Accuracy of Doppler Echocardiography to Estimate Key Hemodynamic Variables in Subjects With Normal Left Ventricular Ejection Fraction

Journal of Cardiac Failure Vol. 17 No. 5 2011

Accuracy of Doppler Echocardiography to Estimate Key Hemodynamic Variables in Subjects With Normal Left Ventricular Ejection Fraction MICHA T. MAEDER, MD,1,2,3 SOFIE KARAPANAGIOTIDIS,1,2 ELIZABETH M. DEWAR,1,2 SARAH E. GAMBONI, BSc(Hons),2 NAY HTUN, MD,2 AND DAVID M. KAYE, MD, PhD1,2 Melbourne, Australia; and St. Gallen, Switzerland

ABSTRACT Background: The accuracy of Doppler echocardiography to estimate key hemodynamic parameters in subjects with normal left ventricular ejection fraction (LVEF) has not been fully investigated. Methods and Results: Thirty-six subjects with LVEF O50% (median age 62 years), with a broad clinical profile, underwent Doppler echocardiography immediately followed by right heart catheterization. Correlation coefficients between invasive and noninvasive right atrial pressure (RAP), systolic (sPAP) and mean (mPAP) pulmonary artery pressure, cardiac output (CO), and pulmonary vascular resistance (PVR) were 0.39, 0.70, 0.72, 0.57, and 0.60 (P ! .001 for all). There was no significant correlation between invasive and noninvasive (based on the peak early transmitral to peak early septal mitral annular velocity ratio) pulmonary capillary wedge pressure (PCWP; r 5 0.23; P 5 .18). Bland-Altman plots revealed variable bias but with consistently large limits of agreement for all noninvasive parameters, particularly PCWP. Areas under the receiver operating characteristic curve for noninvasive sPAP, CO, PVR, and PCWP to predict an invasively assessed mPAP $25 mm Hg, cardiac index !2.5 L min
1 m
2, PVR O3 Wood units, and PCWP #15 mm Hg, respectively, were 0.92, 0.83, 0.70, and 0.58. Conclusions: Single Doppler echocardiography parameters are not accurate enough to reliably estimate key hemodynamic parameters, particularly PCWP, in subjects with normal LVEF. (J Cardiac Fail 2011;17:405e412) Key Words: Heart failure, filling pressures, tissue Doppler, pulmonary hypertension.

The comprehensive evaluation and management of patients with a clinical syndrome of heart failure (HF) is vitally dependent on the development of a clear understanding of the hemodynamic perturbations that contribute to the symptomatic state. In particular, estimation of pulmonary pressures and left ventricular (LV) filling pressures is of

high utility, and it has been proposed that Doppler echocardiography can reliably be used as a noninvasive Swan-Ganz catheter,1e3 thereby avoiding the potential risks of cardiac catheterization. Although some studies have shown an excellent agreement between noninvasive and invasive measures,3e5 they have been performed in patients with HF and significantly impaired LV ejection fraction (LVEF).3e5 As such, those studies were based on a patient group in which LV relaxation is invariably abnormal, and mitral inflow patterns alone are often sufficient to estimate LV filling pressures.1 However, a more common and very challenging clinical scenario is the assessment of the patient with dyspnea in whom LV size and LVEF are normal. The differential diagnosis in this situation is broad and, among other entities, includes lung disease, pulmonary arterial hypertension (PAH), and HF with normal LVEF (HFNEF)6 which may be associated with pulmonary venous hypertension (PVH).7,8 If echocardiography reveals evidence of elevated pulmonary pressures, the differentiation into PAH and PVH

From the 1Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Heart Centre, Alfred Hospital, Melbourne, Australia and 3Division of Cardiology, Kantonsspital St. Gallen, St. Gallen, Switzerland. Manuscript received October 12, 2010; revised manuscript received December 10, 2010; revised manuscript accepted December 20, 2010. Reprint requests: David M. Kaye, MD, PhD, Head, Heart Failure Research Group, Baker IDI Heart and Diabetes Institute, PO Box 6492 St Kilda Road Central, Melbourne 8008 VIC, Australia. Tel: þ61-3-85321111; Fax: þ61-3-9076-8075. E-mail: [email protected] Supported by grants from the National Health and Medical Research Council of Australia (D.K.) and the Swiss National Science Foundation (no. PBZHB-121007; M.M.). See page 411 for disclosure information. 1071-9164/$ - see front matter Ó 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.cardfail.2010.12.003 2

