E/e’ Ratio in Patients with Unexplained Dyspnea: Lack of...

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E/e’ Ratio in Patients with Unexplained Dyspnea: Lack of Accuracy in

Estimating Left Ventricular Filling Pressure

Santos et al: E/e’ in Unexplained Dyspnea

Mário Santos, MD1; Jose Rivero, MD, RDCS2; Shane D. McCullough, RDCS2;

Erin West, MSc2; Alexander R. Opotowsky, MD, MPH2,3; Aaron B. Waxman, MD, PhD4;

David M. Systrom, MD4; Amil M. Shah, MD, MPH2

1Department of Physiology and Cardiothoracic Surgery, Cardiovascular R&D Unit, Faculty

of Medicine, University of Porto, Portugal

2Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, MA

3Department of Cardiology, Boston Children’s Hospital, Boston, MA

4Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital,

Boston, MA

Correspondence to Amil M. Shah Division of Cardiovascular Medicine, Brigham and Women’s Hospital 75 Francis Street, Boston, MA 02115 Email: [email protected] DOI: 10.1161/CIRCHEARTFAILURE.115.002161

Journal Subject Codes: [31] Diagnostic testing, Echocardiography; [11] Heart failure, Other

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Abstract

Background—Elevated left ventricular filling pressure (LVFP) is a cardinal feature of heart

failure with preserved ejection fraction (HFpEF). Mitral E/e’ ratio has been proposed as a

non-invasive measure of LVFP. We studied the accuracy of E/e' to estimate and track

changes of LVFP in patients with unexplained dyspnea.

Methods and Results—We performed supine and upright transthoracic echocardiography in

118 patients with unexplained dyspnea who underwent right heart catheterization. Supine

E/e’ ratio modestly but significantly correlated with supine pulmonary arterial wedge

pressure (PAWP) (r=0.36; p<0.001) and demonstrated poor agreement with PAWP values

(Bland-Altman limits of agreement of -8.3 to 8.3 mmHg; range: 6.5 to 21.2 mmHg).

Similarly, E/e’ ratio cut-off of 13 performed poorly in identifying patients with elevated

LVFP (sensitivity 6%, specificity 90%). The ROC area of E/e’ was 0.65 (95% CI: 0.50-0.79).

With change from the supine to upright position, PAWP decreased (-5±4 mmHg; p<0.001) as

did both E-wave (-17±15 cm/s; p<0.001) and e’ (-2.7±2.7 cm/s; p<0.001) velocities, while

E/e’ remained stable (+0.2±2.6; p=0.57). Positional change in PAWP correlated modestly

with change in E-wave (r=0.37; p<0.001) velocity. There was no appreciable relationship

between change in PAWP and change in average E/e’ (r=-0.04; p=0.77) and in half the

patients the change in PAWP and E/e’ were directionally opposite.

Conclusions—In patients with unexplained dyspnea, E/e’ ratio neither accurately estimates

PAWP nor identifies patients with elevated PAWP consistent with HFpEF. Positional

changes in E/e’ ratio do not reflect changes in PAWP.

Key Words: heart failure, echocardiography, left ventricular filling pressure, E/e’ ratio,

dyspnea, hemodynamics



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Dyspnea is a common symptom, affecting up to half of patients in the inpatient setting and

one quarter of patients in the ambulatory setting1. Dyspnea may be caused by cardiac,

pulmonary, hematologic, neuropsychiatric or neuromuscular diseases. Among patients with

dyspnea and normal left ventricular ejection fraction (LVEF), pulmonary function, and

oxygen carrying capacity, the diagnosis of heart failure with preserved ejection fraction

(HFpEF) is particularly challenging. Because cardiac structural and functional changes in

HFpEF are more subtle and less specific than in heart failure with reduced LVEF, the

demonstration of increased left ventricular filling pressure (LVFP) is central to establishing

this diagnosis2. The invasive assessment of LVFP is usually done during right heart

catheterization (RHC) by measurement of pulmonary arterial wedge pressure (PAWP).

Transthoracic echocardiography can be used to non-invasively estimate LVFP. Several

echocardiographic measures have been used3, but the ratio of the peak early mitral inflow

velocity (E) over the early diastolic mitral annular velocity (e’) has gained wide acceptability

in routine clinical practice4. Although integration of multiple echocardiographic measures is

always preferred, the E/e’ ratio is often used by itself to appraise LVFP due to the relative

ease of acquisition, calculation, and interpretation. The E/e’ ratio has been endorsed by

professional guidelines as a surrogate parameter of LVFP in the diagnostic work-up of

HFpEF5. In theory, a decrease in LV preload (a major determinant of LVFP) will result in a

lower atrial-to-LV diastolic pressure gradient and lower E wave velocity, without

significantly affecting e’ which is considered to be relatively independent of pressure-flow

gradients6. Despite its widespread use, conflicting data have been reported regarding its

accuracy and its ability to track changes in LVFP 4, 7-10. Therefore, we aimed to study the

accuracy of E/e’ to estimate and track changes in LVFP, as well as to identify elevated LVFP

consistent with HFpEF in patients with unexplained dyspnea and a preserved LVEF.



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Methods

Subjects and Study Design

We studied sequential patients with dyspnea of indeterminate cause referred to the Dyspnea

Clinic at Brigham and Women’s Hospital between May 2013 and June 2014. All patients

underwent resting supine and upright invasive hemodynamic evaluations. Patients with

LVEF < 50%, more than mild valvular disease, prosthetic mitral valve and atrial fibrillation

were excluded from this analysis. The Partners Human Research Committee approved this

study and waived the requirement for informed consent.

Invasive Hemodynamic Study

A flow-directed, balloon-tipped, 4-port pacing pulmonary artery catheter (Edwards

Lifesciences, Irvine, CA) was placed into the pulmonary artery, with ultrasound and

fluoroscopic guidance. A second catheter was inserted into the radial artery using a 20-gauge

IV or 5-French sheath. End expiratory systemic arterial, right atrial (RAP), right ventricular

(RVP), pulmonary artery pressures (PAP) and PAWP were measured using a hemodynamic

monitoring system (Xper Cardio Physiomonitoring System, Philips, Andover, Massachusetts)

calibrated before each study. The pressure transducer was leveled using as references the mid

axillary line (supine) and 5cm below the axillary fold (upright). Cardiac output (CO) was

determined by assumed Fick or thermodilution methods during supine RHC, and true Fick

method with direct measurement of VO2, arterial and mixed venous O2 content, during

upright assessments.

