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Original Articles: Adult Cardiac

Outcomes After Repair of the Anterior Mitral Leaflet for Degenerative Disease

^a Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic, Cleveland, Ohio
^b Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio

Accepted for publication May 15, 2008.

^_* Address correspondence to Dr Gillinov, Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic, 9500 Euclid Ave/Desk F24, Cleveland, OH 44195 (Email: gillinom{at}ccf.org).

Presented at the Forty-fourth Annual Meeting of The Society of Thoracic Surgeons, Fort Lauderdale, FL, Jan 28–30, 2008.

ADult cardiac surgery: The Annals of Thoracic Surgery CME Program is located online at http://cme.ctsnetjournals.org. To take the CME activity related to this article, you must have either an STS member or an individual non-member subscription to the journal.

 

	Abstract

Top Abstract Introduction Patients and Methods Results Comment Appendix 1 Appendix 2 Discussion Acknowledgments References

 
Background: Repair of anterior mitral disease is challenging. Objectives of this study were to (1) compare patients with anterior versus posterior disease, (2) identify factors predisposing to replacement rather than repair in anterior disease, (3) determine durability of, and survival after, repair, and (4) compare outcomes with those after posterior repair.

Methods: From January 1985 to January 2006, 3,544 patients underwent primary isolated mitral valve surgery for degenerative disease, including 307 isolated anterior (252 repairs, 82%) and 2,754 isolated posterior (2,650 repairs, 96%) leaflet procedures. Logistic regression analysis was used to identify predictors of valve replacement and to generate propensity scores for risk-adjusted comparisons. Durability was assessed by reoperation and return of mitral regurgitation.

Results: Patients with anterior disease were older and more symptomatic, with more chordal elongation and greater changes in cardiac morphology and function; advanced age was associated with replacement (p < 0.0001). Unadjusted freedom from reoperation was 89% at 10 years, worse than after posterior repair (p < 0.0001). Return of 3+ to 4+ mitral regurgitation was more common in those with anterior than posterior repair (11% versus 4% at 1 year; p = 0.03). Unadjusted survival was 83% versus 88% 10 years after posterior repair, but propensity-adjusted survival was similar (p 0.5).

Conclusions: Patients with anterior disease have more symptoms and greater changes in cardiac structure and function than do patients with posterior disease. Anterior repair is less durable than posterior, but is associated with comparable, excellent long-term survival. More durable repair techniques, applicable to the broader spectrum of anterior disease, are needed.

Dr Gillinov discloses that he has a financial relationship with Edwards Lifesciences, Medtronic, and St. Jude Medical; Dr Salemi with Edwards Lifesciences and Medtronic.

 

Degenerative mitral valve disease includes a spectrum of pathologic and pathophysiologic findings [1, 2]. The pathophysiologic classification of degenerative mitral valve disease focuses on site of prolapse, with posterior leaflet prolapse predominating in most series [3–6]. Although management of posterior leaflet prolapse is standardized, reproducible, and associated with excellent long-term durability, techniques for repairing anterior disease vary widely and generally produce durability inferior to that obtained with posterior repair [3, 5, 7–9]. Recognizing these limitations, surgeons have developed a variety of new approaches to anterior repair, including novel techniques for creating artificial chordae, edge-to-edge repair, and others. Ideally, the decision to apply these techniques for a given pathologic circumstance depends on understanding factors predisposing patients to repair failure. It is possible that the site of prolapse is one of many differences between patients with anterior and posterior disease and that other factors might contribute to the observed limited durability of anterior repair. Objectives of this study were to (1) compare clinical presentations of patients with anterior and posterior disease, (2) identify factors predisposing to replacement rather than repair for anterior disease, (3) determine durability of, and survival after, repair of anterior disease, and (4) compare outcomes with those after posterior repair.

	Patients and Methods

Top Abstract Introduction Patients and Methods Results Comment Appendix 1 Appendix 2 Discussion Acknowledgments References

 
Study Population
From January 1985 to January 2006, 3,544 patients with isolated degenerative mitral valve disease underwent surgery at Cleveland Clinic for mitral regurgitation (MR) as the primary indication. Patients having previous or concomitant operations for coronary artery disease, aortic valve disease, hypertrophic cardiomyopathy, or ascending aortic aneurysm were excluded. Results in an early subset of these patients were reported previously [4]. Of the 3,544 patients, 307 (9%) had isolated anterior leaflet disease and 2,754 (78%), isolated posterior leaflet disease; 483 (13%) had bileaflet disease. The site of prolapse was determined by examination of operative notes and echocardiographic reports. Patients were not routinely classified as having "Barlow disease" or "fibroelastic deficiency."

