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Echocardiographic Assessment of Left Ventricular Filling Pressures Using
Data from Invasive Left Ventricular Filling Pressures in Patients with
Normal Left Ventricular Ejection Fraction
Yi Liang MD, Xinxin Chen MD, Fen Zhang MD, Wei Yuan, MD, PhD,
Liangjie Xu MD, Jinchuan, Yan, MD, PhD
Corresponding authors
Jinchuan, Yan, MD, PhD
Professor of Medicine,
Director, Department of Cardiology
Affiliated Hospital of Jiangsu University, Zhenjiang, China
TeL:86-0511-85026551 Email: yanjinchuan@hotmail.com
Abstract
Objectives The aims of this study were to assess the accuracy of multiple
echo parameters of diastolic dynamics and the 2016 ASE/EACVI algorithm
to detect elevated invasive LV diastolic pressures in patients with normal
ejection fraction; the accuracy of the 2016 algorithm was compared to that
of a newly derived algorithm.
Background Echocardiographic assessment of left ventricular (LV) diastolic
function is an integral part of the routine examination. Simultaneous
measurements of LV pressures and echocardiographic parameters are sparse.
Methods Patients (n=120) underwent left heart catheterization and coronary
angiography for chest pain due to suspected coronary artery disease.
Transthoracic echocardiography and LV pressure recordings were
simultaneous. Receiver-operating characteristic curves were constructed to
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define optimal cut points for multiple echocardiographic parameters. Five
were selected for new algorithm to estimate LV diastolic pressures: velocity
of tricuspid regurgitation (> 280cm/s), average e (Av e < 9), average E/e
ratio (AvE/e’>13), velocity of pulmonary vein A wave reversal (PV ArV >
32 cm/s) and left atrial volume index (LAVi >32 ml/m2). The accuracy of the
algorithm was examined for a LV pre-A >12 mmHg and LV end diastolic
pressure (LVEDP) i.e. post-A >15 mmHg.
Results All patients had a normal LV ejection fraction. Individual
echocardiographic parameters of diastolic function (n=12) had moderate
diagnostic utility. Using the algorithm of the 2016 guidelines, an elevated
LVEDP >15 mmHg was identified with an accuracy of 69.1% (60.1-77.3);
the newly derived algorithm that utilized the 5 echocardiographic variables
had an accuracy of 84.2% (76.4-90.2), p <0.001.
Conclusions Simultaneous recordings of LV diastolic parameters and
invasive LV pressures in a homogenous cohort confirmed that no single
echocardiographic parameter can accurately assess LV diastolic pressures.
Importantly, left ventricular diastolic pressures in patients with a normal
LVEF were fairly reliably assessed by the 2016 guidelines. The new
algorithm improved the accuracy of detecting abnormal LV filling pressures.
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Keywords Left ventricular end diastole pressure• diastolic function•
echocardiography
Condensed Abstract
Echocardiographic assessment of left ventricular diastolic function is an
integral part of the routine examination. This study assessed the accuracy of
multiple echo parameters of diastolic dynamics to detect elevated LV
diastolic pressures in patients with normal ejection fractions. Invasive LV
pressures and echocardiography were performed simultaneously in 120
patients with chest pain suspected to be from coronary artery disease. No
single echocardiographic parameter had a high accuracy. When multiple
echocardiographic parameters were used in both the 2016 algorithm
(ASE/EACVI) and a new alternate algorithm, both exhibited good
diagnostic accuracy for elevated LVEDP and the new algorithm improved
the accuracy.
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Abbreviations
Ar-A = Pulmonary vein atrial reversal duration – Mitral A duration
ArV = Pulmonary vein atrial reversal velocity
ASE = American Society of Echocardiography
Av = Average
CAD = Coronary artery disease
CI = Confidence interval
DD = Diastolic dysfunction
DT = E wave deceleration time
EACVI = European Association of Cardiovascular Imaging
e sep = e velocity at the septum
e lat = e velocity at the lateral wall
HFpEF = Heart failure with preserved ejection fraction
HFrEF = Heart failure with reduced ejection fraction
IVRT = Isovolumic relaxation time
LA = Left atrial
LAVi = Left atrial volume index
LV = Left ventricular
LVEF = Left ventricular ejection fraction
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LVEDP = Left ventricular end diastolic pressure
MV A = mitral A wave duration
NPV = Negative predictive value
PPV = Positive predictive value
PV D = pulmonary vein D velocity
PV S = pulmonary vein S velocity
ROC = Receiver-operating characteristic
STE = Speckle-tracking echocardiography
TRV = Tricuspid regurgitation maximum velocity
Vp = Color flow propagation velocity
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The diagnosis of diastolic dysfunction is an important objective of clinical
cardiology, and echocardiographic assessment is the predominant method
applied. However, no single echocardiographic parameter can confirm the
diagnosis. The 2009 American Society of Echocardiography (ASE) and
European Association of Echocardiography (now European Association of
Cardiovascular Imaging [EACVI]) guidelines for assessment of diastolic
function were comprehensive, including both two-dimensional (2D) and
Doppler parameters to grade diastolic dysfunction and to estimate LV filling
pressures 1. These guidelines have been reported as too complex to use in
clinical practice. Accordingly, the ASE and EACVI recently developed a
new set of guidelines for the evaluation of LV diastolic function 2, which
include a practical, simplified algorithm for estimating LV filling pressures.
