Impact of Moderate Functional Mitral Insufficiency in Patients Undergoing Surgical Revascularization
Background— Mild and moderate functional ischemic mitral insufficiency present at the time of surgical revascularization present clinical uncertainty. It is unclear whether the relatively poor outcomes in this cohort are dependent on valvular function or related to left ventricular dysfunction. The purpose of this study was to examine the early and late outcomes in patients with less-than-severe functional ischemic mitral insufficiency at the time of isolated coronary artery bypass grafting (CABG).
Methods and Results— From 1996 through 2004, 2242 consecutive patients undergoing isolated CABG were identified as having none to moderate mitral regurgitation (MR) and no valve leaflet pathology. All of the patients at this single institution routinely had an intraoperative transesophageal echocardiography, prospectively quantified MR, and ejection fraction (EF). The New York State Cardiac Surgery Reporting System infrastructure was used to prospectively collect in-hospital patient variables and outcomes. Social Security Death Benefit Index was used to determine long-term survival. Odds ratio and significance (P value) are presented for each determined risk factor. There were 841 patients (37.5%) with no MR, 1137 (50.7%) with mild MR, and 264 (11.8%) with moderate MR. The patients with moderate MR were more likely to be older, female, and have more renal disease, previous MI, congestive heart failure, previous cardiac surgery, and lower EFs. Hospital mortality was independently and significantly associated with renal disease, decreasing EF, increasing age, previous cardiac operation, and cerebral vascular disease. Multivariable analysis revealed decreased survival with increasing age, previous operation, congestive heart failure, diabetes, nonelective operation, decreasing EF, and the presence of moderate MR (expβ = 1.49; P=0.007) and mild MR (expβ = 1.34; P=0.033).
Conclusions— Independent of ventricular function, mild and moderate functional mitral insufficiency are associated with significantly decreased survival in patients undergoing CABG. Whether correction of moderate functional MR at the time of CABG improves outcome still needs to be determined.
Functional mitral regurgitation (MR) secondary to coronary artery disease, also known as ischemic MR (IMR), is not rare in patients with coronary artery disease.1 MR, even if mild, is an independent predictor of post-myocardial infarction (MI) mortality.2 Similarly, the presence of MR in patients undergoing percutaneous coronary intervention decreased survival over 3 years.3 MR has also negatively influenced long-term outcomes after surgical revascularization.4 Although it is well accepted to correct severe MR at the time of coronary artery bypass grafting (CABG), there is less consensus about the indications for intervention with either 2+ or 3+ MR.5–8 In addition, it is uncertain whether the poorer outcomes in this group are dependent on the valvular dysfunction or whether it is merely a surrogate marker of extensive comorbidities, particularly the amount of ventricular dysfunction. Short of randomization, the determination of the appropriateness of such valvular intervention will depend on the analysis of the risks and expected benefits. We reviewed our patients to explore the impact of less-than-severe MR at the time of isolated CABG.
All of the patients undergoing isolated CABG from 1996 through 2004 were identified in the cardiac surgery institutional database of New York University Medical Center, Tisch Hospital. All of the patients undergoing cardiac surgery at New York University were intraoperatively studied with transesophageal echocardiography (TEE), which analyzed leaflet pathology and graded MR and left ventricular (LV) ejection fraction (EF). We identified 2242 patients without any structural leaflet pathology and less-than-severe MR, and these are the subjects of this report. Definitions of preoperative risk factors are those used in the New York State Cardiac Surgery Reporting System. This is a state-mandated, audited cardiac risk factor and outcome data collection instrument where the data are prospectively collected by trained nurse clinicians. Follow-up survival information was obtained by querying the Social Security Death Benefit Index.
All of the transesophageal echocardiography examinations were performed after induction of anesthesia and before the start of each case. Examinations were done by an attending cardiologist or appropriately credentialed anesthesiologists and recorded for later interpretation by an attending cardiologist. Examination of the maximal length and width of the regurgitant jet in the 4- and 2-chamber views were used in the determination of the severity of MR.9 Moderate-to-severe and severe MR were excluded from this study; none and trace were analyzed as no MR.
Statistical analysis was performed with SPSS statistical software (SPSS Inc). Continuous variables were analyzed by Student’s t test and categorical variables by the χ2 test. Multivariate analyses of hospital mortality were performed with backwards stepwise logistic regression; survival analysis was performed using the Cox methodology.
We had full access to the data and take full responsibility for its integrity. We have all read and agree to the article as written.
