve opens. LV twist and shear angle parameters were computed using the Fourier Analysis of Stimulated (FAST) echoes method. 3D LV strains were measured from tagged images at end-systole, which was defined by visual inspection of the image data as the time frame with maximum contraction. Tag lines were tracked with the algorithm described in and edited, if necessary, by an expert user. 37 The 3D deformation and Lagrangian strain was computed by fitting a B-spline deformation model in prolate spheroidal coordinates to the tag line data. 38 Normal strains were computed in the radial (Err, maximal shortening), circumferential (Ecc), and longitudinal (EII) directions. Principle strains and associated principal directions and 3D LVES Twist were also computed as described in our laboratory. 39 All normal, shear, and principal strains were computed at the mid-wall of all segments in the American Heart Association 17-segment model (21) except the apex (segment 17). The first principal strain (E1), which represents the maximum thickening strain, was roughly aligned with the radial direction. The second and third principal strains (E2 and E3) were generally aligned with the longitudinal and circumferential directions, respectively. The third principal strain (E3) corresponds to the maximum contraction strain. Angles between the E3 and circumferential directions (Ecc°), between the E2 and longitudinal directions (Ell°), and between the E1 and radial directions (Err°) were computed. We report circumferential (Ecc), longitudinal (Ell), and maximal (E3) shortening instead of raw strain values (Shortening=strain multiplied by -100%. Shortening is positive and larger values of shortening mean more contraction. For purposes of data analysis, the LV was divided into 3 levels: base, mid, and distal. The strain parameters at each individual level were obtained by averaging the ventricular segments encompassing the whole ventricular wall at that level (6 segments at the base and mid-ventricular levels, 4 segments at the distal level). Statistics Analysis Comparisons among four groups control, moderate, severe and pre surgery ( Figures 1 - 3 ) and pre-surgery with post-surgery follow up at 6, 12 and 24 months, ( Figures 4 and 5 ) are tested by Kruskal-Wallis tests, followed by a Benjamini-Krieger-Yekutieli correction. Graphical data are presented as box and whisker plots with median (interquartile range) and minimum and maximum values respectively with each dot representing an individual patient. Spearman correlation was performed between post-surgical LV Twist and LVEF ( Figure 6 ). Analyses of repeated measurements across groups are conducted using repeated measures ANOVA and Friedman tests ( Table 1 ). Download figure Open in new tab Figure 1. Indices of LV remodeling (A-D) in moderate and severe asymptomatic PMR and pre-surgery PMR. LV end-diastolic volume (LVEDV/m 2 ), LVED mass/volume, mid LV 3-D R/T ratio, and LV sphericity index demonstrate similar extremes of eccentric remodeling compared to normals despite an increasing regurgitant volume that is consistent with an increasing left atrial volume (indexed to BSA) ( E and F ). Download figure Open in new tab Figure 2. Indices of LV shortening in moderate and severe asymptomatic PMR and pre-surgery PMR. LVEF does not differ from normals ( A ). LVES circumferential (circ.) shortening ( B ) decreases as LVES longitudinal shortening ( C ) increases in asymptomatic moderate and severe PMR; while maximal shortening ( D ) and twist/length ( E ) do not differ from normals. Radial longitudinal shear strain ( F ) increases starting at moderate PMR consistent with a decrease in LV sphericity index ( Figure 1 D ) which is maintained with increasing severity of PMR. Download figure Open in new tab Figure 3. Group Analysis of Principle Circumferential Strain Angle° (Ecc°) and Ell: Principle Longitudinal Strain Angle° (Ell°) at base, mid and distal LV. There were no differences in principle strain and radial angles in PMR vs. Controls (data not shown). Download figure Open in new tab Figure 4. Group analysis of indices of LV remodeling pre- and post-surgery at six, 12, and 24 months ( A-D ). LV end-diastolic volume (LVEDV/m 2 , A), LVED mass/volume ( B ), and mid LV 3-D R/T ratio ( C ) return toward normal while LV sphericity index ( D ) is unchanged from pre-surgery at all post-surgery time points. Post-surgery indices of LV shortening decrease from pre-surgery at six, 12, and 24 months post-surgery ( E-I ). Download figure Open in new tab Figure 5. Group Analysis of Principle Circumferential Strain Angle° (Ecc°) and Principle Longitudinal Strain Angle° (Ell°) at base, mid and