Background
Recent American Society of Echocardiography (ASE)/European Association of Cardiovascular Imaging (EACVI) guidelines for echocardiographic evaluation of left ventricular (LV) diastolic function provide a practical, simplified diagnostic algorithm for estimating LV filling pressure. The aim of this study was to test the accuracy of this algorithm against invasively measured pressures and compare it with the accuracy of the previous 2009 guidelines in the same patient cohort.
Methods
Ninety patients underwent transthoracic echocardiography immediately before left heart catheterization. Mitral inflow E/A ratio, E/e′, tricuspid regurgitation velocity, and left atrial volume index were used to estimate LV filling pressure as normal or elevated using the ASE/EACVI algorithm. Invasive LV pre-A pressure was used as a reference, with >12 mm Hg defined as elevated.
Results
Invasive LV pre-A pressure was elevated in 40 (44%) and normal in 50 (56%) patients. The 2016 algorithm resulted in classification of 9 of 90 patients (10%) as indeterminate but estimated LV filling pressures in agreement with the invasive reference in 61 of 81 patients (75%), with sensitivity of 0.69 and specificity of 0.81. The 2009 algorithm could not definitively classify 4 of 90 patients (4.4%), but estimated LV filling pressures in agreement with the invasive reference in 64 of 86 patients (74%), with sensitivity of 0.79 and specificity of 0.70.
Conclusions
The 2016 ASE/EACVI guidelines for estimation of filling pressures are more user friendly and efficient than the 2009 guidelines and provide accurate estimates of LV filling pressure in the majority of patients when compared with invasive measurements. The simplicity of the new algorithm did not compromise its accuracy and is likely to encourage its incorporation into clinical decision making.
Highlights
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We tested the accuracy of the 2016 ASE/EACVI guidelines for echocardiographic evaluation of LV diastolic function in 90 patients against invasively measured pressures and compared it with the previous 2009 guidelines.
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The new guidelines are simpler but similarly accurate, correctly estimating LV filling pressure approximately 75% of the time.
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The simplicity of the new algorithm did not compromise its accuracy and is likely to encourage its incorporation into clinical decision making.
The burden of heart failure continues to increase as the population ages, with commensurate increases in the financial and social costs of hospitalizations and readmissions. Projections estimate that >8 million people will have heart failure by 2030 and that health care costs could exceed $50 billion. Determining left ventricular (LV) filling pressure is clinically important for the management of patients with congestive heart failure, as elevated LV filling pressure results in increased risk for hospitalization and poor outcomes.
Although invasive methods are considered the “gold standard” for measuring intracardiac filling pressures, echocardiography is routinely used as a noninvasive alternative. This has been done using an algorithm based on Doppler-derived parameters, described in the joint recommendations of the American Society of Echocardiography (ASE) and the European Association of Cardiovascular Imaging (EACVI) from 2009. These guidelines have been reported as cumbersome to use because of the number and laboriousness of measurements involved, thereby limiting application in clinical practice. In addition, the guidelines proposed the use of different algorithms for patients with normal versus depressed LV function, adding complexity to the diagnostic paradigm.
Accordingly, the ASE and EACVI recently developed a new set of guidelines for the evaluation of LV diastolic function, which includes a practical, simplified algorithm for estimating LV filling pressures that can be used in all patients irrespective of LV ejection fraction (LVEF). As stated in the revised guideline document, this recommended algorithm is based on expert consensus that stems from collective experience. The authors also state that this algorithm needs to be validated in a systematic manner against an invasive reference technique. Two recent multicenter studies compared echocardiographic estimates of LV filling pressures against invasive measurements by cardiac catheterization and reported high feasibility and good accuracy irrespective of LV function, especially when combined with clinical data. These studies were performed by investigators who constituted the core of the guidelines writing group and have extensive specific expertise in the evaluation of diastolic function by echocardiography.
Our primary goal was to assess the validity of the echocardiographic estimates of left-sided filling pressure using the latest guidelines by an independent laboratory that did not participate in the development of the ASE/EACVI guidelines. To achieve this goal, we compared echocardiographic determinations of LV filling pressures against gold-standard invasive measurements, including testing the relationship between their accuracy with LV function and also with gender. In addition, we tested the hypothesis that the accuracy of the new 2016 algorithm would not be compromised by its simplicity compared with the previous 2009 guidelines.