Echocardiography

Supine transthoracic echocardiography was performed before patients underwent RHC (time

interval <1 hour). After catheterization, upright transthoracic echocardiography was



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performed with the patient seated resting on the cycle ergometer simultaneously with the

invasive hemodynamic measurements. All quantitative echocardiographic measurements

were performed by a single reader (M.S.) blinded to invasive hemodynamic data, using a

computerized off-line analysis station as previously described11. Peak early diastolic tissue

velocity (e’) was measured at the septal and lateral mitral annulus. Mitral inflow velocity was

assessed by pulsed wave Doppler from the apical 4-chamber view, positioning the sample

volume at the tip of the mitral leaflets. Deceleration time of the E-wave was measured as the

interval from the peak E-wave to its extrapolation to the baseline. E/e’ ratio was calculated as

E-wave divided by e’ velocities. LV mass was estimated from LV linear dimensions and

indexed to body surface area as recommended by ASE guidelines12. LV hypertrophy (LVH)

was defined as LV mass indexed to body surface area (LV mass index; LVMi) >115 g/m2 in

men or >95 g/m2 in women. LV volumes were estimated by the modified Simpson method

using the apical 4- and 2-chamber views, and LVEF was derived from volumes in the

standard manner. LA volume was estimated by the method of disks using apical 4- and 2-

chamber views at an end-systolic frame preceding mitral valve opening and was indexed to

body surface area to derive LA volume index. Measurements were performed in triplicate

and the average value used for analysis. Intraobserver reproducibility was assessed in 20

studies randomly selected with the following results. E wave: correlation coefficient 0.99,

coefficient of variation 4%; septal e’: correlation coefficient 97%, coefficient of variation

4%; lateral e’: correlation coefficient 98%, coefficient of variation 5%. For the purposes of

generalizability, interobserver reproducibility was assessed in the same 20 studies with the

following results. E wave: correlation coefficient 0.94, coefficient of variation: 6%; septal e’:

correlation coefficient: 0.98, coefficient of variation 7%; lateral e: correlation coefficient

97%, coefficient of variation: 8%.



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Statistical Analysis

Continuous variables are expressed as mean ± standard deviation for normally distributed

variables or median and interquartile range for non-normally distributed variables.

Categorical variables are expressed as number of subjects and proportion [n (%)].

Comparisons between groups were performed using 2-sided parametric or non-parametric

tests (unpaired or paired t or Wilcoxon rank sums) for normally and non-normally distributed

data respectively. Fisher’s exact test was used to compare proportions. Univariate linear

regression analysis was performed to model an equation of the relationship between E/e’ ratio

and PAWP. Univariate logistic regression was used to study the association between E/e’

ratio the dichotomous variable of elevated LVFP (PAWP 15 mmHg). For each analysis,

separate univariate regression models were generated each of the following predictor

variables: lateral E/e’ ratio, septal E/e’ ratio, average E/e’ ratio. To further assess the

potential for E/e’ ratio to identify elevated LVFP, receiver operating characteristic (ROC)

curve analyses were performed. Correlations between those variables were determined using

Pearson or Spearman correlation, as appropriate. Bland-Altman analysis was used to assess

agreement between non-invasive and invasive variables. Two supplemental analyses were

performed. To assess the impact of missing data on our findings, were performed all

analyses restricted to the population of patients with complete data for supine and upright

PAWP and E/e’ ratio. In a second supplemental analysis, to assess the potential impact of an

outlier value, we repeated the analysis excluding this outlier value. A two sided p-value <0.05

was considered significant. Statistical analysis was performed using Stata software Version

12.1 (Stata Corp LP, College Station, TX, USA).



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Results

Studied Sample

Of a total of 140 subjects, we excluded 22 because of: LVEF < 50% (n=3), more than mild

valvular disease (n=13), valvular prosthesis (n=4) and atrial fibrillation (n=2). Of the

remaining 118 patients included in this analysis, 70% were female and the median age was

57 years (1st-3rd quartile: 40-70 years; Table 1). Mean BMI was 27.5±6.5 Kg/m2, and 25% of

patients were obese (defined as BMI 30 kg/m2). The most prevalent comorbidity was

hypertension (46%). Average LVMi was 64±19 g/m2, and LVH was present in 23% of

patients. LVEF was normal (63±8%) and supine invasive hemodynamics revealed normal

average cardiac index (3.0±0.6 L/min/m2), with a mean PAWP of 12±5 mmHg. 26 (22%) had

a supine PAWP > 15 mmHg. Echocardiographic data are summarized in Tables 1 and 2.

Mean E/A ratio was 1.2±0.5, and e’ septal (8.7±2.8 cm/s) was lower than e’ lateral (11.9±4.3

cm/s; p<0.001).

Supine Hemodynamic And Echocardiographic Data

PAWP modestly correlated with E/e’ septal (r=0.41; p<0.001), lateral (r=0.30; p<0.001) and

average (r=0.36; p<0.001) (Table 3; Figure 1). E/e’ refers to average E/e’ throughout the

remainder of this manuscript unless specifically noted. E/A ratio was even more modestly

correlated with PAWP (r=0.21; p=0.04); no correlation was found between DT and PAWP

(r=-0.06; p=0.57). Using supine average E/e’ to predict supine PAWP, the linear regression

model was: PAWP = 0.44*E/e’ average + 7.2 (N= 88; for the slope: p=0.001, 95%CI for

coefficient for E/e’ was: 0.20-0.68). We computed the predicted PAWP estimated by this

linear regression equation, and used the Bland-Altman method to quantify the agreement of

the predicted PAWP with the invasively measured PAWP. There was no bias (mean 0



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mmHg, 95%CI: -0.8; 0.8), and the limits of agreement were wide (-7.7 to 7.7 mmHg) –

Figure 1.

Twenty-two percent (n=26) of the study cohort has a supine RHC PAWP > 15 mmHg13. In a

logistic regression model, average E/e’ ratio was not significantly predictive of elevated

LVFP (OR=1.09; p=0.22, 95%CI: 0.95-1.27), with a ROC area of 0.65 (95%CI: 0.50-0.79).

