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Ann Thorac Surg 2002;74:1476-1481
© 2002 The Society of Thoracic Surgeons
a Section of Cardiothoracic Surgery, Yale University School of Medicine, New Haven, Connecticut, USA
* Address reprint requests to Dr Elefteriades, Section of Cardiothoracic Surgery, Yale University School of Medicine, 121 FMB, 333 Cedar St, New Haven, CT06510, USA.
e-mail: john.elefteriades{at}yale.edu
Presented at the Thirty-eighth Annual Meeting of The Society of Thoracic Surgeons, Fort Lauderdale, FL, Jan 28–30, 2002.
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Abstract |
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METHODS: We examine the clinical and echocardiographic outcome after isolated CABG in 49 patients with ischemic cardiomyopathy and 1+ to 3+ MR undergoing surgical revascularization. The patients were identified for analysis of mitral valve-related issues from a larger series of 183 patients with ischemic cardiomyopathy (MUGA ejection fraction 
30%) undergoing CABG by a single surgeon from 1986 to 1996. Patient age was 66.3 years (mean, range 45 to 83 years). There were 5 women (10.2%) and 44 men (89.8%). Mean ejection fraction was 22.4% with a range of 10% to 30%. Thirty-four patients had preoperative congestive heart failure (70%) and 12 (25%) had pulmonary edema. Number of grafts was 2.8 (mean, range 1 to 5). The MR was 1+ in 18 patients (37.5%), 2+ in 26 (52%) and 3+ in 5 patients (10.5%).
RESULTS: Hospital mortality was 2.0% (1 of 49 patients). Ejection fraction improved from 22.0% to 31.5% (p < 0.05) after CABG. Mean degree of MR improved with CABG alone from 1.73 to 0.54 (p < 0.05) as measured at a mean interval of 36.9 months from CABG. New York Heart-Association congestive heart failure class improved from 3.3 to 1.8 (p < 0.05). Long-term survival was 88%, 65%, and 50% at 1, 3, and 5 years postoperatively. No patient required subsequent mitral valve operation or heart transplantation in long-term follow-up.
CONCLUSIONS: We conclude that, in patients with advanced ischemic cardiomyopathy and mild-to-moderate MR, isolated CABG (without mitral valve, repair) suffices, producing dramatic improvement in ejection fraction, in congestive heart failure, and in degree of MR, with excellent (relative) long-term survival. The improvement in MR likely results from improved left ventricular function and size consequent upon revascularization.
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Introduction |
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30%), the available data are even more scarce [1, 4]. Ischemic mitral insufficiency varies widely from time to time and with changes in loading conditions, both preload and afterload. This has been widely accepted, with several studies demonstrating downgrading of MR with intraoperative transesophageal echocardiography [3, 5, 6] when compared to preoperative transthoracic echocardiography or transesophageal echocardiography under conscious sedation on the patients. Also, in ischemic mitral insufficiency, the pathophysiologic defect is in the ventricle and the papillary muscles, not the valve itself. Therefore, direct approaches to the valve (usually by means of ring annuloplasty) constitute therapeutic maneuvers not specifically geared to the underlying pathology.
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Material and methods |
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Presence of clinical angina or objective evidence of ischemia (by nuclear, echocardiographic, or positron emission tomographic means) was not a necessary preoperative criterion for acceptance of the low EF patients for CABG. Positive evidence of ischemia was welcomed but not required for patient acceptance for revascularization [7]. Critical, proximal, three-vessel coronary artery disease, depressed EF, and adequate distal targets were sufficient indications for surgical intervention. In terms of symptoms, 70% of patients had angina, 66% of patients had congestive heart failure (22% with pulmonary edema), and 25% presented with significant ventricular arrhythmias (multiple symptoms in some patients). Patients with obvious evidence of primary mitral valve disease (leaflet or chordal pathologies) were excluded from this CABG-only treatment. Mitral valve operation plus CABG was used in such excluded patients.
During the corresponding period, 20 combined mitral/CABG procedures were performed by the same surgeon. Five of these combined operation patients had EF more than 30% and do not fit the same cardiomyopathy profile as the patients studied in this article. Among the 15 patients who did fit the low EF profile, three had 4+ MR, three had endocarditis, two had ruptured chordae, three had discrete regions of prolapse of the anterior or posterior mitral valve leaflets, two had acute transmural myocardial infarction with mitral insufficiency, and two have insufficient data to characterize.
Technique
Regarding the technical conduct of the operation, we used the left internal mammary artery routinely (in 88% of our patients). We limited our grafts to significant targets of adequate size likely to sustain long-term patency. The number of grafts ranged from 1 to 5, with a mean of 2.8. All procedures were done on cardiopulmonary bypass, with myocardial preservation by systemic hypothermia to 28°C, topical hypothermia with iced saline and cold crystalloid cardioplegia.
