Echocardiograms and left ventricular (LV) filling pressure were obtained from 95 patients with chronic severe mitral regurgitation (MR) and 16 patients with acute severe MR. All patients underwent catheterization for preoperative examinations and LV filling pressure measurements. A total of 52 age-, gender- and co-morbidity–matched patients with negative coronary angiographic results served as the controls. Echocardiography, including assessment of left atrial (LA) distensibility, was performed simultaneously. LA distensibility correlated logarithmically with the LV filling pressure. However, the early-diastolic mitral inflow velocity divided by the early-diastolic mitral annular velocity (mitral E/E′) correlated linearly with the LV filling pressure. Bivariate correlation analysis revealed that LV filling pressure correlated positively with the maximum and minimum indexed LA volume, as well as the E/E′, but the LV filling pressure correlated negatively with LA distensibility, LA ejection fraction, and LV ejection fraction. However, the MR regurgitation volume was associated only with the maximum and minimum indexed LA volume. Receiver operating characteristic curve analysis indicated that LA distensibility was not inferior to E/E′ for identifying a LV filling pressure >15 mm Hg. However, to identify acute severe MR, LA distensibility was superior to E/E′. In conclusion, LA distensibility, as is E/E′, is a valuable diastolic parameter. In patients with severe MR, it offers adequate power to assess the LV filling pressure and to identify acute severe MR.
Measurement of the left atrial (LA) volume provides significant prognostic information in the general population and in patients with heart disease, including acute myocardial infarction, left ventricular dysfunction, mitral regurgitation (MR), cardiomyopathy, and atrial fibrillation. A large LA volume, which represents chronic diastolic dysfunction, is associated with a poor outcome, regardless of systolic function. Thus, the LA volume provides a long-term view of whether the patient has diastolic dysfunction, regardless of the loading conditions present at the examination, such as hemoglobin A1c in diabetes mellitus. To date, the relation between the LA volume and left ventricular (LV) filling pressure has not been confirmed directly by simultaneous echocardiographic catheterization. The present study, therefore, assessed the correlation between the LA volume and LV filling pressure in patients with severe MR. Because the LA pressure increases to maintain adequate LV diastolic filling, increased atrial wall tension tends to dilate the chamber and stretch the atrial myocardium. Therefore, the lower the ability of the left atrium to stretch, the greater the pressure in the left atrium. The present study examined: (1) the value of LA distensibility for assessing the LV filling pressure in patients with severe MR, (2) differences in LA distensibility between chronic and acute severe MR, and (3) the relation between LA distensibility and LV filling pressure.
Methods
From January 2006 to April 2009, the present study enrolled 111 patients with severe MR who had undergone cardiac catheterization. The exclusion criteria were as follows: (1) the presence of mitral stenosis, (2) aortic valvular problems greater than mild severity, (3) any abnormality of the atrial septum (eg, atrial septal defect or aneurysm), and (4) rhythm other than sinus rhythm. MR was categorized by mapping jet expansion in the left atrium in the 4- and 2-chamber views at end-systole from 3 separate cardiac cycles. MR was considered severe when the regurgitant jet area occupied >40% of the LA area. The grade of MR was increased by one degree (moderate to severe) in cases of an eccentric MR jet according to the on evidence of reduced color-flow jet areas resulting from the loss of momentum in jets adjacent to the chamber walls. Sixteen patients with acute respiratory distress had acute severe MR, and the actual diagnoses are listed in Table 1 . The remaining patients with chronic respiratory distress or exercise intolerance were grouped according to the presence or absence of significant coronary artery disease (CAD). A significant coronary lesion was defined as diameter stenosis >70% in at least one major coronary artery. The control group consisted of 52 patients matched for co-morbidity, age, and gender with negative coronary angiographic result, despite positive screen test findings for CAD (treadmill exercise test, thallium scan, stress echocardiography, or 64-slide computed tomographic angiography). These patients were selected after confirming the absence of evidence of valvular heart disease using echocardiography. All patients and controls gave written informed consent to participate in the present study, and the institutional review board approved the present study.