Several studies have validated these guidelines against an invasive reference
technique and found that the 2016 algorithm detected an elevated LVEDP
better than the 2009 proposal 3,4
. Our study aims were 1) to determine the
diagnostic accuracy of each Doppler and 2D parameter currently being used
to identify elevated LV diastolic pressure, 2) to derive an alternate grading
algorithm to predict the LV filling pressure and 3) to compare the new
algorithm with that of the 2016 Recommendation.
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METHODS
Study population
This was a prospective study of consecutive patients undergoing a
conventional left heart catheterization for evaluation of known or suspected
coronary artery disease. The studies were completed from July 20, 2017 to
January 17, 2018 in the Affiliated Hospital of Jiangsu University, Zhenjiang,
China. The study protocol was approved by the Institutional Review Board
of Affiliated Hospital of Jiangsu University. Each patient signed the consent.
We excluded patients with atrial fibrillation, mitral valve surgery, mitral
stenosis, severe mitral annular calcification, severe mitral or aortic
regurgitation, hemodynamic instability and prior heart transplantation.
Patients were also excluded if image quality was inadequate, their LV
ejection fraction (LVEF) was < 50% by the echocardiographic biplane
method or their heart rate was >100 bpm at the time of examination.
Echocardiographic and imaging analysis
Imaging was performed with Vivid E 9 (General Electric, Milwaukee, WI,
USA). A complete echocardiographic study was performed using standard
views with care taken to avoid foreshortening. All images were recorded for
3 to 5 cardiac cycles. Mitral inflow velocities were obtained from the apical
window using pulsed wave Doppler with the sample volume placed at the
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center of the leaflet tips. Pulmonary venous flow was recorded from one of
the pulmonary veins, guided by color Doppler. Color M-mode was recorded
in the apical 4-chamber view with the sample volume placed in the center of
mitral inflow as guided by color Doppler. Tissue Doppler velocities in early
diastole (e ) were recorded from both the septal and lateral sides of the
mitral annulus. Tricuspid regurgitation velocities were recorded by
continuous wave Doppler from multiple windows. All the images used to
assess the echocardiographic parameters of diastolic function were recorded
simultaneously with the invasive recording of LV diastolic filling pressure.
Measurements were performed using computerized off-line analysis stations
without knowledge of invasively derived hemodynamic data. LV volumes,
LVEF, and left atrial (LA) maximal volume were measured using the
bi-plane method recently recommended 5.
Color M-mode for LV flow propagation velocity (Vp), mitral annulus tissue
Doppler velocities , the velocity of tricuspid regurgitation, Doppler
parameters of mitral and pulmonary vein flow, LV isovolumic relaxation
time (IVRT), filling time (FT) and isovolumic contraction time (IVCT) were
measured according to the ASE recommendations 2 .
Valvular regurgitation, right ventricular function, all routine two-D
parameters, chamber volumes and left atrial volume index were evaluated
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following American Society of Echocardiography (ASE) recommendations 6,
7.
The diagnostic ability of each echocardiographic parameter to correctly
classify abnormal pre-A wave pressure (>12 mmHg) and abnormal post-A
wave LV end-diastolic pressure (LVEDP) (>15 mmHg) was assessed by
creating a receiver-operating characteristic (ROC) curve for each parameter.
Cardiac catheterization
Left heart catheterization was performed according to standard procedures
by an interventional cardiologist blinded to the echocardiographic data.
Invasive LV pressure recordings were obtained using a 6-Fr pigtail catheter
(Impulse; Boston Scientific, Marlborough, MA) placed in the left ventricle
via femoral or radial arterial access. Continuous pressure tracings were
acquired over three consecutive cardiac cycles at end expiration. The
pre-A LV pressure was measured at beginning of the A wave; LVEDP was
measured after the A wave (Figure 1).
