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Ann Thorac Surg 2007;84:750-758
© 2007 The Society of Thoracic Surgeons

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Original Articles: Cardiovascular

A Change in Perspective: Results for Ischemic Mitral Valve Repair Are Similar to Mitral Valve Repair for Degenerative Disease

^a Department of Surgery, University of Virginia, Charlottesville, Virginia
^b Department of Internal Medicine, University of Virginia, Charlottesville, Virginia

Accepted for publication April 23, 2007.

^_* Address correspondence to Dr Gazoni, Department of Surgery, University of Virginia Health System, Charlottesville, VA 22908 (Email: lmg2x{at}virginia.edu).

Presented at the Forty-third Annual Meeting of The Society of Thoracic Surgeons, San Diego, CA, Jan 29–31, 2007.

	Abstract

Top Abstract Introduction Patients and Methods Results Comment Discussion References

 
Background: Although the benefits of mitral valve repair for degenerative disease are well established, many consider surgery for functional ischemic mitral regurgitation (MR) less amenable to operative treatment. We hypothesized that mitral valve repair for ischemic MR results in outcomes similar to those for mitral valve repair for degenerative MR.

Methods: Retrospective review of nonemergent mitral valve repairs for an 8-year period revealed 105 patients with functional ischemic MR, of whom 39 were treated for severe tethering (ischemic group), and 245 patients with degenerative MR (degenerative group).

Results: Patients in the ischemic group had more comorbidities (p < 0.01) and worse preoperative left ventricular dysfunction (ejection fraction 0.29) compared with patients in the degenerative group; (ischemic, 37.1% [39 of 105] versus degenerative, 2.0% [5 of 245]; p < 0.01). Immediate postrepair transesophageal echocardiogram revealed a 0 to 1+ MR in all patients in both groups (not significant). The hospital mortality rate was 1.9% (2 of 105) in the ischemic group and 1.2% (3 of 245) in the degenerative group (p = 1.00). The 5-year survival rate was 83.9% in the ischemic group and 94.3% in the degenerative group (p < 0.01). Five-year freedom from reoperation for recurrent MR was 100% and 97.5% in the ischemic and degenerative groups, respectively (p = 0.14). Postoperative renal failure and stroke rates were similar between both groups (not significant). The incidence of moderate or greater MR after more than 1 year of follow-up was similar between groups (not significant).

Conclusions: Despite the multiple comorbidities that afflict patients with ischemic MR, mitral valve repair for ischemic and degenerative disease produces comparable and satisfactory outcomes. An aggressive approach to repair of functional ischemic MR, including treatment of tethering, leads to durable results.

	Introduction

Top Abstract Introduction Patients and Methods Results Comment Discussion References

 
Ischemic mitral regurgitation (MR) occurs after approximately 30% of myocardial infarctions and significantly increases the risk of cardiovascular mortality [1]. Substantial issues complicate the treatment of patients with ischemic MR. Myriad comorbidities, such as impaired left ventricular function, renal insufficiency, diabetes mellitus, and chronic obstructive pulmonary disease, commonly afflict patients with ischemic MR, compromising recovery from surgery while also negatively impacting long-term survival. The pathologic process of ischemic MR also creates significant challenges that hinder effective surgical treatment. Although simple annular dilatation can be successfully treated by restrictive annuloplasty, Carpentier type IIIb restrictive systolic leaflet motion continues to pose significant surgical challenges that make mitral valve repair a formidable task.

Degenerative mitral valve disease is characterized by patients with fewer comorbidities, and represents a disease process successfully treated by a variety of operative approaches in more than 90% of cases [2, 3]. Previous studies comparing ischemic with degenerative mitral valve disease have demonstrated that long-term survival is determined by baseline patient characteristics rather than the cause of MR [4, 5]. Unfortunately, the patient characteristics associated with those afflicted with ischemic MR are usually inseparable from the disease process causing MR. Despite the inherent challenges associated with ischemic MR, we hypothesize the following: (1) Patients who undergo nonemergent treatment of functional ischemic MR have similar outcomes (except for long-term survival) compared with those with degenerative MR, despite the difference in comorbidities. (2) Patients with ischemic MR who require a subvalvular maneuver for the treatment of severe tethering have comparable outcomes with those with ischemic MR treated primarily by restrictive annuloplasty alone.

