Heart Views. 2011 Jul-Sep; 12(3): 9398. doi: 10.4103/1995-705X.

95063 PMCID: PMC3345146

Mild Functional Ischemic Mitral Regurgitation Following Acute Coronary Syndrome: A Retrospective Study
Sadip Pant, Pritam Neupane,1 Om Biju Pant,2 Raju Paudel,3 M. P. Kavin Kumar,4 C. S. Vijayashankar,5 and Rajendra Man Shrestha6
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Abstract
Background:

Ischemic mitral regurgitation is a frequent complication of acute coronary syndrome. It primarily occurs in patients with a prior myocardial infarction but also may be seen with acute ischemia, a setting in which the MR typically resolves after the ischemia resolves. The vast majority of patients have functional ischemic MR. In these individuals, the papillary muscles, chordae, and valve leaflets are normal. However, the leaflets do not coapt and restricted leaflet motion is frequently noted on echocardiography. Ischemic mitral regurgitation indicates a poor prognosis after acute myocardial infarction. This study addresses the clinical characteristics of patients of acute coronary syndrome with mild functional ischemic mitral regurgitation and its impact on immediate in-hospital cardiovascular outcomes and death.
Patients and Methods:

From March 2006 through May 2007, patients who underwent 2dimensional (2D) color doppler echocardiographic quantification of ischemic mitral regurgitation within 10 days of admission for acute coronary syndrome (ACS) in Manipal Teaching Hospital, a tertiary

hospital in the western region of Nepal were noted. The demographic details, conventional risk factors of coronary artery disease, clinical and laboratory findings, treatment course and in-hospital outcomes of all the patients with mild functional ischemic MR following ACS in that time duration were recorded in a designated Performa. A total of 94 patients enrolled in the study were divided into two groups: Group I with mild functional ischemic MR and Group II without MR on 2D echocardigraphic assessment. Patient characteristics, risk factors, ejection fraction, and cardiovascular outcome and death among the two groups were compared and analyzed using software package SPSS 17.0 version.
Results:

Group I constituted 64.89% of the study population and Group II comprised of 35.11%. The patients in Group I was more likely to be elderly diabetic (P<0.05), and smokers with hypertension (P < 0.05). Mild functional ischemic MR was more common in patients with STEMI as compared to those with unstable angina and NSTEMI (55.7%, 36.1%, and 8.2%; P < 0.05).The mean ejection fraction in the first group was 54.84% in contrast to 58.92% observed in group II (P < 0.05).The type of wall involvement inferred from EKG analysis was homogeneously distributed in both the groups. Finally, there was no difference in immediate in-hospital (within 10 days) mortality or cardiovascular outcomes (heart failure, ventricular tachycardia/fibrillation, hypotension, and cardiogenic shock) between these two groups.
Conclusion:

Ischemic mitral regurgitation following acute coronary syndromeare more likely in elderly diabetics and hypertensive smokers. It is a more common finding in STEMI. Although mild MR following ACS does reduce ejection fraction, the immediate (within 10 days) in-hospital mortality and cardiovascular outcomes are not significantly altered.

Keywords: 2D Doppler Echocardiography, acute coronary syndrome, ischemic mitral regurgitation

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INTRODUCTION
Ischemic mitral regurgitation (MR) is a complication of coronary heart disease. It primarily occurs in patients with a prior myocardial infarction (MI) but also may be seen with acute ischemia, wherein the MR typically resolves after the ischemia resolves.[1] The vast majority of patients have functional ischemic MR.[2] In these individuals, the papillary muscles, chordae, and valve leaflets are normal. However, the leaflets do not coapt and restricted leaflet motion is frequently noted on echocardiography.[35] The reported incidence of MR is as high as 50% in echocardigraphic studies.[6] Ischemic MR is graded based on severity into mild, moderate or severe; mild being the commonest of the three.[68] Detecting and quantifying ischemic mitral regurgitation is necessary since its presence plays an essential role in post-MI risk stratification.[7] Acute ischemic MR is seen with increased frequency in elderly, women and nonsmokers.[6,9] Further, ischemic MR following MI is associated with increased risk of heart failure and death, the magnitude of which correlates with severity of MR.[1,6,7,9 11] Data from Nepal in this regard is missing and hence this study was undertaken with an objective to define patient characteristics associated with mild functional ischemic MR in patients of ACS and also observe its effect on immediate (within 10 days) in-hospital cardiovascular outcomes and mortality.
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PATIENTS AND METHODS

