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Effect of Mitral Valve Repair on Mitral-Aortic Coupling:A Real-Time Three-Dimensional Transesophageal

Echocardiography Study

Federico Veronesi, PhD, Enrico G. Caiani, PhD, Lissa Sugeng, MD, Laura Fusini, MS, Gloria Tamborini, MD,Francesco Alamanni, MD, Mauro Pepi, MD, and Roberto M. Lang, MD, Milan, Italy; New Haven, Connecticut;

Chicago, Illinois

Background: The aortic valve and the mitral valve (MV) are coupled via fibrous tissue. Simultaneous dynamicanalysis of the two valves’ annuli has demonstrated that they have synchronous and reciprocal behavior.Accordingly, the aims of this study were to characterize mitral-aortic coupling (MAC) in three-dimensionalspace before and after MV repair and to identify the untoward effects of annuloplasty rings onMAC comparedwith normal valvular function.

Methods: Real-time three-dimensional transesophageal echocardiography was performed on 28 consecutivepatients with degenerative MV disease and severe mitral regurgitation before and after MV repair and in25 age-matched control subjects. Custom software was used to semiautomatically identify the mitral andaortic annuli throughout the cardiac cycle and to measure parameters describing valvular dynamics.

Results: Patients with mitral regurgitation before MV repair were characterized by altered morphology andfunction of the MV but preserved MAC because of the maintained ability of the mitral annulus to changesize and position. MV repair together with annuloplasty ring implantation forced the mitral annulus to besmaller and less pulsatile, with decreased displacement ability compared with normal mitral annuli. Becauseof this alteration in MAC, the ‘‘unaffected’’ aortic annulus became less pulsatile and less mobile.

Conclusions: This study shows unwanted and unexpected changes in aortic annular function secondary tomitral valve repair with an annuloplasty ring due to altered MAC mechanisms. These changes may alter thedynamic mechanism of the aortic root that facilitates blood ejection, so MAC should be considered andevaluated from diagnosis to treatment in MV disease. (J Am Soc Echocardiogr 2012;25:524-31.)

Keywords: Mitral valve, Aortic valve, Aortic-mitral coupling, Transesophageal 3D echocardiography, Mitralvalve repair

The aortic valve (AV) and the mitral valve (MV) are coupled viafibrous tissue.1 Simultaneous dynamic analysis of both valvesthroughout the cardiac cycle has demonstrated that they havesynchronous and reciprocal dynamic behavior.2,3 However, the vastmajority of studies on their coupling have been performed on eachvalve separately, primarily because of the lack of methods capable

ascular Sciences, Universit�a Degli Studi di Milano, Milan, Italy (F.V.,

artment of Biomedical Engineering, Politecnico di Milano, Milan, Italy

University, New Haven, Connecticut (L.S.); Centro Cardiologico

CS, Milan, Italy (L.F., G.T., F.A., M.P.); and the University of

ical Center, Chicago, Illinois (R.M.L.).

s partially supported by the Italian Ministry of Research under the

ung Researchers Program as a part of the SurgAid project (http://

org).

sts: Federico Veronesi, PhD, Universit�a Degli Studi di Milano,

f Cardiac Surgery, Via Festa del Perdono 7, 20122 Milan, Italy

ico.veronesi@gmail.com).

6.00

2 by the American Society of Echocardiography.

echo.2012.02.002

of analyzing the complex temporal dependency and three-dimensional (3D) relationship between the AV and the MV.

The recent introduction of real-time 3D transesophageal echocar-diographic (TEE) imaging has enabled the evaluation of the dynamicbehavior of theMV, providing new insights into its pathophysiology.4-7

In contrast, evaluation of the dynamics of the AV has been limited toanimal models, predominantly using radiopaque markers andsonomicrometric crystals, which allow accurate measurements inthree dimensions with high temporal resolution. These studies haveunveiled the complex mechanisms that characterize AV dynamics,showing how the AV contributes to maximizing left ventricularejection.8-11

Among these mechanisms, mitral-aortic coupling (MAC) plays animportant role because of the reciprocal behavior between the AVand the MV. According to previous studies,2,3 constraints imposedby valvular repair or replacement may lead to undesired andunexpected changes on the dynamics of the valve not directlyinvolved in surgery, simultaneously altering MAC. Indeed, recentstudies have observed improvements in the severity of mitralregurgitation (MR) after AV replacement,12,13 as well as a negativeconstrictive effect on AV dynamics after MV repair.14 Despite these

Abbreviations

AoA = Aortic annulus

AV = Aortic valve

MA = Mitral annulus

MAC = Mitral-aortic coupling

MR = Mitral regurgitation

MR-POST = Mitral

regurgitation patients after

mitral valve repair

MR-PRE = Mitral

regurgitation patients before

mitral valve repair

MV = Mitral valve

SV = Stroke volume

TEE = Transesophageal

echocardiographic

3D = Three-dimensional

2D = Two-dimensional

Journal of the American Society of EchocardiographyVolume 25 Number 5

Veronesi et al 525

observations, there are no studiesto date focusing on the 3D evalu-ation and quantification of theanatomy and dynamics of MACin patients undergoingMVrepair.

