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Eur J Cardiothorac Surg 2001;20:276-281
© 2001 Elsevier Science NL

The importance of grade 2 ischemic mitral regurgitation in coronary artery bypass grafting

^a Department of Cardiothoracic Surgery Sahlgrenska University Hospital, Göteborg, Sweden
^b Department of Clinical Physiology, Sahlgrenska University Hospital, Göteborg, Sweden

Received 9 October 2000; received in revised form 28 March 2001; accepted 25 April 2001.

Corresponding author. Tel.: +46-31-3421000; fax: +46-31-417991
e-mail: anders.jeppsson{at}sahlgrenska.se

	Abstract

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion Appendix A. Conference... References

 
Objective: To study if grade 2 ischemic mitral regurgitation (MR) influences outcome after coronary artery bypass grafting (CABG). Methods: Results of all CABG patients with grade 2/4 ischemic MR operated during 1995–1998 (n=89) were compared with all CABG patients without MR (n=4709) during the same period. To further evaluate patients with grade 2 ischemic MR, a case-control study focusing on functional status was performed. Control patients without MR (n=89) were matched for age, gender and left ventricular ejection fraction. All patients were interviewed regarding angina symptoms and functional status. Results: Survival according to Kaplan–Meier at 1 and 3 years were inferior in the MR group compared to all CABG patients (91 vs 96% and 84 vs 92%, respectively (P=0.0017). However, MR patients were older (68±9 vs 65±9 years (mean±SD), P=0.008) and had an inferior preoperative left ventricular ejection fraction (42±14 vs 58±14%, P<0.0001). In the case-control study, New York Heart Association (NYHA) class and Higgins’ risk score differed preoperatively between the MR group and controls. Neither 30-day mortality (4,5% in both groups) nor survival at 1 (91 vs 93%) and 3 years (84 vs 88%) differed significantly. NYHA class and angina class (Canadian Cardiovascular Society, CCS) improved similarly in both groups. Postoperatively, 62% of the patients in the MR group had reduced, 36% unchanged and 2% increased MR. Conclusions: CABG on patients with grade 2 ischemic MR reduces angina pectoris and improves functional status to the same extent as in CABG patients without MR. Postoperative morbidity and mortality do not differ significantly between the groups. Grade of MR is reduced or unchanged after CABG in patients with grade 2 ischemic MR. The study supports an operative strategy where grade 2 ischemic mitral regurgitation is treated by CABG alone but the result do not exclude that there might be individual patients that would benefit from a valvular or annular procedure in combination with CABG. How these patients should be identified remains unclear.

Key Words: Coronary artery disease • Mitral regurgitation • Cardiac surgery • Echocardiography

	1. Introduction

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion Appendix A. Conference... References

 
Mitral regurgitation (MR) from coronary artery disease, ischemic MR, is found in approximately 3% of all patients undergoing coronary angiography [1]. MR varies in severity and is judged by echocardiography on a four graded scale. The more severe forms of ischemic MR (grade 3 and 4) is generally treated with coronary artery bypass grafting (CABG) and a valve or annular procedure, while the milder forms (grade 1 and 2) are treated solely with CABG. This strategy is supported in the literature [2–5], although it has been questioned [6–9].

Ischemic MR is not an homogenous entity; at least three subgroups could be distinguished. First, coronary artery disease (CAD) with annular dilation, second CAD with ischemic or infarcted papillary muscles and third, CAD with chordal or leaflet pathology and prolapse in combination with annular dilation [3]. These subgroups may require different therapeutical strategies and make the interpretation of reports about ischemic MR as one entity difficult or even impossible.

The present investigation was undertaken to study the influence of grade 2 ischemic MR from CAD on outcome after CABG. For this purpose, we compared our results after CABG in patients with grade 2 ischemic MR with the results in patients without MR. It is possible that a grade 2 ischemic MR could indicate a more pronounced myocardial and/or valvular dysfunction, and therefore substantially influence the results after CABG. If it is so, these patients may benefit from a changed surgical strategy including annuloplasty.

	2. Materials and methods

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion Appendix A. Conference... References

 
2.1. Patients
During a 4-year period (1995–1998) 4798 patients underwent isolated first time CABG at Sahlgrenska University Hospital. All patients were screened for mitral regurgitation by left ventricular contrast injection during the coronary angiography or by echocardiography. All patients with suspected mitral regurgitation were investigated by transthoracal echocardiography and a group of CABG patients with grade 2/4 ischemic MR were identified. In this group, patients with MR from structural leaflet changes (prolapse) were excluded. Finally, there remained 89 patients with grade 2/4 ischemic MR from coronary artery disease (study group) corresponding to 1.8% of all CABG patients. Preoperative characteristics of the patients are given in Table 1.