The study population consisted of 94 patients of acute coronary syndrome, admitted and managed in the intensive care unit of

Manipal Teaching Hospital from March 2006 to June 2007. The demographic details, clinical and laboratory findings, conventional risk factors of coronary artery disease assessment, echocardiographic findings, management and outcome of the cases were recorded in a designated Performa. Variables were defined at the beginning of the study as follows: 1. Diabetes mellitus (DM): Symptoms of diabetes plus a random plasma glucose concentration greater than 200 mg/dL or prior diagnosis of DM before admission. 2. History of hypertension: Systolic blood pressure of at least 140 mmHg or diastolic blood pressure of at least 90 mmHg on three separate readings at least 6 hours apart within 24 hours of admission or prior history of HTN. 3. Hyperlipidemia: Total cholesterol level exceeding 200 mg/dL or triglycerides greater than 150 mg/ dL within 24 hours of admission or prior history of hyperlipidemia. 4. Obesity: Body mass index > 25 kg/m2. 5. History of smoking: Included smoking cigarette, cigar, pipe, or chewing tobacco. 6. The standard case definition of the American Heart Association (AHA) was used for classifying patients into categories of unstable angina, Non ST Elevation Myocardial Infarction (NSTEMI) and ST Elevation Myocardial Infarction (STEMI).[12] 7. Two-dimensional echocardiogram was used to assess mitral valve regurgitation (MR). Severity of MR was defined based on 2003 American Society of Echocardiography's consensus statement on echocardiographic quantification of valvular regurgitation corroborated by the 2006 ACC/AHA consensus statement on management of valvular heart disease using multiple (structural, qualitative and quantitative Doppler) parameters.[13,14] 8. Immediate in-patient hospital events were defined at the beginning of the study as those occurring within 10 days of

hospitalization. Cardiovascular outcomes referred to heart failure, ventricular tachycardia/fibrillation, hypotension, and cardiogenic shock. Exclusion criteria included patients with congestive heart failure, cardiomyopathy, valvular heart disease, moderate to severe MR, structural MR, and those patients in whom echocardiography was not performed within 10 days of admission. The study population was divided in two groups namely, Group I (those with mild functional ischemic MR) and Group II (those without MR). The two groups were compared for patient characteristics, conventional risk factors, ejection fraction, type of ACS, wall involvement and the immediate inhospital (within 10 days) outcome and all cause mortality. The SPSS package version17.0 was used for statistical analysis. The categorical data was analyzed using 2 test. Continuous data were expressed using measures of central tendency and frequency distribution. Nonparametric test of association was used whenever data was not found to be in normal distribution by 1-Sample Kolmogorov Smirnov test.
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RESULTS
The study included 94 patients with ACS admitted in Manipal Teaching Hospital, a tertiary hospital in the western region of Nepal from March 2006 to May 2007 who had echocardiography assessment within 10 days of admission. Among them, 61(64.89%) patients had mild functional ischemic MR and were categorized into Group I. The rest of patients 33 (35.11%) were categorized into Group II and were devoid of this finding. Baseline characteristics of patients and conventional risk factors of coronary artery disease (CAD) were noted and tabulated in both the groups [Table 1]. Although there was a difference in mean age between Group I and Group II, the higher mean age achieved in Group I (64.08 10.81) was not statistically significant (P = 0.189).