Preoperative MR grade was assessed semiquantitatively by echocardiography using standard techniques; all patients had moderately severe (3+, 9.4%) or severe (4+, 91%) MR. Two hundred fifty-two (82%) patients with anterior prolapse had repair, and 55 (18%) had replacement; 10 patients had initial repair attempt followed by replacement in the same operative session. In contrast, repair was achieved in 96% of patients with isolated posterior disease (p < 0.0001).

Data were extracted from Cleveland Clinic's Cardiovascular Information Registry, a repository of clinical and surgical data manually abstracted concurrently with patient care. Echocardiographic data were extracted from Cleveland Clinic's Echocardiography Database. Use of these data for research was approved by the institutional review board, with patient consent waived.

Anterior Leaflet Repair: Surgical Techniques
Surgical approach was minimally invasive in 94 patients (37%) [10] and full sternotomy in 158 (63%); since 2000, minimally invasive approaches have been used in 51% of those with anterior disease, compared with 72% of those with posterior disease (p < 0.0001). The most common anterior repair technique was chordal transfer, used in 178 patients (71%; Table 1). In recent years, creating artificial chordae has become more common (Fig 1). Repair was supplemented by annuloplasty in 95%. Annuloplasty techniques included a prosthetic annuloplasty (Cosgrove-Edwards Annuloplasty System in 174 [69%], Carpentier-Edwards classic ring in 33 [13%]), or posterior annular suture plication reinforced with bovine pericardium in 33 (13%).

View larger version (8K): [in this window] [in a new window]   Fig 1. Temporal trend in techniques for repair of anterior disease: chordal transfer (triangles) versus creation of artificial chordae (filled circles). Each symbol is a yearly percentage of repairs using that technique. Solid curves are trend lines.

Postoperative mitral regurgitation
A subgroup of 193 patients having anterior repair was followed for residual or recurrent MR by postoperative echocardiography at Cleveland Clinic, yielding 447 echocardiograms for analysis of MR grade; 56 patients (29%) had echocardiograms obtained more than 1 year after surgery. Because only 8% of echocardiograms were obtained past 10 years, depictions of their analysis are truncated at that time point.

Data Analysis
Comparisons between anterior and posterior disease
Preoperative clinical variables were compared between the anterior and posterior disease groups. Univariable comparisons were made using Wilcoxon rank-sum and ² tests (Fisher's exact test when appropriate). Among patients undergoing repair, multivariable logistic regression analysis was performed to identify factors associated with anterior versus posterior repair. The parsimonious logistic model was then augmented with factors from classes of variables that were not represented to form a propensity model. From this final model, a propensity score was estimated for each patient and used for matching or as a balancing score for adjustment in multivariable models.

Factors associated with replacement versus repair in anterior disease
Multivariable logistic regression was performed to identify factors associated with mitral valve replacement. Variables considered (preoperative) are listed in Appendix 1. A directed stepwise approach was used with criteria of probability value less than or equal to 0.05 for retention of variables to form an initial parsimonious model. Bootstrap bagging was used to investigate the validity of these predictors with automated analysis of 500 resampled data sets, followed by tabulating the frequency of occurrence at probability value less than or equal to 0.05 of both single factors and clusters of closely related factors. Factors found in 50% or more of the bootstrapped models were considered reliable.

Prevalence of each MR grade across follow-up time was estimated by longitudinal ordinal logistic regression for repeated measurements (PROC GENMOD; SAS, Inc, Cary, NC). Because the frequency of occurrence of severe MR (4+) was low, grades 3+ and 4+ were combined for analysis. Results are accompanied by crude independent estimates of prevalence of each grade within sequential time frames for informal comparison. Because MR returned rapidly within the first 2 weeks and far more slowly thereafter, separate analyses for risk factors were made for echocardiograms obtained within 2 weeks of operation and those obtained thereafter. To compensate for the limited capability of PROC GENMOD to explore multivariable relations, we screened variables using ordinary ordinal logistic regression (PROC LOGISTIC; SAS, Inc) with a liberal criterion (p < 0.1) assuming independence of observations. This analysis yielded candidates for the repeated-measurements multivariable model. These and their transformations, if any, were entered at once into the model, then eliminated individually until all variables remaining had a probability value less than or equal to 0.05.

