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Ann Thorac Surg 1999;68:2100-2106
© 1999 The Society of Thoracic Surgeons

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Original Articles: Cardiovascular

Restricted posterior leaflet motion after mitral ring annuloplasty

^a Department of Cardiovascular and Thoracic Surgery, Stanford University School of Medicine, Stanford, California, USA
^b University of Santander, Santander, Spain
^c Department of Cardiovascular Physiology and Biophysics, Research Institute of the Palo Alto Medical Foundation, Palo Alto, California, USA

Address reprint requests to Dr Miller, Department of Cardiovascular and Thoracic Surgery, Falk Cardiovascular Research Center, Stanford University School of Medicine, Stanford, CA 94305-5247
e-mail: dcm{at}leland.stanford.edu

Presented at the Poster Session of the Thirty-fifth Annual Meeting of The Society of Thoracic Surgeons, San Antonio, TX, Jan, 25–27, 1999.

	Abstract

Top Abstract Introduction Material and methods Results Comment References

 
Background. The effects of ring annuloplasty on mitral leaflet motion are incompletely known. The three-dimensional dynamics of the mitral valve in vivo were examined to determine how two types of annuloplasty rings affect leaflet motion during valve closure.

Methods. Miniature radiopaque markers on the mitral leaflets, annulus, and left ventricle were implanted in three groups of sheep. One group served as control (n = 7); other sheep were randomly assigned to receive either a flexible Duran (n = 6) or a semirigid Carpentier-Edwards Physio ring (n = 6). After recovery, three-dimensional marker coordinates were computed from simultaneous (60 Hz) biplane videofluoroscopic marker images.

Results. Both types of rings immobilized the middle scallop of the posterior leaflet without affecting anterior leaflet motion. The excursion of the anterior leaflet edge from maximally open to fully closed was not different between the groups (control, 13 ± 2 mm; Duran 13 ± 1 mm; Physio ring, 14 ± 1 mm; p > 0.05), but posterior leaflet edge excursion was restricted (control, 7.4 ± 0.4 mm; 2.3 ± 0.3 mm [p < 0.001]; Physio, 2.7 ± 0.2 mm [p < 0.001]) by both rings.

Conclusions. Mitral annuloplasty with either ring type markedly reduced the mobility of the central posterior leaflet in normal ovine hearts such that valve closure became essentially a single (anterior) leaflet process with the frozen posterior leaflet serving only as a buttress for closing.

	Introduction

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Mitral valve repair has become the preferred procedure to correct mitral regurgitation because it has several advantages over valve replacement [1]. Introduced by Carpentier and Duran, ring annuloplasty is now considered by most surgeons to be an integral component of mitral repair if annular dilatation is present [2, 3]. The wide variety of prosthetic annuloplasty devices available, however, underscores the lack of consensus regarding the essential elements of what the annuloplasty device should provide. Proponents of each type of ring cite theoretical and practical considerations to support superiority of their prosthesis in bringing about alterations of the mitral complex that are considered indispensable for a durable repair. Systolic anterior motion of the anterior leaflet, diastolic gradients, and the impact on postoperative left ventricular (LV) systolic function are some issues in this ongoing debate [4–6]. Consensus does exist, however, that reducing mitral annular area, ie, increasing the ratio of leaflet area to annular area, is important. Decreasing mitral annular area without perturbing the function of the other components of the mitral complex (eg, the anterior and posterior leaflets, subvalvular apparatus) is difficult to achieve because of the inherent tight coupling of all elements of the mitral ventricular-valvular complex. In particular, the effect of mitral annuloplasty on leaflet dynamics heretofore has been limited to reports of systolic anterior motion of the anterior leaflet and a single report of altered excursion of the posterior mitral leaflet in animal hearts [4, 7], although reduced posterior leaflet motion is observed echocardiographically after almost every ring annuloplasty.

We examined how two popular types of prosthetic annuloplasty rings affect leaflet motion during mitral valve closure. We found that ring annuloplasty markedly restricted posterior leaflet motion and transformed the mitral valve into a single (anterior) leaflet mechanism.

	Material and methods

Top Abstract Introduction Material and methods Results Comment References

 
Nineteen adult castrated male sheep (67 ± 8 kg [mean ± 1 standard deviation]) were assigned to three groups. The control group had only placement of myocardial markers (n = 7). The remaining animals had placement of myocardial markers and were randomly assigned to undergo mitral ring annuloplasty with either a semirigid Carpentier-Edwards Physio ring (n = 6) or a flexible Duran ring (n = 6). Subsequent treatment and postoperative data collection were identical in all groups. The details of the experimental design have been previously published and are herein only briefly described [8].