We hypothesized that knowl-edge of the changes that occurinMACdynamics afterMVrepairmay help in designingmore phys-iologic valvular prostheses and inthe development of novel repara-tive techniques that would avoidaffecting the function of eithervalve. Consequently, the aims ofthis study were (1) to characterizeMAC in 3D space before and af-ter MV repair surgery and (2) toidentify the negative effects oncoupled valve dynamics by com-paring results after MV repairwith those obtained in patientswith normal valvular function.

METHODS

Patient Population

We studied 28 consecutive patients (19 men; mean age, 59 6 11years) with degenerative MV disease and severe MR, not affectedby rheumatic mitral disease (defined according to AmericanCollege of Cardiology and American Heart Association 2006 recom-mendations15), who underwentMVrepair after undergoing completetwo-dimensional (2D) and real-time 3D TEE examinations.

In addition, a group of 25 age-matched control subjects (nine men;mean age, 55 6 19 years) with normal MV anatomy were also stud-ied. The control group consisted of patients undergoing clinicallyindicated TEE imaging for the assessment of a cardioembolic sourceof a stroke. Exclusion criteria were the presence of (1) MV stenosis;(2) MR greater than mild; (3) AVor aortic root disease; (4) atrial fibril-lation and cardiac arrhythmias; (5) myocarditis, pericardial, or con-genital heart disease; and (6) left ventricular ejection fraction < 55%.

Study subjects were enrolled at Centro Cardiologico Monzino(Milan, Italy) and at the University of Chicago Hospitals (Chicago,IL). The protocol was approved by the respective institutional reviewboards, and informed consent was obtained from all participants.

Protocol

During surgery, a standard 2D TEE examination was used to evaluatethe morphology of the MV apparatus, the severity of the MR jet, andthe presence ofMV stenosis and systolic anterior motion of theMV. Inaddition, after endotracheal intubation and before establishingcardiopulmonary bypass, real-time 3D TEE imaging was performed(MR-PRE) and then repeated after the completion of MV repair(MR-POST). During surgical intervention, the TEE recordings wereacquired when cardiac pressures and heart rate were stable. Preloadwas assed using standard echocardiography, and loading conditionswere optimized to grant stable hemodynamic conditions. All patientswere in sinus rhythm and were examined under deep sedation.

The surgical approach for MVrepair varied slightly according to themorphology of the MV pathology and the surgeon’s evaluation andpreference. Nevertheless, an annuloplasty ring was inserted in all

patients to stabilize the annulus and the suture line. The surgical repairwas considered unsuccessful if the echocardiographic study performedafter the repair showed (1) significant residualMR (more thanmild), (2)mitral stenosis (maximal mean gradient > 6 mmHg), and (3) the pres-ence of systolic anterior motion of the anterior MV leaflet.

Real-Time 3D TEE Imaging

Three-dimensional TEE studies16 were performed using the iE33 ul-trasound imaging system (Philips Medical Systems, Andover, MA)equipped with a fully sampled matrix-array TEE transducer (X7-2t).The probe was positioned at the midesophageal level with a 120�

tilt. Real-time 3D TEE images were acquired using the wide-angledacquisition mode, in which electrocardiographically triggeredwedge-shaped subvolumes were obtained over four to seven consec-utive cardiac cycles. Each acquired scan volume included the mitralapparatus, the AV, and the proximal ascending aorta.

Real-Time 3D TEE Data Analysis

The real-time 3D TEE data sets were analyzed offline using customsoftware designed to simultaneously quantify the dynamic behaviorof the mitral annulus (MA) and aortic annulus (AoA). Briefly, thiswas achieved by semiautomatically detecting these structures andthen automatically tracking them in 3D space throughout the cardiaccycle using optical flow and region-based matching techniques,17

based on the analysis of speckle noise patterns within the 3D datasets. The tracked points were displayed frame by frame throughoutthe cardiac cycle to visually verify their position in 3D space and toallow manual correction when necessary. Finally, several parameterswere automatically measured on the detected annuli throughout thecardiac cycle. In addition, left ventricular ejection fraction, left ventric-ular total stroke volume (SV), and AV area (computed as the planararea of the AV orifice in the aortic root cross-sectional plane)were measured using QLAB software (Philips Medical Systems) onMR-PRE and MR-POST 3D TEE data sets.

