Download Echocardiography Can Identify Patients With Increased Pulmonary

Echocardiography Can Identify Patients With Increased
Pulmonary Vascular Resistance by Assessing Pressure
Reflection in the Pulmonary Circulation
Odd Bech-Hanssen, MD, PhD; Fredrik Lindgren, MD;
Nedim Selimovic, MD, PhD; Bengt Rundqvist, MD, PhD
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Background—Pulmonary hypertension is a frequent finding in patients with cardiopulmonary disorders. It is important to
recognize pulmonary hypertension due to increased pulmonary vascular resistance (PVR), as this affects treatment and
prognosis. Patients with increased PVR have an increased pulmonary pressure reflection. We hypothesized that pressure
reflection can be described by echocardiography and that variables related to pressure reflection can identify patients
with increased PVR.
Methods and Results—The study comprised 98 patients investigated within 24 hours of right heart catheterization and 20
control subjects. The pressure reflection variables were obtained by pulsed Doppler in the pulmonary artery and
continuous Doppler of tricuspid regurgitation. We selected 3 variables related to pressure reflection: the interval from
valve opening to peak velocity in the pulmonary artery (AcT, ms), the interval between pulmonary artery peak velocity
and peak tricuspid velocity (tPV-PP, ms), and the right ventricular pressure increase after peak velocity in the pulmonary
artery (augmented pressure, AP, mm Hg). The correlation between simultaneous catheter- and echocardiographydetermined AP was strong (n⫽19, R⫽0.83). The AcT, tPV-PP, and AP in patients with a PVR of ⬎3 Woods units
(n⫽71) was (mean⫾SD) 77⫾16 ms, 119⫾36 ms, and 22⫾12 mm Hg, respectively, and differed from patients with a
PVR of ⱕ3 Woods units (n⫽27, P⬍0.0001), 111⫾32 ms, 39⫾54 ms, and 3⫾4 mm Hg, and from controls, 153⫾32 ms,
⫺19⫾45 ms, and 0 mm Hg, respectively (P⬍0.0001). The AcT, tPV-PP, and AP values were not correlated with
capillary wedge pressure (R⫽0.08 – 0.16). The areas under the receiver operator characteristic curve (95% CI) for AcT,
tPV-PP, and AP were 0.87 (0.82 to 0.95), 0.94 (0.89 to 0.99), and 0.98 (0.95 to 1.0), respectively.
Conclusions—In this study, we describe a novel echocardiography method for assessing pressure reflection in the
pulmonary circulation. This method can be used to identify patients with pulmonary hypertension due to increased
PVR. (Circ Cardiovasc Imaging. 2010;3:424-432.)
Key Words: echocardiography 䡲 pulmonary hypertension 䡲 pulmonary vascular resistance
P
ulmonary hypertension is a frequent finding in patients
who undergo Doppler echocardiography. Most of these
patients have left heart disease (LHD) with pulmonary
hypertension secondary to an increase in left ventricular
filling pressure but normal pulmonary vascular resistance
(PVR). Pulmonary vascular disease with increased resistance
to flow leads to pulmonary hypertension, with a poor prognosis owing to right ventricular failure.1 There are many
different pathogenic pathways that might cause an increase in
resistance in the pulmonary circulation: pulmonary artery
hypertension (PAH), pulmonary hypertension associated with
lung disease, and chronic thrombotic embolism (CTEPH). It
is important to distinguish patients with pulmonary hypertension due to increased PVR from those with pulmonary
hypertension due to increased left ventricular filling pressure
without increased PVR, as this affects both treatment and
prognosis.2
Clinical Perspective on p 432
Low pulmonary artery (PA) mean pressure, low peripheral
resistance, and high compliance in the central large arteries
characterize the normal pulmonary circulation, and together
this causes little reflection of the pressure wave. The shape of
the pressure wave in the normal pulmonary circulation is
similar to that of the flow wave.3 From previous invasive
studies in patients without increased PVR, we know that peak
flow and peak pressure normally coincide, and there is no
increase in pressure after peak flow.4,5 On the other hand, in
patients with pulmonary hypertension due to increased PVR,
augmented pressure (AP) after peak flow due to an earlier and
Received October 14, 2009; accepted April 22, 2010.
From the Departments of Cardiology (O.B.-H., N.S., B.R.) and Clinical Physiology (O.B.-H., F.L.), Sahlgrenska University Hospital, Göteborg,
Sweden.
Correspondence to Odd Bech-Hanssen, MD, PhD, Institute of Medicine at Sahlgrenska Academy, Department of Cardiology, Sahlgrenska University
Hospital, SE-413 45 Göteborg, Sweden. E-mail [email protected]
© 2010 American Heart Association, Inc.
