Advertisement

Septal-lateral annular cinching abolishes acute ischemic mitral regurgitation

  • Tomasz A. Timek
    Affiliations
    From the Department of Cardiovascular Surgerya and the Division of Cardiovascular Medicine,b Stanford University School of Medicine, Stanford, Calif, and the Laboratory of Cardiovascular Physiology and Biophysics,c Research Institute of the Palo Alto Medical Foundation, Palo Alto, Calif
    Search for articles by this author
  • David T. Lai
    Affiliations
    From the Department of Cardiovascular Surgerya and the Division of Cardiovascular Medicine,b Stanford University School of Medicine, Stanford, Calif, and the Laboratory of Cardiovascular Physiology and Biophysics,c Research Institute of the Palo Alto Medical Foundation, Palo Alto, Calif
    Search for articles by this author
  • Frederick Tibayan
    Affiliations
    From the Department of Cardiovascular Surgerya and the Division of Cardiovascular Medicine,b Stanford University School of Medicine, Stanford, Calif, and the Laboratory of Cardiovascular Physiology and Biophysics,c Research Institute of the Palo Alto Medical Foundation, Palo Alto, Calif
    Search for articles by this author
  • David Liang
    Affiliations
    From the Department of Cardiovascular Surgerya and the Division of Cardiovascular Medicine,b Stanford University School of Medicine, Stanford, Calif, and the Laboratory of Cardiovascular Physiology and Biophysics,c Research Institute of the Palo Alto Medical Foundation, Palo Alto, Calif
    Search for articles by this author
  • George T. Daughters
    Affiliations
    From the Department of Cardiovascular Surgerya and the Division of Cardiovascular Medicine,b Stanford University School of Medicine, Stanford, Calif, and the Laboratory of Cardiovascular Physiology and Biophysics,c Research Institute of the Palo Alto Medical Foundation, Palo Alto, Calif
    Search for articles by this author
  • Paul Dagum
    Affiliations
    From the Department of Cardiovascular Surgerya and the Division of Cardiovascular Medicine,b Stanford University School of Medicine, Stanford, Calif, and the Laboratory of Cardiovascular Physiology and Biophysics,c Research Institute of the Palo Alto Medical Foundation, Palo Alto, Calif
    Search for articles by this author
  • Neil B. Ingels Jr
    Affiliations
    From the Department of Cardiovascular Surgerya and the Division of Cardiovascular Medicine,b Stanford University School of Medicine, Stanford, Calif, and the Laboratory of Cardiovascular Physiology and Biophysics,c Research Institute of the Palo Alto Medical Foundation, Palo Alto, Calif
    Search for articles by this author
  • D.Craig Miller
    Affiliations
    From the Department of Cardiovascular Surgerya and the Division of Cardiovascular Medicine,b Stanford University School of Medicine, Stanford, Calif, and the Laboratory of Cardiovascular Physiology and Biophysics,c Research Institute of the Palo Alto Medical Foundation, Palo Alto, Calif
    Search for articles by this author