While the mean PAWP was higher among those with an average E/e’ 13 compared to <13

(14±6 vs 11±4 mmHg respectively, p=0.001), an E/e’ average 13 had a sensitivity of 6%

and a specificity of 90% to identify elevated LVFP. Similarly, the ROC areas for E/e’ septal

and lateral were 0.67 (95%CI: 0.53-0.81) and 0.62 (95% CI: 0.46-0.78) respectively. An E/e’

septal 15 had a sensitivity of 6% and a specificity of 92%; an E/e’ lateral 12 had a

sensitivity of 13% and a specificity of 92% to discriminate patients with elevated LVFP.

Positional Changes in Hemodynamic and Echocardiographic Measures: Supine to Upright

There was a decrease in cardiac index (-0.3±0.9 L/min/m2) and PAWP (-5±4 mmHg) from

supine to upright position (Table 2). Mean arterial pressure increased modestly (+4±12

mmHg; p<0.001), as did systemic vascular resistance (+372±585 dyne.s.cm-5; p<0.001) and

heart rate (+8±12 bpm; p<0.001). Both LV diastolic and systolic volumes decreased, with a

mild decrease in LVEF (Table 2).

Despite the significant decrease of PAWP, no significant differences were found between

supine and upright E/e’ ratio (Table 2). We found no correlation between change in E/e’

(septal, lateral or average) and PAWP (Table 3; Figure 2). In fact, 46% (23/50) of patients

had a directionally discordant change of E/e’ when compared to PAWP (Table 4). Those with

concordant E/e’ and PAWP with positional change were older (62±16 vs 45±20 years-old;



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p=0.01), more likely to have hypertension (63 vs 22 %; p=0.003), and had lower myocardial

relaxation velocities (e’ average: 8.2±2.5 vs 12.0±3.8 cm/s; p<0.001) and larger left atria

(22±7 vs 17±4 mL/m2; p=0.007) than those with discordant changes.

With positional change, significant reductions in E-wave (-17±15 cm/s; p<0.001), e’ septal (-

1.8±2.3; p<0.001), and e’ lateral (-3.7±3.5; p<0.001) were noted. The change in E wave

velocity significantly correlated with the observed change in PAWP (r=0.41; p<0.001).

Change in PAWP was not significantly associated with the observed change in e’ septal

(r=0.18; p=0.12), change in e’ lateral (r=0.18; p=0.18), and change in e’ average (r=0.21;

p=0.11) – Figure 2.

Discussion

Supine E/e’ ratio had a significant, though modest, correlation with PAWP, but demonstrated

poor accuracy in estimating PAWP evidenced by the wide limits of agreement in Bland-

Altman analysis. Concordantly, the recommended E/e’ ratio cut-offs performed poorly in

identifying elevated LVFP. Furthermore, change in E/e’ ratio from supine to upright position

did not reliably track changes in PAWP, as both E and e’ were significantly affected by

hemodynamic changes. In fact, half of the studied patients had a directionally opposite

change in E/e’ compared to PAWP, indicating the erratic response of this non-invasive index

to load changes associated with the upright position.

Although several previous studies have compared non-invasive (echocardiography-based)

estimates of LVFP with invasive data (RHC), our study is one of the largest and – to our

knowledge – one of the first to investigate this question in a population of patients with

unexplained dyspnea, in whom assessment of LVFP is particularly important for diagnostic



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purposes. Consistent with previous studies using this methodology, we found a significant

correlation between supine E/e’ ratio and PAWP, 14, 15 with a comparable predictive equation

based on linear regression modeling 14, 16, 17. However, correlative measurements provide

little information about the agreement between supine E/e’ ratio and PAWP. Using Bland-

Altman analysis, we found wide limits of agreement between predicted PAWP based on the

supine E/e’ ratio and invasively measured PAWP. This indicates a large, clinically significant

difference in LVFP estimation when done by these 2 methods. In addition, E/e’ ratio did not

accurately identify patients with PAWP > 15 mmHg, and the recommended E/e’ cut-offs had

a very low sensitivity to identify elevated LVFP (Figure 3).

Change in E/e’ ratio did not correlate with change in PAWP. The mean E/e’ ratio was higher

on average in the upright position compared to supine, while PAWP was significantly lower.

This is concordant with a previous study18 and was explained by a more pronounced decrease

of e’ than E-wave from supine to upright. The 17% decrease in E-wave velocity reflects a

reduced transmitral pressure gradient, which may result from either a lower left atrial

pressure and/or a higher proto-diastolic LV pressure. The e’ average demonstrated a 28%

decrease with position change from supine to upright, with comparable reductions in both e’

septal and e’ lateral. Together with previous studies19-21 that used different interventions to

induce changes in LV preload, these findings clearly demonstrate that e’ is not load-

independent. This preload dependence may be more pronounced in patients with a compliant

myocardium, which may be more susceptible to changes in external load than a stiff

myocardium22. There are several mechanisms that may account for this. First, reduced LV

preload due to decreased venous return may influence e’ by decreasing ventricular filling

during proto-diastole (rapid filling phase)23. Decreased LV preload can also result in reduced

LV systolic torsion, leading to less energy release during early diastolic elastic recoil24.



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Second, the increased SVR is associated with an increase of LV afterload that can influence

the myocardial relaxation25. However, given the minor changes in systemic vascular

resistance and mean arterial pressure relative to the preload changes, and the known LV

diastolic tolerance to afterload when LVEF is preserved26, the contribution of increased

afterload to the observed positional changes in e’ appears limited.

The analysis of more than one pair of measurements from each patient allows a better

understanding of the individual utility of E/e’ ratio, which is often overlooked when only

group-derived variables are calculated from measurements at a single time-point. Notably, we

observed that almost half (46%) of patients had a discordant E/e’ ratio change compared to

PAWP. This expresses a wide inter-individual variation in the way E/e’ ratio relates with

PAWP. Some previous studies have reported a significant correlation between change in E/e’

and change in PAWP in decompensated HF, heart transplant and hypertrophic

cardiomyopathy patients14, 15, 17, 27, although this finding has been inconsistent. Bhella et al.16

actively manipulated LVFP of HF patients and healthy controls. The authors described the

inconsistent relation between group- and individual-derived linear regression slopes.