Circ Cardiovasc Imaging is available at http://circimaging.ahajournals.org
424
DOI: 10.1161/CIRCIMAGING.109.913467
Bech-Hanssen et al
Pulmonary Pressure Reflection and Echocardiography
425
more pronounced pressure reflection has been observed.6,7
The increase in pressure after peak flow imposes a wasted
pressure effort on the right ventricle. This phenomenon has
been studied invasively and by Doppler echocardiography in
patients with pulmonary embolism.8,9 However, to the best of
our knowledge, there are no studies that have used Doppler
echocardiography for a comprehensive description of pressure reflection, the effects of pressure reflection on PA flow,
and the right ventricle pressure profile. In the present study,
we hypothesize that pressure reflection and its effect on the
right ventricle pressure profile can be described noninvasively by Doppler echocardiography. Furthermore, we investigate whether these variables associated with pressure reflection can be used to identify patients with increased PVR.
Methods
Study Population
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The study comprised 98 patients who underwent Doppler echocardiography and right heart catheterization. The inclusion criteria were
(1) regular cardiac rhythm, (2) right heart catheterization within 24
hours of Doppler echocardiography, (3) pulsed Doppler registration
in the PA, and (4) tricuspid regurgitation that enabled assessment of
right ventricular peak systolic pressure (RVPS) by Doppler echocardiography. The pressure reflection variables were also studied in
healthy control subjects (n⫽20) without hypertension or diabetes
mellitus and with normal standard echocardiography findings. Forty
patients had LHD (mean⫾SD left ventricular ejection fraction,
36⫾18%), 42 patients had PAH, and 16 patients had CTEPH. In the
PAH group, 27 cases were idiopathic, 8 were associated with a
connective tissue disorder, and 4 were associated with portal hypertension. Some of the investigations were follow-up catheterizations
of patients on treatment. The diagnosis of PAH or CTEPH was based
on the baseline diagnostic investigation, not the level of PA pressure
or PVR on follow-up. Nineteen catheter investigations performed
simultaneously with Doppler echocardiography were used to investigate the agreement between catheter and Doppler echocardiography
findings.
Informed consent was obtained from all patients participating in
the investigations with simultaneous Doppler and pressure measurements, and the ethics committee at the University of Gothenburg
approved the study.
Pressure Reflection: Theoretical Considerations
In the normal pulmonary arterial tree, the pressure and flow waves
generated by the right ventricle are almost completely dampened,
and the pressure and flow waves therefore have a similar contour. In
the normal right ventricular outflow tract, there is no obstruction to
flow or pressure gradient. The waveform of the systolic portion of
the right ventricular pressure curve is therefore similar to the PA
pressure curve. Changes in pulmonary precapillary properties, such
as reduced compliance and increased resistance, cause a reflection of
the pressure and flow waves, with marked changes in wave contours
(Figure 1). The reflected pressure wave adds to the forward traveling
wave, whereas reflected flow waves subtract from the forward flow
(Figure 1).10 The peak flow velocity in the PA denotes the initial
upstroke of the reflected pressure wave. So if flow and pressure are
measured simultaneously, it is possible to determine the augmentation in pressure due to reflected pressure. The site and magnitude of
pressure reflection influence the timing of peak velocity (AcT), the
timing of peak velocity in relation to peak pressure (tPV-PP), and the
magnitude of AP. In the present study, we assessed these 3 variables
in relation to pressure reflection and increased PVR by Doppler
echocardiography (Figure 2).
Doppler Echocardiography
Echocardiography was performed with the Vivid System Seven
(GE/Vingmed, Milwaukee, Wis) ultrasound system. Left ventricular
Figure 1. Schematic drawing showing the influence of pressure
(P) and flow (Q) wave reflection on the measured waveforms.
The forward pressure and flow waves are identical in shape,
whereas the reflected pressure and flow waves are inverted but
also identical in shape. The reflected pressure wave adds to the
forward wave, and the corresponding reflected flow wave is
subtracted. AcT is the time from the opening of the pulmonary
valve to the peak velocity (acceleration time); tPV-PP is the
interval between peak velocity and peak pressure; and AP is the
increase in pressure from peak velocity to peak pressure (augmented pressure).
diastolic diameter was obtained from M-mode recordings. The left
ventricular ejection fraction was measured either from the M-mode
data with Simpson’s method or by visual inspection. Mitral and
pulmonary vein flow was recorded by pulsed Doppler from the tip of
the valve or the upper right pulmonary vein orifice. All Doppler
echocardiography measurements were performed off-line with a
sweep speed of 100 to 200 mm/s, and the investigator was blinded to
the results of the catheterization investigation. All patients were
examined in several nonstandard projections guided by color Doppler. Most frequently, the highest velocity was obtained in a projection
showing the right ventricle in a position between a standard apical
4-chamber view and a parasternal view. Pulmonary flow velocity
was recorded by placing a 5-mm pulsed-wave Doppler sample
volume in the right ventricular outflow tract at the level of the
pulmonary valve.