      Abstract

      Objective: Ring annuloplasty prevents acute ischemic mitral regurgitation in sheep, but it also abolishes normal mitral annular and posterior leaflet dynamics. We investigated a novel surgical approach of simple septal-lateral annular cinching with sutures to treat acute ischemic mitral regurgitation. Methods: Nine adult sheep underwent implantation of multiple radiopaque markers on the left ventricle, mitral anulus, and mitral leaflets. A septal-lateral transannular suture was anchored to the midseptal mitral anulus and externalized to a tourniquet through the midlateral mitral anulus and left ventricular wall. Open-chest animals were studied immediately postoperatively. Acute ischemic mitral regurgitation was induced by means of proximal left circumflex artery snare occlusion, and 3 progressive steps of septal-lateral annular cinching (each 2-3 mm suture tightening for 5 seconds) were performed with the transannular suture. Biplane videofluoroscopy for 3-dimensional marker coordinates and transesophageal echocardiography were performed continuously before and during left circumflex ischemia and septal-lateral annular cinching. Results: Acute left circumflex ischemia caused ischemic mitral regurgitation (+0.5 ± 0.4 [baseline] vs +2.0 ± 0.7 [ischemia]; P = .005; scale, +0-4), which decreased progressively with each step of septal-lateral annular cinching and was eliminated during the third step (ischemic mitral regurgitation, +0.6 ± 0.5; P = not significant vs baseline). The third step of septal-lateral annular cinching decreased the septal-lateral diameter by 6.0 ± 2.6 mm (P = .005); however, mitral anulus area reduction (8.5% ± 1.0% and 6.9% ± 1.9% for ischemic mitral regurgitation and septal-lateral annular cinching step 3, respectively; P = .006) and posterior leaflet excursion (50° ± 9° and 44° ± 11° for regurgitation and annular cinching step 3, respectively; P = .002) throughout the cardiac cycle were affected only mildly. Normal mitral annular 3-dimensional shape was maintained with septal-lateral annular cinching. Conclusions: Isolated 22% ± 10% reduction in mitral annular septal-lateral dimension abolished acute ischemic mitral regurgitation in normal sheep hearts while allowing near-normal mitral annular and posterior leaflet dynamic motion. Septal-lateral annular cinching may represent a simple method for the surgical treatment of ischemic mitral regurgitation, either as an adjunctive technique or alone, which helps preserve physiologic annular and leaflet function.
      J Thorac Cardiovasc Surg 2002;123:881-8
      Ischemic mitral regurgitation (IMR) continues to frustrate surgeons because neither its mechanism nor an ideal surgical therapy has been clearly defined. MR caused by ischemic heart disease is associated with a far less satisfactory prognosis than other forms of mitral disease.
      • Czer LS
      • Gray RJ
      • DeRobertis MA
      • Bateman TM
      • Stewart ME
      • Chaux A
      • et al.
      Mitral valve replacement: impact of coronary artery disease and determinants of prognosis after revascularization.
      • Connolly MW
      • Gelbfish JS
      • Jacobowitz IJ
      • Rose DM
      • Mendelsohn A
      • Cappabianca PM
      • et al.
      Surgical results for mitral regurgitation from coronary artery disease.
      • Replogle RL
      • Campbell CD
      Surgery for mitral regurgitation associated with ischemic heart disease: results and strategies.
      Although mitral valve repair, usually consisting of simple ring annuloplasty, has been associated with more encouraging results in this challenging patient cohort,
      • Dion R.
      Ischemic mitral regurgitation: when and how should it be corrected?.
      • Rankin JS
      • Feneley MP
      • Hickey MS
      • Muhlbaier LH
      • Wechsler AS
      • Floyd RD
      • et al.
      A clinical comparison of mitral valve repair versus valve replacement in ischemic mitral regurgitation.
      the superiority of valve repair over valve replacement has yet to be firmly established.
      • Hausmann H
      • Siniawski H
      • Hetzer R.
      Mitral valve reconstruction and replacement for ischemic mitral insufficiency: seven years' follow up.
      • Cohn LH
      • Rizzo RJ
      • Adams DH
      • Couper GS
      • Sullivan TE
      • Collins JJ
      • et al.
      The effect of pathophysiology on the surgical treatment of ischemic mitral regurgitation: operative and late risks of repair versus replacement.
      Unfortunately, only approximately 50% of patients are still alive at 5 years, primarily because of left ventricular (LV) dysfunction present at the time of the operation caused by previous LV infarction and ischemia. Mitral ring annuloplasty has been demonstrated to effectively correct IMR in clinical
      • Cohn LH
      • Rizzo RJ
      • Adams DH
      • Couper GS
      • Sullivan TE
      • Collins JJ
      • et al.
      The effect of pathophysiology on the surgical treatment of ischemic mitral regurgitation: operative and late risks of repair versus replacement.
      • Czer LS
      • Maurer G
      • Trento A
      • DeRobertis M
      • Nessim S
      • Blanche C
      • et al.
      Comparative efficacy of ring and suture annuloplasty for ischemic mitral regurgitation.
      • Grossi EA
      • Lapietra A
      • Galloway AC
      • Ribakove GH
      • Culliford AT
      • Sposito RA
      • et al.
      Late results of isolated mitral annuloplasty for ischemic mitral insufficiency [abstract].
      and experimental
      • Timek T
      • Glasson JR
      • Dagum P
      • Green GR
      • Nistal JF
      • Komeda M
      • et al.
      Ring annuloplasty prevents delayed leaflet coaptation and mitral regurgitation during acute left ventricular ischemia.
      studies, most likely by facilitating leaflet coaptation through reduction of the annular septal-lateral (SL; or clinically termed anteroposterior) dimension.
      • Timek T
      • Glasson JR
      • Dagum P
      • Green GR
      • Nistal JF
      • Komeda M
      • et al.
      Ring annuloplasty prevents delayed leaflet coaptation and mitral regurgitation during acute left ventricular ischemia.
      On the other hand, ovine experiments have shown that ring annuloplasty, whether semirigid or flexible, abolishes normal mitral annular dynamics
      • Glasson JR
      • Green GR
      • Nistal JF
      • Dagum P
      • Komeda M
      • Daughters GT
      • et al.
      Mitral annular size and shape in sheep with annuloplasty rings.
      and freezes the posterior mitral leaflet.
      • Green GR
      • Dagum P
      • Glasson JR
      • Nistal JF
      • Daughters GT
      • Ingels Jr, NB
      • et al.
      Restricted posterior leaflet motion after mitral ring annuloplasty.
      Limited posterior leaflet excursion after implantation of a rigid annuloplasty ring has also been reported in a porcine model
      • van Rijk-Zwikker GL
      • Mast F
      • Schipperheyn JJ
      • Huysmans HA
      • Bruschke AV
      Comparison of rigid and flexible rings for annuloplasty of the porcine mitral valve.
      and clinically is seen often after any type of annuloplasty.
      We developed a novel technique of SL annular reduction using a simple transannular suture to enhance leaflet coaptation while avoiding the deleterious effects of ring annuloplasty on annular and leaflet dynamic motion. By using radiopaque marker technology, we carried out a preliminary investigation of the efficacy of septal-lateral annular cinching (SLAC) in an open-chest sheep preparation during acute posterolateral ischemia.