Postoperative assessments
Postoperative congestive heart failure classification was assigned at the time of last follow-up, which ranged from 1 to 122 months postoperatively (mean, 36.9 months). Postoperative MUGA for EF determination were performed from 2 to 94 months postoperatively (mean, 28 months). Postoperative echocardiography to assess degree of residual MR was carried out 1 to 82 months after CABG (mean, 13.6 months).
Statistical analysis
Of these patients, we retrospectively reviewed pre- and postoperative echocardiographic or angiographic studies to determine the degree of MR, if present at all. We excluded intraoperative transesophageal echocardiography studies, given the degree of underestimation of MR that these studies produce, as has been documented by the literature [3, 5, 6]. Detailed pre- and postoperative echocardiographic data on MR were available in 75 (63 men [84%], 12 women [16%]) of the 183 ischemic cardiomyopathy patients undergoing isolated CABG. There was no MR in 26 of 75 (35%) of these patients. Further statistical analysis on these patients was not carried out, except for pre- and postoperative EF determination.
The numerical data were tabulated with Microsoft Excel XP (Microsoft Corporation, Phoenix, Arizona) and a paired t test was performed manually. All p values were obtained from correlation of the t values with a standardized statistical table. Survival analysis was by the Kaplan-Meier technique.
Among the 49 patients with preoperative MR there was 1+ MR in 18 (37%) of the patients, 2+ MR in 26 (53%), and 3+ MR in 5 (10%) of the patients (Table 1). Postoperative echocardiograms were available in all but 2 of the MR patients. No patient with 4+ MR had been accepted into the patient group for isolated CABG. The average preoperative EF for the patients without MR was 22.6% and the average preoperative EF for patients with 1+ to 3+ MR was 22.4%. Mean number of grafts in this group was 2.8, ranging from 1 to 5.
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Left ventricular EF improvement
In the patients with MR, EF improved from 22.0% to 31.5% (Table 2), a dramatic change significant at the p < 0.05 level. In patients with documented absence of MR preoperatively, the EF improved from 22.6% to 33.9%.
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Congestive heart failure improvement
Consistent with this improvement in MR, congestive heart failure class in the patients with some degree of preoperative MR improved significantly, from New York Heart Association class 3.25 preoperatively to 1.75 postoperatively, significant at the p < 0.05 level (Table 2). New York Heart Association comparison data were available for 26 of the 49 patients.
Late survival
Late survival for the patients with documented preoperative MR (including hospital mortality) was 88% at 1 year, 65% at 3 years, and 50% at 5 years (Fig 1).
For the patients with no preoperative MR, late survival was 87% at 1 year, 74% at 3 years, and 65% at 5 years. For the patients with 1+ MR late survival was 73.3% at 1 year, 50% at 3 years, and 40% at 5 years. For the patients with 2+ MR late survival was 90.5% at 1 year, 77.8% at 3 years, and 57% at 5 years. Finally, for the 5 patients with 3+ MR, one was lost to follow-up at 6 months, three were alive at 27, 28, and 82 months postoperatively, and the final patient died at 108 months postoperatively at age 92. The survival difference between the three MR groups is not statistically significant.
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Comment |
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MR in the presence of coronary artery disease
There is no debate that trivial degrees of MR need not be addressed at the time of coronary revascularization. There is also no debate that for 4+ MR, the valvular pathology should be directly addressed. There is significant debate, however, on what is the right approach for patients with coronary artery disease and mild to moderate (2+ or 3+) MR. A recent retrospective study from Brigham & Women’s Hospital [3] suggested that revascularization alone in this group of patients leaves significant residual MR postoperatively, concluding that a valve-directed procedure, such as annuloplasty, should be undertaken at the time of revascularization. The mean preoperative EF of the patients in this study was 38.1%. Only 19% of these patients had a preoperative EF less than or equal to 30%.
MR in the presence of severe ischemic cardiomyopathy
We believe that MR in the presence of severe ischemic cardiomyopathy (EF 30%) is a separate but equally complex issue. The MR in severe cardiomyopathy is the result of a ventricular abnormality directly affecting the mitral valve; it is unlikely to represent a primary valvular structural abnormality. Given the dramatic and sustained improvement of left ventricular ejection fraction in ischemic cardiomyopathy patients undergoing CABG alone, we started with our initial sample of 183 patients with EF less than or equal to 30%, and selected for study those patients for whom there was documented presence or absence of MR preoperatively.
Weaknesses of study
Weaknesses of this study are that it is not a prospective randomized comparison of treatments (none have been published) and that the patient number (although similar to prior reports) is relatively small. On the other hand, as a single surgeon experience, this study ensures a uniform approach to patient management.