Likewise, Mullens et al.7 did not find a correlation between E/e’ ratio and PAWP changes in

decompensated HF patients. The reasons for the discrepancy among these studies may relate

to differences in patient characteristics as the presence of valvular regurgitation,

interventricular dessynchrony, systolic function, and different degrees of diastolic

dysfunction. Consistent with previous studies that showed a greater preload dependence of e’

in subjects with less impaired myocardial relaxation28, 29, we observed greater myocardial

relaxation velocities in those patients with discordant changes in E/e’ and PCWP.

Differences in the study design as the small sample size of the studied groups, potential

selection and ascertainment bias may also account for that discrepancy. Together, these



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findings seriously question the use of this echocardiographic parameter to track LVFP

changes.

This study has several limitations. TDI measurements in the upright position were missing in

a subset of patients. However, the absence of differences of clinical, echocardiographic and

invasive hemodynamics measurements between patients without versus with TDI missing

values argues against a systematic bias in the ascertainment of those echocardiographic

images (Supplemental material). In addition, sensitivity analyses restricted to participants

without missing data for supine or upright PAWP and E/e’ demonstrated consistent results

with primary analysis (Supplemental material). While upright image acquisition was

simultaneous with invasive measurements, supine TDI parameters were acquired within 1

hour before the PAWP measurement. Although we cannot exclude some error due to the non-

simultaneous measurement, the brief time interval makes large changes in measures unlikely.

In addition, we found better correlation on the supine than upright measurements. We used

change in position (supine to upright) to examine the relationship between E/e’ ratio and

LVFP changes. Although this maneuver evokes a complex cardiovascular response, the

observed changes in heart rate and LV afterload surrogates suggest that the predominant

change was that in LV preload, supporting the extrapolation of our results to LVFP changes

occurring in other clinical scenarios. Finally, correlation analyses can suffer from

disproportionate weighting of extreme outliers. We repeated our analysis excluding the

observed extreme outlier (Supplemental material) and had similar findings to our primary

analysis (Supplemental material). The extrapolation of our results to patients with

unexplained dyspnea should be cautious, as this is a very heterogeneous population

comprising patients presenting a wide spectrum of structural and functional cardiac

abnormalities.



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Despite these limitations, our study is one of largest with E/e’ ratio and related invasive

LVFP measurements. The studied population is heterogeneous and representative of patients

to whom LVFP estimation is commonly done in clinical practice to aid their diagnostic work-

up. We did paired measurements for each patient which allows us to go beyond the group

mean estimates and better understand the individual response of E/e’ ratio to LVFP changes.

Conclusions

In patients with preserved LVEF referred for RHC because of unexplained dyspnea, E/e’

ratio did not accurately estimate PAWP or identify patients with elevated PAWP consistent

with HFpEF. Positional changes in PAWP were not related to changes in the E/e’ ratio

especially in those with better myocardial relaxation. These results argues against using E/e’

ratio as an estimator of PAWP in patients with unexplained dyspnea and a preserved LVEF.

Sources of Funding

Work for this manuscript was supported by grant HMSP-ICJ/0013/2012 from the Portuguese

Foundation for Science and Technology (M.S.), 1K08HL116792-01A1 from the National

Institutes of Health (A.M.S.), and 14CRP20380422 from the American Heart Association

(A.M.S.).

Disclosures

Dr Shah reports receiving research support from Novartis, Actelion Pharmaceuticals Ltd, and

Gilead. The other authors have no disclosures.



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References

1. Parshall MB, Schwartzstein RM, Adams L, Banzett RB, Manning HL, Bourbeau J, Calverley PM, Gift AG, Harver A, Lareau SC, Mahler DA, Meek PM, O'Donnell DE. An official american thoracic society statement: Update on the mechanisms, assessment, and management of dyspnea. Am J Respir Crit Care Med. 2012;185:435-452.

2. Wachter R, Edelmann F. Diagnosis of heart failure with preserved ejection fraction. Heart Fail Clin. 2014;10:399-406.

3. Ommen SR, Nishimura RA, Appleton CP, Miller FA, Oh JK, Redfield MM, Tajik AJ. Clinical utility of doppler echocardiography and tissue doppler imaging in the estimation of left ventricular filling pressures: A comparative simultaneous doppler-catheterization study. Circulation. 2000;102:1788-1794.

4. Nagueh SF, Appleton CP, Gillebert TC, Marino PN, Oh JK, Smiseth OA, Waggoner AD, Flachskampf FA, Pellikka PA, Evangelisa A. Recommendations for the evaluation of left ventricular diastolic function by echocardiography. Eur J Echocardiogr. 2009;10:165-193.

5. Paulus WJ, Tschope C, Sanderson JE, Rusconi C, Flachskampf FA, Rademakers FE, Marino P, Smiseth OA, De Keulenaer G, Leite-Moreira AF, Borbely A, Edes I, Handoko ML, Heymans S, Pezzali N, Pieske B, Dickstein K, Fraser AG, Brutsaert DL. How to diagnose diastolic heart failure: A consensus statement on the diagnosis of heart failure with normal left ventricular ejection fraction by the heart failure and echocardiography associations of the european society of cardiology. Eur Heart J. 2007;28:2539-2550.

6. Wang J, Nagueh SF. Echocardiographic assessment of left ventricular filling pressures. Heart Fail Clin. 2008;4:57-70.

7. Mullens W, Borowski AG, Curtin RJ, Thomas JD, Tang WH. Tissue doppler imaging in the estimation of intracardiac filling pressure in decompensated patients with advanced systolic heart failure. Circulation. 2009;119:62-70.

8. Maeder MT, Thompson BR, Brunner-La Rocca HP, Kaye DM. Hemodynamic basis of exercise limitation in patients with heart failure and normal ejection fraction. J Am Coll Cardiol. 2010;56:855-863.

9. Geske JB, Sorajja P, Nishimura RA, Ommen SR. Evaluation of left ventricular filling pressures by doppler echocardiography in patients with hypertrophic cardiomyopathy: Correlation with direct left atrial pressure measurement at cardiac catheterization. Circulation. 2007;116:2702-2708.