distal LV post-surgery. Symptomatic PMR patients scheduled for mitral valve repair/replacement surgery (n=39) had follow up every 6 months up to 2 years after surgery with no effect on measured strain angles. Download figure Open in new tab Figure 6. Significant negative relationship between LVEF and LV twist/length in surgical PMR patients at 6, 12, and 24 months post-surgery. LV twist/length did not differ pre and post surgery. View this table: View inline View popup Download powerpoint Table 1. Repeated Measures Analysis for PMR Patients with CMR at Pre-Surgery, 6, 12, and 24 Months (n=21) and for PMR Patients with CMR Pre-Surgery, 6, and 12 months (n=39). Results Demographics of PMR Patients Normals were significantly younger (45 ± 15 years; n = 55) than moderate (53 ± 12 years; n = 23), severe (57 ± 9 years, n = 25), and pre-surgery PMR patients (56 ± 12 years, n = 54) (p=0.005). Sex distribution also differed significantly (p=0.03), with normals having a more balanced female-to-male ratio (27:25) compared to the PMR groups. 4 , 6 Body surface area was similar across all groups. All moderate and severe PMR patients were asymptomatic (NYHA Class I), with 12 on antihypertensive medications. Pre-surgery PMR patients showed varying symptom levels: 25 Class I, 26 Class II, and 3 Class III. Twenty-two of these patients were taking antihypertensive medications. 4 , 6 Group Analysis of LV Remodeling in PMR versus Controls Major indices of eccentric LV remodeling including LVED volume, LVED mass/volume, LVED Sphericity Index, and 3-D LVED radius to wall thickness (R/T) are significantly different in normal vs. asymptomatic moderate and severe PMR and pre-surgery PMR ( Figure 1 A-D ). LVEDV is greater in pre-surgery vs. asymptomatic moderate PMR. These indices of LV remodeling do not change in the face of a progressive increase in regurgitant volume that is reflected in increasing left atrial maximal volume ( Figure 1 E and F ). Median LVEF and mid LV maximal shortening ( Figure 2 A and D ) do not differ from normals in all PMR groups; while longitudinal shortening is increased above normal in moderate and severe PMR ( Figure 2 C ) and LV mid circumferential shortening is decreased below normals in all PMR groups ( Figure 2 B ). At the same time, radial longitudinal shear strain increases above normal in all PMR groups while LV twist does not differ from controls ( Figure 2 E and F ). Radial Circumferential and circumferential longitudinal shear strains ( data not shown, ) do not differ from normal in moderate and severe asymptomatic and pre-surgery PMR patients. There is a significant increase between principle strain and circumferential (Ecc°) and longitudinal (Ell°) angles at the mid LV ( Figure 3 C and D ); while at the LV base Ell° angles are increased at all PMR stages compared to normal ( Figure 3 B ). Left ventricular radial (Err°) strain angles did not differ at LV base, mid wall, and distal in PMR vs normal ( data not shown ). Left ventricular distal circumferential (Ecc°) angles are increased at all PMR stages compared to normal whereas longitudinal (EII°) angle is increased in severe PMR ( Figure 3 E and F ). Group Analysis of Post-Surgery LV Remodeling and Function vs. Pre-Surgery There is a significant decrease in LVEDV and a normalization of the 3-D LVED R/T and LVED mass/volume at six, 12, and 24 months after surgery ( Figure 4 A-C ); however, LV sphericity index is unchanged ( Figure 4 D ). Circumferential (Ecc), longitudinal (Ell), and maximal shortening decrease significantly from pre-surgery. ( Figure 4 E-G ), as well as peak mitral annular displacement and LVEF ( Figure 4 H and I ). Angles between principle strain and circumferential (Ecc°) and longitudinal (Ell°) are unchanged from pre-surgery ( Figure 5 ) in the LV base, mid, and distal. Although LV twist did not change post-surgery, there is a wide variability ( Figure 6 ), however demonstrates a significant negative correlation between LVEF and LV twist pre-surgery (r 2 = 0.15, p < 0.004) and post-surgery at 6 months (r 2 = 0.30, p < 0.001), 12 months (r 2 = 0.33, p < 0.001), and 24 months (r 2 = 0.38, p < 0.001). Repeated Measures Analysis of LV Remodeling and Function at 6, 12, and 24 Months Post-Surgery ( Table 1 ) To verify group changes of unequal numbers of patients in Figures 4 and 5 , we performed repeated measures analysis on 39 surgery PMR patients who had CMR at pre- and post-surgery at six, 12 months, and 21 patients who had CMR at pre-surgery and six, 12 and 24 months post-surgery. Both analyses demonstrate a consistent reverse LV remodeling with a significant decrease in LVEDV and LVED mass/volume and increase in LV 