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406 Journal of Cardiac Failure Vol. 17 No. 5 May 2011 is critically important for the development of an appropriate treatment plan.9 Accordingly, the reliable estimation of key hemodynamic variables, including systolic and mean pulmonary artery pressure (sPAP and mPAP), pulmonary vascular resistance (PVR) or transpulmonary gradient (TPG), cardiac output (CO), and pulmonary capillary wedge pressure (PCWP), is equally important in patients with normal LVEF to understand the underlying pathophysiology and to guide management. However, data on the ability of Doppler echocardiography to provide a reliable and comprehensive hemodynamic assessment in this setting are very sparse. Accordingly, the aim of the present study was to assess the accuracy of Doppler echocardiography in assessing key hemodynamic variables in subjects with normal LVEF and different pathophysiologic entities. Methods Study Population and Protocol We studied 36 subjects with LVEF O50%, normal sinus rhythm, and a broad clinical profile. Eleven patients previously diagnosed with PAH based on invasive measurements underwent repeated right heart catheterization for the evaluation of changes in treatment. Fifteen patients had clinically suspected HFNEF, which was diagnosed based on symptoms of HF, presence of a nondilated left ventricle with LVEF O50%, objective evidence of impaired exercise capacity, and absence of another explanation for dyspnea such as significant lung disease. In all of these patients with HFNEF, PAH was excluded by invasive measurements. These patients were also characterized by a rapid increase in PCWP at low work rate during exercise right heart catheterization.10 Ten control subjects were also studied, including 8 asymptomatic healthy volunteers who were recruited by advertisement and 2 subjects with atypical symptoms who had been referred for exclusion of pulmonary hypertension. Subjects with angina, cardiomyopathies, or more than mild aortic or mitral valve disease were excluded. All subjects underwent Doppler echocardiography immediately followed by right heart catheterization. Examinations were performed in the nonfasting state and under full medication if applicable. The study was approved by the Alfred Hospital Ethics and Research Committee, and each of the subjects provided written informed consent. Echocardiography Transthoracic echocardiograms (iE33; Philips Healthcare, North Ryde, New South Wales, Australia) were obtained by 1 experienced echocardiographer, using standard views in accordance with current guidelines.11,12 Measurements were performed offline by a single experienced cardiologist blinded to invasive measurements. All reported measurements were averaged from 3 cycles. Cardiac output was calculated based on heart rate, left ventricular outflow tract (LVOT) diameter, and the LVOT velocity time integral (VTI).2 Right atrial pressure (RAP) was estimated based on diameter and respiratory variability of the inferior vena cava (5, 10, 15, or 20 mm Hg).11 sPAP was estimated based on the peak tricuspid regurgitation velocity (VTRpeak) and RAP.13 The mean sPAP was calculated as 0.61  sPAP þ 2.14 Pulmonary vascular resistance (PVR) was estimated from the right ventricular outflow tract (RVOT) VTI and VTRpeak: PVR 5 (VTRpeak/

