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Eur J Cardiothorac Surg 2006;29:348-353
© 2006 Elsevier Science NL
a Division of Cardiology, Loma Linda University Medical Center, Loma Linda, CA, United States
b Division of Cardio-Thoracic Surgery, Loma Linda University Medical Center, Loma Linda, CA, United States
Received 22 August 2005; received in revised form 30 November 2005; accepted 6 December 2005.
* Corresponding author. Address: Division of Cardiology, University of Southern California, 1510 San Pablo Street, 322, Los Angeles, CA 90033, United States. Tel.: +1 323 442 6131; fax: +1 323 442 6133. (Email: rpai{at}usc.edu).
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Abstract |
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 Top Abstract 1. Introduction2. Methods3. Results4. DiscussionReferences |
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2+ MR preoperatively. This yielded 438 patients. Progression to 3–4+ MR post-CABG was correlated with clinical, electrocardiographic, echocardiographic, and operative variables. Results: New 3–4+ MR developed in 11 (10%) of the 108 patients with no prior MR, 21 of the 180 (12%) patients with pre-CABG 1+ MR, and 37 of the 150 (25%) patients with pre-CABG 2+ MR. MR progression correlated with female gender (42% vs 27%, p
= 0.01), history of renal insufficiency (12% vs 5%, p
= 0.05), prior-CABG (30% vs 17%, p
= 0.01), lack of beta-blocker use (19% vs 35%, p
= 0.008), lower incidence of significant PDA stenosis grafted (88% vs 98%, p
= 0.003), lower preoperative LVEF (42 ± 19% vs 50 ± 17%, p
= 0.001), larger LV size (p
= 0.01), pre-CABG MR grade (p
= 0.0002), and pre-CABG presence of LBBB block (20% vs 4%, p
< 0.0001). Independent predictors of MR progression, pre-CABG, were female gender (p
= 0.002), history of renal insufficiency (p
= 0.05), lack of beta-blocker use (p
= 0.006), MR grade (p
= 0.02), and presence of LBBB (p
= 0.005). Conclusion: Development of significant MR following isolated CABG is common and may be related to incomplete myocardium revascularization, especially in the PDA area and LV remodeling. Preoperative, beta-blocker use may be protective against its development.
Key Words: CABG • MR
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1. Introduction |
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TopAbstract1. Introduction2. Methods3. Results4. DiscussionReferences |
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2. Methods |
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TopAbstract1. Introduction2. Methods3. Results4. DiscussionReferences |
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2.2 Clinical data
The following patient characteristics were collected: (1) patient demographics: age and gender; (2) non-cardiac co-morbidities: presence of diabetes mellitus, renal insufficiency (serum creatinine >2 mg/dl), renal replacement therapy with dialysis, CVA, COPD or peripheral vascular disease; (3) cardiac co-morbidities: extent of coronary artery disease (history of left-main disease and the number of diseased coronary vessels), history of myocardial infraction, congestive heart failure, cardiogenic shock and arrthymia; (4) prior cardiac surgical history: history of prior CABG; (5) surgical variables: perfusion time, cross-clamp time, number, type and location of grafts and use of intra-aortic balloon pump; and (6) medication use prior to surgery: use beta-blockers, ACE-inhibitor, digoxin, and diurectics.
2.3 Echocardiographic data
Trans-thoracic or trans-esophageal echocardiographic examinations were performed with the use of standard techniques and commercially available equipment and anatomic measurements were made according to the American Society of Echocardiography guidelines [4]. The following parameters were collected on pre-CABG and post-CABG echocardiograms: (1) LVEF, (2) LV dimensions and wall thickness, (3) relative wall thickness calculated combined wall thickness/LVd, (4) MR grade as follows: 0 = none, 1 = mild, 2 = moderate, 3 = moderate to severe, 4 = severe based on jet size, size of vena contracta and area of flow acceleration and systolic flow reversal in the pulmonary veins, and (5) wall motion abnormalities: hypokinesis, dyskinesis or akinesis in the anterior wall and non-anterior wall (posterior and inferior) walls with or without preserved wall thickness.