	Patients and Methods

Top Abstract Introduction Patients and Methods Results Comment Discussion References

 
This study was reviewed and approved by the Human Investigation Committee of the University of Virginia Health System with a waiver of individual patient consent. A retrospective analysis was performed on all nonemergent mitral valve operations for severe functional ischemic and degenerative mitral valve regurgitation during an 8-year period (1998 to 2006) at a single institution. A review based on intention to treat subsequently identified 105 patients with functional ischemic MR and 245 patients with degenerative MR who underwent a planned mitral valve repair. Sixty-six patients (62.9%) received a restrictive annuloplasty as the primary treatment of functional ischemic MR. Thirty-nine patients (39 of 105, 37.1%) with severe Carpentier type IIIb restrictive systolic leaflet motion or tethering underwent a subvalvular procedure as an adjunct to restrictive annuloplasty. A subvalvular procedure included papillary muscle relocation (31 of 105, 29.5%) as described by Kron and colleagues [6] or a Dor procedure [7] (8 of 105, 7.6%), which stabilized the papillary muscle base in patients with MR and a severely dilated left ventricle (>6 cm end-systolic diameter). Severe tethering was characterized during intraoperative transesophageal echocardiogram and was defined as tethering resulting in leaflet concavity (concave leaflet configuration toward the left atrium in long-axis views) [8]. Preoperative left ventricular dimensions were similar in patients with ischemic MR and did not affect the decision to relocate the posterior papillary muscle. This is supported by examination of the left ventricular dimensions in patients with ischemic MR for the last 2 years of the study (subvalvular procedure [n = 15], 5.71 ± 0.84 cm [diastolic] versus annuloplasty alone [n = 23], 5.56 ± 0.85 cm [diastolic], p = 0.61; subvalvular procedure [n = 15], 4.70 ± 0.94 cm [systolic] versus annuloplasty alone [n = 23], 4.46 ± 1.14 cm [systolic], p = 0.50). However, as previously mentioned, patients with severely dilated left ventricles (>6 cm end-systolic diameter) with severe tethering underwent a Dor procedure. Twenty-eight nonemergent mitral valve replacements for functional ischemic disease (Table 1) and 30 mitral valve replacements for degenerative disease were performed during the study period. The most common indications for mitral valve replacement in patients with ischemic disease were severe Carpentier type IIIb disease and associated leaflet fibrosis or calcification or patients with mixed diseases of the mitral valve. Severe mitral annular calcification was the most common indication for mitral valve replacement in patients with degenerative disease.

Operative Technique
All procedures were performed through full or partial sternotomy. Patients were placed on cardiopulmonary bypass using standard techniques. Dual venous cannulation was used either percutaneously or directly and antegrade or retrograde cardioplegia were used, depending on the surgeon’s preference. When performed, CABG or atrial ablation procedure was done before the mitral procedure. Tricuspid and aortic valve procedures were done after the mitral procedure. Transesophageal echocardiogram was used before repair to help characterize the mechanism of MR and then after repair to evaluate the adequacy of repair in all patients. Patients with ischemic MR received a rigid or semirigid annuloplasty (93.3%; 98 of 105) or flexible annuloplasty (6.7%; 7 of 105; surgeon preference) sized to the intertrigonal distance. The annuloplasty ring was then undersized by two.

Follow-Up
Follow-up information was obtained during outpatient appointments and phone interviews with the referring cardiologist and primary care physicians. The mean duration of follow-up was 45.2 ± 50.1 months (range, 2 to 96 months) and 43.9 ± 24.2 months (range, 6 to 96 months) in patients with degenerative and ischemic disease, respectively, with 1,278 patient-years of follow-up information. The mean duration of echocardiographic follow-up was 23.2 ± 28.8 months (range, 0 to 94 months) and 31.9 ± 24.3 months (range, 1 to 84 months) in patients with degenerative and ischemic disease, respectively. The last known echocardiogram was found in 86.7% (213 of 245) of degenerative group patients and 96.2% (101 of 105) of ischemic group patients. The closing interval for echocardiographic follow-up was 12 months in the degenerative group and 26 months for the ischemic group.