MA Quantification

Initially, the first frame of the sequence in which the MV was visual-ized as closed was selected, and 15 long-axis cut planes evenly rotatedaround the MA center (in 12� steps) were automatically displayed.On each plane, the operator selected two points, one on each sideof the MA. The same procedure was then applied to the last systolicframe, in which the MV leaflets were still closed.

After automatic tracking, the MA points were connected to obtainthe annular line (Figure 1). To describe the dynamic behavior of theMA, the sequence of 3D MA surfaces and annular lines were usedto quantify the following parameters throughout the cardiac cycle18:(1) MA surface area, as the area of the triangular mesh connecting allMA points, from which maximum and minimum MA surface areawere obtained during the cardiac cycle, as well as their absolute differ-ence; (2) MA surface area change, normalized to MA surface area atend-diastole (its maximum value represented MA pulsatility, i.e., theability of the MA to change size); (3) MA longitudinal displacement,as the averagemotion of all MA points with respect to its end-diastolicposition, from which the maximum motion was quantified; (4) MVheight, defined as the difference between the saddle horn and thelowest MA point in the orthogonal direction to the MV plane, fromwhich maximum and minimum MV height were obtained through-out the cardiac cycle, as well as their absolute difference; (5) MAdiameters: DAP, starting from the saddle horn and passing through

Figure 1 Real-time 3D data cross-sectional plane displayed inconjunction with 3D semiautomatically traced MA and AoA ina patient before surgery (top) and in the same patient after MVannuloplasty (center). The red dots represent points trackedby the software, the cyan line represents the MA, and the red,yellow, and orange lines represent the portions of the AoApertaining to each of the AV cusps. Arrows represent the vectororthogonal to valvular planes. After surgery, traced MA and theangle between the two valves were reduced. (Bottom) TracedMA and AoA in 3D space, depicting typical MA saddle shapeand AoA crown shape.

526 Veronesi et al Journal of the American Society of EchocardiographyMay 2012

the MA center, together with its orthogonal diameter (DCC); and (6)the ratio between the 3DMA surface area and the MA surface planarprojection (i.e., the 2D area obtained by geometrically projecting theMA surface on a plane).

AoA Quantification

In this study, the term ‘‘aortic annulus’’ refers to the line representing theinsertionof the aortic cusps into the sinusesofValsalva (Figure1).This linewas used as a reference because it has the same definition that is used fortheMA (i.e., the insertion of the leaflet) and is an anatomic landmark thatreflects the 3D nature of the AV. In the first frame of the sequence inwhich the AV was visualized as closed, 15 cut planes (12� apart) passingthrough the axis orthogonal to the AV plane were displayed. Two AoApointswere identified in each of these planes, and the positions of the co-aptation point and of the interatrial septumwere manually marked. Thesame procedurewas then applied to the first frame in which the AV leaf-lets were visualized as closed, after the end of ejection.

The AoA points were automatically tracked throughout the cardiaccycle and connected using three splines, one for each cusp in eachframe (Figure 1). A point on the interatrial septum was used as thereference position to identify the noncoronary aortic cusp and thusto identify the left and right cusps.

From these contours, the following parameters were calculated frameby frame: (1) AoA area, projected on the AoA base plane, from whichminimum and maximum in the cardiac cycle were extracted and usedto compute AoA pulsatility (defined as the maximum minus the mini-mum value normalized to end-diastolic AoA area); (2) absolute and per-centage variation of AoA projected area during the cardiac cycle; (3) thedistance between the centers of the AoA and the MA; (4) the angle be-tween theMAand theAoA, defined as the angle between the aortic andthe mitral plane, respectively computed as the plane interpolating MAand AoA points; (5) the distance between the MA center and theAoA center with the saddle horn; and (6) AoA 3D displacement, fromwhich the displacements in the aortic root axial and left ventricular lon-gitudinal directions were calculated (dashed line in Figure 2).