RVOT VTI)  10 þ 0.6.15 We decided not to use another published, more complex, formula for the estimation of PVR, because that formula has been developed exclusively in patients with advanced HF and impaired LVEF.16 Pulsed-wave Doppler recordings of the transmitral inflow were obtained between the mitral leaflet tips from the apical 4-chamber view to assess the peak early transmitral velocity (E). Peak early diastolic mitral annular velocities were measured by pulsed-wave tissue Doppler at the septal and lateral annulus, and averaged values were also calculated (e0 septal/lateral/av).12 The E/e0 ratio was calculated for the septal (E/e0 septal) and the lateral (E/e0 lateral) annulus as well as based on e0 av (E/e0 av).12 A published formula to estimate PCWP was used: PCWP 5 11.96 þ 0.596  E/e0 septal.8 This formula had previously been used to estimate PCWP in patients with normal LVEF.8 We also assessed the relationship between PCWP and E/e0 lateral and E/e0 av. We did not use another formula to estimate PCWP derived from a study in patients with HF and impaired LVEF,5 because that formula is based on mitral inflow parameters that exhibit a linear relationship with the severity of LV diastolic dysfunction in patients with HF and impaired LVEF (no normal patterns) but not in subjects with normal LVEF, where there is a J-shaped relationship between mitral inflow patterns and the severity of LV diastolic function.12 Right Heart Catheterization Cardiac catheterization was performed immediately after completion of the echocardiogram. A 3F arterial line (Cook, Brisbane, Queensland, Australia) was placed in a radial or brachial artery for blood pressure measurement. A 7-F balloon-tipped pulmonary artery catheter (Edwards Lifesciences, Irvine, California, USA) was inserted via an introducer sheath placed in the right internal jugular or a brachial vein for measurement of RAP, pulmonary artery pressures, and PCWP. The wedge position was confirmed by fluoroscopy and pressure waveform, and the mean PCWP was measured at end-expiration. Cardiac output was measured by using thermodilution with measurements taken in triplicate. Transpulmonary gradient and PVR were calculated according to standard formulas. Statistical Analyses Data are presented as counts and percentages, mean 6 standard deviation, or median (interquartile range) as appropriate. Control subjects, patients with clinically suspected HFNEF, and patients with PAH were compared using chi-squared test, 1-way analysis of variance, and Kruskal-Wallis tests, respectively, and appropriate post hoc tests. Pearson or Spearman correlation coefficients between invasive and noninvasive measures were calculated as appropriate. Bland-Altman plots were constructed to visualize bias and limits of agreement between invasive and noninvasive hemodynamic measures. Receiver operating characteristic curves were constructed to evaluate the ability of noninvasive measures to predict clinically important hemodynamic categories, such as RAP O8 mm Hg,9 mPAP O25 mm Hg,9 cardiac index !2.5 L/m,29 PCWP #15 mm Hg,9 PCWP O12 mm Hg,12,17 PVR O3 Wood units,18 and TPG O12 mm Hg.9 We performed calculations for 2 different clinically important PCWP cutoffs: PCWP #15 mm Hg is a prerequisite for the diagnosis of PAH,9 and PCWP O12 mm Hg has been suggested as an important invasive measure to obtain the diagnosis of HFNEF in a patient with symptoms or signs of HF and nondilated left ventricle and a LVEF O50%.17 A P value of !.05 was considered to be statistically significant. Analysis

Echo Hemodynamics in Subjects With Normal EF



Maeder et al

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Table 1. Clinical and Hemodynamic Characteristics of the Study Population Asymptomatic (n 5 10) Age (y) Gender (female) Body mass index (kg/m2) Hemoglobin (g/L) Creatinine (mmol/L) Treatment ACEI/ARB Diuretic Beta-blocker Calcium-channel blocker Warfarin Selective pulmonary vasodilator Hemodynamics Heart rate (beats/min) Systolic blood pressure (mm Hg) Diastolic blood pressure (mm Hg) Mean arterial pressure (mm Hg) Right atrial pressure (mm Hg) Systolic pulmonary artery pressure (mm Hg) Mean pulmonary pressure (mm Hg) Pulmonary capillary wedge pressure (mm Hg) Cardiac output (L/min) Cardiac index (L min
1 m
2) Transpulmonary gradient (mm Hg) Pulmonary vascular resistance (Wood units)

55 6 15 4 (40%) 27.5 6 7.2 145 6 15 69 6 7 0 0 0 0 0 0 68 6 15 152 6 25 75 6 12 94 6 14 6 (1e8) 28 6 7 17 6 4 10 6 3 7.0 6 1.7 3.6 6 0.9 762 1.0 6 0.4

Suspected HFNEF (n 5 15) 66 6 12 6 (40%) 31.0 6 7.2 136 6 16 83 6 22 8 5 5 8 2

(53%)* (33%) (33%)* (53%)* (13%) 0

67 6 11 149 6 11 75 6 9 93 6 7 4 (1e13) 31 6 9 19 6 6 11 6 5 5.4 6 1.5 2.6 6 0.5* 966 1.8 6 1.3