Surgical preparation
Animals were intubated and placed on mechanical ventilation; general anesthesia was maintained with inhalational isoflurane (1% to 2.2%). A left thoracotomy was performed and pneumatic occluders (In Vivo Metric Systems, Healdsburg, CA) were placed around the superior and inferior vena cavae for subsequent abrupt preload reduction during data acquisition. Nine miniature radiopaque tantalum markers (inside diameter (ID) = 0.8 mm, outside diameter (OD) 1.3 mm, length 1.5 to 3.0 mm) were inserted into the LV epicardium and septum as previously described [9]. Epicardial echocardiography with color Doppler flow mapping was used to assess initial mitral competence and anatomy of the valve. Figure 1A shows the myocardial marker array analyzed in this experiment.

View larger version (22K): [in this window] [in a new window]   Fig 1. (A) The myocardial, annular and leaflet marker array used in this experiment. (B) Expanded view of the annular, anterior, and posterior leaflet markers shows that leaflet markers (open black circles) were placed down a line from the mid-anterior annulus (or saddlehorn) marker (located midway between the right [RFT] and left [LFT] fibrous trigone markers) to the mid-posterior annulus marker. (AML = anterior mitral leaflet; PML = posterior mitral leaflet.)

Experimental protocol
After an 8 ± 1 day (mean ± 1 SD) recovery period, data were collected in the experimental animal cardiac catheterization laboratory. The animals were premedicated, intubated, and mechanically ventilated (veterinary anesthesia ventilator 2000; Hallowell EMC, Pittsfield, MA). A calibrated, micromanometer-tipped catheter (Millar MPC-500, Millar Instruments, Houston, TX) was advanced into the descending thoracic aorta to measure aortic pressure. Heart rate was slowed by administration of UL-FS49, a highly specific negative chronotropic agent that does not alter inotropic state or blood pressure (Boehringer-Ingelheim, Ridgefield, CT), esmolol (20 to 40 µg/per minute by intravenous infusion), and atropine (to abolish sympathetic response) to a target heart rate of 110 beats per minute to facilitate videofluoroscopic visualization and tracking of the miniature radiopaque myocardial markers. Transthoracic echocardiography with color Doppler imaging was done to ensure proper seating of the annuloplasty ring and competence of the valve.

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 Care and Use of Laboratory Animals" prepared by the National Academy of Sciences and published by the National Institutes of Health (DHEW[NIH] publication 85-23, revised 1985). This study was approved by the Stanford Medical Center Laboratory Research Animal Review Committee and conducted according to Stanford University policy.

Data acquisition and reduction
A Philips Optimus 2000 biplane Lateral ARC 2/poly DIAGNOST C2 system (Philips Medical Systems, North America Company, Pleasanton, CA) was used to collect simultaneous biplane videofluoroscopic data at 60 Hz. Data were acquired under steady-state conditions and over a range of LV filling volumes during preload reduction. All animals were studied in normal sinus rhythm with ventilation arrested at end expiration. Two-dimensional images from each of the two x-ray views were digitized and merged to yield three-dimensional coordinates for each radiopaque marker each 16.7 milliseconds by custom-designed software, as previously reported [10]. Hemodynamic parameters and electrocardiographic voltage were digitized simultaneously and recorded in real time during data acquisition.

Data analysis
All physiologic data were time aligned at end diastole (ED), which was defined as the videofluoroscopic frame preceding maximum positive dP/dt (dP/dt_max). The mean and standard error of the mean were then calculated for each variable at each of ten time samples before and after end diastole. These 21 time samples span a 333-millisecond interval centered on the expected time of valve closure. The time of end systole (ES) was defined as two frames preceding maximum negative LV dP/dt and was used to compare hemodynamic parameters between groups of animals.

Instantaneous LV volume was measured every 16.7 milliseconds from the mitral annular and epicardial LV markers using a space-filling multiple tetrahedral volume algorithm [9]. Stroke volume was calculated as (EDV - ESV), where end-diastolic volume (EDV) and end-systolic volume (ESV) are LV volumes at ED and ES, respectively. Left ventricular ejection fraction was calculated as [(EDV - ESV)/EDV]. Preload recruitable stroke work was computed as a load-insensitive estimate of LV contractile state [11].