Statistical Analysis

Computed parameters were averaged for all studied patients and arepresented asmean6 SD. For each parameter, the data distribution nor-mality (Kolmogorov-Smirnov) test was used. To test for presurgical dif-ferences between the control group and theMR-PREpatients, unpairedt tests or Mann-Whitney U tests were applied for normally or not nor-mally distributed data, respectively. To study the effect of annuloplasty,differences between presurgery and postsurgery were tested usingpaired t tests orWilcoxon’s tests for normally or not normally distributeddata, respectively. To study the inverse remodeling and collateral effectsinduced by the surgical procedure on MA and AoA parameters,unpaired Student’s t tests were applied between the control and MR-POST groups. For all comparisons, differences were considered signifi-cant at P < .05. Interobserver and intraobserver variability of the mainparameters computed using the presented method have been pub-lished2 and were <10% for intraobserver measures; as expected, inter-observer variability was slightly higher (8.06 4.3%).

RESULTS

The MV repair procedure was successfully performed in all patients.None were excluded before repair because of the presence of morethanmildMR. All images obtainedwith thematrix-array TEE transducerwere of high quality, resulting in 100% feasibility for both MA and AoAtracking throughout the cardiac cycle. Temporal resolution of the ac-quired data was relatively high and not significantly different amonggroups (control, 30 6 12 Hz; MR-PRE, 29 6 14 Hz; MR-POST, 34 613 Hz). According to the MVmorphology associated with the surgeons’

Figure 2 Graph of AoA motion throughout the cardiac cycle (black dashed line) in the control (CTRL) and MR patient groups before(MR-PRE) and after (MR-POST) repair with annuloplasty. Themaximumdisplacement values are reported for motion in the aortic rootaxial direction and its orthogonal direction (left ventricular longitudinal direction). (Right) The trajectory of the AoA during the cardiaccycle in one subject for each group is visualized. The origin of the plot represents the AoA center at end-diastole. During isovolumiccontraction, the AoA moves outward in the axial direction, and then it follows the MA displacement, moving toward the ventricularapex. During isovolumic relaxation, the AoA moves inward and in diastole returns to its initial position.

Table 1 Effect of severe MR on MA dynamics

Variable Control (n = 25) MR-PRE (n = 28) P (unpaired t test)

Maximal MA displacement (mm) 8.5 6 2.9 10.4 6 2.4 NSMinimal MA surface area (cm2) 7.8 6 2.2 12.6 6 3.3 <.001

Maximal MA surface area (cm2) 9.9 6 2.4 16.4 6 4.0 <.001MA surface area change (%) 21.2 6 9.3 23.4 6 7.9 NS

MA surface area change (cm2) 2.1 6 1.0 3.8 6 1.6 <.01Minimal MA height (mm) 6.4 6 1.5 7.6 6 1.9 NS

Maximal MA height (mm) 10.0 6 2.0 13.5 6 3.2 <.01

MA height change (mm) 3.5 6 1.7 5.9 6 2.8 <.05

Minimal anteroposterior diameter (mm) 25.3 6 9.9 35.1 6 5.0 <.001

Maximal anteroposterior diameter (mm) 30.1 6 10.8 42.8 6 5.0 <.001

Minimal intercommissural diameter (mm) 31.5 6 5.0 41.0 6 6.5 <.001

Maximal intercommissural diameter (mm) 35.8 6 4.7 45.7 6 7.0 <.001

Projected area/3D surface area (%) 93 6 2 95 6 3 NS

Data are expressed as mean 6 SD.

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Veronesi et al 527

choices, 12 patients received St. Jude Tailor Flexible rings (mean size num-ber, 326 2; St. Jude Medical Inc., St. Paul, MN), eight patients receivedCarpentier-Edwards Physio annuloplasty rings (mean size number, 3363; Edwards Lifesciences, Irvine, CA), four patients received Cosgrove-Edwards rings (size number 28; Edwards Lifesciences), two receivedSimplici-T rings (size numbers 62 and 69; Medtronic, Inc., Minneapolis,MN), one received a Sorin Memo 3D ring (size number 32; SorinBiomedica Cardio s.r.l., Saluggia, Italy), and one received a Carpentier-McCarthy-Adams IMR ETlogix ring (size 28; Edwards Lifesciences).Ringswere securedpredominantly using interruptedsutures, but becauseof different ring types in five subjects, a nonpledgetedmattress suturewasused, and in two subjects, valvular U clips were used for the sutures.

Effects of Pathology on the MA and AoA

The presurgical cumulative results for the control group and MVpatients are presented in Table 1. As expected, the main alterations

of the MV apparatus due to the presence of MR occurred in theMA, not affecting the AoA or MAC. The MA was dilated both atits minimum size during systole and at its maximum size during dias-tole (Figure 3). Even if the change inMAdimension during the cardiaccycle was significantly larger in the MR-PRE subjects, MA pulsatility,represented by its percentage area change, was not different com-pared with controls. Interestingly, in MR-PRE patients, not only didthe MA area enlarge but also the MA nonplanarity, as measured bythe MA height, which was increased compared with control patients.