The timing of the pulmonary valve opening, the peak velocity, and
closing were determined as the time from the QRS complex (most
often, the R-wave) and the onset (a-b), peak velocity (a-c), and
ending (a-d) of systolic flow in the PA registered by pulsed-wave
Doppler (Figure 2). The time interval (a-c) was superimposed onto
the velocity spectrum of the tricuspid regurgitant jet to calculate the
right ventricular pressure corresponding to the peak velocity in the
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July 2010
pulmonary artery (RVPV; Figure 2). The velocity across the tricuspid valve at this time interval was measured, and the pressure
gradients between the right ventricle and right atrium were calculated
(pressure gradient⫽4⫻velocity2). The mean right atrial pressure was
estimated from the vena cava inferior dimension and collapsibility
index with inspiration.11 The timing of the right ventricular peak
systolic pressure (RVSP) was determined as the time from the QRS
to peak velocity of the regurgitant jet (a-d). The right ventricular
ejection time was calculated as [(a-b)⫺(a-d)]. The time from peak
pressure in the right ventricle to peak velocity in the pulmonary
artery (tPV-PP) was calculated as [(a-e)⫺(a-c)]. The time from onset
of flow in the pulmonary artery to peak velocity (acceleration time,
AcT) was calculated from [(a-c)⫺(a-b)]. The AP in the right
ventricle from peak velocity in the PA RVSP was calculated as
RVSP⫺RVPV (Figure 2). The augmentation index was calculated as
AP/RVSP⫻100.
Hemodynamic Measurements
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A Swan-Ganz catheter (7F, Baxter Healthcare, Edwards Critical
Care Division, Deerfield, Ill) was introduced through the right
internal jugular vein under fluoroscopic guidance with the Seldinger
technique. Pressures and cardiac output were obtained after 10
minutes of rest. All patients were awake and breathing spontaneously. In patients with simultaneous catheter and Doppler echocardiography registrations, the right ventricular pressure corresponding
to the peak velocity (ie, RVPV) was measured by superimposing the
time interval from onset of flow in the PA until peak velocity (AcT),
as assessed by pulsed Doppler on the right ventricular pressure
curve. Onset of flow was defined as the point on the right ventricular
pressure curve corresponding to PA diastolic pressure. PA compliance was calculated as stroke volume/pulse pressure (PA systolic
pressure⫺PA diastolic pressure).12
Statistical Methods
Continuous variables with a normal distribution are expressed as
mean⫾SD and median (range) when the distribution is not normal.
The degree of linear relation between catheter measurements and
Doppler echocardiography was assessed by the correlation coefficient (R). The magnitude of differences between 2 variables was
assessed by Bland-Altman analyses, calculating the mean difference ⫾
SD.13 To compare multiple groups, we used a 1-way ANOVA when
the distribution was normal or the Kruskal-Wallis test when the
distribution was not normal. In cases where the null hypothesis was
rejected (probability value ⬍0.05 considered statistically significant), we continued with a post hoc analysis by using the
independent-sample t test or Mann-Whitney test where appropriate.
We then performed comparisons between 3 groups, and the probability value considered significant was 0.016, according to the
Bonferroni adjustment. The receiver operator characteristic (ROC)
curve for the detection of increased PVR defined as ⬎3 Woods units
(WU) with the area under the curve (95% CI) was determined for the
3 pressure reflection variables. To evaluate the diagnostic ability of
the 3 variables, we compared the 95% CIs for the area under the
curve. To determine clinically useful cutoff levels for the different
variables, we selected from the ROC analysis the value corresponding to the best combination of sensitivity and specificity. To evaluate
the interindividual variability, measurements were made by 2 different investigators on the same Doppler echocardiography recording
(n⫽14). The variability was described by the coefficient of variation,
which was expressed as the mean value of differences (group
variability) or the SD of differences (individual variability) divided
by the mean value of 2 measurements.