10. Galderisi M, Lancellotti P, Donal E, Cardim N, Edvardsen T, Habib G, Magne J, Maurer G, Popescu BA. European multicentre validation study of the accuracy of e/e' ratio in estimating invasive left ventricular filling pressure: Euro-filling study. EurHeart J Cardiovasc Imaging. 2014;15:810-816.

11. Shah AM, Cheng S, Skali H, Wu J, Mangion JR, Kitzman D, Matsushita K, Konety S, Butler KR, Fox ER, Cook N, Ni H, Coresh J, Mosley TH, Heiss G, Folsom AR, Solomon SD. Rationale and design of a multicenter echocardiographic study to assess the relationship between cardiac structure and function and heart failure risk in a biracial cohort of community-dwelling elderly persons: The atherosclerosis risk in communities study. Circ Cardiovasc Imaging. 2014;7:173-181.

12. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, Picard MH, Roman MJ, Seward J, Shanewise JS, Solomon SD, Spencer KT, Sutton MS, Stewart WJ. Recommendations for chamber quantification: A report from the american society of echocardiography's guidelines and standards committee and the



ownloaded from


15

chamber quantification writing group, developed in conjunction with the european association of echocardiography, a branch of the european society of cardiology. J Am Soc Echocardiogr. 2005;18:1440-1463.

13. Hoeper MM, Bogaard HJ, Condliffe R, Frantz R, Khanna D, Kurzyna M, Langleben D, Manes A, Satoh T, Torres F, Wilkins MR, Badesch DB. Definitions and diagnosis of pulmonary hypertension. J Am Coll Cardiol. 2013;62:D42-50.

14. Nagueh SF, Middleton KJ, Kopelen HA, Zoghbi WA, Quinones MA. Doppler tissue imaging: A noninvasive technique for evaluation of left ventricular relaxation and estimation of filling pressures. J Am Coll Cardiol. 1997;30:1527-1533.

15. Sundereswaran L, Nagueh SF, Vardan S, Middleton KJ, Zoghbi WA, Quinones MA, Torre-Amione G. Estimation of left and right ventricular filling pressures after heart transplantation by tissue doppler imaging. Am J Cardiol. 1998;82:352-357.

16. Bhella PS, Pacini EL, Prasad A, Hastings JL, Adams-Huet B, Thomas JD, Grayburn PA, Levine BD. Echocardiographic indices do not reliably track changes in left-sided filling pressure in healthy subjects or patients with heart failure with preserved ejection fraction. Circ Cardiovasc Imaging. 2011;4:482-489.

17. Nagueh SF, Lakkis NM, Middleton KJ, Spencer WH, 3rd, Zoghbi WA, Quinones MA. Doppler estimation of left ventricular filling pressures in patients with hypertrophic cardiomyopathy. Circulation. 1999;99:254-261.

18. Rowland T, Unnithan V, Barker P, Guerra M, Roche D, Lindley M. Orthostatic effects on echocardiographic measures of ventricular function. Echocardiography. 2012;29:523-527.

19. Hung KC, Huang HL, Chu CM, Chen CC, Hsieh IC, Chang ST, Fang JT, Wen MS. Evaluating preload dependence of a novel doppler application in assessment of left ventricular diastolic function during hemodialysis. Am J Kidney Dis. 2004;43:1040-1046.

20. Pela G, Regolisti G, Coghi P, Cabassi A, Basile A, Cavatorta A, Manca C, Borghetti A. Effects of the reduction of preload on left and right ventricular myocardial velocities analyzed by doppler tissue echocardiography in healthy subjects. Eur J Echocardiogr. 2004;5:262-271.

21. Jonassen AA, Bjornerheim R, Edvardsen T, Veel T, Kirkeboen KA. Effects of preload alterations on peak early diastolic mitral annulus velocities evaluated by tissue doppler echocardiography. Eur J Anaesthesiol. 2007;24:159-165.

22. Firstenberg MS, Greenberg NL, Main ML, Drinko JK, Odabashian JA, Thomas JD, Garcia MJ. Determinants of diastolic myocardial tissue doppler velocities: Influences of relaxation and preload. Journal of applied physiology. 2001;90:299-307.

23. Hinghofer-Szalkay H. Gravity, the hydrostatic indifference concept and the cardiovascular system. Eur J Appl Physiol. 2011;111:163-174.

24. Weiner RB, Weyman AE, Khan AM, Reingold JS, Chen-Tournoux AA, Scherrer-Crosbie M, Picard MH, Wang TJ, Baggish AL. Preload dependency of left ventricular torsion: The impact of normal saline infusion. Circ Cardiovasc Imaging. 2010;3:672-678.

25. Borlaug BA, Melenovsky V, Redfield MM, Kessler K, Chang HJ, Abraham TP, Kass DA. Impact of arterial load and loading sequence on left ventricular tissue velocities in humans. J Am Coll Cardiol. 2007;50:1570-1577.

26. Leite-Moreira AF, Lourenco AP, Roncon-Albuquerque R, Jr., Henriques-Coelho T, Amorim MJ, Almeida J, Pinho P, Gillebert TC. Diastolic tolerance to systolic pressures closely reflects systolic performance in patients with coronary heart disease. Basic Res Cardiol. 2012;107:251.



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27. Dokainish H, Zoghbi WA, Lakkis NM, Al-Bakshy F, Dhir M, Quinones MA, Nagueh SF. Optimal noninvasive assessment of left ventricular filling pressures: A comparison of tissue doppler echocardiography and b-type natriuretic peptide in patients with pulmonary artery catheters. Circulation. 2004;109:2432-2439.

28. Nagueh SF, Mikati I, Kopelen HA, Middleton KJ, Quinones MA, Zoghbi WA. Doppler estimation of left ventricular filling pressure in sinus tachycardia. A new application of tissue doppler imaging. Circulation. 1998;98:1644-1650.

29. Firstenberg MS, Levine BD, Garcia MJ, Greenberg NL, Cardon L, Morehead AJ, Zuckerman J, Thomas JD. Relationship of echocardiographic indices to pulmonary capillary wedge pressures in healthy volunteers. J Am Coll Cardiol. 2000;36:1664-1669.