Statistical analysis
Baseline characteristics are presented as mean ±SD for continuous variables
or numbers (percentage) for categorical variables. Comparison of baseline
characteristic between two groups was performed using ANOVA or χ2 test
as appropriate. The ROC curves were generated using MedCalc®
software.
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The sensitivity, specificity, accuracy and 95% confidence interval for the
comprehensive echocardiography algorithm to detect elevated left
ventricular diastolic pressures were calculated using MedCalc® software.
For these calculations the indeterminate cases (Class I diastolic dysfunction)
were classified as elevated diastolic pressures. Statistical significance was
defined as a 2-tailed p < 0.05 for all tests. A statistical comparison of the
differing algorithms was assessed by comparing the areas under the ROC
curves.
RESULTS
Baseline characteristics of study subjects
None of the 120 patients had structural heart disease or atrial fibrillation.
Invasive LV pre-A pressure was normal in 39 (33%) and elevated in 81 (77%)
patients; The LVEDP was normal in 43 (36%) and elevated in 77 (64%)
cases. The high frequency of elevated LV diastolic pressures is likely due to
the high prevalence of hypertension and/or coronary aretery disease.
Additional clinical characteristics of the two study groups are listed in Table
1. When patients with normal diastolic pressures were compared to those
with either an elevated pre-A LV pressure or an elevated LVEDP, there were
no significant intergroup differences.
Echocardiographic measurements of study subjects
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Echocardiographic parameters of the two patient groups, as defined by the
invasive LV filling pressures, are listed in Table 2. Significant intergroup
differences were found in most of the two-dimensional and Doppler
parameters of diastolic function. Notably, no significant differences were
observed for the mitral E/A ratio, A duration, and pulmonary vein S/D ratio
in both pre-A and LVEDP groups. Significant differences were found for
both the septal e and lateral e when using > 15 mmHg as the elevated
threshold.
The sensitivity and specificity, derived from the ROC curves, for the
cut-points of each echocardiographic parameter of diastolic function are
listed in Table 3. The areas under the ROC curves for the detection of an
abnormal LVEDP>15 mmHg for each echocardiographic parameter of
diastolic dysfunction are listed in Table 4 and shown in Figure 2. There
was no diagnostic value for the mitral E/A, the mitral deceleration time and
the pulmonary vein ratio of systolic and diastolic velocities (PV S/D).
A new algorithm to predict elevated LVEDP in patients with normal
LVEF
The comparison of the ROC curves showed that there was no single
parameter that could reliably predict an elevated LVEDP in patients with a
normal LVEF. Based upon the optimal value derived from the ROC curves,
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a new algorithm was constructed using the following measurements; 1)
average e (Av e ), 2) average E/e (Av E/e ), 3) velocity of pulmonary vein
A wave reversal (PV ArV), 4) tricuspid regurgitation velocity and 5) left
atrial volume index (LAVi). The optimal value (criterion) used to define
abnormal for each of the echocardiographic parameters was the value with
the highest specificity/sensitivity for the diagnosis of elevated LV pressure
(MedCalc software). Note that all of these variables, except the PV ArV,
were also used in the 2016 guidelines but with different optimal values.
Variables not used had lesser areas under the ROC curves. When ≤1 of the 5
variables met the cut off threshold, LVDP was categorized as normal. If 2
variables met the cutoff threshold, LVDP then might be normal or mildly
elevated and so classified as grade I diastolic dysfunction. If ≥3 parameters
met the cutoff threshold, LV diastolic dysfunction was classified as Grade II
diastolic dysfunction. See Figure 3 to compare the 2016 algorithm with the
proposed algorithm. The application of the new algorithm is illustrated in
Figure 4.
In the new algorithm we classified the LV diastolic pressure of patients as
normal when only 1 abnormal parameter was present; 2 abnormal
parameters indicated a mild to moderate elevation of LVEDP (defined as
16-26mmHg). Of the 17 patients in this study group with 2 abnormal
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parameters, 12 had elevated LVEDP and 5 had normal LVEDP (≤15
mmHg). There were 54 (70%) patients with 3 or more abnormal
parameters, all of them with elevated LVEDP (≥15 mmHg). Viewed in an
alternate way, the patients with a very high LVEDP, we found that there
were no false negatives among the 24 of 26 patients with LVEDP > 26
mmHg. In our study population there were no patients with a Grade 3
(restrictive filling pattern) since patients with structure and myocardial
diseases were excluded.