We identified 2242 patients undergoing isolated surgical revascularization without any structural mitral valve abnormalities. Of this group, 841 patients (37.5%) had no MR, 1137 (50.7%) had mild MR, and 264 (11.8%) had moderate MR. The patients with moderate MR were more likely to be older, female, and have more renal disease, previous MI, congestive heart failure (CHF), previous cardiac surgery, and lower EFs (Table 1.) The comorbidities of diabetes, cerebral vascular disease, peripheral vascular disease, chronic obstructive pulmonary disease, and the presence of multivessel disease did not significantly differ among the groups.
Overall hospital mortality was 1.9%. The incidence of mortality associated with the presence of each risk factor, as well the subanalysis by MR category, is presented in Table 2. Almost universally, increased MR was associated with an increased risk ratio for any given individual risk factor. Multivariable analysis revealed that hospital mortality was independently and significantly associated with renal disease, decreasing EF, increasing age, previous cardiac operation, and cerebral vascular disease (Table 3). Nonemergent operation, CHF, and worse MR category were weakly associated with increased mortality.
Five-year all-cause mortality survival was 84±1.0% for all of the patients. Survival was 86±1.0% for patients with no MR, 84±1.0% for patients with mild MR, and 70±1.0% for patients with moderate MR (P<0.001; Figure 1). Multivariable analysis for all survival revealed that age, previous operation, CHF, diabetes, nonelective operation, and decreasing EF were all associated with decreased overall survival (Table 4). Likewise, both the presence of moderate MR (expβ = 1.49; P=0.007) and mild MR (expβ = 1.34; P=0.033) were independently associated with decreased overall survival.
This study demonstrates that, independent of ventricular dysfunction, both mild and moderate MR are associated with decreased survival. This contravenes the previous assumption that the poor outcomes associated with coronary disease and functional MR were a direct result of the ventricular injury and associated comorbidities, that is, functional MR is not a surrogate variable for LV dysfunction and coronary disease burden. This is similar to the recent findings of Schroder et al10 at Duke University who saw worse outcomes associated with both mild and moderate MR. Unlike their study, which included MR of all types, not just functional, we limited our analysis to those patients with functional MR only. In addition to the etiologic differences of the mitral dysfunction, the Duke group routinely used provocative testing with afterload challenge and volume loading in the operating room to “offset” the potential effects of general anesthesia in assessing the MR; this is not our protocol. The negative long-term survival impact of mild MR parallels the findings in the post-MI2 and the postpercutaneous coronary intervention3 patient populations. This is despite the fact that neither of these often quoted series had a very in-depth analysis of patient comorbidities as in our current series.
The recent case-controlled CABG alone study by Lam et al11demonstrated a significant increase in relative risk of hospital death in the presence of moderate MR (mild MR was not analyzed). Using propensity-matched cohorts, they found the presence of moderate IMR as an independent risk factor for mortality and that this risk persisted for 5 years as compared with controls without MR. They concluded that there was no reliable improvement in MR after CABG, and there was an increased mortality, similar to series, which persisted into the late period. The importance of moderate MR as an independent risk factor for hospital mortality only reached borderline significance in our series. Of note, moderate MR in their series was composed of both 2+ and 3+ MR.
The potential surgical impact of repairing MR was evaluated by the recent Cleveland Clinic analysis,12 which compared survival outcomes of degenerative and functional ischemic MR patients who underwent revascularization and repair. Via propensity analysis, they found that the “large survival discrepancies between patients with ischemic and degenerative MR is attributable to the differences in patient profiles, particularly the extent of ischemic disease and LV dysfunction.” Although their patient population was skewed toward severe MR, 15% of ischemic patients had 2+ MR. and 51% had 3+ MR. By correcting the MR, long-term survival became dependent on the preexisting comorbidities.
Despite the prospective collection of our data, this study is retrospective. The strength of the study is that it represents a very large cohort of consecutive patients from an institution very experienced with IMR. Although it is acknowledged that there is a significant incidence of intraoperative MR underestimation by TEE,13 this methodology was applied equally to our entire cohort, and this is exactly the information that is presented to the surgeon in the operating room. Using this type of data will help establish an understanding of the incremental risk imposed on the patient as viewed intraoperatively by the surgeon. In addition, the presence of advanced degrees of MR can lead to an overestimation of ventricular performance based on EF. However, this value is still the most widely reliable and applicable clinical indicator of LV performance available.
In all patients undergoing isolated CABG without severe MR, the presence of moderate MR, and even mild MR, is associated with decreased survival. This association is independent of the severity of LV dysfunction and the numerous comorbidities seen in this patient cohort. Furthermore, no association was found between the amount of coronary artery disease and the outcomes in these patients. However, it remains unknown whether MV repair at the time of CABG will improve the survival of patients with mild or moderate MR or alter the unfavorable natural history of this disease.
Presented at the American Heart Association Scientific Sessions, Dallas, Tex, November 13–16, 2005.
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