2.4 Electrocardiographic data
EKG data were collected from the MUSE system (digitally stored EKG database). Following parameters were collected on all EKGs: (1) rhythm: sinus rhythm, atrial fibrillation (AF) or paced, (2) right and left bundle branch blocks (RBBB, LBBB), and (3) pathological Q-waves in: anterior wall and non-anterior distributions.
2.5 Surgical data
This was an observational study; hence, choice of number of grafts, and cardioplegic technique, were made entirely by the operating surgeon. None had mitral valve or any other valvular surgery.
2.6 Statistical analysis
Pre-CABG and post-CABG clinical, echocardiographic, and EKG variables associated with progression to 3 or 4+ MR (progressors) were identified. Statview 5.01 (SAS Institute Inc., Cary, NC, USA) program was used to assist in the statistical analysis. Groups with and without MR progression were compared using the unpaired t-test or chi-square test. Multivariate logistic regression was used to identify independent predictors of MR progression. The p-value 0.05 was considered to be statistically significant.
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3. Results |
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TopAbstract1. Introduction2. Methods3. Results4. DiscussionReferences |
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3.2 Pattern of MR progression (Fig. 1)
Post-CABG, the mean MR grade increased from 1.1 ± 0.8 to 1.4 ± 1. In patients without pre-CABG MR (n
= 108), de novo 3–4+ MR developed in 11 (10%) patients after CABG (3+ in 8 and 4+ in 3). Patients with 1+ MR pre-CABG (n
= 180) progressed to 3–4+ MR post-CABG in 21 (12%) patients (3+ in 17 and 4+ in 4). In patients with 2+ MR pre-CABG (n
= 150), 3–4+ MR developed in 37 (25%) patients (3+ in 25 and 4+ in 12). In total, de novo 3+ MR developed in 50 (11%) and 4+ MR in 19 (4%) patients post-CABG. Of the 69 patients with 3–4+ MR, in 17 patients (25%), the 3–4+ MR was diagnosed within the first 6 months of CABG.
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3.3.3 Operative variables
In the study population, the mean number of bypass vessels grafted was 3.1 ± 1. In the groups with and without MR progression, there was no difference in the distribution of coronary artery disease, number of vessels grafted, whether arterial or venous grafts were used. However, those with MR progression had a significantly lower incidence of having a significantly stenosed posterior descending artery (PDA) being grafted (88% vs 98%, p
= 0.003).
3.3.4 Preoperative echocardiographic variables
Patients with 0–2+ MR progression on pre-CABG echocardiogram had lower mean LVEF (42 ± 19% vs 50 ± 17%, p
= 0.001), and a larger left ventricle dimension [LVd (54 ± 9 mm vs 51 ± 8 mm, p
= 0.01), LVs (39 ± 12 mm vs 36 ± 11 mm, p
= 0.03)]. Progressors also had a higher prevalence of pre-CABG 2+ MR compared to the non-progressors (54% vs 31%, p
= 0.0002).
3.3.5 Changes in echocardiographic variables post-CABG
Post-CABG echocardiogram was done with a mean duration of follow-up of 1.6 years. The mean MR grade increased from 1.1 ± 0.8 to 1.4 ± 1. Progression of MR was associated with reduction in left ventricle ejection function (negative 4 ± 17% vs +1.9 ± 13%, p
= 0.002), and increase in left ventricle size [LVd (2 ± 7 mm vs negative 1 ± 6 mm, p
= 0.004), and LVs (4 ± 8 mm vs 2 ± 8 mm, p
= 0.002)]. Post-CABG, development of new wall motion abnormality in anterior wall was not different in the two groups, yet, development of a new wall motion abnormality in the non-anterior wall motion with preserved myocardium thickness was associated with MR progression (28% vs 16%, p
= 0.02).
3.3.6 Perioperative variables
Of the total patients with pre-CABG and post-CABG echocardiograms, only 34 patients that had echocardiogram day of surgery and 45 patients had echocardiogram within a week post-CABG. Only six of these patients had both an echocardiogram day of surgery and an echo within a week post-CABG. Only one of these six had MR progression from 1+ to 4+ MR. Because of the limited number of patients with perioperative echocardiograms, we could not study the risk factors that may contribute to MR progression due to perioperative factors.