3D radius/wall thickness. Despite reverse remodeling there is a decrease in LVEF and LV circumferential, longitudinal and maximal strains while radial longitudinal shear strain and LV twist do not change from pre-surgical values. Discussion The current study evokes the conundrum that LV remodeling is inherently maladaptive with an early LV spherical transition and decrease in 3-D LV R/T and LVED mass/volume in the low-pressure volume overload of PMR. A decrease in sphericity index parallels a decrease in radial longitudinal shear strain and directional changes in LV principle strain angles in the circumferential and longitudinal direction. These directional changes suggest an early realignment of orientation of laminar planes that persist two years after surgery despite a reversal of eccentric LV remodeling. The extent and persistence after surgery result in a decrease in circumferential, longitudinal, and maximal shortening below normal and a negative correlation between post-surgery LV twist and LVEF for up to two years. Taken together, loss of the normal orientation of the double helical laminar planes may underlie a heretofore-unexplained post-surgery decrease in LVEF. The current study utilizes a state-of-the-art 3-D analysis that enables calculation of in-plane strains, shear angles, and 3D principle strains occurring in an oblique direction not aligned with any imaging plane. An increase in principal strain angles in the longitudinal and circumferential directions (Ell° and Ecc°) at the mid LV reflects spherical remodeling of the LV. This indicates that LV myocardial fiber sheets are not contracting in their typical aligned pattern especially at the mid LV level and coincides with a significant increase in radial longitudinal shear strain ( Figure 2F ). 38 , 39 This occurs at the early moderate stage of PMR and coincides with the decrease in the LV sphericity index. Radial longitudinal shear strain quantifies the interaction or “sliding” between radial thickening and longitudinal shortening. Enhanced radial strain relative to longitudinal strain affects the orientation of the principal strain axes, causing the concomitant increase in radial longitudinal shear strain and increase in Ecc° and Ell° angles. As demonstrated in Figure 3 , there is a variability across the base to mid to distal LV, consistent with regionally heterogeneous LV remodeling in the dog with volume overload of aortocaval fistula. 24 While radial longitudinal shear strain is important, global longitudinal strain is widely used clinically and represents the overall shortening of the heart muscle along its length. 40 – 44 In the current study, there is an increase in mid LV longitudinal shortening at moderate and severe asymptomatic PMR, while mid LV circumferential shortening decreases at moderate, severe, and pre-surgery stages of PMR. Radial circumferential and circumferential longitudinal shear strains remain normal (data not shown). This is consistent with models that demonstrate the importance of circumferential strain over longitudinal strain in maintaining LVEF in the spherically dilated LV. 45 Accordingly, we have reported that LV mid circumferential strain rate predicts LVEF below 50% after surgical correction 3 and signals an incipient decrease in LVEF < 60% in patients with asymptomatic moderate to severe PMR. 4 To test the validity of the findings in the current study, using the same 3-D analysis with CMR tagging, we demonstrated a directionally opposite decrease in 3-D LV mid and apical principle Ecc° and Ell° angles and an increase in twist in patients with concentric hypertrophy and resistant hypertension. 37 Thus, the concentric hypertrophic adaptation to pressure overload requires deformation in line with the natural elliptical double helical alignment of laminar planes. In contrast, a reorientation of laminar planes is required to accommodate the low-pressure volume overload of PMR, beyond the limits of individual cardiomyocyte length that begets LV spherical dilatation in PMR. Our findings are consistent with Covell and coworkers who report a time dependent LV spherical remodeling concomitant with a shift of laminar planes using implanted radio-opaque beads in dogs with aortocaval fistula volume overload. 24 , 25 The novel finding in the current study is that after surgery, despite a decrease in LVEDV and normalization of LV mid 3-D R/T and LVED mass/volume, there is a persistent 1) increase in principle strain angles (Ecc° and Ell°), 2) decrease in radial longitudinal shear strain, and 3) unchanged sphericity index by group and repeated measures analysis ( Table 1 ). The laminar planes are connected by epimysial and perimysial collagen. 