Comparison between the 2016 Guidelines and the new algorithm
The accuracy of the various algorithms for detecting abnormal LV filling
pressures was then assessed. The sensitivity was 87 % (CI 5.1-94.6%),
specifity was 54.6 % (CI 41.8-66.9%) and accuracy was 69.2 % (CI
60.1-77.3%) as estimated by the 2016 guidelines for LEDVP >15 mmHg.
When LVEDP was estimated by the new algorithm, the sensitivity was 90.3 %
(CI 81.0-96.0%), specifity was 75% (CI 60.4-86.4 %) and accuracy was 84.2%
(CI 76.4-90.2) p<0.001 (Tables 5 and 6).
Although our cutpoints for the parameters in our proposed algorithm
differed slightly from those In the 2016 guidelines, the major difference
between the 2016 algorithm and our newly proposed version is that the 2016
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guidelines did not incorporate the pulmonary vein atrial reversal velocity
(PArV). When this is added as a fifth echo parameter to the 4 already in
the 2016 guideline, the accuracy is significantly improved and becomes
fairly similar to that of the newly proposed algorithm (p = 0.052, Figures
5).
Discussion
The current study was designed to evaluate all individual echocardiographic
parameters of diastolic function as to their ability to detect both an abnormal
LV diastolic pre-A pressure >12 mmHg and an elevated LVEDP > 15 mmHg
in patients with normal LVEF. Our results confirmed that no single
echocardiographic variable can identify patients with elevated LV filling
pressures with acceptable accuracy. Although the algorithm of the 2016
guidelines had an acceptable accuracy for the detection of an elevated
LVEDP, we derived a new algorithm to estimate invasive LV pre-A and
post-A pressure based upon ROC analysis of individual parameters. This
algorithm used new cut-points for some of the echocardiographic variables
and also incorporated the pulmonary vein atrial reversal velocity. When we
compared the accuracy of the 2016 guidelines with our proposed algorithm
in the same population, we found that the proposed algorithm had an
improved accuracy.
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Our study had several important features: 1. echocardiography was
performed simultaneously with invasive LV diastolic pressure recordings; 2.
ROC curves for each parameter were used to determine the optimal cut-point
for defining an abnormal LV filling pressure and 3. all study patients had a
normal LVEF.
Several studies have assessed the utility of the 2016 guidelines. Sato K et al.
compared the 2016 algorithm with the 2009 guidelines to predict the LVEDP
in 460 patients with a normal LVEF. The echocardiogram was completed
within 24 hours of the invasive study 4. They did not assess the actual
accuracy of either algorithm. They found that the 2016 guidelines resulted in
reclassification of many patients. Using multivariable analysis only the
average E/e and LV volume index had a statistically significant association
with LVEDP. Balaney et al. assessed the 2016 algorithm to detect an
elevated pre-A wave pressure > 12 mmHg in a study of 90 patients. The
echocardiogram was performed immediately prior to the invasive study 3.
The 2016 and the 2009 guidelines had very similar sensitivities and
specificities and a concordance with the invasive LVEDP in approximately
74%. A comprehensive assessment of the 2016 guidelines was recently
carried out in 450 patients from 6 cardiac centers 8. Right or left heart
catheterization was performed shortly before or after the echocardiographic
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assessment. The study found that individual echocardiographic parameters
had only a modest correlation with the invasive pressures in a cohort with
normal as well as depressed LVEF. Specifically, they observed an accuracy
of 84% using the 2016 gudelines to detect elevations of the pulmonary
capillary pressure in patients with a normal LVEF. Lancellotti et al
performed a multicenter assessment of the 2016 guidelines in 159 patients
from 9 centers; 120 had a normal LVEF 9
. Echo-Doppler parameters were
performed nearly simultaneously (within 1/2 h the invasive and non-invasive
assessment of LVFP) with the invasive LV pressures. The 2016 guidelines
had an improved accuracy as compared to the 2009 guidelines. The
correlations between individual echo-Doppler parameters and LVEDP > 15
mmHg were generally poor. ROC curves were not performed to select the
cutpoints; rather, the 2016 consensus determined guidelines were used. We
believe that our study is unique in that the cutpoints were determined from
ROC curves rather than from expert consensus. Nevertheless, the differences
in cutpoints for the individual parameters for the 2 approaches were small
(Figure 3)
The prognostic value of the 2016 guidelines was assessed in a retrospective
Danish study 10
. They proposed a modified algorithm that began with the
AVe ; when this was < 7 cm/s, the other variables of E/A, LAVi > 34ml/m2,
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and an E/e´ ≥13 were applied similar to the 2016 guidelines. This
modification performed quite well in predicting adverse outcomes over a 10
year period of observation.