Mean follow-up time was 28±15 months (mean±SD) and was 100% complete regarding survival and 98.4% complete regarding postoperative angina and function.

2.2. Echocardiography
Echocardiography was performed using an Acuson Computed Sonograph (Acuson, Mountain View, CA, USA) or Vingmed Ultrasound equipment (Vingmed Sound AS, Horten, Norway). M-mode measurements were made according to the recommendations of the American Society of Echocardiography [10]). The ejection fraction was calculated either from M-mode according to Teichholtz [11], or from two-dimensional recordings according to Simpson's rule [12].

All the patients were investigated by color Doppler, as well as by pulsed and continuous wave Doppler. Mitral flow was recorded at the tips of the mitral leaflets in the four-chamber view. Pulmonary venous flow velocities were obtained by placing the sample volume at the orifice of the upper right pulmonary vein. Peak velocity during systole (S) and diastole (D) was measured. Continuous wave Doppler signals were recorded by a 2 MHz non-imaging probe to obtain an optimal signal-to-noise ratio and multiple windows were used.

The assessment of mitral regurgitation severity was based on a number of variables: color Doppler jet characteristics including jet width and area [13,14], continuous wave Doppler intensity and shape of the spectral recording, mitral inflow [15] and pulmonary vein flow pattern by pulsed wave Doppler [16], left atrial size, left ventricular dimensions and pulmonary artery pressure. These variables are either directly influenced by mitral regurgitation severity or related to compensatory changes in the heart. All patients were graded on a four graded scale. Grade 1 regurgitation was characterized by a weak holosystolic continuous wave Doppler signal and a small color Doppler area. Grade 2 regurgitation was characterized by a continuous wave Doppler signal with intermediate intensity, normal pulmonary vein flow pattern and no marked increase in the mitral inflow velocity. Left ventricular and atrial enlargement, high continuous Doppler intensity, large color Doppler area, high mitral inflow velocity, blunted or reversed systolic pulmonary vein flow and pulmonary artery hypertension characterizes grade 3 and 4 mitral regurgitation.

2.3. Study variables
All pre- and peroperative variables were registered prospectively. Mortality after the hospital stay was collected from the county's database. Postoperative heart failure was defined as the need for IABP and/or inotropic support postoperatively. Higgins’ risk score was used for preoperative risk evaluation [17]. Follow-up in surviving patients in the study group and the matched control group was obtained by telephone interview. Predefined inquiries were made regarding level of physical activity that could be performed without causing angina, dyspnea or fatigue. Angina was graded according to Canadian Cardiovascular Society (CCS) [18] and physical function according to New York Heart Association, NYHA [19]. Postoperative echocardiography was performed only when indicated, as determined by the patient's cardiologist. The echocardiographic investigations were performed either at Sahlgrenska University Hospital or at the local hospital. The same criteria for mitral regurgitation grading was used by all investigators. In the study group, postoperative echocardiogram was available in 40 patients (45%) 346±78 days (range 8–1114) after surgery.

2.4. Statistics
All continuous data are given as mean±standard deviation. Unpaired t-test or Mann–Whitney U-test (abnormally distributed data) were used to compare continuous variables and Fisher's exact test to compare categorical data between the groups. To compare changes in NYHA and CCS class, Fisher's test for paired comparisons [20], was used within the groups and Fisher's permutation test [21] between the groups. Survival curves were calculated according to Kaplan–Meier, followed by Log-Rank test to compare the groups. A P-value of 0.05 was considered significant.

	3. Results

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion Appendix A. Conference... References

 
3.1. Study group vs all CABG patients (Study 1)
3.1.1. Preoperative data (Table 1)
When patients with MR grade 2 were compared to all CABG patients, the study patients were older and a greater proportion were females. Study patients had a higher incidence of previous stroke, obstructive pulmonary disease and diabetes. The study group had also inferior LVEF (P<0.0001), higher Higgins’ risk score (P<0.0001) and inferior preoperative functional status (P<0.0001).

3.2. Early postoperative parameters (Table 2)
Mean number of anastomoses was higher and extracorporeal circulation time and aortic cross clamp time were longer in the study group compared to all CABG patients. In addition, postoperative heart failure and postoperative myocardial infarction were more common in the study group. Thirty-day mortality tended to be higher in the study (4.5 vs 2.2%) but did not reach statistical significance.