Survival
Nonparametric survival estimates after repair were obtained by the Kaplan–Meier method. A parametric method was used to resolve the number of phases of instantaneous risk (hazard function) and to estimate shaping parameters (see http://www.clevelandclinic.org/heartcenter/hazard) [13]; multivariable analyses were performed simultaneously for each hazard phase. Variable selection used bagging [14, 15] and 200 bootstrap resampled data sets as described in the previous text. Survival after anterior repair was compared with that after posterior repair between 1:1 propensity-matched groups.

Presentation
Categorical data are summarized by frequencies and percentages and continuous variables by means and standard deviations. Uncertainty is expressed consistently as ±1 standard deviation, ±1 standard error, or equivalent 68% asymmetric confidence limits. The hazard function is presented as rate per 100 patients (%/year).

	Results

Top Abstract Introduction Patients and Methods Results Comment Appendix 1 Appendix 2 Discussion Acknowledgments References

 
Anterior Versus Posterior Disease
Compared with patients with posterior disease, those with anterior disease were more likely to be older and female and to have more symptoms and comorbid conditions (Table 2). Their mitral valve disease was more frequently characterized by chordal elongation versus chordal rupture. They had more pronounced changes in cardiac structure and function, with greater left atrial enlargement, more atrial fibrillation, and reduced left ventricular function.

View larger version (5K): [in this window] [in a new window]   Fig 2. Temporal trend in probability of valve repair versus replacement in patients with anterior disease. Each symbol is a yearly percentage of repairs. Solid curve is a trend line.

View larger version (5K): [in this window] [in a new window]   Fig 3. Probability of valve repair versus replacement according to age in patients with anterior disease. Each symbol is a yearly percentage of repairs. Solid curve is a trend line.

View larger version (9K): [in this window] [in a new window]   Fig 4. Unadjusted freedom from mitral valve reoperation after repair of anterior () versus posterior disease (). Each symbol represents a reoperation, vertical bars are 68% confidence limits, and numbers in parentheses indicate patients remaining at risk. Solid lines enclosed within dashed 68% confidence limits are parametric estimates.

Residual and recurrent mitral regurgitation
All patients undergoing anterior mitral repair left the operating room with an MR grade of 1+ or less on epicardial or transesophageal echocardiogram. In the first 2 weeks after repair, the percentage with an MR grade of 0 decreased steeply to 71%, and the percentage with MR grades of 2+, 3+, or 4+ increased to 14% (Fig 5). After 2 weeks, the percentage of patients with an MR grade of 0 decreased at a slow but constant rate, with corresponding increases in percentages with MR grades of 2+, 3+, or 4+. At 5 years, 81% of patients had 0 or 1+ MR, 8% had 2+ MR, and 11% had 3+ or 4+ MR. Risk factors for late return of MR included failure to use a prosthetic annuloplasty ring and both early and late date of operation; the former may represent an early learning phase and a recent aggressive approach to repair in patients with complex anterior disease (Table 3, Fig 6).

View larger version (8K): [in this window] [in a new window]   Fig 5. Unadjusted mitral regurgitation (MR) grades 2+, 3+, or 4+ after anterior versus posterior repair. Solid lines enclosed within dashed 68% confidence limits are parametric estimates.

View larger version (8K): [in this window] [in a new window]   Fig 6. Unadjusted percentage of patients with mitral regurgitation (MR) grades 2+, 3+, or 4+ at 1 year according to date of operation. Solid line is trend line enclosed within 68% confidence limits. Each symbol represents actual data summarized as means by date of operation.

Survival
Among patients undergoing mitral valve repair, unadjusted early survival was slightly lower among those with anterior than posterior disease (p = 0.03), but late survival was similar (p 0.4; Fig 7). However, after propensity adjustment, survival was similar early and late after repair.

View larger version (9K): [in this window] [in a new window]   Fig 7. Unadjusted survival after repair of anterior () versus posterior () disease. Vertical bars 68% confidence limits, and numbers in parentheses patients remaining at risk. Solid lines enclosed within dashed 68% confidence limits are parametric estimates.