      Methods

      Surgical preparation

      Figure thumbnail gr1
      Fig. 1Array of LV (circles), mitral annular (squares), and leaflet (triangles) markers used in this ovine experiment. AML, Anterior mitral leaflet; PML, posterior mitral leaflet.
      Figure thumbnail gr2
      Fig. 2Schematic illustration of the mitral valve with annular (squares) and leaflet (triangles) markers and the aortic valve included for orientation. SLAC suture (dashed line) spans the annular SL dimension and was externalized to an epicardial tourniquet. Arrow shows the direction of annular cinching. AV, Aortic valve; ACOM, anterior commissure; PCOM, posterior commissure; AML, anterior mitral leaflet; PML, posterior mitral leaflet.
      All animals received humane care in compliance with the “Principles of Laboratory Animal Care” formulated by the National Society for Medical Research and the “Guide for the Care and Use of Laboratory Animals” prepared by the Institute of Laboratory Animal Resources, National Research Council, and published by the National Academy Press, revised 1996. This study was approved by the Stanford Medical Center Laboratory Research Animal Review committee and conducted according to Stanford University policy.

      Data acquisition and analysis

      Data acquisition,
      • Glasson JR
      • Komeda M
      • Daughters GT
      • Foppiano LE
      • Bolger AF
      • Tye TL
      • et al.
      Most ovine mitral annular 3-D size reduction occurs before ventricular systole and is abolished with ventricular pacing.
      digital transformation,
      • Niczyporuk MA
      • Miller DC
      Automatic tracking and digitization of multiple radiopaque myocardial markers.
      and 3-dimensional reconstruction
      • Daughters GT
      • Sanders WJ
      • Miller DC
      • Schwarzkopf A
      • Mead CW
      • Ingels NBJ
      A comparison of two analytical systems for 3-D reconstruction from biplane videoradiograms.
      were performed as described previously. Two to 3 consecutive steady-state beats during IMR and each of the 3 steps of SLAC were designated as IMR, SLAC-1, SLAC-2, and SLAC-3 data for each animal, respectively. For each cardiac cycle, end-systole was defined as the frame containing the peak rate of fall of LV pressure (-dP/dt), and end-diastole as the videofluoroscopic frame containing the peak of the electrocardiographic R wave. Instantaneous LV volume was computed from the epicardial LV markers by using a space-filling multiple tetrahedral volume method.
      • Moon MR
      • DeAnda A
      • Daughters GT
      • Ingels NBJ
      • Miller DC
      Experimental evaluation of different chordal preservation methods during mitral valve replacement.
      MR was graded subjectively by an experienced cardiologist (D.L.) according to the extent and width of the regurgitant jet and categorized as none (0), mild (+1), moderate (+2), moderate to severe (+3), or severe (+4).

      Mitral annular dynamics

      Mitral annular area was computed from the 3-dimensional coordinates of the 8 markers sutured to the mitral anulus by using an annular centroid.
      • Timek T
      • Glasson JR
      • Dagum P
      • Green GR
      • Nistal JF
      • Komeda M
      • et al.
      Ring annuloplasty prevents delayed leaflet coaptation and mitral regurgitation during acute left ventricular ischemia.
      The SL annular diameter was calculated as the distance in 3-dimensional space between markers placed on the midseptal and midlateral mitral anulus, and the commissure-commissure (CC) diameter was determined as the distance between the markers on the anterior and posterior commissures. Angular position of the anterior leaflet edge was calculated as the angle (θAML) between the anterior leaflet edge marker and the SL annular diameter.
      • Karlsson MO
      • Glasson JR
      • Bolger AF
      • Daughters GT
      • Komeda M
      • Foppiano LE
      • et al.
      Mitral valve opening in the ovine heart.
      Posterior leaflet edge angular position (θPML) was calculated in similar fashion. Leaflet excursion was calculated from diastolic maximum to systolic minimum angle. For 3-dimensional reconstruction of mitral annular shape, a right-handed Cartesian coordinate system was used with the origin located at the midseptal anulus marker, with the Y-axis passing through the LV apex (positive toward the apex), with the positive X axis directed toward the midlateral anulus such that the midlateral marker was contained in the X-Y plane, and with the positive Z-axis directed toward the posterior commissure. The midseptal anulus was chosen as the origin because it is at the center of the fibrous anulus, the position and geometry of which are minimally affected by posterolateral LV ischemia.

      Statistical analysis

      All data are reported as means ± 1 SD. Hemodynamic and marker-derived data from consecutive steady-state beats from each heart were time aligned at end-diastole. Marker data were calculated over 20 frames before and after end-diastole, thus allowing evaluation over a time period of 650 ms. The mean and SD for each variable at each sampling instant were computed for each condition. Data were compared by using repeated-measures analysis of variance, followed by the Student t test for paired observations when a significant F value was detected.

      Results

      Hemodynamics

      Table 1Hemodynamics
      Pre-IMRIMRP value*
      HR (beats/min)106 ± 9106 ± 13.9
      dP/dtmax (mm Hg)2385 ± 3531265 ± 300.0001
      EDV (mL)146 ± 25170 ± 23.007
      ESV (mL)108 ± 27139 ± 18.0002
      SV (mL)38 ± 730 ± 10.2
      LVEDP (mm Hg)11 ± 518 ± 7.009
      LVPmax110 ± 1084 ± 12.0001
      *Student t test for paired observations.
      Data are presented as mean ± SD.
      HR, Heart rate; dP/dtmax, maximum positive rate of change of LV pressure; EDV, LV end-diastolic volume; ESV, LV end-systolic volume; SV, stroke volume; LVEDP, LV end-diastolic pressure; LVPmax, maximum LV pressure.
      Table 2SLAC hemodynamics
      IMRSLAC-1SLAC-2SLAC-3
      HR (beats/min)106 ± 13106 ± 12107 ± 13106 ± 12
      dP/dtmax (mm Hg)1265 ± 3001262 ± 3431217 ± 3551298 ± 424
      EDV (mL)170 ± 23169 ± 23169 ± 23168 ± 24
      ESV (mL)139 ± 18140 ± 19140 ± 18139 ± 19
      SV (mL)30 ± 1030 ± 929 ± 1028 ± 11
      LVEDP (mm Hg)18 ± 719 ± 921 ± 1022 ± 10
      LVPmax84 ± 1284 ± 1283 ± 1681 ± 16
      Data are presented as mean ± SD.
      HR, Heart rate; dP/dtmax, maximum positive rate of change of LV pressure; EDV, LV end-diastolic volume; ESV, LV end-systolic volume; SV, stroke volume; LVEDP, LV end-diastolic pressure; LVPmax, maximum LV pressure.