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Table 1. Clinical characteristics of the studied patients

Characteristic N=118

Age, y 57 [40-70]

Female gender, n (%) 83 (70)

Ethnicity

White, n (%)

Black, n (%)

Asian, n (%)

105 (91)

7 (6)

3 (3)

BMI, Kg/m2 27.5±6.5

BSA, m2 1.9±0.3

Comorbidities

Hypertension, n (%) 54 (46)

Diabetes, n (%) 14 (12)

Smoking, n (%) 8 (7)

Obesity, n (%) 30 (25)

CAD, n (%) 15 (13)

CKD, n (%) 21 (18)

Medication

ASA, n (%) 30 (25)

CCB, n (%) 5 (4)

-blockers, n (%) 26 (22)

ACEi/ARBs, n (%) 26 (22)

Diuretics, n (%) 35 (30)

Statins, n (%) 36 (29)



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Blood analysis

Hemoglobin, g/dL 13.9±1.5

Creatinine, g/dL 0.9±0.3

eGFR, mL/min/m2 71±12

Echocardiographic parameters

LVEDVi, mL/m2 35±9

LVESVi, mL/m2 14±5

LVEF, % 63±8

Septal wall thickness, cm 0.9±0.2

Posterior wall thickness, cm 0.9±0.2

LV mass index, g/m2 64±19

LVH, n (%) 27 (23)

LAVi, mL/m2 18±6

Abbreviations: ACEi, angiotensin-converting-enzyme inhibitor; ARB, Angiotensin II

receptor blockers; ASA, acetylsalicylic acid; BMI, body mass index; BSA, body surface area;

CAD, coronary artery disease; CCB, calcium-channel blockers; CKD, chronic kidney disease

(eGFR < 60 mL/min/m2); eGFR, estimated glomerular filtration rate (calculated using

Cockcroft-Gault equation); LAVi, left atrium volume index; LV, left ventricular; LVESVi,

left ventricular end-systolic volume index; LVH, left ventricular hypertrophy; LVEDVi, left

ventricular end-diastolic volume index; LVEF, left ventricular ejection fraction.

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Table 2. Invasive hemodynamic and echocardiographic data in supine and upright

positions

Characteristic Supine N Upright N Delta N P-value

Invasive hemodynamic data

PAWP, mmHg 12±5 118 7±4 118 -5±4 118 <0.001

CI, L/min/m2 3.0±0.6 113 2.6±0.9 114 -0.3±0.9 109 <0.001

Systolic BP,

mmHg 134±23 117 145±26 118 +11±20 117 <0.001

Diastolic BP,

mmHg 78±11 117 79±13 118 +1±12 117 0.40

MAP, mmHg 97±13 117 101±15 118 +4±12 117 <0.001

SVR,

dyne.s.cm-5 1385±368 112 1750±574 112 +372±585 106 <0.001

HR, bpm 72±15 113 81±16 118 +8±12 113 <0.001

Echocardiographic data

E, cm/s 77±17 98 64±16 92 -17±15 75 <0.001

A, cm/s 71±21 95 67±20 88 -7±15 73 <0.001

E/A ratio 1.2±0.5 95 1.0±0.4 87 -0.2±0.4 72 <0.001

DT, ms 223±48 84 259±72 62 +30±65 47 0.002

e’ septal, cm/s 8.7±2.8 93 6.7±2.2 94 -1.8±2.3 76 <0.001

e’ lateral, cm/s 11.9±4.3 89 7.9±2.1 69 -3.7±3.5 58 <0.001

e’ average,

cm/s 10.3±3.4 88 7.4±2.0 67 -2.7±2.7 56 <0.001

E/e’ septal 9.7±3.6 93 10.3±3.7 80 -0.14±3.0 64 0.70



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E/e’ lateral 7.3±3.4 89 8.5±3.2 61 +0.6±2.9 52 0.17

E/e’ average 8.2±3.4 88 9.2±3.3 59 +0.2±2.6 50 0.57

LVEDVi,

mL/m2 35±9 90 29±9 81 -7±8 65 <0.001

LVESVi,

mL/m2 14±5 90 12±5 81 -2±4 65 <0.001

LVEF, % 63±8 90 61±10 81 -2±9 65 0.04

LAVi, mL/m2 18±7 92 13±5 82 -7±4 68 <0.001

Abbreviations: A, peak late mitral inflow velocity; BP, blood pressure; CI, cardiac index; DT,

deceleration time; E, peak early mitral inflow velocity; e’, peak early diastolic mitral annular

velocity; HR, heart rate; LAVi, left atrium volume index; LVEDSi, left ventricular end-

systolic volume index; LVEDVi, left ventricular end-diastolic volume index; LVEF, left

ventricular ejection fraction; MAP, mean arterial pressure; PAWP, pulmonary artery wedge

pressure; SVR, systemic vascular resistance.



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Table 3. Correlation between E wave, E/e’ and PAWP, and their orthostatic-induced

changes

Variable N Correlation

coefficient P-value

Supine

E/e’ septal 93 0.41 <0.001

E/e’ lateral 89 0.30 <0.001

E/e’ average 88 0.36 <0.001

E-wave 98 0.45 <0.001

E/A 95 0.21 0.04

LAVi 92 0.14 0.18

Upright

E/e’ septal 80 0.19 0.09

E/e’ lateral 61 0.03 0.80

E/e’ average 59 0.10 0.45

E-wave 92 0.21 0.05

E/A 87 -0.13 0.23

LAVi 82 0.39 <0.001

Delta

E/e’ septal 64 0.07 0.61

E/e’ lateral 52 -0.07 0.61

E/e’ average 50 -0.04 0.77

E wave 75 0.41 <0.001

e’ septal 76 0.18 0.12



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e’ lateral 58 0.18 0.18

e’ average 56 0.21 0.11

E/A 72 0.20 0.10

LAVi 68 -0.21 0.09

Abbreviations: E, peak early mitral inflow velocity; e’, peak early diastolic mitral annular

velocity; LAVi, left atrium volume index; PAWP, pulmonary artery wedge pressure.