The 2016 guidelines have performed well in predicting both an elevated
LVEDP and adverse outcomes. Our proposed new algorithm classified the
LV diastolic pressure of patients as normal when none or 1 abnormal
parameter was present; 2 abnormal parameters indicated a mild to moderate
elevation of LVEDP (defined as 16-23 mmHg); of the 17 patients in this
group, 12 had elevated LVEDP and 5 had normal LVEDP (≤15 mmHg).
There were 54 (70%) patients with 3 or more abnormal parameters, all of
them with elevated LVEDP (≥15 mmHg).
Patients with diastolic dysfunction and a normal LVEF are very common in
clinical practice. Significant abnormalities in active relaxation and passive
stiffness are the mechanisms of elevated diastolic pressures in these patients
11. These pathophysiological changes may occur as early manifestations of
diastolic dysfunction. Echocardiographic parameters change as both LV
relaxation and LV stiffness are altered; the velocity of mitral annulus e
reflects LV early relaxation, and the velocity and duration of pulmonary vein
A wave reversal will be increased as the LV stiffness increases. The LA
volume index is an indicator of long-term elevations of LV filling
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pressures 2. Recognition of abnormal LV filling pressures is important in
patients with dyspnea and suspected diastolic dysfunction. Because
stiffening of the left ventricle contributes to heart failure with preserved
ejection fraction, an accurate grading of diastolic dysfunction can lead to
possible successful medical treatment 12,13
.
Study limitations
This study was performed in a population with a relatively simple clinical
condition, that is chest pain with normal EF and no structural heart disease.
The proposed algorithm to estimate left ventricle diastolic filling pressures
may not be suitable in patients with more complex clinical conditions such
as infiltrative cardiomyopathy. Since the majority of cases in our study
population had coronary artery disease and/or hypertension, the results may
not be usable in the general patient population. Our study is hypothesis
generating since we did not test the new algorithm in another population.
The accuracy of the newly proposed algorithm will need to be validated in
additional patient groups with normal LVEF. We recognize that high quality
recordings from a pulmonary vein and measurement of the A reversal
velocity may be difficult in many patients yet was very successful (the
obtained rate was 92.9%) in this Chinese population; given the importance
of the A reversal velocity , the new algorithm may not be applicable when a
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high quality assessment of pulmonary vein flow is not attainable.
It is important to recognize that our data relate to the assessment of LV
diastolic pressure, and not to diastolic dysfunction per se. While an increase
in LV diastolic pressure typically accompanies diastolic dysfunction,
pressures may be normal, especially at rest. Therefore, our data are most
applicable to the evaluation of pressure, and the approach to the presence or
absence of diastolic dysfunction remains best done using the 2016
ASE/EACVI recommendations.
CONCLUSION
The current study was novel in that the noninvasive and invasive data were
obtained simultaneously and optimal cutponts for each parameter were
determined from ROC curves. The ability of most but not all
echocardiographic variables to modestly reflect diastolic function was
confirmed. A new algorithm for estimating the invasive left ventricle
diastolic filling pressures was designed and compared to that proposed by
the 2016 guidelines for subjects with a normal LVEF. The diagnostic
accuracy of the 2016 guidelines had an acceptable accuracy, and in this
specific cohort the new algorithm had an improved accuracy.
Sources of Funding
This project was supported by social development project of Jiangsu
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Province (BE2017152, BE2016719) and Jiangsu medical innovation team
project (CXTDA2017010).
