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Ann Thorac Surg 2005;80:1309-1314
© 2005 The Society of Thoracic Surgeons

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Original article: Cardiovascular

Isolated Mitral Valve Repair in Patients With Depressed Left Ventricular Function

Department of General and Thoracic Surgery, Duke University Medical Center, Durham, North Carolina

Accepted for publication April 22, 2005.

^_* Address reprint requests to Dr Shah, PO Box 3458, Duke University Medical Center, Durham, NC 27710 (Email: ashah{at}duke.edu).

Presented at the Fifty-first Annual Meeting of the Southern Thoracic Surgical Association, Cancun, Mexico, Nov 2–4, 2004.

	Abstract

Top Abstract Introduction Patients and Methods Results Comment Discussion References

 
BACKGROUND: The utility of mitral valve repair (MV repair) has been well documented in patients with normal left ventricular function. Few studies, however, have specifically examined outcomes of isolated MV repair in patients with decreased left ventricular function. The purpose of the present study is to review a modern experience with isolated MV repair in patients with depressed left ventricular function and to examine intermediate outcomes.

METHODS: A retrospective review of patients who underwent MV repair from 1996 to 2003 was performed to identify consecutive patients who had isolated MV repair. Preoperative studies were reviewed to further identify patients with an ejection fraction less than 0.45. Clinical operative data were collected from the medical record, and survival was determined with the Social Security Death Index. Further end points of reoperation and transplantation were also noted.

RESULTS: A total of 101 patients were identified with a mean follow-up of 1,124 days. Mean ejection fraction and age was 0.34 ± 0.09 and 56 ± 14 years, respectively. Thirty-day mortality was 2.9%. One- and 5-year survival was 94% ± 2% and 70% ± 6%, respectively. There was no statistically significant difference in actuarial survival for functional versus primary mitral disease, or for ejection fraction less than 0.35 versus greater than 0.35. Six patients required transplantation. Five-year freedom from reoperation, transplantation, and death was 61% ± 11% and 54% ± 8% for patients with primary and secondary mitral valve disease, respectively (p = 0.279). Minimally invasive MV repair was performed in 57 patients with a mean ejection fraction of 0.369 ± 0.07 and a 30-day mortality of 1.7%.

CONCLUSIONS: In patients with isolated MV regurgitation and depressed left ventricular function, MV repair can be achieved with low operative mortality, but there remains a persistent risk of death, reoperation, or transplantation irrespective of valve disease. Minimally invasive MV repair was safe in this group.

	Introduction

Top Abstract Introduction Patients and Methods Results Comment Discussion References

 
Mitral valve (MV) repair has been an important development in MV surgery, offering durable reconstruction without anticoagulation. The results in patients with symptomatic mitral regurgitation (MR) are outstanding, with operative mortality of 0% to 2% and freedom from reintervention 90% at 10 years [1, 2]. Left ventricular (LV) function, however, remains an important determinant of short-term and long-term outcomes [3, 4]. In patients with depressed LV function, the use of MV repair instead of valve replacement has been questioned, with some centers reporting equivalent outcomes in select patients [5, 6].

Increasingly, MV repair has been applied to patients without primary valve abnormalities, ie, functional or secondary MR [7]. These patients represent a unique cohort in that they have MR related to alterations of ventricular geometry and depressed contractile function. Bolling and colleagues [7] and Romano and Bolling [8] have reported excellent outcomes with MV repair in a group of patients with dilated cardiomyopathy and severe MR, but few reports have reproduced their outcomes.

Finally, as surgeons have become more experienced and less invasive techniques have gained popularity, the nature, approach, and quality of repairs have evolved. This renders comparisons of large cohorts over time difficult. Therefore, we reviewed surgical outcomes of isolated MV repair in a modern series of patients with depressed LV function.

	Patients and Methods

Top Abstract Introduction Patients and Methods Results Comment Discussion References

 
From March 1996 to September 2003, 692 MV repairs were performed at Duke University Medical Center, and of this group 101 consecutive patients were identified with an ejection fraction (EF) less than 0.45 by preoperative conscious echocardiography or ventriculography. Patients with associated coronary artery bypass grafting, other valve procedures, or previous cardiac surgery were excluded. All operative reports and echocardiograms were reviewed. To quantify ventricular dysfunction, LV end-systolic volume was calculated. Left ventricular end-systolic volume was measured from the apical four-chamber view according to the modified Simpson's rule. Furthermore, LV end-diastolic internal dimension was also recorded from standard parasternal long-axis views. Primary MR was defined by the presence of leaflet or chordal pathology. Secondary MR was defined by the presence of normal mitral leaflets and chordae. Patients were further classified in the secondary MR group by the cause of their myopathy. Ischemic cardiomyopathy was defined by a history of myocardial infarction (corroborated by perfusion scan or cardiac magnetic resonance imaging) and cardiac catheterization confirming coronary artery disease. In the absence of significant coronary artery disease patients were designated as idiopathic.