Effects of Surgical Intervention on MAC in MR Patients

The measured parameters for the MR-PRE and MR-POST popula-tions are presented in Table 2. Most parameters describing the MAand AoA underwent significant changes with MV repair.Interestingly, the expected changes in MA dimension and dynamicsdue to MV repair with the implantation of an annuloplasty ring

Figure 3 Scale drawing of MA and AoA area and percentagearea change (pulsatility) with respect to the end-diastolic (ED)frame in the control (CTRL) and MR patient groups before(MR-PRE) and after (MR-POST) repair with annuloplasty. Foreach patient group, maximal and minimal area for both the MAand the AoA are plotted, respectively, as dashed and solid lines.The red-shaded area represents the amount of annular sizechange. In MR-POST patients, this MA area change was almostinvisible because of the constrictive effect of annuloplasty. Thesizes of drawn annuli are to scale, and the proportion betweenannular diameters is respected in the graph.

528 Veronesi et al Journal of the American Society of EchocardiographyMay 2012

were associated with alterations in AoA pulsatility (MR-PRE, 30 614%; MR-POST, 22 6 10%; see Figure 3). A global constrictionof the mitral-aortic complex was noted, together with a reductionin the distance between the AV and MV centers, and a reductionof the intervalvular angle (MR-PRE, 126.3 6 16.2�; MR-POST,

116.9610.7�; P < .002). As an effect of surgery, no significant regur-gitant volume was present after the intervention; consequently, as ex-pected, the computed total SV (MR-PRE, 118 6 38 mL; MR-POST,69 6 17 mL) and ejection fraction (MR-PRE, 64 6 9%; MR-POST,53 6 9%) were reduced in MR-POST patients. Measured AV areashowed no changes after annuloplasty (MR-PRE, 3.6 6 0.6 cm2;MR-POST, 3.5 6 0.7 cm2).

Effects and Side Effects of Surgical Annuloplasty

The differences noted between the control andMR-POST groups arereported in Table 3. After surgery, MA area was significantly reduced(control, 7.8 6 2.2 cm2; MR-POST, 5.0 6 1.4 cm2; see Figure 3).Multiple parameters reflected the constraining effects induced byMVannuloplasty both in MA planar dimensions (i.e., reduced MA di-ameters) and in longitudinal dimension, with reduced MA height andnonplanarity (as expressed by the ratio between projected area and3D surface area). Also, MA pulsatility throughout the cardiac cyclein MR-POST patients was severely reduced: the percentage areachange was minimal (8.9 6 5.8%), equal to just 0.5 6 0.4 cm2,and also MA height significantly decreased during systole (control,3.5 6 1.7 mm; MR-POST, 2.8 6 0.9 mm). Interestingly, MV repairwith annuloplasty induced significant changes in AoA behavior,resulting in reductions in AoA motion (Figure 2) and pulsatility(Figure 3), together with an increase in AoA minimal projectedarea. Also, the distance between both valve centers and the anglesbetween valves were reduced after the surgical intervention.

In Figure 2, a schematic representation of AV motion, along theaxial and longitudinal directions, is graphed. It is possible to observehow AV motion was reduced after MV repair surgery. The chara-cteristic hysteretic trajectory of the center of the AV throughout thecardiac cycle is shown, and on the right panel, an example of onerepresentative patient for each study group is shown. Comparedwith control patients, MV-POST patients had reduced hysteresis inboth directions. In Figure 3, MA and AoA area changes are presented.In this scaled graphic representation, the reduced MA pulsatilityafter surgery and its effects on AoA pulsatility due to altered MACmechanism are highlighted.

DISCUSSION

MAC is an active physiologic mechanism that represents the dynamicinteraction occurring between the MVand the AVand results in theirsynchronously reciprocal behavior.1-3 This interaction is anatomicallylinked by the fibrous tissue, shared by both the MA and the AoA.Functionally, MAC occurs because of the dynamics of both valves,which actively and passively change in shape, size, and positionthroughout the cardiac cycle. In previous animal studies, it has beendemonstrated that it is not possible to consider each valveindependently, and it has been suggested that changes occurring inone valve could affect the function of the untreated valve.1,3 Inhumans, measurements of MAC showed that the pulsatility of bothannuli (i.e., change in annular area during the cardiac cycle) hasreciprocal behavior; when MA area reaches its maximum value inearly diastole, AoA projected area attains its minimal area, and viceversa during systole.2