Figure 2. Pulsed Doppler in the right ventricular outflow tract
(middle), continuous-wave Doppler of the tricuspid regurgitant
jet (bottom), and the right ventricular pressure recording (top) in
a patient with CTEPH. The time intervals from the QRS to the
opening (a-b) of the pulmonary valve, peak velocity (a-c) in the
outflow tract, closure (a-d) of the pulmonary valve, and the peak
right ventricular pressure (a-e) are determined. The AcT is then
[(a-c)⫺(a-b)], and the tPV-PP is [(a-e)⫺(a-c)]. The interval (a-c) is
superimposed on the tricuspid velocity envelope to determine
RVPV. The AP is calculated as RVPS-RVPV. The catheter
RVPS was 70 mm Hg, and 66 mm Hg estimated from Doppler
echocardiography. The AcT was 50 ms, the RVPV was
36 mm Hg, the tPV-PP was 140 ms, and the AP 30
was mm Hg.
Bech-Hanssen et al
Table 1.
Pulmonary Pressure Reflection and Echocardiography
427
Data From Right Heart Catheterization and Doppler Echocardiography
Post Hoc Analysis
Variable
LHD (n⫽40)
PAH (n⫽42)
CTEPH (n⫽16)
Overall P Value
LHD vs PAH
LHD vs CTEPH
PAH vs CTEPH
Cardiac index,
(L/min)/m2
2.3⫾0.7
2.7⫾0.8
2.3⫾0.5
0.046
0.06
1.00
0.27
RAP, mm Hg
9 (1–25)
6 (0–21)
5 (0–20)
PASP, mm Hg
48⫾17
82⫾26
81⫾20
⬍0.0001
⬍0.0001
⬍0.0001
1.00
PAMP, mm Hg
31⫾11
52⫾17
45⫾12
⬍0.0001
⬍0.0001
0.002
0.08
PADP, mm Hg
20⫾7
32⫾13
26⫾7
⬍0.0001
⬍0.0001
0.03
0.01
PCWP, mm Hg
19 (3–34)
8 (2–19)
9 (2–25)
⬍0.0001
⬍0.0001
⬍0.0001
0.80
PVR, WU
2.5 (0.4–13)
8.9 (2.8–23)
8.9 (2.8–13.7)
⬍0.0001
⬍0.0001
⬍0.0001
0.52
SV/PP, ml/mm Hg
2.0 (0.6–7.6)
1.1 (0.6–4.4)
1.0 (0.6–2.9)
⬍0.0001
⬍0.0001
⬍0.0001
0.45
LVEF, %
36⫾18
60⫾6
60⫾8
⬍0.0001
⬍0.0001
⬍0.0001
0.93
LV diastolic diameter,
cm
6.6⫾1.4
4.5⫾0.7
4.8⫾0.7
⬍0.0001
⬍0.0001
⬍0.0001
0.17
LA area, cm2
27⫾6
19⫾6
19⫾3
⬍0.0001
⬍0.0001
⬍0.0001
0.82
E/A
2.5 (0.6–4.8)
0.8 (0.4–4.7)
0.8 (0.5–1.1)
⬍0.0001
⬍0.0001
⬍0.0001
0.22
S/D
0.6 (0.2–1.5)
1.2 (0.5–3.4)
1.8 (1.1–2.5)
⬍0.0001
⬍0.0001
⬍0.0001
0.05
Right heart catheterization
0.064
Doppler echocardiography
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Values are mean⫾SD for variables with a normal distribution and median (range) for variables with a nonparametric distribution. RAP indicates right atrial pressure;
PASP, PA systolic pressure; PAMP, PA mean pressure; PADP, PA diastolic pressure; SV, stroke volume; PP, pulse pressure; LVEF, left ventricular ejection fraction; LA,
left atrium; E/A, ratio between early and late mitral filling velocity; and S/D, ratio between systolic and diastolic pulmonary vein velocity. Other abbreviations are as
defined in text.
The authors had full access to and take full responsibility for the
integrity of the data. All the authors have read and agree to the
manuscript as written.
Results
Patient Characteristics
The mean⫾SD (range) age in the total patient group was
55⫾14 (19 –78) years, and the percentage of females was
55%. Mild tricuspid regurgitation was present in 60%, moderate regurgitation in 29%, and moderately severe regurgitation in 11%. Table 1 summarizes the hemodynamic data from
right heart catheterization. Patients with PAH and CTEPH
had more pronounced pulmonary hypertension compared
with LHD patients. Thirty-eight percent of patients with LHD
had increased PVR (⬎3 WU). Eighty-three percent of patients with LHD had increased pulmonary capillary wedge
pressure (PCWP ⬎12 mm Hg), whereas patients with PAH
and CTEPH had a normal PCWP in overall terms. Patients
with PAH and CTEPH had reduced compliance compared
with those with LHD. Compared with those with PAH and
CTEPH, patients with LHD had reduced left ventricular
ejection fraction, increased diastolic volume, a disturbed
mitral and pulmonary vein flow pattern, and a dilated left
atrium, indicating increased left ventricular filling pressure.