PAH (n 5 11) y

P Value

47 6 18 11 (100%)*,y 46.8 6 17.9 129 6 12 61 6 8y

.01 .003 .45 .09 .004

1 (9%) 5 (45%)* 0y 4 (36%) 11 (100%)*,y 10 (91%)*,y

.005 .03 .02 .02 !.001 !.001

74 6 9 129 6 17*,y 69 6 12 84 6 13 5 (0e22) 79 6 33*,y 47 6 18*,y 10 6 4 5.9 6 2.2 3.3 6 1.2 37 6 18*,y 7.4 6 5.0*,y

.28 .01 .41 .09 .9 !.001 !.001 .92 .14 .03 !.001 !.001

HFNEF, heart failure with normal left ventricular ejection fraction; PAH, pulmonary arterial hypertension; LVEF, left ventricular ejection fraction; ACEI/ ARB, angiotensin-converting enzyme inhibitor/angiotensin-receptor blocker. Data are given as n (%), mean 6 SD, or median (range) as appropriate. *P ! .05 vs asymptomatic control subjects. y P ! .05 vs HFNEF.

was performed using commercially available software packages (SPSS, version 15.0; SPSS, Chicago, Illinois, USA; Analyse-it, Leeds, UK).

Results Study Population

We studied a heterogeneous population with a large spectrum of clinical characteristics and a wide range of important hemodynamic parameters. The clinical characteristics of the 3 study groups are presented in Table 1. These subjects represented all consecutive subjects undergoing right heart catheterization at our institution during the study period and fulfilling the criteria outlined above apart from those not willing to participate in research (n 5 3). Invasive Measurements

Invasive hemodynamic data are presented in Table 1. The median (interquartile range) mPAP in the entire population was 19 (16e37) mm Hg. Thirteen subjects had mPAP $25 mm Hg and thereby fulfilled criteria for pulmonary hypertension. The mean PCWP in the entire population was 10 6 4 mm Hg. In 5 patients, PCWP was O15 mm Hg, and in 9 patients PCWP was O12 mm Hg. Noninvasive Measurements

Detailed echocardiographic characteristics are presented in Table 2. An acceptable tricuspid regurgitation signal could be obtained in all but 2 subjects. The inferior vena

cava could be sufficiently visualized in all but 3 subjects. All other noninvasive parameters could be obtained in all subjects. Agreement Between Noninvasive and Invasive Measurements

Correlation coefficients between invasive and noninvasive RAP, sPAP, mPAP, CO, and PVR were 0.39, 0.70, 0.72, 0.57, 0.60 (P ! .001 for all; Fig. 1). The correlation coefficient between invasive sPAP and the VTRpeak was 0.75 (P ! .001). There was no significant correlation between invasive and noninvasive (E/e0 septal-based) PCWP (r 5 0.23; P 5 .18). There was no significant correlation between invasive PCWP and E/e0 lateral (r 5
0.04; P 5 .84) and E/e0 av (r 5 0.13; P 5 .45), either. In addition, there was no significant correlation between invasive PCWP and other measures of LV diastolic function that are given in Table 2 (data not shown). There were no patients with restrictive mitral inflow patterns. Bland-Altman plots (Fig. 2) revealed a mild overestimation of invasive RAP by noninvasive RAP (bias þ1.4 mm Hg). However, there were very large limits of agreement (
5.9 to 8.7 mm Hg). There was a nonsignificant bias for the noninvasive prediction of sPAP (
4 mm Hg) and mPAP (0 mm Hg). Limits of agreement were large, however (
43 to 35 mm Hg and
22 to 22 mm Hg, respectively), which was explained at least in part by the poor agreement between noninvasive and invasive RAP. However, if the invasively assessed RAP rather than the estimated RAP was added to VTRpeak to calculate