| Diagnosis of Acute Severe Mitral Regurgitation | Patients (n) |
|---|---|
| Infective endocarditis with perforation of mitral valve | 2 |
| Infective endocarditis with chordae rupture | 6 |
| Inferior wall myocardial infarction with papillary muscle dysfunction | 5 |
| Inferior wall myocardial infarction with papillary muscle rupture | 2 |
| Chest contusion with flail of mitral valve | 1 |
Coronary angiography was performed to evaluate the hemodynamic condition and to test for CAD. The LV filling pressure was continuously recorded (50 mm/s) using a 6F pigtail catheter placed at the apex of the left ventricle and taken from 3 to 5 end-respiratory cycles if the patient could tolerate breath holding. The LV filling pressure value was calculated as the mean of ≥3 consecutive cardiac cycles. An LV filling pressure >15 mm Hg was considered elevated. In patients with acute severe MR, the mean interval between symptom onset and cardiac catheterization was 4.2 ± 5.3 days.
Echocardiography was performed immediately after the LV filling pressure measurements. The LV ejection fraction was calculated using Simpson’s method for biplane images. Mitral inflow was assessed by pulsed-wave Doppler echocardiography from the apical 4-chamber view. From the mitral inflow profile, the E-wave velocity, A-wave velocity, and E-deceleration time were measured. Pulsed-wave tissue Doppler imaging was performed using spectral pulsed Doppler signal filters, by adjusting the Nyquist limit to 15 to 20 cm/s and using the minimum optimal gain. In the apical 4-chamber view, a 3-mm, pulsed-wave Doppler sample volume was placed at the level of the mitral annulus over the septal border. The pulsed-wave tissue Doppler imaging results were characterized by a myocardial systolic wave (S′) and 2 diastolic waves: early (E′) and atrial contraction (A′). The pulsed-wave tissue Doppler imaging tracing was recorded for 5 cardiac cycles at a sweep speed of 100 mm/s and was used for off-line calculations.
All LA volume measurements were calculated from the apical 4- and 2-chamber views using the biplane area-length method. The LA volumes were measured at 3 points: (1) immediately before the mitral valve opening (maximal LV volume or Vol max ); (2) at the onset of the P-wave on the electrocardiogram (preatrial contraction volume or Vol p ); and (3) at mitral valve closure (minimum LV volume or Vol min ). The LA distensibility was calculated as (Vol max − Vol min )/Vol min . The LA ejection fraction was calculated as (Vol p − Vol min ) / Vol p . In all patients, the LA volumes were indexed to the body surface area.
The apical window was used to record the pulsed-wave velocities at the LV outflow tract and at the mitral annulus and to measure the diameter of the mitral annulus. The time–velocity integral was assessed. The stroke volumes of the mitral annulus and LV outflow tract were obtained by multiplying the cross-sectional area by the respective time–velocity integral. The MR regurgitation volume was calculated as the regurgitation volume = (stroke volume of mitral annulus) − (stroke volume of LV outflow tract).
In the first 50 enrolled cases, the Vol max , Vol min , and Vol p were measured by 2 independent observers. Interobserver variability was calculated as the difference between the values obtained by the 2 observers divided by the mean. The interobserver difference and variability of Vol max was 4.1 ± 5.4 ml and 6.6 ± 8.7%, respectively. The interobserver variability and difference was 8.1 ± 8.9% and 2.9 ± 3.2 ml for Vol min and 6.7 ± 7.4% and 3.1 ± 3.4 ml for Vol p , respectively. Therefore, the interobserver variability in the LA distensibility and LA ejection fraction measurements was 7.8 ± 6.6% and 3.1 ± 3.2%, respectively.