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Table 4. Contingent table of the direction of PAWP and E wave, e’ average and E/e’

average changes with moving from the supine to the upright position. 19% (14/75), 16%

(9/56), 46% (23/50) of patients had a discordant change of E-wave, e’ average, E/e’

average, respectively, when compared to PAWP

E wave

E < 0 E > 0 Total

PAWP < 0 60 (80%) 10 (13%) 70 (93%)

PAWP > 0 4 (5%) 1 (1%) 5 (7%)

Total 64 (85%) 11 (15%) 75 (100%)

e’ average

e’ < 0 e’ > 0 Total

PAWP < 0 45 (80%) 5 (9%) 50 (89%)

PAWP > 0 4 (7%) 2 (4%) 6 (11%)

Total 49 (88%) 7 (13%) 56 (100%)

E/e’ average

E/e’ < 0 E/e’ > 0 Total

PAWP < 0 23 (46%) 22 (44%) 45 (90%)

PAWP > 0 1 (2%) 4 (8%) 5 (10%)

Total 24 (48%) 26 (52%) 50 (100%)

Abbreviations: E, peak early mitral inflow velocity; e’, peak early diastolic mitral annular

velocity; PAWP, pulmonary artery wedge pressure.



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Figure Legends

Figure 1. Relationship between PAWP measured by RHC and estimated by E/e’ ratio.

Legend: The modest correlation between the PAWP derived by E/e’ and directly measured

by RHC is shown in the scatter plot (A). The Bland-Altman plot (B) demonstrates no bias,

but wide a limits of agreement (±7.7 mmHg).

Figure 2. Response of E wave, e’ average and E/e’ ratio to PAWP changes (supine to

upright).

Legend: Both E wave (A) and e’ average (B) had a positive correlation to PAWP changes,

although the latter was not statistically significant. No linear relationship between E/e’ ratio

and PAWP (C) was found.

Figure 3. Supine PAWP by average E/e’ ratio groups using the recommended cut-off of 13.

Legend: Despite the observed differences of mean PAWP (11±4 vs 14±6 mmHg; p=0.001),

the overlap between groups is significant.



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Waxman, David M. Systrom and Amil M. ShahMário Santos, Jose Rivero, Shane D. McCullough, Erin West, Alexander R. Opotowsky, Aaron B.

Ventricular Filling PressureE/e' Ratio in Patients with Unexplained Dyspnea: Lack of Accuracy in Estimating Left

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SUPPLEMENTAL MATERIAL

Supplemental Methods

Supplement Analysis to Assess Missing data

We performed a sensitivity analysis to assess the influence of missing data in our

results by restricting our analysis to patients with no missing data both at supine and

upright average E/e’ (n=50). We noted no differences in the study results using this

subset of patients (see Table 1-3) compared to the overall study population. We

found a significant correlation between supine E/e’ ratio and PAWP (r=0.34; p=0.02).

The linear regression model was: PAWP = 0.39*E/e’ + 7.4 (p=0.009; 95%CI: 0.10-

0.68). Using this equation to predict PAWP, we found a similar width in agreement

(Bland-Altman method) between predicted and measured PAWP (95% limits of

agreement: -7.7 to 7.7 mmHg, range of 6.5 to 20.8 mmHg). Regarding the diagnostic

utility of E/e’ to identify elevated LVFP (PAWP > 15 mmHg), we found that the

ROC area was 0.66 (95%CI: 0.37-0.95); an E/e’ above 13 had a sensitivity of 17%

and specificity of 86%. The findings of this sensitivity analysis were, therefore,

consistent with the results of our primary analysis.

Supplemental Analysis of Extreme Outliers

We performed a sensitivity analysis to assess the weight of an identified extreme

outlier (Supplement Figure 1) in our main results. We found a significant correlation

between supine E/e’ ratio and PAWP (r=0.34; p=0.001), but still no correlation

between PAWP change and E/e’ change (r=-0.08; p=0.57). The linear regression

model was: PAWP = 0.31*E/e’ + 8.1 (p=0.02; 95%CI: 0.06-0.54). Using this

equation to predict PAWP, we found a similar width in agreement (Bland-Altman

method) between predicted and measured PAWP (95% limits of agreement: -7.3 to

7.3 mmHg). Regarding the diagnostic utility of E/e’ to identify elevated LVFP

(PAWP > 15 mmHg), we found that the ROC area was 0.62 (95%CI: 0.47-0.77); an

E/e’ above 13 had a sensitivity of 0% and specificity of 89%.

Hence, we can conclude that this outlier has no significant influence in our main

results.

Supplemental Tables

Supplemental Table 1 – Clinical, echocardiographic and invasive hemodynamics

supine features between patients with and without upright TDI missing values.

Characteristic No missing

(n=61)

Missing

(n=57) P-value

Age, y 54±19 53±19 0.69

Female, n (%) 42 (69) 41 (72) 0.71

BMI, Kg/m2 27.1±6.1 28.0±7.0 0.44

BSA, m2 1.9±0.3 1.9±0.3 0.39

LVEDVi, mL/m2 37±9 33±9 0.01

LVESVi, mL/m2 15±5 12±5 0.06

LVEF, % 62±7 63±9 0.76

LAVi, mL/m2 19±6 17±6 0.14

Septal wall

thickness, cm

0.94±0.18 0.94±0.15 0.84

Posterior wall

thickness, cm

0.90±0.14 0.86±0.20 0.21

LV mass index,

g/m2

67±18 60±20 0.07

E, cm/s 78±18 77±18 0.75

A, cm/s 70±22 73±19 0.63

E/A ratio 1.2±0.5 1.1±0.4 0.45

DT, ms 228±53 217±41 0.27

e’ septal, cm/s 8.4±2.9 9.0±2.5 0.32

e’ lateral, cm/s 11.5±4.4 12.4±4.2 0.34

e’ average, cm/s 10.0±3.6 10.7±3.2 0.33

E/e’ septal 10.2±4.2 9.1±2.6 0.13

E/e’ lateral 7.8±3.7 6.6±2.6 0.10

E/e’ average 8.7±3.8 7.5±2.5 0.09

PAWP, mmHg 11±5 12±5 0.88

CI, L/min/m2 3.0±0.6 3.0±0.6 0.98

Systolic BP,

mmHg

138±23 130±22 0.06

Diastolic BP,

mmHg

78±10 78±12 0.88

MAP, mmHg 98±12 96±13 0.30

SVR, dyne.s.cm-5 1431±393 1337±338 0.18

HR, bpm 70±15 75±14 0.08

Abbreviations: A, peak late mitral inflow velocity; BP, blood pressure; BMI, body

mass index; BSA, body surface area; CI, cardiac index; DT, deceleration time; E,

peak early mitral inflow velocity; e’, peak early diastolic mitral annular velocity; HR,

heart rate; LAVi, left atrium volume index; LVESVi, left ventricular end-systolic

volume index; LVEDVi, left ventricular end-diastolic volume index; LVEF, left

ventricular ejection fraction; MAP, mean arterial pressure; PAWP, pulmonary artery

wedge pressure; SVR, systemic vascular resistance.