Comparison Between Catheter and Doppler
Echocardiography Findings
Table 2 shows the results of catheter pressure measurements
and simultaneously obtained estimations from Doppler echocardiography. There was a strong, linear correlation between
estimated and measured right atrial pressure, RVSP, and
RVPV. In absolute terms, there was a small yet significant
difference between catheter-measured and Doppler echocardiography– estimated AP. Furthermore, there was no difference between catheter- and nonsimultaneous Dopplerestimated RVSP in the study population (65⫾27 vs
66⫾26 mm Hg, P⫽0.52). The correlation was strong
(R⫽0.90), but the limits of agreement were relatively wide
(mean⫾SD difference, 0.5⫾12 mm Hg).
Pressure Reflection in Controls and Patients With
and Without Increased PVR
The difference in RR interval between pulsed Doppler recordings in the PA and continuous-wave Doppler in the
tricuspid valve was 0.4⫾4%. Table 3 shows Doppler findings
in controls and patients with and without increased PVR.
There was no difference in age between controls and patients
with and without increased PVR. In the majority of controls,
we observed peak velocity in the PA after the peak velocity
in the tricuspid regurgitant jet (15/20, 75%), or else the peak
velocity in the PA was equal to peak pressure in the right
Table 2. Comparison Between Catheter and Simultaneous
Doppler Echocardiography
Variable, mm Hg (n⫽19)
RAP
RVSP
RVPV
AP
Catheter
9⫾6
76⫾20
49⫾13
27⫾10
Simultaneous Doppler
9⫾5
73⫾17
50⫾12
23⫾9
Mean difference⫾SD
1⫾3
2⫾9
⫺1⫾8
4⫾6
Correlation coefficient (R)
0.84
0.89
0.82
0.83
P value
0.21
0.27
0.49
0.007
Values are mean⫾SD. RAP, mean right atrial pressure. Other abbreviations
are as defined in text.
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Circ Cardiovasc Imaging
Table 3.
July 2010
Age and Doppler Echocardiography Findings in Controls and in Patients With and Without Increased PVR
Post Hoc Analysis
Variable
Age, y
Controls
(n⫽20)
PVR ⱕ3 WU
(n⫽27)
PVR ⬎3 WU
(n⫽71)
Overall
P Value
Controls vs PVR
ⱕ3 WU
Controls vs PVR
⬎3 WU
PVR
ⱕ3 WU vs PVR ⬎3 WU
52⫾13
51⫾14
57⫾15
0.14
344⫾33
292⫾46
299⫾40
⬍0.0001
⬍0.0001
⬍0.0001
0.45
38⫾4
34⫾5
37⫾5
0.019
0.010
0.44
0.02
153⫾32
111⫾32
77⫾16
⬍0.0001
⬍0.0001
⬍0.0001
⬍0.0001
44⫾7
38⫾8
26⫾6
⬍0.0001
0.006
⬍0.0001
⬍0.0001
tPV-PP, ms
⫺20 (⫺96–86)
39 (⫺88–151)
116 (41–255)
⬍0.0001
0.001
⬍0.0001
⬍0.0001
AP, mm Hg
. . .*
2 (0–14)
21 (2–56)
...
...
...
⬍0.0001
Augmentation index, %
...
6 (0–32)
26 (4–79)
...
...
...
⬍0.0001
RVET, ms
RVET/RR, %
AcT, ms
AcT/RVET, %
RVET indicates right ventricular ejection time; RR, interval between 2 heart beats. Other abbreviations are as defined in text.
*Only 2 individuals in the control group had AP.