The Statistical Package for Social Sciences, version 12, software (SPSS, Chicago, Illinois) was used for all statistical analyses. All continuous variables are presented as the mean ± SD. Analysis of variance and the post hoc test (Scheffe F-test) for unpaired data were used to evaluate the significance of differences between the groups. A p value of <0.05 was considered statistically significant. A comparison of the clinical characteristics was performed using chi-square analysis for categorical variables. Bivariate analysis, simple correlation, and linear regression analysis were used as appropriate. The relation curve between LA distensibility and LV filling pressure was estimated using the Statistical Package for Social Sciences (SPSS) software. The receiver operating characteristic curve analysis was also performed to assess the sensitivity and specificity when predicting an elevated LV filling pressure (>15 mm Hg) and acute severe MR using an optimal cutoff value for the variables.
Results
Table 1 lists the causes of acute severe MR. Table 2 lists the echocardiographic parameters and other patient characteristics. Of the 111 patients, 51 had chronic severe MR without CAD, 44 had chronic severe MR and CAD, and 16 had acute severe MR. The prevalence of diabetes mellitus, hypertension, and current smoker status was greater in the patients with CAD and acute severe MR. The mitral annular velocities (S′, E′, and A′) and LV ejection fraction tended to be low in the patients with CAD and acute severe MR. Regardless of MR type, the indexed LA volumes for all phases substantially exceeded those of the normal controls. All cases of severe MR were complicated by a high LV filling pressure, with the highest in those with acute severe MR (p <0.0001). Therefore, most of the patients with acute severe MR had tachycardia and respiratory failure. In addition, the group with chronic severe MR and CAD had a lower regurgitation volume than the group with chronic severe MR but no CAD, and both groups had similar LV filling pressures. Additionally, the ratios of LA volume occupied by the regurgitation volume were similar (approximately 70%) for all MR types. The LA ejection fraction tended to be low in the patients with severe MR. Those with acute severe MR had the lowest LA ejection fraction (11.3%). LA distensibility revealed trends similar to the findings for the LA ejection fraction. Normal controls with a normal LV filling pressure consistently exhibited a small LA volume, a high LA ejection fraction, and high LA distensibility. In normal subjects, LA distensibility was > 200% (214 ± 103%) and the LA ejection fraction was approximately 42% (42.8 ± 14.6%). However, the LA distensibility of patients with severe MR was almost < 100%, and was even only 29% in patients with acute severe MR ( Figure 1 ).
| Variable | Control (n = 52) | Chronic Severe MR Without CAD (n = 51) | Chronic Severe MR With CAD (n = 44) | Acute Severe MR (n = 16) | p Value ⁎ |