3.3.7 Electrocardiographic variables
Pre-CABG EKGs were available in 382 patients and post-CABG EKGs in 338 patients. On the pre-CABG EKG, there was no association between prevalence of sinus rythum, atrial fibrillation, and paced rythum in patients with MR progression. Patients with MR progression had no difference in the prevalence of RBBB, but had a significant higher presence of LBBB (20% vs 4%, p
< 0.0001). Pre-CABG, presence of pathological Q-waves in anterior and non-anterior leads was not associated with MR progression. On the post-CABG EKG, MR progression correlated with lack of development of new Q waves in the non-anterior walls (2% vs 17%, p
= 0.01) but not in the anterior wall (13% vs 14%, p
= ns).
3.3.8 Independent predictors of post-CABG 0–2 ± MR progression
In multivariate logistic regression analysis, pre-CABG variables significant on univariate analysis were entered into the model: female gender, history of renal insufficiency, history of CABG, use of beta-blocker, LVEF, LVd, MR grade, and presence of LBBB. The independent pre-CABG predictors of post-CABG MR progression were as follows: female gender (p
= 0.002, RR = 3.3), history of renal insufficiency (p
= 0.05, RR = 3.8), lack of use of beta-blocker (p
= 0.006, RR = 0.29), MR grade (p
= 0.02, RR = 1.9), and presence of LBBB (p
= 0.005, RR = 5.9). Pre-CABG, history of CABG, LVEF and LV size were not independent predictors of MR progression in the multivariate analysis. The PDA stenosis grafted variable was not used in the analysis as it was a small subset of the entire population.
3.3.9 Subgroup analysis of patients with CABG 2 ± MR
Patients with pre-CABG abnormal mitral valve function and 2+ MR (n
= 150) had mean age of 68 ± 10 years, mean LVEF 42 ± 17%, predominance of male gender 84 (56%). Mean MR decreased from 2 to 1.7 ± 1.1 post-CABG. MR progression to 3–4 + MR developed in 37 (25%) patients (3+ in 25 and 4+ in 12). The pre-CABG variables associated with 2+ MR progression were lack of beta-blocker use (19% vs 40%, p
= 0.02), greater use of ace-inhibitor (perhaps due to heart failure symptoms) (43% vs 26%, p
= 0.04), higher prevalence of LBBB (19% vs 3%, p
= 0.001), and significant PDA stenosis not being grafted (93% vs 100%, p
= 0.05).
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4. Discussion |
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TopAbstract1. Introduction2. Methods3. Results4. DiscussionReferences |
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4.2 Predictors of MR progression
Predictors of MR progression post-CABG correlated with having poor targets. Patients with smaller coronary arteries like women, patients that have diffuse vascular disease, like patients with renal disease and patients with patchy areas of ischemia like those with prior-CABG, are associated with MR progression. MR progression correlated with the presence of pre-CABG LV dysfunction and large LV size. Although, there was no correlation between MR progression and the extent of coronary artery disease (incidence of left main disease, mean number of diseased vessels), or the mean number of arterial or vein grafts used, having incomplete revascularization in the PDA territory correlated with the progression of MR. The highest rate of MR progression was seen in patients with pre-existing abnormal mitral valve function with 2+ MR pre-CABG (p
= 0.0002). These patients may require very little additional insult for further deterioration of their MR. Beta-blockers were protective, possibly through preoperative or perioperative protection against ischemia and possibly through prevention of LV remodeling which would increase functional MR. Presence of inter-ventricular asynchrony with LBBB presence was also correlated with MR progression.