      Mitral regurgitation

      Before circumflex occlusion, 3 animals had mild MR, 3 had trace MR, and 3 had no MR for a baseline average of +0.5 ± 0.4. The significant increase in the mean degree of MR during acute posterolateral ischemia and subsequent decreases with SLAC steps are summarized in Table 3. IMR was mostly central and holosystolic during circumflex occlusion. The final step of annular cinching completely abolished IMR because there was no difference in the degree of MR between SLAC-3 and the baseline value (+0.6 ± 0.5 and +0.5 ± 0.4, P = .6).
      Table 3Mitral leaflet and annular dynamics
      IMRSLAC-1SLAC-2SLAC-3P value*
      MR+2.0 ± 0.7+1.8 ± 0.7+1.0 ± 0.4†+0.6 ± 0.5†.0005
      SLED (mm)27.7 ± 2.726.0 ± 3.424.5 ± 3.0†21.7 ± 3.9†.0005
      CCED (mm)40.1 ± 2.740.4 ± 2.7†40.5 ± 2.6†41.0 ± 2.7†.0005
      MAAED (mm2)856 ± 97823 ± 110798 ± 103†737 ± 118†.0005
      MAACONT (%)8.5 ± 1.08.0 ± 1.07.4 ± 0.9†6.9 ± 1.9†.005
      Θ-PMLEXC (°)50 ± 948 ± 1047 ± 944 ± 11†.0005
      Θ-AMLEXC (°)50 ± 550 ± 548 ± 648 ± 7.30
      *Repeated-measures ANOVA. †P < 0.016 (0.05/3) by Student t test for paired observation versus IMR.
      Data are presented as mean ± SD.
      SLED, End-diastolic mitral annular septal-lateral diameter; CCED, end-diastolic mitral annular commissure-commissure diameter; MAAED, end-diastolic mitral annular area; MAACONT, mitral annular area contraction during the cardiac cycle; Θ-PMLEXC, posterior mitral leaflet angular excursion with respect to the annular septal-lateral diameter; Θ-AMLEXC, anterior mitral leaflet angular excursion with respect to the annular septal-lateral diameter.

      Mitral annular dynamics

      Figure thumbnail gr3
      Fig. 3Group mean data for SL annular diameter (in millimeters, top), mitral annular area (in square millimeters, center), and CC annular diameter (in millimeters, bottom) throughout the cardiac cycle before (pre-IMR) and during acute IMR and progressive SLAC (SLAC-1, SLAC-2, and SLAC-3). A 650-ms time interval centered at end-diastole (t = 0) is illustrated for all 4 groups.
      Figure thumbnail gr4
      Fig. 4Left, Group mean 3-dimensional reconstruction of the mitral anulus at end-diastole during acute IMR and subsequent progressive SLAC (SLAC-1, SLAC-2, and SLAC-3). Drop lines are shown for IMR and SLAC-3 data points in the apical-basal and SL planes as solid (IMR) and dashed (SLAC-3) lines. Right, Rotated view of each reconstruction to the approximate level of the annular plane viewed from the lateral to septal anulus to illustrate the 3-dimensional shape of the anulus. ACOM, Anterior commissure; PCOM, posterior commissure.

      Mitral leaflet dynamics

      Figure thumbnail gr5
      Fig. 5Group mean data for angular displacement of the anterior mitral leaflet (top) and posterior mitral leaflet (bottom) throughout the cardiac cycle before (pre-IMR) and during acute IMR and progressive SLAC (SLAC-1, SLAC-2, and SLAC-3). Leaflet edge angular displacement was calculated with respect to the line between the midseptal and midlateral anulus. A 650-ms time window centered at end-diastole (t = 0) is shown.