11 – 14 An increase in extracellular volume by CMR with T1 and gadolinium is an important predictor of outcome in patients with PMR. 30 – 34 Although identified as a surrogate of fibrosis, these studies do not include T2 weighting to rule out interstitial edema as a cause of the increase in extracellular volume. 46 We have reported an increase in interstitial space and extracellular matrix breakdown in both human 6 and experimentally induced PMR in the dog. 47 As such, an increase in extracellular volume could also indicate edema and breakdown of epimysial and perimysial structural collagen—a necessary process for realignment of laminar planes. 24 , 25 However, development of fibrosis at the level of perimysial and epimysial collagen in a later stage of PMR may prevent realignment of laminar planes after surgery. A recent study reported a small but significant decrease in extracellular volume % following mitral valve repair without a change in late gadolinium enhancement in one third of patients, which may suggest a fibrosis that prevents realignment of laminar planes at a later stage of PMR. 32 Limitations The limited number of patients did not allow for differences between mitral valve repair (n=44) versus replacement (n=10). Although not all patients returned for follow-up CMR, results did not differ for group effects and repeated measures including pre-surgery and post-surgery time points. Using CMR tagging we have assumed that changes in principle strain angles and shear strains reflect changes in the underlying laminar plane architecture and collagen matrix in PMR. Studies using diffusion tensor imaging have demonstrated similar changes in laminar planes in the spherical dilatation of heart failure patients. 48 Studies using diffusion tensor imaging in PMR will support our novel results in the current investigation, especially in the presence of interstitial edema due to collagen breakdown at earlier stages of PMR. 48 While the findings of the current investigation are supported in the literature, 38 , 39 longitudinal studies are needed to validate the relationship between laminar plane shift and LV remodeling in PMR. Conclusions There is an unmet need for defining optimal timing for surgical intervention in patients with moderate to severe PMR especially in the asymptomatic patient with LVEF > 60%. The current study provides possible evidence for a point of no return of the 3-D laminar structure that is so important in LV twist and its contribution to LV stroke volume and LVEF. Development of symptoms or LVEF < 60% are clearly associated with less favorable outcomes with surgery. 49 , 50 There is a need for prospective longitudinal clinical studies that compare the value of strain imaging by Echo speckle tracking or CMR feature tracking or tagging that warn of incipient symptoms or decrease in LVEF < 60% when making clinical decisions for surgical intervention. Data Availability All data will be made available upon request. Sources of Funding This work was supported by the National Heart, Lung, and Blood Institute and Specialized Centers of Clinically Oriented Research grant [P50HL077100 to L.J.D] in Cardiac Dysfunction; Department of Veteran Affairs for Merit Review grant [1CX000993-01 to L.J.D]; and National Institutes of Health Grant [P01 HL051952 to L.J.D]. No relationships to industry. Disclosures None Acknowledgements None Footnotes louis.dellitalia{at}va.gov , mariame.kane{at}va.gov , jzz0121{at}auburn.edu , szh0136{at}auburn.edu , bettypat{at}uabmc.edu , dennets{at}auburn.edu Funding: This work was supported by the National Heart, Lung, and Blood Institute and Specialized Centers of Clinically Oriented Research grant [P50HL077100 to L.J.D] in Cardiac Dysfunction; Department of Veteran Affairs for Merit Review grant [1CX000993-01 to L.J.D]; and National Institutes of Health Grant [P01 HL051952 to L.J.D]. No relationships to industry. Non-standard Abbreviations and Acronyms Circ. circumferential CMR cardiac magnetic resonance imaging EII longitudinal Ecc circumferential LVED left ventricular end-diastolic LVES left ventricular end-systole MA mitral annular Max. maximal M/V mass to volume PMR primary mitral regurgitation R/T radius to wall thickness RV regurgitant volume SI sphericity index References 1. ↵ Triposkiadis F , Giamouzis G , Boudoulas KD , Karagiannis G , Skoularigis J , Boudoulas H , Parissis J . Left ventricular geometry as a major determinant of left ventricular ejection fraction: physiological considerations and clinical implications . Eur J Heart Fail . 