Ann Thorac Surg 2005;80:1706-1711
© 2005 The Society of Thoracic Surgeons
Original article: Cardiovascular
Intraoperative Effects of the Coapsys Annuloplasty System in a Randomized Evaluation (RESTOR-MV) of Functional Ischemic Mitral Regurgitation
Eugene A. Grossi, MD
a
,
*
,
Paul C. Saunders, MD
a
,
Y. Joseph Woo, MD
b
,
Deepak M. Gangahar, MD
c
,
John C. Laschinger, MD
d
,
David C. Kress, MD
e
,
Michael P. Caskey, MD
f
,
Charles F. Schwartz, MD
a
,
James Wudel, MD
g
a New York University Medical Center, New York, New York
b Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
c University of Nebraska Medical Center, Omaha, Nebraska
d St. Joseph's Medical Center, Towson, Maryland
e St. Luke's Medical Center, Milwaukee, Wisconsin
f St. Joseph's Hospital and Medical Center, Phoenix, Arizona
g Nebraska Heart Institute, Lincoln, Nebraska
Accepted for publication April 25, 2005.
* Address correspondence to Dr Grossi, NYU Medical Center, Suite 9-V, 530 First Ave, New York, NY 10028 (Email: grossi{at}cv.med.nyu.edu).
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Abstract
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BACKGROUND: Functional ischemic mitral regurgitation (MR) frequently arises after myocardial infarction; it is characterized by annular enlargement or lateral displacement of the subvalvular apparatus. Coapsys is a ventricular–annular remodeling device designed to treat functional ischemic MR; it does not require cardiopulmonary bypass. Initial intraoperative results of the RESTOR-MV randomized clinical trial are presented.
METHODS: Patients referred for coronary artery bypass grafting with preoperative MR grade of 2 or greater were studied, excluding those with structural valve abnormalities. The Coapsys device, which consists of two epicardial pads connected by a flexible cord, was surgically implanted in 19 patients. Under epicardial echocardiographic guidance, the cord was passed through the left ventricle and tightened externally to improve leaflet coaptation and stabilize the ventricular wall; tightening was conducted with color flow Doppler imaging.
RESULTS: Patients were 64.5 ± 9.2 years old with an ejection fraction of 0.383 ± 0.089 and received 2.7 ± 1.1 grafts. Intraoperative MR grade was 2.7 ± 0.8 after induction and was reduced to 0.4 ± 0.7 after implantation (p < 0.0001). Mean epicardial dimension was reduced from 8.5 ± 1.2 to 6.4 ± 0.9 cm (p < 0.0001). Intraoperative MR was reduced in 95% (18 of 19) of patients, and 84% (16 of 19) had MR grade 1 or less after implantation. All implants were performed without cardiopulmonary bypass or conversion to standard annuloplasty. No hemodynamic compromise or structural damage to the mitral apparatus was noted. Significant acute remodeling was noted in the left ventricular dimensions.
CONCLUSIONS: In patients without structural valve disease, the Coapsys device acutely reduces functional MR. Further randomized evaluation will assess long-term stability and compare it with standard annuloplasty techniques.
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Introduction
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Functional ischemic mitral regurgitation (FIMR) results from geometric changes in the mitral annulus and subvalvular apparatus secondary to ischemic myocardial injury. Typically, it involves dilatation of the posterior annulus [1] and displacement of the papillary muscles because of postinfarct ventricular remodeling [2]. Standard surgical therapy for FIMR is based on a corrective undersized annuloplasty [3, 4], which primarily corrects the annulus and improves leaflet coaptation with some effect on the ventricular geometry [5]. The results of this approach, in association with coronary revascularization, can be disappointing with respect to mortality and recurrent mitral regurgitation (MR) [6, 7].
The Coapsys device provides the opportunity for a novel off-pump treatment of FIMR, as it both corrects annular dilatation and restores ventricular geometry [8]. The Coapsys device is currently being evaluated as part of a U.S. Food and Drug Administration–regulated Investigational Device Exemption, randomized, pivotal study with efficacy and safety end points comparing it with standard mitral valve repair. This report documents the intraoperative experience of the initial phase of this study.
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Material and Methods
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The RESTOR-MV (Randomized Evaluation of a Surgical Treatment for Off-pump Repair of the Mitral Valve) multicenter Investigational Device Exemption primary study group randomizes patients with coronary artery disease and FIMR to either coronary artery bypass grafting plus traditional open mitral repair or coronary artery bypass grafting plus correction of the MR using the Coapsys device (Myocor, Maple Grove, MN). The initial intraoperative effect of the Coapsys device is the primary subject of this report. These 19 patients with coronary artery disease and FIMR were randomized to receive coronary artery bypass grafting and Coapsys device implantation. Patients with structural valve abnormalities were excluded from the study; full inclusion and exclusionary criteria are listed in the Appendix. All investigators had institutional review board approval, and all patients signed informed consents for the study.