Statistical Analysis
Statistical analysis of patient characteristics and postoperative outcomes between the two groups were performed with a two-sample Student’s t test. All probability values are two-tailed. The ² test was used for comparison of proportions. Values are expressed as the mean ± standard deviation unless otherwise indicated. The Kaplan–Meier method was used to determine survival and freedom from reoperation, and survival functions between groups were compared by the log-rank test. Probability values less than 0.05 were considered significant. The analysis was performed using SAS statistical software (SAS Institute Inc, Cary, NC).

	Results

Top Abstract Introduction Patients and Methods Results Comment Discussion References

 
Clinical Profile
Preoperative characteristics comparing patients with ischemic and degenerative disease are shown in Table 2. Patients with ischemic MR had a significantly higher incidence of diabetes mellitus, peripheral vascular disease, chronic obstructive pulmonary disease, hypertension, and renal insufficiency (all p < 0.05). All patients undergoing MV repair had 3+ to 4+ MR graded by preoperative transthoracic echocardiogram. The mean New York Heart Association functional class was 2.12 ± 0.65 in patients with degenerative disease versus 2.91 ± 0.77 in patients with ischemic disease (p < 0.001). Sixty-four percent (67 of 105) of patients with ischemic disease had at least moderate left ventricular dysfunction (EF 0.39) compared with 10.2% (25 of 245) of patients with degenerative disease (p < 0.001). In a subgroup analysis of patients with ischemic MR who underwent a subvalvular procedure compared with those treated with annuloplasty alone, preoperative characteristics were similar in all observed variables between the two subgroups (Table 3).

View larger version (18K): [in this window] [in a new window]   Fig 1. Kaplan–Meier analysis of survival for patients with degenerative (x) versus ischemic () mitral regurgitation.

View larger version (17K): [in this window] [in a new window]   Fig 2. Kaplan–Meier analysis of survival of patients with ischemic mitral regurgitation who underwent a subvalvular procedure for sever tethering () versus annuloplasty alone (thin line).

View larger version (18K): [in this window] [in a new window]   Fig 3. Kaplan–Meier analysis of freedom for reoperation for patients with degenerative (x) versus ischemic () mitral regurgitation.

View larger version (19K): [in this window] [in a new window]   Fig 4. Histogram of the most recent known echocardiogram for patients with degenerative (black bars) versus ischemic open bars) mitral regurgitation. (Mld = mild; Mod = moderate; Sev = severe; Tr = trace.)

View larger version (19K): [in this window] [in a new window]   Fig 5. Histogram of the most recent known echocardiogram of patients with ischemic mitral regurgitation who underwent a subvalvular procedure for sever tethering black bars) versus annuloplasty alone (open bars). (Mld = mild; Mod = moderate; Sev = severe; Tr = trace.)

	Comment

Top Abstract Introduction Patients and Methods Results Comment Discussion References

Despite overall poor long-term survival in patients with ischemic MR, the survival advantage seen with the surgical correction of severe ischemic MR is significant and well established. The surgical treatment of ischemic MR has demonstrated increasingly improved outcomes as survival rates and quality of life determined by New York Heart Association class have improved during the last decade [9, 13–15]. Operative mortality for mitral valve surgery has also significantly decreased as reparative procedures have become more common. During the 1990s, Filsoufi and colleagues [16] demonstrated decreased mortality rates for combined CABG and mitral valve repair from 14% to 3.7%.

The associated comorbidities in patients with functional ischemic MR failed to affect perioperative morbidity and mortality and the incidence of recurrent MR in this study. Our low operative mortality rate (1.9%) disputes the not uncommonly held idea by referring physicians (anecdotal) that certain patients with ischemic MR are not surgical candidates because of the severity of their comorbidities. The presence of severe tethering also failed to affect the incidence of postoperative complications, survival, and long-term freedom from reoperation and from moderate or greater MR. We are, however, reminded that patients with ischemic MR require significant support and resources to recuperate from surgery as indicated by the lengthier intensive care unit and hospital stay and increased nosocomial infection rates compared with the healthier patients with degenerative MR. Although 5-year survival in patients with ischemic MR was significantly lower compared with those with degenerative MR (ischemic, 83.9% versus degenerative, 94.3%; p < 0.01), the survival rates for ischemic MR are still encouraging.