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ventricle. As a result, most control subjects did not have any
AP after peak velocity (18/20, 90%). Compared with controls, patients with increased PVR had significantly shorter
AcT, longer tPV-PP, and more pronounced AP. In patients
without increased PVR, AcT, tPV-PP, and AP differed
significantly from controls and from patients with increased
PVR. Figure 3 shows the right ventricular pressure recording,
pulsed-wave Doppler from the PA, and the tricuspid
continuous-wave Doppler in a patient without increased PVR
and a patient with PAH. In the patient without increased PVR
(left), the peak velocity in the PA coincides with peak
velocity in the tricuspid jet. The pressure reflection variables
in patients with LHD differed significantly from those in
controls (Figure 4). Compared with those with PAH, patients
with CTEPH had shorter AcT, and the tPV-PP tended to be
longer and the AP more pronounced (Figure 4). The AcT,
tPV-PP, and AP values in patients with LHD and a PVR ⬎3
WU (n⫽15) were 82⫾20 ms, 102⫾37 ms, and
13⫾9 mm Hg, respectively, and these differed from the
values of patients with LHD and a PVR ⱕ3 WU (n⫽25,
P⬍0.0001; 113⫾32 ms, 36⫾54 ms, and 3⫾4 mm Hg,
respectively).
Determinants of PA Pressure Reflection
Table 4 shows the results of a correlation analysis of a
relation between the different variables describing the pressure reflection (AcT, tPV-PP, AP) and possible determinants
(cardiac index, PCWP, compliance, PVR). There was a weak
correlation between cardiac index and AcT. PCWP was not
correlated with any of the pressure reflection variables.
Pulmonary arterial compliance and PVR showed a moderate
correlation with the pressure reflection variables (R range of
0.43 to 0.68).
Pressure Reflection Variables and Increased PVR
Figure 5 shows the ROC curves for the pressure reflection
variables. All 3 variables had large areas under the ROC
curve. The 95% CI for AcT did not overlap with that
corresponding to AP but it did with tPV-PP. The cutoff values
that gave the best combined sensitivity and specificity were
⬍103 ms for AcT, ⬎89 ms for tPV-PP, and ⬎8 mm Hg for
AP. Table 5 shows diagnostic performance when these cutoff
values were used.
Interobserver Variability
The respective interobserver group variability for measurements made on the same recording was 4%, 3%, 6%, 8%, and
9% for RVPS, RVPV, AcT, tPV-PP, and AP. The corresponding interobserver individual variability was 4%, 7%,
7%, 9%, and 13%.
Discussion
In the present study, we used the pressure reflection phenomenon assessed by Doppler echocardiography to identify patients with pulmonary hypertension due to increased PVR and
pulmonary vascular disease. Importantly, noninvasive estimation of pressure reflection and pressure augmentation in
the pulmonary circulation is easy to perform and is not
obtained during routine cardiac catheterization.
Several previous reports have shown a close agreement
between catheter and Doppler echocardiography during simultaneous measurements of PA systolic pressure.14 –16 The
direct, noninvasive estimation of PVR has not previously
been possible. Some investigators have used Doppler echocardiography methods indirectly related to PVR in patients
with heart failure.17 The ratio between peak tricuspid regurgitant velocity (a surrogate for PA mean pressure) and the
right ventricular outflow tract time-velocity integral (a surrogate for cardiac output) showed good agreement with
catheter-derived PVR. This ratio is, however, more an estimate of total pulmonary resistance (PA mean pressure/
cardiac output) than PVR, and it is therefore conceivable that
the variable cannot be used to identify patients with an
increased transpulmonary gradient. Characteristic changes of
the flow profile in the PA due to pressure reflection with a
notch after peak velocity (see Figure 2) have been described
in patients with pulmonary embolism.8,9 In the presence of a
notch, we should suspect increased PVR, but absence of the
notch has a low predictive value. In patients with PAH, we
have shown in a recent study that PVR can be calculated with
a strong correlation (R⫽0.93) between catheter and Doppler
methods.16 These results were obtained in a group of patients
with normal PCWP and a relatively high PA mean pressure.
Bech-Hanssen et al
Pulmonary Pressure Reflection and Echocardiography
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Figure 3. Right ventricular pressure curves (top), pulsed Doppler
from the PA (middle), and continuous-wave Doppler (bottom)
from an individual without increased PVR (left) and a patient
with increased PVR due to PAH (right). In the individual with
normal PVR (1.2 WU), the AcT is long (186 ms), and the peak
flow in the PA (c-d) coincides with the RVPS. The RVPS (**) was
41 mm Hg measured by Doppler and 29 mm Hg measured by
catheter. In the patient with increased PVR (14.3 WU), the AcT
is short (66 ms), the peak flow in the PA is earlier than the RVPS
(tPV-PP⫽91 ms), and there is marked augmentation in pressure.
The AP measured by both catheter and Doppler was 17 mm Hg.
The catheter RVPS was 69 mm Hg, whereas the Doppler RVPS
was 67 mm Hg.