Methods
Population and Study Design
We prospectively studied 90 patients (mean age, 61 ± 13; 41 men [46%]) referred for clinically indicated left heart catheterization (including for chest pain, acute coronary syndrome excluding ST-segment elevation myocardial infarction, transcatheter aortic valve replacement, preoperative evaluation, and history of ventricular arrhythmia or cardiac arrest) who also underwent transthoracic two-dimensional echocardiography just before catheterization. Hemodynamically unstable patients as well as those with atrial fibrillation, moderate or greater mitral regurgitation, moderate or greater calcification of the mitral annulus, mitral stenosis, heart transplantation, sinus tachycardia, or prosthetic valves were excluded. The study was approved by the institutional review board.
Echocardiographic measurements were performed by a panel of three board-certified echocardiographers blinded to the invasive data who finalized each measurement by consensus. These measurements were used to obtain estimates of LV filling pressure using the 2016 algorithm, resulting in classification as normal, elevated, or indeterminate. After excluding indeterminate estimates, the echocardiographic determinations of normal or elevated filling pressures were compared with invasive LV preatrial contraction (pre-A) pressure measurements, which were defined as either normal or elevated if >12 mm Hg, using the same cutoff as used by Andersen et al In addition, cutoffs of 15 and 18 mm Hg were also evaluated in a subanalysis to take into account interlaboratory variability. Comparisons were first performed for the entire study group to test the accuracy of the algorithm, using κ statistics of agreement. Subsequently, these comparisons were repeated for two subgroups of patients with normal (LVEF ≥ 50%) and reduced LV function, as well as male versus female patients, to determine the accuracy of this methodology in these subgroups.
In addition, to test whether the simplification of the new guidelines algorithm affected the accuracy, the same panel of three board-certified echocardiographers used the 2009 guidelines to estimate filling pressures and compare the results against the same invasive reference. Because the 2009 algorithm includes two separate flowcharts to estimate filling pressures in patients with normal and reduced LVEF, the appropriate chart was used in each patient according to LV function. All available parameters were examined in the context of the algorithm, and the determination was made on the basis of which arm of the algorithm had more parameters meeting criteria. When the numbers were similar in both arms of the algorithm, simultaneously suggesting normal and elevated left atrial (LA) pressure, these cases were classified as “indeterminate.” The readers were blinded to both the invasive data and the results of the classification using the 2016 guidelines.
Echocardiographic Imaging and Analysis
Two-dimensional echocardiographic imaging was performed using commercial equipment (iE33 imaging system with an X5 transducer; Philips Medical Systems, Andover, MA). Imaging included apical two- and four-chamber views, from which LA and LV volumes were measured using the method of disks (Xcelera; Philips Medical Systems). These volumes were used to calculate LA volume index (LAVi) and LVEF. Pulsed-wave Doppler of the mitral inflow at the level of valve leaflet tips was used to measure the peak early (E-wave) and late (A-wave) diastolic flow velocities and calculate the E/A ratio. In addition, pulsed-wave Doppler tissue imaging was performed with the sample volume at the lateral and septal mitral annulus to obtain average peak longitudinal early diastolic annular (e′) velocity, which was used to calculate the E/e′ ratio. Peak velocity of the tricuspid regurgitant jet was determined using continuous-wave Doppler. Subcostal windows were acquired to assess diameter and respiratory variation of the inferior vena cava to estimate right atrial pressure. Pulsed-wave Doppler of the pulmonary vein flow was also acquired in the apical views to allow S- and D-wave measurements.
Invasive LV Pressure Measurements
Left heart catheterization was performed according to standard procedure by an interventional cardiologist blinded to the echocardiographic data. Invasive LV pressure measurements were performed using a 6-Fr pigtail catheter (Impulse; Boston Scientific, Marlborough, MA) placed in the left ventricle via femoral or radial arterial access. A fluid-filled transducer was balanced before the measurements with the zero level at the midaxillary line. Continuous pressure tracings were acquired over three consecutive respiratory cycles. LV pre-A pressure, which best reflects the mean LA pressure that is the focus of the ASE/EACVI algorithm, was determined at end-expiration ( Figure 1 ) and considered elevated if >12 mm Hg.
Statistical Analysis
Continuous variables are presented as mean ± SD and categorical variables as numbers and percentages. To determine the accuracy of the echocardiographic detection of elevated filling pressures, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy were calculated from the numbers of true/false positive/negative classifications, using standard definitions. Contingency tables of normal and elevated pressure values by both echocardiographic algorithms and the invasive technique were created to depict intertechnique agreement, which was tested using κ statistics (GraphPad Software, La Jolla, CA). The calculated κ coefficients were judged as follows: 0 to 0.2, low; 0.21 to 0.4, moderate; 0.41 to 0.6, substantial; 0.61 to 0.8 good; and >0.8, excellent.