The encouraging midterm results for the treatment of functional ischemic MR can likely by attributed to specific factors. Although restrictive annuloplasty alone adequately treats annular dilatation, recurrence rates of greater than mild MR ranging from 15% to 30% indicate that annuloplasty alone does not sufficiently address all cases of ischemic MR [17, 18]. In a review of 585 patients undergoing undersized annuloplasty for ischemic MR, McGee and associates [19] reported an incidence of moderate MR or greater in 28% of patients within 6 months of repair. A likely culprit for recurrent MR and obstacle to successful repair is Carpentier type IIIb disease. Acknowledging that annuloplasty alone is limited in its ability to correct Carpentier type IIIb MR is critical to overall success. Moderate MR or greater on postrepair transesophageal echocardiogram was not accepted in our practice, especially as intraoperative transesophageal echocardiogram can downgrade the severity of MR. In our hands, a subvalvular maneuver used to address severe tethering was required to achieve this end. The opportunity to positively affect outcome in patients with ischemic MR is small, and the failure to adequately decrease the severity of MR obviously negates the benefits of mitral repair. Greater than mild MR after repair has also been shown to be an independent risk factor for death [20] and congestive heart failure, and the incomplete correction of MR or the return of MR greater than mild perpetuates the deterioration of left ventricular function [2].

Semirigid or rigid annuloplasty rings were also used in the vast majority of patients in this study. Several groups support the idea that semirigid or rigid annuloplasty rings lead to a more durable repair although significant controversy exists [5, 13, 14, 19, 21, 22]. The downsizing of the annuloplasty ring is yet another important factor in the treatment of functional ischemic MR used in this study. Downsizing has been successfully used by Bolling and colleagues [13] for more than a decade. Bax and coworkers [14] reported a mean MR grade of 0.8 ± 0.8 18 months after the placement of annuloplasty rings downsized by two in a series of 51 patients with severe ischemic MR. The downsizing of two to four sizes in another series of 38 patients also led to similar results with a mean MR grade of 0.6 ± 0.8 and a mean New York Heart Association class of 1.5 ± 0.6 at 13 ± 7 months after repair [21]. The fact that the vast majority of patients with ischemic MR in this study had lesions amenable to revascularization (86.7%) also contributed to favorable improvements in mitral valve function and low reoperation rates.

With regard to subvalvular maneuvers, many techniques exist such as second-order chordal cutting, infarct placation, papillary muscle sling, or papillary muscle imbrication, although no technique has been found to be clearly superior to the other. Our group has endorsed the use of papillary muscle relocation [6] for severe cases of tethering in which restrictive annuloplasty is thought to be insufficient, and the Dor procedure when ischemic MR is associated with severe left ventricular dilatation. Although there is no simple or straightforward solution supported by all surgeons, most would agree that restrictive annuloplasty alone is inadequate in treating many cases of functional ischemic MR. Moreover, the ability to use complex repair techniques should not preclude the use of mitral valve replacement in select cases of functional ischemic MR. If an echocardiogram demonstrates complex regurgitant jets and significant tethering, and associated leaflet fibrosis is seen intraoperatively, bioprosthesis placement has been preferred by some groups. The use of mitral valve replacement, however, is not without consequence. Despite preserving the subvalvular apparatus with mitral valve replacement, Reece and associates [23] recently demonstrated that mitral valve repair continues to be superior to mitral valve replacement in terms of morbidity and perioperative mortality when associated with CABG. With appropriate patient selection and the recognition of the role of complex repair techniques, patients with severe Carpentier type IIIb restricted systolic leaflet motion have comparable outcomes to those with predominantly Carpentier type I disease.

Ultimately, operating on patients with ischemic mitral valve regurgitation is safer and more efficacious now than it has ever been, even in the presence of severe tethering. The comparison of outcomes between the vastly different patients with degenerative MR and those with ischemic MR also highlights that successful repair and good outcomes should be expected in most patients with significant MR, regardless of the cause and irrespective of the number of comorbidities. An important correlate to these encouraging results is that patients with functional ischemic MR may be better served by undergoing mitral valve repair at an earlier point in time when the possibility of living at a lower New York Heart Association class is more likely [24]. Mitral valve repair continues to demonstrate its versatility and success in treating the majority of mitral valve disease.