3.4. Case-control study (Study 2)
3.4.1. Preoperative parameters (Table 1)
When the study group was compared to a matched population, the study group had preoperatively higher Higgins’ risk score and inferior functional status (Fig. 1) , while all other preoperative variables were comparable.

View larger version (40K): [in this window] [in a new window]   Fig. 1. NYHA functional class before and after surgery in the study group and in the matched control group (n=89 each). There was a significant preoperative difference between the two groups (P<0.01). Functional class improved significantly after surgery in the study group (P<0.05).

3.5. Follow-up
Survival curves are given in Fig. 2 . Survival did not differ significantly between the groups (P=0.21). One-year survival for the study group and the control group was 91 and 93%, respectively. Three-year survival was 84 and 88%, respectively.

View larger version (14K): [in this window] [in a new window]   Fig. 2. Survival in the study group (n=89) and in an age, gender and LVEF matched control population of CABG patients (n=89). There was no significant difference in survival between the groups (P<0.21).

View larger version (38K): [in this window] [in a new window]   Fig. 3. CCS angina class before and after surgery in the study group and in the matched control group (n=89 each). CCS class decreased significantly in both groups (P<0.001).

View larger version (12K): [in this window] [in a new window]   Fig. 4. Postoperative mitral regurgitation in the study group (n=40).

	4. Discussion

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion Appendix A. Conference... References

Mitral regurgitation may be degenerative, rheumatic or ischemic in origin [3]. It is difficult to distinguish between different forms of MR and combinations are probably common. Ischemic MR in itself is complex with different mechanisms resulting in regurgitation. Thus, results from studies where different definitions of ischemic MR have been used are difficult to compare and should be interpreted with caution. In addition, different grading systems, based on either angiography or echocardiography, have been used and there is also a lack of consistency in the terminology. In some papers a grade 2 MR is referred to as moderate [4,8,22] and in some papers as mild [6,7,9] which further increases the degree of difficulty to read and interpret previous studies. Therefore, in the present paper we chose to use only the term ‘grade 2 MR’ exclusively based on echocardiography.

In the present study, we included only patients with significant coronary disease and MR grade 2 while patients with prolapse were excluded. This was done to receive an as homogenous study population as possible and therefore simplify interpretation. It is appreciated that the selection restricts the validity of our conclusions to the same patient category.

At our institution, patients with grade 2 ischemic MR is treated with CABG alone while patients with more severe ischemic MR (grade 3 and 4) are treated with CABG and annuloplasty. According to published reports [2–5], this is the most widespread strategy. However, it has been questioned both by those who advocate a more aggressive attitude towards annuloplasty [9] in patients with less severe forms of ischemic MR (after intra-operative dynamic testing) and those who have a more conservative attitude and treat patient with severe MR by CABG alone [6–8]. Connolly et al. [2] showed significantly inferior survival for CABG patients with grade 3 ischemic MR than CABG patients without MR and suggested that MR grade 3 and 4 should be corrected at the time for CABG. On the other hand, Arcidi et al. [6] presented 1988 results indicating that patients with grade 3 ischemic MR undergoing CABG alone had comparable results to patients undergoing CABG and valve replacement/annuloplasty. Christenson et al. [7] in 1995, reported good survival and functional improvement after CABG alone in patients with MR grade 1 to 3 in combination with poor ventricular function. Recently, Duarte reported that long time survival is comparable in CABG patients with or without grade 3 MR, 20 years after the operation [8]. However, none of these studies are randomized and therefore differences in patient selection may explain the results.

In the present study, we compared outcome after CABG in patients with ischemic MR grade 2 with CABG patients without MR. We reasoned that if the results in the CABG+MR grade 2 group were equivalent to those obtained in comparable patients without MR, this would indicate that CABG alone in patients with ischemic MR grade 2 is justified, while other operative strategies may be considered if the results were evidently inferior.

When the results in the study group were compared with those in the whole CABG population, there was an obvious difference in outcome. However, when the preoperative parameters were analyzed, it became evident that we did not have comparable groups. It was a marked discrepancy between the groups in, among others, age, gender and LVEF. Therefore, we chose to make a case control study with controls matched for age, gender and LVEF.