      Discussion

      IMR remains a challenging entity for surgeons. The valve is morphologically and structurally normal, but myocardial injury and dysfunction inherent in the pathophysiology of IMR adversely influence postoperative outcome.
      • Dion R.
      Ischemic mitral regurgitation: when and how should it be corrected?.
      Ring annuloplasty can effectively correct IMR in many patients,
      • Cohn LH
      • Rizzo RJ
      • Adams DH
      • Couper GS
      • Sullivan TE
      • Collins JJ
      • et al.
      The effect of pathophysiology on the surgical treatment of ischemic mitral regurgitation: operative and late risks of repair versus replacement.
      • Czer LS
      • Maurer G
      • Trento A
      • DeRobertis M
      • Nessim S
      • Blanche C
      • et al.
      Comparative efficacy of ring and suture annuloplasty for ischemic mitral regurgitation.
      but complete or partial, flexible or rigid annuloplasty rings abolish normal annular
      • Glasson JR
      • Green GR
      • Nistal JF
      • Dagum P
      • Komeda M
      • Daughters GT
      • et al.
      Mitral annular size and shape in sheep with annuloplasty rings.
      and posterior leaflet dynamic motion.
      • Green GR
      • Dagum P
      • Glasson JR
      • Nistal JF
      • Daughters GT
      • Ingels Jr, NB
      • et al.
      Restricted posterior leaflet motion after mitral ring annuloplasty.
      In the current ovine experiment, SLAC with a simple transannular suture abolished acute IMR without markedly perturbing normal mitral annular dynamics and posterior leaflet motion.
      Previous ovine experiments have suggested that annular dilatation may be the chief mechanism of acute IMR,
      • Glasson JR
      • Komeda M
      • Daughters GT
      • Bolger AF
      • Karlsson MO
      • Foppiano LE
      • et al.
      Early systolic mitral leaflet “loitering” during acute ischemic mitral regurgitation.
      although other experimental studies have identified changes in subvalvular geometry as playing the primary role in the genesis of IMR.
      • Gorman 3rd, JH
      • Jackson BM
      • Gorman RC
      • Kelley ST
      • Gikakis N
      • Edmunds Jr, LH
      Papillary muscle discoordination rather than increased annular area facilitates mitral regurgitation after acute posterior myocardial infarction.
      • He S
      • Fontaine AA
      • Schwammenthal E
      • Yoganathan AP
      • Levine RA
      Integrated mechanism for functional mitral regurgitation: leaflet restriction versus coapting force: in vitro studies.
      • Otsuji Y
      • Nathan N
      • Handschumacher MD
      • Coulter S
      • Liel-Cohen N
      • D'Ambra M
      • et al.
      Mechanism of ischemic mitral regurgitation: intraoperative evaluation of leaflet tethering geometry by three-dimensional geometry [abstract].
      Ring annuloplasty prevents acute IMR in normal sheep by facilitating leaflet coaptation through reduction of the annular SL (anterior-posterior in clinical jargon) dimension
      • Timek T
      • Glasson JR
      • Dagum P
      • Green GR
      • Nistal JF
      • Komeda M
      • et al.
      Ring annuloplasty prevents delayed leaflet coaptation and mitral regurgitation during acute left ventricular ischemia.
      because this is the principal direction of annular enlargement during acute left circumflex artery ischemia.
      • Glasson JR
      • Komeda M
      • Daughters GT
      • Bolger AF
      • Karlsson MO
      • Foppiano LE
      • et al.
      Early systolic mitral leaflet “loitering” during acute ischemic mitral regurgitation.
      • Kay GL
      • Kay JH
      • Zubiate P
      • Yokoyama T
      • Mendez M.
      Mitral valve repair for mitral regurgitation secondary to coronary artery disease.
      • Gorman 3rd, JH
      • Gorman RC
      • Jackson BM
      • Hiramatsu Y
      • Gikakis N
      • Kelley ST
      • et al.
      Distortions of the mitral valve in acute ischemic mitral regurgitation.
      Annular enlargement caused by CC diameter increase, on the other hand, does not seem to lead to MR,
      • Green GR
      • Dagum P
      • Glasson JR
      • Daughters GT
      • Bolger AF
      • Foppiano LE
      • et al.
      Mitral annular dilatation and papillary muscle dislocation without mitral regurgitation in sheep.
      and in the current experiment a slight increase in CC diameter was actually observed with SLAC. Conversely, ring annuloplasty has also been shown to attenuate apical leaflet tethering in acute ovine IMR,
      • Lai DTM
      • Timek T
      • Green GR
      • Glasson JR
      • Daughters GT
      • Liang D
      • et al.
      The effects of ring annuloplasty on mitral leaflet geometry during acute left ventricular ischemia.
      suggesting an influence on the subvalvular apparatus. It is possible that SLAC abolished IMR by altering subvalvular geometry, although annular SL reduction leading to improved leaflet coaptation is more likely the predominant mechanism. Central MR during myocardial ischemia, as seen in the current study, is more likely to be associated with annular dilatation,
      • Izumi S
      • Miyatake K
      • Beppu S
      • Park YD
      • Nagata S
      • Kinoshita N
      • et al.
      Mechanism of mitral regurgitation in patients with myocardial infarction: a study using real-time two-dimensional Doppler flow imaging and echocardiography.
      and it is therefore not surprising that reduction of the annular SL dimension would correct this type of IMR. Clinically, surgical therapy designed to increase leaflet coaptation, such as implantation of an undersized ring annuloplasty, is usually effective in ameliorating MR in patients with advanced dilated cardiomyopathy, either idiopathic or ischemic.
      • Bolling SF
      • Pagani FD
      • Deeb GM
      • Bach DS
      Intermediate-term outcome of mitral reconstruction in cardiomyopathy.
      Furthermore, the extent of annular SL reduction may be a determinant of operative success in patients with IMR undergoing valve repair.
      • Czer LS
      • Maurer G
      • Trento A
      • DeRobertis M
      • Nessim S
      • Blanche C
      • et al.
      Comparative efficacy of ring and suture annuloplasty for ischemic mitral regurgitation.
      Any technique that reduces the size of the mitral anulus, however, also changes the 3-dimensional geometric relationships between the anulus and subvalvular apparatus because these structures are tightly coupled.