2018 ; 20 ( 3 ): 436 – 444 . DOI: 10.1002/ejhf.1055 . Epub 2017 Nov 6. OpenUrl CrossRef PubMed 2. ↵ Reyhan M , Wang Z , Li M , Kim HJ , Gupta H , Lloyd SG , Dell’Italia LJ , Denney T , Ennis DB . Left Ventricular Twist and Shear in Patients With Primary Mitral Regurgitation . J Magn Reson Imaging . 2015 ; 42 ( 2 ): 400 – 406 . DOI: 10.1002/jmri.24811 OpenUrl CrossRef PubMed 3. ↵ Zheng J , Huang SW , Ahmed MI , Pat B , Lloyd SG , Sharifov OF , Denney TS Jr . , Dell’Italia LJ . Imminent risk of LVEF decline in asymptomatic patients with primary mitral regurgitation . Front Cardiovasc Med . 2024 ; 11 : 1410859 . DOI: 10.3389/fcvm.2024.1410859 OpenUrl CrossRef 4. ↵ Zheng J , Li Y , Billor N , Ahmed MI , Fang YD , Pat B , Denney TS , Dell’Italia LJ . Understanding post-surgical decline in left ventricular function in primary mitral regurgitation using regression and machine learning models . Front Cardiovasc Med . 2023 ; 10 : 1112797 . DOI: 10.3389/fcvm.2023.1112797 OpenUrl CrossRef 5. ↵ Schiros CG , Ahmed MI , Sanagala T , Zha W , McGiffin DC , Bamman MM , Gupta H , Lloyd SG , Denney TS Jr , Dell’Italia LJ . Importance of three-dimensional geometric analysis in the assessment of the athlete’s heart . Am J Cardiol . 2013 ; 111 ( 7 ): 1067 – 1072 . DOI: 10.1016/j.amjcard.2012.12.027 OpenUrl CrossRef PubMed 6. ↵ Ahmed MI , Andrikopoulou E , Zheng J , Ulasova E , Pat B , Kelley EE , Powell PC , Denney TS Jr , Lewis C , Davies JE , Darley-Usmar V , Dell’Italia LJ . Interstitial collagen loss, myocardial remodeling, and function in Primary Mitral Regurgitation . JACC Basic Transl Sci . 2022 ; 7 ( 10 ): 973 – 981 . DOI: 10.1016/j.jacbts.2022.04.014 OpenUrl CrossRef PubMed 7. ↵ Schiros CG , Dell’Italia LJ , Gladden JD , Clark D , 3rd , Aban I , Gupta H , Lloyd SG , McGiffin DC , Perry G , Denney TS , Jr . , Ahmed MI . Magnetic resonance imaging with 3-dimensional analysis of left ventricular remodeling in isolated mitral regurgitation: implications beyond dimensions . Circulation . 2012 ; 125 : 2334 – 2342 . DOI: 10.1161/CIRCULATIONAHA.111.073239 OpenUrl Abstract / FREE Full Text 8. ↵ Grossman W . Cardiac hypertrophy: useful adaptation or pathologic process? Am J Med . 1980 ; 69 ( 4 ): 576 – 584 . DOI: 10.1016/0002-9343(80)90471-4 OpenUrl CrossRef PubMed Web of Science 9. ↵ Ryan TD , Rothstein EC , Aban I , Tallaj JA , Husain A , Lucchesi PA , Dell’Italia LJ . Left ventricular eccentric remodeling and matrix loss are mediated by bradykinin and precede cardiomyocyte elongation in rats with volume overload . J Am Coll Cardiol . 2007 ; 49 ( 7 ): 811 – 821 . DOI: 10.1016/j.jacc.2006.06.083 OpenUrl FREE Full Text 10. ↵ Chandrashekhar Y . Embracing diversity in remodeling: a step in therapeutic decision making in heart failure? J Am Coll Cardiol . 2007 ; 49 ( 7 ): 822 – 825 . DOI: 10.1016/j.jacc.2006.11.025 OpenUrl FREE Full Text 11. ↵ LeGrice IJ , Smaill BH , Chai LZ , Edgar SG , Gavin JB , Hunter PJ . Laminar structure of the heart: ventricular myocyte arrangement and connective tissue architecture in the dog . Am J Physiol . 1995 ; 269 ( 2 Pt 2): H571 – H582 . DOI: 10.1152/ajpheart.1995.269.2.H571 OpenUrl CrossRef Web of Science 12. Pope AJ , Sands GB , Smaill BH , LeGrice IJ . Three-dimensional transmural organization of perimysial collagen in the heart . Am J Physiol Heart Circ Physiol . 2008 ; 295 ( 3 ): H1243 – H1252 . DOI: 10.1152/ajpheart.00484.2008 OpenUrl CrossRef PubMed Web of Science 13. Takayama Y , Costa KD , and Covell JW . Contribution of laminar myofiber architecture to load-dependent changes in mechanics of LV myocardium . Am J Physiol Heart Circ Physiol . 2002 ; 282 : H1510 – H1520 . DOI: 10.1152/ajpheart.00261.2001 OpenUrl CrossRef PubMed Web of Science 14. ↵ Costa KD , Takayama Y , McCulloch AD , Covell JW . Laminar fiber architecture and three-dimensional systolic mechanics in canine ventricular myocardium . Am J Physiol . 1999 ; 276 ( 2 ): H595 – 607 . DOI: 10.1152/ajpheart.1999.276.2.H595 OpenUrl CrossRef PubMed Web of Science 15. ↵ Streeter DD Jr . , Spotnitz HM , Patel DP , Ross J Jr . , Sonnenblick EH . Fiber orientation in the canine left ventricle during diastole and systole . Circ Res . 24 : 339 – 347 , 1969 . DOI: 10.1161/01.res.24.3.339 OpenUrl Abstract / FREE Full Text 16. ↵ Spotnitz HM , Spotnitz WD , Cottrell TS , Spiro D , Sonnenblick EH . Cellular basis for volume related wall thickness changes in the rat left ventricle . J Mol Cell Cardiol . 1974 ; 6 ( 4 ): 317 – 331 . DOI: 10.1016/0022-2828(74)90074-1 OpenUrl CrossRef PubMed Web of Science 17. ↵ Kazui T , Niinuma H , Tsuboi J , Okabayashi H . Changes in left ventricular twist after mitral valve repair . J Thorac Cardiovasc Surg . 