Table 1 Baseline patient characteristics in the two groups A separate analysis by splitting the study population into two groups, elderly (>65 years) and younger (<65 years) patients, did not reveal statistically significant association with mild functional ischemic MR either (P = 0.864). Similarly, there was no significant difference in these groups with regard to gender, or presence or absence of any of the conventional risk factors of CAD (hypertension, smoking, diabetes mellitus, obesity, or dyslipidemia). However, when a combined analysis of conventional risk factors was performed, two significant associations were evident. First, hypertensive smokers were significantly higher in Group I compared to Group II (P = 0.021, OR = 3.693, and 95% CI = 1.19211.441). Second, there was a significant association of elderly (>65 years) diabetics with mild functional ischemic MR in Group I compared to Group II (P = 0.020, OR = 6.000, and 95% CI = 1.21129.727). Furthermore, ejection fraction (as a measure of systolic function) in the two groups was observed. The distribution of ejection fraction data among these two groups was not found to be normal using 1-Sample Kolmogorov Smirnov test (P = 0.024). Therefore, the comparison of mean ejection fraction in Group I (54.84 8.27) and Group II (58.91 10.25) was done using non parametric test (Mann Whitney U test). On analysis, there was a significant difference in mean ejection fraction between the two groups (P = 0.008, U = 649.5). The three variants of ACS namely, unstable angina, NSTEMI and STEMI were also evaluated in each group and presented in Table 2. On categorizing and comparing these three entities in each group [Table 3], parametric test of association revealed that among patients

in group I, STEMI was 4.25 times more likely than unstable angina (P = 0.03, OR = 4.25, and 95% CI = 1.61011.220) and 3.935 times more likely than unstable angina and NSTEMI together (P = 0.05, OR = 3.935, 95% CI 1.533-10.103). There was however no significant difference between unstable angina and NSTEMI among these two groups.

Table 2 Type of ACS in the two groups

Table 3 Association of various types of ACS with mild functional ischemic MR The electrocardiography (EKG) of patients in both the groups were analyzed and grouped into 10 categories, viz. septal, lateral, anterior, anteroseptal, anterolateral, extensive anterior, inferior with or without posterior, inferior with extensive anterior, right ventricular, new onset LBBB and no EKG changes. Their distribution in group I and group II is represented in Table 4. The type of involvement was not grouped into pairs and tested separately with reference to each group due to very few sample size in some type of involvement. Statistical analysis revealed that the number of cases with each wall involvement was homogenously distributed in group I compared to group II (P value .706).

Table 4 Cross tabulation of various types of wall involvement in the two groups. The wall Involvement was inferred from EKG analysis of the patients Finally, the in-hospital complications and all-cause mortality within 10 days of admission in each group were recorded. The distribution of heart failure, VT/ VF, hypotension, cardiogenic shock, and death in each group has been presented in Table 5.There was no significant difference among these two groups with regards to heart failure (P = 0.826), VT/VF (P = 0.656), hypotension (P = 0.133), cardiogenic shock (P = 0.293) and death (P = 0.195) within 10 days of hospitalization. Although, 4.1% of the patients in group I died during the period of hospitalization as compared to 0% in group II, this difference failed to achieve statistical significance (P = 0.195).

Table 5 Comparison of immediate (within 10 days) cardiovascular outcomes and all cause mortality during the period of hospitalization in the two groups
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DISCUSSION
Mild functional ischemic MR is a common finding following acute coronary syndrome.[2] The incidence of ischemic mitral regurgitation

varies considerably among patients with acute coronary syndrome. Diagnostic modality plays an important role for this great disparity in the reported incidence of Ischemic MR following ACS.[1,6,9] Other factors that may affect the reported incidence include degree of MR, reported, therapy rendered, time from onset of infarct, and selection bias.[15] Studies have reported its incidence from 9-13% using cardiac catheterization[9,16,17] to 50% in echocardiographic studies.[1,6,17] In our study assessment was done using a 2D Doppler echocardiography and we found mild ischemic MR in 64.5% of patients with acute coronary syndrome. The reported prevalence of functional ischemic MR also varied considerably across the spectrum of acute coronary syndrome in our study. It was evident in 50% of patients with unstable angina, 80.9% of patients with NSTEMI and 62.5% of patients with STEMI. STEMI patients were found to have nearly 4 times more chance of having mild functional ischemic MR compared to unstable angina and NSTEMI combined. It has been observed in various study population that ischemic mitral regurgitation following acute coronary syndrome are more common in elderly, women and nonsmokers.[6,9] Bursi et al. reported a graded positive association between ischemic mitral regurgitation and hypertension and diabetes mellitus.[6] However, Pellizzon et al.[9] and Lamas et al.[18] reported that ischemic mitral regurgitation and diabetes or hypertension was not significantly related. In our study, we did not find a significant association of mild functional ischemic MR with age, sex or any of the conventional risk factors alone. However, on combining the conventional risk factors, mild functional MR following acute coronary syndrome was found to be 3.7 times more common in elderly (>65 years) diabetics and 6 times more likely in hypertensives who were smokers. Mild ischemic functional MR is rarely associated with any hemodynamic change. However, it is quite possible that mild MR