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Tables
Table 1 Clinical characteristics. Data are grouped by LV filling pressures
Variable LV filling pressure, pre-A LV filling pressure, end-diastolic
≤12
mm Hg
>12
mm Hg
p ≤15
mm Hg
>15
mm Hg
p
Patients, n=120 39 81 43 77
Male, n (%) 25
(64)
54
(67)
0.78 29 (67) 50 (65) 0.78
BSA, m2 1.80±0.21 1.82±9.18 0.64 1.81±0.2 1.81±0.1 0.83
Hypertension, n (%) 22 (56) 55 (68) 0.15 27 (63) 58 (75) 0.59
Diabetes, n (%) 6 (15) 10 (12) 0.75 5 (12) 13 (17) 0.57
CAD, n (%) 23
(64)
33
(41)
0.13 25 (58) 41 (59) 0.36
24
ACE inhibitor, n (%) 25 (64) 43 (53) 0.25 27 (63) 45 (58) 0.64
ARB, n (%) 10 (26) 19 (23) 0.79 10 (23) 19 (25) 0.86
Spironolactone, n (%) 3 (8) 7 (9) 0.86 4 (9) 6 (8) 0.77
Hydralazine, n (%) 5 (13) 7 (9) 0.47 6 (14) 6 (8) 0.28
ß-blocker, n (%) 28 (72) 54 (67) 0.32 28 (65) 54 (70) 0.57
Nitrates, n (%) 11 (28) 30 (37) 0.34 13 ((30) 28 (36) 0.50
Urgent PCI, n (%) 8 (21) 15 (19) 0.79 9 (21) 14 (18) 0.71
SBP, mm Hg* 131±13 135±20 0.31 128±12 137±19 0.02
DBP, mm Hg* 79±9 79±10 0.80 79±8 78±10 0.80
Heart rate, bpm* 71±11 72±12 0.68 70±10 69±11 0.80
*Obtained at the time of echocardiography and cardiac catheterization
Table 2 Echocardiographic parameters. Data are grouped by LV filling pressures.
Variable LV filling pressure, pre-A LV filling pressure, end-diastolic
≤12
mm Hg
>12
mm Hg
p ≤15
mm Hg
>15
mm Hg
p
Number of patients 39 81 43 77
LVEF, % 64±7 64±10 0.72 64±7 64±10 0.72
LAVi, ml/BSA 24±6 31±8 0.0001 25±6 31±9 <0.0001
Vp, cm/sec 54±16 46±16 0.01 55±17 46±15 0.004
E velocity, cm/sec 75±20 79±20 0.34 73±20 80±20 0.05
A velocity, cm/sec 82±20 85±24 0.51 79±21 87±24 0.09
E/A ratio 0.95±0.3 1.0±0.34 0.48 1.0±0.3 1.00±0.4 0.63
DT, msec 200±42 205±62 0.67 201±44 203±62 0.89
25
MV A duration, msec 126±28 120±21 0.21 124±24 120±23 0.39
e septal (cm/sec) 6.5±2.0 6.0±1.8 0.14 6.9±1.9 5.9±1.7 0.003
e lateral, cm/sec 9.4±1.9 8.1±2.3 0.004 9.7±2.2 7.9±2.0 <0.0001
Av e , cm/sec 8.1±1.9 7.0±1.8 0.002 8.3±1.8 6.9±1.7 <0.0001
E/e ratio, septal 11.7±4.1 13.5±4.5 0.04 11.0±3.5 14.5±4.6 <0.0001
E/e ratio, lateral 7.9±2.8 10.1±3.6 0.002 7.8±2.5 10.7±3.5 <0.0001
Average (Av) E/e 10,0±3.2 12.2±3.8 0.003 9.4±2.8 12.6±4 <0.0001
IVRT/LV filling time 0.21±0.1 .29±0.1
1
0.0003 0.2±0.1 0.3±0.11 <0.0001
TR velocity, cm/sec 240±35 263±35 0.001 241±34 264±35 <0.0001
Pulmonary Vein Variables
S wave, cm/sec 61±13 60±14 0.94 59±11 61±15 0.55
D wave, cm/sec 45±11 46±17 0.84 45±13 46±17 0.88
S/D ratio 1.4±0.3 1.5±0.4 0.71 1.4±0.3 1.4±0.4 0.58
ArV, mm/sec 27±4 32±5 <0.0001 26±3 32±5 <0.0001
Ar duration, msec 119±20 144±26
<0.0001
116±17 148±24 <0.0001
Ar- A, msec -6±29 25±25 <0.0001 -8±26 32±5 <0.0001
26
Table 3 Sensitivity and specificity for specific cut points as derived from the ROC curves for
each echocardiographic parameter of diastolic function. Data are shown for both LVEDP >
15 mmHg and pre-A > 12 mmHg.