Mitral leaflet kinematics were analyzed using an internal Cartesian reference system (Fig 2), where individual marker coordinates were rotated and translated from the laboratory reference system into an internal reference frame at each time sample [12]. The x-axis is defined as the line between the mid-anterior annulus marker and the mid-posterior annulus marker (also termed the septal-lateral mitral dimension); the midpoint of this line represents the origin of the coordinate system. The y-axis (left ventricular long axis) is defined from the origin to the LV apex marker, and the z-axis is directed from the origin through the anterolateral commissure marker. The distance in three dimensions between any two markers (eg, a and b) was calculated as

An estimate of the coaptation point of the anterior and posterior leaflet edges was made by calculating the three-dimensional coordinates of both leaflet edge markers with the valve closed. The closed position of the leaflet edges was defined as the videofluoroscopic frame in which the distance between the leaflet edge markers decreased by less than 10% of the previous mean value. An average of the three coordinates (x, y, and z) of both leaflet edge markers was then taken as the point of coaptation.

View larger version (13K): [in this window] [in a new window]   Fig 2. Schematic of the mitral annulus and anterior and posterior leaflets, showing the internal Cartesian coordinate system used in the experiment. See text for anatomic details. (AML = anterior mitral leaflet; PML = posterior mitral leaflet.)

	Results

Top Abstract Introduction Material and methods Results Comment References

 
There were no significant differences in the weight of the animals (control, 62 ± 9 kg; Duran, 70 ± 8 kg; Physio, 69 ± 8 kg; p > 0.05). The duration of cardiopulmonary bypass and aortic cross-clamp times, respectively, were longer in animals that had ring annuloplasty (Duran, 134 ± 14 and 94 ± 11 minutes; Physio, 138 ± 15 and 95 ± 10 minutes; p > 0.05) compared with the control group (control, 103 ± 11 and 56 ± 7 minutes; p < 0.05). Transthoracic color Doppler echocardiography at the time of data acquisition revealed no changes in mitral valve competence compared with the postcardiopulmonary bypass study done at the time of operation (controls, 7 none; Duran, 5 none, 1 trace; Physio, 5 none, 1 mild); proper seating of the annuloplasty ring in the Duran and Physio groups was confirmed in all animals.

Hemodynamic data are summarized in Table 1. There were no significant differences in heart rate, LV end-diastolic pressure, end-diastolic volume, end-systolic pressure, end-systolic volume, or stroke volume. Left ventricular preload recruitable stroke work in the Duran group was significantly lower compared with controls (p = 0.04), but there was no difference between the Duran and Physio groups.

Figure 3 illustrates the coordinates of the four anterior leaflet markers and the two posterior leaflet markers relative to the mitral annulus in two dimensions. The positions of these markers are shown in the x-y plane at several time points in all three groups. The three plots are aligned along the mid-anterior annulus marker; as expected, the x-axis annular (septal-lateral) dimension was smaller in the Duran and Physio ring groups. In the control group, all markers along both the anterior and posterior leaflets assumed a widely open position during valve opening. When the valve was closed, the anterior and posterior leaflet markers shifted upward toward the atrium. In the Duran and Physio groups, anterior leaflet marker motion and position between the open and closed conditions were similar in magnitude to those of controls. The posterior leaflet markers, however, did not move in the Duran and Physio groups. The middle scallop of the posterior leaflet appeared immobile, as if the ring annuloplasty had frozen it in the open position.

View larger version (23K): [in this window] [in a new window]   Fig 3. The locations (mean ± standard error of the mean) of the four anterior leaflet and the two posterior (middle scallop) leaflet markers are plotted in the x-y plane in the maximally open and closed positions and at five intervening time points studied in the control group (A), Physio group (B), and Duran group (C). The positions of the mid-anterior and mid-posterior annulus markers are also shown for reference (located at each end of the double-ended arrow).

View larger version (28K): [in this window] [in a new window]   Fig 4. The distance (mean ± standard error of the mean) in three dimensions between the anterior and posterior leaflet edge markers (closed circles) during the 333-millisecond interval studied is shown for the control group (A), the Physio group (B), and the Duran group (C). Left ventricular pressure (open squares; mean ± standard error of the mean) is also shown for each group.