The significance of the difference in the frequency of discordant determinations between the two sets of guidelines and the invasive reference was tested using χ 2 tests for ratios. Similarly, χ 2 tests were used to evaluate the differences in the frequency of discordant determinations between patients with normal and reduced LVEF, as well as between male and female patients.
Results
Invasive LV pre-A pressure was elevated in 40 of the 90 patients (44%) and normal in 50 (56%). Table 1 shows the characteristics of these two subgroups. Significant intergroup differences were found only in the prevalence of chronic kidney disease and aortic valve stenosis, which were more common in the patients with elevated filling pressures, and the number of urgent catheterizations and coronary interventions. Significant differences between groups were also found in two-dimensional and Doppler parameters of diastolic function. Notably, vital signs were not significantly different between the times when echocardiography and catheterization were performed.
| Variable | Normal invasive LV filling pressure (≤12 mm Hg) | Elevated invasive LV filling pressure (>12 mm Hg) | P |
|---|---|---|---|
| Number of patients | 50 | 40 | |
| Sex | |||
| Male | 24 | 17 | .75 |
| Female | 26 | 23 | .78 |
| Body surface area (m 2 ) | 1.91 ± 0.39 | 1.96 ± 0.23 | .50 |
| Medical history | |||
| HTN | 37 | 37 | .48 |
| Diabetes | 23 | 29 | .19 |
| CAD | 17 | 19 | .40 |
| COPD | 7 | 5 | .86 |
| CKD (stage ≥3) or ESRD | 10 | 21 | .03 |
| AS, at least moderate | 0 | 8 | .003 |
| AI, at least moderate | 0 | 0 | — |
| Medications before catheterization ∗ | |||
| Diuretic † | 20 | 27 | .15 |
| BB | 33 | 29 | .78 |
| ACE inhibitor | 20 | 19 | .65 |
| ARB | 7 | 11 | .20 |
| Spironolactone | 0 | 3 | .06 |
| Hydralazine | 3 | 3 | .79 |
| Nitrate ‡ | 13 | 3 | .053 |
| Digoxin | 0 | 3 | .06 |
| Echocardiographic parameters | |||
| Reduced LVEF (<50%) | 15 | 19 | .26 |
| Normal LVEF (≥50%) | 35 | 21 | .41 |
| E/A ratio | 1.02 ± 0.34 | 1.43 ± 0.77 | .005 |
| E/e′ ratio | 11.1 ± 5.1 | 17.5 ± 8.1 | .001 |
| LAVi (ml/m 2 ) | 33.2 ± 16.6 | 40.4 ± 14.7 | .05 |
| Catheterization | |||
| Inpatient | 33 | 24 | .78 |
| Outpatient | 17 | 16 | .69 |
| Urgent | 7 | 0 | .02 |
| Coronary stent placed | 30 | 8 | .01 |
| SBP at time of echocardiography (mm Hg) | 128 ± 20 | 132 ± 17 | |
| SBP at time of catheterization (mm Hg) | 133 ± 27 | 142 ± 25 | |
| P values (paired t test) | .38 | .11 | |
| HR at time of echocardiography (beats/min) | 72 ± 10 | 72 ± 15 | |
| HR at time of catheterization (beats/min) | 76 ± 13 | 80 ± 13 | |
| P values (paired t test) | .21 | .08 |
∗ Patients received these medications either prior to or during admission at some point before catheterization.
† Diuretics include furosemide and hydrochlorothiazide.
Using the 2016 guidelines, filling pressure was indeterminate in 9 of 90 patients (10%), of whom only one had elevated invasive filling pressure. Of the remaining 81 patients, the echocardiographic algorithm accurately estimated LV filling pressures in agreement with the invasive reference in 61 patients (75%; Figures 2 and 3 ), while in 20 (25%), the estimates were incorrect ( Figures 4 and 5 ). Of the 20 patients in whom the echocardiographic algorithm disagreed with the reference, it underestimated elevated LV filling pressure in 12 (false negatives; Figure 4 ) and overestimated normal LV filling pressure in eight (false positives; Figure 5 ). The κ coefficient was 0.504, indicating substantial intertechnique agreement ( Figure 6 , top left ). After excluding the nine indeterminate patients, the sensitivity of the detection of elevated LV filling pressure was 0.69, specificity was 0.81, PPV was 0.77, NPV was 0.74, and overall accuracy was 0.75 ( Table 2 ).