Surgical Technique
During this period, MV repair was performed by means of a median sternotomy (n = 44) or a right minithoracotomy using port-access techniques (n = 57) [9]. In the sternotomy group, the MV was exposed using a modified transseptal approach. Myocardial protection was achieved with moderate hypothermia (28°C) and blood cardioplegia delivered antegrade and retrograde.

In the minimally invasive group, a small right anterior thoracotomy was used to expose the MV through the left atrium. As in the sternotomy group, myocardial protection consisted of moderate hypothermia and cardioplegic arrest.

All patients had a semirigid, complete annuloplasty ring as part of the repair. In patients with primary MR, concomitant leaflet and chordal procedures were also used to complete the repair. The annuloplasty ring was sized in the primary group using the surface area of the anterior leaflet. In the secondary MR group, our early institutional practice has been to aggressively downsize the ring by 2 mm from the measured size. After 2000, we placed 24-mm rings empirically in the majority of patients.

Follow-Up
With institutional approval, a retrospective review of the medical records of these patients was performed to record preoperative and postoperative data. Intermediate outcomes were determined from the medical records, Social Security Death Index, and telephone interviews. Mean follow-up was 1,123 days.

Statistical Analysis
All dichotomous variables were compared using ² analysis, whereas analysis of variance was used for continuous variables. Nonparametric variables were compared with a Mann-Whitney rank sum test. Data not normally distributed are presented as median (25th percentile, 75th percentile). End points of death, transplantation, and reintervention were represented graphically using the Kaplan-Meier method, and comparisons were made using the log-rank test. Multivariable analysis was performed using a Cox proportional hazards model. All statistical analysis was performed with Statistica (Statsoft, Tulsa OK).

	Results

Top Abstract Introduction Patients and Methods Results Comment Discussion References

 
Primary Versus Secondary Mitral Regurgitation
Table 1 summarizes the patient characteristics. In comparing patients with primary and secondary MR, there were no statistically significant differences in most baseline characteristics. However, EF was significantly lower in the secondary MR patients as compared with in the primary MR patients. Patients with secondary MR had significantly shorter cardiopulmonary bypass times as compared with the entire cohort, reflecting simpler reconstructions. Annuloplasty rings were placed in all patients, and the median ring size was 26 mm. Operative mortality (in-hospital or 30-day) was 2.9% for the entire cohort with a median hospital length of stay of 6 days (5 days, 9 days). Patients with secondary MR had a higher mortality and longer hospital stay but this did not reach statistical significance. Preoperative LV end-systolic volume was significantly higher in patients with secondary MR (Table 1).

View larger version (13K): [in this window] [in a new window]   Fig 1. Actuarial survival of all patients after mitral valve repair with ejection fraction less than 0.45.

View larger version (19K): [in this window] [in a new window]   Fig 2. Actuarial survival after mitral valve repair for patients with primary (solid line) versus secondary (dashed line) mitral regurgitation (p = 0.19).

View larger version (18K): [in this window] [in a new window]   Fig 3. Actuarial survival after mitral valve repair in patients with an ejection fraction (EF) less than 0.35 (dashed line) versus greater than 0.35 (solid line; p = 0.33).

View larger version (18K): [in this window] [in a new window]   Fig 4. Actuarial freedom from valve reintervention, transplantation, or death in patients with primary (solid line) versus secondary (dashed line) mitral regurgitation (p = 0.28).

	Comment

Top Abstract Introduction Patients and Methods Results Comment Discussion References

Mitral Valve Repair in Patients With Impaired Left Ventricular Function
Beginning with Carpentier's seminal contribution in 1983 [10], MV repair has gained broad acceptance as the favored method to correct mitral insufficiency. Several studies have documented improved survival, excellent freedom from reoperation, and preservation of ventricular function with MV repair [1, 2, 11–13]. Importantly, these outcomes have been reproduced by multiple centers during the years, emboldening cardiothoracic surgeons to expand the use of MV repair. The 1998 American Heart Association guidelines, however, question the utility of MV procedures in patients with EF less than 0.30 [14]. A recent review of The Society of Thoracic Surgery database suggests that MV repair in patients with EF less than 0.35 is associated with a 5% mortality versus 1% in those with an EF greater than 0.50 [15]. Moreover, certain patient cohorts have not necessarily benefited from MV repair versus MV replacement. Gillinov and associates [6] reported a large series of patients with ischemic MR and found that, in sicker patients, outcomes were similar between repair or replacement. More recently Thourani and coworkers [5] from Emory showed that, in patients older than 60 years of age, MV repair did not have a statistically significant survival advantage over replacement. Most studies of MV repair involve heterogeneous cohorts: primary and secondary MR, a range of LV function, concomitant coronary artery bypass grafting, and, perhaps most importantly, long periods reflecting learning curves.