2010 ; 141 : 716 – 724 . DOI: 10.1016/j.jtcvs.2010.05.004 OpenUrl CrossRef PubMed 18. Borg AN , Harrison JL , Argyle RA , Ray SG . Left ventricular torsion in primary chronic mitral regurgitation . Heart . 2008 ; 94 : 597 – 603 . DOI: 10.1136/hrt.2007.126284 OpenUrl Abstract / FREE Full Text 19. ↵ Moustafa SE , Kansal M , Alharthi M , Deng Y , Chandrasekaran K , Mookadam F . Prediction of incipient left ventricular dysfunction in patients with chronic primary mitral regurgitation: a velocity vector imaging study . Eur J Echocardiogr . 2011 ; 12 ( 4 ): 291 – 298 . DOI: 10.1093/ejechocard/jer003 OpenUrl CrossRef PubMed 20. ↵ Ennis DB , Nguyen TC , Itoh A , Bothe W , Liang DH , Ingels NB , Miller DC . Reduced systolic torsion in chronic “pure” mitral regurgitation . Circ Cardiovasc Imaging . 2009 ; 2 ( 2 ): 85 – 92 . DOI: 10.1161/CIRCIMAGING.108.785923 OpenUrl Abstract / FREE Full Text 21. Tibayan FA , Yun KL , Fann JI , Lai DT , Timek TA , Daughters GT , Ingels NB , Miller DC . Torsion dynamics in the evolution from acute to chronic mitral regurgitation . J Heart Valve Dis . 2002 ; 11 : 39 – 46 . OpenUrl PubMed Web of Science 22. Carlhäll CJ , Nguyen TC , Itoh A , Ennis DB , Bothe W , Liang D , Ingels NB , Miller DC . Alterations in Transmural Myocardial Strain An Early Marker of Left Ventricular Dysfunction in Mitral Regurgitation? Circulation . 2008 ; 118 ( 14 Suppl): S256 – S262 . DOI: 10.1161/CIRCULATIONAHA.107.753525 OpenUrl Abstract / FREE Full Text 23. ↵ Ennis DB , Nguyen TC , Itoh A , Bothe W , Liang DH , Ingels NB , Miller DC . Reduced systolic torsion in chronic “pure” mitral regurgitation . Circ Cardiovasc Imaging . 2009 ; 2 : 85 – 92 . DOI: 10.1161/CIRCIMAGING.108.785923 OpenUrl Abstract / FREE Full Text 24. ↵ Ashikaga H , Omens JH , Covell JW . Time dependent remodeling of transmural architecture underlying abnormal ventricular geometry in chronic volume overload heart failure . Am J Physiol Heart Circ Physiol . 2004 ; 287 ( 5 ): H1994 – H2002 . DOI: 10.1152/ajpheart.00326.2004 OpenUrl CrossRef PubMed Web of Science 25. ↵ Ashikaga H , Covell JW , Omens JH . Diastolic dysfunction in volume-overload hypertrophy is associated with abnormal shearing of myolaminar sheets . Am J Physiol Heart Circ Physiol . 2005 ; 288 ( 6 ): H2603 – H2610 . DOI: 10.1152/ajpheart.01276.2004 OpenUrl CrossRef PubMed 26. ↵ Ross J , Jr . Afterload mismatch in aortic and mitral valve disease: implications for surgical therapy . J Am Coll Cardiol . 1985 ; 5 ( 4 ): 811 – 826 . DOI: 10.1016/s0735-1097(85)80418-6 OpenUrl FREE Full Text 27. ↵ Goldfine H , Aurigemma GP , Zile MR , Gaasch WH . Left ventricular length-force-shortening relations before and after surgical correction of chronic mitral regurgitation . J Am Coll Cardiol . 1998 ; 31 ( 1 ): 180 – 185 . DOI: 10.1016/s0735-1097(97)00453-1 OpenUrl FREE Full Text 28. ↵ Ahmed MI , Guichard JL , Soorappan RN , Ahmad S , Mariappan N , Litovsky S , Gupta H , Lloyd SG , Denney TS , Powell PC , Aban I , Collawn J , Davies JE , McGiffin DC , Dell’Italia LJ . Disruption of desmin-mitochondrial architecture in patients with regurgitant mitral valves and preserved ventricular function . J Thorac Cardiovasc Surg . 2016 ; 152 : 1059 – 1070 . DOI: 10.1016/j.jtcvs.2016.06.017 OpenUrl CrossRef PubMed 29. ↵ Ahmed MI , Gladden JD , Litovsky SH , Lloyd SG , Gupta H , Inusah S , Denney T Jr , Powell P , McGiffin DC , Dell’Italia LJ . Increased oxidative stress and cardiomyocyte myofibrillar degeneration in patients with chronic isolated mitral regurgitation and ejection fraction >60% . J Am Coll Cardiol . 2010 ; 55 : 671 – 679 . DOI: 10.1016/j.jacc.2009.08.074 OpenUrl FREE Full Text 30. ↵ Liu B , Neil DAH , Bhabra M , Patel R , Barker TA , Nikolaidis N , Billing JS , Hayer M , Baig S , Price AM , Vijapurapu R , Treibel TA , Edwards NC , Steeds RP . Reverse Myocardial Remodeling Following Valve Repair in Patients With Chronic Severe Primary Degenerative Mitral Regurgitation . JACC Cardiovasc Imaging . 2022 ; 15 ( 2 ): 224 – 236 . DOI: 10.1016/j.jcmg.2021.07.007 OpenUrl CrossRef PubMed 31. ↵ Weinsaft JW , Kim J . Beyond the Mitral Valve: Myocardial Fibrosis for Therapeutic Decision-Making and Prognostication of Degenerative Mitral Regurgitation . JACC Cardiovasc Imaging . 2022 ; 15 ( 2 ): 237 – 239 . DOI: 10.1016/j.jcmg.2021.07.025 OpenUrl CrossRef PubMed 32. ↵ Liu B , Neil DAH , Premchand M , Bhabra M , Patel R , Barker T , Nikolaidis N , Billing JS , Treibel TA , Moon JC , González A , Hodson J , Edwards NC , Steeds RP . Myocardial fibrosis in asymptomatic and symptomatic chronic severe primary mitral regurgitation and relationship to tissue characterization and left ventricular function on cardiovascular magnetic resonance . J Cardiovasc Magn Reson . 