	Comment

Top Abstract Introduction Patients and Methods Results Comment Appendix 1 Appendix 2 Discussion Acknowledgments References

Degenerative Disease: Site of Prolapse
Degenerative mitral valve disease is the most common indication for surgical mitral valve repair [1–9]. This condition is not rare: using strict echocardiographic criteria, Framingham Heart Study investigators determined that prevalence of mitral valve prolapse is 2.4% in the general population [16]. Up to 5% of these patients ultimately develop MR of sufficient severity to require intervention [17]. Pathologic changes associated with degenerative mitral valve disease vary and include annular dilatation, leaflet thickening, myxoid degeneration, chordal elongation and rupture, and annular and leaflet calcification [1–9]. Leaflet and chordal tissue is structurally abnormal, with increased concentrations of water, collagen, and glycosaminoglycans [18]. Carpentier suggested that patients with degenerative mitral valve disease should be assessed by considering a pathophysiologic triad: etiology, lesions(s), and leaflet dysfunction resulting from the lesions(s) [2, 6]. In our clinical practice, the site of prolapse (posterior, anterior, or bileaflet) has the greatest bearing on choice of repair technique.

Patient Characteristics
Our data demonstrate important preoperative differences between patients based on the site of prolapse. Patients with anterior disease were older and had more extensive changes in cardiac morphology and function. Others have also observed clinical differences between patients with anterior versus posterior disease. Suri and colleagues [8] noted that patients with anterior prolapse were more often female, with more symptoms, a greater likelihood of atrial fibrillation, lower left ventricular ejection fraction, and greater left ventricular size; however, unlike our series, patients with anterior prolapse were younger than those with posterior prolapse. David and colleagues [7] found that patients with anterior prolapse had more left ventricular dysfunction and atrial fibrillation at the time of surgery, but again were younger than those with posterior prolapse. These two series included patients with additional structural heart disease (coronary artery disease and aortic valve disease, respectively), and inclusion of patients with concomitant conditions may contribute to some differences between these studies and ours. Nevertheless, the data from these studies are concordant with our findings that at the time of surgery, patients with anterior disease are more likely to have deleterious structural and functional changes in the heart.

There are several possible explanations for these findings. Suri and colleagues [8] suggest that patients with anterior disease (1) present at a later stage in the progression of their disease or (2) have more advanced disease to begin with. It is possible that patients with anterior disease are referred later in their course because of the perception that repair is less likely than in those with posterior disease. Natural history studies further distinguish these patient groups, documenting different rates of progression of prolapse in patients with anterior versus posterior disease [19]. In addition, outcome studies suggest that postrepair progression of degenerative disease is more rapid in those with anterior disease [7]. It is possible that dysfunction of the anterior leaflet, which represents two thirds of the surface area of the mitral valve, is a more severe lesion than classic prolapse of the middle scallop of the posterior leaflet. If this supposition is correct, quantitative echocardiography would demonstrate greater regurgitant area and volume in patients with anterior disease, and this might explain in part the more pronounced alterations of cardiac structure and function in such patients. However, we are not aware of a study that addresses this possibility.

Repair of Anterior Prolapse
It has long been recognized that repair of anterior prolapse is more challenging than repair of posterior prolapse and that results of anterior prolapse repair are frequently inferior to those obtained in treatment of posterior prolapse [3, 7, 8]. These tenets may explain the sharp decrease in the probability of anterior leaflet repair with advancing age, as bioprosthetic replacement in such patients is a durable operation; however, the influence of age on repair rate is far less pronounced in patients with posterior disease. A variety of surgical techniques have been used to repair anterior disease, including chordal shortening, chordal transfer, leaflet resection, artificial chordae, edge-to-edge repair, and others [2, 3, 5–9]. Lately, there has been considerable interest in use of artificial chordae, which are generally constructed from polytetrafluoroethylene [20–22]. Choice of chordal length is the primary challenge in creating artificial chordae, and there are a variety of aids for estimating appropriate length [20–22]. In the current series, we relied primarily on chordal transfer. Its theoretical advantage over artificial chordae is that transfer of normal chordae eliminates the need for estimating chordal length. Nevertheless, in recent years we have expanded our use of artificial chordae, incorporating a caliper that facilitates estimation of chordal length [20,21]. Recent reports also document successful correction of anterior prolapse with edge-to-edge repair [9]. Statistical analysis did not demonstrate clear superiority of any of these techniques, perhaps related to the relatively small number of patients in each group. Currently, we favor creating artificial chordae to correct anterior prolapse, as this technique has been associated with excellent durability and is suitable for minimally invasive approaches.