Thus the present study examined MV repair in patients with depressed LV function during a modern period in which our experience with MV repair has matured. Our results support the use of MV repair in patients with depressed LV function. The in-hospital mortality was low, and, importantly, 5-year survival was 72% in this cohort and was similar to multiple other reports. Trichon and colleagues [16] reported a 5-year survival of 40% in a large cohort with moderate to severe MR and LV dysfunction managed medically.

We found that major cardiac-related intervention including death, need for transplantation, or valve reintervention was reasonable at 5 years. Six patients were ultimately referred for transplantation. Only 3 patients required MV replacement, suggesting that MV repair instead of replacement can provide a durable result in patients with reduced EF. Although the majority of patients avoid reintervention, need for transplantation is not eliminated and these patients require close follow-up.

Minimally Invasive Approach
The majority of patients in this study had successful MV repair by means of a minimally invasive approach. MV repair performed using port-access methods offered results comparable to conventional sternotomy. Cardiopulmonary bypass time was longer and hospital stays found to be shorter compared with patients who underwent a sternotomy in this series. The lower EF and higher LV end-systolic volume in the sternotomy group reflected our institutional bias at the time to prefer to use sternotomy in patients with severe myopathies. Particularly if the preoperative cardiac index was less than 2.0, we offered these patients MV repair by means of median sternotomy. Although sternotomy allows for more flexibility in perioperative protection strategies and postoperative support, MV repair may be done during ventricular fibrillation through either approach, thus eliminating concerns about myocardial protection. Most studies on minimally invasive MV repair have centered on patients with preserved LV function with superb results. Greelisch and associates [17] have reported 5-year survival of 95% and no hospital mortality in a large series of patients with a mean EF greater than 0.50. Similarly patients undergoing reoperation, a high-risk cohort, appear to have better outcomes using port-access approaches [18]. There is no study that has specifically examined minimally invasive MV repair in patients with impaired LV function, and our study confirms the safety of the approach.

Secondary Mitral Regurgitation
To date the largest group of patients with secondary MR remains the group studied by Romano and Bolling [8] from the University of Michigan. In their last report more than 200 patients with functional MR secondary to cardiomyopathies were offered MV repair with a 5% operative mortality. All patients received small annuloplasty rings, and several received concomitant tricuspid valve procedures [8]. Few institutions have such a dedicated program, but as our experience with MV repair has matured so has our willingness to offer MV repair in patients with secondary MR. We identified 55 patients in the 5-year period with MR secondary to cardiomyopathy. These patients had short-term and long-term outcomes comparable to the University of Michigan series. Of note, our patients had higher EFs and lower LV end-systolic volumes than reported by Romano and Bolling [8], and a larger percentage of our patients went on to transplantation, making a direct comparison difficult. As more centers embrace this philosophy, a broader evaluation of MV repair in cardiomyopathy will be necessary to corroborate these results.

Study Limitations
The present report is a retrospective study with a relatively short follow-up. To date there are no large randomized prospective studies involving MV repair compared with medical management or MV replacement. Many studies have used large retrospective cohorts and propensity analysis to control for bias and patient characteristics, but the fact remains that these studies examined long periods in which experience and practices change. A recent report from David and coworkers [2] reviewing 400 MV repairs for degenerative valve disease documented a major shift from chord transfer to polytetrafluoroethylene chords during the study for patients with anterior prolapse. How this practice shift will alter outcomes remains unknown. Similarly the short-term follow-up in this study makes long-term outcome analysis difficult. Nonetheless, very little is known about the intermediate outcomes of patients with depressed LV function and isolated MV repair, and this study provides new information in this regard in the modern era using modern techniques. Lastly, although the current patient cohort represents a mix of valve disease, we were able to identify patients with functional MR and to provide more information on this entity. The issue of valve disease makes interpretation of the literature very difficult and seems to reflect surgeon and referral bias. For example, some studies will include a large number of patients with concomitant coronary artery bypass grafting, whereas others report a minority of patients with ischemic heart disease. This certainly alters mortality outcomes. Thus in our current study we excluded patients with concomitant coronary artery bypass grafting.

Conclusions
Mitral valve repair in patients with depressed LV function is safe and provides good intermediate outcomes. Minimally invasive techniques can be effective in selected patients. Nonetheless, a minority of patients may still require cardiac transplantation, emphasizing the acuity of these patients and the value of close follow-up. Primary versus secondary MR has relatively little impact on survival or outcome in patients with reduced LV function.