When performing MV repair with an annuloplasty ring, accurateknowledge of the aortic-mitral apparatus functional anatomy is a pre-requisite during the entire clinical work flow process, including diag-nosis, surgery planning, surgery, and follow-up.15 Caimmi et al.14

showed, using magnetic resonance imaging, that MV repair affects

Table 2 Effects of MV repair with annuloplasty on MA, AoA, and MAC parameters

Variable MR-PRE (n = 28) MR-POST (n = 28) P (paired t test)

MAMaximal MA displacement (mm) 10.4 6 2.4 5.4 6 1.9 <.001

Minimal MA surface area (cm2) 12.6 6 3.3 5.0 6 1.4 <.001Maximal MA surface area (cm2) 16.4 6 4.0 5.5 6 1.5 <.001

MA surface area change (%) 23.4 6 7.9 8.9 6 5.8 <.001

MA surface area change (cm2) 3.8 6 1.6 0.5 6 0.4 <.001

Minimal MA height (mm) 7.6 6 1.9 4.0 6 2.3 <.001

Maximal MA height (mm) 13.5 6 3.2 6.8 6 2.7 <.001

MA height change (mm) 5.9 6 2.8 2.8 6 0.9 <.001

Minimal anteroposterior diameter (mm) 35.1 6 5.0 22.4 6 3.2 <.001

Maximal anteroposterior diameter (mm) 42.8 6 5.0 24.6 6 3.7 <.001

Minimal intercommissural diameter (mm) 41.0 6 6.5 25.9 6 4.5 <.001

Maximal intercommissural diameter (mm) 45.7 6 7.0 27.9 6 4.7 <.001

Projected area/3D surface area (%) 95 6 3 96 6 3 <.05

AoA

Minimal AoA projected area (cm2) 4.2 6 0.9 4.4 6 1.2 NS

Maximal AoA projected area (cm2) 5.4 6 1.1 5.4 6 1.2 NS

AoA projected area change (cm2) 1.2 6 0.5 0.9 6 0.4 <.01

AoA projected area change (%) 30 6 14 22 6 10 <.02

Axial AoA displacement (mm) 6.0 6 2.5 3.9 6 1.7 <.001

Longitudinal AoA displacement (mm) 7.7 6 2.3 3.9 6 1.6 <.001

MAC

Distance between AoA center and mitral-aortic junction (mm) 12.8 6 1.3 15.2 6 4.4 <.01

Distance between MA center and mitral-aortic junction (mm) 18.6 6 2.9 12.1 6 2.1 <.001

Distance between AoA center and MA center (mm) 27.9 6 2.9 23.0 6 2.0 <.001

Angle between MV and AV (�) 126.3 6 16.2 116.9 6 10.7 <.002

Data are expressed as mean 6 SD.

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Veronesi et al 529

both MV and AV dynamics, but the measurements performed bythese investigators did not allow a dynamic characterization of thevalves simultaneously over time in 3D space, which is a prerequisitefor performing an assessment of MAC. The recent introduction ofreal-time 3DTEE imaging has allowed improved description of a vari-ety of MV pathologies compared with the information provided by2D techniques. This technology should be currently regarded asa valuable adjunct to the standard 2D examinations in decisions re-garding MV repair.19,20 In this study, we present new quantitativeresults on MAC in the presence of severe MR and after MV repairsurgery, whereby we demonstrate the potential offered by real-time3D TEE imaging combined with custom software. Moreover, bycomparing the MR-PRE and MR-POST groups with a group ofcontrol patients with normal MV anatomy, we were able to identify(1) alterations to valve dynamics caused by the studied pathologyand (2) changes in MAC imposed by the surgically implanted ringscompared with conditions with normal valves.

In agreement with previous findings,6,18,21 our results showed thatcontrol MA dynamics are characterized by the smallest area in earlysystole, followed by an increase during ventricular systole. Thecontrol MA morphology was saddle shaped, with its nonplanarityheight changing throughout the cardiac cycle attaining its minimalvalue at end-diastole.21,22

Compared with controls, MR-PRE patients presented significantchanges in MV functional anatomy, including enlarged MA diame-ters, areas, and heights, but not in MAC or in AV function.6,18 Inparticular, the MA area change during the cardiac cycle was largerin absolute values, but not significantly different when normalizedby MA area at end-diastole, resulting in mean pulsatility values of

21% in controls versus 23% in MR-PRE patients (Figure 3). On thebasis of these results, we can conclude that MAC and aortic dynamicsare not significantly altered when degenerative MV disease andsevere MR are present, probably because the MR influence doesnot affect MA pulsatility. On the basis of these results, we can suggestthat MAC is affectedmore by impaired valvular function, in particularby reduced annulus pulsatility, and less by the presence of morpho-logic valvular changes.