The Coapsys device consists of two epicardial pads connected by a flexible suture cord between the papillary muscles that bisects the ventricle (Fig 1). Under epicardial echocardiographic guidance, the cord is passed through the left ventricle and then sequentially tightened to improve leaflet coaptation and stabilize the ventricular wall [9]. A suction cup–stabilized c-clamp with anterior and posterior locators is placed around the left ventricle (LV). The posterior locator is positioned externally between the papillary muscle insertions, about 2 cm below the insertion of the posterior leaflet. The anterior locator is placed on the right ventricle side of the left anterior descending coronary artery, halfway down the longitudinal axis of the ventricle. Verification of these locations is determined by handheld epicardial echocardiography (Fig 2). The jig guides a thin blunt-tipped needle through the LV from one locator to the other. The needle is followed by the Coapsys cord. The Coapsys device, with pads attached to either end, is initially placed with no tension. Sizing is then conducted under real-time color flow Doppler imaging to quantify MR. The suture length is shortened, and the final length is determined by elimination of MR or a maximum shortening of 35% (Fig 3). The procedure is performed without the use of cardiopulmonary bypass [10].
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Fig 2. (A) Verification of positioning, long-axis view of handheld epicardial echocardiography with cartoon of implantation jig. (B) Verification of positioning, short-axis view of handheld epicardial echocardiography with cartoon of implantation jig.
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Fig 3. (A) Transesophageal echocardiography after device implant before cordal tightening. (B) Transesophageal echocardiography after device implant after cordal tightening.
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For the purpose of this study, functional mitral valve regurgitation was defined as mitral valve dysfunction caused by dilatation of the mitral valve annulus, displacement of the LV papillary muscles, chordal tethering of the mitral valve leaflets, or any combination of these characteristics. Intraoperative transesophageal echocardiography was used to acquire the long-axis, two-chamber, and four-chamber views required to measure geometric changes as well as quantify MR (0 to 4 scale; Fig 4). Several measures were then recorded. The tenting area is a triangle whose base is the line connecting the hinge points of anterior and posterior leaflets and whose apex is the point of coaptation; this was measured by the area enclosed between the annular plane and mitral leaflets from the four-chamber, two-chamber, and long-axis views [11]. The sphericity index is the ratio of ventricular short-axis to long-axis dimensions. Endocardial axial dimensions of the chamber were measured in each view at the level of the papillary muscle heads. Four Coapsys patients did not have sufficient acquisition of all echocardiographic views to measure all distances; this is reflected in the data tables.
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Fig 4. Schematic drawing of the standard echocardiographic views. (AML = anterior mitral leaflet; Ao = aorta; PML = posterior mitral leaflet.)
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Intraoperative data are also reported from the concurrent control group. Standard reduction annuloplasty was accomplished with the following devices: Future Band (Medtronic, MN; sizes 28 [n = 1] and 26 [n = 4]), Edwards 4450 (Edwards Life Science, CA; sizes 28 [n = 1] and 26 [n = 1]), Carpentier-Edwards Classic (Edwards Life Science, CA; sizes 30 [n = 1]), and Duran (Medtronic, MN; 27 [n = 1]).
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Results
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Coapsys patient hospital mortality was 0.0% (0 of 19). The majority of patients (16 of 19) had bypass grafts completed before device implant. Patient demographics are recorded in Table 1. The majority of patients were male with a known history of myocardial infarction; patients with myocardial infarction within 30 days before the procedure were not eligible to serve as study candidates. Mitral regurgitation as measured by preoperative transthoracic echocardiogram was grade 3 or 4 in 63% of the patients (12 of 19). Mitral regurgitation was evaluated both before device placement and after sizing of the device. For Coapsys patients, intraoperative MR by means of transesophageal echocardiography was 2.7 ± 0.8 after induction and 2.3 ± 1.0 after coronary artery bypass grafting, decreasing to 0.4 ± 0.7 after Coapsys implantation (p < 0.0001). For traditional annuloplasty patients, intraoperative MR was 2.7 ± 0.8 after induction and 0.0 ± 0.0 after repair. There was one hospital death in the traditional annuloplasty group.
Geometric Effects of the Coapsys Device
The intraoperative annular changes are quantified in Table 2. The overall annular dimension decreased significantly in the long-axis and four-chamber views; insignificant reduction occurred in the two-chamber view. Likewise, the tenting area decreased significantly as calculated in both the long-axis and four-chamber views. The distances from the posterior and anterior annulus to the point of coaptation were reduced significantly almost universally in all views.
Table 3
provides the relative distances from the annular regions to the papillary muscles. After Coapsys device placement, the anterolateral papillary muscle was significantly closer to both the anterior and posterior annulus. The posteromedial papillary muscle was unchanged with respect to the anterior annulus. However, there was a borderline trend for it to move away from the posterior annulus. Ventricular effects are quantitated in Table 4. The regional sphericity indexes were significantly reduced at the papillary equator in long-axis and four-chamber views. Table 5
demonstrates the patients' hemodynamics during the procedure.