408 Journal of Cardiac Failure Vol. 17 No. 5 May 2011 Table 2. Noninvasive Measurements (n 5 36) Asymptomatic (n 5 10) 2

Left ventricular end-diastolic volume index (mL/m ) Left ventricular ejection fraction (%) Left ventricular mass index (g/m2) Left atrial volume index (mL/m2) Left ventricular diastolic function Peak early transmitral flow velocity (E, cm/s) Peak atrial transmitral flow velocity (A, cm/s) Duration of atrial transmitral flow (A dur, ms) E/A ratio Deceleration time (ms) Peak systolic pulmonary vein velocity (S, cm/s) Peak diastolic pulmonary vein velocity (D, cm/s) Duration of pulmonary flow reversal during atrial contraction (Ar dur, ms) S/D ratio Ar dur
A dur (ms) Isovolemic relaxation time (ms) Tei index e0 septal (cm/s) e0 lateral (cm/s) e0 av (cm/s) E/e0 septal E/e0 lateral E/e0 av Right ventricular function Right ventricular fractional area contraction (%) Tricuspid annular plane systolic excursion (mm) Right ventricular s0 (cm/s) Tricuspid regurgitation severity (0/1/2/3) Noninvasively estimated hemodynamics Right atrial pressure (mm Hg) Systolic pulmonary artery pressure (mm Hg) Mean pulmonary artery pressure (mm Hg) Pulmonary vascular resistance (Wood units) Pulmonary capillary wedge pressure (mm Hg) Cardiac output (L/min)

55 65 90 34

6 6 6 6

18 7 27 13

80 71 149 1.28 215 62 50 126

6 6 6 6 6 6 6 6

1.24
18 96 39 9.2 12.6 10.9 9.5 6.9 8.2

6 6 6 6 6 6 6 6 6 6

6 6 6 6 6 6

PAH (n 5 11)

P Value

46 66 81 28

6 6 6 6

21 8 26 7

.04 .27 .63 .32

38 69 83 28

6 6 6 6

8* 6 17 8

18 30 28 0.49 77 16 12 24

79 86 167 0.98 223 49 44 129

6 6 6 6 6 6 6 6

18 24 48 0.39 60 16 14 17

80 75 165 1.18 232 54 54 118

6 6 6 6 6 6 6 6

24 30 15 0.48 36 18 22 14

.98 .38 .46 .24 .81 .17 .32 .37

0.23 24 27 14 3.1 4.2 3.5 3.3 2.0 2.4

1.16
38 105 46 6.1 8.3 7.2 13.4 10.3 11.9

6 6 6 6 6 6 6 6 6 6

0.34 53 22 13 1.5* 3.0* 1.9* 4.0 3.5* 3.3

1.11
48 100 51 7.6 12.4 10.0 12.6 7.6 10.0

6 6 6 6 6 6 6 6 6 6

0.40 20 34 17 3.6 5.4y 4.2 7.0 3.6 5.1

.66 .28 .74 .27 .03 .02 .02 .16 .03 .07

52 6 9 25 6 6 13.0 6 3.2 1/9/0/0 9 29 20 1.6 18 5.8

Suspected HFNEF (n 5 15)

5 2 1 0.3 2 1.3

51 6 7 23 6 4 12.6 6 2.3 1/11/3/0 8 36 24 1.7 20 5.1

6 6 6 6 6 6

4 13 8 0.3 2 1.2

31 6 12*,y 22 6 6 12.1 6 3.3 0/9/1/1 10 61 39 2.7 19 5.6

6 6 6 6 6 6

5 30*,y 18*,y 1.5*,y 4 1.8

!.001 .31 .25 .46 .42 .001 .001 .02 .16 .41

HFNEF, heart failure with normal left ventricular ejection fraction; PAH, pulmonary arterial hypertension; e0 septal/lateral/av, peak early diastolic mitral annular velocity measured at the septal/lateral annulus and the average value from both; E/e0 septal/lateral/av, peak early transmitral velocity to peak early diastolic mitral annular velocity ratio with e0 assessed at the septal/lateral annulus and the average value from both. Data are given as mean 6 SD. *P ! .05 vs asymptomatic control subjects. y P ! .05 vs HFNEF.