	Discussion

Top Abstract Introduction Patients and Methods Results Comment Discussion References

 
DR W. RANDOLPH CHITWOOD (Greenville, NC): Dr. Shah, I congratulate you on this good work. As you know, I am very much an advocate of minimally invasive techniques, and more of a comment than a question. You are using cardioplegic arrest in most of these patients, is that correct?

DR SHAH: Correct.

DR CHITWOOD: Actually, your ejection fractions aren't that low. I mean, 35%, 40%, that's kind of normal in a lot of folk's practices these days except in the very, very elective class I and class II patients. We found that using ventricular fibrillation through a 4-cm incision does avoid ischemia during that time, and we have gotten very similar results to this. So I think that for the group it is important to know that many of us are operating on very low ejection fractions, either cross-clamped or fibrillating, and going back to the work of Blaise Carabello and others, that it is safe to operate on these patients.

Now, your long-term survival was not too bad at 5 years. I think in a lot of groups when you get around 15% to 20%, if you look at Steve Bolling's patients, the survivability drops off. You may want to comment on that. Do you think you have a cohort with a little bit better ejection fractions than in Bolling's group for your patients with secondary mitral regurgitation?

DR SHAH: We certainly do. Doctor Bolling's group has reported patients where I think their mean ejection fraction (EF) is around 25%, and interestingly, we didn't really see much difference when we looked at patients whose EFs were severely depressed, at less than 35%, in terms of long-term outcomes. It may well be that measuring ejection fraction in these patients is sort of a crude marker, but it is one that we have used more consistently preoperatively.

I think the other message here is that the idea of having a mitral valve repair doesn't eliminate the process that has caused the ventricular problem, and that problem persists after the repair, and that means that these folks need to be followed up very carefully, because they can decompensate, they can require transplantation. And although I think the actuarial results are quite good, if you compare patients, for example, in large studies of medical management of heart failure with severe mitral regurgitation (MR), their 5-year survival is on the order of 30%, and so we are emboldened that we are getting better results, but we certainly may be selecting for patients that we think are better.

DR CHITWOOD: Another question is I always look at your sizing. It is interesting, you have a 28 size for patients who have valvular dysfunction, not just annular dysfunction. That is fairly small. I think most people are around 30 or so. I am not sure it matters that much. But the question is, how do you size? We size from four or five parameters from the echocardiogram, so we size before we ever open the chest. Because we are getting more and more minimally invasive, we are trying to simplify the techniques, making incisions smaller and smaller so this can be done totally endoscopically essentially.

So how do you size, and are all those just one size or one size fits all like Steve Bolling does, or are you sizing them meticulously?

DR SHAH: It depends on the etiology of the MR. So patients with primary MR, where there is leaflet pathology, are sized using traditional techniques, looking at the anterior leaflet, et cetera. On the other hand, patients with secondary MR, we have agreed with Dr Bolling's bias and have gone with just small rings in those patients.

DR JOHN H. CALHOON (San Antonio, TX): Doctor Shah, I have one question. I thought it was a very nicely presented and efficiently presented paper. My question is, having looked at your series, how do you decide now whether to use a minimally invasive approach or a median sternotomy? What are the things that lead you to do one way or the other?

DR SHAH: Thanks for the question. The conventional criteria that we use for the minimally invasive approach goes to patient factors beyond their ejection fraction, anatomic considerations, do they have a prior right chest procedure, things that technically would make the operation very difficult. If we think that anatomically and surgically the patient is a candidate, I think that we are emboldened to offer this approach to almost all the patients. However, there is one other consideration, which we don't really have a good answer for.

There are a number of patients with severe pulmonary hypertension who we have had poor outcomes with MV repair and we don't know if they should get an operation at all. So that is the first decision that needs to be made.

And then secondly, I think that those patients who do have a cardiac index less than 2 by preoperative right heart catheterization, some degree of pulmonary hypertension, I think we still will refer them for median sternotomy, mostly because it allows for easier mechanical circulatory support, if needed. We only had about 3 patients who required that, but those are hard lessons to learn, for sure.

	References

Top Abstract Introduction Patients and Methods Results Comment Discussion References

 

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6. Gillinov AM, Wierup PN, Blackstone EH. Is repair preferable to replacement in ischemic mitral regurgitation J Thorac Cardiovasc Surg 2001;122:1125-1141.[Abstract/Free Full Text]
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13. Braunberger E, Deloche A, Berrebi A, et al. Very long-term results (more than 20 years) of valve repair with Carpentier's techniques in nonrheumatic mitral valve insufficiency Circulation 2001;104(Suppl 1):I-8-I-11.
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