In patients with LHD and less severe pulmonary hypertension, we anticipated that the uncertainty in PCWP and cardiac
output assessments would make the direct estimation of PVR
less precise. Patients with pulmonary vascular disease have
increased pressure reflection due to increased PVR, reduced
compliance, or a combination of the 2, leading to pressure
429
augmentation in late systole. In the present study, we found
that the Doppler echocardiography variables were able to
identify these patients with a high degree of accuracy. The
proposed variables are easy to obtain and not influenced by
PCWP. This implies that these variables are able to identify
patients with a combination of increased PVR and increased
PCWP.
Pulmonary hypertension is characterized by an increase in
right ventricular afterload. The right ventricle initially adapts
to the pressure overload, but the cause of death is most often
right ventricular failure. Right ventricular afterload in patients
with pulmonary vascular disease and pulmonary hypertension
is most frequently defined with a PVR that reflects the load in
relation to steady flow. Blood flow is pulsatile, however, and
a more comprehensive description of right ventricular afterload should include variables that assess the load in relation
to pulsatile flow. Wave reflection arises from any discontinuation in caliber or change in elastic properties. The observed
pressure reflection is a composite parameter that contains
information on precapillary pathologic changes in the pulmonary vascular bed, consistent with the moderate correlation
with PVR in the present study. The 3 Doppler echocardiography variables were able to discriminate patients with
increased PVR from those without. However, in patients with
a PVR ⱕ3 WU, these variables differed significantly from
controls, indicating that although PVR was not elevated, they
had some degree of pressure reflection. The underlying
pathophysiologic explanation of this observation or the clinical importance of this finding is unclear. Importantly, we are
able to conclude that, by combining information from the
flow profile in the PA and the tricuspid regurgitant jet, we can
obtain important information on right ventricular afterload
due to pulmonary vascular impedance. Today, it is part of
clinical routine to assess PA systolic pressure with Doppler
echocardiography, and pulmonary hypertension is a frequent
finding.18 The majority of these patients have pulmonary
hypertension due to systolic or diastolic LHD or valvular
heart disease and normal PVR. It is important to recognize
when LHD is associated with increased PVR. In patients who
are candidates for left ventricular assist or heart transplant,
right heart catheterization should be performed to confirm the
finding and to assess the severity and reversibility of the
increased PVR. In some LHD patients undergoing optimal
treatment and a normalized or only slightly elevated PCWP,
residual pulmonary hypertension and increased PVR might
indicate that PAH-specific therapy could be beneficial.2 The
diagnosis of PAH is known to be difficult, and diagnostic
delay is a problem.19,20 In PAH patients, even a mild elevation
of PA pressure with normal right ventricular function is often
associated with extensive pulmonary vascular damage.21 The
suspicion of pulmonary vascular disease in patients with
pulmonary hypertension should therefore be high to detect
the disease in an earlier phase. In every patient with pulmonary hypertension, the investigator should therefore also
make a statement about the likelihood of increased PVR. In a
recently published diagnostic algorithm aiming at earlier
detection of PAH, the first question when pulmonary hypertension has been diagnosed by Doppler echocardiography is
whether the patient has pulmonary hypertension due to
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July 2010
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Figure 4. Scatterplot shows the AcT, tPV-PP, and AP in controls and in patients with LHD, PAH, and CTEPH. Closed circles shows
individuals with a PVR ⱕ3 WU and open circles, individuals with a PVR ⬎3 WU.
LHD.2,21 In clinical practice, this is often difficult to determine, in particular among patients with a normal left ventricular ejection fraction and normal valve function. Normal
filling pressure at rest does not exclude left ventricular
systolic and diastolic dysfunction, and the relation between
Doppler echocardiography variables and filling pressure is no
more than moderate.22–24 Today, with the opportunity to treat
PAH, many patients with pulmonary hypertension and inconclusive Doppler echocardiography results in terms of wedge
pressure are referred for invasive evaluation. A noninvasive
method with a high negative predictive value would therefore
be of interest, as it can reduce the need for catheterization.
Study Limitations
The patients included in the study were those undergoing
diagnostic right heart catheterization. The percentage of
patients with pulmonary hypertension, increased PVR, and
increased PCWP was therefore high, and we can expect this
population to differ from the patient population investigated
with Doppler echocardiography. Theoretically, this could
have a particular impact on our assessment of positive and
negative predictive values.
