Background
There are few data on adding left atrial volume index (LAVi) or pulmonary artery systolic pressure (PAP) to the ratio of early mitral inflow to mitral annular velocity (E/e′) for the estimation of left ventricular (LV) filling pressure in patients with preserved LV ejection fractions (LVEFs) (>50%).
Methods
Patients underwent echocardiography within 20 minutes of cardiac catheterization. Echocardiographic variables were compared with invasively measured LV preatrial contraction pressure (pre-A).
Results
Of the 122 patients studied (mean age, 55 ± 9 years; mean LVEF, 61 ± 6%), 67 (55%) were women, 108 (88%) had hypertension, and 79 (65%) had significant coronary artery disease at catheterization. E/e′ was significantly correlated with pre-A ( R = 0.63, P < .0001) compared with LAVi (R = 0.49, P < .001) and PAP ( R = 0.48, P < .001). E/e′ > 13 had sensitivity of 70% and specificity of 93% (area under the curve [AUC], 0.82; P < .0001), LAVi > 31 mL/m 2 had sensitivity of 78% and specificity of 76% (AUC, 0.80, P < .001), and PAP > 28 mm Hg had sensitivity of 80% and specificity of 64% for pre-A > 15 mm Hg (AUC, 0.77, P < .001). Adding LAVi >31 mL/m 2 for E/e′ = 8 to 13 significantly increased the accuracy of E/e′ > 13 alone (sensitivity, 87%; specificity, 88%; AUC, 0.89; P = .01 for comparison). However, adding PAP > 28 mm Hg for E/e′ = 8 to 13 did not significantly increase the accuracy of E/e′ > 13 alone (AUC, 0.82; sensitivity, 82%; specificity, 72%; P = NS for comparison).
Conclusions
In patients with preserved LVEFs, adding LAVi > 31 mL/m 2 to E/e′ (when E/e′ was in the gray zone, but not when E/e′ was >13) significantly increased the accuracy of E/e′ alone for the estimation of LV filling pressure. These data support the notion of using several, rather than any single, Doppler echocardiographic parameter for the accurate assessment of LV diastolic function.
Diastolic heart failure constitutes a major portion of the heart failure epidemic. Along with a suitable clinical picture and preserved left ventricular (LV) ejection fraction (LVEF) (>50%), recent clinical guidelines have recommended the use of echocardiography with Doppler (or cardiac catheterization) for the demonstration of a level of diastolic dysfunction required for a diagnosis of diastolic heart failure. Echocardiographic peak mitral inflow/early diastolic annular velocity (E/e′) has been shown to correlate with LV filling pressure, including during exercise, and is currently recommended by the American Society of Echocardiography and the European Society of Echocardiography as the initial screening variable for estimating LV filling pressure in patients with preserved LVEFs. Given that the accuracy of E/e′ has been recently challenged as an estimate of LV filling pressure, we sought to determine whether there was any incremental benefit to adding other echocardiographic variables shown to correlate with LV filling pressure—left atrial volume index (LAVi) and pulmonary artery systolic pressure (PAP) —to E/e′ for the estimation of LV filling pressure.
Methods
This study protocol was approved by the institutional review board of the Baylor College of Medicine. Consecutive patients referred to the cardiac catheterization laboratory for coronary angiography for clinical reasons were approached for recruitment. After informed consent, patients underwent left-heart catheterization via a retrograde approach from the femoral artery. The aortic valve was crossed to determine LV diastolic pressures, and coronary angiography was performed by selective injection of the coronary ostia. LV preatrial contraction pressure (pre-A) and end-diastolic pressure were measured over 10 cardiac cycles during free respiration and then averaged. Standard diagnostic views of the left and right coronary anatomy were obtained, and lesions >70% in diameter in major epicardial arteries represented significant coronary artery disease (CAD). Readings of invasive cardiac hemodynamics and coronary anatomy were performed by an invasive cardiologist blinded to all clinical and echocardiographic data. A comprehensive transthoracic Doppler echocardiographic examination was performed immediately after catheterization (all studies <20 minutes from catheterization). Patients were excluded if they had nonsinus rhythm, severe mitral regurgitation, any mitral stenosis, or prosthetic mitral valves, because these conditions render Doppler estimations of LV filling pressures less reliable.