sPAP, limits of agreement were still large (
24.5 to 31.4 mm Hg). There was only a relatively small bias for the noninvasive CO for the prediction of invasive CO (bias
0.6 L/min) but limits of agreement were large (
3.4 to 2.2 L/min). Noninvasive PVR underestimated invasive PVR (bias
1.4 Wood units), and limits of agreement were large (
7.9 to 5.1 Wood units). Noninvasive PCWP overestimated invasive PCWP systematically and in a clinically highly relevant degree (bias 8.9 mm Hg), and limits of agreement were also large (
0.2 to 17.6 mm Hg). Noninvasive Measurements for the Prediction of Clinically Important Cutoffs

The areas under the receiver operating characteristic curve (AUCs) for noninvasive RAP, sPAP (or mPAP), and CO, respectively, to predict an invasively assessed RAP O8 mm Hg, mPAP $25 mm Hg, and cardiac index !2.5 L min
1 m
2 were 0.87 (95% confidence interval 0.68e1.00), 0.95 (0.89e1.00), and 0.83 (0.69e0.97),

respectively (P ! .001 for all). The AUCs for noninvasive PVR to predict PVR O3 Wood units and TPG O12 mm Hg, respectively, were 0.76 (0.58e0.94) and 0.74 (0.54e0.93) (P ! .05 for both). The AUCs for E/e0 septal, E/e0 lateral, and E/e0 av for predicting a PCWP #15 mm Hg were 0.58 (0.30e0.85), 0.51 (0.28e0.74), and 0.54 (0.28e0.79), respectively (P $ .29 for all). The AUCs for E/e0 septal, E/e0 lateral, and E/e0 av for predicting a PCWP O12 mm Hg were 0.66 (0.44e0.89), 0.54 (0.32e0.77), and 0.62 (0.39e0.85), respectively (P $ 0.08 for all). Discussion In the present study, we found that the degree of agreement between most noninvasive Doppler echocardiographyebased parameters and key invasive hemodynamic measurements in subjects with LVEF O50% was limited, such that their utility as single-parameter tools for clinical evaluation and management should be considered to be modest only.

Echo Hemodynamics in Subjects With Normal EF

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Fig. 1. Scatter plots showing the correlations between noninvasive and invasive right atrial pressure (RAP, panel A), systolic pulmonary artery pressure (sPAP, panel B), mean pulmonary artery pressure (mPAP, panel C), cardiac output (CO, panel D), pulmonary vascular resistance (PVR, panel E), and pulmonary capillary wedge pressure (PCWP, panel F). Solid circles: control subjects; open circles: heart failure with normal left ventricular ejection fraction; triangles: pulmonary arterial hypertension.

In particular, the correlation between invasive PCWP and the E/e0 ratio was very weak, although we excluded patients with significant mitral regurgitation and atrial fibrillation to avoid conditions confounding interpretation of the E/e0 ratio. Notably, our findings regarding the ability of the E/e0 ratio to predict PCWP are in accordance with a large study among patients with HF and impaired LVEF.19 A relationship between E/e0 and left-sided filling pressure clearly does exist, at least in some settings;20 however, it appears that its utility as a diagnostic test on an individual patient basis is limited. For example, in the study by Ommen et al.,20 the correlation coefficient between E/e0 septal and the mean LV diastolic pressure was 0.60 in patients with LVEF !50% and only 0.47 in those with LVEF O50%. Moreover, it has also been shown that the E/e0 ratio is not accurate to predict left atrial pressure in patients with hypertrophic cardiomyopathy.21 Both E and e0 are early diastolic events, and therefore the correlation with early or mean diastolic pressure can be expected to be better than with LVEDP. In the present study, we demonstrated a weak relationship between PCWP and E/e0 septal and E/e0 lateral. In part, this might be explained by the fact that PCWP is a measure of mean LV end-diastolic pressure rather than early diastolic pressure. Similarly the PCWP may not necessarily correlate closely with LV enddiastolic pressure, particularly when it is markedly