Parameters Criterion Sensitivity %
(95%CI)
Specificity %
(95%CI)
+PV -PV
TR V, cm/sec >15 >278 * 44.2 (32.8-55.9) 97.7 (87.7-99.6) 97.1 49.4
>12 >259 * 63.0 (51.5-73.4) 74.4 (57.9-86.9) 83.6 49.2
DT, cm/sec >15 <=168 * 32.5 (22.2-44.1) 81.4 (66.6-91.6) 75.8 40.2
>12 <=170 * 35.8 (25.5-47.2) 84.6 (69.5-94.1) 82.9 38.8
E/A >15 >1.2 * 28 (18.2-39.6) 81.4 (66.6-91.6) 72.4 39.3
>12 >1.2 * 28.4 (18.9-39.5) 84.6 (69.5-94.1) 79.3 36.3
e sep, cm/sec >15 <=7 * 83.1 (72.9- 90.7) 44.2 (29.1-60.1) 72.7 59.4
>12 <=7 * 82.7 (72.7- 90.2) 46.2 (30.1-62.8) 76.1 56.2
e lat cm/sec
>15 >7.8 * 80.5 (69.9-88.7) 62.8 (46.7-77.0) 79.5 64.3
>12 <9 * 76.5 (65.8-85.2) 53.9 (37.2-69.9) 77.5 52.8
Av e , cm/sec >15 <=8.5 * 87.0 (77.4-93.6) 46.5 (31.2-62.3) 74.4 66.7
>12 <=8.5 * 85.2 (75.5-92.1) 46.2 (30.1-62.8) 76.7 60.0
E/e septal >15 >12.7* 62.3 (50.6-73.1) 79.1 (64.0-89.9) 84.2 54
>12 >10.3 * 77.8 (67.2-86.3) 53.9 (37.2-69.9) 77.8 53.8
E/e lateral >15 >7.8 * 80.5 (69.9-88.7) 62.8 (46.7-77) 79.5 64.3
>12 >7.8 * 75.3 (64.5-84.2) 56.4 (39.6-72.2) 78.2 52.4
Av E/e >15 >10.5 * 66.2 (54.6-76.6) 76.7 (61.4-88.2) 83.6 55.9
>12 >8.8 * 80.3 (69.9-88.3) 51.3 (34.8-67.6) 77.4 55.6
Vp, cm/sec >15 <=55 * 82.9 (72.5-90.6) 47.6 (32.0-63.6) 74.1 60.6
>12 <=50 * 74.1 (63.1‑83.2) 56.8 (39.5‑72.9) 78.9 50
27
PV S/PV D >15 >1.33 * 61.0 (49.2-72.0) 51.2 (35.5-66.7) 69.1 42.3
>12 <=0.97 * 14.8 (7.9 -24.5) 97.44 (86.5-99.6) 92.3 35.5
ArV, cm/sec >15 >31 * 53.3 (41.5-64.7) 95.4 (84.2-99.3) 95.3 53.2
>12 >31 * 50.6 (39.3-61.9) 94.9 (82.6-99.2) 95.3 48.1
Ar-A, msec
>15 >7 * 88.3 (79.0- 94.5) 81.4 (66.6-91.6) 89.5 79.5
>12 >7 * 81.48 (71.3-89.2) 74.36 (57.9-86.9) 86.8 65.9
LAVi, ml/m2 >15 >31.5 * 48.1 (36.5-59.7) 92.9 (80.5-98.4) 92.5 49.4
>12 >26.8 * 73.75 (62.7-83.0) 76.92 (60.7-88.8) 86.8 48.1
IVRT, msec
>15 >99 * 80.5 (69.9-88.7) 69.8 (53.9-82.8) 82.7 66.7
>12 >99 * 77.8 (67.2-86.3) 69.2 (52.4 - 83.0) 84 60
IVRT/LFT >15 >0.27 * 55.8 (44.1-67.2) 90.7 (77.8-97.3) 91.5 53.4
>12 >0.27* 51.9 (40.5-63.1) 87.18 (72.6-95.7) 89.4 46.6
28
Table 4 Comparison of the areas of ROC curves for detection of a LVEDP >15
mmHg for each echocardiographic parameter of diastolic dysfunction
Echocardiographic parameter Area (95% CI) P value for Area > 0.5
TR V, cm/sec 0.71 (0.62, 0.79) 0.0001
E/A 0.52 (0.42, 0.61) 0.764
DT, msec 0.51 (0.41, 0.60) 0.891
Ar-A, msec 0.85 (0.77, 0.91) 0.0001
e septal, cm/sec 0.67 (0.58, 0.75) 0.001
e lateral, cm/sec 0.74 (0.65,0.82) 0.0001
e average, cm/sec 0.72 (0.63,0.80) 0.0001
E/ e septal 0.76 (0.66, 0.82) 0.0001
E/e lateral 0.75 (0.66, 0.82) 0.0001
E/e average 0.76 (0.68, 0.84) 0.0001
PArV, cm/sec 0.82 (0.74, 0.89) 0.0001
Vp, cm/sec 0.65 (0.56, 0.74) 0.005
LAVi, ml/BSA 0.74 (0.65, 0.82) 0.0001
PV S/D 0.53 (0.43, 0.62) 0.624
Table 5 Agreement between the observed LV filling pressures and the
29
echocardiographic estimates in patients with a normal LVEF
Echocardiographic algorithms Left ventricular filling pressure
Elevated (>15
mmHg)
Normal (≤15 mmHg)
2016 guidelines
Elevated 22 1
Normal 30 36
Indeterminate 25 6
2016 criteria plus
ArV > 32 cm/sec
Elevated 35 1
Normal 21 35
Indeterminate 21 7
Proposed:
LVEDP >15 mmHg
Elevated 55 2
Normal 10 36
Indeterminate 12 5