Studies were performed on a GE Vivid 7 ultrasonographic machine (GE Healthcare, Milwaukee, WI). Two-dimensional measurements were performed according to the American Society of Echocardiography and included LVEF by the biplane method of discs, maximal left atrial volume by the biplane method of discs, and LV mass by the area-length method; the latter two variables were indexed to body surface area. Preserved LVEF was defined as >50%. Pulsed Doppler was used to record transmitral inflow in the apical 4-chamber view. Tissue Doppler velocities were then acquired at the septal and lateral annular sites and averaged as previously described.
Studies were analyzed by an echocardiologist blinded to all clinical and catheterization data. Mitral inflow measurements included peak early (E) and peak late (A) velocities, the E/A ratio, and the deceleration time of E. PAP was estimated by adding the peak tricuspid regurgitation velocity, converted to peak pressure by the modified Bernoulli equation, to an estimate of right atrial pressure. The estimate of right atrial pressure was made using the following: right atrial pressure = 5 mm Hg if the inferior vena cava (IVC) was <2 cm in diameter and had >50% inspiratory collapse, 10 mm Hg if the IVC was >2 cm in diameter and had >50% inspiratory collapse, and 15 mm Hg if the IVC was >2 cm in diameter and had <50% inspiratory collapse. The early diastolic (e′) velocity by tissue Doppler at the septal and lateral annular sites was measured and the E/e′ ratio computed using the average of septal and lateral e′, as previously described. Three cardiac cycles were measured and averaged for all Doppler measurements.
Continuous data are presented as mean ± SD and categorical data as number (percentage). For continuous variables, Student’s t test was performed, and for dichotomous variables, the χ 2 test was used. Linear regression was performed to determine the correlations between continuous variables. Sensitivity, specificity, and positive and negative predictive values were calculated according to standard definitions, and receiver operating characteristic curves were constructed and the areas under the curve (AUCs) calculated to determine the optimal cutoff values of the best correlates with LV pre-A for the prediction of LV pre-A > 15 mm Hg. For incremental accuracy, in addition to E/e′ > 13 (the optimum cutoff from AUC calculation), LAVi > 31 mL/m 2 was added (the optimum cutoff from AUC calculation) for E/e′ = 8 to 13 to indicate elevated LV filling pressure. The same approach was applied for PAP > 28 mm Hg (the optimum cutoff from AUC calculation). The accuracy of these combined variables for predicting LV pre-A > 15 mm Hg was then recalculated. The Hanley-McNeil test was used to assess for significant differences between AUCs. P values < .05 were considered significant. Analyses were performed with SigmaStat 3.0 (Systat Software, Point Richmond, CA) and GraphPad Prism Plus (GraphPad Software, San Diego, CA).
Results
Of 275 patients referred for cardiac catheterization screened, 110 were excluded for depressed LVEFs (<50%), 27 for nonsinus rhythm, 9 for mitral stenosis or prosthetic mitral valves, and 7 in whom the aortic valve could not be crossed. Thus, 122 patients with preserved LVEFs (>50%) were enrolled, of whom 67 (55%) were women, 107 (88%) had hypertension, 67 (55%) had diabetes, and 27 (22%) were current smokers. The mean age was 55.4 ± 9.0 years, the mean LVEF was 60.9 ± 6.1%, and 79 (65%) had significant CAD at catheterization. When the population was divided into the 54 patients with LV pre-A < 15 mm Hg and the 68 patients with pre-A > 15 mm Hg, there were no significant differences in age ( P = .94), systolic blood pressure ( P = .98), the prevalence of diabetes ( P = .91), the prevalence of hypertension ( P = .61), current smoking status ( P = .92), hypercholesterolemia ( P = .16), and the numbers of patients on β-blockers ( P = .57), angiotensin-converting enzyme inhibitors ( P = .61), and statins ( P = .44) ( Table 1 ). Among echocardiographic variables, LV diastolic dimension and LAVi were larger and LV mass index, peak mitral E velocity, and PAP were higher in patients with LV pre-A > 15 mm Hg compared with those with LV pre-A < 15 mm Hg ( Table 1 ).