Also, we are not able to distinguish between MR due to infarct/ischemia and that due to pure left ventricular dilatation in this group of patients with advanced ischemic cardiomyopathy, although it appears from our data that both mechanisms respond beneficially to CABG.
General approach to MR in ischemic cardiomyopathy
There was no significant difference in the pre- and post-CABG EF between the 0 MR and the 1+ to 3+ MR groups. The MR improved significantly after revascularization alone. The improvement of EF and MR was reflected in a significant improvement in New York Heart Association class. The improvement in postoperative MR in this group of patients may very well be related to the dramatic improvement in EF and a partial "correction" of left ventricular and mitral valve anatomy after revascularization.
There are scattered reports in the literature regarding the outcome of patients with MR and depressed EF treated with revascularization alone. There are even fewer reports dealing with ischemic MR in the presence of severely depressed EF. Christenson and colleagues [1] studied a group of 56 patients with a mean preoperative EF of 17.9% and concluded that revascularization alone for patients with coronary artery disease and MR resulted in improvement of MR documented by postoperative echocardiography, acceptable mortality (3.6%), improvement in New York Heart Association congestive heart failure status (3.4 to 1.9), and no need for late mitral valve-directed intervention. These results provide close support for our findings.
In a separate study, Duarte and associates [2] showed that late survival in a group of patients with coronary artery disease and preoperative MR undergoing CABG alone was similar to a matched control group of patients with coronary artery disease but no preoperative MR. Although no postoperative determination of residual MR was performed in that study, the equivalent operative mortality and long-term survival rates (mean follow-up, 4.3 years) led them to conclude that moderate MR at the time of revascularization does not always warrant operative correction, This also supports our findings.
Proponents of concomitant annuloplasty with CABG believe that the benefit of addressing the mitral valve directly outweighs the additional cross-clamp time and overall complexity added to the procedure. Chen and colleagues [4] presented in 1998 their data on 81 patients with ischemic MR, and EF <30% preoperatively, who underwent CABG plus mitral repair (77%) or mitral repair alone (23%). Comparison of their survival curves with our data (Fig. 2) show a slightly higher operative and early mortality in their group, but a remarkably parallel course of both survival curves during the next 5 years. We believe that this comparison suggests that no long-term survival benefit was achieved by addressing the MR at the time of operation. Performance of a more complex procedure, however, may have contributed to additional operative mortality.
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We do not maintain that concomitant annuloplasty in these patients is a flawed approach. Centers applying this approach have realized excellent results in this challenging group of patients. We believe, however, that the low operative mortality, improved functional and symptomatic state, and reasonable long-term survival demonstrated in this study indicate that revascularization alone is a safe and effective approach.
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Discussion |
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To try to understand this controversial issue and the contradictory results, the question is whether you have been able to correlate the mitral valve insufficiency with whether the ischemia is chronic or long-lasting ischemia, because this may be the explanation of the different results obtained by different people.
The second question I have is whether you have been able to correlate the residual mitral insufficiency with the reversibility or the improvement of ejection fraction, because one may have a correlation between these two.
And the third question I have is I noticed that you have a 50% mortality at 5 years, which reflects, of course, the severity of ischemic mitral valve insufficiency. My question is whether the deaths you have observed are correlated with a residual severe mitral valve insufficiency or whether there is no correlation.
Thank you very much.
DR TOLIS: Thank you very much for your kind comments, Dr Carpentier. To answer the first part of the question, we determined the preoperative degree of mitral regurgitation with preoperative transthoracic studies or transesophageal under sedation, but not through preoperative transesophageal echocardiographic studies just at the time of the operation. When the studies were being done, the preoperative studies, the patients were not actively ischemic. So we believe that these patients did actually have chronic 3+ mitral regurgitation, and it was not just an issue of being ischemic at the time and suffering an acute episode.
To answer the second question, we have noted a direct correlation between the improvement of mitral regurgitation, congestive haert failure, and the improvement in the left ventricular function, and that comparison is statistically significant.
In terms of your third question, we do not have all the data as to whether these deaths were cardiac or not because we do not have that many patients in the 3+ sample. For the 2+ group, there were very few patients whose deaths were directly related to cardiac issues and more deaths that were related to noncardiac issues, but we do not have an accurate breakdown of these numbers at this time.
DR LISHAN AKLOG (New York, NY): One of my concerns is the severity of mitral regurgitation in these patients. I am not sure that a group of patients where the majority had 1+ mitral regurgitation and only 10% had 3+ mitral regurgitation can be described as having mild-to-moderate ischemic mitral regurgitation. We would typically reserve this description for those with 2 to 3+ mitral regurgitation. Therefore, I would question the forcefulness of your conclusions based on the extent of preoperative mitral regurgitation. It is also unclear to me, based on average mean mitral regurgitation grades, what the real distribution of residual mitral regurgitation was in your patients. This is important because there is certainly data in the medical literature, and we are presenting data at the American Association for Thoracic Surgery, that even modest degrees of residual mitral regurgitation after annuloplasty (as low as 1+) have an impact on long-term survival.