In the present study, we have shown that the pressure
reflection variables can be used to identify patients with
increased PVR. However, the linear relation between these
Bech-Hanssen et al
Pulmonary Pressure Reflection and Echocardiography
Table 4. Relation Between Variables Describing Pressure
Reflection and Possible Determinants
AcT
R
Cardiac index
0.28
P Value
0.004
tPV–PP
R
0.06
P Value
0.54
AP
R
0.03
P Value
0.74
PCWP
0.16
0.12
0.08
0.41
0.15
0.14
SV/PP
0.68
⬍0.0001
0.50
⬍0.0001
0.59
⬍0.0001
PVR
0.54
⬍0.0001
0.43
⬍0.0001
0.58
⬍0.0001
See Tables 1 and 3 and text for explanation of abbreviations.
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variables and PVR was only moderate (R range of 0.43 to
0.68), and therefore we cannot directly estimate the PVR.
In the World Health Organization classification of pulmonary hypertension, there are 5 different subgroups.2 The most
important subgroups are represented in the present study
(PAH, LVD, and CTEPH), but we do not have data on
patients with pulmonary hypertension associated with lung
disease or hypoxemia. Pulmonary hypertension in patients
with lung disease is due to multiple factors, including the loss
of small vessels due to emphysema or fibrosis, intimal
thickening, and vasoconstriction secondary to alveolar hypoxia. From these pathophysiologic mechanisms, we can
expect increased pressure reflection. The new proposed
method for diagnosing pressure reflection and thereby pulmonary vascular disease might be a useful tool, but further
studies are needed in patients with lung disease.
To what extent these pressure reflection variables are
influenced by treatment can be used to monitor changes,
improvement, or worsening has not been studied. Furthermore, the potential prognostic information from pressure
reflection variables is unknown. The possible confounding
effects of right ventricular failure or the presence of severe
tricuspid regurgitation is another important issue. In the
present study, we identified patients with LHD and both
Figure 5. ROC curves for the detection of increased PVR for
AcT, tPV-PP, and AP.
431
Table 5. Diagnostic Performance of Pressure Reflection Variables
Variable (Cutoff
Value)
Sensitivity
(95% CI)
Specificity
(95% CI)
NPV
PPV
AcT (⬍103 ms)
94 (86 –98)
74 (60 – 86)
90
85
tPV-PP (⬎89 ms)
87 (77–94)
89 (77–96)
82
92
AP (⬎8 mm Hg)
90 (81–96)
94 (82–99)
86
95
NPV indicates negative predictive value; PPV, positive predictive value. Other
abbreviations are as defined in text.
increased PVR and increased PCWP. This is an important and
promising ability of the pressure reflection variables. However, we have not studied patients with mixed diseases with
increased PCWP (secondary to coronary artery disease) and
increased PVR due pulmonary vascular disease (PAH, lung
disease). Therefore, further studies are needed to evaluate the
possible use of these Doppler echocardiography variables.
Conclusions
In the present study, we found that the effects of pressure
reflection in the pulmonary arterial tree on the right ventricular pressure waveform can be described by a new Doppler
echocardiography method. Importantly, these easily obtainable Doppler echocardiography variables can be used to
identify patients with increased PVR.
Disclosures
None.
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CLINICAL PERSPECTIVE
Pulmonary hypertension is a frequent finding in patients investigated with Doppler echocardiography. Most of these
patients have left heart disease with pulmonary hypertension secondary to an increase in the left ventricular filling pressure
with normal pulmonary vascular resistance. Pulmonary vascular disease with increased resistance to flow leads to
pulmonary hypertension with a poor prognosis due to right ventricular failure. Diagnostic delay is a well-known problem
in patients with pulmonary hypertension due to pulmonary vascular disease. It is important to distinguish patients with
pulmonary hypertension due to increased pulmonary vascular resistance from those with pulmonary hypertension due to
increased left ventricular filling pressure without increased resistance, as this affects both treatment and prognosis. Low
pulmonary artery mean pressure, low peripheral resistance and high compliance in the central large arteries characterize
the normal pulmonary circulation and together this causes little reflection of the pressure wave. In the present study, we
hypothesized that pressure reflection and its effect on the right ventricle pressure profile can be described noninvasively
by using Doppler echocardiography. Further, we tested the hypothesis that variables associated with pressure reflection can
be used to identify patients with increased pulmonary vascular resistance. We found that Doppler echocardiography can
be used to describe pressure reflection in the pulmonary circulation and, importantly, the method can be used to identify
patients with increased pulmonary vascular resistance.
Echocardiography Can Identify Patients With Increased Pulmonary Vascular Resistance
by Assessing Pressure Reflection in the Pulmonary Circulation
Odd Bech-Hanssen, Fredrik Lindgren, Nedim Selimovic and Bengt Rundqvist
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Circ Cardiovasc Imaging. 2010;3:424-432; originally published online May 6, 2010;
doi: 10.1161/CIRCIMAGING.109.913467
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