      • Dagum P
      • Timek T
      • Green GR
      • Lai D
      • Daughters GT
      • Liang D
      • et al.
      Coordinate-free analysis of mitral valve dynamics and ischemic hearts.
      Perhaps restoration of this perturbed relationship partially accounts for the efficacy of SLAC in this ovine model of acute IMR.
      SLAC effectively abolished IMR, but this novel technique only mildly altered normal mitral annular geometry and dynamic motion. The 6-mm annular SL reduction with SLAC-3 is comparable with the degree of annular reduction needed to prevent IMR with either a flexible or semirigid annuloplasty ring,
      • Timek T
      • Glasson JR
      • Dagum P
      • Green GR
      • Nistal JF
      • Komeda M
      • et al.
      Ring annuloplasty prevents delayed leaflet coaptation and mitral regurgitation during acute left ventricular ischemia.
      but SLAC-3 reduced end-diastolic annular area by only 14%, which is considerably less than the 30% to 35% annular area reduction associated with annuloplasty rings.
      • Glasson JR
      • Green GR
      • Nistal JF
      • Dagum P
      • Komeda M
      • Daughters GT
      • et al.
      Mitral annular size and shape in sheep with annuloplasty rings.
      Even though annular area was significantly smaller with SLAC, the magnitude of this decrease was modest; perhaps it is smaller total annular size reduction that permits continued dynamic motion of the anulus in SLAC. Annular flexibility serves a dual role by aiding LV filling in diastole and by facilitating leaflet coaptation in late diastole-early systole by virtue of its sphincteric action.
      • Tsakiris AG
      • Von Bernuth G
      • Rastelli GC
      • Bourgeois MJ
      • Titus JL
      • Wood EH
      Size and motion of the mitral valve annulus in anesthetized intact dogs.
      Therefore, preservation of annular flexibility may have physiologic advantages, yet ring annuloplasty generally minimizes dynamic area change.
      • Glasson JR
      • Green GR
      • Nistal JF
      • Dagum P
      • Komeda M
      • Daughters GT
      • et al.
      Mitral annular size and shape in sheep with annuloplasty rings.
      Although SLAC substantially decreased annular SL diameter and mitral area, the 3-dimensional saddle shape of the anulus remained intact, with elevation of the midseptal anulus (or saddle horn) above the annular plane. Recent finite-element analysis of annular shape suggests that this saddle-shaped configuration may have important implications for reducing systolic stress on the valve leaflets.
      • Salgo IS GJ
      • Gorman RC
      • Jackson BM
      • Bowen F
      • Plappert TT
      • St John Sutton MG
      • et al.
      Structural implication of mitral annular geometry and the saddle shape: a finite element analysis [abstract].
      Perturbed posterior leaflet motion has been observed after implantation of an annuloplasty ring in animal models
      • Green GR
      • Dagum P
      • Glasson JR
      • Nistal JF
      • Daughters GT
      • Ingels Jr, NB
      • et al.
      Restricted posterior leaflet motion after mitral ring annuloplasty.
      • van Rijk-Zwikker GL
      • Mast F
      • Schipperheyn JJ
      • Huysmans HA
      • Bruschke AV
      Comparison of rigid and flexible rings for annuloplasty of the porcine mitral valve.
      and is frequently observed clinically on postoperative echocardiography. Indeed, annuloplasty rings, whether flexible or semirigid, freeze the motion of the posterior leaflet, effectively converting the mitral valve into a single leaflet valve.
      • Green GR
      • Dagum P
      • Glasson JR
      • Nistal JF
      • Daughters GT
      • Ingels Jr, NB
      • et al.
      Restricted posterior leaflet motion after mitral ring annuloplasty.
      Although SLAC inhibited posterior leaflet excursion modestly, the posterior leaflet remained mobile. Whether maintained posterior leaflet motion offers an advantage in terms of effectiveness or durability of valve repair remains to be determined. This could possibly distribute systolic closing stresses more favorably in a bileaflet valve, but further studies are needed to answer this question.
      This experiment assessed a novel technique to reduce mitral annular SL dimension to enhance leaflet coaptation and correct IMR in an ovine model of acute ischemia. Progressive SLAC decreased MR because the SL diameter was cinched smaller, yet annular dynamics and posterior leaflet motion were only modestly affected. SLAC potentially represents an expedient and simple surgical method for the treatment of IMR, either alone or as an adjunctive technique.
      Although SLAC was effective in abolishing IMR in this experiment, this model of acute IMR is distinctly different than the clinical situation consisting of chronic MR and LV dilatation and systolic dysfunction, which makes clinical extrapolation difficult. The above findings can only be interpreted in the setting of acute LV ischemia in a normal sheep heart under open-chest conditions. These observations cannot be applied to patients with chronic IMR under closed-chest conditions in which subvalvular geometric perturbations may play a more predominant role in the pathogenesis of MR. We are currently exploring a protocol of chronic ovine IMR to validate the efficacy of SLAC in a more clinically relevant setting. Nonetheless, these preliminary findings can provide valuable surgical insight into the mechanisms and treatment of IMR and serve as a foundation for future studies. The myocardial marker method requires suturing small metal markers to intracardiac structures, but echocardiographic studies suggest that the markers do not interfere with mitral annular or leaflet motion because they are very small (aggregate mass = 20 ± 6 mg). Although there are many limitations inherent in this particular animal model, reliable models of cardiac pathophysiology have been established in ovine models.
      • Markovitz SE
      • Ratcliffe MB
      • Bavaria JE
      • Kreiner G
      • Iozzo RV
      • Hargrove WC
      • et al.
      Large animal model of left ventricular aneurysm.
      • Llaneras MR
      • Nance ML
      • Streicher JT
      • Lima JA
      • Savino JS
      • Bogen DK
      • et al.
      Large animal model of ischemic mitral regurgitation.