Durability of Repair: Anterior Versus Posterior
Most large series suggest that durability of anterior repair is inferior to that of posterior repair [2, 5, 7]. Possible reasons for this discrepancy include (1) greater difficulty associated with achieving repair, (2) application of inadequate repair techniques, and (3) more rapid progression of degenerative changes after repair. Certainly, technical aspects of repair influence results in anterior disease. For example, chordal shortening is associated with more failures than chordal transfer [23]. In addition, time-related improvements in repair durability, associated with increased surgeon experience and improved surgical technique, highlight the importance of conduct of the operation [8].

In the current series, return of MR was more likely early after anterior repair, and freedom from reoperation and from recurrent MR were greater after posterior than anterior repair. With posterior leaflet prolapse, quadrangular resection and annuloplasty is a reproducible operation associated with excellent durability in the hands of virtually all surgeons. In the case of anterior disease, there is no consensus that an analogous situation exists with our current repair techniques. As such, it is possible that a portion of the early postoperative MR was residual MR resulting from application of inadequate repair techniques.

Survival
Although patients with anterior disease presented with more pronounced cardiac changes and had less durable repair, they had similar risk-adjusted survival to those with posterior disease. Earlier work suggested a survival advantage in those with posterior disease [2]; however, more recent data support the finding that survival is similar between groups [7–9]. This finding is somewhat surprising.

Study Limitations
By design, this study focused only on patients with documented isolated anterior disease and compared them with patients with posterior disease. Patients with bileaflet disease were not included because this designation is often heterogeneous, including those with primary posterior leaflet disease and those with true bileaflet disease. In addition, we did not include patients with coronary artery disease; such patients have important clinical differences compared with the cohort that was analyzed [24].

Echocardiographic follow-up at Cleveland Clinic was available in 193 of 252 patients having repair for anterior disease (77%) and was not obtained by a fixed schedule. In addition, echocardiographic follow-up was not available beyond 10 years in most patients. It is possible that patients with recurrent MR were more symptomatic, prompting them to seek medical attention and obtain echocardiograms, and thus our findings might underestimate durability. Alternatively, it is possible that patients with recurrent MR were more likely to die, eliminating the ability to obtain repeat echocardiograms. The relationship between return of MR and survival could not be evaluated, because both are outcomes of mitral valve repair, and statistical methodology to examine such a relationship is just beginning to emerge. Echocardiograms obtained during this study included semiquantitative assessments of MR using established techniques that represented standard care at the time; quantitative echocardiography was not performed routinely during the time frame of this study [25]. We did not perform extensive analyses of outcomes related to mitral valve repair versus replacement; this is the subject of previous work [4].

Conclusions
Surgical repair should not be delayed in patients with anterior disease and severe MR as such delay may contribute to changes in cardiac structure and function. With current surgical techniques, the majority of mitral valves with anterior disease can be repaired rather than replaced. However, development of more durable repair techniques applicable to the broader spectrum of isolated anterior disease is warranted.

	Appendix 1

Top Abstract Introduction Patients and Methods Results Comment Appendix 1 Appendix 2 Discussion Acknowledgments References

 

	Appendix 2

Top Abstract Introduction Patients and Methods Results Comment Appendix 1 Appendix 2 Discussion Acknowledgments References

 

	Discussion

Top Abstract Introduction Patients and Methods Results Comment Appendix 1 Appendix 2 Discussion Acknowledgments References

 
DR J. SCOTT RANKIN (Nashville, TN): Mark, congratulations again for a very lucid presentation, as usual. Several years ago we published in the Journal of Heart Valve Disease (JHVD 2004;13:399–409), and then 2 years ago in The Annals of Thoracic Surgery (ATS 2006;81:1526–8), our approach to repair, using artificial chordal replacement (ACR). Since 1995, we have repaired all mitral valve prolapse with ACR, without leaflet resection. The first advantage is that all prolapse can be repaired, 100%. Barlow's cases, anterior leaflet prolapse, commissural prolapse, etc, are no different than posterior leaflet cases, and ACR facilitates repair in these tougher situations. The second advantage, which we are going to hear in the next presentation, is that ACR preserves leaflet surface area, which reduces residual mitral regurgitation. In our series, 95% of patients had no residual leak postoperatively, and 5% mild leak. The third advantage is that long-term recurrence is extremely low, and with the techniques we published in The Annals of Thoracic Surgery 2 years ago, our recurrence rate has been 2% to 3% over a 10-year follow-up. The final advantage is that ACR is ideal to merge with minimally invasive techniques like the robot. Now at our center and under the leadership of Dr Brunsting, virtually all isolated posterior leaflet prolapse is being repaired with the robot and ACR, a very simple, easy operation. So I have two questions:

At the Valve Symposium of this meeting a few years ago, I asked Dr Cosgrove if he ever used ACR, and I got a very stern "never" back; I see you are starting to use some now. At this point in time, what percentage of your prolapse cases receive an ACR procedure? Do you do it as a bailout? Do you do it without leaflet resection? How are you using it? And secondly, since you have both procedures now, perhaps you have some, at least early, follow-up data to compare repair and recurrence rates of ACR with chordal transfer, which was your predominant technique earlier.

Thank you again for a great paper.

DR GILLINOV: Thank you. We are familiar with your data and that of others like Tirone David and Patrick Perier, and these have caused us to use more artificial chords. How often do we use artificial chords today versus chordal transfer? It depends on the surgeon. My practice is to use artificial chords for most patients with anterior leaflet prolapse, and I use a technique developed by Dr Mohr in which we actually measure the chords. So for me it is about 98% artificial chords for the anterior leaflet, although it is not similar for all of my colleagues.

Because our switch to artificial chords is recent, we don't yet have enough data to compare long-term results of chordal transfer to those with artificial chords; they appear equal in the early going in our hands. We will keep following these patients and determine if in our hands one technique is better than another.

DR OTTAVIO ALFIERI (Milan Italy): I enjoyed your paper very much. It is really a superb study. We conducted a similar study a few years ago showing that there was no difference in the freedom from reoperation in patients with segmental anterior leaflet prolapse treated with the edge-to-edge technique compared to patients with posterior leaflet prolapse treated with quadrangular resection. I want to emphasize that only patients with segmental leaflet prolapse were treated with the edge-to-edge technique. After a follow-up of 10 years, we didn't find any difference in freedom from reoperation. As a matter of fact, the two groups of patients had a 96% freedom from reoperation. And also in regard to echocardiographic studies which have been conducted many years after the operation, we found that with the edge-to-edge technique for anterior leaflet prolapse, the great majority of patients had no or trivial regurgitation and only 7% of the patients had 2+ regurgitation.

What do you think about the application in selected patients with a segmental leaflet prolapse of the edge-to-edge technique?

DR GILLINOV: Clearly, your data support the use of the edge-to-edge technique with segmental prolapse. In addition, data from percutaneous mitral valve repair demonstrates that this works in many people.

We have used the edge-to-edge technique when there is segmental prolapse at a commissure and more or less simply close the commissure, with excellent results.

DR JORGE CHIU QUEVEDO (Guatemala City, Guatemala): Very nice paper, Dr Gillinov. Right now in Third World countries we still have a lot of rheumatic disease and we have been challenged to try to repair these rheumatic diseased valves, and that has been the tendency instead of trying to replace it, but we have noticed that we have been getting much more teenaged patients with the problem of rheumatic disease in the mitral valve. Do you have any comments about what do you think will be the better way to approach it, whether it is artificial or chordal transfer according to your experience?

DR GILLINOV: Do these young rheumatic patients have regurgitation, stenosis, or mixed lesions?

DR QUEVEDO: Generally they have mixed pathology, but we have been faced with some cases of just insufficiency and prolapse of both valves.

DR GILLINOV: For pure regurgitation I would favor the application of artificial chordae so that you are putting in new chords that will not be affected by the rheumatic process. Perhaps that will enhance durability. These are difficult repairs to achieve.

	Acknowledgments

Top Abstract Introduction Patients and Methods Results Comment Appendix 1 Appendix 2 Discussion Acknowledgments References

 
This work is supported in part by a gift from the Broyhill Family (A.M.G.), by the Judith Dion Pyle Chair in Heart Valve Research (A.M.G.), and by the Kenneth Gee and Paula Shaw, PhD, Chair in Heart Research (E.H.B.).

	References

Top Abstract Introduction Patients and Methods Results Comment Appendix 1 Appendix 2 Discussion Acknowledgments References

 

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