Background
Although the prognostic impact of a moderate degree of ischemic mitral regurgitation (IMR) is well known, there are no data regarding the potential role of a mild degree of IMR. The aim of this study was to evaluate the impact of a mild degree (effective regurgitant orifice area < 20 mm 2 ) of IMR on left ventricular (LV) remodeling and heart failure (HF).
Methods
A retrospective study was conducted in 35 patients with mild IMR that were propensity matched with 35 patients without IMR (controls). The population was evaluated between 3 and 6 months after first myocardial infarction and at 6 and 12 months, measuring LV volumes, ejection fraction, and the degree of mitral regurgitation. HF events requiring hospitalization were recorded.
Results
The two groups were similar at baseline. During follow-up, patients with IMR showed significant increases in LV end-diastolic and end-systolic volumes and no change in ejection fractions, whereas controls did not show significant changes in volumes but did show increases in ejection fractions. Patients with IMR showed significantly higher end-systolic volumes at 6 months ( P = .003) and 12 months ( P = .007) and significantly higher end-diastolic volumes at 6 months ( P = .048) and 12 months ( P = .03) and lower ejection fractions at 6 months ( P = .0001) and 12 months ( P = .002) compared with controls. Patients with IMR experienced a significantly higher incidence of HF than controls (62% vs 23%, P = .001). At 6 months, in six patients mitral regurgitation degree changed from mild to moderate, and in one patient from mild to severe. Interestingly, 71.5% of patients who experienced increases in mitral regurgitation degree had no coronary revascularization ( P = .04).
Conclusions
Mild IMR affects the LV remodeling process, increases its degree over time, and determines a higher rate of HF.
Ischemic mitral regurgitation (IMR) is a common complication of the chronic phase after myocardial infarction, occurring as a consequence of left ventricular (LV) dysfunction and remodeling. Its presence is associated with an increased risk for death and heart failure (HF) regardless of the degree of LV systolic function but with a graded positive relation between IMR severity and risk for death and HF.
It is well known that a moderate degree of IMR (effective regurgitant orifice area [EROA] < 20 mm 2 ) conveys a more than threefold risk for HF and a more than twofold risk for death in these patients. Moreover, it is demonstrated that mild IMR (EROA < 20 mm 2 ) detected in the chronic phase after Q-wave myocardial infarction is associated with a better prognosis compared with patients with EROA > 20 mm 2 and with worse outcomes compared with controls, whereas there are no data regarding the potential impact of the presence of a mild degree of IMR in the chronic phase after myocardial infarction on LV remodeling and its effects on prognosis. Nevertheless, there is agreement that patients with moderate to severe IMR should undergo mitral valve surgery at the time of coronary artery bypass grafting, but there is no consensus about the management of mild IMR. Patients with mild IMR are treated with revascularization alone, because a mild degree of IMR is presumed to have no prognostic implications.
Therefore, the aim of the present study was to evaluate the impact of a mild degree of IMR (EROA < 20 mm 2 ) on LV remodeling and HF episodes.
Methods
Eligibility Criteria
We conducted a retrospective study in which eligible patients (patients and controls) were initially selected from our database if all the following inclusion criteria were satisfied: (1) prior myocardial infarction; (2) echocardiography between 3 and 6 months after first myocardial infarction; (3) ischemic LV systolic dysfunction, defined as LV ejection fraction < 50% measured by two-dimensional echocardiography; (4) presence or absence of mild IMR (EROA ≤ 20 mm 2 ); (5) 1-year complete echocardiographic and clinical follow-up; and (6) quantification of mitral regurgitation (MR) using the proximal isovelocity surface area method at baseline and at echocardiographic follow-up.
Myocardial infarction was defined using European Society of Cardiology, American College of Cardiology Foundation, American Heart Association, and World Health Organization 2000 and 2007 criteria. Exclusion criteria were (1) recent myocardial infarction (<3 months), (2) moderate to severe MR (EROA ≥ 20 mm 2 ), (3) previous cardiac surgery, (4) MR due to organic valve disease, and (5) clinical or echocardiographic evidence of other cardiac diseases, such as organic valvular, pericardial, congenital, or infiltrative heart diseases. New York Heart Association class, medications, cardiac resynchronization therapy with implantable cardioverter-defibrillator implantation, revascularization procedures, and comorbidities such as hypertension, diabetes mellitus, atrial fibrillation, renal insufficiency, and chronic obstructive pulmonary disease were also recorded.