2020 ; 22 ( 1 ): 86 . DOI: 10.1186/s12968-020-00674-4 OpenUrl CrossRef PubMed 33. Kitkungvan D , Yang EY , El Tallawi KC , Nagueh SF , Nabi F , Khan MA , Nguyen DT , Graviss EA , Lawrie GM , Zoghbi WA , Bonow RO , Quinones MA , Shah DJ . Prognostic Implications of Diffuse Interstitial Fibrosis in Asymptomatic Primary Mitral Regurgitation . Circulation . 2019 ; 140 ( 25 ): 2122 – 2124 . DOI: 10.1161/CIRCULATIONAHA.119.043250 OpenUrl CrossRef PubMed 34. ↵ Kitkungvan D , Yang EY , El Tallawi KC , Nagueh SF , Nabi F , Khan MA , Nguyen DT , Graviss EA , Lawrie GM , Zoghbi WA , Bonow RO , Quinones MA , Shah DJ . Extracellular volume in primary mitral regurgitation . JACC Cardiovasc Imaging . 2021 ; 14 ( 6 ): 1146 – 1160 . DOI: 10.1161/CIRCULATIONAHA.119.043250 OpenUrl CrossRef PubMed 35. Denney TS Jr . , Gerber BL , Yan L . Unsupervised reconstruction of a three-dimensional left ventricular strain from parallel tagged cardiac images . Magn Reson Med . 2003 ; 49 ( 4 ): 743 – 754 . DOI: 10.1002/mrm.10434 OpenUrl CrossRef PubMed Web of Science 36. Li J , Denney TS Jr . . Left ventricular motion reconstruction with a prolate spheroidal B-spline model . Phys Med Biol . 2006 ; 51 ( 3 ): 517 – 537 . DOI: 10.1088/0031-9155/51/3/004 OpenUrl CrossRef PubMed Web of Science 37. ↵ Ahmed MI , Desai RV , Gaddam KK , Venkatesh BA , Agarwal S , Inusah S , Lloyd SG , Denney TS Jr . , Calhoun D , Dell’italia LJ , Gupta H . Relation of Torsion and Myocardial Strains to LV Ejection Fraction in Hypertension . JACC Cardiovasc Imaging . 2012 ; 5 ( 3 ): 273 – 281 . DOI: 10.1016/j.jcmg.2011.11.013 OpenUrl Abstract / FREE Full Text 38. ↵ Ingels NB , Jr . Myocardial fiber architecture and left ventricular function . Tech Health Care . 1997 ; 5 : 45 – 52 . OpenUrl 39. ↵ Waldman LK , Nosan D , Villarreal F , Covell JW . Relation between transmural deformation and local myofiber direction in canine left ventricle . Circ Res . 1988 ; 63 ( 3 ): 550 – 562 . DOI: 10.1161/01.res.63.3.550 OpenUrl Abstract / FREE Full Text 40. ↵ Alashi A , Mentias A , Patel K , Gillinov AM , Sabik JF , Popović ZB , Mihaljevic T , Suri RM , Rodriguez LL , Svensson LG , Griffin BP , Desai MY . Synergistic utility of BNP and Left Ventricular Global Longitudinal Strain in Asymptomatic Patients With Significant Primary Mitral Regurgitation and Preserved Systolic Function Undergoing Mitral Valve Surgery . Circ Cardiovasc Imaging . 2016 ; 5 ( 1 ): e002561 . DOI: 10.1161/CIRCIMAGING.115.004451 OpenUrl CrossRef 41. Modaragamage Dona AC , Afoke J , Punjabi PP , Kanaganayagam GS . Global longitudinal strain to determine optimal timing for surgery in primary mitral regurgitation: A systematic review . J Card Surg . 2021 ; 36 ( 7 ): 2458 – 2466 . DOI: 10.1111/jocs.15521 OpenUrl CrossRef PubMed 42. Ueyama H , Kuno T , Takagi H , Krishnamoorthy P , Prandi FR , Palazzuoli A , Sharma SK , Kini A , Lerakis S . Prognostic value of left ventricular global longitudinal strain in mitral regurgitation: a systematic review . Heart Fail Rev . 2023 ; 28 ( 2 ): 465 – 483 . DOI: 10.1007/s10741-022-10265-3 OpenUrl CrossRef PubMed 43. Riebel CIB , Ilie Orzan R , Negru A , Agoston-Coldea L . The Role of Global Longitudinal Strain in the Follow-Up of Asymptomatic Patients with Chronic Primary Mitral Regurgitation . J Clin Med . 2024 ; 13 ( 17 ): 5304 . DOI: 10.3390/jcm13175304 OpenUrl CrossRef PubMed 44. ↵ Romano S , Kitkungvan D , Nguyen DT , El-Tallawi C , Graviss EA , Farzaneh Far A , Shah DJ . Implications of myocardial strain in primary mitral regurgitation—a cardiovascular magnetic resonance study . Eur Heart J Cardiovasc Imaging . 2024 ; 26 ( 1 ): 126 – 134 . doi: 10.1093/ehjci/jeae245 . OpenUrl CrossRef PubMed 45. ↵ Stokke TM , Hasselberg NE , Smedsrud MK , Sarvari SI , Haugaa KH , Smiseth OA , Edvardsen T , Remme EW . Geometry as a confounder when assessing ventricular systolic function. Comparison between ejection fraction and strain . J Am Coll Cardiol . 2017 ; 70 ( 8 ): 942 – 954 . DOI: 10.1016/j.jacc.2017.06.046 OpenUrl FREE Full Text 46. ↵ Dell’Italia LJ , Balcells E , Meng QC , Su X , Schultz D , Bishop SP , Machida N , Straeter-Knowlen IM , Hankes GH , Dillon R , Cartee RE , Oparil S . Volume-overload cardiac hypertrophy is unaffected by ACE inhibitor treatment in dogs . Am J Physiol Heart Circ Physiol . 1997 ; 273 ( 2 Pt 2): H961 – H970 . DOI: 10.1152/ajpheart.1997.273.2.H961 OpenUrl CrossRef PubMed Web of Science 47. ↵ Sinigiani G , De Michieli L , De Conti G , Ricci F , De Lazzari M , Migliore F , Perazzolo Marra M , Zorzi A , Corrado D , Cipriani A . Cardiac Magnetic Resonance—Detected Acute Myocardial Edema as Predictor of Favourable Prognosis: A Comprehensive Review . J Cardiovasc Dev Dis . 