shortly after acute coronary syndrome might increase or decrease in severity following recovery and remodeling of the left ventricle.[15] We found that mild functional MR following ACS reduces ejection fraction (a measure of systolic function) significantly by a mean of approximately 4%. But there was no clinically or statistically significant association of this finding with hypotension, cardiogenic shock or heart failure. It has been established by various studies that ischemic MR is an important predictor of the development of heart failure, even in patients with a normal left ventricular ejection fraction at the time of the MI.[6,10,11] In one study, patients with ischemic MR had a much higher risk of heart failure than those without ischemic MR (adjusted relative risk of 3.65) at five years after ST elevation MI.[10] Similar finding of increased risk of heart failure at five years post MI was also observed in the study by Bursi et al.[6] In one series, the heart failure risk associated with moderate to severe MR was substantially increased even at two years post MI in patients with normal left ventricular ejection fraction at initial evaluation.[11] Due to lack of follow-up data on the patients, our analysis was limited to events within the 10 days of hospitalization due to acute coronary syndrome. Moreover, we included only mild functional MR in our study. At 10 days, we found no increased risk of heart failure among patients with mild functional ischemic MR compared to those patients with ACS devoid of this finding. Finally, ischemic MR following MI is associated with increased mortality, the magnitude of the mortality risk correlating with the severity of the MR.[1,2,6,9,11,1619] In an analysis from the CADILLAC trial of 1976 patients with an acute ST elevation MI, 192 (10 %) had mild MR and 58 (3 %) had moderate to severe MR.[9] Patients with worse MR had significantly higher mortality rates at 30 days (1.4, 3.7, and 8.6 % for no MR, mild MR, and moderate to severe MR, respectively) and at 1 year (2.9, 8.5, and 20.8 %). A similar increase in risk was also noted in a prospective study of 303 patients with a previous Q wave MI among which 194 had ischemic MR.[1] At five years, those with ischemic MR had a higher rate of cardiac

mortality (50 versus 30 %). In a report limited to patients with NSTEMI, survival at 431 days decreased as the severity or MR increased.[7] MR was the only predictor of poor survival in multivariate analysis in that study. Furthermore, Lehmann et al. had reported 10 day all cause morality among patients with no, mild, and moderate to severe MR following ACS to be 2.25, 9.1%, and 20%, respectively.[17] In our study, although the group with mild functional MR following ACS had 4.9% mortality at 10 days as compared to the group without this finding (0%), this difference could not achieve statistical significance (P = 0.195). One reason could be the small sample size in our study. A larger sample size and long term follow up data would be required to further comment on this finding in our population. Also, we could not further categorize mortality data into all cause mortality and cardiovascular mortality as autopsy was not done in many cases for various reasons.
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LIMITATIONS
First, our study had a small sample size with a total of only 94 cases. Second, the study involved observation of in-hospital events only and follow up studies were not done subsequently after discharge. Therefore, time to event analysis could not be performed thereby making the data on cardiovascular outcome and death primitive. Third, interobserver variation in the grading of MR could not be eliminated. Further, cardiac catheterization in patients could have added better insight into the hemodynamic changes associated with mild ischemic functional MR in these patients. However, cardiac catheterization was not done in the studied samples. Finally, exercise echocardiography was not done in the study, which could have increased the yield of cases as well as aided in assessing the prognosis better.
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CONCLUSION
Mild functional ischemic mitral regurgitation following acute coronary syndrome is a very common finding on echocariographic analysis. It was found to be more likely in elderly diabetics, hypertensive smokers and STEMI as compared to unstable angina and NSTEMI. Mild functional MR following ACS does not result in significant hemodynamic changes. The immediate (within 10 days) in-hospital mortality and cardiovascular outcomes are not significantly altered by this finding.
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ACKNOWLEDGEMENTS
We thank Dr. R Paudel for his logistic support.
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Footnotes
Source of Support: Nil Conflict of Interest: None declared. Go to:

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