Matching
Patients and controls were all post–myocardial infarction and satisfied all eligibility criteria. Patients without MR were matched to those with MR for age, sex, ejection fraction, and LV end-diastolic volume using propensity score matching, to ensure baseline comparability of these major determinants of outcome, as previously described by Rosenbaum and Rubin. The matching was computerized, blinded, and performed before any outcome information was obtained. The procedure was as follows: multivariate logistic regression was used to identify variables predictive of two-group membership: age, sex, ejection fraction, and end-diastolic and end-systolic volumes. A propensity score was calculated for each patient. A logistic regression analysis generated a coefficient for each variable. A given patient’s value for a variable was transformed into risk units by multiplying it by the coefficient. For example, if the coefficient was 2.5 and the variable was male gender, with a value of 1 (for “yes”), the result would be 2.5 risk units. If the coefficient was 0.43 for the variable end-diastolic volume and a patient had a volume of 100 mL, the result would be 43 risk units. This procedure was continued through the list of model variables, multiplying the coefficient by the specific value for each variable. The resulting products were then summed. To this sum was added the intercept of the model. The final score was the propensity score. A propensity score difference of 0.1 was used as a maximum caliper width for matching the two groups.
Echocardiographic Evaluation
After the exclusion of patients with organic MR, the severity of MR, the degree of LV remodeling and dysfunction, and diastolic function were evaluated. After inclusion, the echocardiographic evaluation was performed at 6-month and 12-month follow-up. The presence or absence of MR was determined by color flow imaging. The severity of MR was graded with quantitative measurement using the proximal isovelocity surface area method, always in the four-chamber view. MR was classified as mild (0.10 cm 2 ≤ EROA < 0.20 cm 2 ), moderate (0.20 cm 2 ≤ EROA < 0.40 cm 2 ), or severe (EROA ≥ 0.40 cm 2 ). In patients with atrial fibrillation, the measure of EROA was done in triplicate and averaged. LV remodeling was evaluated from LV end-diastolic and end-systolic volumes calculated using biplane Simpson’s method. LV function was assessed using the ejection fraction. Wall motion score index was calculated using a 17-segment model. Diastolic function was evaluated using pulsed-wave Doppler performed in the apical four-chamber view to obtain mitral inflow velocities. Early (E) and atrial (A) peak velocities, the E/A ratio, and E velocity deceleration time were measured. Furthermore, pulsed-wave Doppler tissue imaging was performed in the apical four-chamber view to acquire early (Em) and late (Am) lateral mitral annular velocities. The E/Em ratio was calculated.
Left atrial size was evaluated by left atrial volume using the biplane Simpson’s rule for the left atrium and was measured at end–ventricular systole, when the left atrial chamber is at its greatest dimension. LV volumes and left atrial volume were indexed to body surface area.
Blood pressure, heart rate, and New York Heart Association class were also recorded.
Follow-Up
Follow-up data were obtained from inpatient and outpatient medical records and from telephone interviews. Beta-blockers and angiotensin-converting enzyme inhibitors were up-titrated in all patients until the evidence-based target dose or maximum tolerated dose was reached. Diuretics were used in patients with clinical signs or symptoms of congestion, and the dosage was adjusted on the basis of these symptoms using the lowest achievable dose. All HF events requiring hospitalization and deaths were recorded. HF events required hospitalization during follow-up were defined as follows: acute exacerbation of chronic HF requiring hospitalization or acute cardiogenic dyspnea characterized by signs of pulmonary congestion, including pulmonary edema, using validated criteria. Cardiac deaths were ascertained by reviewing death certificates or autopsy records when available.
The institutional review board and ethics committee approved the study protocol.
Statistical Analysis
Data are expressed as mean ± SD for continuous variables and as percentages for categorical variables. Group comparisons were performed using analysis of variance, paired and unpaired t tests, and χ 2 tests as appropriate. P values < .05 were considered significant.
To determine the intraobserver and interobserver variability of EROA, all measurements were repeated by the same observer in two sessions and by a second independent observer in 12 randomly selected patients. All measurements were obtained from the series of cardiac cycles digitally stored. Intraobserver and interobserver variability was measured using the Bland-Altman method. These were also expressed as the ratio of the standard deviations of the differences between the two measurements divided by the respective mean values.
Results
Baseline Characteristics
From 2002 to 2009, 258 patients were identified. The 169 patients with IMR were propensity matched with 89 patients without IMR, leading to a final study population of 35 pairs of patients and controls. No patient died during follow-up.