	Discussion

Top Abstract Introduction Patients and Methods Results Comment Discussion References

 
DR ROBERT A. E. DION (Leiden, the Netherlands): I first want to congratulate you for the quality of your presentation and also for the message that you deliver, that ischemic mitral regurgitation is not necessarily a lethal disease in the short term. A paper from our group later in the session will confirm it. I just have two questions. The first, what is the indication in your group to perform the so-called tethering operation? And second, did you find a relation between the ventricular dimensions before the operation and the recurrence of mitral regurgitation at follow-up?

DR GAZONI: Thank you, Dr Dion. As far as who gets a subvalvular procedure is a difficult question to answer, and part of it is there are not specific criteria that we use. We rely heavily on our cardiology colleagues, and we discuss at great length with them who would require and benefit from a subvalvular procedure. In general, severe tethering or a very large ventricle gets a Dor procedure and/or subvalvular procedure.

In regards to your second question, we do not have data looking at the ventricular dimension and recurrent mitral regurgitation (MR) rates. We did include the Dor procedure as a subvalvular operation. There is only a handful of patients, maybe seven out of the entire cohort, who received this procedure, and all of those did well, but we did not specifically look at that, sir.

DR AUBREY C. GALLOWAY (New York, NY): This is an excellent surgical approach and report, and I have similar questions to those of Professor Dion. In retrospect couldn’t you have looked at the cases that required a subvalvular procedure, and then defined them in terms of coaptation depth, interpapillary distance, and ventricular dimensions, and compared those findings to patients who required no subvalvular procedure? I think that that would have been very helpful data in establishing some criteria for when you thought subvalvular procedures are indicated. Again, an excellent study.

DR GAZONI: Thank you, sir. Dr Kron has mentioned to me that he has a grant into the NHLBI trying to prospectively study this, as we all have much interest in this, and so hopefully we will have more objective criteria in the future.

DR MICHAEL A. BORGER (Leipzig, Germany): Excellent paper, very impressive results. You have much lower MR recurrence rates than the large series from Cleveland and from our data from Toronto, and you are to be congratulated for that.

I have two quick questions. How many emergency operations were excluded, and how did you deal with those patients that had multiple postoperative echoes? As you know, ischemic MR is a very dynamic lesion depending on the loading conditions. If you had a patient that had three postoperative echoes and one of them showed moderate MR and the other two showed mild, how did you deal with that statistically?

DR GAZONI: As far as the emergency operations, I would say that over the 8-year time period there were approximately 20 emergent operations, but I cannot tell you specifically. In the patients who had multiple postoperative echoes, there were two patients in the cohort who we started off performing a repair, and at the end of the procedure the intraoperative TEE demonstrated greater than mild MR. Those two patients received replacement of their valve. We do not leave the operating room with more than mild MR.

And as far as the transthoracic echocardiograms predischarge, all our patients continued to have 0 to 1+ MR before leaving the hospital. One of the points of this paper is that we do not let people leave the operating room without their mitral regurgitation adequately addressed, meaning more than mild MR.

And I am sorry if I lost the last point.

DR BORGER: Multiple postoperative echoes, 1, 2, 3, 4 years down the road.

DR GAZONI: Many of our patients, especially in the ischemic group had multiple echocardiograms. At any point in time, no patient in that group had an operation to fix greater than mild MR. These five patients out of the cohort of 105 who had more than mild MR continue to be followed although I am not sure how we could make any statistical conclusions on only five patients echocardiograms.

DR MICHAEL MACK (Dallas, TX): I think the question is, if you had three echoes on a patient afterward and two of them were mild MR and one was moderate, did you categorize those as moderate for purposes of this study?

DR GAZONI: Yes, definitely. The echocardiogram with the greatest degree of MR was captured. I am sorry for the misunderstanding. Thank you, Dr Mack.

	References

Top Abstract Introduction Patients and Methods Results Comment Discussion References

 

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): John A. Kern Philip W. Smith Lynn M. Fedoruk Turner C. Lisle Benjamin B. Peeler Irving L. Kron Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gazoni, L. M. Articles by Kron, I. L. Search for Related Content PubMed PubMed Citation Articles by Gazoni, L. M. Articles by Kron, I. L. Related Collections Valve disease