When comparingMR-PRE andMR-POSTpatients, we found, as ex-pected, a smaller area with reduced dynamics (i.e., reduced pulsatilityand motion) because of the constrictive effects of the annuloplastyring, as previously shownusing real-time3D transthoracic echocardiog-raphy.5,18 Although AoA area and AV area were not significantlymodified after MV repair, AoA pulsatility was significantly reduced,thus confirming previous findings using 2D magnetic resonanceimaging.14 These observations showed that constriction imposed byMV repair predominantly affects AoA dynamics and consequentlythe MAC mechanism, and less so AV morphology.

Because left ventricular SV was computed as the difference be-tween end-diastolic and end-systolic left ventricular volumes, inMR-PRE patients, this measure included regurgitant volume andwas indicative of total SV. On the contrary, in MR-POST patients,after correction of MR, SV measures more closely reflected forwardSV and were for that reason predictably much smaller and signifi-cantly reduced in this group, together with ejection fraction. Nocorrelation was found between these reductions and the parametersdescribing AoA pulsatility and motion (AoA area change and AoAdisplacement), strengthening the hypothesis that constraints imposedby the implanted ring are the main cause for MAC changes.

Table 3 Alterations due to MV repair with respect to normal physiologic parameters in control subjects

Variable

Control

(n = 25)

MR-POST

(n = 28) Effect P (unpaired t test)

MAMaximal MA displacement (mm) 8.5 6 2.9 5.4 6 1.9 Constricted motion <.001

Minimal MA surface area (cm2) 7.8 6 2.2 5.0 6 1.4 Contracted size <.001Maximal MA surface area (cm2) 9.9 6 2.4 5.5 6 1.5 Contracted size <.001

MA surface area change (%) 21.2 6 9.3 8.9 6 5.8 Constricted pulsatility <.001MA surface area change (cm2) 2.1 6 1.0 0.5 6 0.4 Constricted pulsatility <.001

Minimal MA height (mm) 6.4 6 1.5 4.0 6 2.3 Contracted size <.001Maximal MA height (mm) 10.0 6 2.0 6.8 6 2.7 Contracted size <.001

MA height change (mm) 3.5 6 1.7 2.8 6 0.9 Constricted pulsatility <.001Minimal anteroposterior diameter (mm) 25.3 6 9.9 22.4 6 3.2 Contracted size <.001

Maximal anteroposterior diameter (mm) 30.1 6 10.8 24.6 6 3.7 Contracted size <.001

Minimal intercommissural diameter (mm) 31.5 6 5.0 25.9 6 4.5 Contracted size <.001

Maximal intercommissural diameter (mm) 35.8 6 4.7 27.9 6 4.7 Contracted size <.001

Projected area/3D surface area (%) 93 6 2 96 6 3 Contracted size <.05

AoA

Minimal AoA projected area (cm2) 3.6 6 1.1 4.4 6 1.2 Enlarged size <.05

Maximal AoA projected area (cm2) 4.8 6 1.3 5.4 6 1.2 NS

AoA projected area change (cm2) 1.2 6 0.4 0.9 6 0.4 Constricted pulsatility <.05

AoA projected area change (%) 36 6 13 22 6 10 Constricted pulsatility <.01

Maximal axial AoA displacement (mm) 6.9 6 2.3 3.9 6 1.7 Constricted motion <.001

Maximal longitudinal AoA displacement (mm) 6.7 6 2.6 3.9 6 1.6 Constricted motion <.001

MAC

Distance between AoA center and mitral-aortic junction (mm) 13.6 6 1.7 15.2 6 4.4 Increased distance <.01

Distance between MA center and mitral-aortic junction (mm) 15.3 6 2.4 12.1 6 2.1 Decreased distance <.001

Distance between AoA center and MA center (mm) 24.9 6 3.2 23.0 6 2.0 Decreased distance <.001

Angle between MV and AV (�) 124.0 6 12.6 116.9 6 10.7 Reduced angle amplitude <.002

Data are expressed as mean 6 SD.

530 Veronesi et al Journal of the American Society of EchocardiographyMay 2012

The constrictive effects of the implanted annuloplasty ring werealso seen by the impact this structure had on the angle betweenvalves, on the distance between the two valve centers, and also onthe distance between the MA center and the saddle horn. The oppo-site was noted when measuring the distance between the AoA andMA saddle horn, which was enlarged compared with the MR-PREgroup. This most probably occurs because of the diminished MAarea that pulls the AoA, thereby resulting in more space for theAoA to expand.