| LV pre-A < 15 mm Hg | LV pre-A > 15 mm Hg | ||
|---|---|---|---|
| Variable | (n = 54) | (n = 68) | P |
| Baseline characteristics | |||
| Age (y) | 55.4 ± 9.6 | 55.3 ± 8.4 | .94 |
| Women | 30 (56%) | 37 (54%) | .91 |
| Body surface area (m 2 ) | 2.0 ± 0.3 | 2.0 ± 0.3 | .90 |
| Hypertension | 46 (85%) | 62 (91%) | .61 |
| Diabetes mellitus | 29 (53%) | 38 (55%) | .91 |
| Hypercholesterolemia | 39 (72%) | 59 (86%) | .16 |
| Current smokers | 11 (20%) | 16 (23%) | .92 |
| Medications | |||
| β-blockers | 39 (72%) | 48 (70%) | .57 |
| ACE inhibitors/angiotensin receptor blockers | 32 (59%) | 47 (69%) | .61 |
| Calcium channel blockers | 7 (13%) | 11 (16%) | .92 |
| Statins | 34 (63%) | 51 (75%) | .44 |
| Diuretics | 13 (24%) | 28 (41%) | .12 |
| Echocardiography and Doppler | |||
| LV diastolic dimension (cm) | 4.3 ± 0.8 | 4.7 ± 0.7 | .05 |
| LV mass index (g/m 2 ) | 89.6 ± 26.9 | 105.7 ± 40.8 | .01 |
| LAVi (mL/m 2 ) | 27.9 ± 6.9 | 37.1 ± 16.1 | <.001 |
| RV diastolic dimension (cm) | 3.1 ± 0.5 | 3.2 ± 0.4 | .88 |
| Right atrial volume index (mL/m 2 ) | 19.5 ± 8.2 | 20.1 ± 4.8 | .69 |
| LV ejection fraction (%) | 61.6 ± 6.4 | 60.5 ± 6.2 | .40 |
| RV fractional area change (%) | 41.2 ± 4.9 | 42.0 ± 7.4 | .77 |
| Mitral E (cm/s) | 72.8 ± 15.4 | 89.1 ± 18.0 | <.001 |
| Mitral A (cm/s) | 74.6 ± 16.1 | 81.4 ± 22.0 | .06 |
| Mitral E/A | 0.98 ± 0.19 | 1.10 ± 0.30 | .007 |
| Mitral deceleration time (cm/s) | 206.3 ± 54.1 | 206.7 ± 49.3 | .96 |
| PAP (mm Hg) | 26.1 ± 5.4 | 33.3 ± 9.4 | <.001 |
| Mitral E′ average (cm/s) | 7.2 ± 1.8 | 7.0 ± 2.7 | .63 |
| Mitral E/e′, septal annulus | 12.2 ± 3.1 | 17.6 ± 6.5 | <.001 |
| Mitral E/e′, lateral annulus | 9.3 ± 2.3 | 14.0 ± 5.7 | <.001 |
| Mitral E/e′, average of annuli | 10.7 ± 2.6 | 15.8 ± 4.8 | <.001 |
| Catheterization data | |||
| Heart rate (beats/min) | 69.9 ± 9.7 | 67.0 ± 11.8 | .30 |
| Systolic blood pressure (mm Hg) | 140.6 ± 22.3 | 140.1 ± 26.5 | .98 |
| Diastolic blood pressure (mm Hg) | 79.1 ± 11.8 | 76.0 ± 12.1 | .25 |
| LV end-diastolic pressure (mm Hg) | 16.3 ± 4.0 | 26.4 ± 6.7 | <.001 |
| LV pre-A (mm Hg) | 10.8 ± 2.4 | 19.5 ± 4.5 | <.001 |
| Significant CAD on angiography | 30 (56%) | 49 (72%) | .14 |
E/e′ had a reasonable correlation with LV pre-A ( R = 0.63, P < .001), compared with LAVi ( R = 0.49, P < .001) and PAP ( R = 0.48, P < .001) ( Figure 1 ). Peak E velocity was also a significant echocardiographic correlate of LV pre-A ( R = 0.48, P < .001); however, mitral deceleration time ( R = 0.04, P = .66) was not correlated with LV pre-A. In the 79 patients (62%) with significant angiographic CAD, correlation of LV pre-A with E/e′ was R = 0.66 ( P < .001) compared with R = 0.58 ( P < .001) in the 43 patients (38%) without significant angiographic CAD ( P = NS for comparison). Similarly, in patients with CAD, the correlation of LAVi with LV pre-A was R = 0.49 ( P < .001) compared with R = 0.48 ( P < .001) in patients without significant CAD ( P = NS for comparison). PAP too had a similar correlation with LV pre-A in patients with versus without significant angiographic CAD ( R = 0.47, P < .001 vs R = 0.49, P < .001; P = NS for comparison).