DR TOLIS: We have not done a statistical analysis of the 5 patients that we had 3+ mitral regurgitation, but one of them was downgraded to 2+, 2 of them were downgraded to 1+, and 2 of them had no residual mitral regurgitation in long-term follow-up. I definitely share your concerns about this patient population not having a great representation from the 3+ group, but unlike other reports from the past, we are discussing mitral regurgitation in patients with severe ischemic cardiomyopathy. Our preoperative average ejection fraction for these patients was 22%, unlike the major study that came from the Brigham in September of 2001 where the mean ejection fraction was 39%.
We believe that patients with severe ischemic cardiomyopathy represent a different group than the average patient undergoing coronary artery bypass grafting with some degree of mitral regurgitation, and we believe the benefit that these patients derive from revascularization is more significant than the benefit that the average patient gets. We have objective evidence both in terms of decrease of ventricular size, increase of ejection fraction, and also decrease of mitral regurgitation.
DR FRANCIS PAGANI (Ann Arbor, MI): Is this strategy dependent on achieving complete revascularization of the ischemic myocardium? If not, what would you do in a situation where you had incomplete revascularization and 2+ mitral regurgitation?
DR TOLIS: The average number of grafts that we used were three, 2.8, actually, and they ranged from 1 to 5. In this select group of patients with an ejection fraction less than 30%, we try to limit our revascularization to good targets rather than going for smaller targets of questionable importance. We do not require any viability studies preoperatively. We always welcome them, but we do not accept or reject a patient based on their viability studies. The ultimate test for viability is the dramatic increase in ejection fraction that these patients have after coronary artery bypass grafting.
DR PAGANI: Therefore, in a situation of an inferior infarct with no revascularization in that area and a restricted posterior leaflet and moderate regurgitation of the mitral valve, what would you do?
DR TOLIS: If we believe that we cannot achieve a complete revascularization and there is evidence from the echo report that a specific portion of the valve may be affected, then we would proceed with mitral valve repair.
DR AHMAD RAJAII KHORASANI (Newark, NJ): I would like to congratulate you for your nice presentation. In the past several years, I have chosen an off-pump surgical strategy as the first intraoperative step in management of patients with moderate-to-severe ischemic mitral regurgitation and poor left ventricular function. I have been very pleased with the comforting role of intraoperative transesophageal echocardiography, which has demonstrated the improvement in mitral regurgitation and left ventricular function, after revascularization. My experience is limited to only several patients. In your series the number of patients in this clinical subgroup is also small.
Do you believe that a better surgical strategy for these patients is off-pump revascularization first, and intraoperative comparative reevaluation with transesophageal echocardiography after revascularization and before final intraoperative decision regarding mitral valve management is made?
DR TOLIS: Thank you for your comments. We cannot extrapolate conclusively to off-pump coronary artery bypass grafting. All these procedures were done under full cardiopulmonary bypass. If a surgeon’s preference is to perform the majority of their coronary artery bypass graftings off-pump, we do not believe that 2+ or even 3+ mitral regurgitation should make them change their technique to an on-pump technique so they can address the valve. The data presented in our report becomes more important because more people are doing coronary artery bypass graftings off-pump.
I would not put undo emphasis on the intraoperative transesophageal echocardiogram, because the literature suggests that it downgrades the degree of mitral regurgitation significantly. We rely more heavily on preoperative clinical status and preoperative echo under "real world" conditions for assessment of the severity of mitral regurgitation.
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H. R. Mallidi, M. P. Pelletier, J. Lamb, N. Desai, J. Sever, G. T. Christakis, G. Cohen, B. S. Goldman, and S. E. Fremes Late outcomes in patients with uncorrected mild to moderate mitral regurgitation at the time of isolated coronary artery bypass grafting J. Thorac. Cardiovasc. Surg., March 1, 2004; 127(3): 636 - 644. [Abstract] [Full Text] [PDF]
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R. A. Levine and J. Hung Ischemic mitral regurgitation, the dynamic lesion: clues to the cure J. Am. Coll. Cardiol., December 3, 2003; 42(11): 1929 - 1932. [Full Text] [PDF]
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P. S. Dahlberg, T. A. Orszulak, C. J. Mullany, R. C. Daly, M. Enriquez-Sarano, and H. V. Schaff Late outcome of mitral valve surgery for patients with coronary artery disease Ann. Thorac. Surg., November 1, 2003; 76(5): 1539 - 1548. [Abstract] [Full Text] [PDF]
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