In the case-control study, morbidity and mortality were comparable in both groups, which not is surprising given that the MR was reduced postoperatively in the majority of the study patients. In addition, both groups improved similarly after CABG in functional status. The results imply that a grade 2 ischemic MR from annular dilation does not substantially influence the results after CABG. Therefore, the results suggest that the present operational strategy is appropriate, but it should be emphasized that the follow-up period is short and there is a tendency towards a more complicated postoperative course and decreased long-time survival in the study group, which may be more evident after a longer follow-up period. On the other hand, in spite of the efforts to match the groups, it appears that the groups were not completely comparable. Preoperatively, the study group had significantly higher risk score (Table 1) and worse functional status (Fig. 3) compared to the control group. Thus, a more complicated postoperative course could be expected in the study population and in fact, the absence of significant differences in postoperative morbidity and mortality argues for the present surgical strategy.

Echocardiography demonstrated that grade 2 MR decreased or remained unchanged postoperatively which is in accordance with Christensen et al.'s findings [7]. However, postoperative echo was only performed when the treating cardiologist found it indicated and therefore only about 45% of the patients had been examined at different time points after the operation. Of course, this restricts the validity of the findings considerably. On the other hand, one may speculate that the cardiologists only examined patients when they, from physical examination, suspected impaired cardiac function and/or worsened mitral regurgitation. Subsequently this indicates that only the patients with more severe symptoms were investigated and that the reported improvement of MR may be underestimated.

In the present study, all patients with ischemic MR grade 2 was treated by CABG solely. Even though the majority of patients had less severe MR and improved their functional status postoperatively, does the result not exclude that there might be patients that would benefit from a valvular or annular procedure in combination with CABG. The present study gives no information about this issue. An open question remain, how should these patients be identified. It is possible that dynamic testing as suggested by Dion et al. [9] can be one alternative.

In summary, the results of the study support a surgical strategy where grade 2 ischemic MR from annular dilation is treated solely with CABG.

	Acknowledgments

 
Statistical advice was given by Anders Odén PhD, Kungälv, Sweden.

	Footnotes

 
Presented at the 14th Annual Meeting of the European Association for Cardio-thoracic Surgery, Frankfurt, Germany, October 7–11, 2000.

	Appendix A. Conference discussion

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion Appendix A. Conference... References

 
Dr P. Sergeant (Leuven, Belgium): In our own studies, following more patients over a longer follow-up, up to 20 years, we have similar findings as yours. The only difference is that your sample size and the duration of your follow-up might be too small, because if you look at the actual curves, the Kaplan–Meier curves, you see that they go a little bit apart, and that is exactly after correction for all variability that we have been able to identify. We support your inferences. It is just that there is an impact on survival just by the fact that these patients have mitral regurgitation, even after correction for all variability.

Dr G. Mani (New Delhi, India): The mitral incompetence which is secondary to an infarction is different from a mitral incompetence secondary to ischemia, and I would think the latter would be more amenable to bypass surgery alone and the former would need some kind of a repair. In this we have observed more so in the beating heart group, and when we do OPCAB, the ischemic mitral incompetence disappears completely, whereas the infarcted mitral incompetence stays on, and that is where the curves are likely to differ as the days go on.

Dr Sergeant: I support this statement completely. We have identified exactly the same observations in the off-pump surgery patients, that mitral insufficiency disappears through the operation. Have you done off-pump procedures in your institution on patients with moderate mitral insufficiency and have you observed the effect on mitral regurgitation?

Dr Brandrup-Wognsen: We have quite an extensive off-pump surgery program, exceeding 20% of our CABGS. What you are describing is something we have seen. However, today we are not using intraoperative echoes regularly so I cannot answer if this is a constant finding.

Dr R. Lorusso (Brescia, Italy): I wonder whether you can comment on the fact that these patients at rest when you make the diagnosis with the echocardiography at rest, they have plus 2 mitral regurgitation, but very frequently when they are submitted to exercise condition, this mitral valve regurgitation may worsen. So do you think that we can use a different diagnostic process in order to identify better the patient who during exercise condition can do worse? Then in that case we should do something more to the mitral valve, because, as the colleague said, you can have two different mechanisms of mitral regurgitation and these mechanisms can make a big difference in terms of exercise under high flow conditions.

Dr Brandrup-Wognsen: I think it would be of interest to do some kind of dynamic testing but since it is not done I cannot comment on this.

	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): Anders Jeppsson Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rydén, T. Articles by Jeppsson, A. Search for Related Content PubMed PubMed Citation Articles by Rydén, T. Articles by Jeppsson, A. Related Collections Coronary disease Valve disease