Baseline clinical and echocardiographic characteristics of patients with and without MR are summarized in Tables 1 and 2 . The baseline EROA in the patient group was 15.3 ± 2.5 mm 2 , whereas at 12 months, the mean value of EROA of subjects with MR was 18.2 ± 7.1 mm 2 ( P = .10). Importantly, gender, ejection fraction, end-diastolic and end-systolic volumes, and therapy were similar in both groups. The wall motion score index and the location and number of hypokinetic and akinetic segments were similar in both groups ( Table 3 ). Forty-nine patients (70%) were revascularized, 35 (70%) by percutaneous transluminal coronary angioplasty, 10 (20%) by coronary artery bypass grafting, and five (10%) by both procedures. With regard to comorbidities, 35% of patients had diabetes mellitus, 29.2% had chronic renal failure, and 12.5% had atrial fibrillation. Implantable cardioverter-defibrillators were placed in 21% of patients and a implantable cardioverter-defibrillator–cardiac resynchronization therapy in 5.6% of patients.
| Variable | Patients with IMR | Controls | P |
|---|---|---|---|
| Age (y) | 73.4 ± 8.6 | 63.1 ± 11.6 | .0001 |
| Men | 85.7% | 91.4% | .45 |
| NYHA class | 2.1 ± 0.3 | 1.8 ± 0.6 | .01 |
| One-vessel disease | 15.7% | 11.4% | .40 |
| Two-vessel disease | 17.1% | 22.8% | .30 |
| Three-vessel disease | 17.1% | 15.7% | .80 |
| Systolic BP (mm Hg) | 134.4 ± 9 | 132 ± 8 | .80 |
| Diastolic BP (mm Hg) | 81 ± 6.1 | 81.4 ± 7.2 | .70 |
| HR (beats/min) | 69 ± 7.1 | 67.7 ± 5.1 | .40 |
| Revascularization | 59% | 83.3% | .06 |
| ACE inhibitors | 82.7% | 80% | 1.00 |
| β-blockers | 70.5% | 70% | 1.00 |
| Spironolactone | 23.5% | 10% | .34 |
| Anterior MI | 48% | 40% | .63 |
| Inferior-lateral MI | 52% | 60% | .63 |
| Diabetes | 51.4% | 20% | .022 |
| Renal failure | 34% | 22.8% | .042 |
| Atrial fibrillation | 20% | 5.7% | .12 |
| ICD | 25.7% | 17% | .56 |
| ICD-CRT | 8.5% | 2.8% | .60 |
| Variable | Patients with IMR | Controls | P |
|---|---|---|---|
| EDV (mL/m 2 ) | 83.1 ± 19.2 | 85.2 ± 22.4 | .60 |
| ESV (mL/m 2 ) | 54.7 ± 20.4 | 51.8 ± 15.2 | .50 |
| SI | 0.56 ± 0.12 | 0.48 ± 0.07 | .09 |
| EF (%) | 35.7 ± 8.2 | 39.3 ± 7.8 | .06 |
| E/A ratio | 0.97 ± 0.58 | 0.80 ± 0.17 | .40 |
| DT (msec) | 281.5 ± 59 | 231.4 ± 73 | .20 |
| E/Em ratio | 11.6 ± 2.4 | 11 ± 2.3 | .50 |
| Atrial volume (mL/m 2 ) | 51.4 ± 17.7 | 34.4 ± 10.7 | .01 |
| Tenting area (cm 2 ) | 2.5 ± 0.22 | — | — |
| Coaptation depth (cm) | 0.8 ± 0.12 | — | — |
| Variable | Patients with IMR | Controls | P | With MR progression | Without MR progression | P |
|---|---|---|---|---|---|---|
| WMSI | 1.6 ± 0.2 | 1.5 ± 0.2 | .18 | 1.7 ± 0.2 | 1.6 ± 0.19 | .10 |
| Akinetic segments | 3.9 ± 1.5 | 3.6 ± 1.1 | .40 | 4.4 ± 1.7 | 3.7 ± 1.5 | .30 |
| Hypokinetic segments | 2.8 ± 2.9 | 2.1 ± 2.2 | .20 | 3.4 ± 4.8 | 2.7 ± 2.3 | .70 |
| Akinetic segments in LAD | 2.1 ± 2.3 | 1.6 ± 2.1 | .40 | 2.0 ± 0.7 | 2.2 ± 2.4 | .40 |
| Hypokinetic segments in LAD | 1.0 ± 1.7 | 0.9 ± 1.3 | .70 | 1.4 ± 2.6 | 1.0 ± 1.5 | .60 |
| Akinetic segments in Cx | 1.2 ± 1.6 | 1.4 ± 1.7 | .60 | 1.5 ± 1.9 | 1.1 ± 1.6 | .60 |
| Hypokinetic segments in Cx | 1.2 ± 1.6 | 1.0 ± 1.3 | .40 | 1.3 ± 1.4 | 1.2 ± 1.6 | .50 |
| Akinetic segments in RCA | 0.5 ± 0.9 | 0.6 ± 0.9 | .80 | 1.2 ± 1.2 | 0.4 ± 0.7 | .10 |
| Akinetic segments in RCA | 0.6 ± 0.9 | 0.2 ± 0.6 | .05 | 0.7 ± 0.9 | 0.6 ± 0.9 | .70 |
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