	Comment

Top Abstract Introduction Material and methods Results Comment References

The principal finding in this experiment was that both flexible and semirigid mitral annuloplasty rings produced a frozen posterior mitral leaflet in normal sheep hearts. Only one other group has reported altered mitral leaflet motion after ring annuloplasty [7]. Van Rijk-Zwikker and colleagues [7] imaged leaflet opening using videoendoscopy in an ex vivo porcine heart preparation. The two mitral leaflets opened and closed simultaneously and symmetrically in three control animals. In one group with a Carpentier-Edwards annuloplasty ring, mobility of the posterior annulus was reduced, as was excursion of the posterior leaflet. A similar observation of posterior leaflet immobilization with reduced mobility of the posterior annulus occurred in two of six hearts with a flexible Duran ring. The authors concluded that rigid annular fixation resulted in the mitral valve opening as a single leaflet valve (these observations were made only during valve opening). The data from our experiment were obtained during the time of valve closure but revealed similar findings. Ring annuloplasty was associated with markedly impaired motion of the posterior mitral leaflet and transformed valve closure into a single, anterior leaflet process. We observed no difference in flexibility of the posterior annulus (both were immobile) between the Duran and Physio groups compared with controls, whereas van Rijk-Zwikker and colleagues concluded that preserving posterior annular flexibility (Duran ring) was associated with normal posterior mitral leaflet motion [17]. These differences might be related to the time period during which the data were acquired or to the major technical differences between the experimental preparations; eg, van Rijk-Zwikker and associates [7] recorded data in explanted porcine hearts ex vivo 4 to 6 weeks postoperatively compared with our in vivo three dimensional data collection in sedated sheep 7 to 10 days postoperatively. Mitral annular flexibility might change after annuloplasty as the ring becomes incorporated into the annular tissue, and leaflet motion might also change; serial longitudinal experiments are needed to address these questions.

In the clinical setting, Kreindel and colleagues [4] were the first to describe a potential effect of annuloplasty on leaflet motion. In their study, 5 of 45 patients who had mitral ring annuloplasty with a Carpentier "classic" ring had systolic anterior motion of the anterior mitral leaflet. The rigid, complete ring was thought to diminish the size of the left ventricular outflow tract, which was then further obstructed by redundant mitral valve tissue during early systole. Some years later, Carpentier and colleagues [6] analyzed the mechanism of postannuloplasty systolic anterior motion and identified the following two predisposing factors: excessively high posterior leaflet height and placement of too small a ring (compared with the size of the anterior leaflet). Of the 137 patients they studied, 67 had quadralateral resection and 36 had quadrangular resection plus posterior leaflet sliding-plasty. Although no postoperative imaging of leaflet motion was reported, one must question whether posterior leaflet function was altered by annuloplasty similar to that observed in our sheep experiment. Did the leaflets of the newly competent valve close symmetrically over a smaller reshaped orifice or were the mechanics of leaflet closure altered?

Human experience and the intriguing endoscopic qualitative visual study by van Rijk-Zwikker and associates have resulted in clinical acceptance of posterior leaflet immobilization after mitral ring annuloplasty [18, 19]. Conventional wisdom is that the ring stabilizes the posterior annulus and reinforces the posterior leaflet, creating a buttress against which the anterior leaflet closes. Although our study did not identify a direct mechanism that explains this phenomenon, it demonstrated that it occurs universally (at least in normal sheep hearts) and is identical with either a semirigid or flexible complete annuloplasty ring. Perhaps this immobilization of the posterior leaflet simply results from the smaller mitral annulus produced by the ring pulling the posterior annulus toward the center of the valve orifice, which is therefore farther away from the papillary muscle tips. This dislocation could tether the posterior leaflet in its open position, because the overall length of the leaflet and its chordae tendineae have a fixed dimension.

One must ask whether changing such a multifaceted system as the mitral ventricular-valvular complex from a bileaflet valve to essentially a unileaflet valve after ring annuloplasty has any potential untoward effects. By altering the motion of the posterior leaflet, it is conceivable that the distribution of stresses on both leaflets during systole is perturbed. Although mitral valve repair with ring annuloplasty is a safe and reliable procedure, more comprehensive knowledge of the consequences of this procedure on the mechanics of the leaflets and the subvalvular apparatus can only improve the surgeon’s ability to utilize ring annuloplasty most appropriately and effectively [20].

This experiment used normal adult sheep hearts; differences between human and ovine cardiac anatomy have been described, and therefore these results might not be directly applicable to human subjects [8]. Also, data were collected 7 to 10 days after ring implantation; behavior of the leaflets could differ months and years later. The animals were not randomly assigned to three groups; only the animals that had Physio and Duran implants were randomized. Although ring sizing was done according to usual clinical criteria, making a normal mitral annular orifice smaller is different from reducing the size of a markedly dilated mitral annulus resulting from long-standing mitral regurgitation. Finally, at the time of data acquisition, 2 animals were each missing one leaflet marker.

	Acknowledgments

 
We appreciate the assistance provided by Linda E. Foppiano, MD, Ann F. Bolger, MD, Mary K. Zasio, Carol W. Mead, and Erin M. Schultz. This work was supported in part by grants HL-29589, HL-48837 and HL-09569 from the National Heart, Lung, and Blood Institute.

	References

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