2023 ; 10 ( 8 ): 319 . doi: 10.3390/jcdd10080319 OpenUrl CrossRef PubMed 48. ↵ Khalique Z , Ferreira PF , Scott AD , Nielles-Vallespin S , Firmin DN , Pennell DJ . Diffusion Tensor Cardiovascular Magnetic Resonance Imaging: A Clinical Perspective . JACC Cardiovasc Imaging . 2020 ; 13 ( 5 ): 1235 – 1255 . OpenUrl Abstract / FREE Full Text 49. ↵ Gammie JS , Chikwe J , Badhwar V , Thibault DP , Vemulapalli S , Thourani VH , Gillinov M , Adams DH , Rankin JS , Ghoreishi M , Wang A , Ailawadi G , Jacobs JP , Suri RM , Bolling SF , Foster NW , Quinn RW . Isolated Mitral Valve Surgery: The Society of Thoracic Surgeons Adult Cardiac Surgery Database Analysis . Ann Thorac Surg . 2018 ; 106 ( 3 ): 716 – 727 . DOI: 10.1016/j.athoracsur.2018.03.086 OpenUrl CrossRef PubMed 50. ↵ Desai A , Thomas JD , Bonow RO , Kruse J , Andrei AC , Cox JL , McCarthy PM . Asymptomatic degenerative mitral regurgitation repair: Validating guidelines for early intervention . J Thorac Cardiovasc Surg . 2021 ; 161 ( 3 ): 981 – 994.e5 . OpenUrl CrossRef PubMed View the discussion thread. Back to top Previous Next Posted April 11, 2025. Download PDF Data/Code Email Thank you for your interest in spreading the word about medRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. You are going to email the following Persistent Shift in Laminar Planes Contribute to Post-Surgical Decline in LVEF in Patients with Primary Mitral Regurgitation Message Subject (Your Name) has forwarded a page to you from medRxiv Message Body (Your Name) thought you would like to see this page from the medRxiv website. Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. Share Persistent Shift in Laminar Planes Contribute to Post-Surgical Decline in LVEF in Patients with Primary Mitral Regurgitation Louis J. Dell’Italia , Mariame Selma Kane , Jingyi Zheng , Shao-Wei Huang , Betty Pat , Thomas S. Denney Jr medRxiv 2025.04.10.25325619; doi: https://doi.org/10.1101/2025.04.10.25325619 Share This Article: Copy Citation Tools Persistent Shift in Laminar Planes Contribute to Post-Surgical Decline in LVEF in Patients with Primary Mitral Regurgitation Louis J. Dell’Italia , Mariame Selma Kane , Jingyi Zheng , Shao-Wei Huang , Betty Pat , Thomas S. Denney Jr medRxiv 2025.04.10.25325619; doi: https://doi.org/10.1101/2025.04.10.25325619 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Area Cardiovascular Medicine Subject Areas All Articles Addiction Medicine (567) Allergy and Immunology (863) Anesthesia (297) Cardiovascular Medicine (4411) Dentistry and Oral Medicine (443) Dermatology (380) Emergency Medicine (606) Endocrinology (including Diabetes Mellitus and Metabolic Disease) (1505) Epidemiology (15205) Forensic Medicine (30) Gastroenterology (1119) Genetic and Genomic Medicine (6575) Geriatric Medicine (666) Health Economics (994) Health Informatics (4511) Health Policy (1365) Health Systems and Quality Improvement (1608) Hematology (537) HIV/AIDS (1264) Infectious Diseases (except HIV/AIDS) (15903) Intensive Care and Critical Care Medicine (1103) Medical Education (620) Medical Ethics (144) Nephrology (666) Neurology (6573) Nursing (345) Nutrition (998) Obstetrics and Gynecology (1139) Occupational and Environmental Health (954) Oncology (3319) Ophthalmology (968) Orthopedics (369) Otolaryngology (420) Pain Medicine (435) Palliative Medicine (129) Pathology (662) Pediatrics (1689) Pharmacology and Therapeutics (691) Primary Care Research (710) Psychiatry and Clinical Psychology (5423) Public and Global Health (9205) Radiology and Imaging (2191) Rehabilitation Medicine and Physical Therapy (1367) Respiratory Medicine (1191) Rheumatology (593) Sexual and Reproductive Health (709) Sports Medicine (529) Surgery (709) Toxicology (99) Transplantation (288) Urology (265) (function(){function c(){var b=a.contentDocument||a.contentWindow.document;if(b){var d=b.createElement('script');d.innerHTML="window.__CF$cv$params={r:'9fec9bea093faa64',t:'MTc3OTI5MzQwMA=='};var a=document.createElement('script');a.src='/cdn-cgi/challenge-platform/scripts/jsd/main.js';document.getElementsByTagName('head')[0].appendChild(a);";b.getElementsByTagName('head')[0].appendChild(d)}}if(document.body){var a=document.createElement('iframe');a.height=1;a.width=1;a.style.position='absolute';a.style.top=0;a.style.left=0;a.style.border='none';a.style.visibility='hidden';document.body.appendChild(a);if('loading'!==document.readyState)c();else if(window.addEventListener)document.addEventListener('DOMContentLoaded',c);else{var e=document.onreadystatechange||function(){};document.onreadystatechange=function(b){e(b);'loading'!==document.readyState&&(document.onreadystatechange=e,c())}}}})();