      Acknowledgements

      We appreciate the superb technical assistance provided by Mary K. Zasio, BA, Carol W. Mead, BA, and Maggie Brophy, AS.

      Discussion

      Dr Irving L. Kron (Charlottesville, Va). Dr Timek, the mechanism you have created obviously is an acutely ischemic model, and this is a very interesting approach. I know your laboratory knows more about IMR than probably anyone on earth. The typical patient, obviously, has some retraction of the posterior leaflets, some scarring, annular dilatation, and such. Would this technique or some adaptation of it work in those situations, do you think?
      Dr Timek. Thank you for that question. That is a very good point. This is an acute model in healthy, normal sheep, and therefore it does not reflect the clinical situation, where chronic changes and volume overload are present. However, this model gives us some insight into the mechanisms of IMR. We are currently working on a model of chronic ovine IMR, and we will try to investigate this method in that setting, which will be more clinically pertinent.

      References

        • Czer LS
        • Gray RJ
        • DeRobertis MA
        • Bateman TM
        • Stewart ME
        • Chaux A
        • et al.
        Mitral valve replacement: impact of coronary artery disease and determinants of prognosis after revascularization.
        Circulation. 1984; 70: I-198-I-207
        • Connolly MW
        • Gelbfish JS
        • Jacobowitz IJ
        • Rose DM
        • Mendelsohn A
        • Cappabianca PM
        • et al.
        Surgical results for mitral regurgitation from coronary artery disease.
        J Thorac Cardiovasc Surg. 1986; 91: 379-388
        • Replogle RL
        • Campbell CD
        Surgery for mitral regurgitation associated with ischemic heart disease: results and strategies.
        Circulation. 1989; 79: I-122-I-125
        • Dion R.
        Ischemic mitral regurgitation: when and how should it be corrected?.
        J Heart Valve Dis. 1993; 2: 536-543
        • Rankin JS
        • Feneley MP
        • Hickey MS
        • Muhlbaier LH
        • Wechsler AS
        • Floyd RD
        • et al.
        A clinical comparison of mitral valve repair versus valve replacement in ischemic mitral regurgitation.
        J Thorac Cardiovasc Surg. 1988; 95: 165-177
        • Hausmann H
        • Siniawski H
        • Hetzer R.
        Mitral valve reconstruction and replacement for ischemic mitral insufficiency: seven years' follow up.
        J Heart Valve Dis. 1999; 8: 536-542
        • Cohn LH
        • Rizzo RJ
        • Adams DH
        • Couper GS
        • Sullivan TE
        • Collins JJ
        • et al.
        The effect of pathophysiology on the surgical treatment of ischemic mitral regurgitation: operative and late risks of repair versus replacement.
        Eur J Cardiothorac Surg. 1995; 9: 568-574
        • Czer LS
        • Maurer G
        • Trento A
        • DeRobertis M
        • Nessim S
        • Blanche C
        • et al.
        Comparative efficacy of ring and suture annuloplasty for ischemic mitral regurgitation.
        Circulation. 1992; 86: II-46-II-52
        • Grossi EA
        • Lapietra A
        • Galloway AC
        • Ribakove GH
        • Culliford AT
        • Sposito RA
        • et al.
        Late results of isolated mitral annuloplasty for ischemic mitral insufficiency [abstract].
        Circulation. 2000; 102: II-491
        • Timek T
        • Glasson JR
        • Dagum P
        • Green GR
        • Nistal JF
        • Komeda M
        • et al.
        Ring annuloplasty prevents delayed leaflet coaptation and mitral regurgitation during acute left ventricular ischemia.
        J Thorac Cardiovasc Surg. 2000; 119: 774-783
        • Glasson JR
        • Green GR
        • Nistal JF
        • Dagum P
        • Komeda M
        • Daughters GT
        • et al.
        Mitral annular size and shape in sheep with annuloplasty rings.
        J Thorac Cardiovasc Surg. 1999; 117: 302-309
        • Green GR
        • Dagum P
        • Glasson JR
        • Nistal JF
        • Daughters GT
        • Ingels Jr, NB
        • et al.
        Restricted posterior leaflet motion after mitral ring annuloplasty.
        Ann Thorac Surg. 1999; 68: 2100-2106
        • van Rijk-Zwikker GL
        • Mast F
        • Schipperheyn JJ
        • Huysmans HA
        • Bruschke AV
        Comparison of rigid and flexible rings for annuloplasty of the porcine mitral valve.
        Circulation. 1990; 82: IV-58-IV-64
        • Glasson JR
        • Komeda M
        • Daughters GT
        • Foppiano LE
        • Bolger AF
        • Tye TL
        • et al.
        Most ovine mitral annular 3-D size reduction occurs before ventricular systole and is abolished with ventricular pacing.
        Circulation. 1997; 96: II-115-II-123
        • Niczyporuk MA
        • Miller DC
        Automatic tracking and digitization of multiple radiopaque myocardial markers.