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Table 5. Intraoperative Pressures (mm Hg) During the Coapsys Implant Procedure in Patients Undergoing Coronary Artery Bypass Grafting First
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Comment
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The treatment of FIMR remains a clinical challenge [12] with mediocre mid-term and long-term results [13]. The traditional approach of placement of an undersized annuloplasty device [3, 4] addresses annular dilatation but does not deal with the disarray of the subvalvular apparatus. It has been speculated that papillary muscle dislocation associated with severe regional LV wall injury is the cause of FIMR repair failure [14]. The concept of the Coapsys device is intriguing because it not only treats the annular abnormality but also attempts to directly restore the subannular ventricular geometry. Recently, laboratory studies have confirmed the hypothesis that FIMR is the result of ventricular disease [2]. Of note, although the entry criteria into this study are functional mitral insufficiency and concomitant coronary artery disease requiring revascularization, there are patients included with no history of myocardial infarction or electrocardiographic evidence of prior myocardial infarction who had functional mitral insufficiency. These patients had more global ventricular dysfunction or dilatation without a distinct regional infarction, presumably on the basis of ischemic cardiomyopathy.
Preclinical work for the Coapsys device was done in animal models as well as explanted human hearts with functional MR [15, 16]. The most effective device position was in the long-axis plane of the LV. In this plane, the position of the posterior pad is in the center of the posterior wall external and equidistant from each papillary muscle. The suture cord evenly transverses the LV chamber to the anterior anchor pad. Thus, the device's line of force is normal to the plane of coaptation allowing for a symmetric decrease in anteroposterior dimension; this also prevents disruptive shearing from occurring along the coaptation area. Additionally, this position reduces the possibility of the cord interfering with the leaflets or chordae tendineae.
This report confirms the immediate efficacy of the Coapsys device for the treatment of FIMR. Additionally, the echocardiographic dimensions demonstrate significant ventricular dimensional reduction at both the annular and subvalvular levels. This is evidenced by reduction of the annular dimensions, improvement in leaflet coaptation, relocation of the papillary muscles closer to the anterior annulus, and a decrease in regional sphericity. Surprisingly, this dataset indicates that although the posterolateral papillary muscle moved toward the anterior annulus, there was a trend to move away from the posterior annulus. It may be speculated that this effect is caused by flattening of a posterolateral LV bulge, effectively shifting down the posterolateral papillary muscle. It is yet to be determined whether this will be of clinical significance.
Multiple newer methods being explored to correct FIMR include anterior leaflet augmentation [17], papillary muscle relocation [18], interventional "Alfieri" stitches, and various coronary sinus pessaries, as well as external LV support [19]. Recent data have demonstrated that eliminating FIMR alone is insufficient to prevent further ventricular remodeling and functional deterioration; as Guy and colleagues [2] concluded in a recent report "ischemic mitral regurgitation is a consequence, not a cause, of postinfarction remodeling." The potential advantage of the Coapsys approach above all of these with the exception of the external pillow is that the Coapsys device provides direct ventricular remodeling.
Limitations
This is a substudy of an ongoing clinical trial comparing standard annuloplasty techniques and the Coapsys device. It is anticipated that the full clinical trial will require at least 150 patients before statistical power can be achieved to make determinations regarding the comparison of the device's safety and efficacy.
Conclusions
In patients with FIMR, the Coapsys device acutely reduces MR and positively remodels the LV. Further randomized evaluation will assess long-term stability and compare it with standard annuloplasty techniques.
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Appendix
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RESTOR-MV Inclusion and Exclusion Criteria and Randomization Details
Inclusion Criteria
- 1 Grade 2, 3, or 4 functional mitral valve regurgitation per two-dimensional echocardiography
- 2 Patient undergoing concomitant coronary artery bypass graft surgery, either on-pump or off-pump (CABG or OP-CAB)
- 3 Left ventricular ejection fraction > 0.25 per two-dimensional echocardiography
- 4 Age between 18 and 80 years, inclusive
- 5 Patient is willing and available to return for study follow-up
- 6 Ability of the patient or legal representative to understand and provide signed consent for participating in the study
Exclusion Criteria
- 1 Structural abnormality of the mitral valve (eg, calcification or thickening of valve leaflets, ruptured papillary muscle, ruptured chordae tendineae, mitral valve prolapse, mitral stenosis)
- 2 Organic valve disease resulting in insufficiency or stenosis of the aortic, pulmonary, or tricuspid valve requiring surgical intervention
- 3 Myocardial infarction within 30-day period before surgical placement of Coapsys
- 4 New York Heart Association class IV
- 5 Left ventricular end diastolic diameter > 7.0 cm
- 6 Cardiac surgery on an emergency or salvage basis
- 7 Left atrial or left ventricular thrombus
- 8 Left ventricular aneurysm
- 9 Previous mitral valve surgery or other previous cardiac surgery that would preclude proper placement of the Coapsys
- 10 Chronic renal failure requiring dialysis
- 11 Open chest surgery contraindication (eg, acute respiratory distress, endocarditis, myocarditis, pericarditis)
- 12 Active infection
- 13 Life expectancy of less than 12 months
- 14 Participation in another investigational drug or device protocol
Randomization
1. Patient randomization must be performed before the start of cardiopulmonary bypass or off-pump coronary artery bypass grafting. Randomization is done by means of sealed envelope; the majority of patients were randomized after sternotomy and pericardiotomy.
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Abstract
Introduction