Supplemental Table 2 – Invasive hemodynamic and echocardiographic data in

supine and upright positions of patients with no missing value of E-wave, e’ septal

and lateral data (upright and supine).

Characteristic Supine N Upright N Delta N P-value

Invasive hemodynamic data

PAWP, mmHg 11±4 50 6±3 50 -5±4 50 <0.001

CI, L/min/m2 3.0±0.6 47 2.6±0.8 49 -0.3±0.9 46 0.01

Systolic BP,

mmHg 139±22 49 146±26 50 +8±19 49 0.003

Diastolic BP,

mmHg 79±9 49 79±11 50 0±8 49 0.81

MAP, mmHg 100±11 49 102±13 50 +2±11 49 0.05

SVR,

dyne.s.cm-5 1446±370 46 1744±593 48 +356±557 44 <0.001

HR, bpm 69±15 47 79±14 50 +10±14 47 <0.001

Echocardiographic data

E, cm/s 78±18 50 60±13 50 -18±12 50 <0.001

A, cm/s 71±22 50 67±17 48 -5±13 48 <0.001

E/A ratio 1.2±0.5 50 1.0±0.3 48 -0.2±0.4 48 <0.001

DT, ms 227±53 46 262±67 31 +37±59 30 0.001

e’ septal, cm/s 8.4±3.0 50 6.5±1.9 50 -1.9±2.1 50 <0.001

e’ lateral, cm/s 11.5±4.5 50 7.8±2.1 50 -3.8±3.5 50 <0.001

e’ average,

cm/s 9.9±3.6 50 7.1±1.8 50 -2.8±2.6 50 <0.001

E/e’ septal 10.3±4.2 50 10.1±3.7 50 -0.25±2.6 50 0.54

E/e’ lateral 7.9±3.9 50 8.4±3.2 50 +0.6±3.0 50 0.19

E/e’ average 8.8±3.9 50 9.0±3.2 50 +0.2±2.6 50 0.57

LVEDVi,

mL/m2 37±9 49 31±8 37 -8±8 37 <0.001

LVESVi,

mL/m2 15±5 49 12±5 37 -3±4 37 <0.001

LVEF, % 62±7 49 61±10 37 -2±9 37 0.15

LAVi, mL/m2 19±6 49 13±5 40 -7±5 40 <0.001

Abbreviations: A, peak late mitral inflow velocity; BP, blood pressure; CI, cardiac

index; DT, deceleration time; E, peak early mitral inflow velocity; e’, peak early

diastolic mitral annular velocity; HR, heart rate; LAVi, left atrium volume index;

LVEDSi, left ventricular end-systolic volume index; LVEDVi, left ventricular end-

diastolic volume index; LVEF, left ventricular ejection fraction; MAP, mean arterial

pressure; PAWP, pulmonary artery wedge pressure; SVR, systemic vascular

resistance.

Supplemental Table 3 – Correlation between E wave, E/e’ and PAWP, and their

orthostatic-induced changes of patients with no missing value of E-wave, e’ septal

and lateral data (upright and supine).

Parameter N Coefficient P-value

Supine

E/e’ septal 50 0.32 0.02

E/e’ lateral 50 0.29 0.04

E/e’ average 50 0.34 0.02

E-wave 50 0.33 0.03

E/A 50 0.11 0.46

LAVi 49 0.19 0.20

Upright

E/e’ septal 50 0.06 0.70

E/e’ lateral 50 -0.12 0.42

E/e’ average 50 -0.09 0.56

E-wave 50 0.18 0.22

E/A 48 -0.18 0.22

LAVi 40 0.38 0.01

Delta

ΔE/e’ septal 50 0.03 0.83

ΔE/e’ lateral 50 -0.11 0.43

ΔE/e’ average 50 -0.04 0.77

ΔE wave 50 0.42 0.003

Δe’ septal 50 0.14 0.33

Δe’ lateral 50 0.20 0.17

Δe’ average 50 0.22 0.12

Δ E/A 72 0.20 0.10

Δ LAVi 40 -0.30 0.06

Abbreviations: E, peak early mitral inflow velocity; e’, peak early diastolic mitral

annular velocity; LAVi, left atrium volume index; PAWP, pulmonary artery wedge

pressure.

Supplemental Table 4 – Contingent table of the direction of PAWP and E wave (A),

e’ average (B) and E/e’ average (C) changes with moving from the supine to the

upright position of patients with no missing value of E-wave, e’ septal and lateral data

(upright and supine). 16% (8/50), 16% (8/50), 46% (23/50) of patients had a

discordant change of E-wave, e’ average, E/e’ average, respectively, when compared

to PAWP.

A

ΔE < 0 ΔE > 0 Total

ΔPAWP < 0 41 (82%) 4 (8%) 45 (90%)

ΔPAWP > 0 4 (8%) 1 (2%) 5 (10%)

Total 45 (90%) 5 (10%) 50 (100%)

B

Δe’ < 0 Δe’ > 0 Total

ΔPAWP < 0 41 (82%) 4 (8%) 45 (90%)

ΔPAWP > 0 4 (8%) 1 (2%) 5 (10%)

Total 49 (90%) 7 (10%) 50 (100%)

C

ΔE/e’ < 0 ΔE/e’ > 0 Total

ΔPAWP < 0 23 (46%) 22 (44%) 45 (90%)

ΔPAWP > 0 1 (2%) 4 (8%) 5 (10%)

Total 24 (48%) 26 (52%) 50 (100%)

Abbreviations: E, peak early mitral inflow velocity; e’, peak early diastolic mitral

annular velocity; PAWP, pulmonary artery wedge pressure.

Supplemental Figures Supplemental Figure 1 – The outlier Supplemental Figure 1 Legend: The excluded outlier in the sensitivity analysis.

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