Proposed: pre-A >12
mmHg
Elevated 48 4
Normal 13 27
Indeterminate 20 8
30
Table 6 Comparison of different echocardiographic algorithms in predicting
abnormal LV filling pressures in patients with a normal LVEF
Algorithms Sensitivity
%
(95%CI)
Specificity
%
(95%CI)
+LR
%
(95%CI)
-LR
%
(95%CI)
+PV
%
(95%CI)
-PV
%
(95%CI)
Accuracy
%
(95%CI)
2016 guidelines for
LVEDP >15 mmHg
87
(75.1-94.6)
54.6
(41.8-66.9)
1.91
(1.4-2.5)
0.24
(0.1-0.5)
61.0
(54.1-67.5)
83.7
(71.4-91.4)
69.2
(60.1-77.3)
2016 criterion plus
ArV > 32 cm/sec
87.5
(76.9-94.5)
62.5
(48.6-75)
2.3
(1.6-3.3)
0.2
(0.1-0.4)
72.7
(65.3-79.1)
81.4
(68.9-89.6)
75.8
(67.2-83.2)
Newly proposed for
LVEDP >15 mmHg
90.3
(81.0-96.0)
75
(60.4-86.4)
3.6
(2.2-5.9)
0.13
(0.1-0.3)
84.4
(76.7-89.9)
83.7
(71.4-91.4)
84.2
(76.4-90.2)
Newly proposed for
pre-A >12 mmHg
84
(74.1-91.1)
69.2
(75.8-97.1)
2.7
(1.7-4.4)
0.2
(0.1-0.3)
85
(77.8-90.2)
67.5
(54.8-78.1)
79.2
(70.8-86.0)
31
Figure 1 These LV pressure waveforms were recorded from one patient
The solid arrow points to left ventricular minimal pressure (18 mmHg), the
dashed arrow to left ventricular pre-A pressure (28 mmHg), and the
dotted arrow to left ventricular end-diastolic pressure (37 mmHg). The
patient is a 59 years male with hypertension and coronary artery disease
(LCX stenosis 70%). Cardiac catheterization was performed for chest pain
and ST T changes.
32
Figure 2 Comparison of the ROC curve for each of the Doppler
parameters of diastolic function that are used to identify an LV end
diastolic pressure > 15 mmHg. The areas under the curves for most
parameters are similar and range from 0.65 to 0.85. There is no single
parameters that can reliably predict an elevated LV pressure. In particular,
the mitral valve E/A ratio and septal eˊ were not useful.
Abbreviations: AvE/e = average E/e ; LAVi = left atrial volume index;
ArV = pulmonary vein A reversal velocity; TR velocity = tricuspid
regurgitation velocity; E/e sep = the ratio when e is obtained at the
septum; E/e lat = the ratio when e is obtained from the lateral wall;
33
Figure 3 The proposed algorithm (A) and the 2016 guidelines
algorithm (B) are compared. The modest differences in the proposed
criteria are highlighted in red. Both identify patients as normal if there
are 0-1 abnormal criteria and as abnormal if there are ≥ 3 criteria.
However, the 2016 guidelines did not include the velocity of the
pulmonary vein A reversal.
34
Figure 4 Echocardiographic data from the same patient in Figure 1.
The left ventricular ejection fraction was 73%. The parameters shown in
this figure show a septal E/eˊ of 13.8, a pulmonary vein A reversal
velocity of 0.33 m/s and an increased TR velocity of 2.85 m/s; these 3
values plus the LA volume index of 35 ml/m2 indicate that the LV end
diastolic pressure is elevated (invasive LVEDP =37 mmHg), consistent
with diastolic dysfunction grade II.
35
Figure 5 Accuracies of 2 algorithms to detect a LVEDP > 15 mmHg.
The new algorithm showed a trend towards a greater accuracy when
compared to that of the 2016 algorithm that included the PArV
(pulmonary A reversal velocity), (p = 0.052).
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