|---|---|---|---|---|---|
| Age (years) | 67 ± 15 | 68 ± 18 | 70 ± 12 | 68 ± 15 | 0.132 |
| Gender | 0.312 | ||||
| Female | 25 | 26 | 21 | 8 | |
| Male | 27 | 25 | 23 | 8 | |
| Diabetes mellitus | 7 (13.5%) | 6 (11.8%) | 19 (43.1%) | 6 (37.5%) | <0.0001 † ‡ |
| Hypertension | 18 (34.6%) | 17 (33.3%) | 28 (63.6%) | 8 (50%) | 0.001 † ‡ |
| Current smoker | 8 (15.4%) | 9 (17.6%) | 16 (36.4%) | 5 (31.3%) | 0.012 † ‡ |
| Respiratory failure | 0 (0%) | 0 (0%) | 3 (6.8%) | 12 (75%) | <0.0001 ‡ § |
| Creatinine >1.5 mg/dl | 3 (5.8%) | 9 (17.6%) | 11 (25%) | 4 (25%) | 0.195 |
| Total cholesterol (mg/dl) | 189 ± 32 | 181 ± 39 | 178 ± 43 | 168 ± 53 | 0.193 |
| Low-density lipoprotein cholesterol (mg/dl) | 103 ± 26 | 101 ± 29 | 105 ± 33 | 97 ± 41 | 0.611 |
| Heart rate (beats/min) | 70 ± 13 | 79 ± 14 | 80 ± 16 | 108 ± 16 | <0.0001 ‡ § |
| Aortic root diameter (mm) | 29 ± 4 | 30 ± 4 | 30 ± 4 | 30 ± 4 | 0.998 |
| Left atrial diameter (mm) | 34 ± 4 | 44 ± 6 | 43 ± 5 | 39 ± 4 | 0.044 ‡ |
| Ventricular septum thickness (mm) | 9.5 ± 1.5 | 10.3 ± 1.3 | 10.8 ± 1.7 | 10.8 ± 1.2 | 0.143 |
| Maximum internal diameter of left ventricle in diastole (mm) | 48 ± 3 | 56 ± 6 | 54 ± 6 | 51 ± 6 | 0.112 |
| Minimum internal diameter of left ventricle in systole (mm) | 25 ± 3 | 35 ± 9 | 37 ± 7 | 35 ± 9 | 0.794 |
| Mitral E velocity (cm/s) | 73 ± 20 | 113 ± 37 | 104 ± 25 | 113 ± 27 | 0.356 |
| Mitral A velocity (cm/s) | 75 ± 20 | 78 ± 28 | 79 ± 25 | 69 ± 26 | 0.403 |
| Deceleration time (ms) | 209 ± 58 | 180 ± 52 | 176 ± 51 | 158 ± 47 | 0.233 |
| Pulmonary arterial systolic pressure (mm Hg) | 25 ± 6 | 46 ± 13 | 45 ± 10 | 40 ± 8 | 0.608 |
| Left ventricular ejection fraction (%) | 61 ± 9 | 51 ± 13 | 44 ± 11 | 43 ± 15 | 0.006 † ‡ |
| Regurgitation volume (ml) | 77 ± 28 | 62 ± 20 | 68 ± 24 | 0.017 † | |
| Septal mitral annulus | |||||
| S′ (cm/s) | 7.8 ± 1.6 | 6.9 ± 2.4 | 5.5 ± 1.3 | 6.6 ± 2.2 | 0.011 † § |
| E′ (cm/s) | 7.3 ± 2.4 | 6.9 ± 2.6 | 5.2 ± 1.4 | 6.0 ± 2.4 | 0.007 † |
| A′ (cm/s) | 9.7 ± 2.1 | 7.8 ± 2.6 | 6.5 ± 2.3 | 5.9 ± 2.8 | 0.011 † ‡ |
| Maximum indexed left atrial volume (ml/m 2 ) | 22.2 ± 13.4 | 71.4 ± 37.2 | 57.7 ± 16.0 | 64.3 ± 31.2 | 0.085 |
| Pre-P wave indexed left atrial volume (ml/m 2 ) | 14.6 ± 10.9 | 55.4 ± 31.0 | 47.9 ± 15.7 | 56.2 ± 27.3 | 0.296 |
| Minimum indexed left atrial volume (ml/m 2 ) | 8.5 ± 6.9 | 42.8 ± 29.2 | 38.5 ± 20.4 | 50.1 ± 25.4 | 0.139 |
| Regurgitation volume/maximum left atrial volume (%) | 72 ± 31 | 66 ± 25 | 75 ± 32 | 0.419 | |
| Left atrial ejection fraction (%) | 42.8 ± 14.6 | 25.0 ± 14.5 | 19.4 ± 9.4 | 11.3 ± 4.7 | <0.0001 † ‡ § |
| Left atrial distensibility (%) | 214 ± 103 | 85 ± 54 | 55 ± 24 | 29 ± 14 | <0.0001 † ‡ § |
| Mitral E/septal E′ | 11.2 ± 6.4 | 19.0 ± 9.3 | 21.6 ± 8.2 | 21.2 ± 8.1 | 0.368 |
| Left ventricular filling pressure (mm Hg) | 12.4 ± 3.4 | 22.6 ± 5.7 | 24.5 ± 5.7 | 33.3 ± 5.8 | <0.0001 ‡ § |
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