elevated.22 Given that significant differences between e0 septal and e0 lateral can occur in certain conditions such as PAH,23 but also in normal hearts, guidelines recommend the use of e0 av.12,17 However, E/e0 av was not accurate for predicting PCWP, either. The prognostic value of the E/e0 ratio in a variety of settings (reviewed by Nagueh et al.12) remains undisputed. However, the studies mentioned above19,21 as well as our data support the notion that a critical reappraisal of the E/e0 ratio in predicting LV filling pressures is warranted24 and that the E/e0 ratio as a single parameter to predict filling pressures is insufficient but must be used in conjunction with clinical information and other 2-dimensional (2D) and Doppler parameters, as also emphasized in current guidelines.12,17 Estimation of sPAP based on VTRpeak has been validated in many studies, and agreement between noninvasive and invasive data was generally good.13 However, at least in some settings, Doppler-based estimation of systolic PAP can be associated with significant inaccuracies,25,26 and guidelines highlight that echocardiography can be inaccurate on a patient to patient basis.9 Although the correlation between invasive and noninvasive sPAP was only moderate in the present study, which may be related in part to the relative importance of inaccuracies in estimated RAP if pulmonary pressures are relatively low, echocardiography

410 Journal of Cardiac Failure Vol. 17 No. 5 May 2011

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Fig. 2. Bland-Altman plots showing the agreement between noninvasive and invasive right atrial pressure (RAP, panel A), systolic pulmonary artery pressure (sPAP, panel B), mean pulmonary artery pressure (mPAP, panel C), cardiac output (CO, panel D), pulmonary vascular resistance (PVR, panel E), and pulmonary capillary wedge pressure (PCWP, panel F). Bias (bold dashed line) and limits of agreement (thin dashed lines) are shown. Solid circles: control subjects; open circles: heart failure with normal left ventricular ejection fraction; triangles: pulmonary arterial hypertension.

had a high accuracy to identify or exclude pulmonary hypertension defined as a mPAP O25 mm Hg. Unfortunately, parameters needed to differentiate pulmonary hypertension into PAH and PVH could not be reliably estimated noninvasively, although we could confirm a correlation between noninvasive15 and invasive PVR. Another study had shown poor agreement between noninvasive PVR calculated using the same method and invasive PVR in patients with higher PVR.27 In current guidelines, PVR has been dropped, and TPG is used to differentiate PAH versus PVH.9 We showed that noninvasive PVR was associated with invasive TPG, but again, this association was not strong enough to be clinically useful. A recent study had suggested that patients with PAH and PVH can reliably be differentiated by E/e0 lateral.28 However, that study looked at the 2 extremes of PAH and PVH, ie, patients with PAH and high pressures (mPAP 48 mm Hg) and patients with advanced HF with significantly impaired LVEF or other forms of cardiomyopathies,28 where discrimination is usually possible even based on 2D echocardiography, although this data was not given. Our study has some potential limitations. Consistent with normal clinical practice, noninvasive measurements were

performed in the left lateral decubitus position and invasive measurements were obtained in the supine position, which may have slightly affected the result. In addition, the number of subjects studied was relatively modest. However, the availability of very detailed and near-simultaneous noninvasive and invasive data from a group of patients with different hemodynamic characteristics, including healthy control subjects, is a strength of our study, and our results in this population provide novel and clinically relevant information despite the relatively small numbers that potentially limit the power of our study. It is also possible that the broader interpretation of our observations may be limited by the selection of a group with relatively normal PCWP; however, we believe the exclusion of patients with markedly increased PCWP provides important insights into the limitations of noninvasive methods in this specific group. We did not formally assess intraobserver and interobserver variability in this study, but we performed only commonly used measurements. Our invasive method for assessing cardiac output relied upon the thermodilution technique, and the accuracy of thermodilution in patients with significant tricuspid regurgitation has been questioned.29 The number of patients with more than mild tricuspid

Echo Hemodynamics in Subjects With Normal EF

regurgitation was low in the present study, and recent experimental30 and clinical26 data did not confirm these results. Taken together, our findings do not invalidate earlier studies on the utility of Doppler echocardiography to estimate hemodynamics but point to the fact that the use of these parameters as isolated measures in real-life patients with normal LVEF may be misleading on a patientto-patient basis. In conclusion, the present data clearly indicate that single Doppler echocardiography parameters are not accurate enough to reliably estimate key hemodynamic parameters, particularly PCWP, in subjects with normal LVEF and a range of symptoms and underlying cardiovascular disorders. Acknowledgments The authors greatly appreciate the excellent technical assistance by Donna Vizi and Jenny Starr. Disclosures None.

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