        Comput Biomed Res. 1991; 24: 129-142
        • Daughters GT
        • Sanders WJ
        • Miller DC
        • Schwarzkopf A
        • Mead CW
        • Ingels NBJ
        A comparison of two analytical systems for 3-D reconstruction from biplane videoradiograms.
        IEEE Comput Cardiol. 1989; 15: 79-82
        • Moon MR
        • DeAnda A
        • Daughters GT
        • Ingels NBJ
        • Miller DC
        Experimental evaluation of different chordal preservation methods during mitral valve replacement.
        Ann Thorac Surg. 1994; 58: 931-944
        • Karlsson MO
        • Glasson JR
        • Bolger AF
        • Daughters GT
        • Komeda M
        • Foppiano LE
        • et al.
        Mitral valve opening in the ovine heart.
        Am J Physiol. 1998; 274: H552-H563
        • Glasson JR
        • Komeda M
        • Daughters GT
        • Bolger AF
        • Karlsson MO
        • Foppiano LE
        • et al.
        Early systolic mitral leaflet “loitering” during acute ischemic mitral regurgitation.
        J Thorac Cardiovasc Surg. 1998; 116: 193-205
        • Gorman 3rd, JH
        • Jackson BM
        • Gorman RC
        • Kelley ST
        • Gikakis N
        • Edmunds Jr, LH
        Papillary muscle discoordination rather than increased annular area facilitates mitral regurgitation after acute posterior myocardial infarction.
        Circulation. 1997; 96: II-124-II-127
        • He S
        • Fontaine AA
        • Schwammenthal E
        • Yoganathan AP
        • Levine RA
        Integrated mechanism for functional mitral regurgitation: leaflet restriction versus coapting force: in vitro studies.
        Circulation. 1997; 96: 1826-1834
        • Otsuji Y
        • Nathan N
        • Handschumacher MD
        • Coulter S
        • Liel-Cohen N
        • D'Ambra M
        • et al.
        Mechanism of ischemic mitral regurgitation: intraoperative evaluation of leaflet tethering geometry by three-dimensional geometry [abstract].
        Circulation. 1997; 96: I-156
        • Kay GL
        • Kay JH
        • Zubiate P
        • Yokoyama T
        • Mendez M.
        Mitral valve repair for mitral regurgitation secondary to coronary artery disease.
        Circulation. 1986; 74: I-88-I-98
        • Gorman 3rd, JH
        • Gorman RC
        • Jackson BM
        • Hiramatsu Y
        • Gikakis N
        • Kelley ST
        • et al.
        Distortions of the mitral valve in acute ischemic mitral regurgitation.
        Ann Thorac Surg. 1997; 64: 1026-1031
        • Green GR
        • Dagum P
        • Glasson JR
        • Daughters GT
        • Bolger AF
        • Foppiano LE
        • et al.
        Mitral annular dilatation and papillary muscle dislocation without mitral regurgitation in sheep.
        Circulation. 1999; 100: II-95-II-102
        • Lai DTM
        • Timek T
        • Green GR
        • Glasson JR
        • Daughters GT
        • Liang D
        • et al.
        The effects of ring annuloplasty on mitral leaflet geometry during acute left ventricular ischemia.
        J Thorac Cardiovasc Surg. 2000; 120: 966-975
        • Izumi S
        • Miyatake K
        • Beppu S
        • Park YD
        • Nagata S
        • Kinoshita N
        • et al.
        Mechanism of mitral regurgitation in patients with myocardial infarction: a study using real-time two-dimensional Doppler flow imaging and echocardiography.
        Circulation. 1987; 76: 777-785
        • Bolling SF
        • Pagani FD
        • Deeb GM
        • Bach DS
        Intermediate-term outcome of mitral reconstruction in cardiomyopathy.
        J Thorac Cardiovasc Surg. 1998; 115: 381-388
        • Dagum P
        • Timek T
        • Green GR
        • Lai D
        • Daughters GT
        • Liang D
        • et al.
        Coordinate-free analysis of mitral valve dynamics and ischemic hearts.
        Circulation. 2000; 102: III-62-III-69
        • Tsakiris AG
        • Von Bernuth G
        • Rastelli GC
        • Bourgeois MJ
        • Titus JL
        • Wood EH
        Size and motion of the mitral valve annulus in anesthetized intact dogs.
        J Appl Physiol. 1971; 30: 611-618
        • Salgo IS GJ
        • Gorman RC
        • Jackson BM
        • Bowen F
        • Plappert TT
        • St John Sutton MG
        • et al.
        Structural implication of mitral annular geometry and the saddle shape: a finite element analysis [abstract].
        Circulation. 2000; 102: II-631
        • Markovitz SE
        • Ratcliffe MB
        • Bavaria JE
        • Kreiner G
        • Iozzo RV
        • Hargrove WC
        • et al.
        Large animal model of left ventricular aneurysm.
        Ann Thorac Surg. 1989; 48: 838-845
        • Llaneras MR
        • Nance ML
        • Streicher JT
        • Lima JA
        • Savino JS
        • Bogen DK
        • et al.
        Large animal model of ischemic mitral regurgitation.
        Ann Thorac Surg. 1994; 57: 432-439