4.3 Mechanistic insights of MR progression
Pathogenesis of MR in patients undergoing CABG is multi-factorial. In patients with CAD, functional MR has been related to 3D change in the geometry and distance between the papillary muscle and mitral apparatus [2,3,5,6]. Our data suggest that an increase in LV size is central to MR progression in patients undergoing CABG. This may occur due to inadequate revascularization, especially in the PDA area or natural progression of LV remodeling. This may be facilitated by LBBB and seems to be inhibited by use of beta-blockers. Recently, we have shown that post-CABG 3–4+ MR regression may depend upon adequate revascularization of hibernating myocardium to increase in LV function and decrease LV size [3]. Regional wall motion abnormality in the inferior–posterior LV wall due to development of new ischemia without infract, may additionally, progress MR post-CABG due to change in regional LV geometry.
Presence of pre-existing abnormal mitral valve function with 2+ MR had the highest rate of MR progression. This may probably be due to the fact that an abnormal mitral coaptation mechanism in these patients needed very little additional disturbance to cause worsening of the mitral valve function. Beta-blocker use provided protection presumably through both reduction of ischemia and inhibition of LV remodeling. Use of beta-blocker such as carvedilol has been shown to reduce MR due to prevention or reversal of LV dilation [7,8].
The association between LBBB and MR progression is fascinating. This may be due to either faster worsening of LV function with LBBB or intra-ventricular asynchrony caused by LBBB. Cardiac resynchronization therapy (CRT) has been shown to decrease functional MR [9–11]. In patients with LBBB and low LVEF, MR decreases with LVEF improvement and decrease in the mitral annulus diameter with CRT [10]. Also, MR may improve immediately after CRT therapy due to improved inter-papillary muscle distance and coordinated LV function [11]. A decrease in effective regurgitant orifice area and regurgitant volume by as much as 40% was seen with CRT presumably due to an increase in trans-mitral closing force and improved LVEF [9].
4.4 Clinical implications of our findings
In our patients, MR progression was seen in 69 (16%) of all patients undergoing CABG. We recommend preoperative and post-CABG echocardiogram in patients with risk factors for MR including presence of PDA lesion. Also, our study gives insights into how MR may be prevented post-CABG. Initially, aggressive revascularization strategy should be encouraged; especially, in patients with risk factors for MR development, PDA disease, hibernating myocardium or 2+ MR. Secondly, as development of 3–4+ MR is very common in those with 2+ MR, strong consideration should be given to mitral valve repair concomitantly with CABG in these patients. Thirdly, beta-blocker therapy use should be strongly encouraged in these patients. Lastly, in patients with LBBB (with poor LV function), CRT may potentially prevent MR progression. However, our study was not designed to address this issue.
4.5 Study limitations
This is a retrospective observational study, hence has its inherited limitations. Also this study has a small number of patients because pre-CABG and post-CABG echocardiograms were not done in all patients undergoing CABG. Performance of a postoperative echocardiogram may have been triggered by some symptoms or signs and may introduce a selection bias and potentially lead to overestimation of postoperative MR occurrence. Only, prospective data collection with systematic echocardiographic follow-up in all may eliminate this bias. We have no specific viability study to relate pre-CABG and post-CABG wall motion abnormalities. The quantitative details of medical therapy before and after surgery are not available. Despite of these limitations, the findings of this study give insights into predictors of MR progression and potential strategies to prevent its occurrence, in those patients undergoing CABG alone.
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References |
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TopAbstract1. Introduction2. Methods3. Results4. DiscussionReferences |
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  W. Y. Szeto, R. C. Gorman, J. H. Gorman III, and M. A. Acker Ischemic Mitral Regurgitation Card. Surg. Adult, January 1, 2008; 3(2008): 785 - 802. [Full Text]
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 A. R. Srivastava, A. Banerjee, S. Jacob, and J. Dunning Should patients undergoing coronary artery bypass grafting with mild to moderate ischaemic mitral regurgitation also undergo mitral valve repair or replacement? Interactive CardioVascular and Thoracic Surgery, August 1, 2007; 6(4): 538 - 546. [Abstract] [Full Text] [PDF]
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 M. J. Antunes Editorial comment: Mild-moderate ischemic mitral regurgitation: should it be treated together with CABG? Eur. J. Cardiothorac. Surg., March 1, 2006; 29(3): 353 - 354. [Full Text] [PDF]
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