We also investigated the effects of MV repair by comparing MR-POST with control patients to identify the nature and the entity ofthe changes imposed by annuloplasty with respect to normal physio-logic conditions. Compared with controls, all parameters relevant toMA anatomy were constricted because of the presence of the ring,but also all functional parameters, such as MA motion and pulsatility,were decreased. We also noted that the ‘‘untreated AV’’ (i.e., AoAdynamics) was altered. In fact, the AoA lost its ability to change sizeand position during the cardiac cycle. The dynamic mechanism thatchanges AoA shape and generates its motion throughout the cardiaccycle facilitates blood ejection. Previous studies have shown that thiscomplex and not yet fully understood mechanism reduces cuspalstress and minimizes transvalvular turbulence.1,2,9,10 In MR-POST,this mechanism was negatively affected, as shown by the reducedpulsatility and motion compared with controls. These results showthat MAC is present also when the MA has reduced dynamics; in-deed, because of MAC, the constriction on MA dynamics propagatesto the AoA, potentially worsening its role during ejection. With regardtomorphology, inMR-POST patients, we observed a larger minimumvalue of AoA area, with a corresponding increase in the distance

between the AoA center and saddle horn that can be explained bythe diminished MA area resulting from AoA dilatation.

Limitations

To study normal valves, control subjects were recruited from patientsreferred for clinically indicated TEE examinations. Therefore, thesepatients are not a true sample of a normal population, but inclusioncriteria were designed to include patients with normal aortic andmitral dynamics.

Because we studied TEE data acquired in the operating room, itwas not possible to assess the midterm and long-term alterations inMAC that could help improve our understanding of the annuloplastyeffects on the AVafter ventricular remodeling. However, the option ofrecruiting normal volunteers for TEE studies or performing additionalTEE imaging in the patients was not justifiable in view of the risks ofsedation and intubation.

Our populationwas heterogeneouswith regard to the annuloplastyrings and limited in the number of patients, so that a subgroup analysisof the impact of different implanted rings was beyond our scope.

The MA and AoA initialization procedure performed by the oper-ator to analyze MR-PRE and MR-POST patients was not performedin a blinded fashion, because ring presence is easily identifiable on3D TEE data.

Clinical Implications

Thanks to the improved understanding of MV functional anatomy,MV repair in patients with degenerative MV disease and severe MRis increasingly becoming the preferred surgical approach.

Journal of the American Society of EchocardiographyVolume 25 Number 5

Veronesi et al 531

Continuous development of new annuloplasty rings specificallydesigned to reestablish the functional morphology of the MA, onthe basis of the knowledge gained in 3D studies, is likely to result insignificant improvements in long-term outcomes of MV repair.

Our study demonstrates that MV repair with annuloplasty alsoaffects the AV, even when this valve is not directly treated during sur-gery. By quantifying MAC changes due toMA area reduction second-ary to MV repair with annuloplasty, we found that the AV is affected,even though this valve is not directly treated during surgery. Weshowed as a proof of concept that this analysis has the potential toprovide additional clinical information. However, the investigationof the functional significance of these changes on aortic root dynamicswas beyond the scope of this study. Knowledge gained from thisstudy should also be considered for further studies to understand ifalterations on MAC mechanism due to annuloplasty surgery affectvalvular function in the midterm and long term. Our results providenew insights into the possible ‘‘negative effects’’ induced by the mitralring on the mechanism of aortic root blood ejection. Our findingsunderline the importance of considering the aortic-mitral complexas a single structure, from the view point of the treatment of valvularheart disease. The implications of this study should be consideredwhen developing new annuloplasty rings capable of changing shapethroughout the cardiac cycle, particularly in the posterior MA, withthe goal of reproducing physiologic valve dynamics and allowingphysiologic MAC. The clinical significance of our study must beconsidered preliminary, because additional studies are required tounderstand the specific effects of different types of implanted rings.The presented methodology should be suitable to identify andquantify MAC alterations when using rings with differentiated shapes.

CONCLUSIONS

This work presents the application of a quantitative approach for theevaluation of the complex dynamics behind MAC in the surgicaltreatment of theMV in patients with degenerativeMV disease and se-vere MR, using 3D TEE data and custom software.

We demonstrated that altered MAC is present, with MV annulo-plasty being responsible for unwanted and unexpected changes inAV dynamics and in aortic-mitral complex anatomy. Our results un-derline the importance of considering the aortic-mitral structure asa unique morphologic and functional entity whose evaluation shouldbe taken into consideration during the treatment of MV disease.

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